Amy Karon

Over the past decade, Helicobacter pylori strains have reached “alarming levels” of antimicrobial resistance worldwide, investigators reported in the November issue of Gastroenterology.

In a large meta-analysis spanning 2007-2017, H. pylori isolates showed a 15% or higher pooled prevalence of primary and secondary resistance to clarithromycin, metronidazole, and levofloxacin in almost all World Health Organization (WHO) regions. “Local surveillance networks are required to select appropriate eradication regimens for each region,” concluded Alessia Savoldi, MD, of the University of Tübingen (Germany) and her associates.

Typically, the threshold of antimicrobial resistance for choosing empiric regimens is 15%, Dr. Savoldi and her associates noted. Their systematic review and meta-analysis included 178 studies comprising 66,142 isolates from 65 countries. They defined H. pylori infection as a positive histology, serology, stool antigen, urea breath test, or rapid urease test. They excluded studies of fewer than 50 isolates, studies that only reported resistance as a percentage with no denominator, studies that failed to specify time frames or clustered data over more than 3 years, and data reported in guidelines, conference presentations, or letters without formal publication.

Patho/Wikimedia Commons/CC BY-SA 3.0

SOURCE: Savoldi A et al. Gastroenterology. 2018 Nov. doi: 10.1053/j.gastro.2018.07.007.

Over the past decade, Helicobacter pylori strains have reached “alarming levels” of antimicrobial resistance worldwide, investigators reported in the November issue of Gastroenterology.

In a large meta-analysis spanning 2007-2017, H. pylori isolates showed a 15% or higher pooled prevalence of primary and secondary resistance to clarithromycin, metronidazole, and levofloxacin in almost all World Health Organization (WHO) regions. “Local surveillance networks are required to select appropriate eradication regimens for each region,” concluded Alessia Savoldi, MD, of the University of Tübingen (Germany) and her associates.

Typically, the threshold of antimicrobial resistance for choosing empiric regimens is 15%, Dr. Savoldi and her associates noted. Their systematic review and meta-analysis included 178 studies comprising 66,142 isolates from 65 countries. They defined H. pylori infection as a positive histology, serology, stool antigen, urea breath test, or rapid urease test. They excluded studies of fewer than 50 isolates, studies that only reported resistance as a percentage with no denominator, studies that failed to specify time frames or clustered data over more than 3 years, and data reported in guidelines, conference presentations, or letters without formal publication.

Patho/Wikimedia Commons/CC BY-SA 3.0

SOURCE: Savoldi A et al. Gastroenterology. 2018 Nov. doi: 10.1053/j.gastro.2018.07.007.

Over the past decade, Helicobacter pylori strains have reached “alarming levels” of antimicrobial resistance worldwide, investigators reported in the November issue of Gastroenterology.

In a large meta-analysis spanning 2007-2017, H. pylori isolates showed a 15% or higher pooled prevalence of primary and secondary resistance to clarithromycin, metronidazole, and levofloxacin in almost all World Health Organization (WHO) regions. “Local surveillance networks are required to select appropriate eradication regimens for each region,” concluded Alessia Savoldi, MD, of the University of Tübingen (Germany) and her associates.

Typically, the threshold of antimicrobial resistance for choosing empiric regimens is 15%, Dr. Savoldi and her associates noted. Their systematic review and meta-analysis included 178 studies comprising 66,142 isolates from 65 countries. They defined H. pylori infection as a positive histology, serology, stool antigen, urea breath test, or rapid urease test. They excluded studies of fewer than 50 isolates, studies that only reported resistance as a percentage with no denominator, studies that failed to specify time frames or clustered data over more than 3 years, and data reported in guidelines, conference presentations, or letters without formal publication.

Patho/Wikimedia Commons/CC BY-SA 3.0

SOURCE: Savoldi A et al. Gastroenterology. 2018 Nov. doi: 10.1053/j.gastro.2018.07.007.

For patients with inflammatory bowel disease (IBD), thiopurine exposure was associated with a significantly increased risk of herpes zoster, compared with 5-aminosalicylic acid (5-ASA) monotherapy, according to the results of two large retrospective cohort studies.

Joloei/Thinkstock

In the multivariable analysis, thiopurine monotherapy was linked to about a 47% increase in the risk of herpes zoster, compared with 5-ASA monotherapy (adjusted hazard ratio, 1.47; 95% confidence interval, 1.31-1.65; P less than .001). Combination therapy with thiopurines and tumor necrosis factor antagonists conferred about a 65% increase in zoster risk (aHR, 1.65; 95% CI, 1.22-2.23; P = .001). However, tumor necrosis factor–antagonist monotherapy did not appear to significantly increase the risk of zoster when compared with 5-ASA monotherapy, reported Nabeel Khan, MD, of the University of Pennsylvania in Philadelphia, and his associates.

“Compared to [patients without] IBD, ulcerative colitis (UC) and Crohn’s disease (CD) each were associated with significantly increased risk of herpes zoster infection,” the researchers wrote online in Clinical Gastroenterology and Hepatology. “With the approval of a new and potentially safer vaccine for herpes zoster, the effects of immunization of patients with IBD should be investigated.”

Past studies have linked IBD with a 1.2- to 1.8-fold increase in the risk of zoster, but these studies date to the prebiologic era or excluded patients who were in their midsixties or older, the researchers wrote. “Additionally, these prior studies have not assessed the validity of the codes used to identify herpes zoster and also did not account for the impact of vaccination,” they added. “They also did not take into consideration the severity of the disease or degree of steroid exposure.”

Therefore, the researchers conducted two retrospective cohort studies of patients in the United States Department of Veterans Affairs between 2000 and 2016. The first cohort study compared the incidence of herpes zoster among patients with IBD who received 5-ASA alone with matched patients without IBD. The second cohort study measured the incidence of herpes zoster in patients with IBD who received various medications and combination regimen. “The VA has a predominantly older population, which makes it an ideal cohort to study herpes zoster incidence in a high-risk population,” the investigators noted. “Unlike insurance databases, the VA database can be validated internally and vaccination records are documented.”

After adjusting for age, race, sex, geographic region, disease flare, corticosteroid use, and baseline comorbidities, the estimated hazard of developing herpes zoster was 1.81 (95% confidence interval, 1.56-2.11) among patients with ulcerative colitis and 1.56 (95% CI, 1.28-1.91) among patients with Crohn’s disease, as compared with patients without IBD. Regardless of their age or the medications they were receiving, patients with IBD had a higher incidence of zoster than the oldest group of patients without IBD (older than 60 years), regardless of age or medication. “The highest risk of herpes zoster was observed in patients with IBD who were less than 60 years of age and on combination therapy,” the investigators wrote. “Patients with IBD younger than 50 years who were on combination therapy had higher risk of herpes zoster, compared with patients with IBD older than 60 years of age who were not on immunosuppressive therapy.” Based on the findings, they recommended studying the efficacy of widespread use of the new herpes zoster vaccine in patients with IBD.

Pfizer provided unrestricted research funding but was not otherwise involved in the study. One coinvestigator disclosed ties to Pfizer and several other pharmaceutical companies. The remaining investigators reported having no conflicts of interest.
 

SOURCE: Khan N et al. Clin Gastroenterol Hepatol. 2018 Jan 5. doi: 10.1016/j.cgh.2017.12.052.

For patients with inflammatory bowel disease (IBD), thiopurine exposure was associated with a significantly increased risk of herpes zoster, compared with 5-aminosalicylic acid (5-ASA) monotherapy, according to the results of two large retrospective cohort studies.

Joloei/Thinkstock

In the multivariable analysis, thiopurine monotherapy was linked to about a 47% increase in the risk of herpes zoster, compared with 5-ASA monotherapy (adjusted hazard ratio, 1.47; 95% confidence interval, 1.31-1.65; P less than .001). Combination therapy with thiopurines and tumor necrosis factor antagonists conferred about a 65% increase in zoster risk (aHR, 1.65; 95% CI, 1.22-2.23; P = .001). However, tumor necrosis factor–antagonist monotherapy did not appear to significantly increase the risk of zoster when compared with 5-ASA monotherapy, reported Nabeel Khan, MD, of the University of Pennsylvania in Philadelphia, and his associates.

“Compared to [patients without] IBD, ulcerative colitis (UC) and Crohn’s disease (CD) each were associated with significantly increased risk of herpes zoster infection,” the researchers wrote online in Clinical Gastroenterology and Hepatology. “With the approval of a new and potentially safer vaccine for herpes zoster, the effects of immunization of patients with IBD should be investigated.”

Past studies have linked IBD with a 1.2- to 1.8-fold increase in the risk of zoster, but these studies date to the prebiologic era or excluded patients who were in their midsixties or older, the researchers wrote. “Additionally, these prior studies have not assessed the validity of the codes used to identify herpes zoster and also did not account for the impact of vaccination,” they added. “They also did not take into consideration the severity of the disease or degree of steroid exposure.”

Therefore, the researchers conducted two retrospective cohort studies of patients in the United States Department of Veterans Affairs between 2000 and 2016. The first cohort study compared the incidence of herpes zoster among patients with IBD who received 5-ASA alone with matched patients without IBD. The second cohort study measured the incidence of herpes zoster in patients with IBD who received various medications and combination regimen. “The VA has a predominantly older population, which makes it an ideal cohort to study herpes zoster incidence in a high-risk population,” the investigators noted. “Unlike insurance databases, the VA database can be validated internally and vaccination records are documented.”

