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Advanced Tissue Resection in Gastroenterology: Indications, Role, and Outcomes
Endoscopists are often faced with unique challenges in the management and resection of various gastrointestinal tract lesions. These challenges could be lesion-related, endoscopist-related, or practice-related (see Table 1). (ATR). Not only does this organ-sparing approach offer a less invasive alternative to surgery, but it has also proved to have outcomes comparable to those of surgical standard of practice in specific scenarios. 
When Do You Refer to an Advanced Endoscopist?
One of the most critical steps in caring for patients with complex lesions is the ability to accurately determine whether a referral to an advanced endoscopist is warranted. The initial assessment of a lesion should always involve a careful assessment that risk stratifies the lesion depending on the location, size, neoplastic potential, and the feasibility of standard endoscopic resection compared to the need for surgical input.
A practical example in the case of colonic polyps is highlighted by the American Gastroenterology Association (AGA) guidelines recommending the referral of patients with polyps’ size ≥ 20 mm, challenging polypectomy location, or recurrent polyp at a prior polypectomy site to an endoscopic referral center.1 In the case of subepithelial lesions without endoscopic characteristics of benign etiology (i.e., lipomas, pancreatic rests, etc.), the threshold for referral to advanced endoscopists for further diagnostic testing by means of endoscopic ultrasonography or for therapeutic ATR should be lower.
Endoscopic tissue resection follows a spectrum, which often involves deeper layers of the gastrointestinal tract (GIT) as we progress along this spectrum (see Figure 1). 
ATR, a term encompassing a variety of endoscopic techniques ranging from endoscopic mucosal resection to full thickness resection, has gained traction over the last years given the ability to effectively remove various lesions in a precise time and cost-effective manner while maintaining the integrity of the GIT and avoiding major surgery. The indications for ATR vary depending on the technique, but generally include the presence of large or poorly positioned lesions, particularly in high-risk areas of the GIT such as the esophagus and small intestine, lesions extending beyond the mucosal layer or originating from deeper layers, and when en bloc resection of select lesions is necessary.
For providers referring patients for ATR, we recommend a few important endoscopic pearls when caring for these patients.
1) Biopsy the lesion if there is concern for malignancy — While some studies have noted increased fibrosis during endoscopic submucosal dissection (ESD) and some guidelines recommend against biopsies pre ESD, we believe that when there is high pretest probability for malignancy, a biopsy should be obtained. This should involve the area that is most concerning for malignancy (at the margin or center).2
2) While marking a lesion with tattoo is helpful for surgical planning and for lesions difficult to locate endoscopically, we stress the importance of placing tattoos 3 to 5 centimeters distal to the lesion and avoiding tattooing the lesion itself, which has been shown to induce fibrosis and can make resection challenging. Based on an international Delphi consensus, expert recommendations on when and how to endoscopically tattoo a lesion can be instrumental in adequately localizing the lesion, allowing for endoscopic resection, and preventing unnecessary surgeries.3
3) If you encounter a lesion that you are not sure can be resected safely and efficaciously, we recommend against attempting resection that may result in partial resection. This can also induce fibrosis and scarring and limit future attempts at resection.
Endoscopic Mucosal Resection (EMR)
EMR is currently utilized for curative treatment of a wide array of GIT lesions limited to the mucosal layer, whether metaplastic, dysplastic, or even in cases with early mucosal cancer, where the risk of submucosal and lymphatic invasion is minimal.4 This makes EMR a versatile and proven therapy, often serving as the first-line treatment for many GIT lesions.
EMR has various techniques that could be categorized into suction or non-suction (lift and cut) techniques. In the suction technique, devices like multiband mucosectomy (MBM) are commonly used, especially in nodular Barrett’s dysplasia, forming a pseudopolyp for subsequent resection. The procedure is characterized by its safety, efficacy, and cost-effectiveness, contributing to its widespread adoption in clinical practice. In the lift and cut approach, a submucosal injection is utilized to separate the muscularis propria from the lesion, thereby reducing the risk of perforation. Different solutions, such as normal saline, hypertonic saline, 50% dextrose, or proprietary submucosal injection solutions, are employed for submucosal injection.5
The non-suction technique using a snare to resect polyps after injection is more often used in colonic and small intestinal EMR. Resection can be done via thermal energy in the form of cut or coagulation; however, there is rising data on the use of piecemeal cold snare resection for select flat polyps of the colon.6 There is also promising data on the role of underwater EMR, a common technique employed for colonic lesions, particularly if the lesion does not lift well with submucosal injection.7
Adverse events associated with EMR include bleeding (7%-8%) and perforation (0.9%-2%).8-9 Adequate submucosal fluid injection is crucial to prevent perforations. However, the main limitation of EMR is the piecemeal nature of resections for lesions larger than 20 mm, leading to compromised histopathologic evaluation for complete excision, especially in cases with superficial submucosal invasion (SMI). This can result in residual or recurrent tissue, reportedly 8% to 20%.10 Despite this limitation, EMR remains a reliable strategy, and recurrent lesions are generally manageable through repeat sessions. The importance of EMR as a therapeutic modality lies in its role in addressing lesions with favorable characteristics, where the risk of SMI is low.
Endoscopic Submucosal Dissection (ESD)
ESD is an evolving technique that can be utilized for submucosal lesions of the GIT, lesions not amenable to EMR due to submucosal fibrosis, when en bloc removal of a lesion is needed for accurate histopathological diagnosis, and when other techniques fail.11-12
ESD was only recently adopted in the United States, requires specialized training, and usually is a lengthier procedure than EMR.13 Compared to EMR, it has higher en bloc resection rates and lower recurrence rates, making it curative for lesions with superficial SMI and favorable histologic features.4,14 The safety profile of ESD appears favorable, with most of the adverse events managed successfully by endoscopic methods. Major complications include intraoperative and delayed perforation, intraoperative and delayed bleeding, aspiration pneumonia, thromboembolism, and stricture formation in the case of circumferential lesions.15
Despite being technically challenging, ESD may provide a cost-effective long-term solution by avoiding surgery, reducing the need for additional interventions by minimizing recurrence rates. Given the technical complexity of ESD, particularly the submucosal dissection portion, techniques such as hybrid ESD developed. Hybrid ESD combines snaring with circumferential mucosal incision and partial submucosal dissection. Although it promises shorter procedure times, reduced complication rates like perforation, and similar recurrence rates compared to traditional ESD, studies have shown lower success rates in en bloc resection.16-17
Both EMR and ESD are considered complementary strategies, and the choice between them should be dictated by lesion characteristics, patient preferences, and local expertise.
Submucosal Tunneling Endoscopic Resection (STER)
STER has emerged as a well-established technique for the endoscopic resection of GI subepithelial tumors (SETs) originating from the muscularis propria layer. The standard STER procedure involves a series of steps including submucosal elevation proximal to the SET, mucosotomy, creation of a submucosal tunnel, dissection of the SET within the tunnel, enucleation from the deep muscle layer, and subsequent specimen retrieval followed by mucosal closure.
This technique is typically recommended for SETs smaller than 3.5 cm, particularly those located in the mid or distal esophagus, cardia, or along the greater curvature of the gastric body.18 However, STER may pose technical challenges for larger SETs or lesions in anatomically difficult locations, where surgical resection is recommended instead.19 Notably, recent large-scale meta-analyses have showcased the favorable complete resection and en bloc resection rates of STER in treating GI SETs.20
Endoscopic Full Thickness Resection (EFTR)
EFTR has emerged as a valuable technique in the endoscopic management of gastrointestinal lesions, particularly SETs and lesions not amenable to EMR or ESD due to fibrosis. EFTR involves the resection of all layers of the GIT from mucosa to serosa, and therefore is well-suited for SETs arising from the muscularis propria (MP).20
EFTR entails two main concepts: tissue resection and complete defect closure. Conventional EFTR consists of several steps, which include mucosal and submucosal pre-cutting, circumferential incision, and dissection through the MP or serosa. This results in a full thickness defect, for which closure of the wall defect is achieved using standard endoscopic clips or a combination of clips and endoloops or endoscopic suturing.21 For lesions less than 2 cm, EFTR can be performed in a single step using a cap-mounted full thickness resection device (FTRD). This results in deployment of over-the-scope clip over the target lesion followed by snaring the lesions above the clip.21
Location of the SET generally dictates the specific modality of ATR. For example, esophageal SETs may be more amenable to STER given that the lesion typically runs parallel with the lumen of the tubular esophagus, which allows for easier dissection without the need of full or partial retroflexion. While gastric SETs can be resected with STER, it may be challenging and more effectively addressed with EFTR, particularly when the entire lesion can be grasped into the full-thickness resection device.22 Limited data exists for duodenal EFTR, and colorectal SETs closure is particularly challenging.
Conclusion
It is key to emphasize that ATR cannot be safely established in practice without the incorporation of a multidisciplinary team (surgeons, radiologists, etc.), specialized tools, and trained personnel. This requires dedicated endoscopic rooms, careful patient selection, and a comprehensive approach to patient care before, during, and after these procedures.
Moreover, it is important to note that some patients may require post-procedure hospitalization for observation to ensure no early complications are encountered. Optimal surveillance strategies after ATR rely heavily on the potential for residual or recurrent disease, underlying pathology, and the expertise of the advanced endoscopist. As the field continues to evolve, ongoing research and technological advances of devices will further enhance the efficacy and safety of ATR in gastroenterology.
Dr. Madi (@MahMadi90) is based in the Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, Saint Louis, Missouri. Dr. Rengarajan (@ArvindRenga) and Dr. Bazarbashi (@AhmadBazarbashi) are based in the Division of Gastroenterology, Washington University in St. Louis. The authors have no conflicts of interest to disclose, and no funding was required for this project.
References
1. Copland AP, et al. AGA Clinical Practice Update on appropriate and tailored polypectomy: Expert review. Clin Gastroenterol Hepatol. 2024 Mar. doi: 10.1016/j.cgh.2023.10.012.
2. Lee SP, et al. Effect of preceding biopsy on the results of endoscopic submucosal dissection for colorectal laterally spreading tumor. Dig Dis Sci. 2019 Oct. doi: 10.1007/s10620-019-05625-3.
3. Medina-Prado L, et al. When and how to use endoscopic tattooing in the colon: An international Delphi agreement. Clin Gastroenterol Hepatol. 2021 May. doi: 10.1016/j.cgh.2021.01.024.
4. Rashid MU, et al. EMR and ESD: Indications, techniques and results. Surg Oncol. 2022 Aug. doi: 10.1016/j.suronc.2022.101742.
5. Castro R, et al. Solutions for submucosal injection: What to choose and how to do it. World J Gastroenterol. 2019 Feb. doi: 10.3748/wjg.v25.i7.777.
6. Rex DK. Best practices for resection of diminutive and small polyps in the colorectum. Gastrointest Endosc Clin N Am. 2019 Oct. doi: 10.1016/j.giec.2019.06.004.
7. Lv XH, et al. Underwater EMR for nonpedunculated colorectal lesions. Gastrointest Endosc. 2023 Apr. doi: 10.1016/j.gie.2022.10.044.
8. Fujiya M, et al. Efficacy and adverse events of EMR and endoscopic submucosal dissection for the treatment of colon neoplasms: a meta-analysis of studies comparing EMR and endoscopic submucosal dissection. Gastrointest Endosc. 2015 Mar. doi: 10.1016/j.gie.2014.07.034.
9. Kandel P, Wallace MB. Colorectal endoscopic mucosal resection (EMR). Best Pract Res Clin Gastroenterol. 2017 Aug. doi: 10.1016/j.bpg.2017.05.006.
10. Kemper G, et al; ENDOCARE Study Group. Endoscopic techniques to reduce recurrence rates after colorectal EMR: systematic review and meta-analysis. Surg Endosc. 2021 Oct. doi: 10.1007/s00464-021-08574-z.
11. Goto O, et al. Expanding indications for ESD: submucosal disease (SMT/carcinoid tumors). Gastrointest Endosc Clin N Am. 2014 Apr. doi: 10.1016/j.giec.2013.11.006.
12. Wang K, et al. Endoscopic full-thickness resection, indication, methods and perspectives. Dig Endosc. 2023 Jan. doi: 10.1111/den.14474.
13. Herreros de Tejada A. ESD training: A challenging path to excellence. World J Gastrointest Endosc. 2014 Apr 16. doi: 10.4253/wjge.v6.i4.112.
14. Chiba H, et al. Safety and efficacy of simultaneous colorectal ESD for large synchronous colorectal lesions. Endosc Int Open. 2017 Jul. doi: 10.1055/s-0043-110567.
15. Mannath J, Ragunath K. Endoscopic mucosal resection: who and how? Therap Adv Gastroenterol. 2011 Sep. doi: 10.1177/1756283X10388683.
16. Wang XY, et al. Hybrid endoscopic submucosal dissection: An alternative resection modality for large laterally spreading tumors in the cecum? BMC Gastroenterol. 2021 May. doi: 10.1186/s12876-021-01766-w.
17. McCarty TR, et al. Hybrid endoscopic submucosal dissection (ESD) compared with conventional ESD for colorectal lesions: a systematic review and meta-analysis. Endoscopy. 2021 Oct. doi: 10.1055/a-1266-1855.
18. Jain D, et al. Submucosal tunneling endoscopic resection of upper gastrointestinal tract tumors arising from muscularis propria. Ann Gastroenterol. 2017 Feb. doi: 10.20524/aog.2017.0128.
19. Lv XH, et al. Efficacy and safety of submucosal tunneling endoscopic resection for upper gastrointestinal submucosal tumors: a systematic review and meta-analysis. Surg Endosc. 2017 Jan. doi: 10.1007/s00464-016-4978-7.
20. Cao B, et al. Efficacy and safety of submucosal tunneling endoscopic resection for gastric submucosal tumors: a systematic review and meta-analysis. Rev Esp Enferm Dig. 2021 Jan. doi: 10.17235/reed.2020.6989/2020.
21. Cai M, et al. Endoscopic full-thickness resection (EFTR) for gastrointestinal subepithelial tumors. Gastrointest Endosc Clin N Am. 2016 Apr. doi: 10.1016/j.giec.2015.12.013.
22. Brigic A, et al. A systematic review regarding the feasibility and safety of endoscopic full thickness resection (EFTR) for colonic lesions. Surg Endosc. 2013 Oct. doi: 10.1007/s00464-013-2946-z.
Endoscopists are often faced with unique challenges in the management and resection of various gastrointestinal tract lesions. These challenges could be lesion-related, endoscopist-related, or practice-related (see Table 1). (ATR). Not only does this organ-sparing approach offer a less invasive alternative to surgery, but it has also proved to have outcomes comparable to those of surgical standard of practice in specific scenarios.
When Do You Refer to an Advanced Endoscopist?
One of the most critical steps in caring for patients with complex lesions is the ability to accurately determine whether a referral to an advanced endoscopist is warranted. The initial assessment of a lesion should always involve a careful assessment that risk stratifies the lesion depending on the location, size, neoplastic potential, and the feasibility of standard endoscopic resection compared to the need for surgical input.
A practical example in the case of colonic polyps is highlighted by the American Gastroenterology Association (AGA) guidelines recommending the referral of patients with polyps’ size ≥ 20 mm, challenging polypectomy location, or recurrent polyp at a prior polypectomy site to an endoscopic referral center.1 In the case of subepithelial lesions without endoscopic characteristics of benign etiology (i.e., lipomas, pancreatic rests, etc.), the threshold for referral to advanced endoscopists for further diagnostic testing by means of endoscopic ultrasonography or for therapeutic ATR should be lower.
Endoscopic tissue resection follows a spectrum, which often involves deeper layers of the gastrointestinal tract (GIT) as we progress along this spectrum (see Figure 1).
ATR, a term encompassing a variety of endoscopic techniques ranging from endoscopic mucosal resection to full thickness resection, has gained traction over the last years given the ability to effectively remove various lesions in a precise time and cost-effective manner while maintaining the integrity of the GIT and avoiding major surgery. The indications for ATR vary depending on the technique, but generally include the presence of large or poorly positioned lesions, particularly in high-risk areas of the GIT such as the esophagus and small intestine, lesions extending beyond the mucosal layer or originating from deeper layers, and when en bloc resection of select lesions is necessary.
For providers referring patients for ATR, we recommend a few important endoscopic pearls when caring for these patients.
1) Biopsy the lesion if there is concern for malignancy — While some studies have noted increased fibrosis during endoscopic submucosal dissection (ESD) and some guidelines recommend against biopsies pre ESD, we believe that when there is high pretest probability for malignancy, a biopsy should be obtained. This should involve the area that is most concerning for malignancy (at the margin or center).2
2) While marking a lesion with tattoo is helpful for surgical planning and for lesions difficult to locate endoscopically, we stress the importance of placing tattoos 3 to 5 centimeters distal to the lesion and avoiding tattooing the lesion itself, which has been shown to induce fibrosis and can make resection challenging. Based on an international Delphi consensus, expert recommendations on when and how to endoscopically tattoo a lesion can be instrumental in adequately localizing the lesion, allowing for endoscopic resection, and preventing unnecessary surgeries.3
3) If you encounter a lesion that you are not sure can be resected safely and efficaciously, we recommend against attempting resection that may result in partial resection. This can also induce fibrosis and scarring and limit future attempts at resection.
Endoscopic Mucosal Resection (EMR)
EMR is currently utilized for curative treatment of a wide array of GIT lesions limited to the mucosal layer, whether metaplastic, dysplastic, or even in cases with early mucosal cancer, where the risk of submucosal and lymphatic invasion is minimal.4 This makes EMR a versatile and proven therapy, often serving as the first-line treatment for many GIT lesions.
EMR has various techniques that could be categorized into suction or non-suction (lift and cut) techniques. In the suction technique, devices like multiband mucosectomy (MBM) are commonly used, especially in nodular Barrett’s dysplasia, forming a pseudopolyp for subsequent resection. The procedure is characterized by its safety, efficacy, and cost-effectiveness, contributing to its widespread adoption in clinical practice. In the lift and cut approach, a submucosal injection is utilized to separate the muscularis propria from the lesion, thereby reducing the risk of perforation. Different solutions, such as normal saline, hypertonic saline, 50% dextrose, or proprietary submucosal injection solutions, are employed for submucosal injection.5
The non-suction technique using a snare to resect polyps after injection is more often used in colonic and small intestinal EMR. Resection can be done via thermal energy in the form of cut or coagulation; however, there is rising data on the use of piecemeal cold snare resection for select flat polyps of the colon.6 There is also promising data on the role of underwater EMR, a common technique employed for colonic lesions, particularly if the lesion does not lift well with submucosal injection.7
Adverse events associated with EMR include bleeding (7%-8%) and perforation (0.9%-2%).8-9 Adequate submucosal fluid injection is crucial to prevent perforations. However, the main limitation of EMR is the piecemeal nature of resections for lesions larger than 20 mm, leading to compromised histopathologic evaluation for complete excision, especially in cases with superficial submucosal invasion (SMI). This can result in residual or recurrent tissue, reportedly 8% to 20%.10 Despite this limitation, EMR remains a reliable strategy, and recurrent lesions are generally manageable through repeat sessions. The importance of EMR as a therapeutic modality lies in its role in addressing lesions with favorable characteristics, where the risk of SMI is low.
Endoscopic Submucosal Dissection (ESD)
ESD is an evolving technique that can be utilized for submucosal lesions of the GIT, lesions not amenable to EMR due to submucosal fibrosis, when en bloc removal of a lesion is needed for accurate histopathological diagnosis, and when other techniques fail.11-12
ESD was only recently adopted in the United States, requires specialized training, and usually is a lengthier procedure than EMR.13 Compared to EMR, it has higher en bloc resection rates and lower recurrence rates, making it curative for lesions with superficial SMI and favorable histologic features.4,14 The safety profile of ESD appears favorable, with most of the adverse events managed successfully by endoscopic methods. Major complications include intraoperative and delayed perforation, intraoperative and delayed bleeding, aspiration pneumonia, thromboembolism, and stricture formation in the case of circumferential lesions.15
Despite being technically challenging, ESD may provide a cost-effective long-term solution by avoiding surgery, reducing the need for additional interventions by minimizing recurrence rates. Given the technical complexity of ESD, particularly the submucosal dissection portion, techniques such as hybrid ESD developed. Hybrid ESD combines snaring with circumferential mucosal incision and partial submucosal dissection. Although it promises shorter procedure times, reduced complication rates like perforation, and similar recurrence rates compared to traditional ESD, studies have shown lower success rates in en bloc resection.16-17
Both EMR and ESD are considered complementary strategies, and the choice between them should be dictated by lesion characteristics, patient preferences, and local expertise.
Submucosal Tunneling Endoscopic Resection (STER)
STER has emerged as a well-established technique for the endoscopic resection of GI subepithelial tumors (SETs) originating from the muscularis propria layer. The standard STER procedure involves a series of steps including submucosal elevation proximal to the SET, mucosotomy, creation of a submucosal tunnel, dissection of the SET within the tunnel, enucleation from the deep muscle layer, and subsequent specimen retrieval followed by mucosal closure.
This technique is typically recommended for SETs smaller than 3.5 cm, particularly those located in the mid or distal esophagus, cardia, or along the greater curvature of the gastric body.18 However, STER may pose technical challenges for larger SETs or lesions in anatomically difficult locations, where surgical resection is recommended instead.19 Notably, recent large-scale meta-analyses have showcased the favorable complete resection and en bloc resection rates of STER in treating GI SETs.20
Endoscopic Full Thickness Resection (EFTR)
EFTR has emerged as a valuable technique in the endoscopic management of gastrointestinal lesions, particularly SETs and lesions not amenable to EMR or ESD due to fibrosis. EFTR involves the resection of all layers of the GIT from mucosa to serosa, and therefore is well-suited for SETs arising from the muscularis propria (MP).20
EFTR entails two main concepts: tissue resection and complete defect closure. Conventional EFTR consists of several steps, which include mucosal and submucosal pre-cutting, circumferential incision, and dissection through the MP or serosa. This results in a full thickness defect, for which closure of the wall defect is achieved using standard endoscopic clips or a combination of clips and endoloops or endoscopic suturing.21 For lesions less than 2 cm, EFTR can be performed in a single step using a cap-mounted full thickness resection device (FTRD). This results in deployment of over-the-scope clip over the target lesion followed by snaring the lesions above the clip.21
Location of the SET generally dictates the specific modality of ATR. For example, esophageal SETs may be more amenable to STER given that the lesion typically runs parallel with the lumen of the tubular esophagus, which allows for easier dissection without the need of full or partial retroflexion. While gastric SETs can be resected with STER, it may be challenging and more effectively addressed with EFTR, particularly when the entire lesion can be grasped into the full-thickness resection device.22 Limited data exists for duodenal EFTR, and colorectal SETs closure is particularly challenging.
Conclusion
It is key to emphasize that ATR cannot be safely established in practice without the incorporation of a multidisciplinary team (surgeons, radiologists, etc.), specialized tools, and trained personnel. This requires dedicated endoscopic rooms, careful patient selection, and a comprehensive approach to patient care before, during, and after these procedures.
Moreover, it is important to note that some patients may require post-procedure hospitalization for observation to ensure no early complications are encountered. Optimal surveillance strategies after ATR rely heavily on the potential for residual or recurrent disease, underlying pathology, and the expertise of the advanced endoscopist. As the field continues to evolve, ongoing research and technological advances of devices will further enhance the efficacy and safety of ATR in gastroenterology.
Dr. Madi (@MahMadi90) is based in the Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, Saint Louis, Missouri. Dr. Rengarajan (@ArvindRenga) and Dr. Bazarbashi (@AhmadBazarbashi) are based in the Division of Gastroenterology, Washington University in St. Louis. The authors have no conflicts of interest to disclose, and no funding was required for this project.
References
1. Copland AP, et al. AGA Clinical Practice Update on appropriate and tailored polypectomy: Expert review. Clin Gastroenterol Hepatol. 2024 Mar. doi: 10.1016/j.cgh.2023.10.012.
2. Lee SP, et al. Effect of preceding biopsy on the results of endoscopic submucosal dissection for colorectal laterally spreading tumor. Dig Dis Sci. 2019 Oct. doi: 10.1007/s10620-019-05625-3.
3. Medina-Prado L, et al. When and how to use endoscopic tattooing in the colon: An international Delphi agreement. Clin Gastroenterol Hepatol. 2021 May. doi: 10.1016/j.cgh.2021.01.024.
4. Rashid MU, et al. EMR and ESD: Indications, techniques and results. Surg Oncol. 2022 Aug. doi: 10.1016/j.suronc.2022.101742.
5. Castro R, et al. Solutions for submucosal injection: What to choose and how to do it. World J Gastroenterol. 2019 Feb. doi: 10.3748/wjg.v25.i7.777.
6. Rex DK. Best practices for resection of diminutive and small polyps in the colorectum. Gastrointest Endosc Clin N Am. 2019 Oct. doi: 10.1016/j.giec.2019.06.004.
7. Lv XH, et al. Underwater EMR for nonpedunculated colorectal lesions. Gastrointest Endosc. 2023 Apr. doi: 10.1016/j.gie.2022.10.044.
8. Fujiya M, et al. Efficacy and adverse events of EMR and endoscopic submucosal dissection for the treatment of colon neoplasms: a meta-analysis of studies comparing EMR and endoscopic submucosal dissection. Gastrointest Endosc. 2015 Mar. doi: 10.1016/j.gie.2014.07.034.
9. Kandel P, Wallace MB. Colorectal endoscopic mucosal resection (EMR). Best Pract Res Clin Gastroenterol. 2017 Aug. doi: 10.1016/j.bpg.2017.05.006.
10. Kemper G, et al; ENDOCARE Study Group. Endoscopic techniques to reduce recurrence rates after colorectal EMR: systematic review and meta-analysis. Surg Endosc. 2021 Oct. doi: 10.1007/s00464-021-08574-z.
11. Goto O, et al. Expanding indications for ESD: submucosal disease (SMT/carcinoid tumors). Gastrointest Endosc Clin N Am. 2014 Apr. doi: 10.1016/j.giec.2013.11.006.
12. Wang K, et al. Endoscopic full-thickness resection, indication, methods and perspectives. Dig Endosc. 2023 Jan. doi: 10.1111/den.14474.
13. Herreros de Tejada A. ESD training: A challenging path to excellence. World J Gastrointest Endosc. 2014 Apr 16. doi: 10.4253/wjge.v6.i4.112.
14. Chiba H, et al. Safety and efficacy of simultaneous colorectal ESD for large synchronous colorectal lesions. Endosc Int Open. 2017 Jul. doi: 10.1055/s-0043-110567.
15. Mannath J, Ragunath K. Endoscopic mucosal resection: who and how? Therap Adv Gastroenterol. 2011 Sep. doi: 10.1177/1756283X10388683.
16. Wang XY, et al. Hybrid endoscopic submucosal dissection: An alternative resection modality for large laterally spreading tumors in the cecum? BMC Gastroenterol. 2021 May. doi: 10.1186/s12876-021-01766-w.
17. McCarty TR, et al. Hybrid endoscopic submucosal dissection (ESD) compared with conventional ESD for colorectal lesions: a systematic review and meta-analysis. Endoscopy. 2021 Oct. doi: 10.1055/a-1266-1855.
18. Jain D, et al. Submucosal tunneling endoscopic resection of upper gastrointestinal tract tumors arising from muscularis propria. Ann Gastroenterol. 2017 Feb. doi: 10.20524/aog.2017.0128.
19. Lv XH, et al. Efficacy and safety of submucosal tunneling endoscopic resection for upper gastrointestinal submucosal tumors: a systematic review and meta-analysis. Surg Endosc. 2017 Jan. doi: 10.1007/s00464-016-4978-7.
20. Cao B, et al. Efficacy and safety of submucosal tunneling endoscopic resection for gastric submucosal tumors: a systematic review and meta-analysis. Rev Esp Enferm Dig. 2021 Jan. doi: 10.17235/reed.2020.6989/2020.
21. Cai M, et al. Endoscopic full-thickness resection (EFTR) for gastrointestinal subepithelial tumors. Gastrointest Endosc Clin N Am. 2016 Apr. doi: 10.1016/j.giec.2015.12.013.
22. Brigic A, et al. A systematic review regarding the feasibility and safety of endoscopic full thickness resection (EFTR) for colonic lesions. Surg Endosc. 2013 Oct. doi: 10.1007/s00464-013-2946-z.
Endoscopists are often faced with unique challenges in the management and resection of various gastrointestinal tract lesions. These challenges could be lesion-related, endoscopist-related, or practice-related (see Table 1). (ATR). Not only does this organ-sparing approach offer a less invasive alternative to surgery, but it has also proved to have outcomes comparable to those of surgical standard of practice in specific scenarios.
When Do You Refer to an Advanced Endoscopist?
One of the most critical steps in caring for patients with complex lesions is the ability to accurately determine whether a referral to an advanced endoscopist is warranted. The initial assessment of a lesion should always involve a careful assessment that risk stratifies the lesion depending on the location, size, neoplastic potential, and the feasibility of standard endoscopic resection compared to the need for surgical input.
A practical example in the case of colonic polyps is highlighted by the American Gastroenterology Association (AGA) guidelines recommending the referral of patients with polyps’ size ≥ 20 mm, challenging polypectomy location, or recurrent polyp at a prior polypectomy site to an endoscopic referral center.1 In the case of subepithelial lesions without endoscopic characteristics of benign etiology (i.e., lipomas, pancreatic rests, etc.), the threshold for referral to advanced endoscopists for further diagnostic testing by means of endoscopic ultrasonography or for therapeutic ATR should be lower.
Endoscopic tissue resection follows a spectrum, which often involves deeper layers of the gastrointestinal tract (GIT) as we progress along this spectrum (see Figure 1).
ATR, a term encompassing a variety of endoscopic techniques ranging from endoscopic mucosal resection to full thickness resection, has gained traction over the last years given the ability to effectively remove various lesions in a precise time and cost-effective manner while maintaining the integrity of the GIT and avoiding major surgery. The indications for ATR vary depending on the technique, but generally include the presence of large or poorly positioned lesions, particularly in high-risk areas of the GIT such as the esophagus and small intestine, lesions extending beyond the mucosal layer or originating from deeper layers, and when en bloc resection of select lesions is necessary.
For providers referring patients for ATR, we recommend a few important endoscopic pearls when caring for these patients.
1) Biopsy the lesion if there is concern for malignancy — While some studies have noted increased fibrosis during endoscopic submucosal dissection (ESD) and some guidelines recommend against biopsies pre ESD, we believe that when there is high pretest probability for malignancy, a biopsy should be obtained. This should involve the area that is most concerning for malignancy (at the margin or center).2
2) While marking a lesion with tattoo is helpful for surgical planning and for lesions difficult to locate endoscopically, we stress the importance of placing tattoos 3 to 5 centimeters distal to the lesion and avoiding tattooing the lesion itself, which has been shown to induce fibrosis and can make resection challenging. Based on an international Delphi consensus, expert recommendations on when and how to endoscopically tattoo a lesion can be instrumental in adequately localizing the lesion, allowing for endoscopic resection, and preventing unnecessary surgeries.3
3) If you encounter a lesion that you are not sure can be resected safely and efficaciously, we recommend against attempting resection that may result in partial resection. This can also induce fibrosis and scarring and limit future attempts at resection.
Endoscopic Mucosal Resection (EMR)
EMR is currently utilized for curative treatment of a wide array of GIT lesions limited to the mucosal layer, whether metaplastic, dysplastic, or even in cases with early mucosal cancer, where the risk of submucosal and lymphatic invasion is minimal.4 This makes EMR a versatile and proven therapy, often serving as the first-line treatment for many GIT lesions.
EMR has various techniques that could be categorized into suction or non-suction (lift and cut) techniques. In the suction technique, devices like multiband mucosectomy (MBM) are commonly used, especially in nodular Barrett’s dysplasia, forming a pseudopolyp for subsequent resection. The procedure is characterized by its safety, efficacy, and cost-effectiveness, contributing to its widespread adoption in clinical practice. In the lift and cut approach, a submucosal injection is utilized to separate the muscularis propria from the lesion, thereby reducing the risk of perforation. Different solutions, such as normal saline, hypertonic saline, 50% dextrose, or proprietary submucosal injection solutions, are employed for submucosal injection.5
The non-suction technique using a snare to resect polyps after injection is more often used in colonic and small intestinal EMR. Resection can be done via thermal energy in the form of cut or coagulation; however, there is rising data on the use of piecemeal cold snare resection for select flat polyps of the colon.6 There is also promising data on the role of underwater EMR, a common technique employed for colonic lesions, particularly if the lesion does not lift well with submucosal injection.7
Adverse events associated with EMR include bleeding (7%-8%) and perforation (0.9%-2%).8-9 Adequate submucosal fluid injection is crucial to prevent perforations. However, the main limitation of EMR is the piecemeal nature of resections for lesions larger than 20 mm, leading to compromised histopathologic evaluation for complete excision, especially in cases with superficial submucosal invasion (SMI). This can result in residual or recurrent tissue, reportedly 8% to 20%.10 Despite this limitation, EMR remains a reliable strategy, and recurrent lesions are generally manageable through repeat sessions. The importance of EMR as a therapeutic modality lies in its role in addressing lesions with favorable characteristics, where the risk of SMI is low.
Endoscopic Submucosal Dissection (ESD)
ESD is an evolving technique that can be utilized for submucosal lesions of the GIT, lesions not amenable to EMR due to submucosal fibrosis, when en bloc removal of a lesion is needed for accurate histopathological diagnosis, and when other techniques fail.11-12
ESD was only recently adopted in the United States, requires specialized training, and usually is a lengthier procedure than EMR.13 Compared to EMR, it has higher en bloc resection rates and lower recurrence rates, making it curative for lesions with superficial SMI and favorable histologic features.4,14 The safety profile of ESD appears favorable, with most of the adverse events managed successfully by endoscopic methods. Major complications include intraoperative and delayed perforation, intraoperative and delayed bleeding, aspiration pneumonia, thromboembolism, and stricture formation in the case of circumferential lesions.15
Despite being technically challenging, ESD may provide a cost-effective long-term solution by avoiding surgery, reducing the need for additional interventions by minimizing recurrence rates. Given the technical complexity of ESD, particularly the submucosal dissection portion, techniques such as hybrid ESD developed. Hybrid ESD combines snaring with circumferential mucosal incision and partial submucosal dissection. Although it promises shorter procedure times, reduced complication rates like perforation, and similar recurrence rates compared to traditional ESD, studies have shown lower success rates in en bloc resection.16-17
Both EMR and ESD are considered complementary strategies, and the choice between them should be dictated by lesion characteristics, patient preferences, and local expertise.
Submucosal Tunneling Endoscopic Resection (STER)
STER has emerged as a well-established technique for the endoscopic resection of GI subepithelial tumors (SETs) originating from the muscularis propria layer. The standard STER procedure involves a series of steps including submucosal elevation proximal to the SET, mucosotomy, creation of a submucosal tunnel, dissection of the SET within the tunnel, enucleation from the deep muscle layer, and subsequent specimen retrieval followed by mucosal closure.
This technique is typically recommended for SETs smaller than 3.5 cm, particularly those located in the mid or distal esophagus, cardia, or along the greater curvature of the gastric body.18 However, STER may pose technical challenges for larger SETs or lesions in anatomically difficult locations, where surgical resection is recommended instead.19 Notably, recent large-scale meta-analyses have showcased the favorable complete resection and en bloc resection rates of STER in treating GI SETs.20
Endoscopic Full Thickness Resection (EFTR)
EFTR has emerged as a valuable technique in the endoscopic management of gastrointestinal lesions, particularly SETs and lesions not amenable to EMR or ESD due to fibrosis. EFTR involves the resection of all layers of the GIT from mucosa to serosa, and therefore is well-suited for SETs arising from the muscularis propria (MP).20
EFTR entails two main concepts: tissue resection and complete defect closure. Conventional EFTR consists of several steps, which include mucosal and submucosal pre-cutting, circumferential incision, and dissection through the MP or serosa. This results in a full thickness defect, for which closure of the wall defect is achieved using standard endoscopic clips or a combination of clips and endoloops or endoscopic suturing.21 For lesions less than 2 cm, EFTR can be performed in a single step using a cap-mounted full thickness resection device (FTRD). This results in deployment of over-the-scope clip over the target lesion followed by snaring the lesions above the clip.21
Location of the SET generally dictates the specific modality of ATR. For example, esophageal SETs may be more amenable to STER given that the lesion typically runs parallel with the lumen of the tubular esophagus, which allows for easier dissection without the need of full or partial retroflexion. While gastric SETs can be resected with STER, it may be challenging and more effectively addressed with EFTR, particularly when the entire lesion can be grasped into the full-thickness resection device.22 Limited data exists for duodenal EFTR, and colorectal SETs closure is particularly challenging.
