Pancreas and Biliary Tract

CHICAGO – Preoperative clinical diagnoses of pancreatic cystic neoplasms (PCNs) are frequently found to be in error when patients go to surgery as recommended under international guidelines, data from a retrospective study show.

An analysis of all pancreatic resections performed for presumed PCN at the Verona Pancreas Institute, Italy, from 2011 through 2020 showed a high degree of discrepancy between the preoperative clinical diagnosis and the final postoperative pathology, with some lesions being misdiagnosed in nearly two-thirds of cases, reported Anna Burelli, MD, of the department of general and pancreatic surgery at the University of Verona.

“Diagnostic errors are still common for resected PCNs. Morphological and clinical information alone still poorly frame actual targets for surgery, and hopefully the development of new reliable biomarkers will represent the next evolution in pancreatic cystic neoplasm management,” she said in an oral abstract session at the annual Digestive Disease Week^® (DDW).

Diagnostic errors are significant issues in care of patients with PCN, because clinicians must balance the need for prompt, definitive treatment when necessary with the need for avoiding the significant morbidity of pancreatic resection for patients with lesions that turn out to be nonmalignant.

The investigators define “misdiagnosis” as a discrepancy between the preoperative clinical diagnosis and the postoperative pathology, and “mismatch” as a discrepancy between the preoperative suspicion of malignant or benign disease and the final pathology.
 

Checkered history

In previous cases series from Massachusetts General Hospital in Boston (2010) and the Verona Pancreas Institute (2012) – both experienced, high-volume centers – PCN misdiagnosis rates were 30% and 21%, respectively, and results from the current study show that things haven’t changed much since then, Dr. Burelli said.

PCNs are divided into neoplastic and nonneoplastic categories, with mucin-producing subtypes considered to be precancerous lesions that require accurate diagnosis and close monitoring.

Examples of neoplastic PCNs are intraductal papillary mucinous neoplasms (IPMNs) of the main pancreatic duct or side branch and mucinous cystadenomas. In contrast, serous cystadenomas, considered nonneoplastic, are mostly benign lesions discovered incidentally during abdominal imaging for another indication. It is very difficult, however, to distinguish between the two PCN subtypes clinically.

For example, Dr. Burelli showed images from a patient who received a preoperative diagnosis of mixed IPMN that was in fact found to be chronic pancreatitis on postoperative pathology.

Dr. Burelli noted that AGA and joint European guidelines for management of PCNs have been updated over the past decade, with the latest AGA iteration in 2015.

A 2017 study evaluating the 2015 AGA guidelines for management of asymptomatic PCNs found that following the guidelines in a large multicenter cohort “would have resulted in 60 % fewer patients being referred for surgical resection, and accurately recommended surveillance in 95% of patients with asymptomatic PCNs.”

Misdiagnosis and mismatch common

In the current study, Dr. Burelli and colleagues reviewed all pancreatic resections performed for PCNs at their center from 2011 through 2020.

Of 601 patients included in the retrospective study, 301 underwent endoscopic ultrasound (EUS).

The investigators identified misdiagnosis in 19% of cases and mismatch in 34%, and there was no significant improvement in diagnostic accuracy among the 50% of patients who underwent EUS.

The most frequently misdiagnosed lesions were cystic neuroendocrine tumors, in 61% of cases. The least misdiagnosed lesions were pseudopapillary tumors, in 6% of cases.

Many of the diagnostic errors were clinically important. For example, seven cases presumed to be serous cystic neoplasms (an almost always benign lesion) were found on final pathology to have a different, malignant histology.

Mismatch examples included 50 IPMNs with high-risk stigmata that were presumed to be malignant before surgery but were nonmalignant on final pathology, and 38 IPMNs without high-risk stigmata which were thought on clinical examination to be benign but turned out to be malignant on final pathology.

“Our results are in line with the current literature,” Dr. Burelli said, citing a recent meta-analysis showing that among 3,292 patients who underwent resection for mucinous cystic neoplasms (MCNs), the pooled rate of malignancy was 16.1%, yet the 2012 International Association of Pancreatology guidelines recommend surgery for all fit patients with MCNs, and joint European evidence-based guidelines from 2018 recommend surgery for MCNs 40 mm or larger, those with mural nodules, and for patients who are symptomatic.

The 16.1% pooled malignancy rate suggests “that there is space for surveillance in most cases of MCNs,” she said.

In addition, morphologic and clinical evaluation for IPMN with high-risk stigmata have been shown to have low specificity and low sensitivity, “so should guideline recommendations be revised?” Dr. Burelli said.

She pointed to a recent multi-institutional study in Gastroenterology showing that real-time next-generation sequencing of pancreatic cyst fluid “is sensitive and specific for various pancreatic cyst types and advanced neoplasia arising from mucinous cysts, but also reveals the diversity of genomic alterations seen in pancreatic cysts and their clinical significance.”

“This is not the future; this is the present,” she concluded.

Invited discussant R. Matthew Walsh, MD, a surgeon specializing in pancreatic and cancer surgery at the Cleveland Clinic, complimented the contributions of her group.

“The patient that you showed with chronic pancreatitis could have very well benefited from the operation regardless of the diagnosis if they were symptomatic,” he said, addressing Dr. Burelli. “So what is the group that is the regrettable surgical patients, and where are you aiming your studies? Is it really the 24% with high-risk features in IPMN that have low-grade dysplasia, or is it the 58% who we’re not sure why they were operated on because they didn’t have high-grade features who had low-grade dysplasia?”