After adjusting for age, race, sex, geographic region, disease flare, corticosteroid use, and baseline comorbidities, the estimated hazard of developing herpes zoster was 1.81 (95% confidence interval, 1.56-2.11) among patients with ulcerative colitis and 1.56 (95% CI, 1.28-1.91) among patients with Crohn’s disease, as compared with patients without IBD. Regardless of their age or the medications they were receiving, patients with IBD had a higher incidence of zoster than the oldest group of patients without IBD (older than 60 years), regardless of age or medication. “The highest risk of herpes zoster was observed in patients with IBD who were less than 60 years of age and on combination therapy,” the investigators wrote. “Patients with IBD younger than 50 years who were on combination therapy had higher risk of herpes zoster, compared with patients with IBD older than 60 years of age who were not on immunosuppressive therapy.” Based on the findings, they recommended studying the efficacy of widespread use of the new herpes zoster vaccine in patients with IBD.

Pfizer provided unrestricted research funding but was not otherwise involved in the study. One coinvestigator disclosed ties to Pfizer and several other pharmaceutical companies. The remaining investigators reported having no conflicts of interest.
 

SOURCE: Khan N et al. Clin Gastroenterol Hepatol. 2018 Jan 5. doi: 10.1016/j.cgh.2017.12.052.

For patients with inflammatory bowel disease (IBD), thiopurine exposure was associated with a significantly increased risk of herpes zoster, compared with 5-aminosalicylic acid (5-ASA) monotherapy, according to the results of two large retrospective cohort studies.

Joloei/Thinkstock

In the multivariable analysis, thiopurine monotherapy was linked to about a 47% increase in the risk of herpes zoster, compared with 5-ASA monotherapy (adjusted hazard ratio, 1.47; 95% confidence interval, 1.31-1.65; P less than .001). Combination therapy with thiopurines and tumor necrosis factor antagonists conferred about a 65% increase in zoster risk (aHR, 1.65; 95% CI, 1.22-2.23; P = .001). However, tumor necrosis factor–antagonist monotherapy did not appear to significantly increase the risk of zoster when compared with 5-ASA monotherapy, reported Nabeel Khan, MD, of the University of Pennsylvania in Philadelphia, and his associates.

“Compared to [patients without] IBD, ulcerative colitis (UC) and Crohn’s disease (CD) each were associated with significantly increased risk of herpes zoster infection,” the researchers wrote online in Clinical Gastroenterology and Hepatology. “With the approval of a new and potentially safer vaccine for herpes zoster, the effects of immunization of patients with IBD should be investigated.”

Past studies have linked IBD with a 1.2- to 1.8-fold increase in the risk of zoster, but these studies date to the prebiologic era or excluded patients who were in their midsixties or older, the researchers wrote. “Additionally, these prior studies have not assessed the validity of the codes used to identify herpes zoster and also did not account for the impact of vaccination,” they added. “They also did not take into consideration the severity of the disease or degree of steroid exposure.”

Therefore, the researchers conducted two retrospective cohort studies of patients in the United States Department of Veterans Affairs between 2000 and 2016. The first cohort study compared the incidence of herpes zoster among patients with IBD who received 5-ASA alone with matched patients without IBD. The second cohort study measured the incidence of herpes zoster in patients with IBD who received various medications and combination regimen. “The VA has a predominantly older population, which makes it an ideal cohort to study herpes zoster incidence in a high-risk population,” the investigators noted. “Unlike insurance databases, the VA database can be validated internally and vaccination records are documented.”

After adjusting for age, race, sex, geographic region, disease flare, corticosteroid use, and baseline comorbidities, the estimated hazard of developing herpes zoster was 1.81 (95% confidence interval, 1.56-2.11) among patients with ulcerative colitis and 1.56 (95% CI, 1.28-1.91) among patients with Crohn’s disease, as compared with patients without IBD. Regardless of their age or the medications they were receiving, patients with IBD had a higher incidence of zoster than the oldest group of patients without IBD (older than 60 years), regardless of age or medication. “The highest risk of herpes zoster was observed in patients with IBD who were less than 60 years of age and on combination therapy,” the investigators wrote. “Patients with IBD younger than 50 years who were on combination therapy had higher risk of herpes zoster, compared with patients with IBD older than 60 years of age who were not on immunosuppressive therapy.” Based on the findings, they recommended studying the efficacy of widespread use of the new herpes zoster vaccine in patients with IBD.

Pfizer provided unrestricted research funding but was not otherwise involved in the study. One coinvestigator disclosed ties to Pfizer and several other pharmaceutical companies. The remaining investigators reported having no conflicts of interest.
 

SOURCE: Khan N et al. Clin Gastroenterol Hepatol. 2018 Jan 5. doi: 10.1016/j.cgh.2017.12.052.

Factoring hyponatremic status into liver graft allocations led to significant reductions in wait-list mortality, researchers reported in the November issue of Gastroenterology.

©Eraxion/thinkstockphotos.com

Hyponatremic patients with low MELD scores benefited significantly from allocation based on the end-stage liver disease–sodium (MELD-Na) score, while its survival benefit was less evident among patients with higher scores, said Shunji Nagai, MD, PhD, of Henry Ford Hospital, Detroit, and his associates. “Therefore, liver allocation rules such as Share 15 and Share 35 need to be revised to fulfill the Final Rule under the MELD-Na based allocation,” they wrote.

The Share 35 rule offers liver grafts locally and regionally to wait-listed patients with MELD-Na scores of at least 35. Under the Share 15 rule, livers are offered regionally or nationally before considering local candidates with MELD scores under 15. The traditional MELD scoring system excluded hyponatremia, which has since been found to independently predict death from cirrhosis. Therefore, in January 2016, a modified MELD-Na score was implemented for patients with traditional MELD scores of at least 12. The MELD-Na score assigns patients between 1 and 11 additional points, and patients with low MELD scores and severe hyponatremia receive the most points. To assess the impact of this change, Dr. Nagai and his associates compared wait-list and posttransplantation outcomes during the pre and post–MELD-Na eras and the survival benefit of liver transplantation during the MELD-Na period. The study included all adults wait-listed for livers from June 2013, when Share 35 was implemented, through September 2017.

Mortality within 90 days on the wait list fell significantly during the MELD-Na era (hazard ratio, 0.74; P less than .001). Transplantation conferred a “definitive” survival benefit when MELD-Na scores were 21-23 (HR versus wait list, 0.34; P less than .001). During the traditional MELD period, the equivalent cutoff was 15-17 (HR, 0.36; P less than .001). “As such, the current rules for liver allocation may be suboptimal under the MELD-Na–based allocation and the criteria for Share 15 may need to be revisited,” the researchers wrote. They recommended raising the cutoff to 21.

The study also confirmed mild hyponatremia (130-134 mmol/L), moderate hyponatremia (125-129 mmol/L), and severe hyponatremia (less than 125 mmol/L) as independent predictors of wait-list mortality during the traditional MELD era. Hazard ratios were 1.4, 1.8, and 1.7, respectively (all P less than .001). The implementation of MELD-Na significantly weakened these associations, with HRs of 1.1 (P = .3), 1.3 (P = .02), and 1.4 (P = .04), respectively).

The probability of transplantation also rose significantly during the MELD-Na era (HR, 1.2; P less than .001), possibly because of the opioid epidemic, the researchers said. Although greater availability of liver grafts might have improved wait-list outcomes, all score categories would have shown a positive impact if this was the only reason, they added. Instead, MELD-Na most benefited patients with lower scores.

Finally, posttransplantation outcomes worsened during the MELD-Na era, perhaps because of transplant population aging. However, the survival benefit of transplant shifted to higher score ranges during the MELD-Na era even after the researchers controlled for this effect. “According to this analysis,” they wrote, “the survival benefit of liver transplant was definitive in patients with score category of 21-23, which could further validate our proposal to revise Share 15 rule to ‘Share 21.’ ”

The investigators reported having no external funding sources or conflicts of interest.

SOURCE: Nagai S et al. Gastroenterology. 2018 Jul 26. doi: 10.1053/j.gastro.2018.07.025.

Factoring hyponatremic status into liver graft allocations led to significant reductions in wait-list mortality, researchers reported in the November issue of Gastroenterology.

©Eraxion/thinkstockphotos.com

Hyponatremic patients with low MELD scores benefited significantly from allocation based on the end-stage liver disease–sodium (MELD-Na) score, while its survival benefit was less evident among patients with higher scores, said Shunji Nagai, MD, PhD, of Henry Ford Hospital, Detroit, and his associates. “Therefore, liver allocation rules such as Share 15 and Share 35 need to be revised to fulfill the Final Rule under the MELD-Na based allocation,” they wrote.

The Share 35 rule offers liver grafts locally and regionally to wait-listed patients with MELD-Na scores of at least 35. Under the Share 15 rule, livers are offered regionally or nationally before considering local candidates with MELD scores under 15. The traditional MELD scoring system excluded hyponatremia, which has since been found to independently predict death from cirrhosis. Therefore, in January 2016, a modified MELD-Na score was implemented for patients with traditional MELD scores of at least 12. The MELD-Na score assigns patients between 1 and 11 additional points, and patients with low MELD scores and severe hyponatremia receive the most points. To assess the impact of this change, Dr. Nagai and his associates compared wait-list and posttransplantation outcomes during the pre and post–MELD-Na eras and the survival benefit of liver transplantation during the MELD-Na period. The study included all adults wait-listed for livers from June 2013, when Share 35 was implemented, through September 2017.

