John J. Vargo, MD, MPH

The treatment of early esophageal, gastric, and colorectal cancer is changing.¹ For many years, surgery was the mainstay of treatment for early-stage gastrointestinal cancer. Unfortunately, surgery leads to significant loss of function of the organ, resulting in increased morbidity and decreased quality of life.²

Endoscopic techniques, particularly endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD), have been developed and are widely used in Japan, where gastrointestinal cancer is more common than in the West. This article reviews the indications, complications, and outcomes of ESD for early gastrointestinal neoplasms, so that readers will recognize the subset of patients who would benefit from ESD in a Western setting.

ENDOSCOPIC MUCOSAL RESECTION AND SUBMUCOSAL DISSECTION

Since the first therapeutic polypectomy was performed in Japan in 1974, several endoscopic techniques for tumor resection have been developed.³

EMR, one of the most successful and widely used techniques, involves elevating the lesion either with submucosal injection of a solution or with cap suction, and then removing it with a snare.⁴ Most lesions smaller than 20 mm can be removed in one piece (en bloc).⁵ Larger lesions are removed in multiple pieces (ie, piecemeal). Unfortunately, some fibrotic lesions, which are usually difficult to lift, cannot be completely removed by EMR.

ESD was first performed in the late 1990s with the aim of overcoming the limitations of EMR in resecting large or fibrotic tumors en bloc.^6,7 Since then, ESD technique has been standardized and training centers have been created, especially in Asia, where it is widely used for treatment of early gastric cancer.^3,8–10 Since 2012 it has been covered by the Japanese National Health Insurance for treatment of early gastric cancer, and since 2014 for treatment of colorectal malignant tumors measuring 2 to 5 cm.¹¹

Adoption of ESD has been slow in Western countries, where many patients are still referred for surgery or undergo EMR for removal of superficial neoplasms. Reasons for this slow adoption are that gastric cancer is much less common in Western countries, and also that ESD demands a high level of technical skill, is difficult to learn, and is expensive.^3,12,13 However, small groups of Western endoscopists have become interested and are advocating it, first studying it on their own and then training in a Japanese center and learning from experts performing the procedure.

Therefore, in a Western setting, ESD should be performed in specialized endoscopy centers and offered to selected patients.¹  

CANDIDATES SHOULD HAVE EARLY-STAGE, SUPERFICIAL TUMORS

Ideal candidates for endoscopic resection are patients who have early cancer with a negligible risk of lymph node metastasis, such as cancer limited to the mucosa (stage T1a).⁷ Therefore, to determine the best treatment for a patient with a newly diagnosed gastrointestinal neoplasm, it is mandatory to estimate the depth of invasion.

The depth of invasion is directly correlated with lymph node involvement, which is ultimately the main predictive factor for long-term adverse outcomes of gastrointestinal tumors.^4,14–17 Accurate multidisciplinary preprocedure estimations are mandatory, as incorrect evaluations may result in inappropriate therapy and residual cancer.¹⁸

Other factors that have been used to predict lymph node involvement include tumor size, macroscopic appearance, histologic differentiation, and lymphatic and vascular involvement.¹⁹ Some of these factors can be assessed by special endoscopic techniques (chromoendoscopy and narrow-band imaging with magnifying endoscopy) that allow accurate real-time estimation of the depth of invasion of the lesion.^5,17,20–27 Evaluation of microsurface and microvascular arrangements is especially useful for determining the feasibility of ESD in gastric tumors, evaluation of intracapillary loops is useful in esophageal lesions, and assessment of mucosal pit patterns is useful for colorectal lesions.^21–29

Endoscopic ultrasonography is another tool that has been used to estimate the depth of the tumor. Although it can differentiate between definite intramucosal and definite submucosal invasive cancers, its ability to confirm minute submucosal invasion is limited. Its use as the sole tumor staging modality is not encouraged, and it should always be used in conjunction with endoscopic evaluation.¹⁸

Though the aforementioned factors help stratify patients, pathologic staging is the best predictor of lymph node metastasis. ESD provides adequate specimens for accurate pathologic evaluation, as it removes lesions en bloc.³⁰

All patients found to have risk factors for lymph node metastasis on endoscopic, ultrasonographic, or pathologic analysis should be referred for surgical evaluation.^9,19,31,32

ENDOSCOPIC SUBMUCOSAL DISSECTION

Before the procedure, the patient’s physicians need to do the following:

Determine the best type of intervention (EMR, ESD, ablation, surgery) for the specific lesion.³ A multidisciplinary approach is encouraged, with involvement of the internist, gastroenterologist, and surgeon.

Plan for anesthesia, additional consultations, pre- and postprocedural hospital admission, and need for special equipment.³³

During the procedure

Define the lateral extent of the lesion using magnification chromoendoscopy or narrow-band imaging. In the stomach, a biopsy sample should be taken from the worst-looking segment and from normal-looking mucosa. Multiple biopsies should be avoided to prevent subsequent fibrosis.³³ In the colon, biopsy should be avoided.³⁴

Identify and circumferentially mark the target lesion. Cautery or argon plasma coagulation can be used for making markings at a distance of 5 to 10 mm from the edges.³³ This is done to recognize the borders of the lesion, because they can become distorted after submucosal injection.¹⁴ This step is unnecessary in colorectal cases, as tumor margins can be adequately visualized after chromoendoscopy.^16,35

Lift the lesion by injecting saline, 0.5% hyaluronate, or glycerin to create a submucosal fluid cushion.^19,33

Perform a circumferential incision lateral to the mucosal margins to allow for a normal tissue margin.³³ Partial incision is performed for esophageal and colorectal ESD to avoid fluid leakage from the submucosal layer, achieving a sustained submucosal lift and safer dissection.¹⁶

Submucosal dissection. The submucosal layer is dissected with an electrocautery knife until the lesion is completely removed. Dissection should be done carefully to keep the submucosal plane.³³ Hemoclips or hemostat forceps can be used to control visible bleeding. The resected specimen is then stretched and fixed to a board using small pins for further histopathologic evaluation.³⁵

Postprocedural monitoring.  All patients should be admitted for overnight observation. Those who undergo gastric ESD should receive high-dose acid suppression, and the next day they can be started on a liquid diet.¹⁹

STOMACH CANCER

Indications for ESD for stomach cancer in the East

The incidence of gastric cancer is higher in Japan and Korea, where widespread screening programs have led to early identification and early treatment of this disease.³⁶

Pathology studies³⁷ of samples from patients with gastric cancer identified the following as risk factors for lymph node metastasis, which would make ESD unsuitable:

• Undifferentiated type
• Tumors larger than 2 cm
• Lymphatic or venous involvement
• Submucosal invasion
• Ulcerative change.

Based on these findings, the situations in which there was no risk of lymph node involvement (ie, when none of the above factors are present) were accepted as absolute indications for endoscopic resection of early gastric cancer.³⁸ Further histologic studies identified a subset of patients with lesions with very low risk of lymph node metastasis, which outweighed the risk of surgery. Based on these findings, expanded criteria for gastric ESD were proposed,^39,40 and the Japanese gastric cancer treatment guidelines now include these expanded preoperative indications^9,17 (Table 1).

Based on information from the Japanese Gastric Cancer Association, reference 9.

The Japanese Gastric Cancer Association has proposed a treatment algorithm based on the histopathologic evaluation after resection (Figure 2).⁹

Outcomes

In the largest series of patients who underwent curative ESD for early gastric cancer, the 5-year survival rate was 92.6%, the 5-year disease-specific survival rate was 99.9%, and the 5-year relative survival rate was 105%.⁴¹

Similarly, in a Japanese population-based survival analysis, the relative 5-year survival rate for localized gastric cancer was 94.4%.⁴² Rates of en bloc resection and complete resection with ESD are higher than those with EMR, resulting in a lower risk of local recurrence in selected patients who undergo ESD.^8,43,44

Although rare, local recurrence after curative gastric ESD has been reported.⁴⁵ The annual incidence of local recurrence has been estimated to be 0.84%.⁴⁶

ESD entails a shorter hospital stay and requires fewer resources than surgery, resulting in lower medical costs (Table 2).⁴⁴ Additionally, as endoscopic resection is associated with less morbidity, fewer procedure-related adverse events, and fewer complications, ESD could be used as the standard treatment for early gastric cancer.^47,48

The Western perspective on endoscopic submucosal dissection for gastric cancer

Since the prevalence of gastric cancer in Western countries is significantly lower than in Japan and Korea, local data and experience are scarce. However, experts performing ESD in the West have adopted the indications of the Japan Gastroenterological Endoscopy Society. The European Society of Gastrointestinal Endoscopy recommends ESD for excision of most superficial gastric neoplasms, with EMR being preferred only in lesions smaller than 15 mm, Paris classification 0 or IIA.^5,32

Patients with gastric lesions measuring 15 mm or larger should undergo high-quality endoscopy, preferably chromoendoscopy, to evaluate the mucosal patterns and determine the depth of invasion. If superficial involvement is confirmed, other imaging techniques are not routinely recommended.⁵ A surgery consult is also recommended.

ESOPHAGEAL CANCER

Indications for ESD for esophageal cancer in the East

Due to the success of ESD for early gastric cancer, this technique is now also used for superficial esophageal neoplasms.^19,49 It should be done in a specialized center, as it is more technically difficult than gastric ESD: the esophageal lumen is narrow, the wall is thin, and the esophagus moves with respiration and heartbeat.⁵⁰ A multidisciplinary approach including an endoscopist, a surgeon, and a pathologist is highly recommended for evaluation and treatment.

EMR is preferred for removal of mucosal cancer, in view of its safety profile and success rates. ESD can be considered in cases of lesions larger than 15 mm, poorly lifting tumors, and those with the possibility of submucosal invasion (Table 3).^5,45,49,51

Circumference involvement is critical when determining eligible candidates, as a defect involving more than three-fourths of the esophageal circumference can lead to esophageal strictures.⁵² Controlled prospective studies have shown promising results from giving intralesional and oral steroids to prevent stricture after ESD, which could potentially overcome this size limitation.^53,54

Outcomes for esophageal cancer

ESD has been shown to be safe and effective, achieving en bloc resection in 85% to 100% of patients.^19,51 Its advantages over EMR include en bloc resection, complete resection, and high curative rates, resulting in higher recurrence-free survival.^2,55,56 Although the incidence of complications such as bleeding, perforation, and stricture formation are higher with ESD, patients usually recover uneventfully.^2,19,20

ESD in the esophagus: The Western perspective

As data on the efficacy of EMR vs ESD for the treatment of Barrett esophagus with adenocarcinoma are limited, EMR is the gold standard endoscopic technique for removal of visible esophageal dysplastic lesions.^5,51,57 ESD can be considered for tumors larger than 15 mm, for poorly lifting lesions, and if there is suspicion of submucosal invasion.⁵

Patients should be evaluated by an experienced endoscopist, using an advanced imaging technique such as narrow-band imaging or chromoendoscopy. If suspicious features are found, endoscopic ultrasonography should be considered to confirm submucosal invasion or lymph node involvement.⁵

Indications for ESD for colorectal cancer in the East

Colon cancer is one of the leading causes of cancer-related deaths worldwide.⁵⁸ Since ESD has been found to be effective and safe in treating gastric cancer, it has also been used to remove large colorectal tumors.⁵⁹ However, ESD is not universally accepted in the treatment of colorectal neoplasms due to its greater technical difficulty, longer procedural time, and higher risk of perforating the thinner colonic wall compared with EMR.^21,60

Outcomes for colorectal cancer

Tumor size of 50 mm or larger is a risk factor for complications, while a high procedure volume at the center is a protective factor.⁶⁰

Endoscopic treatment of colorectal cancer: The Western perspective

EMR is the gold standard for removal of superficial colorectal lesions. However, ESD can be considered if there is suspicion of superficial submucosal invasion, especially for lesions larger than 20 mm that cannot be resected en bloc by EMR.³² ESD can also be used for fibrotic lesions not amenable to complete EMR removal, or as a salvage procedure after recurrence after EMR.⁶⁷ Proper selection of cases is critical.¹

Patients who have a superficial colonic lesion should be evaluated by means of high-definition endoscopy and chromoendoscopy to assess the mucosal pattern and establish feasibility of endoscopic resection. If submucosal invasion is suspected, staging with endoscopic ultrasonography or magnetic resonance imaging should be considered.⁵

FOLLOW-UP AFTER ESD

Endoscopic surveillance after the procedure is recommended, given the persistent risk of metachronous cancer after curative ESD due to its organ-sparing quality.⁶⁸ Surveillance endoscopy aims to achieve early detection and subsequent endoscopic resection of metachronous lesions.