She replied that “the goal here is to avoid surgery for benign entities, and we know that the only true benign entities are serous cystic neoplasms, and all the others have a malignant potential, but we think at Verona Pancreas Institute there is no reason to operate on low-grade dysplasia free patients. This is what we really would like to avoid.”

Dr. Walsh also asked, given their finding that EUS did not appear to offer a benefit to patients or change decision making, which patients should still get EUS.

“I think that only patients in which the diagnosis is uncertain or in which there are some worrisome features or high-risk stigmata should undergo EUS before surgery, and also to continue follow-up,” Dr. Burelli said. “I don’t think that the conclusion is that EUS is not useful, but it’s not useful in all.”

For example, large, microcystic lesions can be readily identified radiographically, but other, more complex cases may still require EUS to help nail down or refine a diagnosis, she said.

The study was internally funded. Dr. Burelli and Dr. Walsh reported having no conflicts of interest.

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

CHICAGO – Preoperative clinical diagnoses of pancreatic cystic neoplasms (PCNs) are frequently found to be in error when patients go to surgery as recommended under international guidelines, data from a retrospective study show.

An analysis of all pancreatic resections performed for presumed PCN at the Verona Pancreas Institute, Italy, from 2011 through 2020 showed a high degree of discrepancy between the preoperative clinical diagnosis and the final postoperative pathology, with some lesions being misdiagnosed in nearly two-thirds of cases, reported Anna Burelli, MD, of the department of general and pancreatic surgery at the University of Verona.

“Diagnostic errors are still common for resected PCNs. Morphological and clinical information alone still poorly frame actual targets for surgery, and hopefully the development of new reliable biomarkers will represent the next evolution in pancreatic cystic neoplasm management,” she said in an oral abstract session at the annual Digestive Disease Week^® (DDW).

Diagnostic errors are significant issues in care of patients with PCN, because clinicians must balance the need for prompt, definitive treatment when necessary with the need for avoiding the significant morbidity of pancreatic resection for patients with lesions that turn out to be nonmalignant.

The investigators define “misdiagnosis” as a discrepancy between the preoperative clinical diagnosis and the postoperative pathology, and “mismatch” as a discrepancy between the preoperative suspicion of malignant or benign disease and the final pathology.
 

Checkered history

In previous cases series from Massachusetts General Hospital in Boston (2010) and the Verona Pancreas Institute (2012) – both experienced, high-volume centers – PCN misdiagnosis rates were 30% and 21%, respectively, and results from the current study show that things haven’t changed much since then, Dr. Burelli said.

PCNs are divided into neoplastic and nonneoplastic categories, with mucin-producing subtypes considered to be precancerous lesions that require accurate diagnosis and close monitoring.

Examples of neoplastic PCNs are intraductal papillary mucinous neoplasms (IPMNs) of the main pancreatic duct or side branch and mucinous cystadenomas. In contrast, serous cystadenomas, considered nonneoplastic, are mostly benign lesions discovered incidentally during abdominal imaging for another indication. It is very difficult, however, to distinguish between the two PCN subtypes clinically.

For example, Dr. Burelli showed images from a patient who received a preoperative diagnosis of mixed IPMN that was in fact found to be chronic pancreatitis on postoperative pathology.

Dr. Burelli noted that AGA and joint European guidelines for management of PCNs have been updated over the past decade, with the latest AGA iteration in 2015.

A 2017 study evaluating the 2015 AGA guidelines for management of asymptomatic PCNs found that following the guidelines in a large multicenter cohort “would have resulted in 60 % fewer patients being referred for surgical resection, and accurately recommended surveillance in 95% of patients with asymptomatic PCNs.”

Misdiagnosis and mismatch common

In the current study, Dr. Burelli and colleagues reviewed all pancreatic resections performed for PCNs at their center from 2011 through 2020.

Of 601 patients included in the retrospective study, 301 underwent endoscopic ultrasound (EUS).

The investigators identified misdiagnosis in 19% of cases and mismatch in 34%, and there was no significant improvement in diagnostic accuracy among the 50% of patients who underwent EUS.

The most frequently misdiagnosed lesions were cystic neuroendocrine tumors, in 61% of cases. The least misdiagnosed lesions were pseudopapillary tumors, in 6% of cases.

Many of the diagnostic errors were clinically important. For example, seven cases presumed to be serous cystic neoplasms (an almost always benign lesion) were found on final pathology to have a different, malignant histology.

Mismatch examples included 50 IPMNs with high-risk stigmata that were presumed to be malignant before surgery but were nonmalignant on final pathology, and 38 IPMNs without high-risk stigmata which were thought on clinical examination to be benign but turned out to be malignant on final pathology.

“Our results are in line with the current literature,” Dr. Burelli said, citing a recent meta-analysis showing that among 3,292 patients who underwent resection for mucinous cystic neoplasms (MCNs), the pooled rate of malignancy was 16.1%, yet the 2012 International Association of Pancreatology guidelines recommend surgery for all fit patients with MCNs, and joint European evidence-based guidelines from 2018 recommend surgery for MCNs 40 mm or larger, those with mural nodules, and for patients who are symptomatic.

The 16.1% pooled malignancy rate suggests “that there is space for surveillance in most cases of MCNs,” she said.

In addition, morphologic and clinical evaluation for IPMN with high-risk stigmata have been shown to have low specificity and low sensitivity, “so should guideline recommendations be revised?” Dr. Burelli said.

She pointed to a recent multi-institutional study in Gastroenterology showing that real-time next-generation sequencing of pancreatic cyst fluid “is sensitive and specific for various pancreatic cyst types and advanced neoplasia arising from mucinous cysts, but also reveals the diversity of genomic alterations seen in pancreatic cysts and their clinical significance.”