Mortality within 90 days on the wait list fell significantly during the MELD-Na era (hazard ratio, 0.74; P less than .001). Transplantation conferred a “definitive” survival benefit when MELD-Na scores were 21-23 (HR versus wait list, 0.34; P less than .001). During the traditional MELD period, the equivalent cutoff was 15-17 (HR, 0.36; P less than .001). “As such, the current rules for liver allocation may be suboptimal under the MELD-Na–based allocation and the criteria for Share 15 may need to be revisited,” the researchers wrote. They recommended raising the cutoff to 21.

The study also confirmed mild hyponatremia (130-134 mmol/L), moderate hyponatremia (125-129 mmol/L), and severe hyponatremia (less than 125 mmol/L) as independent predictors of wait-list mortality during the traditional MELD era. Hazard ratios were 1.4, 1.8, and 1.7, respectively (all P less than .001). The implementation of MELD-Na significantly weakened these associations, with HRs of 1.1 (P = .3), 1.3 (P = .02), and 1.4 (P = .04), respectively).

The probability of transplantation also rose significantly during the MELD-Na era (HR, 1.2; P less than .001), possibly because of the opioid epidemic, the researchers said. Although greater availability of liver grafts might have improved wait-list outcomes, all score categories would have shown a positive impact if this was the only reason, they added. Instead, MELD-Na most benefited patients with lower scores.

Finally, posttransplantation outcomes worsened during the MELD-Na era, perhaps because of transplant population aging. However, the survival benefit of transplant shifted to higher score ranges during the MELD-Na era even after the researchers controlled for this effect. “According to this analysis,” they wrote, “the survival benefit of liver transplant was definitive in patients with score category of 21-23, which could further validate our proposal to revise Share 15 rule to ‘Share 21.’ ”

The investigators reported having no external funding sources or conflicts of interest.

SOURCE: Nagai S et al. Gastroenterology. 2018 Jul 26. doi: 10.1053/j.gastro.2018.07.025.

Factoring hyponatremic status into liver graft allocations led to significant reductions in wait-list mortality, researchers reported in the November issue of Gastroenterology.

©Eraxion/thinkstockphotos.com

Hyponatremic patients with low MELD scores benefited significantly from allocation based on the end-stage liver disease–sodium (MELD-Na) score, while its survival benefit was less evident among patients with higher scores, said Shunji Nagai, MD, PhD, of Henry Ford Hospital, Detroit, and his associates. “Therefore, liver allocation rules such as Share 15 and Share 35 need to be revised to fulfill the Final Rule under the MELD-Na based allocation,” they wrote.

The Share 35 rule offers liver grafts locally and regionally to wait-listed patients with MELD-Na scores of at least 35. Under the Share 15 rule, livers are offered regionally or nationally before considering local candidates with MELD scores under 15. The traditional MELD scoring system excluded hyponatremia, which has since been found to independently predict death from cirrhosis. Therefore, in January 2016, a modified MELD-Na score was implemented for patients with traditional MELD scores of at least 12. The MELD-Na score assigns patients between 1 and 11 additional points, and patients with low MELD scores and severe hyponatremia receive the most points. To assess the impact of this change, Dr. Nagai and his associates compared wait-list and posttransplantation outcomes during the pre and post–MELD-Na eras and the survival benefit of liver transplantation during the MELD-Na period. The study included all adults wait-listed for livers from June 2013, when Share 35 was implemented, through September 2017.

Mortality within 90 days on the wait list fell significantly during the MELD-Na era (hazard ratio, 0.74; P less than .001). Transplantation conferred a “definitive” survival benefit when MELD-Na scores were 21-23 (HR versus wait list, 0.34; P less than .001). During the traditional MELD period, the equivalent cutoff was 15-17 (HR, 0.36; P less than .001). “As such, the current rules for liver allocation may be suboptimal under the MELD-Na–based allocation and the criteria for Share 15 may need to be revisited,” the researchers wrote. They recommended raising the cutoff to 21.

The study also confirmed mild hyponatremia (130-134 mmol/L), moderate hyponatremia (125-129 mmol/L), and severe hyponatremia (less than 125 mmol/L) as independent predictors of wait-list mortality during the traditional MELD era. Hazard ratios were 1.4, 1.8, and 1.7, respectively (all P less than .001). The implementation of MELD-Na significantly weakened these associations, with HRs of 1.1 (P = .3), 1.3 (P = .02), and 1.4 (P = .04), respectively).

The probability of transplantation also rose significantly during the MELD-Na era (HR, 1.2; P less than .001), possibly because of the opioid epidemic, the researchers said. Although greater availability of liver grafts might have improved wait-list outcomes, all score categories would have shown a positive impact if this was the only reason, they added. Instead, MELD-Na most benefited patients with lower scores.

Finally, posttransplantation outcomes worsened during the MELD-Na era, perhaps because of transplant population aging. However, the survival benefit of transplant shifted to higher score ranges during the MELD-Na era even after the researchers controlled for this effect. “According to this analysis,” they wrote, “the survival benefit of liver transplant was definitive in patients with score category of 21-23, which could further validate our proposal to revise Share 15 rule to ‘Share 21.’ ”

The investigators reported having no external funding sources or conflicts of interest.

SOURCE: Nagai S et al. Gastroenterology. 2018 Jul 26. doi: 10.1053/j.gastro.2018.07.025.

Proximal adenoma location did not predict high-grade dysplasia in a large registry study.

In fact, the odds of high-grade dysplasia were about 25% lower for proximal versus distal adenomas (odds ratio, 0.75), reported Thomas Rösch, MD, of University Hospital Hamburg-Eppendorf, Hamburg, Germany, and his associates. A third of adenomas in the study lacked location data, but in sensitivity analyses, the odds of high-grade dysplasia fell to 0.72 when these lesions were assumed to be proximal and rose to 0.96 when they were assumed to be distal.

Interval colorectal cancers probably are more likely to be proximal than distal because of a “combination of endoscopy-related factors and biology,” not because of histologic differences alone, the researchers wrote. The report was published in Clinical Gastroenterology and Hepatology.

Interval cancers are more common in the right colon, as several studies have noted. However, it was unclear whether this phenomenon represented a higher miss rate, a lower rate of successful polypectomy, or an increased risk of malignant histology in the proximal colon, the researchers wrote. Accordingly, they analyzed data on 594,614 index adenomas detected during more than 2.5 million screening colonoscopies performed between 2007 and 2012 and entered into the German National Screening Colonoscopy Registry.

A total of 3.5% of index adenomas showed high-grade dysplasia, which correlated most strongly with larger size, said the researchers. In fact, the odds of high-grade dysplasia were 10-fold higher when index adenomas measured at least 1 cm than when they were smaller. High-grade dysplasia also was significantly more frequent when patients were older than 64 years, were male, and when they had pedunculated versus flat lesions. Given the large size of the dataset, all these associations were statistically significant.

Sessile lesions were slightly more likely to be high-grade compared with flat lesions, the investigators noted. Many proximal interval cancers arise from sessile serrated polyps, which may be subtle and difficult to detect or to resect completely, they continued. At the same time, colonoscopy also might be more likely to miss flat, serrated lesions when they are located proximally, and these lesions can become more aggressive over time. Thus, “[e]ndoscopist factors, such as missed lesions or incompletely removed lesions, may account for the predominance of proximal interval colorectal cancers.”

Like other registry studies, this study lacked uniform histopathologic definitions or central histopathology review. The dataset also covered only the largest or most histologically remarkable adenoma for each patient. However, the study findings did not change substantially after the researchers controlled for patients with missing location data, which presumably included patients with multiple polyps in both proximal and distal locations.

The researchers did not disclose external funding sources. They reported having no conflicts of interest.

SOURCE: Rösch T et al. Clin Gastroenterol Hepatol. 2018 Jun 11. doi: 10.1016/j.cgh.2018.05.043.

Proximal adenoma location did not predict high-grade dysplasia in a large registry study.

In fact, the odds of high-grade dysplasia were about 25% lower for proximal versus distal adenomas (odds ratio, 0.75), reported Thomas Rösch, MD, of University Hospital Hamburg-Eppendorf, Hamburg, Germany, and his associates. A third of adenomas in the study lacked location data, but in sensitivity analyses, the odds of high-grade dysplasia fell to 0.72 when these lesions were assumed to be proximal and rose to 0.96 when they were assumed to be distal.

Interval colorectal cancers probably are more likely to be proximal than distal because of a “combination of endoscopy-related factors and biology,” not because of histologic differences alone, the researchers wrote. The report was published in Clinical Gastroenterology and Hepatology.

Interval cancers are more common in the right colon, as several studies have noted. However, it was unclear whether this phenomenon represented a higher miss rate, a lower rate of successful polypectomy, or an increased risk of malignant histology in the proximal colon, the researchers wrote. Accordingly, they analyzed data on 594,614 index adenomas detected during more than 2.5 million screening colonoscopies performed between 2007 and 2012 and entered into the German National Screening Colonoscopy Registry.

A total of 3.5% of index adenomas showed high-grade dysplasia, which correlated most strongly with larger size, said the researchers. In fact, the odds of high-grade dysplasia were 10-fold higher when index adenomas measured at least 1 cm than when they were smaller. High-grade dysplasia also was significantly more frequent when patients were older than 64 years, were male, and when they had pedunculated versus flat lesions. Given the large size of the dataset, all these associations were statistically significant.

Sessile lesions were slightly more likely to be high-grade compared with flat lesions, the investigators noted. Many proximal interval cancers arise from sessile serrated polyps, which may be subtle and difficult to detect or to resect completely, they continued. At the same time, colonoscopy also might be more likely to miss flat, serrated lesions when they are located proximally, and these lesions can become more aggressive over time. Thus, “[e]ndoscopist factors, such as missed lesions or incompletely removed lesions, may account for the predominance of proximal interval colorectal cancers.”