Histopathologic evaluation assessing the presence of malignant cells in the margins of a resected sample is mandatory for determining the next step in treatment. If margins are negative, follow-up endoscopy can be done every 6 to 12 months. If margins are positive, the approach includes surgery, reattempting ESD or endoscopic surveillance in 3 or 6 months.^3,32 Although the surveillance strategy varies according to individual risk of metachronous cancer, it should be continued indefinitely.⁶⁸

COMPLICATIONS OF ESD

The most common procedure-related complications of ESD are bleeding, perforation, and stricture. Most intraprocedural adverse events can be managed endoscopically.⁶⁹

Bleeding

Most bleeding occurs during the procedure or early after it and can be controlled with electrocautery.^49,69 No episodes of massive bleeding, defined as causing clinical symptoms and requiring transfusion or surgery, have been reported.^20,43,55

In gastric ESD, delayed bleeding rates have ranged from 0 to 15.6%.⁶⁹ Bleeding may be prevented with endoscopic coagulation of visible vessels after dissection has been completed and by proton pump inhibitor therapy.^70,71 Excessive coagulation should be avoided to lower the risk of perforation.³³

In colorectal ESD the bleeding rate has been reported to be 2.2%; applying coagulation to an area where a blood vessel is suspected before cutting (precoagulation) may prevent subsequent bleeding.²¹

Perforation

For gastric ESD, perforation rates range from 1.2% to 5.2%.⁶⁹ Esophageal perforation rates can be up to 4%.⁴⁹ In colorectal ESD, perforation rates have been reported to be 1.6% to 6.6%.^60,72

Although most of the cases were successfully managed with conservative treatment, some required emergency surgery.^60,73

Strictures

In a case series of 532 patients undergoing gastric ESD, stricture was reported in 5 patients, all of whom presented with obstructive symptoms.⁷⁴ Risk factors for post-ESD gastric stenosis are a mucosal defect with a circumferential extent of more than three-fourths or a longitudinal extent of more than 5 cm.⁷⁵

Strictures are common after esophageal ESD, with rates ranging from 2% to 26%. The risk is higher when longer segments are removed or circumferential resection is performed. As previously mentioned, this complication may be reduced with ingestion or injection of steroids  after the procedure.^53,54

Surprisingly, ESD of large colorectal lesions involving more than three-fourths of the circumference of the rectum is rarely complicated by stenosis.⁷⁶

ESD requires a high level of technical skill, is time-consuming, and has a higher rate of complications than conventional endoscopic resection. A standardized ESD training system is needed, as the procedure is more difficult than EMR. Training in porcine models has been shown to confer competency in ESD in a Western setting.^13,16,33

Colorectal ESD is an even more challenging procedure, given the potential for complications related to its anatomy. Training centers in Japan usually have their trainees first master gastric ESD, then assist in more than 20 colorectal ESDs conducted by experienced endoscopists, and accomplish 30 cases before performing the procedure safely and independently.

As the incidence of gastric cancer is low in Western countries, trainees may also begin with lower rectal lesions, which are easier to remove.⁷⁷ Incorporation of ESD in the West would require a clear treatment algorithm. It is a complex procedure, with higher rates of complications, a prolonged learning curve, and prolonged procedure time. Therefore, it should be performed in specialized centers and under the special situations discussed here to ensure that the benefits for the patients outweigh the risks.

VALUE OF ENDOSCOPIC SUBMUCOSAL DISSECTION

The optimal method for resecting gastrointestinal neoplasms should be safe, cost-effective, and quick and should also completely remove the lesion. The best treatment strategy takes into account the characteristics of the lesion and the comorbidities and wishes of the patient. Internists should be aware of the multiple options available to achieve the best outcome for the patient.¹

Endoscopic resection of superficial gastrointestinal neoplasms, including EMR and ESD, has been a subject of increasing interest due to its minimally invasive and potentially curative character. However, cancer can recur after endoscopic resection because the procedure is organ-sparing.

ESD allows resection of early gastrointestinal tumors with a minimally invasive technique. It can achieve higher curative resection rates and lower recurrence rates compared with EMR. Compared with surgery, ESD leads to less morbidity, fewer procedure-related complications, and lower medical costs. Indications should be rigorously followed to achieve successful treatments in selected patients.

Multiple variables have to be taken into account when deciding which treatment is best, such as tumor characteristics, the patient’s baseline condition, physician expertise, and hospital resources.⁴⁸ Less-invasive treatments may improve the prognosis of patients. No matter the approach, patients should be treated in specialized treatment centers.

Internal medicine physicians should be aware of the advances in treatments for early gastrointestinal cancer so appropriate options can be considered.

The treatment of early esophageal, gastric, and colorectal cancer is changing.¹ For many years, surgery was the mainstay of treatment for early-stage gastrointestinal cancer. Unfortunately, surgery leads to significant loss of function of the organ, resulting in increased morbidity and decreased quality of life.²

Endoscopic techniques, particularly endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD), have been developed and are widely used in Japan, where gastrointestinal cancer is more common than in the West. This article reviews the indications, complications, and outcomes of ESD for early gastrointestinal neoplasms, so that readers will recognize the subset of patients who would benefit from ESD in a Western setting.

ENDOSCOPIC MUCOSAL RESECTION AND SUBMUCOSAL DISSECTION

Since the first therapeutic polypectomy was performed in Japan in 1974, several endoscopic techniques for tumor resection have been developed.³

EMR, one of the most successful and widely used techniques, involves elevating the lesion either with submucosal injection of a solution or with cap suction, and then removing it with a snare.⁴ Most lesions smaller than 20 mm can be removed in one piece (en bloc).⁵ Larger lesions are removed in multiple pieces (ie, piecemeal). Unfortunately, some fibrotic lesions, which are usually difficult to lift, cannot be completely removed by EMR.

ESD was first performed in the late 1990s with the aim of overcoming the limitations of EMR in resecting large or fibrotic tumors en bloc.^6,7 Since then, ESD technique has been standardized and training centers have been created, especially in Asia, where it is widely used for treatment of early gastric cancer.^3,8–10 Since 2012 it has been covered by the Japanese National Health Insurance for treatment of early gastric cancer, and since 2014 for treatment of colorectal malignant tumors measuring 2 to 5 cm.¹¹

Adoption of ESD has been slow in Western countries, where many patients are still referred for surgery or undergo EMR for removal of superficial neoplasms. Reasons for this slow adoption are that gastric cancer is much less common in Western countries, and also that ESD demands a high level of technical skill, is difficult to learn, and is expensive.^3,12,13 However, small groups of Western endoscopists have become interested and are advocating it, first studying it on their own and then training in a Japanese center and learning from experts performing the procedure.

Therefore, in a Western setting, ESD should be performed in specialized endoscopy centers and offered to selected patients.¹  

CANDIDATES SHOULD HAVE EARLY-STAGE, SUPERFICIAL TUMORS

Ideal candidates for endoscopic resection are patients who have early cancer with a negligible risk of lymph node metastasis, such as cancer limited to the mucosa (stage T1a).⁷ Therefore, to determine the best treatment for a patient with a newly diagnosed gastrointestinal neoplasm, it is mandatory to estimate the depth of invasion.

The depth of invasion is directly correlated with lymph node involvement, which is ultimately the main predictive factor for long-term adverse outcomes of gastrointestinal tumors.^4,14–17 Accurate multidisciplinary preprocedure estimations are mandatory, as incorrect evaluations may result in inappropriate therapy and residual cancer.¹⁸

Other factors that have been used to predict lymph node involvement include tumor size, macroscopic appearance, histologic differentiation, and lymphatic and vascular involvement.¹⁹ Some of these factors can be assessed by special endoscopic techniques (chromoendoscopy and narrow-band imaging with magnifying endoscopy) that allow accurate real-time estimation of the depth of invasion of the lesion.^5,17,20–27 Evaluation of microsurface and microvascular arrangements is especially useful for determining the feasibility of ESD in gastric tumors, evaluation of intracapillary loops is useful in esophageal lesions, and assessment of mucosal pit patterns is useful for colorectal lesions.^21–29

Endoscopic ultrasonography is another tool that has been used to estimate the depth of the tumor. Although it can differentiate between definite intramucosal and definite submucosal invasive cancers, its ability to confirm minute submucosal invasion is limited. Its use as the sole tumor staging modality is not encouraged, and it should always be used in conjunction with endoscopic evaluation.¹⁸

Though the aforementioned factors help stratify patients, pathologic staging is the best predictor of lymph node metastasis. ESD provides adequate specimens for accurate pathologic evaluation, as it removes lesions en bloc.³⁰

All patients found to have risk factors for lymph node metastasis on endoscopic, ultrasonographic, or pathologic analysis should be referred for surgical evaluation.^9,19,31,32

ENDOSCOPIC SUBMUCOSAL DISSECTION

Before the procedure, the patient’s physicians need to do the following:

Determine the best type of intervention (EMR, ESD, ablation, surgery) for the specific lesion.³ A multidisciplinary approach is encouraged, with involvement of the internist, gastroenterologist, and surgeon.

Plan for anesthesia, additional consultations, pre- and postprocedural hospital admission, and need for special equipment.³³

During the procedure

Define the lateral extent of the lesion using magnification chromoendoscopy or narrow-band imaging. In the stomach, a biopsy sample should be taken from the worst-looking segment and from normal-looking mucosa. Multiple biopsies should be avoided to prevent subsequent fibrosis.³³ In the colon, biopsy should be avoided.³⁴

Identify and circumferentially mark the target lesion. Cautery or argon plasma coagulation can be used for making markings at a distance of 5 to 10 mm from the edges.³³ This is done to recognize the borders of the lesion, because they can become distorted after submucosal injection.¹⁴ This step is unnecessary in colorectal cases, as tumor margins can be adequately visualized after chromoendoscopy.^16,35

Lift the lesion by injecting saline, 0.5% hyaluronate, or glycerin to create a submucosal fluid cushion.^19,33

Perform a circumferential incision lateral to the mucosal margins to allow for a normal tissue margin.³³ Partial incision is performed for esophageal and colorectal ESD to avoid fluid leakage from the submucosal layer, achieving a sustained submucosal lift and safer dissection.¹⁶

Submucosal dissection. The submucosal layer is dissected with an electrocautery knife until the lesion is completely removed. Dissection should be done carefully to keep the submucosal plane.³³ Hemoclips or hemostat forceps can be used to control visible bleeding. The resected specimen is then stretched and fixed to a board using small pins for further histopathologic evaluation.³⁵

Postprocedural monitoring.  All patients should be admitted for overnight observation. Those who undergo gastric ESD should receive high-dose acid suppression, and the next day they can be started on a liquid diet.¹⁹

STOMACH CANCER

Indications for ESD for stomach cancer in the East

The incidence of gastric cancer is higher in Japan and Korea, where widespread screening programs have led to early identification and early treatment of this disease.³⁶

Pathology studies³⁷ of samples from patients with gastric cancer identified the following as risk factors for lymph node metastasis, which would make ESD unsuitable:

• Undifferentiated type
• Tumors larger than 2 cm
• Lymphatic or venous involvement
• Submucosal invasion
• Ulcerative change.

Based on these findings, the situations in which there was no risk of lymph node involvement (ie, when none of the above factors are present) were accepted as absolute indications for endoscopic resection of early gastric cancer.³⁸ Further histologic studies identified a subset of patients with lesions with very low risk of lymph node metastasis, which outweighed the risk of surgery. Based on these findings, expanded criteria for gastric ESD were proposed,^39,40 and the Japanese gastric cancer treatment guidelines now include these expanded preoperative indications^9,17 (Table 1).

Based on information from the Japanese Gastric Cancer Association, reference 9.

The Japanese Gastric Cancer Association has proposed a treatment algorithm based on the histopathologic evaluation after resection (Figure 2).⁹

Outcomes

In the largest series of patients who underwent curative ESD for early gastric cancer, the 5-year survival rate was 92.6%, the 5-year disease-specific survival rate was 99.9%, and the 5-year relative survival rate was 105%.⁴¹

Similarly, in a Japanese population-based survival analysis, the relative 5-year survival rate for localized gastric cancer was 94.4%.⁴² Rates of en bloc resection and complete resection with ESD are higher than those with EMR, resulting in a lower risk of local recurrence in selected patients who undergo ESD.^8,43,44

Although rare, local recurrence after curative gastric ESD has been reported.⁴⁵ The annual incidence of local recurrence has been estimated to be 0.84%.⁴⁶

ESD entails a shorter hospital stay and requires fewer resources than surgery, resulting in lower medical costs (Table 2).⁴⁴ Additionally, as endoscopic resection is associated with less morbidity, fewer procedure-related adverse events, and fewer complications, ESD could be used as the standard treatment for early gastric cancer.^47,48

The Western perspective on endoscopic submucosal dissection for gastric cancer

Since the prevalence of gastric cancer in Western countries is significantly lower than in Japan and Korea, local data and experience are scarce. However, experts performing ESD in the West have adopted the indications of the Japan Gastroenterological Endoscopy Society. The European Society of Gastrointestinal Endoscopy recommends ESD for excision of most superficial gastric neoplasms, with EMR being preferred only in lesions smaller than 15 mm, Paris classification 0 or IIA.^5,32

Patients with gastric lesions measuring 15 mm or larger should undergo high-quality endoscopy, preferably chromoendoscopy, to evaluate the mucosal patterns and determine the depth of invasion. If superficial involvement is confirmed, other imaging techniques are not routinely recommended.⁵ A surgery consult is also recommended.