“This is not the future; this is the present,” she concluded.

Invited discussant R. Matthew Walsh, MD, a surgeon specializing in pancreatic and cancer surgery at the Cleveland Clinic, complimented the contributions of her group.

“The patient that you showed with chronic pancreatitis could have very well benefited from the operation regardless of the diagnosis if they were symptomatic,” he said, addressing Dr. Burelli. “So what is the group that is the regrettable surgical patients, and where are you aiming your studies? Is it really the 24% with high-risk features in IPMN that have low-grade dysplasia, or is it the 58% who we’re not sure why they were operated on because they didn’t have high-grade features who had low-grade dysplasia?”

She replied that “the goal here is to avoid surgery for benign entities, and we know that the only true benign entities are serous cystic neoplasms, and all the others have a malignant potential, but we think at Verona Pancreas Institute there is no reason to operate on low-grade dysplasia free patients. This is what we really would like to avoid.”

Dr. Walsh also asked, given their finding that EUS did not appear to offer a benefit to patients or change decision making, which patients should still get EUS.

“I think that only patients in which the diagnosis is uncertain or in which there are some worrisome features or high-risk stigmata should undergo EUS before surgery, and also to continue follow-up,” Dr. Burelli said. “I don’t think that the conclusion is that EUS is not useful, but it’s not useful in all.”

For example, large, microcystic lesions can be readily identified radiographically, but other, more complex cases may still require EUS to help nail down or refine a diagnosis, she said.

The study was internally funded. Dr. Burelli and Dr. Walsh reported having no conflicts of interest.

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

CHICAGO – Preoperative clinical diagnoses of pancreatic cystic neoplasms (PCNs) are frequently found to be in error when patients go to surgery as recommended under international guidelines, data from a retrospective study show.

An analysis of all pancreatic resections performed for presumed PCN at the Verona Pancreas Institute, Italy, from 2011 through 2020 showed a high degree of discrepancy between the preoperative clinical diagnosis and the final postoperative pathology, with some lesions being misdiagnosed in nearly two-thirds of cases, reported Anna Burelli, MD, of the department of general and pancreatic surgery at the University of Verona.

“Diagnostic errors are still common for resected PCNs. Morphological and clinical information alone still poorly frame actual targets for surgery, and hopefully the development of new reliable biomarkers will represent the next evolution in pancreatic cystic neoplasm management,” she said in an oral abstract session at the annual Digestive Disease Week^® (DDW).

Diagnostic errors are significant issues in care of patients with PCN, because clinicians must balance the need for prompt, definitive treatment when necessary with the need for avoiding the significant morbidity of pancreatic resection for patients with lesions that turn out to be nonmalignant.

The investigators define “misdiagnosis” as a discrepancy between the preoperative clinical diagnosis and the postoperative pathology, and “mismatch” as a discrepancy between the preoperative suspicion of malignant or benign disease and the final pathology.
 

Checkered history

In previous cases series from Massachusetts General Hospital in Boston (2010) and the Verona Pancreas Institute (2012) – both experienced, high-volume centers – PCN misdiagnosis rates were 30% and 21%, respectively, and results from the current study show that things haven’t changed much since then, Dr. Burelli said.

PCNs are divided into neoplastic and nonneoplastic categories, with mucin-producing subtypes considered to be precancerous lesions that require accurate diagnosis and close monitoring.

Examples of neoplastic PCNs are intraductal papillary mucinous neoplasms (IPMNs) of the main pancreatic duct or side branch and mucinous cystadenomas. In contrast, serous cystadenomas, considered nonneoplastic, are mostly benign lesions discovered incidentally during abdominal imaging for another indication. It is very difficult, however, to distinguish between the two PCN subtypes clinically.

For example, Dr. Burelli showed images from a patient who received a preoperative diagnosis of mixed IPMN that was in fact found to be chronic pancreatitis on postoperative pathology.

Dr. Burelli noted that AGA and joint European guidelines for management of PCNs have been updated over the past decade, with the latest AGA iteration in 2015.

A 2017 study evaluating the 2015 AGA guidelines for management of asymptomatic PCNs found that following the guidelines in a large multicenter cohort “would have resulted in 60 % fewer patients being referred for surgical resection, and accurately recommended surveillance in 95% of patients with asymptomatic PCNs.”

Misdiagnosis and mismatch common

In the current study, Dr. Burelli and colleagues reviewed all pancreatic resections performed for PCNs at their center from 2011 through 2020.

Of 601 patients included in the retrospective study, 301 underwent endoscopic ultrasound (EUS).

The investigators identified misdiagnosis in 19% of cases and mismatch in 34%, and there was no significant improvement in diagnostic accuracy among the 50% of patients who underwent EUS.

The most frequently misdiagnosed lesions were cystic neuroendocrine tumors, in 61% of cases. The least misdiagnosed lesions were pseudopapillary tumors, in 6% of cases.

Many of the diagnostic errors were clinically important. For example, seven cases presumed to be serous cystic neoplasms (an almost always benign lesion) were found on final pathology to have a different, malignant histology.

Mismatch examples included 50 IPMNs with high-risk stigmata that were presumed to be malignant before surgery but were nonmalignant on final pathology, and 38 IPMNs without high-risk stigmata which were thought on clinical examination to be benign but turned out to be malignant on final pathology.