Like other registry studies, this study lacked uniform histopathologic definitions or central histopathology review. The dataset also covered only the largest or most histologically remarkable adenoma for each patient. However, the study findings did not change substantially after the researchers controlled for patients with missing location data, which presumably included patients with multiple polyps in both proximal and distal locations.

The researchers did not disclose external funding sources. They reported having no conflicts of interest.

SOURCE: Rösch T et al. Clin Gastroenterol Hepatol. 2018 Jun 11. doi: 10.1016/j.cgh.2018.05.043.

Proximal adenoma location did not predict high-grade dysplasia in a large registry study.

In fact, the odds of high-grade dysplasia were about 25% lower for proximal versus distal adenomas (odds ratio, 0.75), reported Thomas Rösch, MD, of University Hospital Hamburg-Eppendorf, Hamburg, Germany, and his associates. A third of adenomas in the study lacked location data, but in sensitivity analyses, the odds of high-grade dysplasia fell to 0.72 when these lesions were assumed to be proximal and rose to 0.96 when they were assumed to be distal.

Interval colorectal cancers probably are more likely to be proximal than distal because of a “combination of endoscopy-related factors and biology,” not because of histologic differences alone, the researchers wrote. The report was published in Clinical Gastroenterology and Hepatology.

Interval cancers are more common in the right colon, as several studies have noted. However, it was unclear whether this phenomenon represented a higher miss rate, a lower rate of successful polypectomy, or an increased risk of malignant histology in the proximal colon, the researchers wrote. Accordingly, they analyzed data on 594,614 index adenomas detected during more than 2.5 million screening colonoscopies performed between 2007 and 2012 and entered into the German National Screening Colonoscopy Registry.

A total of 3.5% of index adenomas showed high-grade dysplasia, which correlated most strongly with larger size, said the researchers. In fact, the odds of high-grade dysplasia were 10-fold higher when index adenomas measured at least 1 cm than when they were smaller. High-grade dysplasia also was significantly more frequent when patients were older than 64 years, were male, and when they had pedunculated versus flat lesions. Given the large size of the dataset, all these associations were statistically significant.

Sessile lesions were slightly more likely to be high-grade compared with flat lesions, the investigators noted. Many proximal interval cancers arise from sessile serrated polyps, which may be subtle and difficult to detect or to resect completely, they continued. At the same time, colonoscopy also might be more likely to miss flat, serrated lesions when they are located proximally, and these lesions can become more aggressive over time. Thus, “[e]ndoscopist factors, such as missed lesions or incompletely removed lesions, may account for the predominance of proximal interval colorectal cancers.”

Like other registry studies, this study lacked uniform histopathologic definitions or central histopathology review. The dataset also covered only the largest or most histologically remarkable adenoma for each patient. However, the study findings did not change substantially after the researchers controlled for patients with missing location data, which presumably included patients with multiple polyps in both proximal and distal locations.

The researchers did not disclose external funding sources. They reported having no conflicts of interest.

SOURCE: Rösch T et al. Clin Gastroenterol Hepatol. 2018 Jun 11. doi: 10.1016/j.cgh.2018.05.043.

For patients with treatment-naive anaplastic lymphoma kinase–positive (ALK+) non–small cell lung cancer (NSCLC), twice-daily oral treatment with alectinib (600 mg) was associated with significantly greater activity in the CNS and significantly delayed CNS progression, compared with crizotinib (200 mg), based on secondary analyses from the pivotal phase 3 ALEX trial.

Time to CNS progression was significantly longer with alectinib versus crizotinib (hazard ratio, 0.18; 95% confidence interval, 0.09-0.36) regardless of whether patients had asymptomatic baseline CNS metastases or a prior history of radiotherapy. For patients with baseline asymptomatic CNS metastases, the 12-month cumulative incidence of CNS progression was 16% with alectinib versus 58.3% with crizotinib. Among patients without asymptomatic CNS metastases at baseline, these rates were 4.6% versus 31.5%, respectively.

The findings “consolidate alectinib as the standard of care for untreated, advanced ALK+ NSCLC, irrespective of the presence or absence of baseline CNS metastases,” Shirish M. Gadgeel, MD, of the University of Michigan, Ann Arbor, and his associates wrote in Annals of Oncology.

ALEX was the first study of an ALK inhibitor to include a prospective, standardized intention-to-treat analysis of CNS lesions, regardless of whether patients had these lesions at baseline. All patients underwent brain imaging at baseline and every 8 weeks thereafter. In the primary analysis of 303 patients, alectinib significantly improved progression-free survival in patients with and without baseline CNS disease and showed a significantly higher intracranial overall response rate, irrespective of whether patients had previously received radiotherapy.

Based on these results, National Comprehensive Cancer Network guidelines were updated to include a category 1 recommendation for the first-line use of alectinib in patients with ALK+ NSCLC.

The current analysis focused on CNS efficacy. In all, 122 patients had CNS metastases at baseline. Progression-free survival was similar regardless of whether patients had these lesions (HR, 0.40; 95% CI, 0.25-0.64) or not (HR, 0.51; 95% CI, 0.33-0.80; P = .36). History of radiotherapy also did not significantly affect overall CNS response or progression-free survival.

“Our data are in agreement with a pooled analysis of alectinib phase 2 trials, which demonstrated that central nervous system efficacy of alectinib is maintained regardless of radiotherapy history in crizotinib-pretreated patients,” the investigators wrote.

Because ALEX excluded patients with symptomatic CNS disease, its effects in this population remain unclear, they noted. “ALEX data strongly suggest that in asymptomatic patients, treating CNS metastases with alectinib alone may result in a reduced or delayed need for local CNS treatment.”

F. Hoffman-La Roche funded the study. Dr. Gadgeel reported honoraria and consultancy fees from Roche/Genentech, ARIAD Pharmaceuticals, AstraZeneca, Bristol-Myers Squibb, and Pfizer.

SOURCE: Gadgeel SM et al. Ann Oncol. 2018 Sep 12. doi: 10.1093/annonc/mdy405.

For patients with treatment-naive anaplastic lymphoma kinase–positive (ALK+) non–small cell lung cancer (NSCLC), twice-daily oral treatment with alectinib (600 mg) was associated with significantly greater activity in the CNS and significantly delayed CNS progression, compared with crizotinib (200 mg), based on secondary analyses from the pivotal phase 3 ALEX trial.

Time to CNS progression was significantly longer with alectinib versus crizotinib (hazard ratio, 0.18; 95% confidence interval, 0.09-0.36) regardless of whether patients had asymptomatic baseline CNS metastases or a prior history of radiotherapy. For patients with baseline asymptomatic CNS metastases, the 12-month cumulative incidence of CNS progression was 16% with alectinib versus 58.3% with crizotinib. Among patients without asymptomatic CNS metastases at baseline, these rates were 4.6% versus 31.5%, respectively.

The findings “consolidate alectinib as the standard of care for untreated, advanced ALK+ NSCLC, irrespective of the presence or absence of baseline CNS metastases,” Shirish M. Gadgeel, MD, of the University of Michigan, Ann Arbor, and his associates wrote in Annals of Oncology.

ALEX was the first study of an ALK inhibitor to include a prospective, standardized intention-to-treat analysis of CNS lesions, regardless of whether patients had these lesions at baseline. All patients underwent brain imaging at baseline and every 8 weeks thereafter. In the primary analysis of 303 patients, alectinib significantly improved progression-free survival in patients with and without baseline CNS disease and showed a significantly higher intracranial overall response rate, irrespective of whether patients had previously received radiotherapy.

Based on these results, National Comprehensive Cancer Network guidelines were updated to include a category 1 recommendation for the first-line use of alectinib in patients with ALK+ NSCLC.

The current analysis focused on CNS efficacy. In all, 122 patients had CNS metastases at baseline. Progression-free survival was similar regardless of whether patients had these lesions (HR, 0.40; 95% CI, 0.25-0.64) or not (HR, 0.51; 95% CI, 0.33-0.80; P = .36). History of radiotherapy also did not significantly affect overall CNS response or progression-free survival.

“Our data are in agreement with a pooled analysis of alectinib phase 2 trials, which demonstrated that central nervous system efficacy of alectinib is maintained regardless of radiotherapy history in crizotinib-pretreated patients,” the investigators wrote.

Because ALEX excluded patients with symptomatic CNS disease, its effects in this population remain unclear, they noted. “ALEX data strongly suggest that in asymptomatic patients, treating CNS metastases with alectinib alone may result in a reduced or delayed need for local CNS treatment.”

F. Hoffman-La Roche funded the study. Dr. Gadgeel reported honoraria and consultancy fees from Roche/Genentech, ARIAD Pharmaceuticals, AstraZeneca, Bristol-Myers Squibb, and Pfizer.

SOURCE: Gadgeel SM et al. Ann Oncol. 2018 Sep 12. doi: 10.1093/annonc/mdy405.

For patients with treatment-naive anaplastic lymphoma kinase–positive (ALK+) non–small cell lung cancer (NSCLC), twice-daily oral treatment with alectinib (600 mg) was associated with significantly greater activity in the CNS and significantly delayed CNS progression, compared with crizotinib (200 mg), based on secondary analyses from the pivotal phase 3 ALEX trial.

Time to CNS progression was significantly longer with alectinib versus crizotinib (hazard ratio, 0.18; 95% confidence interval, 0.09-0.36) regardless of whether patients had asymptomatic baseline CNS metastases or a prior history of radiotherapy. For patients with baseline asymptomatic CNS metastases, the 12-month cumulative incidence of CNS progression was 16% with alectinib versus 58.3% with crizotinib. Among patients without asymptomatic CNS metastases at baseline, these rates were 4.6% versus 31.5%, respectively.