Conclusion
It is key to emphasize that ATR cannot be safely established in practice without the incorporation of a multidisciplinary team (surgeons, radiologists, etc.), specialized tools, and trained personnel. This requires dedicated endoscopic rooms, careful patient selection, and a comprehensive approach to patient care before, during, and after these procedures.
Moreover, it is important to note that some patients may require post-procedure hospitalization for observation to ensure no early complications are encountered. Optimal surveillance strategies after ATR rely heavily on the potential for residual or recurrent disease, underlying pathology, and the expertise of the advanced endoscopist. As the field continues to evolve, ongoing research and technological advances of devices will further enhance the efficacy and safety of ATR in gastroenterology.
Dr. Madi (@MahMadi90) is based in the Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, Saint Louis, Missouri. Dr. Rengarajan (@ArvindRenga) and Dr. Bazarbashi (@AhmadBazarbashi) are based in the Division of Gastroenterology, Washington University in St. Louis. The authors have no conflicts of interest to disclose, and no funding was required for this project.
References
1. Copland AP, et al. AGA Clinical Practice Update on appropriate and tailored polypectomy: Expert review. Clin Gastroenterol Hepatol. 2024 Mar. doi: 10.1016/j.cgh.2023.10.012.
2. Lee SP, et al. Effect of preceding biopsy on the results of endoscopic submucosal dissection for colorectal laterally spreading tumor. Dig Dis Sci. 2019 Oct. doi: 10.1007/s10620-019-05625-3.
3. Medina-Prado L, et al. When and how to use endoscopic tattooing in the colon: An international Delphi agreement. Clin Gastroenterol Hepatol. 2021 May. doi: 10.1016/j.cgh.2021.01.024.
4. Rashid MU, et al. EMR and ESD: Indications, techniques and results. Surg Oncol. 2022 Aug. doi: 10.1016/j.suronc.2022.101742.
5. Castro R, et al. Solutions for submucosal injection: What to choose and how to do it. World J Gastroenterol. 2019 Feb. doi: 10.3748/wjg.v25.i7.777.
6. Rex DK. Best practices for resection of diminutive and small polyps in the colorectum. Gastrointest Endosc Clin N Am. 2019 Oct. doi: 10.1016/j.giec.2019.06.004.
7. Lv XH, et al. Underwater EMR for nonpedunculated colorectal lesions. Gastrointest Endosc. 2023 Apr. doi: 10.1016/j.gie.2022.10.044.
8. Fujiya M, et al. Efficacy and adverse events of EMR and endoscopic submucosal dissection for the treatment of colon neoplasms: a meta-analysis of studies comparing EMR and endoscopic submucosal dissection. Gastrointest Endosc. 2015 Mar. doi: 10.1016/j.gie.2014.07.034.
9. Kandel P, Wallace MB. Colorectal endoscopic mucosal resection (EMR). Best Pract Res Clin Gastroenterol. 2017 Aug. doi: 10.1016/j.bpg.2017.05.006.
10. Kemper G, et al; ENDOCARE Study Group. Endoscopic techniques to reduce recurrence rates after colorectal EMR: systematic review and meta-analysis. Surg Endosc. 2021 Oct. doi: 10.1007/s00464-021-08574-z.
11. Goto O, et al. Expanding indications for ESD: submucosal disease (SMT/carcinoid tumors). Gastrointest Endosc Clin N Am. 2014 Apr. doi: 10.1016/j.giec.2013.11.006.
12. Wang K, et al. Endoscopic full-thickness resection, indication, methods and perspectives. Dig Endosc. 2023 Jan. doi: 10.1111/den.14474.
13. Herreros de Tejada A. ESD training: A challenging path to excellence. World J Gastrointest Endosc. 2014 Apr 16. doi: 10.4253/wjge.v6.i4.112.
14. Chiba H, et al. Safety and efficacy of simultaneous colorectal ESD for large synchronous colorectal lesions. Endosc Int Open. 2017 Jul. doi: 10.1055/s-0043-110567.
15. Mannath J, Ragunath K. Endoscopic mucosal resection: who and how? Therap Adv Gastroenterol. 2011 Sep. doi: 10.1177/1756283X10388683.
16. Wang XY, et al. Hybrid endoscopic submucosal dissection: An alternative resection modality for large laterally spreading tumors in the cecum? BMC Gastroenterol. 2021 May. doi: 10.1186/s12876-021-01766-w.
17. McCarty TR, et al. Hybrid endoscopic submucosal dissection (ESD) compared with conventional ESD for colorectal lesions: a systematic review and meta-analysis. Endoscopy. 2021 Oct. doi: 10.1055/a-1266-1855.
18. Jain D, et al. Submucosal tunneling endoscopic resection of upper gastrointestinal tract tumors arising from muscularis propria. Ann Gastroenterol. 2017 Feb. doi: 10.20524/aog.2017.0128.
19. Lv XH, et al. Efficacy and safety of submucosal tunneling endoscopic resection for upper gastrointestinal submucosal tumors: a systematic review and meta-analysis. Surg Endosc. 2017 Jan. doi: 10.1007/s00464-016-4978-7.
20. Cao B, et al. Efficacy and safety of submucosal tunneling endoscopic resection for gastric submucosal tumors: a systematic review and meta-analysis. Rev Esp Enferm Dig. 2021 Jan. doi: 10.17235/reed.2020.6989/2020.
21. Cai M, et al. Endoscopic full-thickness resection (EFTR) for gastrointestinal subepithelial tumors. Gastrointest Endosc Clin N Am. 2016 Apr. doi: 10.1016/j.giec.2015.12.013.
22. Brigic A, et al. A systematic review regarding the feasibility and safety of endoscopic full thickness resection (EFTR) for colonic lesions. Surg Endosc. 2013 Oct. doi: 10.1007/s00464-013-2946-z.
A Simplified Approach to Pelvic Floor Dysfunction
Pelvic floor dysfunction (PFD) represents a spectrum of symptoms involving sensory and emptying abnormalities of the bowel and bladder and pelvic organ prolapse. The pelvic floor refers to a group of muscles that spans the pelvic outlet, providing support to the pelvic organs and coordinating constrictor mechanisms to control urination and defecation. Symptoms reported by patients experiencing PFD include involuntary loss of stool or urine, incomplete emptying of the bowel and bladder, a sensation of fullness, bulging in the vagina, and sexual dysfunction.1
As such, symptoms related to PFD are very common concerns raised by patients to their gastroenterologists. Data from the National Health and Nutrition Examination Survey show that 23.7% of women over the age of 20 had at least one symptom of PFD.2 Unfortunately, patients experiencing pelvic floor dysfunction often are hesitant to seek care because of embarrassment or perception that limited treatment options exist for their symptoms.
Pelvic Floor Anatomy
Regions of the pelvis are often referred to by anatomic compartment: anterior (bladder and urethra), middle (vagina and uterus or prostate), and posterior (colon, rectum, and anal canal). Supporting these compartments is the levator ani, a muscle group that is used synonymously with the term “pelvic diaphragm.”
Continence of stool is provided by the anal sphincter muscles and the puborectalis muscle, which wraps around the posterior aspect of the anorectal canal. Damage to the musculature or sensory perception to this area may result in fecal incontinence. Defecation is a coordinated process during which the abdominal and rectal muscles contract, while the anal sphincter muscles and puborectalis simultaneously relax. A disturbance in neuromuscular coordination (dyssynergic defecation) or structural pathology such as pelvic organ prolapse may lead to obstructed defecation.
PFD is thought to be a result of one or more insults to the pelvic floor such as chronic straining, childbirth, iatrogenic injury, or systemic disease such as diabetes.3
Evaluation of PFD Symptoms
Patients presenting with suspected PFD necessitate a comprehensive interdisciplinary assessment. In addition to obtaining a medical, surgical, and obstetric history, details about symptoms and lifestyle should include toileting habits, diet, and physical activity. The Pelvic Floor Distress Inventory (PFDI-20) is a commonly used tool that can be employed in the clinical setting.4
A pelvic exam can reveal pelvic organ prolapse and other mucosal pathology. The Pelvic Organ Prolapse Quantification System (POP-Q) is a widely used classification system for describing pelvic organ prolapse.5 Protrusion of the rectal wall into the vagina is referred to as a rectocele, while prolapse of small bowel into the upper posterior wall of the vagina is called an enterocele. While the finding of a rectocele on exam is common in parous women and may not cause any symptoms, a larger rectocele may cause a sensation of incomplete evacuation of stool.
A digital rectal exam (DRE) should be performed to assess pelvic floor function and help identify structural abnormalities.
Initial Management
A stepwise approach to the management of PFD can allow many patients to be effectively treated without the need for surgical intervention. For patients reporting liquid stool consistency, the evaluation should pivot toward the workup and management of diarrhea, which can easily overwhelm continence mechanisms and cause fecal incontinence. Fiber supplementation to normalize stool consistency is considered first-line therapy for patients presenting with both fecal incontinence and obstructed defecation. Other tools for fecal incontinence include avoiding foods that trigger diarrhea and use of loperamide.6 For patients with obstructed defecation, a trial of laxatives can be followed by a prescription agent if needed, such as a secretagogue or prokinetic.7
Vaginal splinting is a technique that can be used in patients with rectocele, whereby a finger is inserted into the vagina and pressure is applied on the posterior vaginal wall toward the rectum. Reducing the rectocele can facilitate emptying stool from the rectum and prevent leakage of retained stool.8 Similarly, use of rectal irrigation enemas can also help clear retained stool.
Pelvic floor physical therapists examine the strength, coordination, and tone of the pelvic floor muscles. When hypertonic musculature is present, manual interventions may be performed including trigger point release, myofascial release, and dry needling.9 When hypotonic musculature or dyssynergia is present, strengthening and neuromuscular re-education are recommended. Biofeedback can be administered via surface electromyography and/or balloon training to improve rectal sensitivity. Proper defecation techniques, including positioning, breathing, and behavioral modifications, improve clinical outcomes.
Diagnostic Testing
For patients who do not improve with conservative management, further testing is recommended to characterize the underlying pathology. Typically, anorectal manometry (ARM) is performed in conjunction with the balloon expulsion test and imaging. Each modality has its strengths and limitations (see Table 1).
ARM allows for the assessment of rectal sensation and recto-anal pressures and coordination.10
Dynamic imaging, by barium defecography under fluoroscopy or MRI, captures anatomy at rest and with simulated defecation to identify pelvic organ prolapse, compartmental defects, and organ mobility.11 Endoanal ultrasonography is considered in patients experiencing fecal incontinence to evaluate the integrity of the anal sphincter muscles.
Minimally Invasive Procedures and Surgical Options for PFD
Functional abnormalities such as dyssynergia often coexist with structural abnormalities. Because structural abnormalities are commonly found in asymptomatic patients, noninvasive functional therapy, such as pelvic floor physical therapy and anorectal biofeedback, are preferred prior to surgical repair of a structural finding. For patients with fecal incontinence, sacral nerve stimulation (SNS) has emerged as a preferred therapy due to demonstrated efficacy in symptom improvement.12 Sphincteroplasty is reserved for those with acute sphincter injury or failure of SNS.
In patients with findings of intussusception, prolapse, or rectocele that have not responded to conservative therapy, referral for surgical repair may be considered. While the specific surgical approach will depend on many factors, the goal is typically excision and/or suspension of rectal tissue and reinforcement of the rectovaginal septum.
It is critical that we are equipped with the available knowledge and tools to provide these patients with optimal care.
Dr. Khan, Dr. Menon, Dr. Allen, and Dr. Corning are based at the University of Texas Medical Branch in Galveston, Texas. They report no conflicts of interest.
References
1. Grimes WR and Stratton M. Pelvic floor dysfunction. 2023 Jun 26. In: StatPearls [Internet]. Treasure Island (Fla.): StatPearls Publishing; 2024 Jan. PMID: 32644672.
2. Nygaard I et al. Prevalence of symptomatic pelvic floor disorders in US women. JAMA. 2008 Sep 17. doi: 10.1001/jama.300.11.1311.
3. Lawrence JM et al. Pelvic floor disorders, diabetes, and obesity in women: Findings from the Kaiser Permanente Continence Associated Risk Epidemiology Study. Diabetes Care. 2007 Oct. doi: 10.2337/dc07-0262.
4. Barber MD et al. Short forms of two condition-specific quality-of-life questionnaires for women with pelvic floor disorders (PFDI-20 and PFIQ-7). Am J Obstet Gynecol. 2005 Jul. doi: 10.1016/j.ajog.2004.12.025.
5. Persu C et al. Pelvic Organ Prolapse Quantification System (POP-Q) — A new era in pelvic prolapse staging. J Med Life. 2011 Jan-Mar. PMID: 21505577.
6. Wald A et al. ACG Clinical Guidelines: Management of benign anorectal disorders. Am J Gastroenterol. 2021 Oct 1. doi: 10.14309/ajg.0000000000001507.
7. Bharucha AE and Lacy BE. Mechanisms, evaluation, and management of chronic constipation. Gastroenterology. 2020 Apr. doi: 10.1053/j.gastro.2019.12.034.
8. Menees S and Chey WD. Fecal incontinence: Pathogenesis, diagnosis, and updated treatment strategies. Gastroenterol Clin North Am. 2022 Mar. doi: 10.1016/j.gtc.2021.10.005.
9. Wallace SL et al. Pelvic floor physical therapy in the treatment of pelvic floor dysfunction in women. Curr Opin Obstet Gynecol. 2019 Dec. doi: 10.1097/GCO.0000000000000584.
10. Carrington EV et al. The international anorectal physiology working group (IAPWG) recommendations: Standardized testing protocol and the London classification for disorders of anorectal function. Neurogastroenterol Motil. 2020 Jan. doi: 10.1111/nmo.13679.
11. El Sayed RF et al. Magnetic resonance imaging of pelvic floor dysfunction — Joint recommendations of the ESUR and ESGAR Pelvic Floor Working Group. Eur Radiol. 2017 May. doi: 10.1007/s00330-016-4471-7.
12. Thaha MA et al. Sacral nerve stimulation for faecal incontinence and constipation in adults. Cochrane Database Syst Rev. 2015 Aug 24. doi: 10.1002/14651858.CD004464.pub3.
13. Chiarioni G et al. Biofeedback benefits only patients with outlet dysfunction, not patients with isolated slow transit constipation. Gastroenterology. 2005 Jul. doi: 10.1053/j.gastro.2005.05.015.
14. Grossi U et al. Diagnostic accuracy study of anorectal manometry for diagnosis of dyssynergic defecation. Gut. 2016 Mar. doi: 10.1136/gutjnl-2014-308835.
15. Albuquerque A. Endoanal ultrasonography in fecal incontinence: Current and future perspectives. World J Gastrointest Endosc. 2015 Jun 10. doi: 10.4253/wjge.v7.i6.575.
Pelvic floor dysfunction (PFD) represents a spectrum of symptoms involving sensory and emptying abnormalities of the bowel and bladder and pelvic organ prolapse. The pelvic floor refers to a group of muscles that spans the pelvic outlet, providing support to the pelvic organs and coordinating constrictor mechanisms to control urination and defecation. Symptoms reported by patients experiencing PFD include involuntary loss of stool or urine, incomplete emptying of the bowel and bladder, a sensation of fullness, bulging in the vagina, and sexual dysfunction.1
As such, symptoms related to PFD are very common concerns raised by patients to their gastroenterologists. Data from the National Health and Nutrition Examination Survey show that 23.7% of women over the age of 20 had at least one symptom of PFD.2 Unfortunately, patients experiencing pelvic floor dysfunction often are hesitant to seek care because of embarrassment or perception that limited treatment options exist for their symptoms.
Pelvic Floor Anatomy
Regions of the pelvis are often referred to by anatomic compartment: anterior (bladder and urethra), middle (vagina and uterus or prostate), and posterior (colon, rectum, and anal canal). Supporting these compartments is the levator ani, a muscle group that is used synonymously with the term “pelvic diaphragm.”
Continence of stool is provided by the anal sphincter muscles and the puborectalis muscle, which wraps around the posterior aspect of the anorectal canal. Damage to the musculature or sensory perception to this area may result in fecal incontinence. Defecation is a coordinated process during which the abdominal and rectal muscles contract, while the anal sphincter muscles and puborectalis simultaneously relax. A disturbance in neuromuscular coordination (dyssynergic defecation) or structural pathology such as pelvic organ prolapse may lead to obstructed defecation.
PFD is thought to be a result of one or more insults to the pelvic floor such as chronic straining, childbirth, iatrogenic injury, or systemic disease such as diabetes.3
Evaluation of PFD Symptoms
Patients presenting with suspected PFD necessitate a comprehensive interdisciplinary assessment. In addition to obtaining a medical, surgical, and obstetric history, details about symptoms and lifestyle should include toileting habits, diet, and physical activity. The Pelvic Floor Distress Inventory (PFDI-20) is a commonly used tool that can be employed in the clinical setting.4
A pelvic exam can reveal pelvic organ prolapse and other mucosal pathology. The Pelvic Organ Prolapse Quantification System (POP-Q) is a widely used classification system for describing pelvic organ prolapse.5 Protrusion of the rectal wall into the vagina is referred to as a rectocele, while prolapse of small bowel into the upper posterior wall of the vagina is called an enterocele. While the finding of a rectocele on exam is common in parous women and may not cause any symptoms, a larger rectocele may cause a sensation of incomplete evacuation of stool.
A digital rectal exam (DRE) should be performed to assess pelvic floor function and help identify structural abnormalities.
Initial Management
A stepwise approach to the management of PFD can allow many patients to be effectively treated without the need for surgical intervention. For patients reporting liquid stool consistency, the evaluation should pivot toward the workup and management of diarrhea, which can easily overwhelm continence mechanisms and cause fecal incontinence. Fiber supplementation to normalize stool consistency is considered first-line therapy for patients presenting with both fecal incontinence and obstructed defecation. Other tools for fecal incontinence include avoiding foods that trigger diarrhea and use of loperamide.6 For patients with obstructed defecation, a trial of laxatives can be followed by a prescription agent if needed, such as a secretagogue or prokinetic.7
Vaginal splinting is a technique that can be used in patients with rectocele, whereby a finger is inserted into the vagina and pressure is applied on the posterior vaginal wall toward the rectum. Reducing the rectocele can facilitate emptying stool from the rectum and prevent leakage of retained stool.8 Similarly, use of rectal irrigation enemas can also help clear retained stool.
Pelvic floor physical therapists examine the strength, coordination, and tone of the pelvic floor muscles. When hypertonic musculature is present, manual interventions may be performed including trigger point release, myofascial release, and dry needling.9 When hypotonic musculature or dyssynergia is present, strengthening and neuromuscular re-education are recommended. Biofeedback can be administered via surface electromyography and/or balloon training to improve rectal sensitivity. Proper defecation techniques, including positioning, breathing, and behavioral modifications, improve clinical outcomes.
Diagnostic Testing
For patients who do not improve with conservative management, further testing is recommended to characterize the underlying pathology. Typically, anorectal manometry (ARM) is performed in conjunction with the balloon expulsion test and imaging. Each modality has its strengths and limitations (see Table 1).
ARM allows for the assessment of rectal sensation and recto-anal pressures and coordination.10
Dynamic imaging, by barium defecography under fluoroscopy or MRI, captures anatomy at rest and with simulated defecation to identify pelvic organ prolapse, compartmental defects, and organ mobility.11 Endoanal ultrasonography is considered in patients experiencing fecal incontinence to evaluate the integrity of the anal sphincter muscles.
Minimally Invasive Procedures and Surgical Options for PFD
Functional abnormalities such as dyssynergia often coexist with structural abnormalities. Because structural abnormalities are commonly found in asymptomatic patients, noninvasive functional therapy, such as pelvic floor physical therapy and anorectal biofeedback, are preferred prior to surgical repair of a structural finding. For patients with fecal incontinence, sacral nerve stimulation (SNS) has emerged as a preferred therapy due to demonstrated efficacy in symptom improvement.12 Sphincteroplasty is reserved for those with acute sphincter injury or failure of SNS.
In patients with findings of intussusception, prolapse, or rectocele that have not responded to conservative therapy, referral for surgical repair may be considered. While the specific surgical approach will depend on many factors, the goal is typically excision and/or suspension of rectal tissue and reinforcement of the rectovaginal septum.
It is critical that we are equipped with the available knowledge and tools to provide these patients with optimal care.
Dr. Khan, Dr. Menon, Dr. Allen, and Dr. Corning are based at the University of Texas Medical Branch in Galveston, Texas. They report no conflicts of interest.
References
1. Grimes WR and Stratton M. Pelvic floor dysfunction. 2023 Jun 26. In: StatPearls [Internet]. Treasure Island (Fla.): StatPearls Publishing; 2024 Jan. PMID: 32644672.
2. Nygaard I et al. Prevalence of symptomatic pelvic floor disorders in US women. JAMA. 2008 Sep 17. doi: 10.1001/jama.300.11.1311.
3. Lawrence JM et al. Pelvic floor disorders, diabetes, and obesity in women: Findings from the Kaiser Permanente Continence Associated Risk Epidemiology Study. Diabetes Care. 2007 Oct. doi: 10.2337/dc07-0262.
4. Barber MD et al. Short forms of two condition-specific quality-of-life questionnaires for women with pelvic floor disorders (PFDI-20 and PFIQ-7). Am J Obstet Gynecol. 2005 Jul. doi: 10.1016/j.ajog.2004.12.025.
5. Persu C et al. Pelvic Organ Prolapse Quantification System (POP-Q) — A new era in pelvic prolapse staging. J Med Life. 2011 Jan-Mar. PMID: 21505577.
6. Wald A et al. ACG Clinical Guidelines: Management of benign anorectal disorders. Am J Gastroenterol. 2021 Oct 1. doi: 10.14309/ajg.0000000000001507.
7. Bharucha AE and Lacy BE. Mechanisms, evaluation, and management of chronic constipation. Gastroenterology. 2020 Apr. doi: 10.1053/j.gastro.2019.12.034.
8. Menees S and Chey WD. Fecal incontinence: Pathogenesis, diagnosis, and updated treatment strategies. Gastroenterol Clin North Am. 2022 Mar. doi: 10.1016/j.gtc.2021.10.005.
9. Wallace SL et al. Pelvic floor physical therapy in the treatment of pelvic floor dysfunction in women. Curr Opin Obstet Gynecol. 2019 Dec. doi: 10.1097/GCO.0000000000000584.
10. Carrington EV et al. The international anorectal physiology working group (IAPWG) recommendations: Standardized testing protocol and the London classification for disorders of anorectal function. Neurogastroenterol Motil. 2020 Jan. doi: 10.1111/nmo.13679.
11. El Sayed RF et al. Magnetic resonance imaging of pelvic floor dysfunction — Joint recommendations of the ESUR and ESGAR Pelvic Floor Working Group. Eur Radiol. 2017 May. doi: 10.1007/s00330-016-4471-7.
12. Thaha MA et al. Sacral nerve stimulation for faecal incontinence and constipation in adults. Cochrane Database Syst Rev. 2015 Aug 24. doi: 10.1002/14651858.CD004464.pub3.
13. Chiarioni G et al. Biofeedback benefits only patients with outlet dysfunction, not patients with isolated slow transit constipation. Gastroenterology. 2005 Jul. doi: 10.1053/j.gastro.2005.05.015.
14. Grossi U et al. Diagnostic accuracy study of anorectal manometry for diagnosis of dyssynergic defecation. Gut. 2016 Mar. doi: 10.1136/gutjnl-2014-308835.
15. Albuquerque A. Endoanal ultrasonography in fecal incontinence: Current and future perspectives. World J Gastrointest Endosc. 2015 Jun 10. doi: 10.4253/wjge.v7.i6.575.
Pelvic floor dysfunction (PFD) represents a spectrum of symptoms involving sensory and emptying abnormalities of the bowel and bladder and pelvic organ prolapse. The pelvic floor refers to a group of muscles that spans the pelvic outlet, providing support to the pelvic organs and coordinating constrictor mechanisms to control urination and defecation. Symptoms reported by patients experiencing PFD include involuntary loss of stool or urine, incomplete emptying of the bowel and bladder, a sensation of fullness, bulging in the vagina, and sexual dysfunction.1
As such, symptoms related to PFD are very common concerns raised by patients to their gastroenterologists. Data from the National Health and Nutrition Examination Survey show that 23.7% of women over the age of 20 had at least one symptom of PFD.2 Unfortunately, patients experiencing pelvic floor dysfunction often are hesitant to seek care because of embarrassment or perception that limited treatment options exist for their symptoms.
Pelvic Floor Anatomy
Regions of the pelvis are often referred to by anatomic compartment: anterior (bladder and urethra), middle (vagina and uterus or prostate), and posterior (colon, rectum, and anal canal). Supporting these compartments is the levator ani, a muscle group that is used synonymously with the term “pelvic diaphragm.”
Continence of stool is provided by the anal sphincter muscles and the puborectalis muscle, which wraps around the posterior aspect of the anorectal canal. Damage to the musculature or sensory perception to this area may result in fecal incontinence. Defecation is a coordinated process during which the abdominal and rectal muscles contract, while the anal sphincter muscles and puborectalis simultaneously relax. A disturbance in neuromuscular coordination (dyssynergic defecation) or structural pathology such as pelvic organ prolapse may lead to obstructed defecation.
PFD is thought to be a result of one or more insults to the pelvic floor such as chronic straining, childbirth, iatrogenic injury, or systemic disease such as diabetes.3
Evaluation of PFD Symptoms
Patients presenting with suspected PFD necessitate a comprehensive interdisciplinary assessment. In addition to obtaining a medical, surgical, and obstetric history, details about symptoms and lifestyle should include toileting habits, diet, and physical activity. The Pelvic Floor Distress Inventory (PFDI-20) is a commonly used tool that can be employed in the clinical setting.4
A pelvic exam can reveal pelvic organ prolapse and other mucosal pathology. The Pelvic Organ Prolapse Quantification System (POP-Q) is a widely used classification system for describing pelvic organ prolapse.5 Protrusion of the rectal wall into the vagina is referred to as a rectocele, while prolapse of small bowel into the upper posterior wall of the vagina is called an enterocele. While the finding of a rectocele on exam is common in parous women and may not cause any symptoms, a larger rectocele may cause a sensation of incomplete evacuation of stool.
A digital rectal exam (DRE) should be performed to assess pelvic floor function and help identify structural abnormalities.
Initial Management
A stepwise approach to the management of PFD can allow many patients to be effectively treated without the need for surgical intervention. For patients reporting liquid stool consistency, the evaluation should pivot toward the workup and management of diarrhea, which can easily overwhelm continence mechanisms and cause fecal incontinence. Fiber supplementation to normalize stool consistency is considered first-line therapy for patients presenting with both fecal incontinence and obstructed defecation. Other tools for fecal incontinence include avoiding foods that trigger diarrhea and use of loperamide.6 For patients with obstructed defecation, a trial of laxatives can be followed by a prescription agent if needed, such as a secretagogue or prokinetic.7
Vaginal splinting is a technique that can be used in patients with rectocele, whereby a finger is inserted into the vagina and pressure is applied on the posterior vaginal wall toward the rectum. Reducing the rectocele can facilitate emptying stool from the rectum and prevent leakage of retained stool.8 Similarly, use of rectal irrigation enemas can also help clear retained stool.
Pelvic floor physical therapists examine the strength, coordination, and tone of the pelvic floor muscles. When hypertonic musculature is present, manual interventions may be performed including trigger point release, myofascial release, and dry needling.9 When hypotonic musculature or dyssynergia is present, strengthening and neuromuscular re-education are recommended. Biofeedback can be administered via surface electromyography and/or balloon training to improve rectal sensitivity. Proper defecation techniques, including positioning, breathing, and behavioral modifications, improve clinical outcomes.
Diagnostic Testing
For patients who do not improve with conservative management, further testing is recommended to characterize the underlying pathology. Typically, anorectal manometry (ARM) is performed in conjunction with the balloon expulsion test and imaging. Each modality has its strengths and limitations (see Table 1).
ARM allows for the assessment of rectal sensation and recto-anal pressures and coordination.10
Dynamic imaging, by barium defecography under fluoroscopy or MRI, captures anatomy at rest and with simulated defecation to identify pelvic organ prolapse, compartmental defects, and organ mobility.11 Endoanal ultrasonography is considered in patients experiencing fecal incontinence to evaluate the integrity of the anal sphincter muscles.
Minimally Invasive Procedures and Surgical Options for PFD
Functional abnormalities such as dyssynergia often coexist with structural abnormalities. Because structural abnormalities are commonly found in asymptomatic patients, noninvasive functional therapy, such as pelvic floor physical therapy and anorectal biofeedback, are preferred prior to surgical repair of a structural finding. For patients with fecal incontinence, sacral nerve stimulation (SNS) has emerged as a preferred therapy due to demonstrated efficacy in symptom improvement.12 Sphincteroplasty is reserved for those with acute sphincter injury or failure of SNS.
In patients with findings of intussusception, prolapse, or rectocele that have not responded to conservative therapy, referral for surgical repair may be considered. While the specific surgical approach will depend on many factors, the goal is typically excision and/or suspension of rectal tissue and reinforcement of the rectovaginal septum.
It is critical that we are equipped with the available knowledge and tools to provide these patients with optimal care.
Dr. Khan, Dr. Menon, Dr. Allen, and Dr. Corning are based at the University of Texas Medical Branch in Galveston, Texas. They report no conflicts of interest.
References
1. Grimes WR and Stratton M. Pelvic floor dysfunction. 2023 Jun 26. In: StatPearls [Internet]. Treasure Island (Fla.): StatPearls Publishing; 2024 Jan. PMID: 32644672.
2. Nygaard I et al. Prevalence of symptomatic pelvic floor disorders in US women. JAMA. 2008 Sep 17. doi: 10.1001/jama.300.11.1311.
3. Lawrence JM et al. Pelvic floor disorders, diabetes, and obesity in women: Findings from the Kaiser Permanente Continence Associated Risk Epidemiology Study. Diabetes Care. 2007 Oct. doi: 10.2337/dc07-0262.
4. Barber MD et al. Short forms of two condition-specific quality-of-life questionnaires for women with pelvic floor disorders (PFDI-20 and PFIQ-7). Am J Obstet Gynecol. 2005 Jul. doi: 10.1016/j.ajog.2004.12.025.
5. Persu C et al. Pelvic Organ Prolapse Quantification System (POP-Q) — A new era in pelvic prolapse staging. J Med Life. 2011 Jan-Mar. PMID: 21505577.
6. Wald A et al. ACG Clinical Guidelines: Management of benign anorectal disorders. Am J Gastroenterol. 2021 Oct 1. doi: 10.14309/ajg.0000000000001507.
7. Bharucha AE and Lacy BE. Mechanisms, evaluation, and management of chronic constipation. Gastroenterology. 2020 Apr. doi: 10.1053/j.gastro.2019.12.034.
8. Menees S and Chey WD. Fecal incontinence: Pathogenesis, diagnosis, and updated treatment strategies. Gastroenterol Clin North Am. 2022 Mar. doi: 10.1016/j.gtc.2021.10.005.
9. Wallace SL et al. Pelvic floor physical therapy in the treatment of pelvic floor dysfunction in women. Curr Opin Obstet Gynecol. 2019 Dec. doi: 10.1097/GCO.0000000000000584.
10. Carrington EV et al. The international anorectal physiology working group (IAPWG) recommendations: Standardized testing protocol and the London classification for disorders of anorectal function. Neurogastroenterol Motil. 2020 Jan. doi: 10.1111/nmo.13679.
11. El Sayed RF et al. Magnetic resonance imaging of pelvic floor dysfunction — Joint recommendations of the ESUR and ESGAR Pelvic Floor Working Group. Eur Radiol. 2017 May. doi: 10.1007/s00330-016-4471-7.
12. Thaha MA et al. Sacral nerve stimulation for faecal incontinence and constipation in adults. Cochrane Database Syst Rev. 2015 Aug 24. doi: 10.1002/14651858.CD004464.pub3.
13. Chiarioni G et al. Biofeedback benefits only patients with outlet dysfunction, not patients with isolated slow transit constipation. Gastroenterology. 2005 Jul. doi: 10.1053/j.gastro.2005.05.015.
14. Grossi U et al. Diagnostic accuracy study of anorectal manometry for diagnosis of dyssynergic defecation. Gut. 2016 Mar. doi: 10.1136/gutjnl-2014-308835.
15. Albuquerque A. Endoanal ultrasonography in fecal incontinence: Current and future perspectives. World J Gastrointest Endosc. 2015 Jun 10. doi: 10.4253/wjge.v7.i6.575.
Caring for LGBTQ+ Patients with IBD
Cases
Patient 1: 55-year-old cis-male, who identifies as gay, has ulcerative colitis that has been refractory to multiple biologic therapies. His provider recommends a total proctocolectomy with ileal pouch anal anastomosis (TPC with IPAA), but the patient has questions regarding sexual function following surgery. Specifically, he is wondering when, or if, he can resume receptive anal intercourse. How would you counsel him?
Patient 2: 25-year-old, trans-female, status-post vaginoplasty with use of sigmoid colon and with well-controlled ulcerative colitis, presents with vaginal discharge, weight loss, and rectal bleeding. How do you explain what has happened to her? During your discussion, she also asks you why her chart continues to use her “dead name.” How do you respond?
Patient 3: 32-year-old, cis-female, G2P2, who identifies as a lesbian, has active ulcerative colitis. She wants to discuss medical or surgical therapy and future pregnancies. How would you counsel her?
Many gastroenterologists would likely know how to address patient 3’s concerns, but the concerns of patients 1 and 2 often go unaddressed or dismissed. Numerous studies and surveys have been conducted on patients with inflammatory bowel disease (IBD), but the focus of these studies has always been through a heteronormative cisgender lens. The focus of many studies is on fertility or sexual health and function in cisgender, heteronormative individuals.1-3 In the last few years, however, there has been increasing awareness of the health disparities, stigma, and discrimination that sexual and gender minorities (SGM) experience.4-6 For the purposes of this discussion, individuals within the lesbian, gay, bisexual, transgender, queer/questioning, intersex, and asexual (LGBTQIA+) community will be referred to as SGM. We recognize that even this exhaustive listing above does not acknowledge the full spectrum of diversity within the SGM community.
Clinical Care/Competency for SGM with IBD is Lacking
Almost 10% of the US population identifies as some form of SGM, and that number can be higher within the younger generations.4 SGM patients tend to delay or avoid seeking health care due to concern for provider mistreatment or lack of regard for their individual concerns. Additionally, there are several gaps in clinical knowledge about caring for SGM individuals. Little is known regarding the incidence or prevalence of IBD in SGM populations, but it is perceived to be similar to cisgender heterosexual individuals. Furthermore, as Newman et al. highlighted in their systematic review published in May 2023, there is a lack of guidance regarding sexual activity in the setting of IBD in SGM individuals.5 There is also a significant lack of knowledge on the impact of gender-affirming care on the natural history and treatments of IBD in transgender and gender non-conforming (TGNC) individuals. This can impact providers’ comfort and competence in caring for TGNC individuals.
Another important point to make is that the SGM community still faces discrimination due to sexual orientation or gender identity to this day, which impacts the quality and delivery of their care.7 Culturally-competent care should include care that is free from stigma, implicit and explicit biases, and discrimination. In 2011, an Institute of Medicine report documented, among other issues, provider discomfort in delivering care to SGM patients.8 While SGM individuals prefer a provider who acknowledges their sexual orientation and gender identity and treats them with the dignity and respect they deserve, many SGM individuals share valid concerns regarding their safety, which impact their desire to disclose their identity to health care providers.9 This certainly can have an impact on the quality of care they receive, including important health maintenance milestones and cancer screenings.10
An internal survey at our institution of providers (nurses, physician assistants, surgeons, and physicians) found that among 85 responders, 70% have cared for SGM who have undergone TPC with ileal pouch anal anastomosis (IPAA). Of these, 75% did not ask about sexual orientation or practices before pouch formation (though almost all of them agreed it would be important to ask). A total of 55% were comfortable in discussing SGM-related concerns; 53% did not feel comfortable discussing sexual orientation or practices; and in particular when it came to anoreceptive intercourse (ARI), 73% did not feel confident discussing recommendations.11
All of these issues highlight the importance of developing curricula that focus on reducing implicit and explicit biases towards SGM individuals and increasing the competence of providers to take care of SGM individuals in a safe space.