ESOPHAGEAL CANCER

Indications for ESD for esophageal cancer in the East

Due to the success of ESD for early gastric cancer, this technique is now also used for superficial esophageal neoplasms.^19,49 It should be done in a specialized center, as it is more technically difficult than gastric ESD: the esophageal lumen is narrow, the wall is thin, and the esophagus moves with respiration and heartbeat.⁵⁰ A multidisciplinary approach including an endoscopist, a surgeon, and a pathologist is highly recommended for evaluation and treatment.

EMR is preferred for removal of mucosal cancer, in view of its safety profile and success rates. ESD can be considered in cases of lesions larger than 15 mm, poorly lifting tumors, and those with the possibility of submucosal invasion (Table 3).^5,45,49,51

Circumference involvement is critical when determining eligible candidates, as a defect involving more than three-fourths of the esophageal circumference can lead to esophageal strictures.⁵² Controlled prospective studies have shown promising results from giving intralesional and oral steroids to prevent stricture after ESD, which could potentially overcome this size limitation.^53,54

Outcomes for esophageal cancer

ESD has been shown to be safe and effective, achieving en bloc resection in 85% to 100% of patients.^19,51 Its advantages over EMR include en bloc resection, complete resection, and high curative rates, resulting in higher recurrence-free survival.^2,55,56 Although the incidence of complications such as bleeding, perforation, and stricture formation are higher with ESD, patients usually recover uneventfully.^2,19,20

ESD in the esophagus: The Western perspective

As data on the efficacy of EMR vs ESD for the treatment of Barrett esophagus with adenocarcinoma are limited, EMR is the gold standard endoscopic technique for removal of visible esophageal dysplastic lesions.^5,51,57 ESD can be considered for tumors larger than 15 mm, for poorly lifting lesions, and if there is suspicion of submucosal invasion.⁵

Patients should be evaluated by an experienced endoscopist, using an advanced imaging technique such as narrow-band imaging or chromoendoscopy. If suspicious features are found, endoscopic ultrasonography should be considered to confirm submucosal invasion or lymph node involvement.⁵

Indications for ESD for colorectal cancer in the East

Colon cancer is one of the leading causes of cancer-related deaths worldwide.⁵⁸ Since ESD has been found to be effective and safe in treating gastric cancer, it has also been used to remove large colorectal tumors.⁵⁹ However, ESD is not universally accepted in the treatment of colorectal neoplasms due to its greater technical difficulty, longer procedural time, and higher risk of perforating the thinner colonic wall compared with EMR.^21,60

Outcomes for colorectal cancer

Tumor size of 50 mm or larger is a risk factor for complications, while a high procedure volume at the center is a protective factor.⁶⁰

Endoscopic treatment of colorectal cancer: The Western perspective

EMR is the gold standard for removal of superficial colorectal lesions. However, ESD can be considered if there is suspicion of superficial submucosal invasion, especially for lesions larger than 20 mm that cannot be resected en bloc by EMR.³² ESD can also be used for fibrotic lesions not amenable to complete EMR removal, or as a salvage procedure after recurrence after EMR.⁶⁷ Proper selection of cases is critical.¹

Patients who have a superficial colonic lesion should be evaluated by means of high-definition endoscopy and chromoendoscopy to assess the mucosal pattern and establish feasibility of endoscopic resection. If submucosal invasion is suspected, staging with endoscopic ultrasonography or magnetic resonance imaging should be considered.⁵

FOLLOW-UP AFTER ESD

Endoscopic surveillance after the procedure is recommended, given the persistent risk of metachronous cancer after curative ESD due to its organ-sparing quality.⁶⁸ Surveillance endoscopy aims to achieve early detection and subsequent endoscopic resection of metachronous lesions.

Histopathologic evaluation assessing the presence of malignant cells in the margins of a resected sample is mandatory for determining the next step in treatment. If margins are negative, follow-up endoscopy can be done every 6 to 12 months. If margins are positive, the approach includes surgery, reattempting ESD or endoscopic surveillance in 3 or 6 months.^3,32 Although the surveillance strategy varies according to individual risk of metachronous cancer, it should be continued indefinitely.⁶⁸

COMPLICATIONS OF ESD

The most common procedure-related complications of ESD are bleeding, perforation, and stricture. Most intraprocedural adverse events can be managed endoscopically.⁶⁹

Bleeding

Most bleeding occurs during the procedure or early after it and can be controlled with electrocautery.^49,69 No episodes of massive bleeding, defined as causing clinical symptoms and requiring transfusion or surgery, have been reported.^20,43,55

In gastric ESD, delayed bleeding rates have ranged from 0 to 15.6%.⁶⁹ Bleeding may be prevented with endoscopic coagulation of visible vessels after dissection has been completed and by proton pump inhibitor therapy.^70,71 Excessive coagulation should be avoided to lower the risk of perforation.³³

In colorectal ESD the bleeding rate has been reported to be 2.2%; applying coagulation to an area where a blood vessel is suspected before cutting (precoagulation) may prevent subsequent bleeding.²¹

Perforation

For gastric ESD, perforation rates range from 1.2% to 5.2%.⁶⁹ Esophageal perforation rates can be up to 4%.⁴⁹ In colorectal ESD, perforation rates have been reported to be 1.6% to 6.6%.^60,72

Although most of the cases were successfully managed with conservative treatment, some required emergency surgery.^60,73

Strictures

In a case series of 532 patients undergoing gastric ESD, stricture was reported in 5 patients, all of whom presented with obstructive symptoms.⁷⁴ Risk factors for post-ESD gastric stenosis are a mucosal defect with a circumferential extent of more than three-fourths or a longitudinal extent of more than 5 cm.⁷⁵

Strictures are common after esophageal ESD, with rates ranging from 2% to 26%. The risk is higher when longer segments are removed or circumferential resection is performed. As previously mentioned, this complication may be reduced with ingestion or injection of steroids  after the procedure.^53,54

Surprisingly, ESD of large colorectal lesions involving more than three-fourths of the circumference of the rectum is rarely complicated by stenosis.⁷⁶

ESD requires a high level of technical skill, is time-consuming, and has a higher rate of complications than conventional endoscopic resection. A standardized ESD training system is needed, as the procedure is more difficult than EMR. Training in porcine models has been shown to confer competency in ESD in a Western setting.^13,16,33

Colorectal ESD is an even more challenging procedure, given the potential for complications related to its anatomy. Training centers in Japan usually have their trainees first master gastric ESD, then assist in more than 20 colorectal ESDs conducted by experienced endoscopists, and accomplish 30 cases before performing the procedure safely and independently.

As the incidence of gastric cancer is low in Western countries, trainees may also begin with lower rectal lesions, which are easier to remove.⁷⁷ Incorporation of ESD in the West would require a clear treatment algorithm. It is a complex procedure, with higher rates of complications, a prolonged learning curve, and prolonged procedure time. Therefore, it should be performed in specialized centers and under the special situations discussed here to ensure that the benefits for the patients outweigh the risks.

VALUE OF ENDOSCOPIC SUBMUCOSAL DISSECTION

The optimal method for resecting gastrointestinal neoplasms should be safe, cost-effective, and quick and should also completely remove the lesion. The best treatment strategy takes into account the characteristics of the lesion and the comorbidities and wishes of the patient. Internists should be aware of the multiple options available to achieve the best outcome for the patient.¹

Endoscopic resection of superficial gastrointestinal neoplasms, including EMR and ESD, has been a subject of increasing interest due to its minimally invasive and potentially curative character. However, cancer can recur after endoscopic resection because the procedure is organ-sparing.

ESD allows resection of early gastrointestinal tumors with a minimally invasive technique. It can achieve higher curative resection rates and lower recurrence rates compared with EMR. Compared with surgery, ESD leads to less morbidity, fewer procedure-related complications, and lower medical costs. Indications should be rigorously followed to achieve successful treatments in selected patients.

Multiple variables have to be taken into account when deciding which treatment is best, such as tumor characteristics, the patient’s baseline condition, physician expertise, and hospital resources.⁴⁸ Less-invasive treatments may improve the prognosis of patients. No matter the approach, patients should be treated in specialized treatment centers.

Internal medicine physicians should be aware of the advances in treatments for early gastrointestinal cancer so appropriate options can be considered.

The treatment of early esophageal, gastric, and colorectal cancer is changing.¹ For many years, surgery was the mainstay of treatment for early-stage gastrointestinal cancer. Unfortunately, surgery leads to significant loss of function of the organ, resulting in increased morbidity and decreased quality of life.²

Endoscopic techniques, particularly endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD), have been developed and are widely used in Japan, where gastrointestinal cancer is more common than in the West. This article reviews the indications, complications, and outcomes of ESD for early gastrointestinal neoplasms, so that readers will recognize the subset of patients who would benefit from ESD in a Western setting.

ENDOSCOPIC MUCOSAL RESECTION AND SUBMUCOSAL DISSECTION

Since the first therapeutic polypectomy was performed in Japan in 1974, several endoscopic techniques for tumor resection have been developed.³

EMR, one of the most successful and widely used techniques, involves elevating the lesion either with submucosal injection of a solution or with cap suction, and then removing it with a snare.⁴ Most lesions smaller than 20 mm can be removed in one piece (en bloc).⁵ Larger lesions are removed in multiple pieces (ie, piecemeal). Unfortunately, some fibrotic lesions, which are usually difficult to lift, cannot be completely removed by EMR.

ESD was first performed in the late 1990s with the aim of overcoming the limitations of EMR in resecting large or fibrotic tumors en bloc.^6,7 Since then, ESD technique has been standardized and training centers have been created, especially in Asia, where it is widely used for treatment of early gastric cancer.^3,8–10 Since 2012 it has been covered by the Japanese National Health Insurance for treatment of early gastric cancer, and since 2014 for treatment of colorectal malignant tumors measuring 2 to 5 cm.¹¹

Adoption of ESD has been slow in Western countries, where many patients are still referred for surgery or undergo EMR for removal of superficial neoplasms. Reasons for this slow adoption are that gastric cancer is much less common in Western countries, and also that ESD demands a high level of technical skill, is difficult to learn, and is expensive.^3,12,13 However, small groups of Western endoscopists have become interested and are advocating it, first studying it on their own and then training in a Japanese center and learning from experts performing the procedure.

Therefore, in a Western setting, ESD should be performed in specialized endoscopy centers and offered to selected patients.¹  

CANDIDATES SHOULD HAVE EARLY-STAGE, SUPERFICIAL TUMORS

Ideal candidates for endoscopic resection are patients who have early cancer with a negligible risk of lymph node metastasis, such as cancer limited to the mucosa (stage T1a).⁷ Therefore, to determine the best treatment for a patient with a newly diagnosed gastrointestinal neoplasm, it is mandatory to estimate the depth of invasion.

The depth of invasion is directly correlated with lymph node involvement, which is ultimately the main predictive factor for long-term adverse outcomes of gastrointestinal tumors.^4,14–17 Accurate multidisciplinary preprocedure estimations are mandatory, as incorrect evaluations may result in inappropriate therapy and residual cancer.¹⁸

Other factors that have been used to predict lymph node involvement include tumor size, macroscopic appearance, histologic differentiation, and lymphatic and vascular involvement.¹⁹ Some of these factors can be assessed by special endoscopic techniques (chromoendoscopy and narrow-band imaging with magnifying endoscopy) that allow accurate real-time estimation of the depth of invasion of the lesion.^5,17,20–27 Evaluation of microsurface and microvascular arrangements is especially useful for determining the feasibility of ESD in gastric tumors, evaluation of intracapillary loops is useful in esophageal lesions, and assessment of mucosal pit patterns is useful for colorectal lesions.^21–29

Endoscopic ultrasonography is another tool that has been used to estimate the depth of the tumor. Although it can differentiate between definite intramucosal and definite submucosal invasive cancers, its ability to confirm minute submucosal invasion is limited. Its use as the sole tumor staging modality is not encouraged, and it should always be used in conjunction with endoscopic evaluation.¹⁸

Though the aforementioned factors help stratify patients, pathologic staging is the best predictor of lymph node metastasis. ESD provides adequate specimens for accurate pathologic evaluation, as it removes lesions en bloc.³⁰

All patients found to have risk factors for lymph node metastasis on endoscopic, ultrasonographic, or pathologic analysis should be referred for surgical evaluation.^9,19,31,32

ENDOSCOPIC SUBMUCOSAL DISSECTION

Before the procedure, the patient’s physicians need to do the following:

Determine the best type of intervention (EMR, ESD, ablation, surgery) for the specific lesion.³ A multidisciplinary approach is encouraged, with involvement of the internist, gastroenterologist, and surgeon.