The findings “consolidate alectinib as the standard of care for untreated, advanced ALK+ NSCLC, irrespective of the presence or absence of baseline CNS metastases,” Shirish M. Gadgeel, MD, of the University of Michigan, Ann Arbor, and his associates wrote in Annals of Oncology.

ALEX was the first study of an ALK inhibitor to include a prospective, standardized intention-to-treat analysis of CNS lesions, regardless of whether patients had these lesions at baseline. All patients underwent brain imaging at baseline and every 8 weeks thereafter. In the primary analysis of 303 patients, alectinib significantly improved progression-free survival in patients with and without baseline CNS disease and showed a significantly higher intracranial overall response rate, irrespective of whether patients had previously received radiotherapy.

Based on these results, National Comprehensive Cancer Network guidelines were updated to include a category 1 recommendation for the first-line use of alectinib in patients with ALK+ NSCLC.

The current analysis focused on CNS efficacy. In all, 122 patients had CNS metastases at baseline. Progression-free survival was similar regardless of whether patients had these lesions (HR, 0.40; 95% CI, 0.25-0.64) or not (HR, 0.51; 95% CI, 0.33-0.80; P = .36). History of radiotherapy also did not significantly affect overall CNS response or progression-free survival.

“Our data are in agreement with a pooled analysis of alectinib phase 2 trials, which demonstrated that central nervous system efficacy of alectinib is maintained regardless of radiotherapy history in crizotinib-pretreated patients,” the investigators wrote.

Because ALEX excluded patients with symptomatic CNS disease, its effects in this population remain unclear, they noted. “ALEX data strongly suggest that in asymptomatic patients, treating CNS metastases with alectinib alone may result in a reduced or delayed need for local CNS treatment.”

F. Hoffman-La Roche funded the study. Dr. Gadgeel reported honoraria and consultancy fees from Roche/Genentech, ARIAD Pharmaceuticals, AstraZeneca, Bristol-Myers Squibb, and Pfizer.

SOURCE: Gadgeel SM et al. Ann Oncol. 2018 Sep 12. doi: 10.1093/annonc/mdy405.

For patients with Clostridium difficile infections, undetectable peripheral eosinophils at admission were a significant predictor of severe outcomes, even in the absence of hypotension and tachycardia, researchers wrote in JAMA Surgery.

CDC/Jennifer Hulsey

“In animal models, peripheral eosinopenia is a biologically plausible predictive factor for adverse outcomes, and human data from this study indicate that this frequent addition to an admission complete blood cell count is an inexpensive, widely available risk index in the treatment of C. difficile infection,” wrote Audrey S. Kulaylat, MD, of Penn State University, Hershey, and her associates.

In their cohort study of 2,065 patients admitted to two tertiary referral centers with C. difficile infection, undetectable eosinophil counts at hospital admission were associated with significantly increased odds of in-hospital mortality in both a training dataset (odds ratio, 2.01; 95% confidence interval, 1.08-3.73; P = .03) and a validation dataset (OR, 2.26; 95% CI, 1.33-3.83; P = .002). Undetectable eosinophil counts also were associated with elevated odds of severe disease requiring intensive care, vasopressor use, and emergency total colectomy. Besides eosinopenia, significant predictors of mortality included having more comorbidities and lower systolic blood pressure at admission. Strikingly, when patients had no initial hypotension or tachycardia, an undetectable eosinophil count was the only identifiable predictor of in-hospital death (OR, 5.76; 95% CI, 1.99-16.64). An elevated white blood cell count was not a significant predictor of mortality in this subgroup.

Dr. Kulaylat and her associates are studying the microbiome in C. difficile infection. Their work has identified a host immune reaction marked by an “exaggerated inflammasome response” and peripheral eosinopenia, they explained. Two recent murine models have produced similar results.

Admission eosinophil counts “allow for an immediate assessment of mortality risk at admission that is inexpensive and part of a differential for a standard complete blood count available at any hospital,” they concluded. They are now prospectively evaluating a prognostic score for C. difficile infection that includes eosinopenia and other easily discernible admission factors. The National Institutes of Health supported the work. The researchers reported having no conflicts of interest.
 

SOURCE: Kulaylat AS et al. JAMA Surg. 2018 Sep 12. doi: 10.1001/jamasurg.2018.3174.
 

For patients with Clostridium difficile infections, undetectable peripheral eosinophils at admission were a significant predictor of severe outcomes, even in the absence of hypotension and tachycardia, researchers wrote in JAMA Surgery.

CDC/Jennifer Hulsey

“In animal models, peripheral eosinopenia is a biologically plausible predictive factor for adverse outcomes, and human data from this study indicate that this frequent addition to an admission complete blood cell count is an inexpensive, widely available risk index in the treatment of C. difficile infection,” wrote Audrey S. Kulaylat, MD, of Penn State University, Hershey, and her associates.

In their cohort study of 2,065 patients admitted to two tertiary referral centers with C. difficile infection, undetectable eosinophil counts at hospital admission were associated with significantly increased odds of in-hospital mortality in both a training dataset (odds ratio, 2.01; 95% confidence interval, 1.08-3.73; P = .03) and a validation dataset (OR, 2.26; 95% CI, 1.33-3.83; P = .002). Undetectable eosinophil counts also were associated with elevated odds of severe disease requiring intensive care, vasopressor use, and emergency total colectomy. Besides eosinopenia, significant predictors of mortality included having more comorbidities and lower systolic blood pressure at admission. Strikingly, when patients had no initial hypotension or tachycardia, an undetectable eosinophil count was the only identifiable predictor of in-hospital death (OR, 5.76; 95% CI, 1.99-16.64). An elevated white blood cell count was not a significant predictor of mortality in this subgroup.

Dr. Kulaylat and her associates are studying the microbiome in C. difficile infection. Their work has identified a host immune reaction marked by an “exaggerated inflammasome response” and peripheral eosinopenia, they explained. Two recent murine models have produced similar results.

Admission eosinophil counts “allow for an immediate assessment of mortality risk at admission that is inexpensive and part of a differential for a standard complete blood count available at any hospital,” they concluded. They are now prospectively evaluating a prognostic score for C. difficile infection that includes eosinopenia and other easily discernible admission factors. The National Institutes of Health supported the work. The researchers reported having no conflicts of interest.
 

SOURCE: Kulaylat AS et al. JAMA Surg. 2018 Sep 12. doi: 10.1001/jamasurg.2018.3174.
 

For patients with Clostridium difficile infections, undetectable peripheral eosinophils at admission were a significant predictor of severe outcomes, even in the absence of hypotension and tachycardia, researchers wrote in JAMA Surgery.

CDC/Jennifer Hulsey

“In animal models, peripheral eosinopenia is a biologically plausible predictive factor for adverse outcomes, and human data from this study indicate that this frequent addition to an admission complete blood cell count is an inexpensive, widely available risk index in the treatment of C. difficile infection,” wrote Audrey S. Kulaylat, MD, of Penn State University, Hershey, and her associates.

In their cohort study of 2,065 patients admitted to two tertiary referral centers with C. difficile infection, undetectable eosinophil counts at hospital admission were associated with significantly increased odds of in-hospital mortality in both a training dataset (odds ratio, 2.01; 95% confidence interval, 1.08-3.73; P = .03) and a validation dataset (OR, 2.26; 95% CI, 1.33-3.83; P = .002). Undetectable eosinophil counts also were associated with elevated odds of severe disease requiring intensive care, vasopressor use, and emergency total colectomy. Besides eosinopenia, significant predictors of mortality included having more comorbidities and lower systolic blood pressure at admission. Strikingly, when patients had no initial hypotension or tachycardia, an undetectable eosinophil count was the only identifiable predictor of in-hospital death (OR, 5.76; 95% CI, 1.99-16.64). An elevated white blood cell count was not a significant predictor of mortality in this subgroup.

Dr. Kulaylat and her associates are studying the microbiome in C. difficile infection. Their work has identified a host immune reaction marked by an “exaggerated inflammasome response” and peripheral eosinopenia, they explained. Two recent murine models have produced similar results.

Admission eosinophil counts “allow for an immediate assessment of mortality risk at admission that is inexpensive and part of a differential for a standard complete blood count available at any hospital,” they concluded. They are now prospectively evaluating a prognostic score for C. difficile infection that includes eosinopenia and other easily discernible admission factors. The National Institutes of Health supported the work. The researchers reported having no conflicts of interest.
 

SOURCE: Kulaylat AS et al. JAMA Surg. 2018 Sep 12. doi: 10.1001/jamasurg.2018.3174.
 

Dual HER2 blockade did not significantly improve overall survival, compared with standard treatment of metastatic HER2-positive gastric cancer, according to final readouts from the international, double-blind JACOB trial.

After a median of 24.4 months of follow-up, median overall survival times were 17.5 months among patients who received pertuzumab in addition to standard trastuzumab therapy plus chemotherapy versus 14.2 months in the control arm (hazard ratio, 0.84; 95% confidence interval, 0.71-1.00; P = .057). The pertuzumab arm also had a higher incidence of moderate to severe diarrhea and more interruptions and dose modifications of chemotherapy, perhaps because of overlapping toxicities, wrote Josep Tabernero, MD. of Vall d’Hebron University Hospital and Centro de Investigación Biomedica en Red Cancer, Barcelona, and his colleagues. The report is in Lancet Oncology.