Additionally, it further justifies the need for ethical research that focuses on the needs of SGM individuals to guide evidence-based approaches to care. Given the implicit and explicit heterosexism and transphobia in society and many health care systems, Rainbows in Gastro was formed as an advocacy group for SGM patients, trainees, and staff in gastroenterology and hepatology.4
Research in SGM and IBD is lacking
There are additional needs for research in IBD and how it pertains to the needs of SGM individuals. Figure 1 highlights the lack of PubMed results for the search terms “IBD + LGBT,” “IBD + LGBTQ,” or “IBD + queer.” In contrast, the search terms “IBD + fertility” and “IBD + sexual dysfunction” generate many results. Even a systemic review conducted by Newman et al. of multiple databases in 2022 found only seven articles that demonstrated appropriately performed studies on SGM patients with IBD.5 This highlights the significant dearth of research in the realm of SGM health in IBD.
Newman and colleagues have recently published research considerations for SGM individuals. They highlighted the need to include understanding the “unique combination of psychosocial, biomedical, and legal experiences” that results in different needs and outcomes. There were several areas identified, including minority stress, which comes from existence of being SGM, especially as transgender individuals face increasing legal challenges in a variety of settings, not just healthcare.6 In a retrospective chart review investigating social determinants of health in SGM-IBD populations,12 36% of patients reported some level of social isolation, and almost 50% reported some level of stress. A total of 40% of them self-reported some perceived level of risk with respect to employment, and 17% reported depression. Given that this was a chart review and not a strict questionnaire, this study was certainly limited, and we would hypothesize that these numbers are therefore underestimating the true proportion of SGM-IBD patients who deal with employment concerns, social isolation, or psychological distress.
What Next? Back to the Patients
Circling back to our patients from the introduction, how would you counsel each of them? In patient 1’s case, we would inform him that pelvic surgery can increase the risk for sexual dysfunction, such as erectile dysfunction. He additionally would be advised during a staged TPC with IPAA, he may experience issues with body image. However, should he desire to participate in receptive anal intercourse after completion of his surgeries, the general recommendation would be to wait at least 6 months and with proven remission. It should further be noted that these are not formalized recommendations, only highlighting the need for more research and consensus on standards of care for SGM patients. He should finally be told that because he has ulcerative colitis, removal of the colon does not remove the risk for future intestinal involvement such as possible pouchitis.
In patient 2’s case, she is likely experiencing diversion vaginitis related to use of her colon for her neo-vagina. She should undergo colonoscopy and vaginoscopy in addition to standard work-up for her known ulcerative colitis.13 Management should be done in a multidisciplinary approach between the IBD provider, gynecologist, and gender-affirming provider. The electronic medical record should be updated to reflect the patient’s preferred name, pronouns, and gender identity, and her medical records, including automated clinical reports, should be updated accordingly.
As for patient 3, she would be counseled according to well-documented guidelines on pregnancy and IBD, including risks of medications (such as Jak inhibitors or methotrexate) versus the risk of uncontrolled IBD during pregnancy.1
Regardless of a patient’s gender identity or sexual orientation, patient-centered, culturally competent, and sensitive care should be provided. At Mayo Clinic in Rochester, we started one of the first Pride in IBD Clinics, which focuses on the care of SGM individuals with IBD. Our focus is to address the needs of patients who belong to the SGM community in a wholistic approach within a safe space (https://www.youtube.com/watch?v=pYa_zYaCA6M; https://www.mayoclinic.org/departments-centers/inflammatory-bowel-disease-clinic/overview/ovc-20357763). Our process of developing the clinic included training all staff on proper communication and cultural sensitivity for the SGM community.
Furthermore, providing welcoming and affirming signs of inclusivity for SGM individuals at the provider’s office — including but not limited to rainbow progressive flags, gender-neutral bathroom signs, or pronoun pins on provider identification badges (see Figure 2) — are usually appreciated by patients. Ensuring that patient education materials do not assume gender (for example, using the term “parents” rather than “mother and father”) and using gender neutral terms on intake forms is very important. Inclusive communication includes providers introducing themselves by preferred name and pronouns, asking the patients to introduce themselves, and welcoming them to share their pronouns. These simple actions can provide an atmosphere of safety for SGM patients, which would serve to enhance the quality of care we can provide for them.
For Resources and Further Reading: CDC,14 the Fenway Institute’s National LGBTQIA+ Health Education Center,15 and US Department of Health and Human Services.16
Dr. Chiang and Dr. Chedid are both in the Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. Dr. Chedid is also with the Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic. Neither of the authors have any relevant conflicts of interest. They are on X, formerly Twitter: @dr_davidchiang , @VictorChedidMD .
CITATIONS
1. Mahadevan U et al. Inflammatory bowel disease in pregnancy clinical care pathway: A report from the American Gastroenterological Association IBD Parenthood Project Working Group. Gastroenterology. 2019;156:1508-24.
2. Pires F et al. A survey on the impact of IBD in sexual health: Into intimacy. Medicine (Baltimore). 2022;101:e32279.
3. Mules TC et al. The impact of disease activity on sexual and erectile dysfunction in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2023;29:1244-54.
4. Duong N et al. Overcoming disparities for sexual and gender minority patients and providers in gastroenterology and hepatology: Introduction to Rainbows in Gastro. Lancet Gastroenterol Hepatol. 2023;8:299-301.
5. Newman KL et al. A systematic review of inflammatory bowel disease epidemiology and health outcomes in sexual and gender minority individuals. Gastroenterology. 2023;164:866-71.
6. Newman KL et al. Research considerations in Digestive and liver disease in transgender and gender-diverse populations. Gastroenterology. 2023;165:523-28 e1.
7. Velez C et al. Digestive health in sexual and gender minority populations. Am J Gastroenterol. 2022;117:865-75.
8. Medicine Io. Washington (DC): The National Academies Press, 2011.
9. Austin EL. Sexual orientation disclosure to health care providers among urban and non-urban southern lesbians. Women Health. 2013;53:41-55.
10. Oladeru OT et al. Breast and cervical cancer screening disparities in transgender people. Am J Clin Oncol. 2022;45:116-21.
11. Vinsard DG et al. Healthcare providers’ perspectives on anoreceptive intercourse in sexual and gender minorities with ileal pouch anal anastomosis. Digestive Disease Week (DDW). Chicago, IL, 2023.
12. Ghusn W et al. Social determinants of health in LGBTQIA+ patients with inflammatory bowel disease. American College of Gastroenterology (ACG). Charlotte, NC, 2022.
13. Grasman ME et al. Neovaginal sparing in a transgender woman with ulcerative colitis. Clin Gastroenterol Hepatol. 2016;14:e73-4.
14. Prevention CfDCa. Lesbian, Gay, Bisexual, and Transgender Health — https://www.cdc.gov/lgbthealth/index.htm.
15. Institute TF. National LGBTQIA+ Health Education Center — https://www.lgbtqiahealtheducation.org/.
16. Services UDoHaH. LGBTQI+ Resources — https://www.hhs.gov/programs/topic-sites/lgbtqi/resources/index.html.
Cases
Patient 1: 55-year-old cis-male, who identifies as gay, has ulcerative colitis that has been refractory to multiple biologic therapies. His provider recommends a total proctocolectomy with ileal pouch anal anastomosis (TPC with IPAA), but the patient has questions regarding sexual function following surgery. Specifically, he is wondering when, or if, he can resume receptive anal intercourse. How would you counsel him?
Patient 2: 25-year-old, trans-female, status-post vaginoplasty with use of sigmoid colon and with well-controlled ulcerative colitis, presents with vaginal discharge, weight loss, and rectal bleeding. How do you explain what has happened to her? During your discussion, she also asks you why her chart continues to use her “dead name.” How do you respond?
Patient 3: 32-year-old, cis-female, G2P2, who identifies as a lesbian, has active ulcerative colitis. She wants to discuss medical or surgical therapy and future pregnancies. How would you counsel her?
Many gastroenterologists would likely know how to address patient 3’s concerns, but the concerns of patients 1 and 2 often go unaddressed or dismissed. Numerous studies and surveys have been conducted on patients with inflammatory bowel disease (IBD), but the focus of these studies has always been through a heteronormative cisgender lens. The focus of many studies is on fertility or sexual health and function in cisgender, heteronormative individuals.1-3 In the last few years, however, there has been increasing awareness of the health disparities, stigma, and discrimination that sexual and gender minorities (SGM) experience.4-6 For the purposes of this discussion, individuals within the lesbian, gay, bisexual, transgender, queer/questioning, intersex, and asexual (LGBTQIA+) community will be referred to as SGM. We recognize that even this exhaustive listing above does not acknowledge the full spectrum of diversity within the SGM community.
Clinical Care/Competency for SGM with IBD is Lacking
Almost 10% of the US population identifies as some form of SGM, and that number can be higher within the younger generations.4 SGM patients tend to delay or avoid seeking health care due to concern for provider mistreatment or lack of regard for their individual concerns. Additionally, there are several gaps in clinical knowledge about caring for SGM individuals. Little is known regarding the incidence or prevalence of IBD in SGM populations, but it is perceived to be similar to cisgender heterosexual individuals. Furthermore, as Newman et al. highlighted in their systematic review published in May 2023, there is a lack of guidance regarding sexual activity in the setting of IBD in SGM individuals.5 There is also a significant lack of knowledge on the impact of gender-affirming care on the natural history and treatments of IBD in transgender and gender non-conforming (TGNC) individuals. This can impact providers’ comfort and competence in caring for TGNC individuals.
Another important point to make is that the SGM community still faces discrimination due to sexual orientation or gender identity to this day, which impacts the quality and delivery of their care.7 Culturally-competent care should include care that is free from stigma, implicit and explicit biases, and discrimination. In 2011, an Institute of Medicine report documented, among other issues, provider discomfort in delivering care to SGM patients.8 While SGM individuals prefer a provider who acknowledges their sexual orientation and gender identity and treats them with the dignity and respect they deserve, many SGM individuals share valid concerns regarding their safety, which impact their desire to disclose their identity to health care providers.9 This certainly can have an impact on the quality of care they receive, including important health maintenance milestones and cancer screenings.10
An internal survey at our institution of providers (nurses, physician assistants, surgeons, and physicians) found that among 85 responders, 70% have cared for SGM who have undergone TPC with ileal pouch anal anastomosis (IPAA). Of these, 75% did not ask about sexual orientation or practices before pouch formation (though almost all of them agreed it would be important to ask). A total of 55% were comfortable in discussing SGM-related concerns; 53% did not feel comfortable discussing sexual orientation or practices; and in particular when it came to anoreceptive intercourse (ARI), 73% did not feel confident discussing recommendations.11
All of these issues highlight the importance of developing curricula that focus on reducing implicit and explicit biases towards SGM individuals and increasing the competence of providers to take care of SGM individuals in a safe space.
Additionally, it further justifies the need for ethical research that focuses on the needs of SGM individuals to guide evidence-based approaches to care. Given the implicit and explicit heterosexism and transphobia in society and many health care systems, Rainbows in Gastro was formed as an advocacy group for SGM patients, trainees, and staff in gastroenterology and hepatology.4
Research in SGM and IBD is lacking
There are additional needs for research in IBD and how it pertains to the needs of SGM individuals. Figure 1 highlights the lack of PubMed results for the search terms “IBD + LGBT,” “IBD + LGBTQ,” or “IBD + queer.” In contrast, the search terms “IBD + fertility” and “IBD + sexual dysfunction” generate many results. Even a systemic review conducted by Newman et al. of multiple databases in 2022 found only seven articles that demonstrated appropriately performed studies on SGM patients with IBD.5 This highlights the significant dearth of research in the realm of SGM health in IBD.
Newman and colleagues have recently published research considerations for SGM individuals. They highlighted the need to include understanding the “unique combination of psychosocial, biomedical, and legal experiences” that results in different needs and outcomes. There were several areas identified, including minority stress, which comes from existence of being SGM, especially as transgender individuals face increasing legal challenges in a variety of settings, not just healthcare.6 In a retrospective chart review investigating social determinants of health in SGM-IBD populations,12 36% of patients reported some level of social isolation, and almost 50% reported some level of stress. A total of 40% of them self-reported some perceived level of risk with respect to employment, and 17% reported depression. Given that this was a chart review and not a strict questionnaire, this study was certainly limited, and we would hypothesize that these numbers are therefore underestimating the true proportion of SGM-IBD patients who deal with employment concerns, social isolation, or psychological distress.
What Next? Back to the Patients
Circling back to our patients from the introduction, how would you counsel each of them? In patient 1’s case, we would inform him that pelvic surgery can increase the risk for sexual dysfunction, such as erectile dysfunction. He additionally would be advised during a staged TPC with IPAA, he may experience issues with body image. However, should he desire to participate in receptive anal intercourse after completion of his surgeries, the general recommendation would be to wait at least 6 months and with proven remission. It should further be noted that these are not formalized recommendations, only highlighting the need for more research and consensus on standards of care for SGM patients. He should finally be told that because he has ulcerative colitis, removal of the colon does not remove the risk for future intestinal involvement such as possible pouchitis.
In patient 2’s case, she is likely experiencing diversion vaginitis related to use of her colon for her neo-vagina. She should undergo colonoscopy and vaginoscopy in addition to standard work-up for her known ulcerative colitis.13 Management should be done in a multidisciplinary approach between the IBD provider, gynecologist, and gender-affirming provider. The electronic medical record should be updated to reflect the patient’s preferred name, pronouns, and gender identity, and her medical records, including automated clinical reports, should be updated accordingly.
As for patient 3, she would be counseled according to well-documented guidelines on pregnancy and IBD, including risks of medications (such as Jak inhibitors or methotrexate) versus the risk of uncontrolled IBD during pregnancy.1
Regardless of a patient’s gender identity or sexual orientation, patient-centered, culturally competent, and sensitive care should be provided. At Mayo Clinic in Rochester, we started one of the first Pride in IBD Clinics, which focuses on the care of SGM individuals with IBD. Our focus is to address the needs of patients who belong to the SGM community in a wholistic approach within a safe space (https://www.youtube.com/watch?v=pYa_zYaCA6M; https://www.mayoclinic.org/departments-centers/inflammatory-bowel-disease-clinic/overview/ovc-20357763). Our process of developing the clinic included training all staff on proper communication and cultural sensitivity for the SGM community.
Furthermore, providing welcoming and affirming signs of inclusivity for SGM individuals at the provider’s office — including but not limited to rainbow progressive flags, gender-neutral bathroom signs, or pronoun pins on provider identification badges (see Figure 2) — are usually appreciated by patients. Ensuring that patient education materials do not assume gender (for example, using the term “parents” rather than “mother and father”) and using gender neutral terms on intake forms is very important. Inclusive communication includes providers introducing themselves by preferred name and pronouns, asking the patients to introduce themselves, and welcoming them to share their pronouns. These simple actions can provide an atmosphere of safety for SGM patients, which would serve to enhance the quality of care we can provide for them.
For Resources and Further Reading: CDC,14 the Fenway Institute’s National LGBTQIA+ Health Education Center,15 and US Department of Health and Human Services.16
Dr. Chiang and Dr. Chedid are both in the Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. Dr. Chedid is also with the Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic. Neither of the authors have any relevant conflicts of interest. They are on X, formerly Twitter: @dr_davidchiang , @VictorChedidMD .
CITATIONS
1. Mahadevan U et al. Inflammatory bowel disease in pregnancy clinical care pathway: A report from the American Gastroenterological Association IBD Parenthood Project Working Group. Gastroenterology. 2019;156:1508-24.
2. Pires F et al. A survey on the impact of IBD in sexual health: Into intimacy. Medicine (Baltimore). 2022;101:e32279.
3. Mules TC et al. The impact of disease activity on sexual and erectile dysfunction in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2023;29:1244-54.
4. Duong N et al. Overcoming disparities for sexual and gender minority patients and providers in gastroenterology and hepatology: Introduction to Rainbows in Gastro. Lancet Gastroenterol Hepatol. 2023;8:299-301.
5. Newman KL et al. A systematic review of inflammatory bowel disease epidemiology and health outcomes in sexual and gender minority individuals. Gastroenterology. 2023;164:866-71.
6. Newman KL et al. Research considerations in Digestive and liver disease in transgender and gender-diverse populations. Gastroenterology. 2023;165:523-28 e1.
7. Velez C et al. Digestive health in sexual and gender minority populations. Am J Gastroenterol. 2022;117:865-75.
8. Medicine Io. Washington (DC): The National Academies Press, 2011.
9. Austin EL. Sexual orientation disclosure to health care providers among urban and non-urban southern lesbians. Women Health. 2013;53:41-55.
10. Oladeru OT et al. Breast and cervical cancer screening disparities in transgender people. Am J Clin Oncol. 2022;45:116-21.
11. Vinsard DG et al. Healthcare providers’ perspectives on anoreceptive intercourse in sexual and gender minorities with ileal pouch anal anastomosis. Digestive Disease Week (DDW). Chicago, IL, 2023.
12. Ghusn W et al. Social determinants of health in LGBTQIA+ patients with inflammatory bowel disease. American College of Gastroenterology (ACG). Charlotte, NC, 2022.
13. Grasman ME et al. Neovaginal sparing in a transgender woman with ulcerative colitis. Clin Gastroenterol Hepatol. 2016;14:e73-4.
14. Prevention CfDCa. Lesbian, Gay, Bisexual, and Transgender Health — https://www.cdc.gov/lgbthealth/index.htm.
15. Institute TF. National LGBTQIA+ Health Education Center — https://www.lgbtqiahealtheducation.org/.
16. Services UDoHaH. LGBTQI+ Resources — https://www.hhs.gov/programs/topic-sites/lgbtqi/resources/index.html.
Cases
Patient 1: 55-year-old cis-male, who identifies as gay, has ulcerative colitis that has been refractory to multiple biologic therapies. His provider recommends a total proctocolectomy with ileal pouch anal anastomosis (TPC with IPAA), but the patient has questions regarding sexual function following surgery. Specifically, he is wondering when, or if, he can resume receptive anal intercourse. How would you counsel him?
Patient 2: 25-year-old, trans-female, status-post vaginoplasty with use of sigmoid colon and with well-controlled ulcerative colitis, presents with vaginal discharge, weight loss, and rectal bleeding. How do you explain what has happened to her? During your discussion, she also asks you why her chart continues to use her “dead name.” How do you respond?
Patient 3: 32-year-old, cis-female, G2P2, who identifies as a lesbian, has active ulcerative colitis. She wants to discuss medical or surgical therapy and future pregnancies. How would you counsel her?
Many gastroenterologists would likely know how to address patient 3’s concerns, but the concerns of patients 1 and 2 often go unaddressed or dismissed. Numerous studies and surveys have been conducted on patients with inflammatory bowel disease (IBD), but the focus of these studies has always been through a heteronormative cisgender lens. The focus of many studies is on fertility or sexual health and function in cisgender, heteronormative individuals.1-3 In the last few years, however, there has been increasing awareness of the health disparities, stigma, and discrimination that sexual and gender minorities (SGM) experience.4-6 For the purposes of this discussion, individuals within the lesbian, gay, bisexual, transgender, queer/questioning, intersex, and asexual (LGBTQIA+) community will be referred to as SGM. We recognize that even this exhaustive listing above does not acknowledge the full spectrum of diversity within the SGM community.
Clinical Care/Competency for SGM with IBD is Lacking
Almost 10% of the US population identifies as some form of SGM, and that number can be higher within the younger generations.4 SGM patients tend to delay or avoid seeking health care due to concern for provider mistreatment or lack of regard for their individual concerns. Additionally, there are several gaps in clinical knowledge about caring for SGM individuals. Little is known regarding the incidence or prevalence of IBD in SGM populations, but it is perceived to be similar to cisgender heterosexual individuals. Furthermore, as Newman et al. highlighted in their systematic review published in May 2023, there is a lack of guidance regarding sexual activity in the setting of IBD in SGM individuals.5 There is also a significant lack of knowledge on the impact of gender-affirming care on the natural history and treatments of IBD in transgender and gender non-conforming (TGNC) individuals. This can impact providers’ comfort and competence in caring for TGNC individuals.
Another important point to make is that the SGM community still faces discrimination due to sexual orientation or gender identity to this day, which impacts the quality and delivery of their care.7 Culturally-competent care should include care that is free from stigma, implicit and explicit biases, and discrimination. In 2011, an Institute of Medicine report documented, among other issues, provider discomfort in delivering care to SGM patients.8 While SGM individuals prefer a provider who acknowledges their sexual orientation and gender identity and treats them with the dignity and respect they deserve, many SGM individuals share valid concerns regarding their safety, which impact their desire to disclose their identity to health care providers.9 This certainly can have an impact on the quality of care they receive, including important health maintenance milestones and cancer screenings.10
An internal survey at our institution of providers (nurses, physician assistants, surgeons, and physicians) found that among 85 responders, 70% have cared for SGM who have undergone TPC with ileal pouch anal anastomosis (IPAA). Of these, 75% did not ask about sexual orientation or practices before pouch formation (though almost all of them agreed it would be important to ask). A total of 55% were comfortable in discussing SGM-related concerns; 53% did not feel comfortable discussing sexual orientation or practices; and in particular when it came to anoreceptive intercourse (ARI), 73% did not feel confident discussing recommendations.11
All of these issues highlight the importance of developing curricula that focus on reducing implicit and explicit biases towards SGM individuals and increasing the competence of providers to take care of SGM individuals in a safe space.
Additionally, it further justifies the need for ethical research that focuses on the needs of SGM individuals to guide evidence-based approaches to care. Given the implicit and explicit heterosexism and transphobia in society and many health care systems, Rainbows in Gastro was formed as an advocacy group for SGM patients, trainees, and staff in gastroenterology and hepatology.4
Research in SGM and IBD is lacking
There are additional needs for research in IBD and how it pertains to the needs of SGM individuals. Figure 1 highlights the lack of PubMed results for the search terms “IBD + LGBT,” “IBD + LGBTQ,” or “IBD + queer.” In contrast, the search terms “IBD + fertility” and “IBD + sexual dysfunction” generate many results. Even a systemic review conducted by Newman et al. of multiple databases in 2022 found only seven articles that demonstrated appropriately performed studies on SGM patients with IBD.5 This highlights the significant dearth of research in the realm of SGM health in IBD.
Newman and colleagues have recently published research considerations for SGM individuals. They highlighted the need to include understanding the “unique combination of psychosocial, biomedical, and legal experiences” that results in different needs and outcomes. There were several areas identified, including minority stress, which comes from existence of being SGM, especially as transgender individuals face increasing legal challenges in a variety of settings, not just healthcare.6 In a retrospective chart review investigating social determinants of health in SGM-IBD populations,12 36% of patients reported some level of social isolation, and almost 50% reported some level of stress. A total of 40% of them self-reported some perceived level of risk with respect to employment, and 17% reported depression. Given that this was a chart review and not a strict questionnaire, this study was certainly limited, and we would hypothesize that these numbers are therefore underestimating the true proportion of SGM-IBD patients who deal with employment concerns, social isolation, or psychological distress.
What Next? Back to the Patients
Circling back to our patients from the introduction, how would you counsel each of them? In patient 1’s case, we would inform him that pelvic surgery can increase the risk for sexual dysfunction, such as erectile dysfunction. He additionally would be advised during a staged TPC with IPAA, he may experience issues with body image. However, should he desire to participate in receptive anal intercourse after completion of his surgeries, the general recommendation would be to wait at least 6 months and with proven remission. It should further be noted that these are not formalized recommendations, only highlighting the need for more research and consensus on standards of care for SGM patients. He should finally be told that because he has ulcerative colitis, removal of the colon does not remove the risk for future intestinal involvement such as possible pouchitis.
In patient 2’s case, she is likely experiencing diversion vaginitis related to use of her colon for her neo-vagina. She should undergo colonoscopy and vaginoscopy in addition to standard work-up for her known ulcerative colitis.13 Management should be done in a multidisciplinary approach between the IBD provider, gynecologist, and gender-affirming provider. The electronic medical record should be updated to reflect the patient’s preferred name, pronouns, and gender identity, and her medical records, including automated clinical reports, should be updated accordingly.
As for patient 3, she would be counseled according to well-documented guidelines on pregnancy and IBD, including risks of medications (such as Jak inhibitors or methotrexate) versus the risk of uncontrolled IBD during pregnancy.1
Regardless of a patient’s gender identity or sexual orientation, patient-centered, culturally competent, and sensitive care should be provided. At Mayo Clinic in Rochester, we started one of the first Pride in IBD Clinics, which focuses on the care of SGM individuals with IBD. Our focus is to address the needs of patients who belong to the SGM community in a wholistic approach within a safe space (https://www.youtube.com/watch?v=pYa_zYaCA6M; https://www.mayoclinic.org/departments-centers/inflammatory-bowel-disease-clinic/overview/ovc-20357763). Our process of developing the clinic included training all staff on proper communication and cultural sensitivity for the SGM community.
Furthermore, providing welcoming and affirming signs of inclusivity for SGM individuals at the provider’s office — including but not limited to rainbow progressive flags, gender-neutral bathroom signs, or pronoun pins on provider identification badges (see Figure 2) — are usually appreciated by patients. Ensuring that patient education materials do not assume gender (for example, using the term “parents” rather than “mother and father”) and using gender neutral terms on intake forms is very important. Inclusive communication includes providers introducing themselves by preferred name and pronouns, asking the patients to introduce themselves, and welcoming them to share their pronouns. These simple actions can provide an atmosphere of safety for SGM patients, which would serve to enhance the quality of care we can provide for them.
For Resources and Further Reading: CDC,14 the Fenway Institute’s National LGBTQIA+ Health Education Center,15 and US Department of Health and Human Services.16
Dr. Chiang and Dr. Chedid are both in the Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. Dr. Chedid is also with the Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic. Neither of the authors have any relevant conflicts of interest. They are on X, formerly Twitter: @dr_davidchiang , @VictorChedidMD .
CITATIONS
1. Mahadevan U et al. Inflammatory bowel disease in pregnancy clinical care pathway: A report from the American Gastroenterological Association IBD Parenthood Project Working Group. Gastroenterology. 2019;156:1508-24.
2. Pires F et al. A survey on the impact of IBD in sexual health: Into intimacy. Medicine (Baltimore). 2022;101:e32279.
3. Mules TC et al. The impact of disease activity on sexual and erectile dysfunction in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2023;29:1244-54.
4. Duong N et al. Overcoming disparities for sexual and gender minority patients and providers in gastroenterology and hepatology: Introduction to Rainbows in Gastro. Lancet Gastroenterol Hepatol. 2023;8:299-301.
5. Newman KL et al. A systematic review of inflammatory bowel disease epidemiology and health outcomes in sexual and gender minority individuals. Gastroenterology. 2023;164:866-71.
6. Newman KL et al. Research considerations in Digestive and liver disease in transgender and gender-diverse populations. Gastroenterology. 2023;165:523-28 e1.
7. Velez C et al. Digestive health in sexual and gender minority populations. Am J Gastroenterol. 2022;117:865-75.
8. Medicine Io. Washington (DC): The National Academies Press, 2011.
9. Austin EL. Sexual orientation disclosure to health care providers among urban and non-urban southern lesbians. Women Health. 2013;53:41-55.
10. Oladeru OT et al. Breast and cervical cancer screening disparities in transgender people. Am J Clin Oncol. 2022;45:116-21.
11. Vinsard DG et al. Healthcare providers’ perspectives on anoreceptive intercourse in sexual and gender minorities with ileal pouch anal anastomosis. Digestive Disease Week (DDW). Chicago, IL, 2023.
12. Ghusn W et al. Social determinants of health in LGBTQIA+ patients with inflammatory bowel disease. American College of Gastroenterology (ACG). Charlotte, NC, 2022.
13. Grasman ME et al. Neovaginal sparing in a transgender woman with ulcerative colitis. Clin Gastroenterol Hepatol. 2016;14:e73-4.
14. Prevention CfDCa. Lesbian, Gay, Bisexual, and Transgender Health — https://www.cdc.gov/lgbthealth/index.htm.
15. Institute TF. National LGBTQIA+ Health Education Center — https://www.lgbtqiahealtheducation.org/.
16. Services UDoHaH. LGBTQI+ Resources — https://www.hhs.gov/programs/topic-sites/lgbtqi/resources/index.html.
Advances in endoscopic therapies in inflammatory bowel disease
Introduction
Inflammatory bowel disease (IBD) is a chronic, relapsing and remitting disorder that is becoming increasingly prevalent worldwide.1 Despite major advances in this area, many patients with moderate to severe IBD do not achieve disease remission with immunosuppressive therapy.2 Dysplasia and fibrostenosis are two common consequences of uncontrolled chronic inflammation and these structural complications are often the primary reasons for surgical interventions.3 While there is certainly a time and a place for surgery in IBD, this approach is invasive and postoperative recrudescence of disease is common.4 Moreover patients with complex surgical or medical histories may not make optimal surgical candidates.
Thanks to advancements in a variety of endoscopic technologies, Over the last several years, applications of endoscopic therapies in IBD have been gaining traction and the need for these therapies is expected to continue to rise over time. As such, understanding the domains of available endoscopic options in IBD is important for the modern-day gastroenterologist. In this article, we will discuss some of the recent advancements in endoscopic therapies for IBD and how we may position these in clinical practice.
Protecting against colitis dysplasia and colon cancer
IBD is a risk factor for colorectal cancer because of the dysplasia-carcinoma sequence arising from chronic colitis. Endoscopic resection is the first-line treatment for conventional colitis-associated dysplasia (CAD).5,6 However, larger or complex lesions may not have been previously amenable to this organ-preserving approach. The application of newer techniques has extended the indication for endoscopic resection to include most CAD lesions, as an alternative to proctocolectomy. Endoscopic mucosal resection (EMR) is the most commonly used technique and its outcomes for CAD greater than 2 cm have been excellent (Figure 1).7 However, employing EMR for lesions greater than 2 cm in size may require piecemeal resection and this has been associated with a small risk of local recurrence.8 Endoscopic submucosal dissection (ESD) is an alternate method of endoscopic tissue resection that can reliably achieve en bloc (single specimen) resections even in larger lesions.9
These technical advantages, however, have not been proven to result in broad clinical superiority of ESD over EMR for advanced lesions.10 The other consideration is that ESD is associated with greater risk of perforation and is more technically complex to perform.10 Yet, recent data supporting ESD in larger lesions is amounting and it may be more suitable for situations where conventional techniques fall short.11 To that end, dense submucosal fibrosis is a common characteristic of CAD and may prohibit successful EMR or ESD as a single modality. Different therapeutic methods can be incorporated in these circumstances, including combined ESD and EMR technique, tissue thermal ablation, or even full-thickness resection has been described.11-13
Taken together, we have many effective options for how we can effectively deal with CAD endoscopically and maintain our patients free of colorectal cancer. The method in which this is done may not matter as much at this juncture and may be more dependent on available local clinical expertise. Moreover, we can’t forget that metachronous lesions and neoplastic recurrence after endoscopic resection are not uncommon and a structured, vigilant endoscopic surveillance program for all patients undergoing endoscopic management of CAD is mandated.7,10
Restoring gastrointestinal tract transit
Crohn’s strictures may lead to acute intestinal obstructions or facilitate the onset of penetrating disease, such as fistula formation or abscess. These strictures are often characterized by a combination of inflammation and layered fibrosis, which requires the application of medical therapies alongside structural remodeling to successfully manage. Not all strictures may be clinically overt due to variances in visceral sensitivity, yet experts believe that treatment of all strictures should be considered to avoid occurrence of delayed complications.14 Endoscopic balloon dilation (EBD) is a well-established treatment for Crohn’s strictures up to 4-5 cm in length (Figure 2). This treatment involves inflating a balloon within the narrowed section of intestine, thereby stretching and disrupting the layered fibrotic bands to widen the stricture. EBD improves symptoms 70% of the time and successfully avoids the medium-term need for surgery in most, although it often requires repeat endoscopic procedures.15 In fact, up to 74% of patients will require repeat dilation over 2 years and 43% will require salvage surgery after EBD.16
Endoscopic stricturotomy (Est) is a newer technique that involves making radial and longitudinal incisions within the stricture using an endoscopic knife (Figure 2). The ability to excise fibrotic bands allows for more advanced remodeling and thus a lower need for reintervention or surgery (9%-22.5%) in comparison with EBD, while maintaining similar technical and clinical success rates.17 Est also carries a lower risk of perforation, but a higher risk of delayed bleeding.17 Refinements in Est are ongoing as the technique continues to develop, including the application of prophylactic clips after Est or use of other hemostatic agents such as gels or powders to minimizing bleeding risk. Despite this, Est has clear benefit in durability for treating strictures especially anastomotic subtype or those refractory to balloon dilation.
Stenting is a third option for treating strictures in Crohn’s disease that is reserved for specific situations. This approach involves endoscopic implantation of a covered metallic stent within the stricture in order to promote remodeling throughout a selected dwell time (generally 2-4 weeks). Stents may be considered in nonoperative candidates with strictures longer than 5 cm, which are generally too long for EBD or Est, or in EBD-refractory strictures in which there is no clear plane for Est excision. However, given the risk of migration, stents are currently not considered a first-line treatment of IBD-related strictures.18 Perhaps with further modifications in design and availability of stent-fixation methods, their use may become more practical in the future.19
The future for endoscopic therapy is bright
Structural complications of IBD are common and can pose a significant detriment to quality of life and general well-being for patients. From mucosal resection of CAD to surgery-sparing therapies for intestinal strictures, endoscopic therapies are valuable and effective options for managing disease-related sequelae within the scope of interventional IBD practice. We can expect the availability of these options to grow as the scope of endoscopy training incorporates principles of interventional IBD, along with the concurrent development of additional therapeutic applications beyond the categories discussed here (including perianal disease, fistulas, and abscess formation). It is noteworthy to mention that while endoscopic therapies are separate treatment modalities, should not be considered mutually exclusive; endotherapies are best viewed as a complement to existing medical and surgical approaches. Thus, Interventional IBD endoscopy can serve as an integral part of the multidisciplinary IBD framework to provide comprehensive care for our patients with IBD.
Juan Reyes Genere, MD, is an assistant professor of medicine in gastroenterology at Washington University in St. Louis. He served as the corresponding author of this article. Michael Rubeiz, MD, is a physician in the internal medicine residency program at Washington University in St. Louis. Kemmian Johnson, MD, MPH, is a gastroenterologist at Washington University in St. Louis specializing in inflammatory bowel disease. Dr. Genere is a consultant for Edulis Therapeutics. Dr. Rubeiz and Dr. Johnson had no personal or financial conflicts of interest. Dr. Johnson can be reached on Instagram @KJ.1906; Dr. Rubeiz is on X @MichaelRubeiz1 and Dr. Genere can be reached via X @JPGenereMD.