Plan for anesthesia, additional consultations, pre- and postprocedural hospital admission, and need for special equipment.³³

During the procedure

Define the lateral extent of the lesion using magnification chromoendoscopy or narrow-band imaging. In the stomach, a biopsy sample should be taken from the worst-looking segment and from normal-looking mucosa. Multiple biopsies should be avoided to prevent subsequent fibrosis.³³ In the colon, biopsy should be avoided.³⁴

Identify and circumferentially mark the target lesion. Cautery or argon plasma coagulation can be used for making markings at a distance of 5 to 10 mm from the edges.³³ This is done to recognize the borders of the lesion, because they can become distorted after submucosal injection.¹⁴ This step is unnecessary in colorectal cases, as tumor margins can be adequately visualized after chromoendoscopy.^16,35

Lift the lesion by injecting saline, 0.5% hyaluronate, or glycerin to create a submucosal fluid cushion.^19,33

Perform a circumferential incision lateral to the mucosal margins to allow for a normal tissue margin.³³ Partial incision is performed for esophageal and colorectal ESD to avoid fluid leakage from the submucosal layer, achieving a sustained submucosal lift and safer dissection.¹⁶

Submucosal dissection. The submucosal layer is dissected with an electrocautery knife until the lesion is completely removed. Dissection should be done carefully to keep the submucosal plane.³³ Hemoclips or hemostat forceps can be used to control visible bleeding. The resected specimen is then stretched and fixed to a board using small pins for further histopathologic evaluation.³⁵

Postprocedural monitoring.  All patients should be admitted for overnight observation. Those who undergo gastric ESD should receive high-dose acid suppression, and the next day they can be started on a liquid diet.¹⁹

STOMACH CANCER

Indications for ESD for stomach cancer in the East

The incidence of gastric cancer is higher in Japan and Korea, where widespread screening programs have led to early identification and early treatment of this disease.³⁶

Pathology studies³⁷ of samples from patients with gastric cancer identified the following as risk factors for lymph node metastasis, which would make ESD unsuitable:

• Undifferentiated type
• Tumors larger than 2 cm
• Lymphatic or venous involvement
• Submucosal invasion
• Ulcerative change.

Based on these findings, the situations in which there was no risk of lymph node involvement (ie, when none of the above factors are present) were accepted as absolute indications for endoscopic resection of early gastric cancer.³⁸ Further histologic studies identified a subset of patients with lesions with very low risk of lymph node metastasis, which outweighed the risk of surgery. Based on these findings, expanded criteria for gastric ESD were proposed,^39,40 and the Japanese gastric cancer treatment guidelines now include these expanded preoperative indications^9,17 (Table 1).

Based on information from the Japanese Gastric Cancer Association, reference 9.

The Japanese Gastric Cancer Association has proposed a treatment algorithm based on the histopathologic evaluation after resection (Figure 2).⁹

Outcomes

In the largest series of patients who underwent curative ESD for early gastric cancer, the 5-year survival rate was 92.6%, the 5-year disease-specific survival rate was 99.9%, and the 5-year relative survival rate was 105%.⁴¹

Similarly, in a Japanese population-based survival analysis, the relative 5-year survival rate for localized gastric cancer was 94.4%.⁴² Rates of en bloc resection and complete resection with ESD are higher than those with EMR, resulting in a lower risk of local recurrence in selected patients who undergo ESD.^8,43,44

Although rare, local recurrence after curative gastric ESD has been reported.⁴⁵ The annual incidence of local recurrence has been estimated to be 0.84%.⁴⁶

ESD entails a shorter hospital stay and requires fewer resources than surgery, resulting in lower medical costs (Table 2).⁴⁴ Additionally, as endoscopic resection is associated with less morbidity, fewer procedure-related adverse events, and fewer complications, ESD could be used as the standard treatment for early gastric cancer.^47,48

The Western perspective on endoscopic submucosal dissection for gastric cancer

Since the prevalence of gastric cancer in Western countries is significantly lower than in Japan and Korea, local data and experience are scarce. However, experts performing ESD in the West have adopted the indications of the Japan Gastroenterological Endoscopy Society. The European Society of Gastrointestinal Endoscopy recommends ESD for excision of most superficial gastric neoplasms, with EMR being preferred only in lesions smaller than 15 mm, Paris classification 0 or IIA.^5,32

Patients with gastric lesions measuring 15 mm or larger should undergo high-quality endoscopy, preferably chromoendoscopy, to evaluate the mucosal patterns and determine the depth of invasion. If superficial involvement is confirmed, other imaging techniques are not routinely recommended.⁵ A surgery consult is also recommended.

ESOPHAGEAL CANCER

Indications for ESD for esophageal cancer in the East

Due to the success of ESD for early gastric cancer, this technique is now also used for superficial esophageal neoplasms.^19,49 It should be done in a specialized center, as it is more technically difficult than gastric ESD: the esophageal lumen is narrow, the wall is thin, and the esophagus moves with respiration and heartbeat.⁵⁰ A multidisciplinary approach including an endoscopist, a surgeon, and a pathologist is highly recommended for evaluation and treatment.

EMR is preferred for removal of mucosal cancer, in view of its safety profile and success rates. ESD can be considered in cases of lesions larger than 15 mm, poorly lifting tumors, and those with the possibility of submucosal invasion (Table 3).^5,45,49,51

Circumference involvement is critical when determining eligible candidates, as a defect involving more than three-fourths of the esophageal circumference can lead to esophageal strictures.⁵² Controlled prospective studies have shown promising results from giving intralesional and oral steroids to prevent stricture after ESD, which could potentially overcome this size limitation.^53,54

Outcomes for esophageal cancer

ESD has been shown to be safe and effective, achieving en bloc resection in 85% to 100% of patients.^19,51 Its advantages over EMR include en bloc resection, complete resection, and high curative rates, resulting in higher recurrence-free survival.^2,55,56 Although the incidence of complications such as bleeding, perforation, and stricture formation are higher with ESD, patients usually recover uneventfully.^2,19,20

ESD in the esophagus: The Western perspective

As data on the efficacy of EMR vs ESD for the treatment of Barrett esophagus with adenocarcinoma are limited, EMR is the gold standard endoscopic technique for removal of visible esophageal dysplastic lesions.^5,51,57 ESD can be considered for tumors larger than 15 mm, for poorly lifting lesions, and if there is suspicion of submucosal invasion.⁵

Patients should be evaluated by an experienced endoscopist, using an advanced imaging technique such as narrow-band imaging or chromoendoscopy. If suspicious features are found, endoscopic ultrasonography should be considered to confirm submucosal invasion or lymph node involvement.⁵

Indications for ESD for colorectal cancer in the East

Colon cancer is one of the leading causes of cancer-related deaths worldwide.⁵⁸ Since ESD has been found to be effective and safe in treating gastric cancer, it has also been used to remove large colorectal tumors.⁵⁹ However, ESD is not universally accepted in the treatment of colorectal neoplasms due to its greater technical difficulty, longer procedural time, and higher risk of perforating the thinner colonic wall compared with EMR.^21,60

Outcomes for colorectal cancer

Tumor size of 50 mm or larger is a risk factor for complications, while a high procedure volume at the center is a protective factor.⁶⁰

Endoscopic treatment of colorectal cancer: The Western perspective

EMR is the gold standard for removal of superficial colorectal lesions. However, ESD can be considered if there is suspicion of superficial submucosal invasion, especially for lesions larger than 20 mm that cannot be resected en bloc by EMR.³² ESD can also be used for fibrotic lesions not amenable to complete EMR removal, or as a salvage procedure after recurrence after EMR.⁶⁷ Proper selection of cases is critical.¹

Patients who have a superficial colonic lesion should be evaluated by means of high-definition endoscopy and chromoendoscopy to assess the mucosal pattern and establish feasibility of endoscopic resection. If submucosal invasion is suspected, staging with endoscopic ultrasonography or magnetic resonance imaging should be considered.⁵

FOLLOW-UP AFTER ESD

Endoscopic surveillance after the procedure is recommended, given the persistent risk of metachronous cancer after curative ESD due to its organ-sparing quality.⁶⁸ Surveillance endoscopy aims to achieve early detection and subsequent endoscopic resection of metachronous lesions.

Histopathologic evaluation assessing the presence of malignant cells in the margins of a resected sample is mandatory for determining the next step in treatment. If margins are negative, follow-up endoscopy can be done every 6 to 12 months. If margins are positive, the approach includes surgery, reattempting ESD or endoscopic surveillance in 3 or 6 months.^3,32 Although the surveillance strategy varies according to individual risk of metachronous cancer, it should be continued indefinitely.⁶⁸

COMPLICATIONS OF ESD

The most common procedure-related complications of ESD are bleeding, perforation, and stricture. Most intraprocedural adverse events can be managed endoscopically.⁶⁹

Bleeding

Most bleeding occurs during the procedure or early after it and can be controlled with electrocautery.^49,69 No episodes of massive bleeding, defined as causing clinical symptoms and requiring transfusion or surgery, have been reported.^20,43,55

In gastric ESD, delayed bleeding rates have ranged from 0 to 15.6%.⁶⁹ Bleeding may be prevented with endoscopic coagulation of visible vessels after dissection has been completed and by proton pump inhibitor therapy.^70,71 Excessive coagulation should be avoided to lower the risk of perforation.³³

In colorectal ESD the bleeding rate has been reported to be 2.2%; applying coagulation to an area where a blood vessel is suspected before cutting (precoagulation) may prevent subsequent bleeding.²¹

Perforation

For gastric ESD, perforation rates range from 1.2% to 5.2%.⁶⁹ Esophageal perforation rates can be up to 4%.⁴⁹ In colorectal ESD, perforation rates have been reported to be 1.6% to 6.6%.^60,72

Although most of the cases were successfully managed with conservative treatment, some required emergency surgery.^60,73

Strictures

In a case series of 532 patients undergoing gastric ESD, stricture was reported in 5 patients, all of whom presented with obstructive symptoms.⁷⁴ Risk factors for post-ESD gastric stenosis are a mucosal defect with a circumferential extent of more than three-fourths or a longitudinal extent of more than 5 cm.⁷⁵

Strictures are common after esophageal ESD, with rates ranging from 2% to 26%. The risk is higher when longer segments are removed or circumferential resection is performed. As previously mentioned, this complication may be reduced with ingestion or injection of steroids  after the procedure.^53,54

Surprisingly, ESD of large colorectal lesions involving more than three-fourths of the circumference of the rectum is rarely complicated by stenosis.⁷⁶

ESD requires a high level of technical skill, is time-consuming, and has a higher rate of complications than conventional endoscopic resection. A standardized ESD training system is needed, as the procedure is more difficult than EMR. Training in porcine models has been shown to confer competency in ESD in a Western setting.^13,16,33

Colorectal ESD is an even more challenging procedure, given the potential for complications related to its anatomy. Training centers in Japan usually have their trainees first master gastric ESD, then assist in more than 20 colorectal ESDs conducted by experienced endoscopists, and accomplish 30 cases before performing the procedure safely and independently.

As the incidence of gastric cancer is low in Western countries, trainees may also begin with lower rectal lesions, which are easier to remove.⁷⁷ Incorporation of ESD in the West would require a clear treatment algorithm. It is a complex procedure, with higher rates of complications, a prolonged learning curve, and prolonged procedure time. Therefore, it should be performed in specialized centers and under the special situations discussed here to ensure that the benefits for the patients outweigh the risks.

VALUE OF ENDOSCOPIC SUBMUCOSAL DISSECTION

The optimal method for resecting gastrointestinal neoplasms should be safe, cost-effective, and quick and should also completely remove the lesion. The best treatment strategy takes into account the characteristics of the lesion and the comorbidities and wishes of the patient. Internists should be aware of the multiple options available to achieve the best outcome for the patient.¹

Endoscopic resection of superficial gastrointestinal neoplasms, including EMR and ESD, has been a subject of increasing interest due to its minimally invasive and potentially curative character. However, cancer can recur after endoscopic resection because the procedure is organ-sparing.