“Our results are in line with the current literature,” Dr. Burelli said, citing a recent meta-analysis showing that among 3,292 patients who underwent resection for mucinous cystic neoplasms (MCNs), the pooled rate of malignancy was 16.1%, yet the 2012 International Association of Pancreatology guidelines recommend surgery for all fit patients with MCNs, and joint European evidence-based guidelines from 2018 recommend surgery for MCNs 40 mm or larger, those with mural nodules, and for patients who are symptomatic.

The 16.1% pooled malignancy rate suggests “that there is space for surveillance in most cases of MCNs,” she said.

In addition, morphologic and clinical evaluation for IPMN with high-risk stigmata have been shown to have low specificity and low sensitivity, “so should guideline recommendations be revised?” Dr. Burelli said.

She pointed to a recent multi-institutional study in Gastroenterology showing that real-time next-generation sequencing of pancreatic cyst fluid “is sensitive and specific for various pancreatic cyst types and advanced neoplasia arising from mucinous cysts, but also reveals the diversity of genomic alterations seen in pancreatic cysts and their clinical significance.”

“This is not the future; this is the present,” she concluded.

Invited discussant R. Matthew Walsh, MD, a surgeon specializing in pancreatic and cancer surgery at the Cleveland Clinic, complimented the contributions of her group.

“The patient that you showed with chronic pancreatitis could have very well benefited from the operation regardless of the diagnosis if they were symptomatic,” he said, addressing Dr. Burelli. “So what is the group that is the regrettable surgical patients, and where are you aiming your studies? Is it really the 24% with high-risk features in IPMN that have low-grade dysplasia, or is it the 58% who we’re not sure why they were operated on because they didn’t have high-grade features who had low-grade dysplasia?”

She replied that “the goal here is to avoid surgery for benign entities, and we know that the only true benign entities are serous cystic neoplasms, and all the others have a malignant potential, but we think at Verona Pancreas Institute there is no reason to operate on low-grade dysplasia free patients. This is what we really would like to avoid.”

Dr. Walsh also asked, given their finding that EUS did not appear to offer a benefit to patients or change decision making, which patients should still get EUS.

“I think that only patients in which the diagnosis is uncertain or in which there are some worrisome features or high-risk stigmata should undergo EUS before surgery, and also to continue follow-up,” Dr. Burelli said. “I don’t think that the conclusion is that EUS is not useful, but it’s not useful in all.”

For example, large, microcystic lesions can be readily identified radiographically, but other, more complex cases may still require EUS to help nail down or refine a diagnosis, she said.

The study was internally funded. Dr. Burelli and Dr. Walsh reported having no conflicts of interest.

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

Individuals who are carriers of germline pathogenic variants in susceptibility genes for pancreatic ductal adenocarcinoma (PDAC), or have a strong family history of PDAC, benefit from having annual MRIs, shows a new study published in Gastroenterology.

While other studies have shown potential benefit in screening high-risk individuals, “a concern is that in absence of sufficiently large control groups with unscreened controls,” the outcomes may be influenced by lead-time bias. The current study is the first to address that important limitation.

The study, which was led by Derk C.F. Klatte, MD, of the department of gastroenterology and hepatology at Leiden University Medical Center, the Netherlands, included 43,762 patients from the Netherlands Cancer Registry who were diagnosed with PDAC between January 2000 and December 2020. Using a 1:5 ratio, researchers matched 31 patients who were diagnosed in the pancreatic cancer surveillance cohort against 155 patients in the non-surveillance group.

Leiden University Medical Center

“We show that surveillance for PDAC in high-risk individuals results in significant earlier detection, increased resectability, and improved survival as compared with average-risk individuals diagnosed with PDAC not under surveillance. This reaffirms that pancreatic surveillance for certain in high-risk individuals is beneficial and could have a meaningful impact on disease course,” the authors wrote.

PDAC has the worst outcomes all cancers and is on pace to become the second-leading cause of cancer-related mortality. By the time a tumor is detected, it is usually unresectable or has developed distant metastases. In principle, early detection could improve outcomes, but there is no test that is adequate for population-wide screening. Surveillance must therefore concentrate on individuals deemed to be at heightened risk. Prospective studies have shown a benefit of pancreatic cancer screening in patients who are at high-risk. Such studies may be misleading, however, due to the potential for lead-time bias. This can occur when a condition is detected at an earlier time than it would have been identified based on clinical signs, as usually occurs in nonscreened populations, and this asymptomatic lag time between diagnosis and initial symptoms does not get incorporated into a survival analysis. The result can be an artificially longer survival time following diagnosis in the screened population.

Guidelines from the International Cancer of the Pancreas Screening (CAPS) consortium, the American Society for Gastrointestinal Endoscopy, and American Society of Clinical Oncology recommend surveillance in high-risk cases.

In this study, researchers conducted a propensity score matched cohort analysis of patients from the general population with primary PDAC who were diagnosed outside of a screening program, with carriers of a germline CDKN2A/p16 mutation who were diagnosed after surveillance.

The surveillance group received a stage 1 diagnosis in 38.7% of cases, versus 5.8% of those outside of surveillance (odds ratio [OR], 0.09; 95% confidence interval [CI], 0.04-0.19). Surgical resection occurred in 71.0% of surveillance patients, versus 18.7% of non-surveillance patients (OR, 10.62; 95% CI, 4.56-26.63), and stage 4 diagnoses were much more common in the nonsurveillance population (61.3% versus 9.7%). Among the patients who did not undergo surveillance, 61.3% were diagnosed with stage 4 disease compared with 9.7% of those in the surveillance group.