References
1. Ng SC et al. Lancet. 2017;390(10114):2769-78.
2. Gordon JP et al. Eur J Gastroenterol Hepatol. 2015;27(7):804-12.
3. Sica GS and Biancone L. World J Gastroenterol. 2013;19(16):2445-8.
4. Iborra M et al. Gastroenterol Rep (Oxf). 2019;7(6):411-8.
5. Annese V et al. J Crohns Colitis. 2013;7(12):982-1018.
6. Laine L et al. Gastrointest Endosc. 2015;81(3):489-501.e426.
7. Mohan BP et al. Gastrointest Endosc. 2021;93(1):59-67.e10.
8. Briedigkeit A et al. World J Gastrointest Endosc. 2016;8(5):276-81.
9. Manta R et al. J Crohns Colitis. 2021;15(1):165-8.
10. Mohapatra S et al. Endosc Int Open. 2022;10(5):E593-601.
11. Ngamruengphong S et al. Endosc Int Open. 2022;10(4):E354-60.
12. Baker G et al. Cureus. 2022 May 3;14(5):e24688.
13. Yadav S et al. Endosc Int Open. 2019;7(8):E994-1001.
14. Schwartz DA. Gastrointestinal Endoscopy. 2023;97(5):974-6.
15. Morar PS et al. Aliment Pharmacol Ther. 2015;42(10):1137-48.
16. Bettenworth D et al. Inflamm Bowel Dis. 2017;23(1):133-42.
17. Lan N and Shen B. Inflamm Bowel Dis. 2018;24(4):897-907.
18. Loras C et al. Lancet Gastroenterol Hepatol. 2022;7(4):332-41.
19. Genere JR et al. Lancet Gastroenterol Hepatol. 2022;7(6):503-4.
Introduction
Inflammatory bowel disease (IBD) is a chronic, relapsing and remitting disorder that is becoming increasingly prevalent worldwide.1 Despite major advances in this area, many patients with moderate to severe IBD do not achieve disease remission with immunosuppressive therapy.2 Dysplasia and fibrostenosis are two common consequences of uncontrolled chronic inflammation and these structural complications are often the primary reasons for surgical interventions.3 While there is certainly a time and a place for surgery in IBD, this approach is invasive and postoperative recrudescence of disease is common.4 Moreover patients with complex surgical or medical histories may not make optimal surgical candidates.
Thanks to advancements in a variety of endoscopic technologies, Over the last several years, applications of endoscopic therapies in IBD have been gaining traction and the need for these therapies is expected to continue to rise over time. As such, understanding the domains of available endoscopic options in IBD is important for the modern-day gastroenterologist. In this article, we will discuss some of the recent advancements in endoscopic therapies for IBD and how we may position these in clinical practice.
Protecting against colitis dysplasia and colon cancer
IBD is a risk factor for colorectal cancer because of the dysplasia-carcinoma sequence arising from chronic colitis. Endoscopic resection is the first-line treatment for conventional colitis-associated dysplasia (CAD).5,6 However, larger or complex lesions may not have been previously amenable to this organ-preserving approach. The application of newer techniques has extended the indication for endoscopic resection to include most CAD lesions, as an alternative to proctocolectomy. Endoscopic mucosal resection (EMR) is the most commonly used technique and its outcomes for CAD greater than 2 cm have been excellent (Figure 1).7 However, employing EMR for lesions greater than 2 cm in size may require piecemeal resection and this has been associated with a small risk of local recurrence.8 Endoscopic submucosal dissection (ESD) is an alternate method of endoscopic tissue resection that can reliably achieve en bloc (single specimen) resections even in larger lesions.9
These technical advantages, however, have not been proven to result in broad clinical superiority of ESD over EMR for advanced lesions.10 The other consideration is that ESD is associated with greater risk of perforation and is more technically complex to perform.10 Yet, recent data supporting ESD in larger lesions is amounting and it may be more suitable for situations where conventional techniques fall short.11 To that end, dense submucosal fibrosis is a common characteristic of CAD and may prohibit successful EMR or ESD as a single modality. Different therapeutic methods can be incorporated in these circumstances, including combined ESD and EMR technique, tissue thermal ablation, or even full-thickness resection has been described.11-13
Taken together, we have many effective options for how we can effectively deal with CAD endoscopically and maintain our patients free of colorectal cancer. The method in which this is done may not matter as much at this juncture and may be more dependent on available local clinical expertise. Moreover, we can’t forget that metachronous lesions and neoplastic recurrence after endoscopic resection are not uncommon and a structured, vigilant endoscopic surveillance program for all patients undergoing endoscopic management of CAD is mandated.7,10
Restoring gastrointestinal tract transit
Crohn’s strictures may lead to acute intestinal obstructions or facilitate the onset of penetrating disease, such as fistula formation or abscess. These strictures are often characterized by a combination of inflammation and layered fibrosis, which requires the application of medical therapies alongside structural remodeling to successfully manage. Not all strictures may be clinically overt due to variances in visceral sensitivity, yet experts believe that treatment of all strictures should be considered to avoid occurrence of delayed complications.14 Endoscopic balloon dilation (EBD) is a well-established treatment for Crohn’s strictures up to 4-5 cm in length (Figure 2). This treatment involves inflating a balloon within the narrowed section of intestine, thereby stretching and disrupting the layered fibrotic bands to widen the stricture. EBD improves symptoms 70% of the time and successfully avoids the medium-term need for surgery in most, although it often requires repeat endoscopic procedures.15 In fact, up to 74% of patients will require repeat dilation over 2 years and 43% will require salvage surgery after EBD.16
Endoscopic stricturotomy (Est) is a newer technique that involves making radial and longitudinal incisions within the stricture using an endoscopic knife (Figure 2). The ability to excise fibrotic bands allows for more advanced remodeling and thus a lower need for reintervention or surgery (9%-22.5%) in comparison with EBD, while maintaining similar technical and clinical success rates.17 Est also carries a lower risk of perforation, but a higher risk of delayed bleeding.17 Refinements in Est are ongoing as the technique continues to develop, including the application of prophylactic clips after Est or use of other hemostatic agents such as gels or powders to minimizing bleeding risk. Despite this, Est has clear benefit in durability for treating strictures especially anastomotic subtype or those refractory to balloon dilation.
Stenting is a third option for treating strictures in Crohn’s disease that is reserved for specific situations. This approach involves endoscopic implantation of a covered metallic stent within the stricture in order to promote remodeling throughout a selected dwell time (generally 2-4 weeks). Stents may be considered in nonoperative candidates with strictures longer than 5 cm, which are generally too long for EBD or Est, or in EBD-refractory strictures in which there is no clear plane for Est excision. However, given the risk of migration, stents are currently not considered a first-line treatment of IBD-related strictures.18 Perhaps with further modifications in design and availability of stent-fixation methods, their use may become more practical in the future.19
The future for endoscopic therapy is bright
Structural complications of IBD are common and can pose a significant detriment to quality of life and general well-being for patients. From mucosal resection of CAD to surgery-sparing therapies for intestinal strictures, endoscopic therapies are valuable and effective options for managing disease-related sequelae within the scope of interventional IBD practice. We can expect the availability of these options to grow as the scope of endoscopy training incorporates principles of interventional IBD, along with the concurrent development of additional therapeutic applications beyond the categories discussed here (including perianal disease, fistulas, and abscess formation). It is noteworthy to mention that while endoscopic therapies are separate treatment modalities, should not be considered mutually exclusive; endotherapies are best viewed as a complement to existing medical and surgical approaches. Thus, Interventional IBD endoscopy can serve as an integral part of the multidisciplinary IBD framework to provide comprehensive care for our patients with IBD.
Juan Reyes Genere, MD, is an assistant professor of medicine in gastroenterology at Washington University in St. Louis. He served as the corresponding author of this article. Michael Rubeiz, MD, is a physician in the internal medicine residency program at Washington University in St. Louis. Kemmian Johnson, MD, MPH, is a gastroenterologist at Washington University in St. Louis specializing in inflammatory bowel disease. Dr. Genere is a consultant for Edulis Therapeutics. Dr. Rubeiz and Dr. Johnson had no personal or financial conflicts of interest. Dr. Johnson can be reached on Instagram @KJ.1906; Dr. Rubeiz is on X @MichaelRubeiz1 and Dr. Genere can be reached via X @JPGenereMD.
References
1. Ng SC et al. Lancet. 2017;390(10114):2769-78.
2. Gordon JP et al. Eur J Gastroenterol Hepatol. 2015;27(7):804-12.
3. Sica GS and Biancone L. World J Gastroenterol. 2013;19(16):2445-8.
4. Iborra M et al. Gastroenterol Rep (Oxf). 2019;7(6):411-8.
5. Annese V et al. J Crohns Colitis. 2013;7(12):982-1018.
6. Laine L et al. Gastrointest Endosc. 2015;81(3):489-501.e426.
7. Mohan BP et al. Gastrointest Endosc. 2021;93(1):59-67.e10.
8. Briedigkeit A et al. World J Gastrointest Endosc. 2016;8(5):276-81.
9. Manta R et al. J Crohns Colitis. 2021;15(1):165-8.
10. Mohapatra S et al. Endosc Int Open. 2022;10(5):E593-601.
11. Ngamruengphong S et al. Endosc Int Open. 2022;10(4):E354-60.
12. Baker G et al. Cureus. 2022 May 3;14(5):e24688.
13. Yadav S et al. Endosc Int Open. 2019;7(8):E994-1001.
14. Schwartz DA. Gastrointestinal Endoscopy. 2023;97(5):974-6.
15. Morar PS et al. Aliment Pharmacol Ther. 2015;42(10):1137-48.
16. Bettenworth D et al. Inflamm Bowel Dis. 2017;23(1):133-42.
17. Lan N and Shen B. Inflamm Bowel Dis. 2018;24(4):897-907.
18. Loras C et al. Lancet Gastroenterol Hepatol. 2022;7(4):332-41.
19. Genere JR et al. Lancet Gastroenterol Hepatol. 2022;7(6):503-4.
Introduction
Inflammatory bowel disease (IBD) is a chronic, relapsing and remitting disorder that is becoming increasingly prevalent worldwide.1 Despite major advances in this area, many patients with moderate to severe IBD do not achieve disease remission with immunosuppressive therapy.2 Dysplasia and fibrostenosis are two common consequences of uncontrolled chronic inflammation and these structural complications are often the primary reasons for surgical interventions.3 While there is certainly a time and a place for surgery in IBD, this approach is invasive and postoperative recrudescence of disease is common.4 Moreover patients with complex surgical or medical histories may not make optimal surgical candidates.
Thanks to advancements in a variety of endoscopic technologies, Over the last several years, applications of endoscopic therapies in IBD have been gaining traction and the need for these therapies is expected to continue to rise over time. As such, understanding the domains of available endoscopic options in IBD is important for the modern-day gastroenterologist. In this article, we will discuss some of the recent advancements in endoscopic therapies for IBD and how we may position these in clinical practice.
Protecting against colitis dysplasia and colon cancer
IBD is a risk factor for colorectal cancer because of the dysplasia-carcinoma sequence arising from chronic colitis. Endoscopic resection is the first-line treatment for conventional colitis-associated dysplasia (CAD).5,6 However, larger or complex lesions may not have been previously amenable to this organ-preserving approach. The application of newer techniques has extended the indication for endoscopic resection to include most CAD lesions, as an alternative to proctocolectomy. Endoscopic mucosal resection (EMR) is the most commonly used technique and its outcomes for CAD greater than 2 cm have been excellent (Figure 1).7 However, employing EMR for lesions greater than 2 cm in size may require piecemeal resection and this has been associated with a small risk of local recurrence.8 Endoscopic submucosal dissection (ESD) is an alternate method of endoscopic tissue resection that can reliably achieve en bloc (single specimen) resections even in larger lesions.9
These technical advantages, however, have not been proven to result in broad clinical superiority of ESD over EMR for advanced lesions.10 The other consideration is that ESD is associated with greater risk of perforation and is more technically complex to perform.10 Yet, recent data supporting ESD in larger lesions is amounting and it may be more suitable for situations where conventional techniques fall short.11 To that end, dense submucosal fibrosis is a common characteristic of CAD and may prohibit successful EMR or ESD as a single modality. Different therapeutic methods can be incorporated in these circumstances, including combined ESD and EMR technique, tissue thermal ablation, or even full-thickness resection has been described.11-13
Taken together, we have many effective options for how we can effectively deal with CAD endoscopically and maintain our patients free of colorectal cancer. The method in which this is done may not matter as much at this juncture and may be more dependent on available local clinical expertise. Moreover, we can’t forget that metachronous lesions and neoplastic recurrence after endoscopic resection are not uncommon and a structured, vigilant endoscopic surveillance program for all patients undergoing endoscopic management of CAD is mandated.7,10
Restoring gastrointestinal tract transit
Crohn’s strictures may lead to acute intestinal obstructions or facilitate the onset of penetrating disease, such as fistula formation or abscess. These strictures are often characterized by a combination of inflammation and layered fibrosis, which requires the application of medical therapies alongside structural remodeling to successfully manage. Not all strictures may be clinically overt due to variances in visceral sensitivity, yet experts believe that treatment of all strictures should be considered to avoid occurrence of delayed complications.14 Endoscopic balloon dilation (EBD) is a well-established treatment for Crohn’s strictures up to 4-5 cm in length (Figure 2). This treatment involves inflating a balloon within the narrowed section of intestine, thereby stretching and disrupting the layered fibrotic bands to widen the stricture. EBD improves symptoms 70% of the time and successfully avoids the medium-term need for surgery in most, although it often requires repeat endoscopic procedures.15 In fact, up to 74% of patients will require repeat dilation over 2 years and 43% will require salvage surgery after EBD.16
Endoscopic stricturotomy (Est) is a newer technique that involves making radial and longitudinal incisions within the stricture using an endoscopic knife (Figure 2). The ability to excise fibrotic bands allows for more advanced remodeling and thus a lower need for reintervention or surgery (9%-22.5%) in comparison with EBD, while maintaining similar technical and clinical success rates.17 Est also carries a lower risk of perforation, but a higher risk of delayed bleeding.17 Refinements in Est are ongoing as the technique continues to develop, including the application of prophylactic clips after Est or use of other hemostatic agents such as gels or powders to minimizing bleeding risk. Despite this, Est has clear benefit in durability for treating strictures especially anastomotic subtype or those refractory to balloon dilation.
Stenting is a third option for treating strictures in Crohn’s disease that is reserved for specific situations. This approach involves endoscopic implantation of a covered metallic stent within the stricture in order to promote remodeling throughout a selected dwell time (generally 2-4 weeks). Stents may be considered in nonoperative candidates with strictures longer than 5 cm, which are generally too long for EBD or Est, or in EBD-refractory strictures in which there is no clear plane for Est excision. However, given the risk of migration, stents are currently not considered a first-line treatment of IBD-related strictures.18 Perhaps with further modifications in design and availability of stent-fixation methods, their use may become more practical in the future.19
The future for endoscopic therapy is bright
Structural complications of IBD are common and can pose a significant detriment to quality of life and general well-being for patients. From mucosal resection of CAD to surgery-sparing therapies for intestinal strictures, endoscopic therapies are valuable and effective options for managing disease-related sequelae within the scope of interventional IBD practice. We can expect the availability of these options to grow as the scope of endoscopy training incorporates principles of interventional IBD, along with the concurrent development of additional therapeutic applications beyond the categories discussed here (including perianal disease, fistulas, and abscess formation). It is noteworthy to mention that while endoscopic therapies are separate treatment modalities, should not be considered mutually exclusive; endotherapies are best viewed as a complement to existing medical and surgical approaches. Thus, Interventional IBD endoscopy can serve as an integral part of the multidisciplinary IBD framework to provide comprehensive care for our patients with IBD.
Juan Reyes Genere, MD, is an assistant professor of medicine in gastroenterology at Washington University in St. Louis. He served as the corresponding author of this article. Michael Rubeiz, MD, is a physician in the internal medicine residency program at Washington University in St. Louis. Kemmian Johnson, MD, MPH, is a gastroenterologist at Washington University in St. Louis specializing in inflammatory bowel disease. Dr. Genere is a consultant for Edulis Therapeutics. Dr. Rubeiz and Dr. Johnson had no personal or financial conflicts of interest. Dr. Johnson can be reached on Instagram @KJ.1906; Dr. Rubeiz is on X @MichaelRubeiz1 and Dr. Genere can be reached via X @JPGenereMD.
References
1. Ng SC et al. Lancet. 2017;390(10114):2769-78.
2. Gordon JP et al. Eur J Gastroenterol Hepatol. 2015;27(7):804-12.
3. Sica GS and Biancone L. World J Gastroenterol. 2013;19(16):2445-8.
4. Iborra M et al. Gastroenterol Rep (Oxf). 2019;7(6):411-8.
5. Annese V et al. J Crohns Colitis. 2013;7(12):982-1018.
6. Laine L et al. Gastrointest Endosc. 2015;81(3):489-501.e426.
7. Mohan BP et al. Gastrointest Endosc. 2021;93(1):59-67.e10.
8. Briedigkeit A et al. World J Gastrointest Endosc. 2016;8(5):276-81.
9. Manta R et al. J Crohns Colitis. 2021;15(1):165-8.
10. Mohapatra S et al. Endosc Int Open. 2022;10(5):E593-601.
11. Ngamruengphong S et al. Endosc Int Open. 2022;10(4):E354-60.
12. Baker G et al. Cureus. 2022 May 3;14(5):e24688.
13. Yadav S et al. Endosc Int Open. 2019;7(8):E994-1001.
14. Schwartz DA. Gastrointestinal Endoscopy. 2023;97(5):974-6.
15. Morar PS et al. Aliment Pharmacol Ther. 2015;42(10):1137-48.
16. Bettenworth D et al. Inflamm Bowel Dis. 2017;23(1):133-42.
17. Lan N and Shen B. Inflamm Bowel Dis. 2018;24(4):897-907.
18. Loras C et al. Lancet Gastroenterol Hepatol. 2022;7(4):332-41.
19. Genere JR et al. Lancet Gastroenterol Hepatol. 2022;7(6):503-4.
Advances in endohepatology
Introduction
Historically, the role of endoscopy in hepatology has been limited to intraluminal and bile duct interventions, primarily for the management of varices and biliary strictures. Recently, endoscopic ultrasound (EUS) has broadened the range of endoscopic treatment by enabling transluminal access to the liver parenchyma and associated vasculature. In this review, we will address recent advances in the expanding field of endohepatology.
Endoscopic-ultrasound guided liver biopsy
Liver biopsies are a critical tool in the diagnostic evaluation and management of patients with liver disease. Conventional approaches for obtaining liver tissue have been most commonly through the percutaneous or vascular approaches. In 2007, the first EUS-guided liver biopsy (EUS-LB) was described.1 EUS-LB is performed by advancing a line-array echoendoscope to the duodenal bulb to access the right lobe of the liver or proximal stomach to sample the left lobe. Doppler is first used to identify a pathway with few intervening vessels. Then a 19G or 20G needle is passed and slowly withdrawn to capture tissue (Figure 1). Careful evaluation with Doppler ultrasound to evaluate for bleeding is recommended after EUS-LB and if persistent, a small amount of clot may be reinjected as a blood or “Chang” patch akin to technique to control oozing postlumbar puncture.2
While large prospective studies are needed to compare the methods, it appears that specimen adequacy acquired via EUS-LB are comparable to percutaneous and transjugular approaches.3-5 Utilization of specific needle types and suction may optimize samples. Namely, 19G needles may provide better samples than smaller sizes and contemporary fine-needle biopsy needles with Franseen tips are superior to conventional spring-loaded cutting needles and fork tip needles.6-8 The use of dry suction has been shown to increase the yield of tissue, but at the expense of increased bloodiness. Wet suction, which involves the presence of fluid, rather than air, in the needle lumen to lubricate and improve transmission of negative pressure to the needle tip, is the preferred technique for EUS-LB given improvement in the likelihood of intact liver biopsy cores and increased specimen adequacy.9
There are several advantages to EUS-LB (Table 1). When compared with percutaneous liver biopsy (PC-LB) and transjugular liver biopsy (TJ-LB), EUS-LB is uniquely able to access both liver lobes in a single setting, which minimizes sampling error.3 EUS-LB may also have an advantage in sampling focal liver lesions given the close proximity of the transducer to the liver.10 Another advantage over PC-LB is that EUS-LB can be performed in patients with a large body habitus. Additionally, EUS-LB is better tolerated than PC-LB, with less postprocedure pain and shorter postprocedure monitoring time.4,5
Rates of adverse events appear to be similar between the three methods. Similar to PC-LB, EUS-LB requires capsular puncture, which can lead to intraperitoneal hemorrhage. Therefore, TJ-LB is preferred in patients with significant coagulopathy. While small ascites is not an absolute contraindication for EUS-LB, large ascites can obscure a safe window from the proximal stomach or duodenum to the liver, and thus TJLB is also preferred in these patients.11 Given its relative novelty and logistic challenges, other disadvantages of EUS-LB include limited provider availability and increased cost, especially compared with PC-LB. The most significant limitation is that it requires moderate or deep sedation, as opposed to local anesthetics. However, if there is another indication for endoscopy (that is, variceal screening), then “one-stop shop” procedures including EUS-LB may be more convenient and cost-effective than traditional methods. Nevertheless, rigorous comparative studies are needed.
EUS-guided portal pressure gradient measurement
The presence of clinically significant portal hypertension (CSPH), defined as hepatic venous pressure gradient (HVPG) greater than or equal to 10 is a potent predictor of decompensation. There is growing evidence to support the use of beta-blockers to mitigate this risk.12 Therefore, early identification of patients with CSPH has important diagnostic and therapeutic implications. The current gold standard for diagnosing CSPH is with wedged HVPG measurements performed by interventional radiology.
Since its introduction in 2016, EUS-guided portal pressure gradient measurement (EUS-PPG) has emerged as an alternative to wedged HVPG.13,14 Using a linear echoendoscope, the portal vein is directly accessed with a 25G fine-needle aspiration needle, and three direct measurements are taken using a compact manometer to determine the mean pressure. The hepatic vein, or less commonly the inferior vena cava, pressure is also measured. The direct measurement of portal pressure provides a significant advantage of EUS-PPG over HVPG in patients with presinusoidal and prehepatic portal hypertension. Wedged HVPG, which utilizes the difference between the wedged and free hepatic venous pressure to indirectly estimate the portal venous pressure gradient, yields erroneously low gradients in patients with noncirrhotic portal hypertension.15 An additional advantage of EUS-PPG is that it obviates the need for a central venous line placement, which is associated with thrombosis and, in rare cases, air embolus.16
Observational studies indicate that EUS-PPG has a high degree of consistency with HVPG measurements and a strong correlation between other clinical findings of portal hyper-tension including esophageal varices and thrombocytopenia.13,14 Nevertheless, EUS-PPG is performed under moderate or deep sedation which may impact HVPG measurements.17 In addition, the real-world application of EUS-PPG measurement on clinical care is undefined, but it is the topic of an ongoing clinical trial (ClinicalTrials.gov – NCT05357599).
EUS-guided interventions of gastric varices
Compared with esophageal varices, current approaches to the treatment and prophylaxis of gastric varices are more controversial.18 The most common approach to bleeding gastric varices in the United States is the placement of a transjugular intrahepatic portosystemic shunt (TIPS). Nevertheless, in addition to risks associated with central venous line placement, 5%-35% of individuals develop hepatic encephalopathy after TIPS and ischemic acute liver failure can occur in rare situations.19 Cyanoacrylate (CYA) glue injection is the recommended first-line endoscopic therapy for the treatment of bleeding gastric varices, but use has not been widely adopted in the United States because of a lack of an approved Food and Drug Administration CYA formulation, limited expertise, and risk of serious complications. In particular systemic embolization may result in pulmonary or cerebral infarct.12,18 EUS-guided interventions have been developed to mitigate these safety concerns. EUS-guided coil embolization can be performed, either alone or in combination with CYA injection.20 In the latter approach it acts as a scaffold to prevent migration of the glue bolus. Doppler assessment enables direct visualization of the gastric varix for identification of feeder vessels, more controlled deployment of hemostatic agents, and real-time confirmation of varix obliteration. Fluoroscopy can be used as an adjunct.
EUS-guided interventions in the management of gastric varices appear to be effective and superior to CYA injection under direct endoscopic visualization with improved likelihood of obliteration and lower rebleeding rates, without increase in adverse events.21 Additionally, EUS-guided combination therapy improves technical outcomes and reduces adverse events relative to EUS-guided coil or EUS-guided glue injection therapy alone.21-23 Nevertheless, large-scale prospective trials are needed to determine whether EUS-guided interventions should be considered over TIPS. The role of EUS-guided interventions as primary prophylaxis to prevent bleeding from large gastric varices also requires additional study.24
Future directions
with the goal of optimizing care and increasing efficiency. In addition to new endoscopic procedures to optimize liver biopsy, portal pressure measurement, and gastric variceal treatment, there are a number of emerging technologies including EUS-guided liver elastography, portal venous sampling, liver tumor chemoembolization, and intrahepatic portosystemic shunts.25 However, the practice of endohepatology faces a number of challenges before widespread adoption, including limited provider expertise and institutional availability. Additionally, more robust, multicenter outcomes and cost-effective analyses comparing these novel procedures with traditional approaches are needed to define their clinical impact.
Dr. Bui is a fellow in gastroenterology in the division of gastroenterology and hepatology, University of Southern California, Los Angeles. Dr. Buxbaum is associate professor of medicine (clinical scholar) in the division of gastroenterology and hepatology, University of Southern California. Dr. Buxbaum is a consultant for Cook Medical, Boston Scientific, and Olympus. Dr. Bui has no disclosures.
References
1. Mathew A. Am J Gastroenterol. 2007;102(10):2354-5.
2. Sowa P et al. VideoGIE. 2021;6(11):487-8.
3. Pineda JJ et al. Gastrointest Endosc. 2016;83(2):360-5.
4. Ali AH et al. J Ultrasound. 2020;23(2):157-67.
5. Shuja A et al. Dig Liver Dis. 2019;51(6):826-30.
6. Schulman AR et al. Gastrointest Endosc. 2017;85(2):419-26.
7. DeWitt J et al. Endosc Int Open. 2015;3(5):E471-8.
8. Aggarwal SN et al. Gastrointest Endosc. 2021;93(5):1133-8.
9. Mok SRS et al. Gastrointest Endosc. 2018;88(6):919-25.
10. Lee YN et al. J Gastroenterol Hepatol. 2015;30(7):1161-6.
11. Kalambokis G et al. J Hepatol. 2007;47(2):284-94.
12. de Franchis R et al. J Hepatol. 2022;76(4):959-74.
13. Choi AY et al. J Gastroenterol Hepatol. 2022;37(7):1373-9.
14. Zhang W et al. Gastrointest Endosc. 2021;93(3):565-72.
15. Seijo S et al. Dig Liver Dis. 2012;44(10):855-60.
16. Vesely TM. J Vasc Interv Radiol. 2001;12(11):1291-5.
17. Reverter E et al. Liver Int. 2014;34(1):16-25.
18. Henry Z et al. Clin Gastroenterol Hepatol. 2021;19(6):1098-107.e1091.
19. Ripamonti R et al. Semin Intervent Radiol. 2006;23(2):165-76.
20. Rengstorff DS and Binmoeller KF. Gastrointest Endosc. 2004;59(4):553-8.
21. Mohan BP et al. Endoscopy. 2020;52(4):259-67.
22. Robles-Medranda C et al. Endoscopy. 2020;52(4):268-75.
23. McCarty TR et al. Endosc Ultrasound. 2020;9(1):6-15.
24. Kouanda A et al. Gastrointest Endosc. 2021;94(2):291-6.
25. Bazarbashi AN et al. 2022;24(1):98-107.
Introduction
Historically, the role of endoscopy in hepatology has been limited to intraluminal and bile duct interventions, primarily for the management of varices and biliary strictures. Recently, endoscopic ultrasound (EUS) has broadened the range of endoscopic treatment by enabling transluminal access to the liver parenchyma and associated vasculature. In this review, we will address recent advances in the expanding field of endohepatology.
Endoscopic-ultrasound guided liver biopsy
Liver biopsies are a critical tool in the diagnostic evaluation and management of patients with liver disease. Conventional approaches for obtaining liver tissue have been most commonly through the percutaneous or vascular approaches. In 2007, the first EUS-guided liver biopsy (EUS-LB) was described.1 EUS-LB is performed by advancing a line-array echoendoscope to the duodenal bulb to access the right lobe of the liver or proximal stomach to sample the left lobe. Doppler is first used to identify a pathway with few intervening vessels. Then a 19G or 20G needle is passed and slowly withdrawn to capture tissue (Figure 1). Careful evaluation with Doppler ultrasound to evaluate for bleeding is recommended after EUS-LB and if persistent, a small amount of clot may be reinjected as a blood or “Chang” patch akin to technique to control oozing postlumbar puncture.2
While large prospective studies are needed to compare the methods, it appears that specimen adequacy acquired via EUS-LB are comparable to percutaneous and transjugular approaches.3-5 Utilization of specific needle types and suction may optimize samples. Namely, 19G needles may provide better samples than smaller sizes and contemporary fine-needle biopsy needles with Franseen tips are superior to conventional spring-loaded cutting needles and fork tip needles.6-8 The use of dry suction has been shown to increase the yield of tissue, but at the expense of increased bloodiness. Wet suction, which involves the presence of fluid, rather than air, in the needle lumen to lubricate and improve transmission of negative pressure to the needle tip, is the preferred technique for EUS-LB given improvement in the likelihood of intact liver biopsy cores and increased specimen adequacy.9
There are several advantages to EUS-LB (Table 1). When compared with percutaneous liver biopsy (PC-LB) and transjugular liver biopsy (TJ-LB), EUS-LB is uniquely able to access both liver lobes in a single setting, which minimizes sampling error.3 EUS-LB may also have an advantage in sampling focal liver lesions given the close proximity of the transducer to the liver.10 Another advantage over PC-LB is that EUS-LB can be performed in patients with a large body habitus. Additionally, EUS-LB is better tolerated than PC-LB, with less postprocedure pain and shorter postprocedure monitoring time.4,5
Rates of adverse events appear to be similar between the three methods. Similar to PC-LB, EUS-LB requires capsular puncture, which can lead to intraperitoneal hemorrhage. Therefore, TJ-LB is preferred in patients with significant coagulopathy. While small ascites is not an absolute contraindication for EUS-LB, large ascites can obscure a safe window from the proximal stomach or duodenum to the liver, and thus TJLB is also preferred in these patients.11 Given its relative novelty and logistic challenges, other disadvantages of EUS-LB include limited provider availability and increased cost, especially compared with PC-LB. The most significant limitation is that it requires moderate or deep sedation, as opposed to local anesthetics. However, if there is another indication for endoscopy (that is, variceal screening), then “one-stop shop” procedures including EUS-LB may be more convenient and cost-effective than traditional methods. Nevertheless, rigorous comparative studies are needed.
EUS-guided portal pressure gradient measurement
The presence of clinically significant portal hypertension (CSPH), defined as hepatic venous pressure gradient (HVPG) greater than or equal to 10 is a potent predictor of decompensation. There is growing evidence to support the use of beta-blockers to mitigate this risk.12 Therefore, early identification of patients with CSPH has important diagnostic and therapeutic implications. The current gold standard for diagnosing CSPH is with wedged HVPG measurements performed by interventional radiology.
Since its introduction in 2016, EUS-guided portal pressure gradient measurement (EUS-PPG) has emerged as an alternative to wedged HVPG.13,14 Using a linear echoendoscope, the portal vein is directly accessed with a 25G fine-needle aspiration needle, and three direct measurements are taken using a compact manometer to determine the mean pressure. The hepatic vein, or less commonly the inferior vena cava, pressure is also measured. The direct measurement of portal pressure provides a significant advantage of EUS-PPG over HVPG in patients with presinusoidal and prehepatic portal hypertension. Wedged HVPG, which utilizes the difference between the wedged and free hepatic venous pressure to indirectly estimate the portal venous pressure gradient, yields erroneously low gradients in patients with noncirrhotic portal hypertension.15 An additional advantage of EUS-PPG is that it obviates the need for a central venous line placement, which is associated with thrombosis and, in rare cases, air embolus.16
Observational studies indicate that EUS-PPG has a high degree of consistency with HVPG measurements and a strong correlation between other clinical findings of portal hyper-tension including esophageal varices and thrombocytopenia.13,14 Nevertheless, EUS-PPG is performed under moderate or deep sedation which may impact HVPG measurements.17 In addition, the real-world application of EUS-PPG measurement on clinical care is undefined, but it is the topic of an ongoing clinical trial (ClinicalTrials.gov – NCT05357599).
EUS-guided interventions of gastric varices
Compared with esophageal varices, current approaches to the treatment and prophylaxis of gastric varices are more controversial.18 The most common approach to bleeding gastric varices in the United States is the placement of a transjugular intrahepatic portosystemic shunt (TIPS). Nevertheless, in addition to risks associated with central venous line placement, 5%-35% of individuals develop hepatic encephalopathy after TIPS and ischemic acute liver failure can occur in rare situations.19 Cyanoacrylate (CYA) glue injection is the recommended first-line endoscopic therapy for the treatment of bleeding gastric varices, but use has not been widely adopted in the United States because of a lack of an approved Food and Drug Administration CYA formulation, limited expertise, and risk of serious complications. In particular systemic embolization may result in pulmonary or cerebral infarct.12,18 EUS-guided interventions have been developed to mitigate these safety concerns. EUS-guided coil embolization can be performed, either alone or in combination with CYA injection.20 In the latter approach it acts as a scaffold to prevent migration of the glue bolus. Doppler assessment enables direct visualization of the gastric varix for identification of feeder vessels, more controlled deployment of hemostatic agents, and real-time confirmation of varix obliteration. Fluoroscopy can be used as an adjunct.
EUS-guided interventions in the management of gastric varices appear to be effective and superior to CYA injection under direct endoscopic visualization with improved likelihood of obliteration and lower rebleeding rates, without increase in adverse events.21 Additionally, EUS-guided combination therapy improves technical outcomes and reduces adverse events relative to EUS-guided coil or EUS-guided glue injection therapy alone.21-23 Nevertheless, large-scale prospective trials are needed to determine whether EUS-guided interventions should be considered over TIPS. The role of EUS-guided interventions as primary prophylaxis to prevent bleeding from large gastric varices also requires additional study.24
Future directions
with the goal of optimizing care and increasing efficiency. In addition to new endoscopic procedures to optimize liver biopsy, portal pressure measurement, and gastric variceal treatment, there are a number of emerging technologies including EUS-guided liver elastography, portal venous sampling, liver tumor chemoembolization, and intrahepatic portosystemic shunts.25 However, the practice of endohepatology faces a number of challenges before widespread adoption, including limited provider expertise and institutional availability. Additionally, more robust, multicenter outcomes and cost-effective analyses comparing these novel procedures with traditional approaches are needed to define their clinical impact.
Dr. Bui is a fellow in gastroenterology in the division of gastroenterology and hepatology, University of Southern California, Los Angeles. Dr. Buxbaum is associate professor of medicine (clinical scholar) in the division of gastroenterology and hepatology, University of Southern California. Dr. Buxbaum is a consultant for Cook Medical, Boston Scientific, and Olympus. Dr. Bui has no disclosures.
References
1. Mathew A. Am J Gastroenterol. 2007;102(10):2354-5.
2. Sowa P et al. VideoGIE. 2021;6(11):487-8.
3. Pineda JJ et al. Gastrointest Endosc. 2016;83(2):360-5.
4. Ali AH et al. J Ultrasound. 2020;23(2):157-67.
5. Shuja A et al. Dig Liver Dis. 2019;51(6):826-30.
6. Schulman AR et al. Gastrointest Endosc. 2017;85(2):419-26.
7. DeWitt J et al. Endosc Int Open. 2015;3(5):E471-8.
8. Aggarwal SN et al. Gastrointest Endosc. 2021;93(5):1133-8.
9. Mok SRS et al. Gastrointest Endosc. 2018;88(6):919-25.
10. Lee YN et al. J Gastroenterol Hepatol. 2015;30(7):1161-6.
11. Kalambokis G et al. J Hepatol. 2007;47(2):284-94.
12. de Franchis R et al. J Hepatol. 2022;76(4):959-74.
13. Choi AY et al. J Gastroenterol Hepatol. 2022;37(7):1373-9.
14. Zhang W et al. Gastrointest Endosc. 2021;93(3):565-72.
15. Seijo S et al. Dig Liver Dis. 2012;44(10):855-60.
16. Vesely TM. J Vasc Interv Radiol. 2001;12(11):1291-5.
17. Reverter E et al. Liver Int. 2014;34(1):16-25.
18. Henry Z et al. Clin Gastroenterol Hepatol. 2021;19(6):1098-107.e1091.
19. Ripamonti R et al. Semin Intervent Radiol. 2006;23(2):165-76.
20. Rengstorff DS and Binmoeller KF. Gastrointest Endosc. 2004;59(4):553-8.
21. Mohan BP et al. Endoscopy. 2020;52(4):259-67.
22. Robles-Medranda C et al. Endoscopy. 2020;52(4):268-75.
23. McCarty TR et al. Endosc Ultrasound. 2020;9(1):6-15.
24. Kouanda A et al. Gastrointest Endosc. 2021;94(2):291-6.
25. Bazarbashi AN et al. 2022;24(1):98-107.
Introduction
Historically, the role of endoscopy in hepatology has been limited to intraluminal and bile duct interventions, primarily for the management of varices and biliary strictures. Recently, endoscopic ultrasound (EUS) has broadened the range of endoscopic treatment by enabling transluminal access to the liver parenchyma and associated vasculature. In this review, we will address recent advances in the expanding field of endohepatology.