Gastric cancer remains the fifth most common cancer globally and the third most common cause of cancer-related death. For patients whose metastatic gastric tumors express high levels of HER2, targeted trastuzumab therapy can significantly improve overall survival when added to standard chemotherapy with capecitabine or fluorouracil plus a platinum-based drug. Pertuzumab binds to a HER2 receptor protein epitope different from trastuzumab, and combination treatment with trastuzumab plus pertuzumab has been found to significantly increase overall survival for patients with HER2-positive breast cancer. Although gastric cancer displays more HER2 heterogeneity than does breast cancer, Dr. Tabernero and his associates hypothesized that dual HER2 blockade might show a similar result.

Accordingly, in the phase 3 JACOB trial, 780 patients with HER2-positive metastatic gastric or gastroesophageal junction cancer were randomly assigned to receive treatment every 3 weeks with intravenous pertuzumab (840 mg) or placebo in addition to intravenous trastuzumab (8 mg/kg loading dose, then 6 mg/kg) plus either oral capecitabine (1,000 mg/m² twice daily), intravenous cisplatin (80 mg/m²), or intravenous 5-fluorouracil (800 mg/m²; 120-hour continuous infusion).

The two groups had similar rates of serious adverse events, most commonly diarrhea. Grade 3 or worse diarrhea affected 13% of pertuzumab patients versus 6% of control patients. There were no treatment-related deaths in the pertuzumab group and seven (2%) in the control group. “The study was not powered to assess efficacy endpoints in clinical and biomarker subgroups and there was no multiplicity control for subgroup analyses, so we cannot assess which patients might be more likely to benefit from pertuzumab treatment,” the investigators wrote. They recommended further evaluating other first-line treatments for advanced HER2-positive gastric cancer, predictors of benefit from dual HER2 blockade, and the best chemotherapy backbone for anti-HER2 regimens.

F. Hoffman-La Roche Ltd. sponsored the work. Dr. Tabernero disclosed advisory board relationships with Genentech/Roche, Roche, Sanofi, Symphogen, and other pharmaceutical companies outside the submitted work. Three coinvestigators also disclosed ties to Roche and several other pharmaceutical companies and one reported owning stock in F. Hoffmann-La Roche. The remaining two investigators reported having no conflicts of interest.

SOURCE: Taberno J, et al. Lancet Oncol. 2018 Sep 11. doi: 10.1016/S1470-2045(18)30481-9.

Dual HER2 blockade did not significantly improve overall survival, compared with standard treatment of metastatic HER2-positive gastric cancer, according to final readouts from the international, double-blind JACOB trial.

After a median of 24.4 months of follow-up, median overall survival times were 17.5 months among patients who received pertuzumab in addition to standard trastuzumab therapy plus chemotherapy versus 14.2 months in the control arm (hazard ratio, 0.84; 95% confidence interval, 0.71-1.00; P = .057). The pertuzumab arm also had a higher incidence of moderate to severe diarrhea and more interruptions and dose modifications of chemotherapy, perhaps because of overlapping toxicities, wrote Josep Tabernero, MD. of Vall d’Hebron University Hospital and Centro de Investigación Biomedica en Red Cancer, Barcelona, and his colleagues. The report is in Lancet Oncology.

Gastric cancer remains the fifth most common cancer globally and the third most common cause of cancer-related death. For patients whose metastatic gastric tumors express high levels of HER2, targeted trastuzumab therapy can significantly improve overall survival when added to standard chemotherapy with capecitabine or fluorouracil plus a platinum-based drug. Pertuzumab binds to a HER2 receptor protein epitope different from trastuzumab, and combination treatment with trastuzumab plus pertuzumab has been found to significantly increase overall survival for patients with HER2-positive breast cancer. Although gastric cancer displays more HER2 heterogeneity than does breast cancer, Dr. Tabernero and his associates hypothesized that dual HER2 blockade might show a similar result.

Accordingly, in the phase 3 JACOB trial, 780 patients with HER2-positive metastatic gastric or gastroesophageal junction cancer were randomly assigned to receive treatment every 3 weeks with intravenous pertuzumab (840 mg) or placebo in addition to intravenous trastuzumab (8 mg/kg loading dose, then 6 mg/kg) plus either oral capecitabine (1,000 mg/m² twice daily), intravenous cisplatin (80 mg/m²), or intravenous 5-fluorouracil (800 mg/m²; 120-hour continuous infusion).

The two groups had similar rates of serious adverse events, most commonly diarrhea. Grade 3 or worse diarrhea affected 13% of pertuzumab patients versus 6% of control patients. There were no treatment-related deaths in the pertuzumab group and seven (2%) in the control group. “The study was not powered to assess efficacy endpoints in clinical and biomarker subgroups and there was no multiplicity control for subgroup analyses, so we cannot assess which patients might be more likely to benefit from pertuzumab treatment,” the investigators wrote. They recommended further evaluating other first-line treatments for advanced HER2-positive gastric cancer, predictors of benefit from dual HER2 blockade, and the best chemotherapy backbone for anti-HER2 regimens.

F. Hoffman-La Roche Ltd. sponsored the work. Dr. Tabernero disclosed advisory board relationships with Genentech/Roche, Roche, Sanofi, Symphogen, and other pharmaceutical companies outside the submitted work. Three coinvestigators also disclosed ties to Roche and several other pharmaceutical companies and one reported owning stock in F. Hoffmann-La Roche. The remaining two investigators reported having no conflicts of interest.

SOURCE: Taberno J, et al. Lancet Oncol. 2018 Sep 11. doi: 10.1016/S1470-2045(18)30481-9.

Dual HER2 blockade did not significantly improve overall survival, compared with standard treatment of metastatic HER2-positive gastric cancer, according to final readouts from the international, double-blind JACOB trial.

After a median of 24.4 months of follow-up, median overall survival times were 17.5 months among patients who received pertuzumab in addition to standard trastuzumab therapy plus chemotherapy versus 14.2 months in the control arm (hazard ratio, 0.84; 95% confidence interval, 0.71-1.00; P = .057). The pertuzumab arm also had a higher incidence of moderate to severe diarrhea and more interruptions and dose modifications of chemotherapy, perhaps because of overlapping toxicities, wrote Josep Tabernero, MD. of Vall d’Hebron University Hospital and Centro de Investigación Biomedica en Red Cancer, Barcelona, and his colleagues. The report is in Lancet Oncology.

Gastric cancer remains the fifth most common cancer globally and the third most common cause of cancer-related death. For patients whose metastatic gastric tumors express high levels of HER2, targeted trastuzumab therapy can significantly improve overall survival when added to standard chemotherapy with capecitabine or fluorouracil plus a platinum-based drug. Pertuzumab binds to a HER2 receptor protein epitope different from trastuzumab, and combination treatment with trastuzumab plus pertuzumab has been found to significantly increase overall survival for patients with HER2-positive breast cancer. Although gastric cancer displays more HER2 heterogeneity than does breast cancer, Dr. Tabernero and his associates hypothesized that dual HER2 blockade might show a similar result.

Accordingly, in the phase 3 JACOB trial, 780 patients with HER2-positive metastatic gastric or gastroesophageal junction cancer were randomly assigned to receive treatment every 3 weeks with intravenous pertuzumab (840 mg) or placebo in addition to intravenous trastuzumab (8 mg/kg loading dose, then 6 mg/kg) plus either oral capecitabine (1,000 mg/m² twice daily), intravenous cisplatin (80 mg/m²), or intravenous 5-fluorouracil (800 mg/m²; 120-hour continuous infusion).

The two groups had similar rates of serious adverse events, most commonly diarrhea. Grade 3 or worse diarrhea affected 13% of pertuzumab patients versus 6% of control patients. There were no treatment-related deaths in the pertuzumab group and seven (2%) in the control group. “The study was not powered to assess efficacy endpoints in clinical and biomarker subgroups and there was no multiplicity control for subgroup analyses, so we cannot assess which patients might be more likely to benefit from pertuzumab treatment,” the investigators wrote. They recommended further evaluating other first-line treatments for advanced HER2-positive gastric cancer, predictors of benefit from dual HER2 blockade, and the best chemotherapy backbone for anti-HER2 regimens.

F. Hoffman-La Roche Ltd. sponsored the work. Dr. Tabernero disclosed advisory board relationships with Genentech/Roche, Roche, Sanofi, Symphogen, and other pharmaceutical companies outside the submitted work. Three coinvestigators also disclosed ties to Roche and several other pharmaceutical companies and one reported owning stock in F. Hoffmann-La Roche. The remaining two investigators reported having no conflicts of interest.

SOURCE: Taberno J, et al. Lancet Oncol. 2018 Sep 11. doi: 10.1016/S1470-2045(18)30481-9.

The American Cancer Society’s recent recommendation to lower the age of first screening for colorectal cancer to 45 years does not reflect clear knowledge of risks versus benefits, experts wrote in a recent commentary.

“In the big picture, [the question of whether to start screening at 45 versus 50 years] seems relatively unimportant compared with using individual patient risk for advanced neoplasia in practical, feasible models” that are geared toward adherence, efficiency, and cost-efficacy, wrote Thomas F. Imperiale, MD, of Indiana University, Indianapolis, and his associates. The commentary is in the October issue of Clinical Gastroenterology and Hepatology.

Tailoring age of first screening on an individual level, based on other risk factors and patient preferences, might improve uptake and benefit-risk ratios, balance, they argued.