The 5-year survival rate (unadjusted for lead-time) in the surveillance group was 32.4% and 4.3% in the nonsurveillance group. The median overall survival was 26.8 months in the surveillance group compared with 5.2 months in the nonsurveillance group, (hazard ratio, 0.22; 95% CI, 0.14-0.36). The mortality rate per 100 person-years was 114.5 (95% CI, 96.2–135.3) in nonsurveillance patients and 21.9 (95% CI, 13.4–33.8) in surveillance patients.

Despite the apparent benefit of screening, there is room for improvement. “Although the outcomes presented here are encouraging and endorse our earlier findings, a significant proportion of surveillance patients (61%) still had poor outcomes because of diagnosis in a late stage (T2–4N0M0 and nodal or distant metastatic PDAC), with a 5-year survival of 16%,” the authors wrote.

The study received no funding and the authors declared no conflicts.

Individuals who are carriers of germline pathogenic variants in susceptibility genes for pancreatic ductal adenocarcinoma (PDAC), or have a strong family history of PDAC, benefit from having annual MRIs, shows a new study published in Gastroenterology.

While other studies have shown potential benefit in screening high-risk individuals, “a concern is that in absence of sufficiently large control groups with unscreened controls,” the outcomes may be influenced by lead-time bias. The current study is the first to address that important limitation.

The study, which was led by Derk C.F. Klatte, MD, of the department of gastroenterology and hepatology at Leiden University Medical Center, the Netherlands, included 43,762 patients from the Netherlands Cancer Registry who were diagnosed with PDAC between January 2000 and December 2020. Using a 1:5 ratio, researchers matched 31 patients who were diagnosed in the pancreatic cancer surveillance cohort against 155 patients in the non-surveillance group.

Leiden University Medical Center

“We show that surveillance for PDAC in high-risk individuals results in significant earlier detection, increased resectability, and improved survival as compared with average-risk individuals diagnosed with PDAC not under surveillance. This reaffirms that pancreatic surveillance for certain in high-risk individuals is beneficial and could have a meaningful impact on disease course,” the authors wrote.

PDAC has the worst outcomes all cancers and is on pace to become the second-leading cause of cancer-related mortality. By the time a tumor is detected, it is usually unresectable or has developed distant metastases. In principle, early detection could improve outcomes, but there is no test that is adequate for population-wide screening. Surveillance must therefore concentrate on individuals deemed to be at heightened risk. Prospective studies have shown a benefit of pancreatic cancer screening in patients who are at high-risk. Such studies may be misleading, however, due to the potential for lead-time bias. This can occur when a condition is detected at an earlier time than it would have been identified based on clinical signs, as usually occurs in nonscreened populations, and this asymptomatic lag time between diagnosis and initial symptoms does not get incorporated into a survival analysis. The result can be an artificially longer survival time following diagnosis in the screened population.

Guidelines from the International Cancer of the Pancreas Screening (CAPS) consortium, the American Society for Gastrointestinal Endoscopy, and American Society of Clinical Oncology recommend surveillance in high-risk cases.

In this study, researchers conducted a propensity score matched cohort analysis of patients from the general population with primary PDAC who were diagnosed outside of a screening program, with carriers of a germline CDKN2A/p16 mutation who were diagnosed after surveillance.

The surveillance group received a stage 1 diagnosis in 38.7% of cases, versus 5.8% of those outside of surveillance (odds ratio [OR], 0.09; 95% confidence interval [CI], 0.04-0.19). Surgical resection occurred in 71.0% of surveillance patients, versus 18.7% of non-surveillance patients (OR, 10.62; 95% CI, 4.56-26.63), and stage 4 diagnoses were much more common in the nonsurveillance population (61.3% versus 9.7%). Among the patients who did not undergo surveillance, 61.3% were diagnosed with stage 4 disease compared with 9.7% of those in the surveillance group.

The 5-year survival rate (unadjusted for lead-time) in the surveillance group was 32.4% and 4.3% in the nonsurveillance group. The median overall survival was 26.8 months in the surveillance group compared with 5.2 months in the nonsurveillance group, (hazard ratio, 0.22; 95% CI, 0.14-0.36). The mortality rate per 100 person-years was 114.5 (95% CI, 96.2–135.3) in nonsurveillance patients and 21.9 (95% CI, 13.4–33.8) in surveillance patients.

Despite the apparent benefit of screening, there is room for improvement. “Although the outcomes presented here are encouraging and endorse our earlier findings, a significant proportion of surveillance patients (61%) still had poor outcomes because of diagnosis in a late stage (T2–4N0M0 and nodal or distant metastatic PDAC), with a 5-year survival of 16%,” the authors wrote.

The study received no funding and the authors declared no conflicts.

Individuals who are carriers of germline pathogenic variants in susceptibility genes for pancreatic ductal adenocarcinoma (PDAC), or have a strong family history of PDAC, benefit from having annual MRIs, shows a new study published in Gastroenterology.

While other studies have shown potential benefit in screening high-risk individuals, “a concern is that in absence of sufficiently large control groups with unscreened controls,” the outcomes may be influenced by lead-time bias. The current study is the first to address that important limitation.

The study, which was led by Derk C.F. Klatte, MD, of the department of gastroenterology and hepatology at Leiden University Medical Center, the Netherlands, included 43,762 patients from the Netherlands Cancer Registry who were diagnosed with PDAC between January 2000 and December 2020. Using a 1:5 ratio, researchers matched 31 patients who were diagnosed in the pancreatic cancer surveillance cohort against 155 patients in the non-surveillance group.