Endoscopic-ultrasound guided liver biopsy
Liver biopsies are a critical tool in the diagnostic evaluation and management of patients with liver disease. Conventional approaches for obtaining liver tissue have been most commonly through the percutaneous or vascular approaches. In 2007, the first EUS-guided liver biopsy (EUS-LB) was described.1 EUS-LB is performed by advancing a line-array echoendoscope to the duodenal bulb to access the right lobe of the liver or proximal stomach to sample the left lobe. Doppler is first used to identify a pathway with few intervening vessels. Then a 19G or 20G needle is passed and slowly withdrawn to capture tissue (Figure 1). Careful evaluation with Doppler ultrasound to evaluate for bleeding is recommended after EUS-LB and if persistent, a small amount of clot may be reinjected as a blood or “Chang” patch akin to technique to control oozing postlumbar puncture.2
While large prospective studies are needed to compare the methods, it appears that specimen adequacy acquired via EUS-LB are comparable to percutaneous and transjugular approaches.3-5 Utilization of specific needle types and suction may optimize samples. Namely, 19G needles may provide better samples than smaller sizes and contemporary fine-needle biopsy needles with Franseen tips are superior to conventional spring-loaded cutting needles and fork tip needles.6-8 The use of dry suction has been shown to increase the yield of tissue, but at the expense of increased bloodiness. Wet suction, which involves the presence of fluid, rather than air, in the needle lumen to lubricate and improve transmission of negative pressure to the needle tip, is the preferred technique for EUS-LB given improvement in the likelihood of intact liver biopsy cores and increased specimen adequacy.9
There are several advantages to EUS-LB (Table 1). When compared with percutaneous liver biopsy (PC-LB) and transjugular liver biopsy (TJ-LB), EUS-LB is uniquely able to access both liver lobes in a single setting, which minimizes sampling error.3 EUS-LB may also have an advantage in sampling focal liver lesions given the close proximity of the transducer to the liver.10 Another advantage over PC-LB is that EUS-LB can be performed in patients with a large body habitus. Additionally, EUS-LB is better tolerated than PC-LB, with less postprocedure pain and shorter postprocedure monitoring time.4,5
Rates of adverse events appear to be similar between the three methods. Similar to PC-LB, EUS-LB requires capsular puncture, which can lead to intraperitoneal hemorrhage. Therefore, TJ-LB is preferred in patients with significant coagulopathy. While small ascites is not an absolute contraindication for EUS-LB, large ascites can obscure a safe window from the proximal stomach or duodenum to the liver, and thus TJLB is also preferred in these patients.11 Given its relative novelty and logistic challenges, other disadvantages of EUS-LB include limited provider availability and increased cost, especially compared with PC-LB. The most significant limitation is that it requires moderate or deep sedation, as opposed to local anesthetics. However, if there is another indication for endoscopy (that is, variceal screening), then “one-stop shop” procedures including EUS-LB may be more convenient and cost-effective than traditional methods. Nevertheless, rigorous comparative studies are needed.
EUS-guided portal pressure gradient measurement
The presence of clinically significant portal hypertension (CSPH), defined as hepatic venous pressure gradient (HVPG) greater than or equal to 10 is a potent predictor of decompensation. There is growing evidence to support the use of beta-blockers to mitigate this risk.12 Therefore, early identification of patients with CSPH has important diagnostic and therapeutic implications. The current gold standard for diagnosing CSPH is with wedged HVPG measurements performed by interventional radiology.
Since its introduction in 2016, EUS-guided portal pressure gradient measurement (EUS-PPG) has emerged as an alternative to wedged HVPG.13,14 Using a linear echoendoscope, the portal vein is directly accessed with a 25G fine-needle aspiration needle, and three direct measurements are taken using a compact manometer to determine the mean pressure. The hepatic vein, or less commonly the inferior vena cava, pressure is also measured. The direct measurement of portal pressure provides a significant advantage of EUS-PPG over HVPG in patients with presinusoidal and prehepatic portal hypertension. Wedged HVPG, which utilizes the difference between the wedged and free hepatic venous pressure to indirectly estimate the portal venous pressure gradient, yields erroneously low gradients in patients with noncirrhotic portal hypertension.15 An additional advantage of EUS-PPG is that it obviates the need for a central venous line placement, which is associated with thrombosis and, in rare cases, air embolus.16
Observational studies indicate that EUS-PPG has a high degree of consistency with HVPG measurements and a strong correlation between other clinical findings of portal hyper-tension including esophageal varices and thrombocytopenia.13,14 Nevertheless, EUS-PPG is performed under moderate or deep sedation which may impact HVPG measurements.17 In addition, the real-world application of EUS-PPG measurement on clinical care is undefined, but it is the topic of an ongoing clinical trial (ClinicalTrials.gov – NCT05357599).
EUS-guided interventions of gastric varices
Compared with esophageal varices, current approaches to the treatment and prophylaxis of gastric varices are more controversial.18 The most common approach to bleeding gastric varices in the United States is the placement of a transjugular intrahepatic portosystemic shunt (TIPS). Nevertheless, in addition to risks associated with central venous line placement, 5%-35% of individuals develop hepatic encephalopathy after TIPS and ischemic acute liver failure can occur in rare situations.19 Cyanoacrylate (CYA) glue injection is the recommended first-line endoscopic therapy for the treatment of bleeding gastric varices, but use has not been widely adopted in the United States because of a lack of an approved Food and Drug Administration CYA formulation, limited expertise, and risk of serious complications. In particular systemic embolization may result in pulmonary or cerebral infarct.12,18 EUS-guided interventions have been developed to mitigate these safety concerns. EUS-guided coil embolization can be performed, either alone or in combination with CYA injection.20 In the latter approach it acts as a scaffold to prevent migration of the glue bolus. Doppler assessment enables direct visualization of the gastric varix for identification of feeder vessels, more controlled deployment of hemostatic agents, and real-time confirmation of varix obliteration. Fluoroscopy can be used as an adjunct.
EUS-guided interventions in the management of gastric varices appear to be effective and superior to CYA injection under direct endoscopic visualization with improved likelihood of obliteration and lower rebleeding rates, without increase in adverse events.21 Additionally, EUS-guided combination therapy improves technical outcomes and reduces adverse events relative to EUS-guided coil or EUS-guided glue injection therapy alone.21-23 Nevertheless, large-scale prospective trials are needed to determine whether EUS-guided interventions should be considered over TIPS. The role of EUS-guided interventions as primary prophylaxis to prevent bleeding from large gastric varices also requires additional study.24
Future directions
with the goal of optimizing care and increasing efficiency. In addition to new endoscopic procedures to optimize liver biopsy, portal pressure measurement, and gastric variceal treatment, there are a number of emerging technologies including EUS-guided liver elastography, portal venous sampling, liver tumor chemoembolization, and intrahepatic portosystemic shunts.25 However, the practice of endohepatology faces a number of challenges before widespread adoption, including limited provider expertise and institutional availability. Additionally, more robust, multicenter outcomes and cost-effective analyses comparing these novel procedures with traditional approaches are needed to define their clinical impact.
Dr. Bui is a fellow in gastroenterology in the division of gastroenterology and hepatology, University of Southern California, Los Angeles. Dr. Buxbaum is associate professor of medicine (clinical scholar) in the division of gastroenterology and hepatology, University of Southern California. Dr. Buxbaum is a consultant for Cook Medical, Boston Scientific, and Olympus. Dr. Bui has no disclosures.
References
1. Mathew A. Am J Gastroenterol. 2007;102(10):2354-5.
2. Sowa P et al. VideoGIE. 2021;6(11):487-8.
3. Pineda JJ et al. Gastrointest Endosc. 2016;83(2):360-5.
4. Ali AH et al. J Ultrasound. 2020;23(2):157-67.
5. Shuja A et al. Dig Liver Dis. 2019;51(6):826-30.
6. Schulman AR et al. Gastrointest Endosc. 2017;85(2):419-26.
7. DeWitt J et al. Endosc Int Open. 2015;3(5):E471-8.
8. Aggarwal SN et al. Gastrointest Endosc. 2021;93(5):1133-8.
9. Mok SRS et al. Gastrointest Endosc. 2018;88(6):919-25.
10. Lee YN et al. J Gastroenterol Hepatol. 2015;30(7):1161-6.
11. Kalambokis G et al. J Hepatol. 2007;47(2):284-94.
12. de Franchis R et al. J Hepatol. 2022;76(4):959-74.
13. Choi AY et al. J Gastroenterol Hepatol. 2022;37(7):1373-9.
14. Zhang W et al. Gastrointest Endosc. 2021;93(3):565-72.
15. Seijo S et al. Dig Liver Dis. 2012;44(10):855-60.
16. Vesely TM. J Vasc Interv Radiol. 2001;12(11):1291-5.
17. Reverter E et al. Liver Int. 2014;34(1):16-25.
18. Henry Z et al. Clin Gastroenterol Hepatol. 2021;19(6):1098-107.e1091.
19. Ripamonti R et al. Semin Intervent Radiol. 2006;23(2):165-76.
20. Rengstorff DS and Binmoeller KF. Gastrointest Endosc. 2004;59(4):553-8.
21. Mohan BP et al. Endoscopy. 2020;52(4):259-67.
22. Robles-Medranda C et al. Endoscopy. 2020;52(4):268-75.
23. McCarty TR et al. Endosc Ultrasound. 2020;9(1):6-15.
24. Kouanda A et al. Gastrointest Endosc. 2021;94(2):291-6.
25. Bazarbashi AN et al. 2022;24(1):98-107.
Integrating intestinal ultrasound into inflammatory bowel disease training and practice in the United States
Evolving endpoints and treat-to-target strategies in inflammatory bowel disease (IBD) incorporate a need for more frequent assessments of the disease, including objective measures of inflammation.1,2 Intestinal ultrasound (IUS) is a noninvasive, well-tolerated,3 repeatable, point-of-care (POC) test that is highly sensitive and specific in detection of bowel inflammation, transmural healing,4,5 and response to therapy in both Crohn’s disease (CD) and ulcerative colitis (UC).6-8 As IUS is taking hold in the United States, there is a great need to teach the next generation of gastroenterologists about its value, how to incorporate it into clinical practice, and how to become appropriately trained and maintain competency.
Why incorporate IUS in the United States now?
As IBD management has evolved, so has the appreciation for the value of bedside IUS as a tool that addresses very real needs for the field. Unlike other parts of the world in which ultrasound skills are part of the training curriculum, this has not been the case in internal medicine and gastroenterology training in the United States. In addition, there have been no specific billing codes or clear renumeration processes outlined for IUS,9 nor have there been any local training opportunities. Because of these challenges, it was not until recently that several leaders in IBD in the United States championed the potential of this technology and incorporated it into IBD management. Subsequently, a number of gastroenterologists have been trained and are now leading the effort to disseminate this tool throughout the United States. A consequence of these efforts resulted in support from the Helmsley Charitable Trust (Helmsley) and the creation of the Intestinal Ultrasound Group of the United States and Canada to address the gaps unique to North America as well as to strengthen the quality of IUS research through collaborations across the continent.
What is IUS, and when is it performed?
IUS is a sonographic exam performed by a gastroenterology-trained professional who scans the abdominal wall (and perineum when the rectum and perineal disease is evaluated), using both a convex low-frequency probe and linear high-frequency probe to evaluate the small intestine, colon, and rectum. The bowel is composed of five layers with alternating hyperechoic and hypoechoic layers: the mucosal-lumen interface (not a true part of the bowel wall), deep mucosa, submucosa, muscularis propria, and serosa. (Figure)
The most sensitive parameter for assessment of IBD activity is bowel wall thickness (≤ 3 mm in the small bowel and colon and ≤ 4 mm in the rectum are considered normal in adults).8,10 The second key parameter is the assessment of vascularization, in which presence of hyperemia suggests active disease.11 There are a number of indices to quantify hyperemia, with the most widely used being the Limberg score.12 Additional parameters include assessment of loss of the delineation of the bowel wall layers (loss of stratification signifies active inflammation), increased thickness of the submucosa,13 increased mesenteric fatty proliferation (with increased inflammation, mesenteric fat proliferation will appear as a hyperechoic area surrounding the bowel), lymphadenopathy, bowel strictures, and extramural complications such as fistulae and abscess. Shear wave elastography may be an effective way to differentiate severe fibrotic strictures, but this is an area that requires more investigation.14
IUS has been shown to be an excellent tool in not only assessing disease activity and disease complication (with higher sensitivity than the Harvey-Bradshaw Index, serum C-reactive protein),15 but, unique to IUS, can provide early prediction of response in moderate to severe active UC.6,7 This has also been shown with transperineal ultrasound in patients with UC, with the ability to predict response to therapy as early as 1 week from induction therapy.16 Furthermore, it can be used to assess transmural healing, which has been shown to be associated with improved outcomes in Crohn’s patient, such as lower rates of hospitalizations, surgery, medication escalation, and need for corticosteroids.17 IUS is associated with great patient satisfaction and greater understanding of disease-related symptoms when the patient sees the inflammation of the bowel. (Table)
How can you get trained in IUS?
Training in IUS varies across the globe, from incorporation of IUS into the standard training curriculum to available training programs that can be followed and attended outside of medical training. In the United States, interested gastroenterologists can now be trained by becoming a member of the International Bowel Ultrasound Group (IBUS Group) and applying to the workshops now available. The IBUS Group has developed an IUS-specific training curriculum over the last 16 years, which is comprised of three modules: a 2-day hands-on workshop (Module 1) with final examination of theoretical competency, a preceptorship at an “expert center” with an experienced sonographer for a total of 4 weeks to complete 40 supervised IUS examinations (Module 2), and didactics and a final examination (Module 3). Also with support from Helmsley, the first Module 1 to be offered in the United States was hosted at Mount Sinai Medical Center in New York in 2022, the second was hosted at the University of Chicago in March 2023, and the third is planned to take place at Cedars-Sinai Medical Center in Los Angeles in March 2024.18 With the growing interest and demand for IUS training in the United States, U.S. experts are working to develop new training options that will be less time consuming, scalable, and still provide appropriate training and competency assessment.
How do you integrate IUS into your practice?
The keys to integrating IUS are a section chief or practice manager’s support of a trainee or faculty member for both funding of equipment and protected time for training and building of the program, as well as a permissive environment and collegial relationship with radiology. An ultrasound machine and additional transducers may range in price from $50,000-$120,000. Funding may be a limiting step for many, however. A detailed business plan is imperative to the success and investment of funds in an IUS program. With current billing practices in place that include ”limited abdominal ultrasound” (76705) and “Doppler ultrasound of the abdomen” (93975),19 reimbursement should include a technical fee, professional fee, and if in a hospital-based clinic, a facility fee. IUS pro-fee combined with technical fee is reimbursed at approximately 0.80 relative value units. When possible, the facility fee is included for approximately $800 per IUS visit. For billing and compliance with HIPAA, all billed IUS images must be stored in a durable and accessible format. It is recommended that the images and cine loops be digitally stored to the same or similar platform used by radiologists at the same institution. This requires early communication with the local information technology department for the connection of an ultrasound machine to the storage platform and/or electronic health record. Reporting results should be standardized with unique or otherwise available IUS templates, which also satisfy all billing components.9 The flow for incorporation of IUS into practice can be at the same time patients are seen during their visit, or alternatively, in a dedicated IUS clinic in which patients are referred by other providers and scheduled back to back.
Conclusions
In summary, the confluence of treat-to-target strategies in IBD, new treatment options in IBD, and successful efforts to translate IUS training and billing practices to the United States portends a great future for the field and for our patients.
Dr. Cleveland and Dr. Rubin, of the University of Chicago’s Inflammatory Bowel Disease Center, are speakers for Samsung/Boston Imaging.
References
1. Turner D et al. Gastroenterology. Apr 2021;160(5):1570-83. doi: 10.1053/j.gastro.2020.12.031
2. Hart AL and Rubin DT. Gastroenterology. Apr 2022;162(5):1367-9. doi: 10.1053/j.gastro.2022.02.013
3. Rajagopalan A et al. JGH Open. Apr 2020;4(2):267-72. doi: 10.1002/jgh3.12268
4. Calabrese E et al. Clin Gastroenterol Hepatol. Apr 2022;20(4):e711-22. doi: 10.1016/j.cgh.2021.03.030
5. Ripolles T et al. Inflamm Bowel Dis. Oct 2016;22(10):2465-73. doi10.1097/MIB.0000000000000882
6. Maaser C et al. Gut. Sep 2020;69(9):1629-36. doi: 10.1136/gutjnl-2019-319451
7. Ilvemark J et al. J Crohns Colitis. Nov 23 2022;16(11):1725-34. doi: 10.1093/ecco-jcc/jjac083
8. Sagami S et al. Aliment Pharmacol Ther. Jun 2020;51(12):1373-83. doi: 10.1111/apt.15767
9. Dolinger MT et al. Guide to Intestinal Ultrasound Credentialing, Documentation, and Billing for Gastroenterologists in the United States. Am J Gastroenterol. 2023.
10. Maconi G et al. Ultraschall Med. Jun 2018;39(3):304-17. doi: 10.1055/s-0043-125329
11. Sasaki T et al. Scand J Gastroenterol. Mar 2014;49(3):295-301. doi: 10.3109/00365521.2013.871744
12. Limberg B. Z Gastroenterol. Jun 1999;37(6):495-508.
13. Miyoshi J et al. J Gastroenterol. Feb 2022;57(2):82-9. doi: 10.1007/s00535-021-01847-3
14. Chen YJ et al. Inflamm Bowel Dis. Sep 15 2018;24(10):2183-90. doi: 10.1093/ibd/izy115
15. Kucharzik T et al. Apr 2017;15(4):535-42e2. doi: 10.1016/j.cgh.2016.10.040
16. Sagami S et al. Aliment Pharmacol Ther. May 2022;55(10):1320-9. doi: 10.1111/apt.16817
17. Vaughan R et al. Aliment Pharmacol Ther. Jul 2022;56(1):84-94. doi: 10.1111/apt.16892
18. International Bowel Ultrasound Group. https://ibus-group.org/
19. American Medical Association. CPT (Current Procedural Terminology). https://www.ama-assn.org/amaone/cpt-current-procedural-terminology
Evolving endpoints and treat-to-target strategies in inflammatory bowel disease (IBD) incorporate a need for more frequent assessments of the disease, including objective measures of inflammation.1,2 Intestinal ultrasound (IUS) is a noninvasive, well-tolerated,3 repeatable, point-of-care (POC) test that is highly sensitive and specific in detection of bowel inflammation, transmural healing,4,5 and response to therapy in both Crohn’s disease (CD) and ulcerative colitis (UC).6-8 As IUS is taking hold in the United States, there is a great need to teach the next generation of gastroenterologists about its value, how to incorporate it into clinical practice, and how to become appropriately trained and maintain competency.
Why incorporate IUS in the United States now?
As IBD management has evolved, so has the appreciation for the value of bedside IUS as a tool that addresses very real needs for the field. Unlike other parts of the world in which ultrasound skills are part of the training curriculum, this has not been the case in internal medicine and gastroenterology training in the United States. In addition, there have been no specific billing codes or clear renumeration processes outlined for IUS,9 nor have there been any local training opportunities. Because of these challenges, it was not until recently that several leaders in IBD in the United States championed the potential of this technology and incorporated it into IBD management. Subsequently, a number of gastroenterologists have been trained and are now leading the effort to disseminate this tool throughout the United States. A consequence of these efforts resulted in support from the Helmsley Charitable Trust (Helmsley) and the creation of the Intestinal Ultrasound Group of the United States and Canada to address the gaps unique to North America as well as to strengthen the quality of IUS research through collaborations across the continent.
What is IUS, and when is it performed?
IUS is a sonographic exam performed by a gastroenterology-trained professional who scans the abdominal wall (and perineum when the rectum and perineal disease is evaluated), using both a convex low-frequency probe and linear high-frequency probe to evaluate the small intestine, colon, and rectum. The bowel is composed of five layers with alternating hyperechoic and hypoechoic layers: the mucosal-lumen interface (not a true part of the bowel wall), deep mucosa, submucosa, muscularis propria, and serosa. (Figure)
The most sensitive parameter for assessment of IBD activity is bowel wall thickness (≤ 3 mm in the small bowel and colon and ≤ 4 mm in the rectum are considered normal in adults).8,10 The second key parameter is the assessment of vascularization, in which presence of hyperemia suggests active disease.11 There are a number of indices to quantify hyperemia, with the most widely used being the Limberg score.12 Additional parameters include assessment of loss of the delineation of the bowel wall layers (loss of stratification signifies active inflammation), increased thickness of the submucosa,13 increased mesenteric fatty proliferation (with increased inflammation, mesenteric fat proliferation will appear as a hyperechoic area surrounding the bowel), lymphadenopathy, bowel strictures, and extramural complications such as fistulae and abscess. Shear wave elastography may be an effective way to differentiate severe fibrotic strictures, but this is an area that requires more investigation.14
IUS has been shown to be an excellent tool in not only assessing disease activity and disease complication (with higher sensitivity than the Harvey-Bradshaw Index, serum C-reactive protein),15 but, unique to IUS, can provide early prediction of response in moderate to severe active UC.6,7 This has also been shown with transperineal ultrasound in patients with UC, with the ability to predict response to therapy as early as 1 week from induction therapy.16 Furthermore, it can be used to assess transmural healing, which has been shown to be associated with improved outcomes in Crohn’s patient, such as lower rates of hospitalizations, surgery, medication escalation, and need for corticosteroids.17 IUS is associated with great patient satisfaction and greater understanding of disease-related symptoms when the patient sees the inflammation of the bowel. (Table)
How can you get trained in IUS?
Training in IUS varies across the globe, from incorporation of IUS into the standard training curriculum to available training programs that can be followed and attended outside of medical training. In the United States, interested gastroenterologists can now be trained by becoming a member of the International Bowel Ultrasound Group (IBUS Group) and applying to the workshops now available. The IBUS Group has developed an IUS-specific training curriculum over the last 16 years, which is comprised of three modules: a 2-day hands-on workshop (Module 1) with final examination of theoretical competency, a preceptorship at an “expert center” with an experienced sonographer for a total of 4 weeks to complete 40 supervised IUS examinations (Module 2), and didactics and a final examination (Module 3). Also with support from Helmsley, the first Module 1 to be offered in the United States was hosted at Mount Sinai Medical Center in New York in 2022, the second was hosted at the University of Chicago in March 2023, and the third is planned to take place at Cedars-Sinai Medical Center in Los Angeles in March 2024.18 With the growing interest and demand for IUS training in the United States, U.S. experts are working to develop new training options that will be less time consuming, scalable, and still provide appropriate training and competency assessment.
How do you integrate IUS into your practice?
The keys to integrating IUS are a section chief or practice manager’s support of a trainee or faculty member for both funding of equipment and protected time for training and building of the program, as well as a permissive environment and collegial relationship with radiology. An ultrasound machine and additional transducers may range in price from $50,000-$120,000. Funding may be a limiting step for many, however. A detailed business plan is imperative to the success and investment of funds in an IUS program. With current billing practices in place that include ”limited abdominal ultrasound” (76705) and “Doppler ultrasound of the abdomen” (93975),19 reimbursement should include a technical fee, professional fee, and if in a hospital-based clinic, a facility fee. IUS pro-fee combined with technical fee is reimbursed at approximately 0.80 relative value units. When possible, the facility fee is included for approximately $800 per IUS visit. For billing and compliance with HIPAA, all billed IUS images must be stored in a durable and accessible format. It is recommended that the images and cine loops be digitally stored to the same or similar platform used by radiologists at the same institution. This requires early communication with the local information technology department for the connection of an ultrasound machine to the storage platform and/or electronic health record. Reporting results should be standardized with unique or otherwise available IUS templates, which also satisfy all billing components.9 The flow for incorporation of IUS into practice can be at the same time patients are seen during their visit, or alternatively, in a dedicated IUS clinic in which patients are referred by other providers and scheduled back to back.
Conclusions
In summary, the confluence of treat-to-target strategies in IBD, new treatment options in IBD, and successful efforts to translate IUS training and billing practices to the United States portends a great future for the field and for our patients.
Dr. Cleveland and Dr. Rubin, of the University of Chicago’s Inflammatory Bowel Disease Center, are speakers for Samsung/Boston Imaging.
References
1. Turner D et al. Gastroenterology. Apr 2021;160(5):1570-83. doi: 10.1053/j.gastro.2020.12.031
2. Hart AL and Rubin DT. Gastroenterology. Apr 2022;162(5):1367-9. doi: 10.1053/j.gastro.2022.02.013
3. Rajagopalan A et al. JGH Open. Apr 2020;4(2):267-72. doi: 10.1002/jgh3.12268
4. Calabrese E et al. Clin Gastroenterol Hepatol. Apr 2022;20(4):e711-22. doi: 10.1016/j.cgh.2021.03.030
5. Ripolles T et al. Inflamm Bowel Dis. Oct 2016;22(10):2465-73. doi10.1097/MIB.0000000000000882
6. Maaser C et al. Gut. Sep 2020;69(9):1629-36. doi: 10.1136/gutjnl-2019-319451
7. Ilvemark J et al. J Crohns Colitis. Nov 23 2022;16(11):1725-34. doi: 10.1093/ecco-jcc/jjac083
8. Sagami S et al. Aliment Pharmacol Ther. Jun 2020;51(12):1373-83. doi: 10.1111/apt.15767
9. Dolinger MT et al. Guide to Intestinal Ultrasound Credentialing, Documentation, and Billing for Gastroenterologists in the United States. Am J Gastroenterol. 2023.
10. Maconi G et al. Ultraschall Med. Jun 2018;39(3):304-17. doi: 10.1055/s-0043-125329
11. Sasaki T et al. Scand J Gastroenterol. Mar 2014;49(3):295-301. doi: 10.3109/00365521.2013.871744
12. Limberg B. Z Gastroenterol. Jun 1999;37(6):495-508.
13. Miyoshi J et al. J Gastroenterol. Feb 2022;57(2):82-9. doi: 10.1007/s00535-021-01847-3
14. Chen YJ et al. Inflamm Bowel Dis. Sep 15 2018;24(10):2183-90. doi: 10.1093/ibd/izy115
15. Kucharzik T et al. Apr 2017;15(4):535-42e2. doi: 10.1016/j.cgh.2016.10.040
16. Sagami S et al. Aliment Pharmacol Ther. May 2022;55(10):1320-9. doi: 10.1111/apt.16817
17. Vaughan R et al. Aliment Pharmacol Ther. Jul 2022;56(1):84-94. doi: 10.1111/apt.16892
18. International Bowel Ultrasound Group. https://ibus-group.org/
19. American Medical Association. CPT (Current Procedural Terminology). https://www.ama-assn.org/amaone/cpt-current-procedural-terminology
Evolving endpoints and treat-to-target strategies in inflammatory bowel disease (IBD) incorporate a need for more frequent assessments of the disease, including objective measures of inflammation.1,2 Intestinal ultrasound (IUS) is a noninvasive, well-tolerated,3 repeatable, point-of-care (POC) test that is highly sensitive and specific in detection of bowel inflammation, transmural healing,4,5 and response to therapy in both Crohn’s disease (CD) and ulcerative colitis (UC).6-8 As IUS is taking hold in the United States, there is a great need to teach the next generation of gastroenterologists about its value, how to incorporate it into clinical practice, and how to become appropriately trained and maintain competency.
Why incorporate IUS in the United States now?
As IBD management has evolved, so has the appreciation for the value of bedside IUS as a tool that addresses very real needs for the field. Unlike other parts of the world in which ultrasound skills are part of the training curriculum, this has not been the case in internal medicine and gastroenterology training in the United States. In addition, there have been no specific billing codes or clear renumeration processes outlined for IUS,9 nor have there been any local training opportunities. Because of these challenges, it was not until recently that several leaders in IBD in the United States championed the potential of this technology and incorporated it into IBD management. Subsequently, a number of gastroenterologists have been trained and are now leading the effort to disseminate this tool throughout the United States. A consequence of these efforts resulted in support from the Helmsley Charitable Trust (Helmsley) and the creation of the Intestinal Ultrasound Group of the United States and Canada to address the gaps unique to North America as well as to strengthen the quality of IUS research through collaborations across the continent.
What is IUS, and when is it performed?
IUS is a sonographic exam performed by a gastroenterology-trained professional who scans the abdominal wall (and perineum when the rectum and perineal disease is evaluated), using both a convex low-frequency probe and linear high-frequency probe to evaluate the small intestine, colon, and rectum. The bowel is composed of five layers with alternating hyperechoic and hypoechoic layers: the mucosal-lumen interface (not a true part of the bowel wall), deep mucosa, submucosa, muscularis propria, and serosa. (Figure)
The most sensitive parameter for assessment of IBD activity is bowel wall thickness (≤ 3 mm in the small bowel and colon and ≤ 4 mm in the rectum are considered normal in adults).8,10 The second key parameter is the assessment of vascularization, in which presence of hyperemia suggests active disease.11 There are a number of indices to quantify hyperemia, with the most widely used being the Limberg score.12 Additional parameters include assessment of loss of the delineation of the bowel wall layers (loss of stratification signifies active inflammation), increased thickness of the submucosa,13 increased mesenteric fatty proliferation (with increased inflammation, mesenteric fat proliferation will appear as a hyperechoic area surrounding the bowel), lymphadenopathy, bowel strictures, and extramural complications such as fistulae and abscess. Shear wave elastography may be an effective way to differentiate severe fibrotic strictures, but this is an area that requires more investigation.14
IUS has been shown to be an excellent tool in not only assessing disease activity and disease complication (with higher sensitivity than the Harvey-Bradshaw Index, serum C-reactive protein),15 but, unique to IUS, can provide early prediction of response in moderate to severe active UC.6,7 This has also been shown with transperineal ultrasound in patients with UC, with the ability to predict response to therapy as early as 1 week from induction therapy.16 Furthermore, it can be used to assess transmural healing, which has been shown to be associated with improved outcomes in Crohn’s patient, such as lower rates of hospitalizations, surgery, medication escalation, and need for corticosteroids.17 IUS is associated with great patient satisfaction and greater understanding of disease-related symptoms when the patient sees the inflammation of the bowel. (Table)
How can you get trained in IUS?
Training in IUS varies across the globe, from incorporation of IUS into the standard training curriculum to available training programs that can be followed and attended outside of medical training. In the United States, interested gastroenterologists can now be trained by becoming a member of the International Bowel Ultrasound Group (IBUS Group) and applying to the workshops now available. The IBUS Group has developed an IUS-specific training curriculum over the last 16 years, which is comprised of three modules: a 2-day hands-on workshop (Module 1) with final examination of theoretical competency, a preceptorship at an “expert center” with an experienced sonographer for a total of 4 weeks to complete 40 supervised IUS examinations (Module 2), and didactics and a final examination (Module 3). Also with support from Helmsley, the first Module 1 to be offered in the United States was hosted at Mount Sinai Medical Center in New York in 2022, the second was hosted at the University of Chicago in March 2023, and the third is planned to take place at Cedars-Sinai Medical Center in Los Angeles in March 2024.18 With the growing interest and demand for IUS training in the United States, U.S. experts are working to develop new training options that will be less time consuming, scalable, and still provide appropriate training and competency assessment.
How do you integrate IUS into your practice?
The keys to integrating IUS are a section chief or practice manager’s support of a trainee or faculty member for both funding of equipment and protected time for training and building of the program, as well as a permissive environment and collegial relationship with radiology. An ultrasound machine and additional transducers may range in price from $50,000-$120,000. Funding may be a limiting step for many, however. A detailed business plan is imperative to the success and investment of funds in an IUS program. With current billing practices in place that include ”limited abdominal ultrasound” (76705) and “Doppler ultrasound of the abdomen” (93975),19 reimbursement should include a technical fee, professional fee, and if in a hospital-based clinic, a facility fee. IUS pro-fee combined with technical fee is reimbursed at approximately 0.80 relative value units. When possible, the facility fee is included for approximately $800 per IUS visit. For billing and compliance with HIPAA, all billed IUS images must be stored in a durable and accessible format. It is recommended that the images and cine loops be digitally stored to the same or similar platform used by radiologists at the same institution. This requires early communication with the local information technology department for the connection of an ultrasound machine to the storage platform and/or electronic health record. Reporting results should be standardized with unique or otherwise available IUS templates, which also satisfy all billing components.9 The flow for incorporation of IUS into practice can be at the same time patients are seen during their visit, or alternatively, in a dedicated IUS clinic in which patients are referred by other providers and scheduled back to back.
Conclusions
In summary, the confluence of treat-to-target strategies in IBD, new treatment options in IBD, and successful efforts to translate IUS training and billing practices to the United States portends a great future for the field and for our patients.
Dr. Cleveland and Dr. Rubin, of the University of Chicago’s Inflammatory Bowel Disease Center, are speakers for Samsung/Boston Imaging.
References
1. Turner D et al. Gastroenterology. Apr 2021;160(5):1570-83. doi: 10.1053/j.gastro.2020.12.031
2. Hart AL and Rubin DT. Gastroenterology. Apr 2022;162(5):1367-9. doi: 10.1053/j.gastro.2022.02.013
3. Rajagopalan A et al. JGH Open. Apr 2020;4(2):267-72. doi: 10.1002/jgh3.12268
4. Calabrese E et al. Clin Gastroenterol Hepatol. Apr 2022;20(4):e711-22. doi: 10.1016/j.cgh.2021.03.030
5. Ripolles T et al. Inflamm Bowel Dis. Oct 2016;22(10):2465-73. doi10.1097/MIB.0000000000000882
6. Maaser C et al. Gut. Sep 2020;69(9):1629-36. doi: 10.1136/gutjnl-2019-319451
7. Ilvemark J et al. J Crohns Colitis. Nov 23 2022;16(11):1725-34. doi: 10.1093/ecco-jcc/jjac083
8. Sagami S et al. Aliment Pharmacol Ther. Jun 2020;51(12):1373-83. doi: 10.1111/apt.15767
9. Dolinger MT et al. Guide to Intestinal Ultrasound Credentialing, Documentation, and Billing for Gastroenterologists in the United States. Am J Gastroenterol. 2023.