ESD allows resection of early gastrointestinal tumors with a minimally invasive technique. It can achieve higher curative resection rates and lower recurrence rates compared with EMR. Compared with surgery, ESD leads to less morbidity, fewer procedure-related complications, and lower medical costs. Indications should be rigorously followed to achieve successful treatments in selected patients.

Multiple variables have to be taken into account when deciding which treatment is best, such as tumor characteristics, the patient’s baseline condition, physician expertise, and hospital resources.⁴⁸ Less-invasive treatments may improve the prognosis of patients. No matter the approach, patients should be treated in specialized treatment centers.

Internal medicine physicians should be aware of the advances in treatments for early gastrointestinal cancer so appropriate options can be considered.

Four months after undergoing laparoscopic cholecystectomy for symptomatic gallstones, an otherwise healthy 26-year-old woman begins to have episodes of epigastric and back pain similar to what she experienced before the surgery. The surgery was without complications, and her classic biliary colic disappeared afterward. Histologic evaluation of the surgical specimen revealed chronic cholecystitis with multiple small, mixed gallstones.

Now she describes a burning pain in her epigastrium and mid to upper back, starting about 30 minutes after a meal and lasting up to 4 hours. Sometimes it awakens her at night. She avoids eating for fear of inducing the pain. She has occasional chills but no fever, nausea, vomiting, jaundice, or changes in urine or stool color.

Three years ago she was diagnosed with a gastric ulcer induced by taking a nonsteroidal anti-inflammatory drug (NSAID). The ulcer was treated with a proton pump inhibitor for 1 month. She says the ulcer pain was dull and aching, different from her current pain.

Upper endoscopy 4 months ago (ie, before her laparoscopic cholecystectomy) showed no evidence of esophagitis or peptic ulcer disease.

Apart from her gallbladder operation, she has had no other surgery. According to the surgeon’s notes, intraoperative cholangiography was not performed, and no macroscopic changes of acute cholecystitis or difficult biliary anatomy were noted.

The patient does not smoke, does not drink alcohol, is not currently taking any medications, including NSAIDs or over-the-counter medications, and has not taken any recently. Her mother also had symptomatic gallstones requiring cholecystectomy.

On physical examination, only fever

On examination, her temperature is 101.2°F (38.4°C), blood pressure 117/80 mm Hg, heart rate 82 beats per minute, and blood oxygen saturation 99% on room air. Her weight is 138 lb (62.6 kg), height 5 feet 6 inches (168 cm).

There is no jaundice or pallor. Her heart and lung examinations are normal.

No costovertebral angle or spinal tenderness can be elicited.

Her laboratory values are shown in Table 1.

POSTCHOLECYSTECTOMY SYNDROME

1. After cholecystectomy, preoperative symptoms recur in what percentage of patients?

• 10% to 40%
• 50%
• 60%
• 80%

Postcholecystectomy syndrome—the recurrence of symptoms similar to those before the procedure—occurs in 10% to 40% of patients. The time to the onset of symptoms can range from 2 days to up to 25 years.^1–4 Women may be at higher risk, with symptoms recurring in 43% vs 28% in men.⁵

Postcholecystectomy syndrome can have a biliary or a nonbiliary cause. Biliary causes include strictures, retained calculi, dropped calculi, tumors, sphincter of Oddi dysfunction, and calculi in the cystic duct remnant. Nonbiliary causes include functional and organic disorders such as peptic ulcer disease, gastroesophageal reflux, pancreatic disease, hepatocellular disorders, coronary artery disease, irritable bowel syndrome, and intercostal neuritis.

WHAT IS THE NEXT STEP?

2. Which is the most appropriate next step in the workup of this patient?

• Ultrasonography of the right upper quadrant
• Magnetic resonance cholangiopancreatography (MRCP)
• Endoscopic retrograde cholangiopancreatography (ERCP)
• Observation and reassurance
• Review the operative record and consult with the surgeon

Although the patient is presenting with pain and fever, two features of the classic Charcot triad (pain, fever, jaundice) seen in cholangitis (infection of a bile duct), and although cholangitis almost confirms the diagnosis of common bile duct stones in a patient with gallstones (before or after cholecystectomy), other diagnoses to consider are bile duct injury, bile leak, and biloma.

Biloma can be detected with ultrasonography. Bile duct injuries are identified intraoperatively in up to 25% of patients. For those with an unrecognized injury, the clinical presentation is variable and depends on the type of injury. If a bile leak is present, patients present early, at a median of 3 days postoperatively. However, our patient presented with symptoms 4 months after her surgery. Patients with bile duct strictures without bile leak have a longer symptom-free interval and usually present with signs of biliary obstruction. Ultrasonography can then detect biliary dilatation.⁶

It would be very helpful to review the operative record and to talk to the surgeon to confirm that intraoperative cholangiography had not been done and to determine the level of difficulty of the surgery. (Intraoperative cholangiography involves the introduction of contrast dye into the biliary system by cannulation of the cystic duct or by direct injection into the common bile duct. An intraoperative cholangiogram is considered normal if the entire intrahepatic and extrahepatic biliary tree is seen to be filled with contrast.) A normal cholangiogram has a negative predictive value of 99.8% for the detection of ductal stones. Thus, a normal intraoperative cholangiogram can prevent unnecessary postoperative ECRP, since it almost always indicates a clean bile duct.⁷

Ultrasonography of the right upper quadrant has a low sensitivity (< 50%) for detecting common bile duct stones. However, it is highly operator-dependent, and it may be twice as sensitive if done by expert radiologists than by less experienced ones. Its limitations include poor visualization of the distal portion of the duct and low sensitivity in patients in whom the common bile duct is minimally dilated and also in patients with small stones. In most studies, however, it had a very high specificity—ie, greater than 95%.⁸

MRCP has a sensitivity of 82.6% and a specificity of 97.5% in detecting stones in the common bile duct.⁹ Therefore, normal results on abdominal ultrasonography and MRCP do not completely rule out stones.

Although this patient has a high pretest probability of having common bile duct stones, ERCP should be done only after a thorough review of the previous operative procedure.

Observation and reassurance are not appropriate in a patient with cholangitis, such as this patient, because waiting increases the risk of septicemia.

Review of the operative report and discussion with the surgeon confirm that the laparoscopic procedure was uneventful and that intraoperative cholangiography was not done.

Therefore, the patient undergoes ERCP. The major papilla is normal. Cholangiography reveals nondilated common bile and intrahepatic ducts, with faint filling defects in the mid to distal common bile duct. Endoscopic sphincterotomy is performed, and three small stones are extracted from the common bile duct. Repeat balloon-occlusion cholangiography is normal.

The patient tolerates the procedure well and resumes a normal diet and normal activities.

Her pain persists, prompting an emergency room visit

Five days after her ERCP procedure, however, the same burning epigastric pain returns. As before, the pain occurs after eating and does not occur with fasting. At this time, she has no fever or chills.

WHAT IS CAUSING HER PAIN?

3. Which is the most likely cause of her persistent pain?

• Acute pancreatitis after ERCP
• Peptic ulcer disease
• Sphincter of Oddi dysfunction
• Biliary stones

The most likely cause is persistent biliary stones. The common bile duct was recently explored and stones were removed, but she may still have stones in the intrahepatic ducts or in the cystic duct remnant, both of which were unopacified during the ERCP procedure, indicating that either the test was incomplete or a stone is obstructing the passage of contrast. Her persistent symptoms warrant repeating her liver function tests.

Acute pancreatitis is the most common and feared complication of ERCP, and it should be suspected in any patient who develops abdominal pain within 6 hours of the procedure. It is much less likely to develop after 12 hours, however. Risk factors for post-ERCP pancreatitis include patient factors (young age, female sex, history of recurrent pancreatitis), procedural factors (difficult cannulation, minor papilla sphincterotomy), and, less likely, operator-related factors.^10–13 In general, the more likely a patient is to have an abnormal and irregular common bile duct or pancreatic duct, the lower the risk of post-ERCP pancreatitis. The importance of operator-dependent factors is not yet clear.^10–13

Despite the postprandial pattern of our patient’s pain and her history of gastric ulcer, peptic ulcer disease is unlikely in view of a normal esophagogastroduodenoscopic examination done 4 months earlier, and since she has no recent exposure to NSAIDs.

Sphincter of Oddi dysfunction may explain her symptoms, but she recently underwent endoscopic sphincterotomy, which is regarded as the most definitive treatment.¹⁴

WHAT SHOULD BE DONE NEXT?

4. What would be the best next step in her management?

• Repeat ERCP
• MRCP
• Endoscopic ultrasonography
• Observation and reassurance

MRCP is the most appropriate next step, given her recurrent symptoms. Repeat ERCP is not appropriate, since there is no evidence of cholangitis, and since her liver function tests had completely normalized.

A recent systematic review of endoscopic ultrasonography and MRCP for diagnosing choledocholithiasis found both tests to be highly accurate, with no statistically significant differences in sensitivity or specificity between the two.¹⁵ However, MRCP has the advantage of being noninvasive and of being able to show intrahepatic stones.

Park et al,¹⁶ in a prospective study of 66 patients with primary intrahepatic stones, concluded that MRCP findings were comparable to those of percutaneous transhepatic cholangioscopy, the reference standard for locating intrahepatic stones. The sensitivity, specificity, and accuracy of MRCP for detecting and locating intrahepatic stones were high (97%, 99%, and 98%, respectively).¹⁶ However, after sphincterotomy, pneumobilia may create an appearance that can be mistaken for intraductal stones.

She undergoes MRCP

The patient continues to have pain, and she has lost 5 pounds because she is still avoiding eating. At this point, she is beginning to wonder if her symptoms are psychogenic, since all the test results have been normal.

ERCP, MRCP, ULTRASONOGRAPHY?

5. What would be the best next step?

• Reassurance
• Referral to a psychiatrist
• Referral to a pain management clinic
• Endoscopic ultrasonography
• Repeat ERCP

Endoscopic ultrasonography is needed to look for cystic duct stones. Although several tests have shown normal results, the patient’s pain continues as in the previous episodes, making stone disease the most likely cause.

Although no stones were seen on MRCP and ultrasonography, a detailed evaluation for stones in a cystic duct or retained gallbladder remnant was not done satisfactorily.

Reassurance and referral to a psychiatrist or pain management clinic are not appropriate, since an organic cause of her pain has not been completely ruled out.

Findings on endoscopic ultrasonography

Endoscopic ultrasonography is performed and reveals a large (7-mm) stone in the area of the cystic duct remnant or gallbladder remnant (Figure 3). The common bile duct is normal.

CAUSES OF RETAINED GALLBLADDER AND CYSTIC DUCT REMNANT

6. What may have predisposed this patient to a retained gallbladder or cystic duct remnant after her surgery?

• Laparoscopic cholecystectomy
• Not doing intraoperative cholangiography
• Cholecystectomy for acute cholecystitis
• All of the above

All of the above may have contributed.

Postcholecystectomy syndrome can pose a diagnostic and therapeutic challenge, as in our patient. Although it has been reported since the advent of the operation, it is more common after laparoscopic cholecystectomy than after open surgery. One possible cause is stones in a cystic duct remnant, ie, a stub longer than 1 cm.

During open cholecystectomy, the cystic duct is ligated and cut as close to the common bile duct as possible, leaving only a small remnant. In laparoscopic cholecystectomy, it is divided closer to the gallbladder to avoid iatrogenic injury to the common bile duct, leaving a longer remnant. A long cystic duct remnant can be prevented by accurately locating the junction of the gallbladder and the cystic duct during cholecystectomy and by routinely doing intraoperative cholangiography. The presence of stones in a cystic duct or retained gallbladder remnant is a rare cause of postcholecystectomy syndrome, and suspicion is required to make the diagnosis.^17–19

We should note that stones may also lurk in the short cystic duct remnant left after open cholecystectomy. In fact, the first case of cystic duct remnant, the so-called reformed gallbladder containing stones, was described in 1912 by Flörcken.²⁰

Intraoperative cholangiography was introduced in 1931 by Mirizzi,²¹ who recommended its routine use. Since the advent of laparoscopic cholecystectomy in 1988, the routine use of intraoperative cholangiography has been debated. Advocates point to its ability to detect unsuspected calculi and to delineate the biliary anatomy, thus reducing the risk of biliary duct injury.^7,22–25 Those who argue against its routine use emphasize the low reported rates of unsuspected stones in the common bile duct (2% to 3%), a longer operative time, the additional cost, and false-positive results that may lead to unnecessary common bile duct exploration. Another argument against its routine use is that most small ductal stones pass spontaneously without significant sequelae.^26–28 Surgeons who use intraoperative cholangiography only selectively use it in patients with unclear biliary anatomy and preoperative biochemical or radiologic evidence of choledocholithiasis.