Leiden University Medical Center

“We show that surveillance for PDAC in high-risk individuals results in significant earlier detection, increased resectability, and improved survival as compared with average-risk individuals diagnosed with PDAC not under surveillance. This reaffirms that pancreatic surveillance for certain in high-risk individuals is beneficial and could have a meaningful impact on disease course,” the authors wrote.

PDAC has the worst outcomes all cancers and is on pace to become the second-leading cause of cancer-related mortality. By the time a tumor is detected, it is usually unresectable or has developed distant metastases. In principle, early detection could improve outcomes, but there is no test that is adequate for population-wide screening. Surveillance must therefore concentrate on individuals deemed to be at heightened risk. Prospective studies have shown a benefit of pancreatic cancer screening in patients who are at high-risk. Such studies may be misleading, however, due to the potential for lead-time bias. This can occur when a condition is detected at an earlier time than it would have been identified based on clinical signs, as usually occurs in nonscreened populations, and this asymptomatic lag time between diagnosis and initial symptoms does not get incorporated into a survival analysis. The result can be an artificially longer survival time following diagnosis in the screened population.

Guidelines from the International Cancer of the Pancreas Screening (CAPS) consortium, the American Society for Gastrointestinal Endoscopy, and American Society of Clinical Oncology recommend surveillance in high-risk cases.

In this study, researchers conducted a propensity score matched cohort analysis of patients from the general population with primary PDAC who were diagnosed outside of a screening program, with carriers of a germline CDKN2A/p16 mutation who were diagnosed after surveillance.

The surveillance group received a stage 1 diagnosis in 38.7% of cases, versus 5.8% of those outside of surveillance (odds ratio [OR], 0.09; 95% confidence interval [CI], 0.04-0.19). Surgical resection occurred in 71.0% of surveillance patients, versus 18.7% of non-surveillance patients (OR, 10.62; 95% CI, 4.56-26.63), and stage 4 diagnoses were much more common in the nonsurveillance population (61.3% versus 9.7%). Among the patients who did not undergo surveillance, 61.3% were diagnosed with stage 4 disease compared with 9.7% of those in the surveillance group.

The 5-year survival rate (unadjusted for lead-time) in the surveillance group was 32.4% and 4.3% in the nonsurveillance group. The median overall survival was 26.8 months in the surveillance group compared with 5.2 months in the nonsurveillance group, (hazard ratio, 0.22; 95% CI, 0.14-0.36). The mortality rate per 100 person-years was 114.5 (95% CI, 96.2–135.3) in nonsurveillance patients and 21.9 (95% CI, 13.4–33.8) in surveillance patients.

Despite the apparent benefit of screening, there is room for improvement. “Although the outcomes presented here are encouraging and endorse our earlier findings, a significant proportion of surveillance patients (61%) still had poor outcomes because of diagnosis in a late stage (T2–4N0M0 and nodal or distant metastatic PDAC), with a 5-year survival of 16%,” the authors wrote.

The study received no funding and the authors declared no conflicts.

Based on discussions during PancreasFest 2021, a group of experts and key opinion leaders have proposed a new definition of exocrine pancreatic insufficiency (EPI) and best practices for diagnosis and management, according to a recent report in Gastro Hep Advances

Due to its complex and individualized nature, EPI requires multidisciplinary approaches to therapy, as well as better pancreas function tests and biomarkers for diagnosis and treatment, wrote researchers who were led by David C. Whitcomb, MD, PhD, AGAF, emeritus professor of medicine in the division of gastroenterology, hepatology and nutrition at the University of Pittsburgh.

University of Pittsburgh

“This condition remains challenging even to define, and serious limitations in diagnostic testing and therapeutic options lead to clinical confusion and frequently less than optimal patient management,” the authors wrote.

EPI is clinically defined as inadequate delivery of pancreatic digestive enzymes to meet nutritional needs, which is typically based on a physician’s assessment of a patient’s maldigestion. However, there’s not a universally accepted definition or a precise threshold of reduced pancreatic digestive enzymes that indicates “pancreatic insufficiency” in an individual patient.

Current guidelines also don’t clearly outline the role of pancreatic function tests, the effects of different metabolic needs and nutrition intake, the timing of pancreatic enzyme replacement therapy (PERT), or the best practices for monitoring or titrating multiple therapies.

In response, Dr. Whitcomb and colleagues proposed a new mechanistic definition of EPI, including the disorder’s physiologic effects and impact on health. First, they said, EPI is a disorder caused by failure of the pancreas to deliver a minimum or threshold level of specific pancreatic digestive enzymes to the intestine in concert with ingested nutrients, followed by enzymatic digestion of individual meals over time to meet certain nutritional and metabolic needs. In addition, the disorder is characterized by variable deficiencies in micronutrients and macronutrients, especially essential fats and fat-soluble vitamins, as well as gastrointestinal symptoms of nutrient maldigestion.

The threshold for EPI should consider the nutritional needs of the patient, dietary intake, residual exocrine pancreas function, and the absorptive capacity of the intestine based on anatomy, mucosal function, motility, inflammation, the microbiome, and physiological adaptation, the authors wrote.

Due to challenges in diagnosing EPI and its common chronic symptoms such as abdominal pain, bloating, and diarrhea, several conditions may mimic EPI, be present concomitantly with EPI, or hinder PERT response. These include celiac disease, small intestinal bacterial overgrowth, disaccharidase deficiencies, inflammatory bowel disease (IBD), bile acid diarrhea, giardiasis, diabetes mellitus, and functional conditions such as irritable bowel syndrome. These conditions should be considered to address underlying pathology and PERT diagnostic challenges.