10. Maconi G et al. Ultraschall Med. Jun 2018;39(3):304-17. doi: 10.1055/s-0043-125329
11. Sasaki T et al. Scand J Gastroenterol. Mar 2014;49(3):295-301. doi: 10.3109/00365521.2013.871744
12. Limberg B. Z Gastroenterol. Jun 1999;37(6):495-508.
13. Miyoshi J et al. J Gastroenterol. Feb 2022;57(2):82-9. doi: 10.1007/s00535-021-01847-3
14. Chen YJ et al. Inflamm Bowel Dis. Sep 15 2018;24(10):2183-90. doi: 10.1093/ibd/izy115
15. Kucharzik T et al. Apr 2017;15(4):535-42e2. doi: 10.1016/j.cgh.2016.10.040
16. Sagami S et al. Aliment Pharmacol Ther. May 2022;55(10):1320-9. doi: 10.1111/apt.16817
17. Vaughan R et al. Aliment Pharmacol Ther. Jul 2022;56(1):84-94. doi: 10.1111/apt.16892
18. International Bowel Ultrasound Group. https://ibus-group.org/
19. American Medical Association. CPT (Current Procedural Terminology). https://www.ama-assn.org/amaone/cpt-current-procedural-terminology
Immune checkpoint inhibitor–related gastrointestinal adverse events
Introduction
The field of cancer immunotherapy has exploded in recent years, with new therapies showing promising results for effective treatment of various cancer types. Immune checkpoint inhibitors (ICI) work by blocking checkpoint proteins that prevent breakdown of tumor cells by T-lymphocytes. Checkpoint proteins exist to prevent autoimmunity and destruction of healthy cells, but may allow tumor cells to grow unchallenged. Three checkpoint proteins – cytotoxic T-lymphocyte protein–4 (CTLA-4), programmed cell-death protein–1 (PD-1), and programmed cell-death protein ligand–1 (PDL-1) – are therapeutic targets for current ICIs.1
ICIs are used to treat various cancer types (e.g., lung, renal-cell, and Hodgkin’s lymphoma). Immune-related adverse events (irAE) are frequently seen with ICI use, ranging from 15% to 90%, and can occur at any point during, or even after, treatment.2
Immune checkpoint inhibitor–related gastrointestinal adverse reactions
GI adverse reactions are the second most common irAE, occurring in about 35%-50% of all reported irAEs.3 Anti-CTLA-4 medications have the highest association with GI irAE. The most common GI symptoms are diarrhea, abdominal pain, urgency, and nausea/vomiting. GI involvement can occur along the entirety of the GI tract – from the oral cavity to the colorectum. These are usually seen within 6-8 weeks of starting treatment, but can occur as early as 1 week after initiation or as late as 12 months after the last dose.2 Although colitis is the most common area of luminal inflammation, aphthous ulcers, esophagitis, gastritis, and enteritis can be seen. Anti-CTLA-4 antibodies have the highest associated rate of diarrhea (33%-50%) and colitis (7%-22%) of all ICIs.4 Computed tomography (CT) may show colonic wall thickening or fat stranding, indicating inflammation. Endoscopically, the colon can appear grossly normal or demonstrate erythema, erosions, ulcerations, and/or loss of vascular pattern.5 Inflammation can be patchy or continuous. Typical histology shows increased lamina propria cellularity, neutrophilic infiltration (intraepithelial or crypt abscesses), and increased crypt apoptosis.6
The liver, pancreas, gallbladder, and biliary tract can also be affected by irAE. The liver is most commonly involved (i.e. 5% of irAE), manifesting as asymptomatic liver chemistry elevation, particularly aminotransferases. This can progress to acute symptomatic hepatitis with jaundice, fever, or malaise, and rarely to fulminant hepatitis. ICI-associated hepatitis appears histologically similar to autoimmune hepatitis, with pan-lobular hepatitis and infiltrating CD8+ T lymphocytes seen on liver biopsy.7 Less commonly, pancreatic toxicity can occur (<2% of irAE), seen with anti-CTLA-4 therapy.8 While this typically results in asymptomatic lipase or amylase elevations (2.7%), acute pancreatitis (AP) can occur(1.9%). ICI-associated AP presents with classic symptoms and imaging changes, but can also manifest with exocrine or endocrine pancreatic insufficiency. An increase in rates of acute acalculous cholecystitis has been reported in patients receiving ICIs compared to patients receiving non-ICI chemotherapy.9 There are also rare reports of ICI-associated secondary sclerosing cholangitis.
Management
Evaluation and management of GI irAEs are guided by severity, based on the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) grading classification (Table 1).10
A thorough history of GI and systemic symptoms should be obtained and compared to baseline bowel habits. Patients with mild symptoms should undergo studies to assess alternate etiologies for their symptoms. Bacterial stool cultures and testing for C. difficile should be performed. Erythrocyte sedimentation rate, C-reactive protein, fecal lactoferrin, and calprotectin can help assess the degree of intestinal inflammation and can be used to risk-stratify or assess treatment response. CT scans can assess for colitis and associated complications, including abdominal abscess, toxic megacolon, and bowel perforation.
Patients unresponsive to initial treatment for grade I irAE, with hematochezia, or with at least grade 2 diarrhea, should undergo GI consultation and endoscopic evaluation. Flexible sigmoidoscopy is the test of choice, as 95% of patients will have left-sided colonic inflammation.11 Patients with at least grade 3 diarrhea should be hospitalized for treatment. In cases of failed methylprednisolone and when infliximab is ineffective or contraindicated, vedolizumab is suggested, although evidence is limited.12
Patients responsive to systemic corticosteroids (complete resolution or improvement to grade 1) can continue a tapered regimen over 4-6 weeks. There is conflicting evidence on the effect that corticosteroids have on ICI-related antitumor response rates. While some studies report no change in antitumor response rates or survival, others report reduced overall survival.13 Regardless, given its unfavorable side-effect profile, steroids should be used only for short periods of time.
PD-1 and PD-L1 antibodies can be restarted after symptoms have resolved or improved to grade 1, having finished the corticosteroid taper. CTLA-4 antibodies should be discontinued permanently in the setting of grade 3 toxicity. All ICIs should be discontinued permanently in grade 4 toxicity.
A grading system also exists for ICI-associated hepatitis (Table 2) and AP (Table 3). Patients with elevated aminotransferases greater than 2x upper limit of normal (ULN) should have alternative etiologies excluded. A thorough medication reconciliation, including over-the-counter and nonpharmaceutical supplements, should be performed. All potentially-hepatotoxic drugs and substances (including alcohol) should be discontinued. Viral hepatitis serology (A,B,C), Epstein-Barr virus, and cytomegalovirus also should be performed. Additional tests, including prothrombin time and albumin, can help assess for liver synthetic dysfunction. Abdominal ultrasound or CT can assist in excluding biliary obstruction or metastatic disease. Magnetic resonance cholangiopancreatography (MRCP) can be considered for further evaluation of biliary obstruction in patients with hyperbilirubinemia and normal ultrasound.14
Table 2 reviews the grading system and management of ICI-associated hepatitis. Patients with grade 3 and above should be hospitalized for treatment. As with the management of colitis, patients responding to corticosteroids should be tapered off over 4-6 weeks. In steroid-refractory cases or if there is no improvement after 3 days, mycophenolate mofetil is used. Other immunomodulators such as azathioprine and tacrolimus also can be considered, although evidence is limited.15 ICI-associated cholangitis presenting with elevated bilirubin and alkaline phosphatase is approached similarly to ICI-associated hepatitis. Abnormal findings of biliary obstruction or sclerosing cholangitis should be further evaluated with endoscopic retrograde cholangiopancreatography.
Mild asymptomatic elevation in lipase and amylase <3x ULN can be managed with observation and ICIs can be safely continued. Symptomatic patients should have a diagnostic workup for other etiologies. As with hepatitis, a thorough history including alcohol intake and a medication reconciliation should be performed. In the absence of other etiologies, grade 2 ICI-associated AP is managed by holding immunotherapy, administering steroids, and managing AP with fluid resuscitation and analgesia.
Conclusions
Therapy with ICI is a rapidly expanding and changing field. Side effects of ICIs can affect nearly every organ system, and thus management should involve a multidisciplinary team of oncologists, pathologists, radiologists, pharmacists, and other specialists. Given that GI adverse effects are the second most commonly affected system, all gastroenterologists and hepatologists should be knowledgeable about the spectrum of GI adverse events, as well as with the respective clinical presentations, diagnostics, and management of these events.
Dr. Kwon is with the division of gastroenterology and hepatology, University of California Irvine, Orange. Dr. Kröner is with the division of advanced endoscopy, Riverside Health System, Newport News, Va. The authors certify that they have no financial arrangements (e.g., consultancies, stock ownership, equity interests, patent-licensing arrangements, research support, honoraria, etc.) with a company whose product figures prominently in this manuscript or with a company making a competing product. Funding: None.
References
1. Webster RM. The immune checkpoint inhibitors: where are we now? Nature Reviews: Drug Discovery. 2014;13(12):883.
2. Thompson JA et al. NCCN guidelines insights: Management of immunotherapy-related toxicities, version 1.2020: Featured updates to the NCCN guidelines. J Natl Compr Canc Netw. 2020;18(3):230-41.
3. Bertrand A et al. Immune related adverse events associated with anti-CTLA-4 antibodies: Systematic review and meta-analysis. BMC Med. 2015 Sep 4;13:211.
4. Gupta A et al. Systematic review: Colitis associated with anti‐CTLA‐4 therapy. Aliment Pharmacol Ther. 2015;42(4):406-17.
5. Verschuren EC et al. Clinical, endoscopic, and histologic characteristics of ipilimumab-associated colitis. Clin Gastroenterol Hepatol. 2016;14(6):836-42.
6. Foppen MHG et al. Immune checkpoint inhibition–related colitis: Symptoms, endoscopic features, histology and response to management. ESMO Open. 2018;3(1):e000278.
7. Sanjeevaiah A et al. Approach and management of checkpoint inhibitor–related immune hepatitis. J Gastrointest Oncol. 2018;9(1):220.
8. Abu-Sbeih H et al. Clinical characteristics and outcomes of immune checkpoint inhibitor–induced pancreatic injury. J Immunother Cancer. 2019 Feb 6;7(1):31.
9. Abu-Sbeih H et al. Case series of cancer patients who developed cholecystitis related to immune checkpoint inhibitor treatment. J Immunother Cancer. 2019 May 3;7(1):118.
10. Thompson JA et al. Management of immunotherapy-related toxicities, version 1.2019, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2019;17(3):255-89.
11. Marthey L et al. Cancer immunotherapy with anti-CTLA-4 monoclonal antibodies induces an inflammatory bowel disease. J Crohns Colitis. 2016;10(4):395-401.
12. Abu-Sbeih H et al. Outcomes of vedolizumab therapy in patients with immune checkpoint inhibitor–induced colitis: A multicenter study. J Immunother Cancer. 2018 Dec 5;6(1):142.
13. Das S and Johnson DB. Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors. J Immunother Cancer. 2019 Nov 15;7(1):306.
14. Reddy HG et al. Immune checkpoint inhibitor–associated colitis and hepatitis. Clin Transl Gastroenterol. 2018 Sep 19;9(9):180.
15. Reynolds K et al. Diagnosis and management of hepatitis in patients on checkpoint blockade. Oncologist. 2018;23(9):991-7.
Introduction
The field of cancer immunotherapy has exploded in recent years, with new therapies showing promising results for effective treatment of various cancer types. Immune checkpoint inhibitors (ICI) work by blocking checkpoint proteins that prevent breakdown of tumor cells by T-lymphocytes. Checkpoint proteins exist to prevent autoimmunity and destruction of healthy cells, but may allow tumor cells to grow unchallenged. Three checkpoint proteins – cytotoxic T-lymphocyte protein–4 (CTLA-4), programmed cell-death protein–1 (PD-1), and programmed cell-death protein ligand–1 (PDL-1) – are therapeutic targets for current ICIs.1
ICIs are used to treat various cancer types (e.g., lung, renal-cell, and Hodgkin’s lymphoma). Immune-related adverse events (irAE) are frequently seen with ICI use, ranging from 15% to 90%, and can occur at any point during, or even after, treatment.2
Immune checkpoint inhibitor–related gastrointestinal adverse reactions
GI adverse reactions are the second most common irAE, occurring in about 35%-50% of all reported irAEs.3 Anti-CTLA-4 medications have the highest association with GI irAE. The most common GI symptoms are diarrhea, abdominal pain, urgency, and nausea/vomiting. GI involvement can occur along the entirety of the GI tract – from the oral cavity to the colorectum. These are usually seen within 6-8 weeks of starting treatment, but can occur as early as 1 week after initiation or as late as 12 months after the last dose.2 Although colitis is the most common area of luminal inflammation, aphthous ulcers, esophagitis, gastritis, and enteritis can be seen. Anti-CTLA-4 antibodies have the highest associated rate of diarrhea (33%-50%) and colitis (7%-22%) of all ICIs.4 Computed tomography (CT) may show colonic wall thickening or fat stranding, indicating inflammation. Endoscopically, the colon can appear grossly normal or demonstrate erythema, erosions, ulcerations, and/or loss of vascular pattern.5 Inflammation can be patchy or continuous. Typical histology shows increased lamina propria cellularity, neutrophilic infiltration (intraepithelial or crypt abscesses), and increased crypt apoptosis.6
The liver, pancreas, gallbladder, and biliary tract can also be affected by irAE. The liver is most commonly involved (i.e. 5% of irAE), manifesting as asymptomatic liver chemistry elevation, particularly aminotransferases. This can progress to acute symptomatic hepatitis with jaundice, fever, or malaise, and rarely to fulminant hepatitis. ICI-associated hepatitis appears histologically similar to autoimmune hepatitis, with pan-lobular hepatitis and infiltrating CD8+ T lymphocytes seen on liver biopsy.7 Less commonly, pancreatic toxicity can occur (<2% of irAE), seen with anti-CTLA-4 therapy.8 While this typically results in asymptomatic lipase or amylase elevations (2.7%), acute pancreatitis (AP) can occur(1.9%). ICI-associated AP presents with classic symptoms and imaging changes, but can also manifest with exocrine or endocrine pancreatic insufficiency. An increase in rates of acute acalculous cholecystitis has been reported in patients receiving ICIs compared to patients receiving non-ICI chemotherapy.9 There are also rare reports of ICI-associated secondary sclerosing cholangitis.
Management
Evaluation and management of GI irAEs are guided by severity, based on the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) grading classification (Table 1).10
A thorough history of GI and systemic symptoms should be obtained and compared to baseline bowel habits. Patients with mild symptoms should undergo studies to assess alternate etiologies for their symptoms. Bacterial stool cultures and testing for C. difficile should be performed. Erythrocyte sedimentation rate, C-reactive protein, fecal lactoferrin, and calprotectin can help assess the degree of intestinal inflammation and can be used to risk-stratify or assess treatment response. CT scans can assess for colitis and associated complications, including abdominal abscess, toxic megacolon, and bowel perforation.
Patients unresponsive to initial treatment for grade I irAE, with hematochezia, or with at least grade 2 diarrhea, should undergo GI consultation and endoscopic evaluation. Flexible sigmoidoscopy is the test of choice, as 95% of patients will have left-sided colonic inflammation.11 Patients with at least grade 3 diarrhea should be hospitalized for treatment. In cases of failed methylprednisolone and when infliximab is ineffective or contraindicated, vedolizumab is suggested, although evidence is limited.12
Patients responsive to systemic corticosteroids (complete resolution or improvement to grade 1) can continue a tapered regimen over 4-6 weeks. There is conflicting evidence on the effect that corticosteroids have on ICI-related antitumor response rates. While some studies report no change in antitumor response rates or survival, others report reduced overall survival.13 Regardless, given its unfavorable side-effect profile, steroids should be used only for short periods of time.
PD-1 and PD-L1 antibodies can be restarted after symptoms have resolved or improved to grade 1, having finished the corticosteroid taper. CTLA-4 antibodies should be discontinued permanently in the setting of grade 3 toxicity. All ICIs should be discontinued permanently in grade 4 toxicity.
A grading system also exists for ICI-associated hepatitis (Table 2) and AP (Table 3). Patients with elevated aminotransferases greater than 2x upper limit of normal (ULN) should have alternative etiologies excluded. A thorough medication reconciliation, including over-the-counter and nonpharmaceutical supplements, should be performed. All potentially-hepatotoxic drugs and substances (including alcohol) should be discontinued. Viral hepatitis serology (A,B,C), Epstein-Barr virus, and cytomegalovirus also should be performed. Additional tests, including prothrombin time and albumin, can help assess for liver synthetic dysfunction. Abdominal ultrasound or CT can assist in excluding biliary obstruction or metastatic disease. Magnetic resonance cholangiopancreatography (MRCP) can be considered for further evaluation of biliary obstruction in patients with hyperbilirubinemia and normal ultrasound.14
Table 2 reviews the grading system and management of ICI-associated hepatitis. Patients with grade 3 and above should be hospitalized for treatment. As with the management of colitis, patients responding to corticosteroids should be tapered off over 4-6 weeks. In steroid-refractory cases or if there is no improvement after 3 days, mycophenolate mofetil is used. Other immunomodulators such as azathioprine and tacrolimus also can be considered, although evidence is limited.15 ICI-associated cholangitis presenting with elevated bilirubin and alkaline phosphatase is approached similarly to ICI-associated hepatitis. Abnormal findings of biliary obstruction or sclerosing cholangitis should be further evaluated with endoscopic retrograde cholangiopancreatography.
Mild asymptomatic elevation in lipase and amylase <3x ULN can be managed with observation and ICIs can be safely continued. Symptomatic patients should have a diagnostic workup for other etiologies. As with hepatitis, a thorough history including alcohol intake and a medication reconciliation should be performed. In the absence of other etiologies, grade 2 ICI-associated AP is managed by holding immunotherapy, administering steroids, and managing AP with fluid resuscitation and analgesia.
Conclusions
Therapy with ICI is a rapidly expanding and changing field. Side effects of ICIs can affect nearly every organ system, and thus management should involve a multidisciplinary team of oncologists, pathologists, radiologists, pharmacists, and other specialists. Given that GI adverse effects are the second most commonly affected system, all gastroenterologists and hepatologists should be knowledgeable about the spectrum of GI adverse events, as well as with the respective clinical presentations, diagnostics, and management of these events.
Dr. Kwon is with the division of gastroenterology and hepatology, University of California Irvine, Orange. Dr. Kröner is with the division of advanced endoscopy, Riverside Health System, Newport News, Va. The authors certify that they have no financial arrangements (e.g., consultancies, stock ownership, equity interests, patent-licensing arrangements, research support, honoraria, etc.) with a company whose product figures prominently in this manuscript or with a company making a competing product. Funding: None.
References
1. Webster RM. The immune checkpoint inhibitors: where are we now? Nature Reviews: Drug Discovery. 2014;13(12):883.
2. Thompson JA et al. NCCN guidelines insights: Management of immunotherapy-related toxicities, version 1.2020: Featured updates to the NCCN guidelines. J Natl Compr Canc Netw. 2020;18(3):230-41.
3. Bertrand A et al. Immune related adverse events associated with anti-CTLA-4 antibodies: Systematic review and meta-analysis. BMC Med. 2015 Sep 4;13:211.
4. Gupta A et al. Systematic review: Colitis associated with anti‐CTLA‐4 therapy. Aliment Pharmacol Ther. 2015;42(4):406-17.
5. Verschuren EC et al. Clinical, endoscopic, and histologic characteristics of ipilimumab-associated colitis. Clin Gastroenterol Hepatol. 2016;14(6):836-42.
6. Foppen MHG et al. Immune checkpoint inhibition–related colitis: Symptoms, endoscopic features, histology and response to management. ESMO Open. 2018;3(1):e000278.
7. Sanjeevaiah A et al. Approach and management of checkpoint inhibitor–related immune hepatitis. J Gastrointest Oncol. 2018;9(1):220.
8. Abu-Sbeih H et al. Clinical characteristics and outcomes of immune checkpoint inhibitor–induced pancreatic injury. J Immunother Cancer. 2019 Feb 6;7(1):31.
9. Abu-Sbeih H et al. Case series of cancer patients who developed cholecystitis related to immune checkpoint inhibitor treatment. J Immunother Cancer. 2019 May 3;7(1):118.
10. Thompson JA et al. Management of immunotherapy-related toxicities, version 1.2019, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2019;17(3):255-89.
11. Marthey L et al. Cancer immunotherapy with anti-CTLA-4 monoclonal antibodies induces an inflammatory bowel disease. J Crohns Colitis. 2016;10(4):395-401.
12. Abu-Sbeih H et al. Outcomes of vedolizumab therapy in patients with immune checkpoint inhibitor–induced colitis: A multicenter study. J Immunother Cancer. 2018 Dec 5;6(1):142.
13. Das S and Johnson DB. Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors. J Immunother Cancer. 2019 Nov 15;7(1):306.
14. Reddy HG et al. Immune checkpoint inhibitor–associated colitis and hepatitis. Clin Transl Gastroenterol. 2018 Sep 19;9(9):180.
15. Reynolds K et al. Diagnosis and management of hepatitis in patients on checkpoint blockade. Oncologist. 2018;23(9):991-7.
Introduction
The field of cancer immunotherapy has exploded in recent years, with new therapies showing promising results for effective treatment of various cancer types. Immune checkpoint inhibitors (ICI) work by blocking checkpoint proteins that prevent breakdown of tumor cells by T-lymphocytes. Checkpoint proteins exist to prevent autoimmunity and destruction of healthy cells, but may allow tumor cells to grow unchallenged. Three checkpoint proteins – cytotoxic T-lymphocyte protein–4 (CTLA-4), programmed cell-death protein–1 (PD-1), and programmed cell-death protein ligand–1 (PDL-1) – are therapeutic targets for current ICIs.1
ICIs are used to treat various cancer types (e.g., lung, renal-cell, and Hodgkin’s lymphoma). Immune-related adverse events (irAE) are frequently seen with ICI use, ranging from 15% to 90%, and can occur at any point during, or even after, treatment.2
Immune checkpoint inhibitor–related gastrointestinal adverse reactions
GI adverse reactions are the second most common irAE, occurring in about 35%-50% of all reported irAEs.3 Anti-CTLA-4 medications have the highest association with GI irAE. The most common GI symptoms are diarrhea, abdominal pain, urgency, and nausea/vomiting. GI involvement can occur along the entirety of the GI tract – from the oral cavity to the colorectum. These are usually seen within 6-8 weeks of starting treatment, but can occur as early as 1 week after initiation or as late as 12 months after the last dose.2 Although colitis is the most common area of luminal inflammation, aphthous ulcers, esophagitis, gastritis, and enteritis can be seen. Anti-CTLA-4 antibodies have the highest associated rate of diarrhea (33%-50%) and colitis (7%-22%) of all ICIs.4 Computed tomography (CT) may show colonic wall thickening or fat stranding, indicating inflammation. Endoscopically, the colon can appear grossly normal or demonstrate erythema, erosions, ulcerations, and/or loss of vascular pattern.5 Inflammation can be patchy or continuous. Typical histology shows increased lamina propria cellularity, neutrophilic infiltration (intraepithelial or crypt abscesses), and increased crypt apoptosis.6
The liver, pancreas, gallbladder, and biliary tract can also be affected by irAE. The liver is most commonly involved (i.e. 5% of irAE), manifesting as asymptomatic liver chemistry elevation, particularly aminotransferases. This can progress to acute symptomatic hepatitis with jaundice, fever, or malaise, and rarely to fulminant hepatitis. ICI-associated hepatitis appears histologically similar to autoimmune hepatitis, with pan-lobular hepatitis and infiltrating CD8+ T lymphocytes seen on liver biopsy.7 Less commonly, pancreatic toxicity can occur (<2% of irAE), seen with anti-CTLA-4 therapy.8 While this typically results in asymptomatic lipase or amylase elevations (2.7%), acute pancreatitis (AP) can occur(1.9%). ICI-associated AP presents with classic symptoms and imaging changes, but can also manifest with exocrine or endocrine pancreatic insufficiency. An increase in rates of acute acalculous cholecystitis has been reported in patients receiving ICIs compared to patients receiving non-ICI chemotherapy.9 There are also rare reports of ICI-associated secondary sclerosing cholangitis.
Management
Evaluation and management of GI irAEs are guided by severity, based on the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) grading classification (Table 1).10
A thorough history of GI and systemic symptoms should be obtained and compared to baseline bowel habits. Patients with mild symptoms should undergo studies to assess alternate etiologies for their symptoms. Bacterial stool cultures and testing for C. difficile should be performed. Erythrocyte sedimentation rate, C-reactive protein, fecal lactoferrin, and calprotectin can help assess the degree of intestinal inflammation and can be used to risk-stratify or assess treatment response. CT scans can assess for colitis and associated complications, including abdominal abscess, toxic megacolon, and bowel perforation.
Patients unresponsive to initial treatment for grade I irAE, with hematochezia, or with at least grade 2 diarrhea, should undergo GI consultation and endoscopic evaluation. Flexible sigmoidoscopy is the test of choice, as 95% of patients will have left-sided colonic inflammation.11 Patients with at least grade 3 diarrhea should be hospitalized for treatment. In cases of failed methylprednisolone and when infliximab is ineffective or contraindicated, vedolizumab is suggested, although evidence is limited.12
Patients responsive to systemic corticosteroids (complete resolution or improvement to grade 1) can continue a tapered regimen over 4-6 weeks. There is conflicting evidence on the effect that corticosteroids have on ICI-related antitumor response rates. While some studies report no change in antitumor response rates or survival, others report reduced overall survival.13 Regardless, given its unfavorable side-effect profile, steroids should be used only for short periods of time.
PD-1 and PD-L1 antibodies can be restarted after symptoms have resolved or improved to grade 1, having finished the corticosteroid taper. CTLA-4 antibodies should be discontinued permanently in the setting of grade 3 toxicity. All ICIs should be discontinued permanently in grade 4 toxicity.
A grading system also exists for ICI-associated hepatitis (Table 2) and AP (Table 3). Patients with elevated aminotransferases greater than 2x upper limit of normal (ULN) should have alternative etiologies excluded. A thorough medication reconciliation, including over-the-counter and nonpharmaceutical supplements, should be performed. All potentially-hepatotoxic drugs and substances (including alcohol) should be discontinued. Viral hepatitis serology (A,B,C), Epstein-Barr virus, and cytomegalovirus also should be performed. Additional tests, including prothrombin time and albumin, can help assess for liver synthetic dysfunction. Abdominal ultrasound or CT can assist in excluding biliary obstruction or metastatic disease. Magnetic resonance cholangiopancreatography (MRCP) can be considered for further evaluation of biliary obstruction in patients with hyperbilirubinemia and normal ultrasound.14
Table 2 reviews the grading system and management of ICI-associated hepatitis. Patients with grade 3 and above should be hospitalized for treatment. As with the management of colitis, patients responding to corticosteroids should be tapered off over 4-6 weeks. In steroid-refractory cases or if there is no improvement after 3 days, mycophenolate mofetil is used. Other immunomodulators such as azathioprine and tacrolimus also can be considered, although evidence is limited.15 ICI-associated cholangitis presenting with elevated bilirubin and alkaline phosphatase is approached similarly to ICI-associated hepatitis. Abnormal findings of biliary obstruction or sclerosing cholangitis should be further evaluated with endoscopic retrograde cholangiopancreatography.
Mild asymptomatic elevation in lipase and amylase <3x ULN can be managed with observation and ICIs can be safely continued. Symptomatic patients should have a diagnostic workup for other etiologies. As with hepatitis, a thorough history including alcohol intake and a medication reconciliation should be performed. In the absence of other etiologies, grade 2 ICI-associated AP is managed by holding immunotherapy, administering steroids, and managing AP with fluid resuscitation and analgesia.
Conclusions
Therapy with ICI is a rapidly expanding and changing field. Side effects of ICIs can affect nearly every organ system, and thus management should involve a multidisciplinary team of oncologists, pathologists, radiologists, pharmacists, and other specialists. Given that GI adverse effects are the second most commonly affected system, all gastroenterologists and hepatologists should be knowledgeable about the spectrum of GI adverse events, as well as with the respective clinical presentations, diagnostics, and management of these events.
Dr. Kwon is with the division of gastroenterology and hepatology, University of California Irvine, Orange. Dr. Kröner is with the division of advanced endoscopy, Riverside Health System, Newport News, Va. The authors certify that they have no financial arrangements (e.g., consultancies, stock ownership, equity interests, patent-licensing arrangements, research support, honoraria, etc.) with a company whose product figures prominently in this manuscript or with a company making a competing product. Funding: None.
References
1. Webster RM. The immune checkpoint inhibitors: where are we now? Nature Reviews: Drug Discovery. 2014;13(12):883.
2. Thompson JA et al. NCCN guidelines insights: Management of immunotherapy-related toxicities, version 1.2020: Featured updates to the NCCN guidelines. J Natl Compr Canc Netw. 2020;18(3):230-41.
3. Bertrand A et al. Immune related adverse events associated with anti-CTLA-4 antibodies: Systematic review and meta-analysis. BMC Med. 2015 Sep 4;13:211.
4. Gupta A et al. Systematic review: Colitis associated with anti‐CTLA‐4 therapy. Aliment Pharmacol Ther. 2015;42(4):406-17.
5. Verschuren EC et al. Clinical, endoscopic, and histologic characteristics of ipilimumab-associated colitis. Clin Gastroenterol Hepatol. 2016;14(6):836-42.
6. Foppen MHG et al. Immune checkpoint inhibition–related colitis: Symptoms, endoscopic features, histology and response to management. ESMO Open. 2018;3(1):e000278.
7. Sanjeevaiah A et al. Approach and management of checkpoint inhibitor–related immune hepatitis. J Gastrointest Oncol. 2018;9(1):220.
8. Abu-Sbeih H et al. Clinical characteristics and outcomes of immune checkpoint inhibitor–induced pancreatic injury. J Immunother Cancer. 2019 Feb 6;7(1):31.
9. Abu-Sbeih H et al. Case series of cancer patients who developed cholecystitis related to immune checkpoint inhibitor treatment. J Immunother Cancer. 2019 May 3;7(1):118.
10. Thompson JA et al. Management of immunotherapy-related toxicities, version 1.2019, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2019;17(3):255-89.
11. Marthey L et al. Cancer immunotherapy with anti-CTLA-4 monoclonal antibodies induces an inflammatory bowel disease. J Crohns Colitis. 2016;10(4):395-401.
12. Abu-Sbeih H et al. Outcomes of vedolizumab therapy in patients with immune checkpoint inhibitor–induced colitis: A multicenter study. J Immunother Cancer. 2018 Dec 5;6(1):142.
13. Das S and Johnson DB. Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors. J Immunother Cancer. 2019 Nov 15;7(1):306.
14. Reddy HG et al. Immune checkpoint inhibitor–associated colitis and hepatitis. Clin Transl Gastroenterol. 2018 Sep 19;9(9):180.
15. Reynolds K et al. Diagnosis and management of hepatitis in patients on checkpoint blockade. Oncologist. 2018;23(9):991-7.
Lean and clean: Minimally invasive endoscopic and pharmacologic approaches to obesity
Obesity currently affects more than 40% of the U.S. population. It is the second-leading preventable cause of mortality behind smoking with an estimated 300,000 deaths per year.1,2 Weight loss can reduce the risk of metabolic comorbidities such as diabetes, heart disease, and stroke. However, 5%-10% total body weight loss (TBWL) is required for risk reduction.3 Sustained weight loss involves dietary alterations and physical activity, although it is difficult to maintain long term with lifestyle changes alone. Less than 10% of Americans with a BMI greater than 30 kg/m2 will achieve 5% TBWL each year, and nearly 80% of people will regain the weight within 5 years, a phenomenon known as “weight cycling.”4,5 Not only can these weight fluctuations make future weight-loss efforts more difficult, but they can also negatively impact cardiometabolic health in the long term.5 Thus, additional therapies are typically needed in conjunction with lifestyle interventions to treat obesity.
Current guidelines recommend bariatric surgery for patients unable to achieve or maintain weight loss through lifestyle changes.6 Surgeries like Roux-en-Y gastric bypass and sleeve gastrectomy lead to improvements in morbidity and mortality from metabolic diseases but are often only approved for select patients with a BMI of at least 40 or at least 35 with obesity-related comorbidities.7 These restrictions exclude patients at lower BMIs who may have early metabolic disease. Furthermore, only a small proportion of eligible patients are referred or willing to undergo surgery because of access issues, socioeconomic barriers, and concerns about adverse events.8,9 Endoscopic bariatric therapy and antiobesity medications (AOMs) have blossomed because of the need for other less-invasive options to stimulate weight loss.
Minimally invasive and noninvasive therapies in obesity
Endoscopic bariatric and metabolic therapies
Endoscopic bariatric and metabolic therapies (EBMTs) are used for the treatment of obesity in patients with a BMI of 30 kg/m2, a cohort that may be ineligible for bariatric surgery.10,11 EBMTs involve three categories: space-occupying devices (intragastric balloons [IGBs], transpyloric shuttle [TPS]), aspiration therapy, and gastric remodeling (endoscopic sleeve gastroplasty [ESG]).21,13 Presently, TPS and aspiration therapy are not commercially available in the United States. There are three types of IGB approved by the Food and Drug Administration, and Apollo ESGTM recently received de novo marketing authorization for the treatment of obesity. TBWL with EBMTs is promising at 12 months post procedure. Ranges include 7%-12% TBWL for IGBs and 15%-19% for ESG, with low rates of serious adverse events (AEs).13-18 Weight loss often reaches or exceeds the 10% TBWL needed to improve or completely reverse metabolic complications.
Obesity pharmacotherapy
Multiple professional societies support the use of obesity pharmacotherapy as an effective adjunct to lifestyle interventions.19 AOMs are classified as peripherally-acting to prevent nutrition absorption (e.g. orlistat), centrally acting to suppress appetite and/or cravings (e.g., phentermine/topiramate or naltrexone/bupropion), or incretin mimetics such as glucagonlike peptide–1 agonists (e.g., liraglutide, semaglutide).20 With the exception of orlistat, most agents have some effects on the hypothalamus to suppress appetite.21 Obesity medications tend to lead to a minimum weight loss of 3-10 kg after 12 months of treatment, and newer medications have even greater efficacy.22 Despite these results, discontinuation rates of the popular GLP-1 agonists can be as high as 47.7% and 70.1% at 12 and 24 months, respectively, because of the high cost of medications, gastrointestinal side effects, and poor tolerance.23,24
An ongoing challenge for patients is maintaining weight loss following cessation of pharmacotherapy when weight loss goals have been achieved. In this context, the combination of obesity pharmacotherapy and EBMTs can be utilized for long-term weight loss and weight maintenance given the chronic, relapsing, and complex nature of obesity.25
Advantages of less-invasive therapies in obesity management
The advantages of both pharmacologic and endoscopic weight-loss therapies are numerous. Pharmacotherapies are noninvasive, and their multiple mechanisms allow for combined use to synergistically promote weight reduction.26,27 Medications can be used in both the short- and long-term management of obesity, allowing for flexibility in use for patients pending fluctuations in weight. Furthermore, medications can improve markers of cardiovascular health including total cholesterol, LDL cholesterol, blood pressure, and glycemic control.28
As minimally invasive therapies, EBMTs have less morbidity and mortality, compared with bariatric surgeries.29 The most common side effects of IGBs or ESG include abdominal pain, nausea, and worsening of acid reflux symptoms, which can be medically managed unlike some of the AEs associated with surgery, such as bowel obstruction, anastomotic dehiscence, fistulization, and postoperative infections.30 Long-term AEs from surgery also include malabsorption, nutritional deficiencies, cholelithiasis, and anastomotic stenosis.31 Even with improvement in surgical techniques, the rate of perioperative and postoperative mortality in Roux-en-Y gastric bypass is estimated to be 0.4% and 0.7%, respectively, compared with only 0.08% with IGBs.30,32
In addition, EBMTs are also more cost effective than surgery, as they are often same-day outpatient procedures, leading to decreased length of stay (LOS) for patients. In ongoing research conducted by Sharaiha and colleagues, it was found that patients undergoing ESG had an average LOS of only 0.13 days, compared with 3.09 days for laparoscopic sleeve gastrectomy and 1.68 for laparoscopic gastric banding. The cost for ESG was approximately $12,000, compared with $15,000-$22,000 for laparoscopic bariatric surgeries.33 With their availability to patients with lower BMIs and their less-invasive nature, EBMTs and pharmacotherapy can be utilized on the spectrum of obesity care as bridge therapies both before and after surgery.
Our clinical approach
In 2015, the first Veterans Affairs hospital-based endoscopic bariatric program was established at the VA New York Harbor Healthcare System utilizing IGBs and weight loss pharmacotherapy in conjunction with the VA MOVE! Program to treat obesity and metabolic comorbidities in veterans. Since then, EBMTs have expanded to include ESG and novel medications. Our treatment algorithm accounts for the chronic nature of obesity, the risk of weight regain after any intervention, and the need for longitudinal patient care.
Patients undergo work-up by a multidisciplinary team (MD team) with a nutritionist, psychologist, primary care physician, gastroenterologist, and endocrinologist to determine the optimal treatment plan (Fig. 1).29
Patients are required to attend multiple information sessions, where all weight-loss methods are presented, including surgery, bariatric endoscopy, and pharmacotherapy. Other specialists also help manage comorbid conditions. Prior to selecting an initial intervention, patients undergo intensive lifestyle and behavioral therapy (Fig. 2 and 3). Depending on the selected therapy, initial treatment lasts between 3 and 12 months with ongoing support from the MD team.