Case continued: She undergoes repeat ERCP

IF STONES ARE DIFFICULT TO EXTRACT

7. If the cystic duct stone were not amenable to endoscopic extraction, what would be the best alternative?

• Extracorporeal shock-wave lithotripsy (ESWL)
• Endoscopic biliary laser lithotripsy
• Repeat laparoscopic cholecystectomy
• All of the above

All of the above are alternatives.

A symptomatic stone in a cystic duct remnant is uncommon and is mentioned in the literature only in case series and case reports.

ESWL is effective for treating bile duct calculi.²⁹ In a cohort of 239 patients with bile duct stones treated by ESWL, Benninger et al³⁰ concluded that endoscopy plus ESWL was a definitive treatment for all patients except one, who subsequently underwent cholecystectomy. Once fragmented, the stones are extracted endoscopically.

Another fragmentation technique that can be offered to patients with stones in the cystic duct that are difficult to extract is contact fragmentation with a holmium laser placed in a transpapillary position under visual guidance.¹⁷

Repeat cholecystectomy with removal of stones in the cystic duct remnant (and removal of retained gallbladder remnants and reduction of the cystic duct remnant) has good postoperative results.^17,18,31,32

After incomplete cholecystectomy, the cystic duct remnant and the Calot (cystohepatic) triangle are surrounded by inflamed scar tissue, and this was thought to make laparoscopic reoperation difficult.³³ However, with advances in surgical technique and increasing experience of surgeons, repeat cholecystectomy can be done laparoscopically. It has now been suggested that laparoscopic exploration to remove the gallbladder remnants is safe and feasible in such patients.^34,35

Discharge and follow-up

The patient is discharged home after the procedure. She is still free of symptoms 31 months later.

LESSONS LEARNED

Remnant cystic duct stones are uncommon

The estimated incidence of a retained calculus within the cystic duct remnant after cholecystectomy is less than 2.5%.^2,36 In a series of 322 patients who underwent repeat surgery because of postcholecystectomy syndrome, Rogy et al³⁶ found only 8 who had a stone in the cystic duct or gallbladder remnant, and in a series of 371 patients, Zhou el al² found 4 who had a stone in the cystic duct remnant.

Stones in the cystic duct remnant are difficult to diagnose

Diagnosing stones in surgical remnants of the cystic duct or gallbladder can be difficult. The sensitivity of abdominal ultrasonography in detecting cystic duct stones is low—only 27% in one study, with a specificity of 100% and an accuracy of 75%.³⁷ Ultrasonography may occasionally suggest cystic duct stones by showing an acoustic shadow in the anatomic region of the cystic duct. However, the results should be interpreted with caution.

Determining the accuracy of ERCP and MRCP in detecting cystic duct remnant stones is also difficult, as few cases have been reported and data may be conflicting. In a review of seven patients confirmed to have retained stones in a surgical remnant, Walsh et al¹⁷ found that ERCP correctly diagnosed the retained stone in only four out of six patients; MRCP was done in one patient, and it was read as normal.

In three cases of stones in a postsurgical gallbladder remnant, Hassan and Vilmann³⁸ reported that ERCP and MRCP failed to identify the gallbladder remnant in two out of three cases, likely because the remaining structures are small. The diagnosis was finally made by endoscopic ultrasonography, which the authors concluded was a valuable method to visualize a small gallbladder remnant with stones.

Greater suspicion is needed in patients with typical biliary colic after cholecystectomy

Retained gallbladder remnant is described in the literature as a latent complication. The main problem is not the remnant itself but the chance that it harbors retained stones, which can lead to dilatation and inflammation of the remnant.

The patient can develop symptoms of acute cholecystitis or even acute cholangitis if the stone migrates to the common bile duct. Symptoms can develop as early as 2 weeks or as late as 25 years after laparoscopic cholecystectomy.

Endoscopic ultrasonography may be the best way to look for these remnant stones and to evaluate the bile duct and pancreas. Therefore, it should be part of the diagnostic algorithm in the evaluation of postcholecystectomy pain.

Mixed results with ERCP for extracting cystic duct stones

In case reports of cystic duct calculi after cholecystectomy, ERCP by itself has had mixed results. This traditional means of removing stones may succeed, as in our case. However, the success rate depends largely on anatomic factors such as the position of the stone in the cystic duct, the degree of stone impaction, the diameter of the cystic duct, and the number of valves in the duct.¹⁷

Stones in the cystic duct that cannot be extracted with ERCP may benefit from fragmentation techniques in situ via holmium laser followed by endoscopic extraction.

Repeat cholecystectomy is generally advised for any residual gallbladder, and it can be done laparoscopically.

Four months after undergoing laparoscopic cholecystectomy for symptomatic gallstones, an otherwise healthy 26-year-old woman begins to have episodes of epigastric and back pain similar to what she experienced before the surgery. The surgery was without complications, and her classic biliary colic disappeared afterward. Histologic evaluation of the surgical specimen revealed chronic cholecystitis with multiple small, mixed gallstones.

Now she describes a burning pain in her epigastrium and mid to upper back, starting about 30 minutes after a meal and lasting up to 4 hours. Sometimes it awakens her at night. She avoids eating for fear of inducing the pain. She has occasional chills but no fever, nausea, vomiting, jaundice, or changes in urine or stool color.

Three years ago she was diagnosed with a gastric ulcer induced by taking a nonsteroidal anti-inflammatory drug (NSAID). The ulcer was treated with a proton pump inhibitor for 1 month. She says the ulcer pain was dull and aching, different from her current pain.

Upper endoscopy 4 months ago (ie, before her laparoscopic cholecystectomy) showed no evidence of esophagitis or peptic ulcer disease.

Apart from her gallbladder operation, she has had no other surgery. According to the surgeon’s notes, intraoperative cholangiography was not performed, and no macroscopic changes of acute cholecystitis or difficult biliary anatomy were noted.

The patient does not smoke, does not drink alcohol, is not currently taking any medications, including NSAIDs or over-the-counter medications, and has not taken any recently. Her mother also had symptomatic gallstones requiring cholecystectomy.

On physical examination, only fever

On examination, her temperature is 101.2°F (38.4°C), blood pressure 117/80 mm Hg, heart rate 82 beats per minute, and blood oxygen saturation 99% on room air. Her weight is 138 lb (62.6 kg), height 5 feet 6 inches (168 cm).

There is no jaundice or pallor. Her heart and lung examinations are normal.

No costovertebral angle or spinal tenderness can be elicited.

Her laboratory values are shown in Table 1.

POSTCHOLECYSTECTOMY SYNDROME

1. After cholecystectomy, preoperative symptoms recur in what percentage of patients?

• 10% to 40%
• 50%
• 60%
• 80%

Postcholecystectomy syndrome—the recurrence of symptoms similar to those before the procedure—occurs in 10% to 40% of patients. The time to the onset of symptoms can range from 2 days to up to 25 years.^1–4 Women may be at higher risk, with symptoms recurring in 43% vs 28% in men.⁵

Postcholecystectomy syndrome can have a biliary or a nonbiliary cause. Biliary causes include strictures, retained calculi, dropped calculi, tumors, sphincter of Oddi dysfunction, and calculi in the cystic duct remnant. Nonbiliary causes include functional and organic disorders such as peptic ulcer disease, gastroesophageal reflux, pancreatic disease, hepatocellular disorders, coronary artery disease, irritable bowel syndrome, and intercostal neuritis.

WHAT IS THE NEXT STEP?

2. Which is the most appropriate next step in the workup of this patient?

• Ultrasonography of the right upper quadrant
• Magnetic resonance cholangiopancreatography (MRCP)
• Endoscopic retrograde cholangiopancreatography (ERCP)
• Observation and reassurance
• Review the operative record and consult with the surgeon

Although the patient is presenting with pain and fever, two features of the classic Charcot triad (pain, fever, jaundice) seen in cholangitis (infection of a bile duct), and although cholangitis almost confirms the diagnosis of common bile duct stones in a patient with gallstones (before or after cholecystectomy), other diagnoses to consider are bile duct injury, bile leak, and biloma.

Biloma can be detected with ultrasonography. Bile duct injuries are identified intraoperatively in up to 25% of patients. For those with an unrecognized injury, the clinical presentation is variable and depends on the type of injury. If a bile leak is present, patients present early, at a median of 3 days postoperatively. However, our patient presented with symptoms 4 months after her surgery. Patients with bile duct strictures without bile leak have a longer symptom-free interval and usually present with signs of biliary obstruction. Ultrasonography can then detect biliary dilatation.⁶

It would be very helpful to review the operative record and to talk to the surgeon to confirm that intraoperative cholangiography had not been done and to determine the level of difficulty of the surgery. (Intraoperative cholangiography involves the introduction of contrast dye into the biliary system by cannulation of the cystic duct or by direct injection into the common bile duct. An intraoperative cholangiogram is considered normal if the entire intrahepatic and extrahepatic biliary tree is seen to be filled with contrast.) A normal cholangiogram has a negative predictive value of 99.8% for the detection of ductal stones. Thus, a normal intraoperative cholangiogram can prevent unnecessary postoperative ECRP, since it almost always indicates a clean bile duct.⁷

Ultrasonography of the right upper quadrant has a low sensitivity (< 50%) for detecting common bile duct stones. However, it is highly operator-dependent, and it may be twice as sensitive if done by expert radiologists than by less experienced ones. Its limitations include poor visualization of the distal portion of the duct and low sensitivity in patients in whom the common bile duct is minimally dilated and also in patients with small stones. In most studies, however, it had a very high specificity—ie, greater than 95%.⁸

MRCP has a sensitivity of 82.6% and a specificity of 97.5% in detecting stones in the common bile duct.⁹ Therefore, normal results on abdominal ultrasonography and MRCP do not completely rule out stones.

Although this patient has a high pretest probability of having common bile duct stones, ERCP should be done only after a thorough review of the previous operative procedure.

Observation and reassurance are not appropriate in a patient with cholangitis, such as this patient, because waiting increases the risk of septicemia.

Review of the operative report and discussion with the surgeon confirm that the laparoscopic procedure was uneventful and that intraoperative cholangiography was not done.

Therefore, the patient undergoes ERCP. The major papilla is normal. Cholangiography reveals nondilated common bile and intrahepatic ducts, with faint filling defects in the mid to distal common bile duct. Endoscopic sphincterotomy is performed, and three small stones are extracted from the common bile duct. Repeat balloon-occlusion cholangiography is normal.

The patient tolerates the procedure well and resumes a normal diet and normal activities.

Her pain persists, prompting an emergency room visit

Five days after her ERCP procedure, however, the same burning epigastric pain returns. As before, the pain occurs after eating and does not occur with fasting. At this time, she has no fever or chills.

WHAT IS CAUSING HER PAIN?

3. Which is the most likely cause of her persistent pain?

• Acute pancreatitis after ERCP
• Peptic ulcer disease
• Sphincter of Oddi dysfunction
• Biliary stones

The most likely cause is persistent biliary stones. The common bile duct was recently explored and stones were removed, but she may still have stones in the intrahepatic ducts or in the cystic duct remnant, both of which were unopacified during the ERCP procedure, indicating that either the test was incomplete or a stone is obstructing the passage of contrast. Her persistent symptoms warrant repeating her liver function tests.

Acute pancreatitis is the most common and feared complication of ERCP, and it should be suspected in any patient who develops abdominal pain within 6 hours of the procedure. It is much less likely to develop after 12 hours, however. Risk factors for post-ERCP pancreatitis include patient factors (young age, female sex, history of recurrent pancreatitis), procedural factors (difficult cannulation, minor papilla sphincterotomy), and, less likely, operator-related factors.^10–13 In general, the more likely a patient is to have an abnormal and irregular common bile duct or pancreatic duct, the lower the risk of post-ERCP pancreatitis. The importance of operator-dependent factors is not yet clear.^10–13

Despite the postprandial pattern of our patient’s pain and her history of gastric ulcer, peptic ulcer disease is unlikely in view of a normal esophagogastroduodenoscopic examination done 4 months earlier, and since she has no recent exposure to NSAIDs.

Sphincter of Oddi dysfunction may explain her symptoms, but she recently underwent endoscopic sphincterotomy, which is regarded as the most definitive treatment.¹⁴

WHAT SHOULD BE DONE NEXT?

4. What would be the best next step in her management?

• Repeat ERCP
• MRCP
• Endoscopic ultrasonography
• Observation and reassurance

MRCP is the most appropriate next step, given her recurrent symptoms. Repeat ERCP is not appropriate, since there is no evidence of cholangitis, and since her liver function tests had completely normalized.