Rates of colorectal cancer in persons under age 50 years rose by about 22% between 2000 and 2013. However, estimates for the most recent birth cohorts have wide confidence intervals, “indicating imprecision and uncertainty that this trend will continue,” the experts wrote. Furthermore, the absolute risk of colorectal cancer among individuals younger than 50 years has risen only slightly, from 5.9 cases per 100,000 population to 7.2 cases per 100,000 population. “[This] small increase in incidence may represent a true increase or could be due to increased use of colonoscopy in general, and specifically, for diagnosis or high-risk screening of first-degree relatives of persons with colorectal cancer,” the experts wrote.

Implementing the new recommendation could detect earlier-stage (curable) colorectal cancer “in a youthful and productive age group that may be sandwiched between raising children and caring for aging parents,” they continued. Earlier detection could reduce mortality and reduce the costs of treating a disease that often exceeds $100,000 per person annually.

However, the recommendation was based on a modeling study that assumed 100% adherence. In reality, uptake among 45- to 49-year-olds might be 15%-20%, and “who actually shows up for screening could make or break this recommendation,” the experts said. If younger individuals who underwent screening tended to have few risk factors for colorectal cancer, then the new recommendation would lead to many false positives and unnecessary colonoscopies, with the associated fallout of emotional harm and wasted health care resources, they added.

Population-level studies have identified age as the strongest predictor of colorectal cancer, but age “does not perform as well” at patient level, the experts said. They emphasized the role of other risk factors, such as male sex, having a first-degree relative with colorectal cancer, high body mass index, metabolic syndrome, cigarette smoking, diet, adherence to screening, and use of aspirin, nonsteroidal anti-inflammatory drugs, and hormone therapy. “The goal for providers and health systems is to determine whether and how to change screening practice and policy, and how to incorporate this new recommendation into practice, a necessarily complex process that requires knowing patient risk, patient preferences, and the long-term balance of benefits and burdens,” they concluded (Clin Gastroenterol Hepatol. 2018 Aug 13. doi: 10.1016/j.cgh.2018.08.023).

Dr. Imperiale and coauthor Charles J. Kahi, MD, MS, had no disclosures. Coauthor Douglas K. Rex, MD, disclosed ties to Aries Pharmaceutical, Cosmo Pharmaceuticals, Boston Scientific, Sebela, Medtronic, EndoAid Ltd, Olympus, Paion, Braintree, and Medivators. He also chairs the U.S. Multi-Society Task Force on Colorectal Cancer.

* This story was updated on 10/16/2018.

The American Cancer Society’s recent recommendation to lower the age of first screening for colorectal cancer to 45 years does not reflect clear knowledge of risks versus benefits, experts wrote in a recent commentary.

“In the big picture, [the question of whether to start screening at 45 versus 50 years] seems relatively unimportant compared with using individual patient risk for advanced neoplasia in practical, feasible models” that are geared toward adherence, efficiency, and cost-efficacy, wrote Thomas F. Imperiale, MD, of Indiana University, Indianapolis, and his associates. The commentary is in the October issue of Clinical Gastroenterology and Hepatology.

Tailoring age of first screening on an individual level, based on other risk factors and patient preferences, might improve uptake and benefit-risk ratios, balance, they argued.

Rates of colorectal cancer in persons under age 50 years rose by about 22% between 2000 and 2013. However, estimates for the most recent birth cohorts have wide confidence intervals, “indicating imprecision and uncertainty that this trend will continue,” the experts wrote. Furthermore, the absolute risk of colorectal cancer among individuals younger than 50 years has risen only slightly, from 5.9 cases per 100,000 population to 7.2 cases per 100,000 population. “[This] small increase in incidence may represent a true increase or could be due to increased use of colonoscopy in general, and specifically, for diagnosis or high-risk screening of first-degree relatives of persons with colorectal cancer,” the experts wrote.

Implementing the new recommendation could detect earlier-stage (curable) colorectal cancer “in a youthful and productive age group that may be sandwiched between raising children and caring for aging parents,” they continued. Earlier detection could reduce mortality and reduce the costs of treating a disease that often exceeds $100,000 per person annually.

However, the recommendation was based on a modeling study that assumed 100% adherence. In reality, uptake among 45- to 49-year-olds might be 15%-20%, and “who actually shows up for screening could make or break this recommendation,” the experts said. If younger individuals who underwent screening tended to have few risk factors for colorectal cancer, then the new recommendation would lead to many false positives and unnecessary colonoscopies, with the associated fallout of emotional harm and wasted health care resources, they added.

Population-level studies have identified age as the strongest predictor of colorectal cancer, but age “does not perform as well” at patient level, the experts said. They emphasized the role of other risk factors, such as male sex, having a first-degree relative with colorectal cancer, high body mass index, metabolic syndrome, cigarette smoking, diet, adherence to screening, and use of aspirin, nonsteroidal anti-inflammatory drugs, and hormone therapy. “The goal for providers and health systems is to determine whether and how to change screening practice and policy, and how to incorporate this new recommendation into practice, a necessarily complex process that requires knowing patient risk, patient preferences, and the long-term balance of benefits and burdens,” they concluded (Clin Gastroenterol Hepatol. 2018 Aug 13. doi: 10.1016/j.cgh.2018.08.023).

Dr. Imperiale and coauthor Charles J. Kahi, MD, MS, had no disclosures. Coauthor Douglas K. Rex, MD, disclosed ties to Aries Pharmaceutical, Cosmo Pharmaceuticals, Boston Scientific, Sebela, Medtronic, EndoAid Ltd, Olympus, Paion, Braintree, and Medivators. He also chairs the U.S. Multi-Society Task Force on Colorectal Cancer.

* This story was updated on 10/16/2018.

The American Cancer Society’s recent recommendation to lower the age of first screening for colorectal cancer to 45 years does not reflect clear knowledge of risks versus benefits, experts wrote in a recent commentary.

“In the big picture, [the question of whether to start screening at 45 versus 50 years] seems relatively unimportant compared with using individual patient risk for advanced neoplasia in practical, feasible models” that are geared toward adherence, efficiency, and cost-efficacy, wrote Thomas F. Imperiale, MD, of Indiana University, Indianapolis, and his associates. The commentary is in the October issue of Clinical Gastroenterology and Hepatology.

Tailoring age of first screening on an individual level, based on other risk factors and patient preferences, might improve uptake and benefit-risk ratios, balance, they argued.

Rates of colorectal cancer in persons under age 50 years rose by about 22% between 2000 and 2013. However, estimates for the most recent birth cohorts have wide confidence intervals, “indicating imprecision and uncertainty that this trend will continue,” the experts wrote. Furthermore, the absolute risk of colorectal cancer among individuals younger than 50 years has risen only slightly, from 5.9 cases per 100,000 population to 7.2 cases per 100,000 population. “[This] small increase in incidence may represent a true increase or could be due to increased use of colonoscopy in general, and specifically, for diagnosis or high-risk screening of first-degree relatives of persons with colorectal cancer,” the experts wrote.

Implementing the new recommendation could detect earlier-stage (curable) colorectal cancer “in a youthful and productive age group that may be sandwiched between raising children and caring for aging parents,” they continued. Earlier detection could reduce mortality and reduce the costs of treating a disease that often exceeds $100,000 per person annually.

However, the recommendation was based on a modeling study that assumed 100% adherence. In reality, uptake among 45- to 49-year-olds might be 15%-20%, and “who actually shows up for screening could make or break this recommendation,” the experts said. If younger individuals who underwent screening tended to have few risk factors for colorectal cancer, then the new recommendation would lead to many false positives and unnecessary colonoscopies, with the associated fallout of emotional harm and wasted health care resources, they added.

Population-level studies have identified age as the strongest predictor of colorectal cancer, but age “does not perform as well” at patient level, the experts said. They emphasized the role of other risk factors, such as male sex, having a first-degree relative with colorectal cancer, high body mass index, metabolic syndrome, cigarette smoking, diet, adherence to screening, and use of aspirin, nonsteroidal anti-inflammatory drugs, and hormone therapy. “The goal for providers and health systems is to determine whether and how to change screening practice and policy, and how to incorporate this new recommendation into practice, a necessarily complex process that requires knowing patient risk, patient preferences, and the long-term balance of benefits and burdens,” they concluded (Clin Gastroenterol Hepatol. 2018 Aug 13. doi: 10.1016/j.cgh.2018.08.023).

Dr. Imperiale and coauthor Charles J. Kahi, MD, MS, had no disclosures. Coauthor Douglas K. Rex, MD, disclosed ties to Aries Pharmaceutical, Cosmo Pharmaceuticals, Boston Scientific, Sebela, Medtronic, EndoAid Ltd, Olympus, Paion, Braintree, and Medivators. He also chairs the U.S. Multi-Society Task Force on Colorectal Cancer.

* This story was updated on 10/16/2018.

Diets promoting colonic inflammation were associated with a greater risk of colorectal carcinomas containing Fusobacterium nucleatum bacteria, according to a report in the October issue of Clinical Gastroenterology and Hepatology.

Courtesy American Gastroenterological Association

Proinflammatory diets were not linked to heightened risk for colon cancers without these bacteria, reported Li Liu, MD, PhD, of Dana-Farber Cancer Institute and Harvard Medical School, Boston. “These findings indicate that diet-induced intestinal inflammation alters the gut microbiome to contribute to colorectal carcinogenesis,” they wrote. “Nutritional interventions might be used in precision medicine and cancer prevention.”

Intestinal inflammation, a risk factor for colorectal cancer, is associated with high levels of circulating interleukin 6, C-reactive protein, and tumor necrosis factor–receptor superfamily member 1B. Colonic inflammation impairs the mucosal barrier and alters immune cell responses, which affects the composition of colonic microbiota. Among these, F. nucleatum is known to potentiate colorectal tumors and is associated with proximal tumor location, other tumor features, and cancer progression and chemoresistance.