If patients do not achieve their targeted weight loss after initial treatment, a new strategy is selected. This includes a different EBMT such as ESG, alternate pharmacotherapy, or surgery until the weight and health goals of the patient are achieved and sustained (Fig. 3). From the start, patients are informed that our program is a long-term intervention and that active participation in the MOVE! Program, as well as follow-up with the MD team are keys to success. EBMTs and medications are presented as effective tools that only work to enhance the effects of lifestyle changes.
Our multidisciplinary approach provides flexibility for patients to trial different options depending on their progress. Research on long-term outcomes with weight loss and metabolic parameters is ongoing, though early results are promising. Thus far, we have observed that patients undergoing a combination therapy of EBMTs and AOMs have greater weight loss than patients on a single therapeutic approach with either EBMT or AOMs alone.34 Racial and socioeconomic disparities in referrals to bariatric surgery are yet another barrier for patients to access weight reduction and improvement in cardiovascular health.35 EBMTs and pharmacotherapy are no longer just on the horizon; they are here as accessible, effective, and long-term treatments for all patients with obesity. More expansive insurance coverage is needed for EBMTs and AOMs in order to prevent progression of obesity-related comorbidities, reduce high costs, and ensure more equitable access to these effective therapies.
Dr. Young and Dr. Zenger are resident physicians in the department of internal medicine at New York University. Dr. Holzwanger is an advanced endoscopy fellow in the division of gastroenterology at Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston. Dr. Popov is director of bariatric endoscopy at VA New York Harbor Healthcare System, and assistant professor of medicine at New York University. Dr. Popov reported relationships with Obalon, Microtech, and Spatz, but the remaining authors reported no competing interests.
References
1. Ward ZJ et al. N Engl J Med. 2019;381(25):2440-50.
2. Stein CJ and Colditz GA. J Clin Endocrinol Metab. 2004;89(6):2522-5.
3. Ryan DH and Yockey SR. Curr Obes Rep. 2017;6(2):187-94.
4. Fildes A et al. Am J Public Health. 2015;105(9):e54-9.
5. Rhee E-J. J Obes Metab Syndr. 2017;26(4):237-42.
6. American College of Cardiology/American Heart Association Task Force on Practice Guidelines OEP. Obesity (Silver Spring). 2014;22 Suppl 2:S5-39.
7. Adams TD et al. N Engl J Med. 2018;378(1):93-6.
8. Wharton S et al. Clin Obes. 2016;6(2):154-60.
9. Iuzzolino E and Kim Y. Obes Res Clin Pract. 2020;14(4):310-20.
10. Goyal D, Watson RR. Endoscopic Bariatric Therapies. Curr Gastroenterol Rep. 2016;18(6):26.
11. Ali MR et al. Surg Obes Relat Dis. 2016;12(3):462-467.
12. Turkeltaub JA, Edmundowicz SA. Curr Treat Options Gastroenterol. 2019;17(2):187-201.
13. Reja D et al. Transl Gastroenterol Hepatol. 2022;7:21.
14. Force ABET et al. Gastrointest Endosc. 2015;82(3):425-38e5.
15. Thompson CC et al. Am J Gastroenterol. 2017;112(3):447-57.
16. Nystrom M et al. Obes Surg. 2018;28(7):1860-8.
17. Abu Dayyeh BK et al. Surg Obes Relat Dis. 2019;15(8):1423-4.
18. Sharaiha RZ et al. Clin Gastroenterol Hepatol. 2017;15(4):504-10.
19. Apovian CM et al. J Clin Endocrinol Metab. 2015;100(2):342-62.
20. Son JW and Kim S. Diabetes Metab J. 2020;44(6):802-18.
21. Holst JJ. Int J Obes (Lond). Int J Obes (Lond). 2013;37(9):1161-8.
22. Joo JK and Lee KS. J Menopausal Med. 2014;20(3):90-6.
23. Weiss T et al. Patient Prefer Adherence. 2020;14:2337-45.
24. Sikirica MV et al. Diabetes Metab Syndr Obes. 2017;10:403-12.
25. Kahan S et al. Tech Innov Gastrointest Endosc. 2020;22(3):154-8.
26. Bhat SP and Sharma A. Curr Drug Targets. 2017;18(8):983-93.
27. Pendse J et al. Obesity (Silver Spring). 2021;29(2):308-16.
28. Rucker D et al. BMJ. 2007;335(7631):1194-9.
29. Jirapinyo P and Thompson CC. Clin Gastroenterol Hepatol. 2017;15(5):619-30.
30. Abu Dayyeh BK et al. Gastrointest Endosc. 2015;81(5):1073-86.
31. Schulman AR and Thompson CC. Am J Gastroenterol. 2017;112(11):1640-55.
32. Ma IT and Madura JA, 2nd. Gastroenterol Hepatol (NY). 2015;11(8):526-35.
33. Sharaiha RZ. Endoscopic sleeve gastroplasty as a nonsurgical weight loss alternative. Digestive Disease Week, oral presentation. 2017.
34. Young S et al. Long-term efficacy of a multidisciplinary minimally invasive approach to weight management compared to single endoscopic therapy: A cohort study. P0865. American College of Gastroenterology Meeting, Abstract P0865. 2021.
35. Johnson-Mann C et al. Surg Obes Relat Dis. 2019;15(4):615-20.
Obesity currently affects more than 40% of the U.S. population. It is the second-leading preventable cause of mortality behind smoking with an estimated 300,000 deaths per year.1,2 Weight loss can reduce the risk of metabolic comorbidities such as diabetes, heart disease, and stroke. However, 5%-10% total body weight loss (TBWL) is required for risk reduction.3 Sustained weight loss involves dietary alterations and physical activity, although it is difficult to maintain long term with lifestyle changes alone. Less than 10% of Americans with a BMI greater than 30 kg/m2 will achieve 5% TBWL each year, and nearly 80% of people will regain the weight within 5 years, a phenomenon known as “weight cycling.”4,5 Not only can these weight fluctuations make future weight-loss efforts more difficult, but they can also negatively impact cardiometabolic health in the long term.5 Thus, additional therapies are typically needed in conjunction with lifestyle interventions to treat obesity.
Current guidelines recommend bariatric surgery for patients unable to achieve or maintain weight loss through lifestyle changes.6 Surgeries like Roux-en-Y gastric bypass and sleeve gastrectomy lead to improvements in morbidity and mortality from metabolic diseases but are often only approved for select patients with a BMI of at least 40 or at least 35 with obesity-related comorbidities.7 These restrictions exclude patients at lower BMIs who may have early metabolic disease. Furthermore, only a small proportion of eligible patients are referred or willing to undergo surgery because of access issues, socioeconomic barriers, and concerns about adverse events.8,9 Endoscopic bariatric therapy and antiobesity medications (AOMs) have blossomed because of the need for other less-invasive options to stimulate weight loss.
Minimally invasive and noninvasive therapies in obesity
Endoscopic bariatric and metabolic therapies
Endoscopic bariatric and metabolic therapies (EBMTs) are used for the treatment of obesity in patients with a BMI of 30 kg/m2, a cohort that may be ineligible for bariatric surgery.10,11 EBMTs involve three categories: space-occupying devices (intragastric balloons [IGBs], transpyloric shuttle [TPS]), aspiration therapy, and gastric remodeling (endoscopic sleeve gastroplasty [ESG]).21,13 Presently, TPS and aspiration therapy are not commercially available in the United States. There are three types of IGB approved by the Food and Drug Administration, and Apollo ESGTM recently received de novo marketing authorization for the treatment of obesity. TBWL with EBMTs is promising at 12 months post procedure. Ranges include 7%-12% TBWL for IGBs and 15%-19% for ESG, with low rates of serious adverse events (AEs).13-18 Weight loss often reaches or exceeds the 10% TBWL needed to improve or completely reverse metabolic complications.
Obesity pharmacotherapy
Multiple professional societies support the use of obesity pharmacotherapy as an effective adjunct to lifestyle interventions.19 AOMs are classified as peripherally-acting to prevent nutrition absorption (e.g. orlistat), centrally acting to suppress appetite and/or cravings (e.g., phentermine/topiramate or naltrexone/bupropion), or incretin mimetics such as glucagonlike peptide–1 agonists (e.g., liraglutide, semaglutide).20 With the exception of orlistat, most agents have some effects on the hypothalamus to suppress appetite.21 Obesity medications tend to lead to a minimum weight loss of 3-10 kg after 12 months of treatment, and newer medications have even greater efficacy.22 Despite these results, discontinuation rates of the popular GLP-1 agonists can be as high as 47.7% and 70.1% at 12 and 24 months, respectively, because of the high cost of medications, gastrointestinal side effects, and poor tolerance.23,24
An ongoing challenge for patients is maintaining weight loss following cessation of pharmacotherapy when weight loss goals have been achieved. In this context, the combination of obesity pharmacotherapy and EBMTs can be utilized for long-term weight loss and weight maintenance given the chronic, relapsing, and complex nature of obesity.25
Advantages of less-invasive therapies in obesity management
The advantages of both pharmacologic and endoscopic weight-loss therapies are numerous. Pharmacotherapies are noninvasive, and their multiple mechanisms allow for combined use to synergistically promote weight reduction.26,27 Medications can be used in both the short- and long-term management of obesity, allowing for flexibility in use for patients pending fluctuations in weight. Furthermore, medications can improve markers of cardiovascular health including total cholesterol, LDL cholesterol, blood pressure, and glycemic control.28
As minimally invasive therapies, EBMTs have less morbidity and mortality, compared with bariatric surgeries.29 The most common side effects of IGBs or ESG include abdominal pain, nausea, and worsening of acid reflux symptoms, which can be medically managed unlike some of the AEs associated with surgery, such as bowel obstruction, anastomotic dehiscence, fistulization, and postoperative infections.30 Long-term AEs from surgery also include malabsorption, nutritional deficiencies, cholelithiasis, and anastomotic stenosis.31 Even with improvement in surgical techniques, the rate of perioperative and postoperative mortality in Roux-en-Y gastric bypass is estimated to be 0.4% and 0.7%, respectively, compared with only 0.08% with IGBs.30,32
In addition, EBMTs are also more cost effective than surgery, as they are often same-day outpatient procedures, leading to decreased length of stay (LOS) for patients. In ongoing research conducted by Sharaiha and colleagues, it was found that patients undergoing ESG had an average LOS of only 0.13 days, compared with 3.09 days for laparoscopic sleeve gastrectomy and 1.68 for laparoscopic gastric banding. The cost for ESG was approximately $12,000, compared with $15,000-$22,000 for laparoscopic bariatric surgeries.33 With their availability to patients with lower BMIs and their less-invasive nature, EBMTs and pharmacotherapy can be utilized on the spectrum of obesity care as bridge therapies both before and after surgery.
Our clinical approach
In 2015, the first Veterans Affairs hospital-based endoscopic bariatric program was established at the VA New York Harbor Healthcare System utilizing IGBs and weight loss pharmacotherapy in conjunction with the VA MOVE! Program to treat obesity and metabolic comorbidities in veterans. Since then, EBMTs have expanded to include ESG and novel medications. Our treatment algorithm accounts for the chronic nature of obesity, the risk of weight regain after any intervention, and the need for longitudinal patient care.
Patients undergo work-up by a multidisciplinary team (MD team) with a nutritionist, psychologist, primary care physician, gastroenterologist, and endocrinologist to determine the optimal treatment plan (Fig. 1).29
Patients are required to attend multiple information sessions, where all weight-loss methods are presented, including surgery, bariatric endoscopy, and pharmacotherapy. Other specialists also help manage comorbid conditions. Prior to selecting an initial intervention, patients undergo intensive lifestyle and behavioral therapy (Fig. 2 and 3). Depending on the selected therapy, initial treatment lasts between 3 and 12 months with ongoing support from the MD team.
If patients do not achieve their targeted weight loss after initial treatment, a new strategy is selected. This includes a different EBMT such as ESG, alternate pharmacotherapy, or surgery until the weight and health goals of the patient are achieved and sustained (Fig. 3). From the start, patients are informed that our program is a long-term intervention and that active participation in the MOVE! Program, as well as follow-up with the MD team are keys to success. EBMTs and medications are presented as effective tools that only work to enhance the effects of lifestyle changes.
Our multidisciplinary approach provides flexibility for patients to trial different options depending on their progress. Research on long-term outcomes with weight loss and metabolic parameters is ongoing, though early results are promising. Thus far, we have observed that patients undergoing a combination therapy of EBMTs and AOMs have greater weight loss than patients on a single therapeutic approach with either EBMT or AOMs alone.34 Racial and socioeconomic disparities in referrals to bariatric surgery are yet another barrier for patients to access weight reduction and improvement in cardiovascular health.35 EBMTs and pharmacotherapy are no longer just on the horizon; they are here as accessible, effective, and long-term treatments for all patients with obesity. More expansive insurance coverage is needed for EBMTs and AOMs in order to prevent progression of obesity-related comorbidities, reduce high costs, and ensure more equitable access to these effective therapies.
Dr. Young and Dr. Zenger are resident physicians in the department of internal medicine at New York University. Dr. Holzwanger is an advanced endoscopy fellow in the division of gastroenterology at Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston. Dr. Popov is director of bariatric endoscopy at VA New York Harbor Healthcare System, and assistant professor of medicine at New York University. Dr. Popov reported relationships with Obalon, Microtech, and Spatz, but the remaining authors reported no competing interests.
References
1. Ward ZJ et al. N Engl J Med. 2019;381(25):2440-50.
2. Stein CJ and Colditz GA. J Clin Endocrinol Metab. 2004;89(6):2522-5.
3. Ryan DH and Yockey SR. Curr Obes Rep. 2017;6(2):187-94.
4. Fildes A et al. Am J Public Health. 2015;105(9):e54-9.
5. Rhee E-J. J Obes Metab Syndr. 2017;26(4):237-42.
6. American College of Cardiology/American Heart Association Task Force on Practice Guidelines OEP. Obesity (Silver Spring). 2014;22 Suppl 2:S5-39.
7. Adams TD et al. N Engl J Med. 2018;378(1):93-6.
8. Wharton S et al. Clin Obes. 2016;6(2):154-60.
9. Iuzzolino E and Kim Y. Obes Res Clin Pract. 2020;14(4):310-20.
10. Goyal D, Watson RR. Endoscopic Bariatric Therapies. Curr Gastroenterol Rep. 2016;18(6):26.
11. Ali MR et al. Surg Obes Relat Dis. 2016;12(3):462-467.
12. Turkeltaub JA, Edmundowicz SA. Curr Treat Options Gastroenterol. 2019;17(2):187-201.
13. Reja D et al. Transl Gastroenterol Hepatol. 2022;7:21.
14. Force ABET et al. Gastrointest Endosc. 2015;82(3):425-38e5.
15. Thompson CC et al. Am J Gastroenterol. 2017;112(3):447-57.
16. Nystrom M et al. Obes Surg. 2018;28(7):1860-8.
17. Abu Dayyeh BK et al. Surg Obes Relat Dis. 2019;15(8):1423-4.
18. Sharaiha RZ et al. Clin Gastroenterol Hepatol. 2017;15(4):504-10.
19. Apovian CM et al. J Clin Endocrinol Metab. 2015;100(2):342-62.
20. Son JW and Kim S. Diabetes Metab J. 2020;44(6):802-18.
21. Holst JJ. Int J Obes (Lond). Int J Obes (Lond). 2013;37(9):1161-8.
22. Joo JK and Lee KS. J Menopausal Med. 2014;20(3):90-6.
23. Weiss T et al. Patient Prefer Adherence. 2020;14:2337-45.
24. Sikirica MV et al. Diabetes Metab Syndr Obes. 2017;10:403-12.
25. Kahan S et al. Tech Innov Gastrointest Endosc. 2020;22(3):154-8.
26. Bhat SP and Sharma A. Curr Drug Targets. 2017;18(8):983-93.
27. Pendse J et al. Obesity (Silver Spring). 2021;29(2):308-16.
28. Rucker D et al. BMJ. 2007;335(7631):1194-9.
29. Jirapinyo P and Thompson CC. Clin Gastroenterol Hepatol. 2017;15(5):619-30.
30. Abu Dayyeh BK et al. Gastrointest Endosc. 2015;81(5):1073-86.
31. Schulman AR and Thompson CC. Am J Gastroenterol. 2017;112(11):1640-55.
32. Ma IT and Madura JA, 2nd. Gastroenterol Hepatol (NY). 2015;11(8):526-35.
33. Sharaiha RZ. Endoscopic sleeve gastroplasty as a nonsurgical weight loss alternative. Digestive Disease Week, oral presentation. 2017.
34. Young S et al. Long-term efficacy of a multidisciplinary minimally invasive approach to weight management compared to single endoscopic therapy: A cohort study. P0865. American College of Gastroenterology Meeting, Abstract P0865. 2021.
35. Johnson-Mann C et al. Surg Obes Relat Dis. 2019;15(4):615-20.
Obesity currently affects more than 40% of the U.S. population. It is the second-leading preventable cause of mortality behind smoking with an estimated 300,000 deaths per year.1,2 Weight loss can reduce the risk of metabolic comorbidities such as diabetes, heart disease, and stroke. However, 5%-10% total body weight loss (TBWL) is required for risk reduction.3 Sustained weight loss involves dietary alterations and physical activity, although it is difficult to maintain long term with lifestyle changes alone. Less than 10% of Americans with a BMI greater than 30 kg/m2 will achieve 5% TBWL each year, and nearly 80% of people will regain the weight within 5 years, a phenomenon known as “weight cycling.”4,5 Not only can these weight fluctuations make future weight-loss efforts more difficult, but they can also negatively impact cardiometabolic health in the long term.5 Thus, additional therapies are typically needed in conjunction with lifestyle interventions to treat obesity.
Current guidelines recommend bariatric surgery for patients unable to achieve or maintain weight loss through lifestyle changes.6 Surgeries like Roux-en-Y gastric bypass and sleeve gastrectomy lead to improvements in morbidity and mortality from metabolic diseases but are often only approved for select patients with a BMI of at least 40 or at least 35 with obesity-related comorbidities.7 These restrictions exclude patients at lower BMIs who may have early metabolic disease. Furthermore, only a small proportion of eligible patients are referred or willing to undergo surgery because of access issues, socioeconomic barriers, and concerns about adverse events.8,9 Endoscopic bariatric therapy and antiobesity medications (AOMs) have blossomed because of the need for other less-invasive options to stimulate weight loss.
Minimally invasive and noninvasive therapies in obesity
Endoscopic bariatric and metabolic therapies
Endoscopic bariatric and metabolic therapies (EBMTs) are used for the treatment of obesity in patients with a BMI of 30 kg/m2, a cohort that may be ineligible for bariatric surgery.10,11 EBMTs involve three categories: space-occupying devices (intragastric balloons [IGBs], transpyloric shuttle [TPS]), aspiration therapy, and gastric remodeling (endoscopic sleeve gastroplasty [ESG]).21,13 Presently, TPS and aspiration therapy are not commercially available in the United States. There are three types of IGB approved by the Food and Drug Administration, and Apollo ESGTM recently received de novo marketing authorization for the treatment of obesity. TBWL with EBMTs is promising at 12 months post procedure. Ranges include 7%-12% TBWL for IGBs and 15%-19% for ESG, with low rates of serious adverse events (AEs).13-18 Weight loss often reaches or exceeds the 10% TBWL needed to improve or completely reverse metabolic complications.
Obesity pharmacotherapy
Multiple professional societies support the use of obesity pharmacotherapy as an effective adjunct to lifestyle interventions.19 AOMs are classified as peripherally-acting to prevent nutrition absorption (e.g. orlistat), centrally acting to suppress appetite and/or cravings (e.g., phentermine/topiramate or naltrexone/bupropion), or incretin mimetics such as glucagonlike peptide–1 agonists (e.g., liraglutide, semaglutide).20 With the exception of orlistat, most agents have some effects on the hypothalamus to suppress appetite.21 Obesity medications tend to lead to a minimum weight loss of 3-10 kg after 12 months of treatment, and newer medications have even greater efficacy.22 Despite these results, discontinuation rates of the popular GLP-1 agonists can be as high as 47.7% and 70.1% at 12 and 24 months, respectively, because of the high cost of medications, gastrointestinal side effects, and poor tolerance.23,24
An ongoing challenge for patients is maintaining weight loss following cessation of pharmacotherapy when weight loss goals have been achieved. In this context, the combination of obesity pharmacotherapy and EBMTs can be utilized for long-term weight loss and weight maintenance given the chronic, relapsing, and complex nature of obesity.25
Advantages of less-invasive therapies in obesity management
The advantages of both pharmacologic and endoscopic weight-loss therapies are numerous. Pharmacotherapies are noninvasive, and their multiple mechanisms allow for combined use to synergistically promote weight reduction.26,27 Medications can be used in both the short- and long-term management of obesity, allowing for flexibility in use for patients pending fluctuations in weight. Furthermore, medications can improve markers of cardiovascular health including total cholesterol, LDL cholesterol, blood pressure, and glycemic control.28
As minimally invasive therapies, EBMTs have less morbidity and mortality, compared with bariatric surgeries.29 The most common side effects of IGBs or ESG include abdominal pain, nausea, and worsening of acid reflux symptoms, which can be medically managed unlike some of the AEs associated with surgery, such as bowel obstruction, anastomotic dehiscence, fistulization, and postoperative infections.30 Long-term AEs from surgery also include malabsorption, nutritional deficiencies, cholelithiasis, and anastomotic stenosis.31 Even with improvement in surgical techniques, the rate of perioperative and postoperative mortality in Roux-en-Y gastric bypass is estimated to be 0.4% and 0.7%, respectively, compared with only 0.08% with IGBs.30,32
In addition, EBMTs are also more cost effective than surgery, as they are often same-day outpatient procedures, leading to decreased length of stay (LOS) for patients. In ongoing research conducted by Sharaiha and colleagues, it was found that patients undergoing ESG had an average LOS of only 0.13 days, compared with 3.09 days for laparoscopic sleeve gastrectomy and 1.68 for laparoscopic gastric banding. The cost for ESG was approximately $12,000, compared with $15,000-$22,000 for laparoscopic bariatric surgeries.33 With their availability to patients with lower BMIs and their less-invasive nature, EBMTs and pharmacotherapy can be utilized on the spectrum of obesity care as bridge therapies both before and after surgery.
Our clinical approach
In 2015, the first Veterans Affairs hospital-based endoscopic bariatric program was established at the VA New York Harbor Healthcare System utilizing IGBs and weight loss pharmacotherapy in conjunction with the VA MOVE! Program to treat obesity and metabolic comorbidities in veterans. Since then, EBMTs have expanded to include ESG and novel medications. Our treatment algorithm accounts for the chronic nature of obesity, the risk of weight regain after any intervention, and the need for longitudinal patient care.
Patients undergo work-up by a multidisciplinary team (MD team) with a nutritionist, psychologist, primary care physician, gastroenterologist, and endocrinologist to determine the optimal treatment plan (Fig. 1).29
Patients are required to attend multiple information sessions, where all weight-loss methods are presented, including surgery, bariatric endoscopy, and pharmacotherapy. Other specialists also help manage comorbid conditions. Prior to selecting an initial intervention, patients undergo intensive lifestyle and behavioral therapy (Fig. 2 and 3). Depending on the selected therapy, initial treatment lasts between 3 and 12 months with ongoing support from the MD team.
If patients do not achieve their targeted weight loss after initial treatment, a new strategy is selected. This includes a different EBMT such as ESG, alternate pharmacotherapy, or surgery until the weight and health goals of the patient are achieved and sustained (Fig. 3). From the start, patients are informed that our program is a long-term intervention and that active participation in the MOVE! Program, as well as follow-up with the MD team are keys to success. EBMTs and medications are presented as effective tools that only work to enhance the effects of lifestyle changes.
Our multidisciplinary approach provides flexibility for patients to trial different options depending on their progress. Research on long-term outcomes with weight loss and metabolic parameters is ongoing, though early results are promising. Thus far, we have observed that patients undergoing a combination therapy of EBMTs and AOMs have greater weight loss than patients on a single therapeutic approach with either EBMT or AOMs alone.34 Racial and socioeconomic disparities in referrals to bariatric surgery are yet another barrier for patients to access weight reduction and improvement in cardiovascular health.35 EBMTs and pharmacotherapy are no longer just on the horizon; they are here as accessible, effective, and long-term treatments for all patients with obesity. More expansive insurance coverage is needed for EBMTs and AOMs in order to prevent progression of obesity-related comorbidities, reduce high costs, and ensure more equitable access to these effective therapies.
Dr. Young and Dr. Zenger are resident physicians in the department of internal medicine at New York University. Dr. Holzwanger is an advanced endoscopy fellow in the division of gastroenterology at Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston. Dr. Popov is director of bariatric endoscopy at VA New York Harbor Healthcare System, and assistant professor of medicine at New York University. Dr. Popov reported relationships with Obalon, Microtech, and Spatz, but the remaining authors reported no competing interests.
References
1. Ward ZJ et al. N Engl J Med. 2019;381(25):2440-50.
2. Stein CJ and Colditz GA. J Clin Endocrinol Metab. 2004;89(6):2522-5.
3. Ryan DH and Yockey SR. Curr Obes Rep. 2017;6(2):187-94.
4. Fildes A et al. Am J Public Health. 2015;105(9):e54-9.
5. Rhee E-J. J Obes Metab Syndr. 2017;26(4):237-42.
6. American College of Cardiology/American Heart Association Task Force on Practice Guidelines OEP. Obesity (Silver Spring). 2014;22 Suppl 2:S5-39.
7. Adams TD et al. N Engl J Med. 2018;378(1):93-6.
8. Wharton S et al. Clin Obes. 2016;6(2):154-60.
9. Iuzzolino E and Kim Y. Obes Res Clin Pract. 2020;14(4):310-20.
10. Goyal D, Watson RR. Endoscopic Bariatric Therapies. Curr Gastroenterol Rep. 2016;18(6):26.
11. Ali MR et al. Surg Obes Relat Dis. 2016;12(3):462-467.
12. Turkeltaub JA, Edmundowicz SA. Curr Treat Options Gastroenterol. 2019;17(2):187-201.
13. Reja D et al. Transl Gastroenterol Hepatol. 2022;7:21.
14. Force ABET et al. Gastrointest Endosc. 2015;82(3):425-38e5.
15. Thompson CC et al. Am J Gastroenterol. 2017;112(3):447-57.
16. Nystrom M et al. Obes Surg. 2018;28(7):1860-8.
17. Abu Dayyeh BK et al. Surg Obes Relat Dis. 2019;15(8):1423-4.
18. Sharaiha RZ et al. Clin Gastroenterol Hepatol. 2017;15(4):504-10.
19. Apovian CM et al. J Clin Endocrinol Metab. 2015;100(2):342-62.
20. Son JW and Kim S. Diabetes Metab J. 2020;44(6):802-18.
21. Holst JJ. Int J Obes (Lond). Int J Obes (Lond). 2013;37(9):1161-8.
22. Joo JK and Lee KS. J Menopausal Med. 2014;20(3):90-6.
23. Weiss T et al. Patient Prefer Adherence. 2020;14:2337-45.
24. Sikirica MV et al. Diabetes Metab Syndr Obes. 2017;10:403-12.
25. Kahan S et al. Tech Innov Gastrointest Endosc. 2020;22(3):154-8.
26. Bhat SP and Sharma A. Curr Drug Targets. 2017;18(8):983-93.
27. Pendse J et al. Obesity (Silver Spring). 2021;29(2):308-16.
28. Rucker D et al. BMJ. 2007;335(7631):1194-9.
29. Jirapinyo P and Thompson CC. Clin Gastroenterol Hepatol. 2017;15(5):619-30.
30. Abu Dayyeh BK et al. Gastrointest Endosc. 2015;81(5):1073-86.
31. Schulman AR and Thompson CC. Am J Gastroenterol. 2017;112(11):1640-55.
32. Ma IT and Madura JA, 2nd. Gastroenterol Hepatol (NY). 2015;11(8):526-35.
33. Sharaiha RZ. Endoscopic sleeve gastroplasty as a nonsurgical weight loss alternative. Digestive Disease Week, oral presentation. 2017.
34. Young S et al. Long-term efficacy of a multidisciplinary minimally invasive approach to weight management compared to single endoscopic therapy: A cohort study. P0865. American College of Gastroenterology Meeting, Abstract P0865. 2021.
35. Johnson-Mann C et al. Surg Obes Relat Dis. 2019;15(4):615-20.
Endoscopic management of duodenal and ampullary adenomas
Duodenal polyps are a relatively rare entity with a reported incidence of 0.3%-4.6%.1 There are three major types of duodenal adenomas: sporadic, nonampullary duodenal adenomas (SNDAs), adenomas in familial adenomatous polyposis syndrome, and ampullary adenomas. It is important to distinguish between the different types of duodenal polyps as the management may differ depending on the etiology.
SNDAs constitute <10% of all duodenal polyps, most commonly located in the second portion of the duodenum, and up to 85% have been shown to have malignant transformation over time.2 Most of the studies of SNDAs are small series, and there are no consensus guidelines for management. Villous features increase malignancy risk, thus resection of SNDAs is advised.3-7 It has also been shown that 72% of patients with SNDAs also have colon polyps,8 and therefore these patients should be up to date on colonoscopy screening.
Ampullary adenomas are less common, but up to half may be associated with familial adenomatous polyposis (FAP), and some may be surveyed.9 However, those that are larger than 10 mm or have villous features may raise concern for malignancy with up to half harboring small foci of adenocarcinoma.10,11 These require ERCP with ampullectomy. For the purposes of this paper, we will focus on endoscopic resection of SNDAs and ampullary adenomas.
Endoscopic mucosal resection (EMR) of duodenal polyps can be technically challenging. There are considerations specific to the duodenum: thin muscle layer, increased motility, and significant vascular supply including two major arterial supplies – the gastroduodenal artery from the celiac branch and the inferior pancreaticoduodenal artery from the superior mesenteric artery. These factors may explain higher reported rates of perforation and bleeding compared to colon EMR.
After a detailed inspection is performed to define the duodenal polyp in terms of size, location, and position relative to the ampulla, a submucosal injection is performed using a dye solution. Once adequate lift is achieved, the lesion is resected using stiff monofilament snares. If possible, resection sites are closed with hemostatic clips, although their utility in preventing delayed complications may be less than that in the colon because of increased motility causing them to become dislodged more easily. We avoid using snares larger than 2 cm given increased risk of perforation. Intraprocedural bleeding may be controlled with coagulation graspers on soft coagulation setting; using a bipolar electrocoagulation therapy or argon plasma coagulation is avoided, as these have been shown to increase rates of complications. Figure 1 provides examples of duodenal adenomas that have been resected.
The ampullectomy technique is slightly different from duodenal EMRs and carries the additional risk of pancreatitis.12,13 In our opinion, there is low utility for submucosal injection unless there is a laterally spreading component onto the duodenal wall, as injection of the ampulla itself does not lift well and simply distorts views. Typically, both the common bile duct and the pancreatic duct are injected with contrast, and we typically perform a biliary sphincterotomy prior to ampullectomy. Based on endoscopist preference, one can also leave a guide wire in the pancreatic duct (PD) and pass the snare over it to perform resection to maintain access for a subsequent stent placement. This technique has the advantage of never losing pancreatic duct access, which can occur after resection from edema or bleeding and allows easy PD stent placement. The snare should be opened in a line corresponding to the long axis of the mound with the snare tip anchored above the apex of the papilla and snare opened and drawn down over the papilla. After resection, the PD must be stented to minimize pancreatitis risk.14 Figure 2 shows an ampullary adenoma pre and post EMR, with a PD stent.
Recurrence of duodenal adenomas, both SNDAs and ampullary, can be quite high, with reports up to 39%.15-18 Risk factors include histology and size, but interestingly were not shown to be associated with en-bloc resection.15,19 On the other hand, intraprocedural bleeding also occurs in up to 43% of patients and is associated with size, number of resections, and procedure time.20 Per 2015 ASGE Standards of Practice, duodenal lesions warrant short follow-up at 3- to 6-month intervals given high recurrence rates, then at 6- to 12-month intervals for 2-5 years thereafter.21
When a duodenal polyp is detected, it is important to determine which type of adenoma it is to guide management. There are various techniques utilized to perform duodenal EMR and ampullectomy with some highlighted in this article. It is important to understand how to recognize, prevent, and manage associated adverse events, as well as to have a surveillance plan given the risk of recurrence.
Dr. Kim has no disclosures. Dr. Siddiqui has financial relationships with Boston Scientific (research support, consulting fees, speaking honoraria); Cook, Medtronic, ConMed (consulting fees, speaking honoraria); and Pinnacle Biologic, Ovesco (speaking honoraria).
Dr. Kim is a GI fellow, section of gastroenterology, hepatology, and nutrition, department of internal medicine, University of Chicago. Dr. Siddiqui is a professor of medicine and the director of the Center for Endoscopic Research and Therapeutics (CERT), section of gastroenterology, hepatology, and nutrition, department of internal medicine, University of Chicago.
References
1. Jepsen JM et al. Scand J Gastroenterol. Jun 1994;29(6):483-7.
2. Sellner F. Cancer. 1990 Aug 15;66(4):702-15.
3. Witteman BJ et al. Neth J Med. 1993 Feb;42(1-2):5-11.
4. Reddy RR et al. J Clin Gastroenterol. 1981 Jun;3(2):139-47.
5. Sakorafas GH et al. Scand J Gastroenterol. 2000 Apr;35(4):337-44.
6. Galandiuk S et al. Ann Surg. 1988 Mar;207(3):234-9.
7. Farnell MB et al. J Gastrointest Surg. 2000 Jan-Feb;4(1):13-21, discussion 22-3.
8. Apel D et al. Gastrointest Endosc. 2004 Sep;60(3):397-9.
9. Kashiwagi H et al. Lancet. 1994 Dec 3;344(8936):1582.
10. Clary BM et al. Surgery. 2000 Jun;127(6):628-33.
11. Posner S et al. Surgery. 2000 Oct;128(4):694-701.
12. Harewood GC et al. Gastrointest Endosc. 2005 Sep;62(3):367-70.
13. Chini P et al. World J Gastrointest Endosc. 2011 Dec 16;3(12):241-7.
14. Chang WI et al. Gut Liver. May 2014;8(3):306-12.
15. Hoibian S et al. Ann Gastroenterol. 2021;34(2):169-176. doi: 10.20524/aog.2021.0581.
16. Kakushima N et al. World J Gastroenterol. 2014 Sep 21;20(35):12501-8.
17. Lienert A and Bagshaw PF. ANZ J Surg. 2007 May;77(5):371-3.
18. Singh A et al. Gastrointest Endosc. 2016 Oct;84(4):700-8.
19. Tomizawa Y and Ginsberg GG. Gastrointest Endosc. 2018 May;87(5):1270-8.
20. Klein A et al. Gastrointest Endosc. 2016 Oct;84(4):688-96.
21. Chathadi KV et al. Gastrointest Endosc. 2015 Nov;82(5):773-81.
Duodenal polyps are a relatively rare entity with a reported incidence of 0.3%-4.6%.1 There are three major types of duodenal adenomas: sporadic, nonampullary duodenal adenomas (SNDAs), adenomas in familial adenomatous polyposis syndrome, and ampullary adenomas. It is important to distinguish between the different types of duodenal polyps as the management may differ depending on the etiology.
SNDAs constitute <10% of all duodenal polyps, most commonly located in the second portion of the duodenum, and up to 85% have been shown to have malignant transformation over time.2 Most of the studies of SNDAs are small series, and there are no consensus guidelines for management. Villous features increase malignancy risk, thus resection of SNDAs is advised.3-7 It has also been shown that 72% of patients with SNDAs also have colon polyps,8 and therefore these patients should be up to date on colonoscopy screening.
Ampullary adenomas are less common, but up to half may be associated with familial adenomatous polyposis (FAP), and some may be surveyed.9 However, those that are larger than 10 mm or have villous features may raise concern for malignancy with up to half harboring small foci of adenocarcinoma.10,11 These require ERCP with ampullectomy. For the purposes of this paper, we will focus on endoscopic resection of SNDAs and ampullary adenomas.