A recent systematic review of endoscopic ultrasonography and MRCP for diagnosing choledocholithiasis found both tests to be highly accurate, with no statistically significant differences in sensitivity or specificity between the two.¹⁵ However, MRCP has the advantage of being noninvasive and of being able to show intrahepatic stones.

Park et al,¹⁶ in a prospective study of 66 patients with primary intrahepatic stones, concluded that MRCP findings were comparable to those of percutaneous transhepatic cholangioscopy, the reference standard for locating intrahepatic stones. The sensitivity, specificity, and accuracy of MRCP for detecting and locating intrahepatic stones were high (97%, 99%, and 98%, respectively).¹⁶ However, after sphincterotomy, pneumobilia may create an appearance that can be mistaken for intraductal stones.

She undergoes MRCP

The patient continues to have pain, and she has lost 5 pounds because she is still avoiding eating. At this point, she is beginning to wonder if her symptoms are psychogenic, since all the test results have been normal.

ERCP, MRCP, ULTRASONOGRAPHY?

5. What would be the best next step?

• Reassurance
• Referral to a psychiatrist
• Referral to a pain management clinic
• Endoscopic ultrasonography
• Repeat ERCP

Endoscopic ultrasonography is needed to look for cystic duct stones. Although several tests have shown normal results, the patient’s pain continues as in the previous episodes, making stone disease the most likely cause.

Although no stones were seen on MRCP and ultrasonography, a detailed evaluation for stones in a cystic duct or retained gallbladder remnant was not done satisfactorily.

Reassurance and referral to a psychiatrist or pain management clinic are not appropriate, since an organic cause of her pain has not been completely ruled out.

Findings on endoscopic ultrasonography

Endoscopic ultrasonography is performed and reveals a large (7-mm) stone in the area of the cystic duct remnant or gallbladder remnant (Figure 3). The common bile duct is normal.

CAUSES OF RETAINED GALLBLADDER AND CYSTIC DUCT REMNANT

6. What may have predisposed this patient to a retained gallbladder or cystic duct remnant after her surgery?

• Laparoscopic cholecystectomy
• Not doing intraoperative cholangiography
• Cholecystectomy for acute cholecystitis
• All of the above

All of the above may have contributed.

Postcholecystectomy syndrome can pose a diagnostic and therapeutic challenge, as in our patient. Although it has been reported since the advent of the operation, it is more common after laparoscopic cholecystectomy than after open surgery. One possible cause is stones in a cystic duct remnant, ie, a stub longer than 1 cm.

During open cholecystectomy, the cystic duct is ligated and cut as close to the common bile duct as possible, leaving only a small remnant. In laparoscopic cholecystectomy, it is divided closer to the gallbladder to avoid iatrogenic injury to the common bile duct, leaving a longer remnant. A long cystic duct remnant can be prevented by accurately locating the junction of the gallbladder and the cystic duct during cholecystectomy and by routinely doing intraoperative cholangiography. The presence of stones in a cystic duct or retained gallbladder remnant is a rare cause of postcholecystectomy syndrome, and suspicion is required to make the diagnosis.^17–19

We should note that stones may also lurk in the short cystic duct remnant left after open cholecystectomy. In fact, the first case of cystic duct remnant, the so-called reformed gallbladder containing stones, was described in 1912 by Flörcken.²⁰

Intraoperative cholangiography was introduced in 1931 by Mirizzi,²¹ who recommended its routine use. Since the advent of laparoscopic cholecystectomy in 1988, the routine use of intraoperative cholangiography has been debated. Advocates point to its ability to detect unsuspected calculi and to delineate the biliary anatomy, thus reducing the risk of biliary duct injury.^7,22–25 Those who argue against its routine use emphasize the low reported rates of unsuspected stones in the common bile duct (2% to 3%), a longer operative time, the additional cost, and false-positive results that may lead to unnecessary common bile duct exploration. Another argument against its routine use is that most small ductal stones pass spontaneously without significant sequelae.^26–28 Surgeons who use intraoperative cholangiography only selectively use it in patients with unclear biliary anatomy and preoperative biochemical or radiologic evidence of choledocholithiasis.

Case continued: She undergoes repeat ERCP

IF STONES ARE DIFFICULT TO EXTRACT

7. If the cystic duct stone were not amenable to endoscopic extraction, what would be the best alternative?

• Extracorporeal shock-wave lithotripsy (ESWL)
• Endoscopic biliary laser lithotripsy
• Repeat laparoscopic cholecystectomy
• All of the above

All of the above are alternatives.

A symptomatic stone in a cystic duct remnant is uncommon and is mentioned in the literature only in case series and case reports.

ESWL is effective for treating bile duct calculi.²⁹ In a cohort of 239 patients with bile duct stones treated by ESWL, Benninger et al³⁰ concluded that endoscopy plus ESWL was a definitive treatment for all patients except one, who subsequently underwent cholecystectomy. Once fragmented, the stones are extracted endoscopically.

Another fragmentation technique that can be offered to patients with stones in the cystic duct that are difficult to extract is contact fragmentation with a holmium laser placed in a transpapillary position under visual guidance.¹⁷

Repeat cholecystectomy with removal of stones in the cystic duct remnant (and removal of retained gallbladder remnants and reduction of the cystic duct remnant) has good postoperative results.^17,18,31,32

After incomplete cholecystectomy, the cystic duct remnant and the Calot (cystohepatic) triangle are surrounded by inflamed scar tissue, and this was thought to make laparoscopic reoperation difficult.³³ However, with advances in surgical technique and increasing experience of surgeons, repeat cholecystectomy can be done laparoscopically. It has now been suggested that laparoscopic exploration to remove the gallbladder remnants is safe and feasible in such patients.^34,35

Discharge and follow-up

The patient is discharged home after the procedure. She is still free of symptoms 31 months later.

LESSONS LEARNED

Remnant cystic duct stones are uncommon

The estimated incidence of a retained calculus within the cystic duct remnant after cholecystectomy is less than 2.5%.^2,36 In a series of 322 patients who underwent repeat surgery because of postcholecystectomy syndrome, Rogy et al³⁶ found only 8 who had a stone in the cystic duct or gallbladder remnant, and in a series of 371 patients, Zhou el al² found 4 who had a stone in the cystic duct remnant.

Stones in the cystic duct remnant are difficult to diagnose

Diagnosing stones in surgical remnants of the cystic duct or gallbladder can be difficult. The sensitivity of abdominal ultrasonography in detecting cystic duct stones is low—only 27% in one study, with a specificity of 100% and an accuracy of 75%.³⁷ Ultrasonography may occasionally suggest cystic duct stones by showing an acoustic shadow in the anatomic region of the cystic duct. However, the results should be interpreted with caution.

Determining the accuracy of ERCP and MRCP in detecting cystic duct remnant stones is also difficult, as few cases have been reported and data may be conflicting. In a review of seven patients confirmed to have retained stones in a surgical remnant, Walsh et al¹⁷ found that ERCP correctly diagnosed the retained stone in only four out of six patients; MRCP was done in one patient, and it was read as normal.

In three cases of stones in a postsurgical gallbladder remnant, Hassan and Vilmann³⁸ reported that ERCP and MRCP failed to identify the gallbladder remnant in two out of three cases, likely because the remaining structures are small. The diagnosis was finally made by endoscopic ultrasonography, which the authors concluded was a valuable method to visualize a small gallbladder remnant with stones.

Greater suspicion is needed in patients with typical biliary colic after cholecystectomy

Retained gallbladder remnant is described in the literature as a latent complication. The main problem is not the remnant itself but the chance that it harbors retained stones, which can lead to dilatation and inflammation of the remnant.

The patient can develop symptoms of acute cholecystitis or even acute cholangitis if the stone migrates to the common bile duct. Symptoms can develop as early as 2 weeks or as late as 25 years after laparoscopic cholecystectomy.

Endoscopic ultrasonography may be the best way to look for these remnant stones and to evaluate the bile duct and pancreas. Therefore, it should be part of the diagnostic algorithm in the evaluation of postcholecystectomy pain.

Mixed results with ERCP for extracting cystic duct stones

In case reports of cystic duct calculi after cholecystectomy, ERCP by itself has had mixed results. This traditional means of removing stones may succeed, as in our case. However, the success rate depends largely on anatomic factors such as the position of the stone in the cystic duct, the degree of stone impaction, the diameter of the cystic duct, and the number of valves in the duct.¹⁷

Stones in the cystic duct that cannot be extracted with ERCP may benefit from fragmentation techniques in situ via holmium laser followed by endoscopic extraction.

Repeat cholecystectomy is generally advised for any residual gallbladder, and it can be done laparoscopically.

Four months after undergoing laparoscopic cholecystectomy for symptomatic gallstones, an otherwise healthy 26-year-old woman begins to have episodes of epigastric and back pain similar to what she experienced before the surgery. The surgery was without complications, and her classic biliary colic disappeared afterward. Histologic evaluation of the surgical specimen revealed chronic cholecystitis with multiple small, mixed gallstones.

Now she describes a burning pain in her epigastrium and mid to upper back, starting about 30 minutes after a meal and lasting up to 4 hours. Sometimes it awakens her at night. She avoids eating for fear of inducing the pain. She has occasional chills but no fever, nausea, vomiting, jaundice, or changes in urine or stool color.

Three years ago she was diagnosed with a gastric ulcer induced by taking a nonsteroidal anti-inflammatory drug (NSAID). The ulcer was treated with a proton pump inhibitor for 1 month. She says the ulcer pain was dull and aching, different from her current pain.

Upper endoscopy 4 months ago (ie, before her laparoscopic cholecystectomy) showed no evidence of esophagitis or peptic ulcer disease.

Apart from her gallbladder operation, she has had no other surgery. According to the surgeon’s notes, intraoperative cholangiography was not performed, and no macroscopic changes of acute cholecystitis or difficult biliary anatomy were noted.

The patient does not smoke, does not drink alcohol, is not currently taking any medications, including NSAIDs or over-the-counter medications, and has not taken any recently. Her mother also had symptomatic gallstones requiring cholecystectomy.

On physical examination, only fever

On examination, her temperature is 101.2°F (38.4°C), blood pressure 117/80 mm Hg, heart rate 82 beats per minute, and blood oxygen saturation 99% on room air. Her weight is 138 lb (62.6 kg), height 5 feet 6 inches (168 cm).

There is no jaundice or pallor. Her heart and lung examinations are normal.

No costovertebral angle or spinal tenderness can be elicited.

Her laboratory values are shown in Table 1.

POSTCHOLECYSTECTOMY SYNDROME

1. After cholecystectomy, preoperative symptoms recur in what percentage of patients?

• 10% to 40%
• 50%
• 60%
• 80%

Postcholecystectomy syndrome—the recurrence of symptoms similar to those before the procedure—occurs in 10% to 40% of patients. The time to the onset of symptoms can range from 2 days to up to 25 years.^1–4 Women may be at higher risk, with symptoms recurring in 43% vs 28% in men.⁵

Postcholecystectomy syndrome can have a biliary or a nonbiliary cause. Biliary causes include strictures, retained calculi, dropped calculi, tumors, sphincter of Oddi dysfunction, and calculi in the cystic duct remnant. Nonbiliary causes include functional and organic disorders such as peptic ulcer disease, gastroesophageal reflux, pancreatic disease, hepatocellular disorders, coronary artery disease, irritable bowel syndrome, and intercostal neuritis.

WHAT IS THE NEXT STEP?

2. Which is the most appropriate next step in the workup of this patient?

• Ultrasonography of the right upper quadrant
• Magnetic resonance cholangiopancreatography (MRCP)
• Endoscopic retrograde cholangiopancreatography (ERCP)
• Observation and reassurance
• Review the operative record and consult with the surgeon

Although the patient is presenting with pain and fever, two features of the classic Charcot triad (pain, fever, jaundice) seen in cholangitis (infection of a bile duct), and although cholangitis almost confirms the diagnosis of common bile duct stones in a patient with gallstones (before or after cholecystectomy), other diagnoses to consider are bile duct injury, bile leak, and biloma.