For the study, the investigators examined self-reported data from more than 124,000 individuals followed for 28 years as part of the Nurses’ Health Study and the Health Professionals Follow-Up Study. They calculated average dietary patterns based on the empiric dietary inflammatory pattern (EDIP) score, which sums weighted intake scores for 18 foods (such as red and processed meat, coffee, tea, and leafy green or dark yellow vegetables) that are known to affect plasma levels of interleukin 6, C-reactive protein, tumor necrosis factor–receptor superfamily member 1B, and tumor necrosis factor alpha–receptor 2. A higher EDIP score denotes a more inflammatory diet.

During the 28-year follow-up period, 951 individuals developed colorectal carcinomas that were tested with a polymerase chain reaction assay for F. nucleatum DNA. A total of 115 tumors tested positive for F. nucleatum. After the researchers controlled for potential confounders, individuals whose EDIP scores were in the highest tertile were significantly more likely to develop F. nucleatum–positive colorectal cancer than were those who scored in the lowest tertile (adjusted hazard ratio, 1.63; 95% confidence interval, 1.03 to 2.58; P = .03). This differential association “appeared to be stronger in proximal colon cancer than in distal colon and rectal cancer,” the researchers said.

More than 90% of individuals in this study were non-Hispanic white, the researchers noted. Tumor tissue was not available from all cases of colorectal cancer and a fairly small number of cases tested positive for tumor F. nucleatum. Nonetheless, the findings suggest that an inflammatory diet could help amplify gut microbiota involved in tumorigenesis, they said. Pending confirmatory studies, they recommended an anti-inflammatory diet with high intake of green leafy vegetables, dark yellow vegetables, coffee, and tea, and with low intake of red meat, processed meat, refined grain, and sugary beverages. They also recommended studying whether F. nucleatum tumor or stool tests could help personalize dietary interventions.

Funders included the National Institutes of Health, Dana Farber Harvard Cancer, Project P. Fund for Colorectal Cancer Research, Friends of the Dana-Farber Cancer Institute, Bennett Family Fund, the Entertainment Industry Foundation, and American Association for Cancer Research, National Natural Science Foundation of China, Chinese Scholarship Council, Huazhong University of Science and Technology, and others. Dr. Liu had no disclosures. One coinvestigator disclosed ties to Genentech/Roche, Lilly, Sanofi, Bayer, and several other biomedical companies.

SOURCE: Liu L et al. Clin Gastroenterol Hepatol. 2018 Apr 24. doi: 10.1016/j.cgh.2018.04.030.

Diets promoting colonic inflammation were associated with a greater risk of colorectal carcinomas containing Fusobacterium nucleatum bacteria, according to a report in the October issue of Clinical Gastroenterology and Hepatology.

Courtesy American Gastroenterological Association

Proinflammatory diets were not linked to heightened risk for colon cancers without these bacteria, reported Li Liu, MD, PhD, of Dana-Farber Cancer Institute and Harvard Medical School, Boston. “These findings indicate that diet-induced intestinal inflammation alters the gut microbiome to contribute to colorectal carcinogenesis,” they wrote. “Nutritional interventions might be used in precision medicine and cancer prevention.”

Intestinal inflammation, a risk factor for colorectal cancer, is associated with high levels of circulating interleukin 6, C-reactive protein, and tumor necrosis factor–receptor superfamily member 1B. Colonic inflammation impairs the mucosal barrier and alters immune cell responses, which affects the composition of colonic microbiota. Among these, F. nucleatum is known to potentiate colorectal tumors and is associated with proximal tumor location, other tumor features, and cancer progression and chemoresistance.

For the study, the investigators examined self-reported data from more than 124,000 individuals followed for 28 years as part of the Nurses’ Health Study and the Health Professionals Follow-Up Study. They calculated average dietary patterns based on the empiric dietary inflammatory pattern (EDIP) score, which sums weighted intake scores for 18 foods (such as red and processed meat, coffee, tea, and leafy green or dark yellow vegetables) that are known to affect plasma levels of interleukin 6, C-reactive protein, tumor necrosis factor–receptor superfamily member 1B, and tumor necrosis factor alpha–receptor 2. A higher EDIP score denotes a more inflammatory diet.

During the 28-year follow-up period, 951 individuals developed colorectal carcinomas that were tested with a polymerase chain reaction assay for F. nucleatum DNA. A total of 115 tumors tested positive for F. nucleatum. After the researchers controlled for potential confounders, individuals whose EDIP scores were in the highest tertile were significantly more likely to develop F. nucleatum–positive colorectal cancer than were those who scored in the lowest tertile (adjusted hazard ratio, 1.63; 95% confidence interval, 1.03 to 2.58; P = .03). This differential association “appeared to be stronger in proximal colon cancer than in distal colon and rectal cancer,” the researchers said.

More than 90% of individuals in this study were non-Hispanic white, the researchers noted. Tumor tissue was not available from all cases of colorectal cancer and a fairly small number of cases tested positive for tumor F. nucleatum. Nonetheless, the findings suggest that an inflammatory diet could help amplify gut microbiota involved in tumorigenesis, they said. Pending confirmatory studies, they recommended an anti-inflammatory diet with high intake of green leafy vegetables, dark yellow vegetables, coffee, and tea, and with low intake of red meat, processed meat, refined grain, and sugary beverages. They also recommended studying whether F. nucleatum tumor or stool tests could help personalize dietary interventions.

Funders included the National Institutes of Health, Dana Farber Harvard Cancer, Project P. Fund for Colorectal Cancer Research, Friends of the Dana-Farber Cancer Institute, Bennett Family Fund, the Entertainment Industry Foundation, and American Association for Cancer Research, National Natural Science Foundation of China, Chinese Scholarship Council, Huazhong University of Science and Technology, and others. Dr. Liu had no disclosures. One coinvestigator disclosed ties to Genentech/Roche, Lilly, Sanofi, Bayer, and several other biomedical companies.

SOURCE: Liu L et al. Clin Gastroenterol Hepatol. 2018 Apr 24. doi: 10.1016/j.cgh.2018.04.030.

Diets promoting colonic inflammation were associated with a greater risk of colorectal carcinomas containing Fusobacterium nucleatum bacteria, according to a report in the October issue of Clinical Gastroenterology and Hepatology.

Courtesy American Gastroenterological Association

Proinflammatory diets were not linked to heightened risk for colon cancers without these bacteria, reported Li Liu, MD, PhD, of Dana-Farber Cancer Institute and Harvard Medical School, Boston. “These findings indicate that diet-induced intestinal inflammation alters the gut microbiome to contribute to colorectal carcinogenesis,” they wrote. “Nutritional interventions might be used in precision medicine and cancer prevention.”

Intestinal inflammation, a risk factor for colorectal cancer, is associated with high levels of circulating interleukin 6, C-reactive protein, and tumor necrosis factor–receptor superfamily member 1B. Colonic inflammation impairs the mucosal barrier and alters immune cell responses, which affects the composition of colonic microbiota. Among these, F. nucleatum is known to potentiate colorectal tumors and is associated with proximal tumor location, other tumor features, and cancer progression and chemoresistance.

For the study, the investigators examined self-reported data from more than 124,000 individuals followed for 28 years as part of the Nurses’ Health Study and the Health Professionals Follow-Up Study. They calculated average dietary patterns based on the empiric dietary inflammatory pattern (EDIP) score, which sums weighted intake scores for 18 foods (such as red and processed meat, coffee, tea, and leafy green or dark yellow vegetables) that are known to affect plasma levels of interleukin 6, C-reactive protein, tumor necrosis factor–receptor superfamily member 1B, and tumor necrosis factor alpha–receptor 2. A higher EDIP score denotes a more inflammatory diet.

During the 28-year follow-up period, 951 individuals developed colorectal carcinomas that were tested with a polymerase chain reaction assay for F. nucleatum DNA. A total of 115 tumors tested positive for F. nucleatum. After the researchers controlled for potential confounders, individuals whose EDIP scores were in the highest tertile were significantly more likely to develop F. nucleatum–positive colorectal cancer than were those who scored in the lowest tertile (adjusted hazard ratio, 1.63; 95% confidence interval, 1.03 to 2.58; P = .03). This differential association “appeared to be stronger in proximal colon cancer than in distal colon and rectal cancer,” the researchers said.

More than 90% of individuals in this study were non-Hispanic white, the researchers noted. Tumor tissue was not available from all cases of colorectal cancer and a fairly small number of cases tested positive for tumor F. nucleatum. Nonetheless, the findings suggest that an inflammatory diet could help amplify gut microbiota involved in tumorigenesis, they said. Pending confirmatory studies, they recommended an anti-inflammatory diet with high intake of green leafy vegetables, dark yellow vegetables, coffee, and tea, and with low intake of red meat, processed meat, refined grain, and sugary beverages. They also recommended studying whether F. nucleatum tumor or stool tests could help personalize dietary interventions.

Funders included the National Institutes of Health, Dana Farber Harvard Cancer, Project P. Fund for Colorectal Cancer Research, Friends of the Dana-Farber Cancer Institute, Bennett Family Fund, the Entertainment Industry Foundation, and American Association for Cancer Research, National Natural Science Foundation of China, Chinese Scholarship Council, Huazhong University of Science and Technology, and others. Dr. Liu had no disclosures. One coinvestigator disclosed ties to Genentech/Roche, Lilly, Sanofi, Bayer, and several other biomedical companies.

SOURCE: Liu L et al. Clin Gastroenterol Hepatol. 2018 Apr 24. doi: 10.1016/j.cgh.2018.04.030.