Endoscopic mucosal resection (EMR) of duodenal polyps can be technically challenging. There are considerations specific to the duodenum: thin muscle layer, increased motility, and significant vascular supply including two major arterial supplies – the gastroduodenal artery from the celiac branch and the inferior pancreaticoduodenal artery from the superior mesenteric artery. These factors may explain higher reported rates of perforation and bleeding compared to colon EMR.
After a detailed inspection is performed to define the duodenal polyp in terms of size, location, and position relative to the ampulla, a submucosal injection is performed using a dye solution. Once adequate lift is achieved, the lesion is resected using stiff monofilament snares. If possible, resection sites are closed with hemostatic clips, although their utility in preventing delayed complications may be less than that in the colon because of increased motility causing them to become dislodged more easily. We avoid using snares larger than 2 cm given increased risk of perforation. Intraprocedural bleeding may be controlled with coagulation graspers on soft coagulation setting; using a bipolar electrocoagulation therapy or argon plasma coagulation is avoided, as these have been shown to increase rates of complications. Figure 1 provides examples of duodenal adenomas that have been resected.
The ampullectomy technique is slightly different from duodenal EMRs and carries the additional risk of pancreatitis.12,13 In our opinion, there is low utility for submucosal injection unless there is a laterally spreading component onto the duodenal wall, as injection of the ampulla itself does not lift well and simply distorts views. Typically, both the common bile duct and the pancreatic duct are injected with contrast, and we typically perform a biliary sphincterotomy prior to ampullectomy. Based on endoscopist preference, one can also leave a guide wire in the pancreatic duct (PD) and pass the snare over it to perform resection to maintain access for a subsequent stent placement. This technique has the advantage of never losing pancreatic duct access, which can occur after resection from edema or bleeding and allows easy PD stent placement. The snare should be opened in a line corresponding to the long axis of the mound with the snare tip anchored above the apex of the papilla and snare opened and drawn down over the papilla. After resection, the PD must be stented to minimize pancreatitis risk.14 Figure 2 shows an ampullary adenoma pre and post EMR, with a PD stent.
Recurrence of duodenal adenomas, both SNDAs and ampullary, can be quite high, with reports up to 39%.15-18 Risk factors include histology and size, but interestingly were not shown to be associated with en-bloc resection.15,19 On the other hand, intraprocedural bleeding also occurs in up to 43% of patients and is associated with size, number of resections, and procedure time.20 Per 2015 ASGE Standards of Practice, duodenal lesions warrant short follow-up at 3- to 6-month intervals given high recurrence rates, then at 6- to 12-month intervals for 2-5 years thereafter.21
When a duodenal polyp is detected, it is important to determine which type of adenoma it is to guide management. There are various techniques utilized to perform duodenal EMR and ampullectomy with some highlighted in this article. It is important to understand how to recognize, prevent, and manage associated adverse events, as well as to have a surveillance plan given the risk of recurrence.
Dr. Kim has no disclosures. Dr. Siddiqui has financial relationships with Boston Scientific (research support, consulting fees, speaking honoraria); Cook, Medtronic, ConMed (consulting fees, speaking honoraria); and Pinnacle Biologic, Ovesco (speaking honoraria).
Dr. Kim is a GI fellow, section of gastroenterology, hepatology, and nutrition, department of internal medicine, University of Chicago. Dr. Siddiqui is a professor of medicine and the director of the Center for Endoscopic Research and Therapeutics (CERT), section of gastroenterology, hepatology, and nutrition, department of internal medicine, University of Chicago.
References
1. Jepsen JM et al. Scand J Gastroenterol. Jun 1994;29(6):483-7.
2. Sellner F. Cancer. 1990 Aug 15;66(4):702-15.
3. Witteman BJ et al. Neth J Med. 1993 Feb;42(1-2):5-11.
4. Reddy RR et al. J Clin Gastroenterol. 1981 Jun;3(2):139-47.
5. Sakorafas GH et al. Scand J Gastroenterol. 2000 Apr;35(4):337-44.
6. Galandiuk S et al. Ann Surg. 1988 Mar;207(3):234-9.
7. Farnell MB et al. J Gastrointest Surg. 2000 Jan-Feb;4(1):13-21, discussion 22-3.
8. Apel D et al. Gastrointest Endosc. 2004 Sep;60(3):397-9.
9. Kashiwagi H et al. Lancet. 1994 Dec 3;344(8936):1582.
10. Clary BM et al. Surgery. 2000 Jun;127(6):628-33.
11. Posner S et al. Surgery. 2000 Oct;128(4):694-701.
12. Harewood GC et al. Gastrointest Endosc. 2005 Sep;62(3):367-70.
13. Chini P et al. World J Gastrointest Endosc. 2011 Dec 16;3(12):241-7.
14. Chang WI et al. Gut Liver. May 2014;8(3):306-12.
15. Hoibian S et al. Ann Gastroenterol. 2021;34(2):169-176. doi: 10.20524/aog.2021.0581.
16. Kakushima N et al. World J Gastroenterol. 2014 Sep 21;20(35):12501-8.
17. Lienert A and Bagshaw PF. ANZ J Surg. 2007 May;77(5):371-3.
18. Singh A et al. Gastrointest Endosc. 2016 Oct;84(4):700-8.
19. Tomizawa Y and Ginsberg GG. Gastrointest Endosc. 2018 May;87(5):1270-8.
20. Klein A et al. Gastrointest Endosc. 2016 Oct;84(4):688-96.
21. Chathadi KV et al. Gastrointest Endosc. 2015 Nov;82(5):773-81.
Duodenal polyps are a relatively rare entity with a reported incidence of 0.3%-4.6%.1 There are three major types of duodenal adenomas: sporadic, nonampullary duodenal adenomas (SNDAs), adenomas in familial adenomatous polyposis syndrome, and ampullary adenomas. It is important to distinguish between the different types of duodenal polyps as the management may differ depending on the etiology.
SNDAs constitute <10% of all duodenal polyps, most commonly located in the second portion of the duodenum, and up to 85% have been shown to have malignant transformation over time.2 Most of the studies of SNDAs are small series, and there are no consensus guidelines for management. Villous features increase malignancy risk, thus resection of SNDAs is advised.3-7 It has also been shown that 72% of patients with SNDAs also have colon polyps,8 and therefore these patients should be up to date on colonoscopy screening.
Ampullary adenomas are less common, but up to half may be associated with familial adenomatous polyposis (FAP), and some may be surveyed.9 However, those that are larger than 10 mm or have villous features may raise concern for malignancy with up to half harboring small foci of adenocarcinoma.10,11 These require ERCP with ampullectomy. For the purposes of this paper, we will focus on endoscopic resection of SNDAs and ampullary adenomas.
Endoscopic mucosal resection (EMR) of duodenal polyps can be technically challenging. There are considerations specific to the duodenum: thin muscle layer, increased motility, and significant vascular supply including two major arterial supplies – the gastroduodenal artery from the celiac branch and the inferior pancreaticoduodenal artery from the superior mesenteric artery. These factors may explain higher reported rates of perforation and bleeding compared to colon EMR.
After a detailed inspection is performed to define the duodenal polyp in terms of size, location, and position relative to the ampulla, a submucosal injection is performed using a dye solution. Once adequate lift is achieved, the lesion is resected using stiff monofilament snares. If possible, resection sites are closed with hemostatic clips, although their utility in preventing delayed complications may be less than that in the colon because of increased motility causing them to become dislodged more easily. We avoid using snares larger than 2 cm given increased risk of perforation. Intraprocedural bleeding may be controlled with coagulation graspers on soft coagulation setting; using a bipolar electrocoagulation therapy or argon plasma coagulation is avoided, as these have been shown to increase rates of complications. Figure 1 provides examples of duodenal adenomas that have been resected.
The ampullectomy technique is slightly different from duodenal EMRs and carries the additional risk of pancreatitis.12,13 In our opinion, there is low utility for submucosal injection unless there is a laterally spreading component onto the duodenal wall, as injection of the ampulla itself does not lift well and simply distorts views. Typically, both the common bile duct and the pancreatic duct are injected with contrast, and we typically perform a biliary sphincterotomy prior to ampullectomy. Based on endoscopist preference, one can also leave a guide wire in the pancreatic duct (PD) and pass the snare over it to perform resection to maintain access for a subsequent stent placement. This technique has the advantage of never losing pancreatic duct access, which can occur after resection from edema or bleeding and allows easy PD stent placement. The snare should be opened in a line corresponding to the long axis of the mound with the snare tip anchored above the apex of the papilla and snare opened and drawn down over the papilla. After resection, the PD must be stented to minimize pancreatitis risk.14 Figure 2 shows an ampullary adenoma pre and post EMR, with a PD stent.
Recurrence of duodenal adenomas, both SNDAs and ampullary, can be quite high, with reports up to 39%.15-18 Risk factors include histology and size, but interestingly were not shown to be associated with en-bloc resection.15,19 On the other hand, intraprocedural bleeding also occurs in up to 43% of patients and is associated with size, number of resections, and procedure time.20 Per 2015 ASGE Standards of Practice, duodenal lesions warrant short follow-up at 3- to 6-month intervals given high recurrence rates, then at 6- to 12-month intervals for 2-5 years thereafter.21
When a duodenal polyp is detected, it is important to determine which type of adenoma it is to guide management. There are various techniques utilized to perform duodenal EMR and ampullectomy with some highlighted in this article. It is important to understand how to recognize, prevent, and manage associated adverse events, as well as to have a surveillance plan given the risk of recurrence.
Dr. Kim has no disclosures. Dr. Siddiqui has financial relationships with Boston Scientific (research support, consulting fees, speaking honoraria); Cook, Medtronic, ConMed (consulting fees, speaking honoraria); and Pinnacle Biologic, Ovesco (speaking honoraria).
Dr. Kim is a GI fellow, section of gastroenterology, hepatology, and nutrition, department of internal medicine, University of Chicago. Dr. Siddiqui is a professor of medicine and the director of the Center for Endoscopic Research and Therapeutics (CERT), section of gastroenterology, hepatology, and nutrition, department of internal medicine, University of Chicago.
References
1. Jepsen JM et al. Scand J Gastroenterol. Jun 1994;29(6):483-7.
2. Sellner F. Cancer. 1990 Aug 15;66(4):702-15.
3. Witteman BJ et al. Neth J Med. 1993 Feb;42(1-2):5-11.
4. Reddy RR et al. J Clin Gastroenterol. 1981 Jun;3(2):139-47.
5. Sakorafas GH et al. Scand J Gastroenterol. 2000 Apr;35(4):337-44.
6. Galandiuk S et al. Ann Surg. 1988 Mar;207(3):234-9.
7. Farnell MB et al. J Gastrointest Surg. 2000 Jan-Feb;4(1):13-21, discussion 22-3.
8. Apel D et al. Gastrointest Endosc. 2004 Sep;60(3):397-9.
9. Kashiwagi H et al. Lancet. 1994 Dec 3;344(8936):1582.
10. Clary BM et al. Surgery. 2000 Jun;127(6):628-33.
11. Posner S et al. Surgery. 2000 Oct;128(4):694-701.
12. Harewood GC et al. Gastrointest Endosc. 2005 Sep;62(3):367-70.
13. Chini P et al. World J Gastrointest Endosc. 2011 Dec 16;3(12):241-7.
14. Chang WI et al. Gut Liver. May 2014;8(3):306-12.
15. Hoibian S et al. Ann Gastroenterol. 2021;34(2):169-176. doi: 10.20524/aog.2021.0581.
16. Kakushima N et al. World J Gastroenterol. 2014 Sep 21;20(35):12501-8.
17. Lienert A and Bagshaw PF. ANZ J Surg. 2007 May;77(5):371-3.
18. Singh A et al. Gastrointest Endosc. 2016 Oct;84(4):700-8.
19. Tomizawa Y and Ginsberg GG. Gastrointest Endosc. 2018 May;87(5):1270-8.
20. Klein A et al. Gastrointest Endosc. 2016 Oct;84(4):688-96.
21. Chathadi KV et al. Gastrointest Endosc. 2015 Nov;82(5):773-81.
Integrating psychogastroenterology into GI care
Psychogastroenterology, or gastrointestinal psychology, refers to psychosocial research and clinical practice related to GI conditions. This field is situated within a biopsychosocial model of illness and grounded in an understanding of the gut-brain axis. A key feature of GI psychology intervention is behavioral symptom management. Commonly referred to as “brain-gut psychotherapies,” the primary goal of these interventions is to reduce GI symptoms and their impact on those experiencing them. Additionally, GI-focused psychotherapies can help patients with GI disorders cope with their symptoms, diagnosis, or treatment.
GI psychology providers
GI-focused psychotherapies are typically provided by clinical health psychologists (PhDs or PsyDs) with specialized training in GI disorders, although sometimes they are provided by a clinical social worker or advanced-practice nursing provider. Psychologists that identify GI as their primary specialty area often refer to themselves as “GI psychologists.” Psychologists that treat patients with a variety of medical concerns, which may include GI disorders, typically refer to themselves with the broader term, “health psychologists.”
Interventions
A variety of psychological treatments have been applied to GI populations, including cognitive behavioral therapy (CBT), gut-directed hypnotherapy (GDH), psychodynamic interpersonal therapy, relaxation training, and mindfulness-based stress reduction. Psychological therapies have been shown to be useful in a variety of GI disorders, with a number needed to treat of four in IBS.1 Common ingredients of GI-focused psychotherapy interventions include psychoeducation regarding the gut-brain relationship and relaxation strategies to provide in-the-moment tools to deescalate the body’s stress response.
CBT and GDH are the most commonly used interventions across a range of GI conditions, with the bulk of empirical evidence in IBS.2-5 CBT is a theoretical orientation in which thoughts and behaviors are understood to be modifiable factors that impact emotions and physical sensations. When utilized in a GI setting (i.e., GI-CBT), treatment aims to address GI-specific outcomes such as reducing GI symptoms, optimizing health care utilization, and improving quality of life. These interventions target cognitive and behavioral factors common among GI patient populations, such as GI-specific anxiety, symptom hypervigilance, and rigid coping strategies. See Figure 1 for a GI-CBT model.
While research studies often implement manualized protocols, in clinical practice many GI psychologists use cognitive-behavioral interventions flexibly to tailor them to each patient’s presentation, while also integrating theory and practice from other types of therapies such as acceptance and commitment therapy (ACT; pronounced as one word). ACT, a “new wave” therapy derived from traditional CBT, emphasizes acceptance of distress (including GI symptoms), with a focus on engaging in values-based activities rather than symptom reduction.
Clinical hypnotherapy is utilized in a variety of medical specialties and has been studied in GI disorders for over 30 years. There are two evidence-based gut-directed hypnotherapy protocols, the Manchester6 and the North Carolina,7 that are widely used by GI psychologists. Though the exact mechanisms of hypnotherapy are unknown, it is thought to improve GI symptoms by modulating autonomic arousal and nerve sensitivity in the GI tract.
Evaluation
GI psychologists typically meet with patients for a 1-hour evaluation to determine appropriateness for psychogastroenterology intervention and develop a treatment plan. If GI-focused psychotherapy is indicated, patients are typically offered a course of treatment ranging from four to eight sessions. Depending on the nature of the patient’s concerns, longer courses of treatment may be offered, such as for with patients with active inflammatory bowel disease undergoing changes in medical treatment.
Appropriateness for psychogastroenterology treatment
Ideal patients are those who are psychologically stable and whose distress is primarily related to GI concerns, as opposed to family, work, or other situational stressors. While these other stressors can certainly impact GI symptoms, general mental health professionals are best suited to assist patients with these concerns. Patients experiencing more severe mental health concerns may be recommended to pursue a different treatment, such as mental health treatment for depression or anxiety or specialized treatments for trauma, eating disorders, or substance use. In both cases, once these general, non-GI, stressors or significant mental health concerns are more optimally managed, patients are likely to benefit from a GI-focused psychological treatment. Note, however, that because a GI psychologist’s particular practice can vary because of interest, experience, and institutional factors, it is best to connect directly with the GI psychologist you work with to clarify the types of referrals they are comfortable seeing and any specific characteristics of their practice.
Best practice recommendations for gastroenterologists
Developing a collaborative relationship with the GI psychologist, as well as any therapists to whom you regularly refer patients, is key to the success of integrated care. When talking to patients about the referral, refer to the GI psychologist as your colleague and a member of the treatment team. Maintain communication with the GI psychologist, and let the patient know that you are doing so.
When referring a patient, do so after you have completed your work-up and have optimized basic medical management for their condition but suspect that psychosocial factors may be negatively impacting their symptoms or ability to cope. Present the referral as an evaluation rather than implying a guarantee of treatment. This is particularly helpful in those cases where the patient is recommended to pursue a different treatment prior to GI-focused psychotherapy. Additionally, avoid telling patients that they are being referred for a specific intervention such as “a referral for CBT” or “a referral for hypnotherapy,” as the GI psychologist will recommend the most appropriate treatment for the patient upon evaluation. See Figure 2 for example scripts to use when referring.
Expect to maintain communication with the GI psychologist after making the referral. GI psychologists typically send the referring provider a written summary following the initial evaluation and conclusion of treatment and, in some cases, provide updates throughout. Be prepared to answer questions or provide input as requested. Not only may the psychologist have questions about the medical diagnosis or treatment, but they may enlist your help for medical expert opinion during treatment to address misinformation, which can often fuel concerns like treatment nonadherence or anxiety.
Identifying a psychogastroenterology provider
In recent years there has been significant growth in the training and hiring of GI psychologists, and it is increasingly common for GI psychologists to be employed at academic medical centers. However, the majority of gastroenterologists do not have access to a fully integrated or co-located GI psychologist. In these cases, gastroenterologists should search for other health psychology options in their area, such as psychologists or clinical social workers with experience with patients with chronic medical conditions and CBT. One positive product of the COVID-19 pandemic is that telemedicine has become increasingly utilized, and in some cases GI psychologists are able to provide virtual therapy to patients across state lines. However, this should be confirmed with the therapy practice as there are numerous factors to consider regarding virtual practice.
Dr. Bedell is assistant professor in the department of psychiatry and behavioral neuroscience at the University of Chicago. She has no conflicts of interest to disclose.
Resources available
To locate a GI psychology provider in your area: Search the Rome Psychogastroenterology directory (https://romegipsych.org/).
To locate general mental health providers: Search the Psychology Today website using the therapist finder function, which allows patients or providers to search by insurance, location, and specialty area (www.psychologytoday.com/us). The patient can also request a list of in-network psychotherapy providers from their insurance company and may find it helpful to cross-check these providers for potential fit by searching them online.
References
1. Ford AC et al. Effect of antidepressants and psychological therapies in irritable bowel syndrome: An updated systematic review and meta-analysis. Am J Gastroenterol. 2019 Jan;114(1):21-39. doi: 10.1038/s41395-018-0222-5.
2. Laird KT et al. Short-term and long-term efficacy of psychological therapies for irritable bowel syndrome: A systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2016 Jul;14(7):937-47.e4. doi: 10.1016/j.cgh.2015.11.020.
3. Lackner JM et al. Improvement in gastrointestinal symptoms after cognitive behavior therapy for refractory irritable bowel syndrome. Gastroenterology. 2018 Jul;155(1):47-57. doi: 10.1053/j.gastro.2018.03.063.
4. Lövdahl J et al. Nurse-administered, gut-directed hypnotherapy in IBS: Efficacy and factors predicting a positive response. Am J Clin Hypn. 2015 Jul;58(1):100-14. doi: 10.1080/00029157.2015.1030492.
5. Smith GD. Effect of nurse-led gut-directed hypnotherapy upon health-related quality of life in patients with irritable bowel syndrome. J Clin Nurs. 2006 Jun;15(6):678-84. doi: 10.1111/j.1365-2702.2006.01356.x.
6. Gonsalkorale WM. Gut-directed hypnotherapy: the Manchester approach for treatment of irritable bowel syndrome. Int J Clin Exp Hypn. 2006 Jan;54(1):27-50. doi: 10.1080/00207140500323030.
7. Palsson OS. Standardized hypnosis treatment for irritable bowel syndrome: The North Carolina protocol. Int J Clin Exp Hypn. 2006 Jan;54(1):51-64. doi: 10.1080/00207140500322933.
Psychogastroenterology, or gastrointestinal psychology, refers to psychosocial research and clinical practice related to GI conditions. This field is situated within a biopsychosocial model of illness and grounded in an understanding of the gut-brain axis. A key feature of GI psychology intervention is behavioral symptom management. Commonly referred to as “brain-gut psychotherapies,” the primary goal of these interventions is to reduce GI symptoms and their impact on those experiencing them. Additionally, GI-focused psychotherapies can help patients with GI disorders cope with their symptoms, diagnosis, or treatment.
GI psychology providers
GI-focused psychotherapies are typically provided by clinical health psychologists (PhDs or PsyDs) with specialized training in GI disorders, although sometimes they are provided by a clinical social worker or advanced-practice nursing provider. Psychologists that identify GI as their primary specialty area often refer to themselves as “GI psychologists.” Psychologists that treat patients with a variety of medical concerns, which may include GI disorders, typically refer to themselves with the broader term, “health psychologists.”
Interventions
A variety of psychological treatments have been applied to GI populations, including cognitive behavioral therapy (CBT), gut-directed hypnotherapy (GDH), psychodynamic interpersonal therapy, relaxation training, and mindfulness-based stress reduction. Psychological therapies have been shown to be useful in a variety of GI disorders, with a number needed to treat of four in IBS.1 Common ingredients of GI-focused psychotherapy interventions include psychoeducation regarding the gut-brain relationship and relaxation strategies to provide in-the-moment tools to deescalate the body’s stress response.
CBT and GDH are the most commonly used interventions across a range of GI conditions, with the bulk of empirical evidence in IBS.2-5 CBT is a theoretical orientation in which thoughts and behaviors are understood to be modifiable factors that impact emotions and physical sensations. When utilized in a GI setting (i.e., GI-CBT), treatment aims to address GI-specific outcomes such as reducing GI symptoms, optimizing health care utilization, and improving quality of life. These interventions target cognitive and behavioral factors common among GI patient populations, such as GI-specific anxiety, symptom hypervigilance, and rigid coping strategies. See Figure 1 for a GI-CBT model.
While research studies often implement manualized protocols, in clinical practice many GI psychologists use cognitive-behavioral interventions flexibly to tailor them to each patient’s presentation, while also integrating theory and practice from other types of therapies such as acceptance and commitment therapy (ACT; pronounced as one word). ACT, a “new wave” therapy derived from traditional CBT, emphasizes acceptance of distress (including GI symptoms), with a focus on engaging in values-based activities rather than symptom reduction.
Clinical hypnotherapy is utilized in a variety of medical specialties and has been studied in GI disorders for over 30 years. There are two evidence-based gut-directed hypnotherapy protocols, the Manchester6 and the North Carolina,7 that are widely used by GI psychologists. Though the exact mechanisms of hypnotherapy are unknown, it is thought to improve GI symptoms by modulating autonomic arousal and nerve sensitivity in the GI tract.
Evaluation
GI psychologists typically meet with patients for a 1-hour evaluation to determine appropriateness for psychogastroenterology intervention and develop a treatment plan. If GI-focused psychotherapy is indicated, patients are typically offered a course of treatment ranging from four to eight sessions. Depending on the nature of the patient’s concerns, longer courses of treatment may be offered, such as for with patients with active inflammatory bowel disease undergoing changes in medical treatment.
Appropriateness for psychogastroenterology treatment
Ideal patients are those who are psychologically stable and whose distress is primarily related to GI concerns, as opposed to family, work, or other situational stressors. While these other stressors can certainly impact GI symptoms, general mental health professionals are best suited to assist patients with these concerns. Patients experiencing more severe mental health concerns may be recommended to pursue a different treatment, such as mental health treatment for depression or anxiety or specialized treatments for trauma, eating disorders, or substance use. In both cases, once these general, non-GI, stressors or significant mental health concerns are more optimally managed, patients are likely to benefit from a GI-focused psychological treatment. Note, however, that because a GI psychologist’s particular practice can vary because of interest, experience, and institutional factors, it is best to connect directly with the GI psychologist you work with to clarify the types of referrals they are comfortable seeing and any specific characteristics of their practice.
Best practice recommendations for gastroenterologists
Developing a collaborative relationship with the GI psychologist, as well as any therapists to whom you regularly refer patients, is key to the success of integrated care. When talking to patients about the referral, refer to the GI psychologist as your colleague and a member of the treatment team. Maintain communication with the GI psychologist, and let the patient know that you are doing so.
When referring a patient, do so after you have completed your work-up and have optimized basic medical management for their condition but suspect that psychosocial factors may be negatively impacting their symptoms or ability to cope. Present the referral as an evaluation rather than implying a guarantee of treatment. This is particularly helpful in those cases where the patient is recommended to pursue a different treatment prior to GI-focused psychotherapy. Additionally, avoid telling patients that they are being referred for a specific intervention such as “a referral for CBT” or “a referral for hypnotherapy,” as the GI psychologist will recommend the most appropriate treatment for the patient upon evaluation. See Figure 2 for example scripts to use when referring.
Expect to maintain communication with the GI psychologist after making the referral. GI psychologists typically send the referring provider a written summary following the initial evaluation and conclusion of treatment and, in some cases, provide updates throughout. Be prepared to answer questions or provide input as requested. Not only may the psychologist have questions about the medical diagnosis or treatment, but they may enlist your help for medical expert opinion during treatment to address misinformation, which can often fuel concerns like treatment nonadherence or anxiety.
Identifying a psychogastroenterology provider
In recent years there has been significant growth in the training and hiring of GI psychologists, and it is increasingly common for GI psychologists to be employed at academic medical centers. However, the majority of gastroenterologists do not have access to a fully integrated or co-located GI psychologist. In these cases, gastroenterologists should search for other health psychology options in their area, such as psychologists or clinical social workers with experience with patients with chronic medical conditions and CBT. One positive product of the COVID-19 pandemic is that telemedicine has become increasingly utilized, and in some cases GI psychologists are able to provide virtual therapy to patients across state lines. However, this should be confirmed with the therapy practice as there are numerous factors to consider regarding virtual practice.
Dr. Bedell is assistant professor in the department of psychiatry and behavioral neuroscience at the University of Chicago. She has no conflicts of interest to disclose.
Resources available
To locate a GI psychology provider in your area: Search the Rome Psychogastroenterology directory (https://romegipsych.org/).
To locate general mental health providers: Search the Psychology Today website using the therapist finder function, which allows patients or providers to search by insurance, location, and specialty area (www.psychologytoday.com/us). The patient can also request a list of in-network psychotherapy providers from their insurance company and may find it helpful to cross-check these providers for potential fit by searching them online.
References
1. Ford AC et al. Effect of antidepressants and psychological therapies in irritable bowel syndrome: An updated systematic review and meta-analysis. Am J Gastroenterol. 2019 Jan;114(1):21-39. doi: 10.1038/s41395-018-0222-5.
2. Laird KT et al. Short-term and long-term efficacy of psychological therapies for irritable bowel syndrome: A systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2016 Jul;14(7):937-47.e4. doi: 10.1016/j.cgh.2015.11.020.
3. Lackner JM et al. Improvement in gastrointestinal symptoms after cognitive behavior therapy for refractory irritable bowel syndrome. Gastroenterology. 2018 Jul;155(1):47-57. doi: 10.1053/j.gastro.2018.03.063.
4. Lövdahl J et al. Nurse-administered, gut-directed hypnotherapy in IBS: Efficacy and factors predicting a positive response. Am J Clin Hypn. 2015 Jul;58(1):100-14. doi: 10.1080/00029157.2015.1030492.
5. Smith GD. Effect of nurse-led gut-directed hypnotherapy upon health-related quality of life in patients with irritable bowel syndrome. J Clin Nurs. 2006 Jun;15(6):678-84. doi: 10.1111/j.1365-2702.2006.01356.x.
6. Gonsalkorale WM. Gut-directed hypnotherapy: the Manchester approach for treatment of irritable bowel syndrome. Int J Clin Exp Hypn. 2006 Jan;54(1):27-50. doi: 10.1080/00207140500323030.
7. Palsson OS. Standardized hypnosis treatment for irritable bowel syndrome: The North Carolina protocol. Int J Clin Exp Hypn. 2006 Jan;54(1):51-64. doi: 10.1080/00207140500322933.
Psychogastroenterology, or gastrointestinal psychology, refers to psychosocial research and clinical practice related to GI conditions. This field is situated within a biopsychosocial model of illness and grounded in an understanding of the gut-brain axis. A key feature of GI psychology intervention is behavioral symptom management. Commonly referred to as “brain-gut psychotherapies,” the primary goal of these interventions is to reduce GI symptoms and their impact on those experiencing them. Additionally, GI-focused psychotherapies can help patients with GI disorders cope with their symptoms, diagnosis, or treatment.
GI psychology providers
GI-focused psychotherapies are typically provided by clinical health psychologists (PhDs or PsyDs) with specialized training in GI disorders, although sometimes they are provided by a clinical social worker or advanced-practice nursing provider. Psychologists that identify GI as their primary specialty area often refer to themselves as “GI psychologists.” Psychologists that treat patients with a variety of medical concerns, which may include GI disorders, typically refer to themselves with the broader term, “health psychologists.”
Interventions
A variety of psychological treatments have been applied to GI populations, including cognitive behavioral therapy (CBT), gut-directed hypnotherapy (GDH), psychodynamic interpersonal therapy, relaxation training, and mindfulness-based stress reduction. Psychological therapies have been shown to be useful in a variety of GI disorders, with a number needed to treat of four in IBS.1 Common ingredients of GI-focused psychotherapy interventions include psychoeducation regarding the gut-brain relationship and relaxation strategies to provide in-the-moment tools to deescalate the body’s stress response.
CBT and GDH are the most commonly used interventions across a range of GI conditions, with the bulk of empirical evidence in IBS.2-5 CBT is a theoretical orientation in which thoughts and behaviors are understood to be modifiable factors that impact emotions and physical sensations. When utilized in a GI setting (i.e., GI-CBT), treatment aims to address GI-specific outcomes such as reducing GI symptoms, optimizing health care utilization, and improving quality of life. These interventions target cognitive and behavioral factors common among GI patient populations, such as GI-specific anxiety, symptom hypervigilance, and rigid coping strategies. See Figure 1 for a GI-CBT model.
While research studies often implement manualized protocols, in clinical practice many GI psychologists use cognitive-behavioral interventions flexibly to tailor them to each patient’s presentation, while also integrating theory and practice from other types of therapies such as acceptance and commitment therapy (ACT; pronounced as one word). ACT, a “new wave” therapy derived from traditional CBT, emphasizes acceptance of distress (including GI symptoms), with a focus on engaging in values-based activities rather than symptom reduction.
Clinical hypnotherapy is utilized in a variety of medical specialties and has been studied in GI disorders for over 30 years. There are two evidence-based gut-directed hypnotherapy protocols, the Manchester6 and the North Carolina,7 that are widely used by GI psychologists. Though the exact mechanisms of hypnotherapy are unknown, it is thought to improve GI symptoms by modulating autonomic arousal and nerve sensitivity in the GI tract.
Evaluation
GI psychologists typically meet with patients for a 1-hour evaluation to determine appropriateness for psychogastroenterology intervention and develop a treatment plan. If GI-focused psychotherapy is indicated, patients are typically offered a course of treatment ranging from four to eight sessions. Depending on the nature of the patient’s concerns, longer courses of treatment may be offered, such as for with patients with active inflammatory bowel disease undergoing changes in medical treatment.
Appropriateness for psychogastroenterology treatment
Ideal patients are those who are psychologically stable and whose distress is primarily related to GI concerns, as opposed to family, work, or other situational stressors. While these other stressors can certainly impact GI symptoms, general mental health professionals are best suited to assist patients with these concerns. Patients experiencing more severe mental health concerns may be recommended to pursue a different treatment, such as mental health treatment for depression or anxiety or specialized treatments for trauma, eating disorders, or substance use. In both cases, once these general, non-GI, stressors or significant mental health concerns are more optimally managed, patients are likely to benefit from a GI-focused psychological treatment. Note, however, that because a GI psychologist’s particular practice can vary because of interest, experience, and institutional factors, it is best to connect directly with the GI psychologist you work with to clarify the types of referrals they are comfortable seeing and any specific characteristics of their practice.
Best practice recommendations for gastroenterologists
Developing a collaborative relationship with the GI psychologist, as well as any therapists to whom you regularly refer patients, is key to the success of integrated care. When talking to patients about the referral, refer to the GI psychologist as your colleague and a member of the treatment team. Maintain communication with the GI psychologist, and let the patient know that you are doing so.
When referring a patient, do so after you have completed your work-up and have optimized basic medical management for their condition but suspect that psychosocial factors may be negatively impacting their symptoms or ability to cope. Present the referral as an evaluation rather than implying a guarantee of treatment. This is particularly helpful in those cases where the patient is recommended to pursue a different treatment prior to GI-focused psychotherapy. Additionally, avoid telling patients that they are being referred for a specific intervention such as “a referral for CBT” or “a referral for hypnotherapy,” as the GI psychologist will recommend the most appropriate treatment for the patient upon evaluation. See Figure 2 for example scripts to use when referring.
Expect to maintain communication with the GI psychologist after making the referral. GI psychologists typically send the referring provider a written summary following the initial evaluation and conclusion of treatment and, in some cases, provide updates throughout. Be prepared to answer questions or provide input as requested. Not only may the psychologist have questions about the medical diagnosis or treatment, but they may enlist your help for medical expert opinion during treatment to address misinformation, which can often fuel concerns like treatment nonadherence or anxiety.
Identifying a psychogastroenterology provider
In recent years there has been significant growth in the training and hiring of GI psychologists, and it is increasingly common for GI psychologists to be employed at academic medical centers. However, the majority of gastroenterologists do not have access to a fully integrated or co-located GI psychologist. In these cases, gastroenterologists should search for other health psychology options in their area, such as psychologists or clinical social workers with experience with patients with chronic medical conditions and CBT. One positive product of the COVID-19 pandemic is that telemedicine has become increasingly utilized, and in some cases GI psychologists are able to provide virtual therapy to patients across state lines. However, this should be confirmed with the therapy practice as there are numerous factors to consider regarding virtual practice.
Dr. Bedell is assistant professor in the department of psychiatry and behavioral neuroscience at the University of Chicago. She has no conflicts of interest to disclose.
Resources available
To locate a GI psychology provider in your area: Search the Rome Psychogastroenterology directory (https://romegipsych.org/).
To locate general mental health providers: Search the Psychology Today website using the therapist finder function, which allows patients or providers to search by insurance, location, and specialty area (www.psychologytoday.com/us). The patient can also request a list of in-network psychotherapy providers from their insurance company and may find it helpful to cross-check these providers for potential fit by searching them online.
References
1. Ford AC et al. Effect of antidepressants and psychological therapies in irritable bowel syndrome: An updated systematic review and meta-analysis. Am J Gastroenterol. 2019 Jan;114(1):21-39. doi: 10.1038/s41395-018-0222-5.
2. Laird KT et al. Short-term and long-term efficacy of psychological therapies for irritable bowel syndrome: A systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2016 Jul;14(7):937-47.e4. doi: 10.1016/j.cgh.2015.11.020.
3. Lackner JM et al. Improvement in gastrointestinal symptoms after cognitive behavior therapy for refractory irritable bowel syndrome. Gastroenterology. 2018 Jul;155(1):47-57. doi: 10.1053/j.gastro.2018.03.063.
4. Lövdahl J et al. Nurse-administered, gut-directed hypnotherapy in IBS: Efficacy and factors predicting a positive response. Am J Clin Hypn. 2015 Jul;58(1):100-14. doi: 10.1080/00029157.2015.1030492.
5. Smith GD. Effect of nurse-led gut-directed hypnotherapy upon health-related quality of life in patients with irritable bowel syndrome. J Clin Nurs. 2006 Jun;15(6):678-84. doi: 10.1111/j.1365-2702.2006.01356.x.
6. Gonsalkorale WM. Gut-directed hypnotherapy: the Manchester approach for treatment of irritable bowel syndrome. Int J Clin Exp Hypn. 2006 Jan;54(1):27-50. doi: 10.1080/00207140500323030.
7. Palsson OS. Standardized hypnosis treatment for irritable bowel syndrome: The North Carolina protocol. Int J Clin Exp Hypn. 2006 Jan;54(1):51-64. doi: 10.1080/00207140500322933.