Biloma can be detected with ultrasonography. Bile duct injuries are identified intraoperatively in up to 25% of patients. For those with an unrecognized injury, the clinical presentation is variable and depends on the type of injury. If a bile leak is present, patients present early, at a median of 3 days postoperatively. However, our patient presented with symptoms 4 months after her surgery. Patients with bile duct strictures without bile leak have a longer symptom-free interval and usually present with signs of biliary obstruction. Ultrasonography can then detect biliary dilatation.⁶

It would be very helpful to review the operative record and to talk to the surgeon to confirm that intraoperative cholangiography had not been done and to determine the level of difficulty of the surgery. (Intraoperative cholangiography involves the introduction of contrast dye into the biliary system by cannulation of the cystic duct or by direct injection into the common bile duct. An intraoperative cholangiogram is considered normal if the entire intrahepatic and extrahepatic biliary tree is seen to be filled with contrast.) A normal cholangiogram has a negative predictive value of 99.8% for the detection of ductal stones. Thus, a normal intraoperative cholangiogram can prevent unnecessary postoperative ECRP, since it almost always indicates a clean bile duct.⁷

Ultrasonography of the right upper quadrant has a low sensitivity (< 50%) for detecting common bile duct stones. However, it is highly operator-dependent, and it may be twice as sensitive if done by expert radiologists than by less experienced ones. Its limitations include poor visualization of the distal portion of the duct and low sensitivity in patients in whom the common bile duct is minimally dilated and also in patients with small stones. In most studies, however, it had a very high specificity—ie, greater than 95%.⁸

MRCP has a sensitivity of 82.6% and a specificity of 97.5% in detecting stones in the common bile duct.⁹ Therefore, normal results on abdominal ultrasonography and MRCP do not completely rule out stones.

Although this patient has a high pretest probability of having common bile duct stones, ERCP should be done only after a thorough review of the previous operative procedure.

Observation and reassurance are not appropriate in a patient with cholangitis, such as this patient, because waiting increases the risk of septicemia.

Review of the operative report and discussion with the surgeon confirm that the laparoscopic procedure was uneventful and that intraoperative cholangiography was not done.

Therefore, the patient undergoes ERCP. The major papilla is normal. Cholangiography reveals nondilated common bile and intrahepatic ducts, with faint filling defects in the mid to distal common bile duct. Endoscopic sphincterotomy is performed, and three small stones are extracted from the common bile duct. Repeat balloon-occlusion cholangiography is normal.

The patient tolerates the procedure well and resumes a normal diet and normal activities.

Her pain persists, prompting an emergency room visit

Five days after her ERCP procedure, however, the same burning epigastric pain returns. As before, the pain occurs after eating and does not occur with fasting. At this time, she has no fever or chills.

WHAT IS CAUSING HER PAIN?

3. Which is the most likely cause of her persistent pain?

• Acute pancreatitis after ERCP
• Peptic ulcer disease
• Sphincter of Oddi dysfunction
• Biliary stones

The most likely cause is persistent biliary stones. The common bile duct was recently explored and stones were removed, but she may still have stones in the intrahepatic ducts or in the cystic duct remnant, both of which were unopacified during the ERCP procedure, indicating that either the test was incomplete or a stone is obstructing the passage of contrast. Her persistent symptoms warrant repeating her liver function tests.

Acute pancreatitis is the most common and feared complication of ERCP, and it should be suspected in any patient who develops abdominal pain within 6 hours of the procedure. It is much less likely to develop after 12 hours, however. Risk factors for post-ERCP pancreatitis include patient factors (young age, female sex, history of recurrent pancreatitis), procedural factors (difficult cannulation, minor papilla sphincterotomy), and, less likely, operator-related factors.^10–13 In general, the more likely a patient is to have an abnormal and irregular common bile duct or pancreatic duct, the lower the risk of post-ERCP pancreatitis. The importance of operator-dependent factors is not yet clear.^10–13

Despite the postprandial pattern of our patient’s pain and her history of gastric ulcer, peptic ulcer disease is unlikely in view of a normal esophagogastroduodenoscopic examination done 4 months earlier, and since she has no recent exposure to NSAIDs.

Sphincter of Oddi dysfunction may explain her symptoms, but she recently underwent endoscopic sphincterotomy, which is regarded as the most definitive treatment.¹⁴

WHAT SHOULD BE DONE NEXT?

4. What would be the best next step in her management?

• Repeat ERCP
• MRCP
• Endoscopic ultrasonography
• Observation and reassurance

MRCP is the most appropriate next step, given her recurrent symptoms. Repeat ERCP is not appropriate, since there is no evidence of cholangitis, and since her liver function tests had completely normalized.

A recent systematic review of endoscopic ultrasonography and MRCP for diagnosing choledocholithiasis found both tests to be highly accurate, with no statistically significant differences in sensitivity or specificity between the two.¹⁵ However, MRCP has the advantage of being noninvasive and of being able to show intrahepatic stones.

Park et al,¹⁶ in a prospective study of 66 patients with primary intrahepatic stones, concluded that MRCP findings were comparable to those of percutaneous transhepatic cholangioscopy, the reference standard for locating intrahepatic stones. The sensitivity, specificity, and accuracy of MRCP for detecting and locating intrahepatic stones were high (97%, 99%, and 98%, respectively).¹⁶ However, after sphincterotomy, pneumobilia may create an appearance that can be mistaken for intraductal stones.

She undergoes MRCP

The patient continues to have pain, and she has lost 5 pounds because she is still avoiding eating. At this point, she is beginning to wonder if her symptoms are psychogenic, since all the test results have been normal.

ERCP, MRCP, ULTRASONOGRAPHY?

5. What would be the best next step?

• Reassurance
• Referral to a psychiatrist
• Referral to a pain management clinic
• Endoscopic ultrasonography
• Repeat ERCP

Endoscopic ultrasonography is needed to look for cystic duct stones. Although several tests have shown normal results, the patient’s pain continues as in the previous episodes, making stone disease the most likely cause.

Although no stones were seen on MRCP and ultrasonography, a detailed evaluation for stones in a cystic duct or retained gallbladder remnant was not done satisfactorily.

Reassurance and referral to a psychiatrist or pain management clinic are not appropriate, since an organic cause of her pain has not been completely ruled out.

Findings on endoscopic ultrasonography

Endoscopic ultrasonography is performed and reveals a large (7-mm) stone in the area of the cystic duct remnant or gallbladder remnant (Figure 3). The common bile duct is normal.

CAUSES OF RETAINED GALLBLADDER AND CYSTIC DUCT REMNANT

6. What may have predisposed this patient to a retained gallbladder or cystic duct remnant after her surgery?

• Laparoscopic cholecystectomy
• Not doing intraoperative cholangiography
• Cholecystectomy for acute cholecystitis
• All of the above

All of the above may have contributed.

Postcholecystectomy syndrome can pose a diagnostic and therapeutic challenge, as in our patient. Although it has been reported since the advent of the operation, it is more common after laparoscopic cholecystectomy than after open surgery. One possible cause is stones in a cystic duct remnant, ie, a stub longer than 1 cm.

During open cholecystectomy, the cystic duct is ligated and cut as close to the common bile duct as possible, leaving only a small remnant. In laparoscopic cholecystectomy, it is divided closer to the gallbladder to avoid iatrogenic injury to the common bile duct, leaving a longer remnant. A long cystic duct remnant can be prevented by accurately locating the junction of the gallbladder and the cystic duct during cholecystectomy and by routinely doing intraoperative cholangiography. The presence of stones in a cystic duct or retained gallbladder remnant is a rare cause of postcholecystectomy syndrome, and suspicion is required to make the diagnosis.^17–19

We should note that stones may also lurk in the short cystic duct remnant left after open cholecystectomy. In fact, the first case of cystic duct remnant, the so-called reformed gallbladder containing stones, was described in 1912 by Flörcken.²⁰

Intraoperative cholangiography was introduced in 1931 by Mirizzi,²¹ who recommended its routine use. Since the advent of laparoscopic cholecystectomy in 1988, the routine use of intraoperative cholangiography has been debated. Advocates point to its ability to detect unsuspected calculi and to delineate the biliary anatomy, thus reducing the risk of biliary duct injury.^7,22–25 Those who argue against its routine use emphasize the low reported rates of unsuspected stones in the common bile duct (2% to 3%), a longer operative time, the additional cost, and false-positive results that may lead to unnecessary common bile duct exploration. Another argument against its routine use is that most small ductal stones pass spontaneously without significant sequelae.^26–28 Surgeons who use intraoperative cholangiography only selectively use it in patients with unclear biliary anatomy and preoperative biochemical or radiologic evidence of choledocholithiasis.

Case continued: She undergoes repeat ERCP

IF STONES ARE DIFFICULT TO EXTRACT

7. If the cystic duct stone were not amenable to endoscopic extraction, what would be the best alternative?

• Extracorporeal shock-wave lithotripsy (ESWL)
• Endoscopic biliary laser lithotripsy
• Repeat laparoscopic cholecystectomy
• All of the above

All of the above are alternatives.

A symptomatic stone in a cystic duct remnant is uncommon and is mentioned in the literature only in case series and case reports.

ESWL is effective for treating bile duct calculi.²⁹ In a cohort of 239 patients with bile duct stones treated by ESWL, Benninger et al³⁰ concluded that endoscopy plus ESWL was a definitive treatment for all patients except one, who subsequently underwent cholecystectomy. Once fragmented, the stones are extracted endoscopically.

Another fragmentation technique that can be offered to patients with stones in the cystic duct that are difficult to extract is contact fragmentation with a holmium laser placed in a transpapillary position under visual guidance.¹⁷

Repeat cholecystectomy with removal of stones in the cystic duct remnant (and removal of retained gallbladder remnants and reduction of the cystic duct remnant) has good postoperative results.^17,18,31,32

After incomplete cholecystectomy, the cystic duct remnant and the Calot (cystohepatic) triangle are surrounded by inflamed scar tissue, and this was thought to make laparoscopic reoperation difficult.³³ However, with advances in surgical technique and increasing experience of surgeons, repeat cholecystectomy can be done laparoscopically. It has now been suggested that laparoscopic exploration to remove the gallbladder remnants is safe and feasible in such patients.^34,35

Discharge and follow-up

The patient is discharged home after the procedure. She is still free of symptoms 31 months later.

LESSONS LEARNED

Remnant cystic duct stones are uncommon

The estimated incidence of a retained calculus within the cystic duct remnant after cholecystectomy is less than 2.5%.^2,36 In a series of 322 patients who underwent repeat surgery because of postcholecystectomy syndrome, Rogy et al³⁶ found only 8 who had a stone in the cystic duct or gallbladder remnant, and in a series of 371 patients, Zhou el al² found 4 who had a stone in the cystic duct remnant.

Stones in the cystic duct remnant are difficult to diagnose

Diagnosing stones in surgical remnants of the cystic duct or gallbladder can be difficult. The sensitivity of abdominal ultrasonography in detecting cystic duct stones is low—only 27% in one study, with a specificity of 100% and an accuracy of 75%.³⁷ Ultrasonography may occasionally suggest cystic duct stones by showing an acoustic shadow in the anatomic region of the cystic duct. However, the results should be interpreted with caution.

Determining the accuracy of ERCP and MRCP in detecting cystic duct remnant stones is also difficult, as few cases have been reported and data may be conflicting. In a review of seven patients confirmed to have retained stones in a surgical remnant, Walsh et al¹⁷ found that ERCP correctly diagnosed the retained stone in only four out of six patients; MRCP was done in one patient, and it was read as normal.

In three cases of stones in a postsurgical gallbladder remnant, Hassan and Vilmann³⁸ reported that ERCP and MRCP failed to identify the gallbladder remnant in two out of three cases, likely because the remaining structures are small. The diagnosis was finally made by endoscopic ultrasonography, which the authors concluded was a valuable method to visualize a small gallbladder remnant with stones.

Greater suspicion is needed in patients with typical biliary colic after cholecystectomy

Retained gallbladder remnant is described in the literature as a latent complication. The main problem is not the remnant itself but the chance that it harbors retained stones, which can lead to dilatation and inflammation of the remnant.

The patient can develop symptoms of acute cholecystitis or even acute cholangitis if the stone migrates to the common bile duct. Symptoms can develop as early as 2 weeks or as late as 25 years after laparoscopic cholecystectomy.

Endoscopic ultrasonography may be the best way to look for these remnant stones and to evaluate the bile duct and pancreas. Therefore, it should be part of the diagnostic algorithm in the evaluation of postcholecystectomy pain.

Mixed results with ERCP for extracting cystic duct stones

In case reports of cystic duct calculi after cholecystectomy, ERCP by itself has had mixed results. This traditional means of removing stones may succeed, as in our case. However, the success rate depends largely on anatomic factors such as the position of the stone in the cystic duct, the degree of stone impaction, the diameter of the cystic duct, and the number of valves in the duct.¹⁷

Stones in the cystic duct that cannot be extracted with ERCP may benefit from fragmentation techniques in situ via holmium laser followed by endoscopic extraction.

Repeat cholecystectomy is generally advised for any residual gallbladder, and it can be done laparoscopically.