Although there is consensus that exocrine pancreatic function testing (PFT) is important to diagnosis EPI, no optimal test exists, and pancreatic function is only one aspect of digestion and absorption that should be considered. PFT may be needed to make an objective EPI diagnosis related to acute pancreatitis, pancreatic cancer, pancreatic resection, gastric resection, cystic fibrosis, or IBD. Direct or indirect PFTs may be used, which typically differs by center.

“The medical community still awaits a clinically useful pancreas function test that is easy to perform, well tolerated by patients, and allows personalized dosing of PERT,” the authors wrote.

After diagnosis, a general assessment should include information about symptoms, nutritional status, medications, diet, and lifestyle. This information can be used for a multifaceted treatment approach, with a focus on lifestyle changes, concomitant disease treatment, optimized diet, dietary supplements, and PERT administration.

PERT remains a mainstay of EPI treatment and has shown improvements in steatorrhea, postprandial bloating and pain, nutrition, and unexplained weight loss. The Food and Drug Administration has approved several formulations in different strengths. The typical starting dose is based on age and weight, which is derived from guidelines for EPI treatment in patients with cystic fibrosis. However, the recommendations don’t consider many of the variables discussed above and simply provide an estimate for the average subject with severe EPI, so the dose should be titrated as needed based on age, weight, symptoms, and the holistic management plan.

For optimal results, regular follow-up is necessary to monitor compliance and treatment response. A reduction in symptoms can serve as a reliable indicator of effective EPI management, particularly weight stabilization, improved steatorrhea and diarrhea, and reduced postprandial bloating, pain, and flatulence. Physicians may provide patients with tracking tools to record their PERT compliance, symptom frequency, and lifestyle changes.

For patients with persistent concerns, PERT can be increased as needed. Although many PERT formulations are enteric coated, a proton pump inhibitor or H2 receptor agonist may improve their effectiveness. If EPI symptoms persist despite increased doses, other causes of malabsorption should be considered, such as the concomitant conditions mentioned above.

“As EPI escalates, a lower fat diet may become necessary to alleviate distressing gastrointestinal symptoms,” the authors wrote. “A close working relationship between the treating provider and the [registered dietician] is crucial so that barriers to optimum nutrient assimilation can be identified, communicated, and overcome. Frequent monitoring of the nutritional state with therapy is also imperative.”

PancreasFest 2021 received no specific funding for this event. The authors declared grant support, adviser roles, and speaking honoraria from several pharmaceutical and medical device companies and health care foundations, including the National Pancreas Foundation.

Based on discussions during PancreasFest 2021, a group of experts and key opinion leaders have proposed a new definition of exocrine pancreatic insufficiency (EPI) and best practices for diagnosis and management, according to a recent report in Gastro Hep Advances

Due to its complex and individualized nature, EPI requires multidisciplinary approaches to therapy, as well as better pancreas function tests and biomarkers for diagnosis and treatment, wrote researchers who were led by David C. Whitcomb, MD, PhD, AGAF, emeritus professor of medicine in the division of gastroenterology, hepatology and nutrition at the University of Pittsburgh.

University of Pittsburgh

“This condition remains challenging even to define, and serious limitations in diagnostic testing and therapeutic options lead to clinical confusion and frequently less than optimal patient management,” the authors wrote.

EPI is clinically defined as inadequate delivery of pancreatic digestive enzymes to meet nutritional needs, which is typically based on a physician’s assessment of a patient’s maldigestion. However, there’s not a universally accepted definition or a precise threshold of reduced pancreatic digestive enzymes that indicates “pancreatic insufficiency” in an individual patient.

Current guidelines also don’t clearly outline the role of pancreatic function tests, the effects of different metabolic needs and nutrition intake, the timing of pancreatic enzyme replacement therapy (PERT), or the best practices for monitoring or titrating multiple therapies.

In response, Dr. Whitcomb and colleagues proposed a new mechanistic definition of EPI, including the disorder’s physiologic effects and impact on health. First, they said, EPI is a disorder caused by failure of the pancreas to deliver a minimum or threshold level of specific pancreatic digestive enzymes to the intestine in concert with ingested nutrients, followed by enzymatic digestion of individual meals over time to meet certain nutritional and metabolic needs. In addition, the disorder is characterized by variable deficiencies in micronutrients and macronutrients, especially essential fats and fat-soluble vitamins, as well as gastrointestinal symptoms of nutrient maldigestion.

The threshold for EPI should consider the nutritional needs of the patient, dietary intake, residual exocrine pancreas function, and the absorptive capacity of the intestine based on anatomy, mucosal function, motility, inflammation, the microbiome, and physiological adaptation, the authors wrote.

Due to challenges in diagnosing EPI and its common chronic symptoms such as abdominal pain, bloating, and diarrhea, several conditions may mimic EPI, be present concomitantly with EPI, or hinder PERT response. These include celiac disease, small intestinal bacterial overgrowth, disaccharidase deficiencies, inflammatory bowel disease (IBD), bile acid diarrhea, giardiasis, diabetes mellitus, and functional conditions such as irritable bowel syndrome. These conditions should be considered to address underlying pathology and PERT diagnostic challenges.

Although there is consensus that exocrine pancreatic function testing (PFT) is important to diagnosis EPI, no optimal test exists, and pancreatic function is only one aspect of digestion and absorption that should be considered. PFT may be needed to make an objective EPI diagnosis related to acute pancreatitis, pancreatic cancer, pancreatic resection, gastric resection, cystic fibrosis, or IBD. Direct or indirect PFTs may be used, which typically differs by center.

“The medical community still awaits a clinically useful pancreas function test that is easy to perform, well tolerated by patients, and allows personalized dosing of PERT,” the authors wrote.

After diagnosis, a general assessment should include information about symptoms, nutritional status, medications, diet, and lifestyle. This information can be used for a multifaceted treatment approach, with a focus on lifestyle changes, concomitant disease treatment, optimized diet, dietary supplements, and PERT administration.

PERT remains a mainstay of EPI treatment and has shown improvements in steatorrhea, postprandial bloating and pain, nutrition, and unexplained weight loss. The Food and Drug Administration has approved several formulations in different strengths. The typical starting dose is based on age and weight, which is derived from guidelines for EPI treatment in patients with cystic fibrosis. However, the recommendations don’t consider many of the variables discussed above and simply provide an estimate for the average subject with severe EPI, so the dose should be titrated as needed based on age, weight, symptoms, and the holistic management plan.

For optimal results, regular follow-up is necessary to monitor compliance and treatment response. A reduction in symptoms can serve as a reliable indicator of effective EPI management, particularly weight stabilization, improved steatorrhea and diarrhea, and reduced postprandial bloating, pain, and flatulence. Physicians may provide patients with tracking tools to record their PERT compliance, symptom frequency, and lifestyle changes.

For patients with persistent concerns, PERT can be increased as needed. Although many PERT formulations are enteric coated, a proton pump inhibitor or H2 receptor agonist may improve their effectiveness. If EPI symptoms persist despite increased doses, other causes of malabsorption should be considered, such as the concomitant conditions mentioned above.

“As EPI escalates, a lower fat diet may become necessary to alleviate distressing gastrointestinal symptoms,” the authors wrote. “A close working relationship between the treating provider and the [registered dietician] is crucial so that barriers to optimum nutrient assimilation can be identified, communicated, and overcome. Frequent monitoring of the nutritional state with therapy is also imperative.”

PancreasFest 2021 received no specific funding for this event. The authors declared grant support, adviser roles, and speaking honoraria from several pharmaceutical and medical device companies and health care foundations, including the National Pancreas Foundation.

Based on discussions during PancreasFest 2021, a group of experts and key opinion leaders have proposed a new definition of exocrine pancreatic insufficiency (EPI) and best practices for diagnosis and management, according to a recent report in Gastro Hep Advances

Due to its complex and individualized nature, EPI requires multidisciplinary approaches to therapy, as well as better pancreas function tests and biomarkers for diagnosis and treatment, wrote researchers who were led by David C. Whitcomb, MD, PhD, AGAF, emeritus professor of medicine in the division of gastroenterology, hepatology and nutrition at the University of Pittsburgh.

University of Pittsburgh

“This condition remains challenging even to define, and serious limitations in diagnostic testing and therapeutic options lead to clinical confusion and frequently less than optimal patient management,” the authors wrote.

EPI is clinically defined as inadequate delivery of pancreatic digestive enzymes to meet nutritional needs, which is typically based on a physician’s assessment of a patient’s maldigestion. However, there’s not a universally accepted definition or a precise threshold of reduced pancreatic digestive enzymes that indicates “pancreatic insufficiency” in an individual patient.

Current guidelines also don’t clearly outline the role of pancreatic function tests, the effects of different metabolic needs and nutrition intake, the timing of pancreatic enzyme replacement therapy (PERT), or the best practices for monitoring or titrating multiple therapies.

In response, Dr. Whitcomb and colleagues proposed a new mechanistic definition of EPI, including the disorder’s physiologic effects and impact on health. First, they said, EPI is a disorder caused by failure of the pancreas to deliver a minimum or threshold level of specific pancreatic digestive enzymes to the intestine in concert with ingested nutrients, followed by enzymatic digestion of individual meals over time to meet certain nutritional and metabolic needs. In addition, the disorder is characterized by variable deficiencies in micronutrients and macronutrients, especially essential fats and fat-soluble vitamins, as well as gastrointestinal symptoms of nutrient maldigestion.

The threshold for EPI should consider the nutritional needs of the patient, dietary intake, residual exocrine pancreas function, and the absorptive capacity of the intestine based on anatomy, mucosal function, motility, inflammation, the microbiome, and physiological adaptation, the authors wrote.

Due to challenges in diagnosing EPI and its common chronic symptoms such as abdominal pain, bloating, and diarrhea, several conditions may mimic EPI, be present concomitantly with EPI, or hinder PERT response. These include celiac disease, small intestinal bacterial overgrowth, disaccharidase deficiencies, inflammatory bowel disease (IBD), bile acid diarrhea, giardiasis, diabetes mellitus, and functional conditions such as irritable bowel syndrome. These conditions should be considered to address underlying pathology and PERT diagnostic challenges.

Although there is consensus that exocrine pancreatic function testing (PFT) is important to diagnosis EPI, no optimal test exists, and pancreatic function is only one aspect of digestion and absorption that should be considered. PFT may be needed to make an objective EPI diagnosis related to acute pancreatitis, pancreatic cancer, pancreatic resection, gastric resection, cystic fibrosis, or IBD. Direct or indirect PFTs may be used, which typically differs by center.

“The medical community still awaits a clinically useful pancreas function test that is easy to perform, well tolerated by patients, and allows personalized dosing of PERT,” the authors wrote.

After diagnosis, a general assessment should include information about symptoms, nutritional status, medications, diet, and lifestyle. This information can be used for a multifaceted treatment approach, with a focus on lifestyle changes, concomitant disease treatment, optimized diet, dietary supplements, and PERT administration.

PERT remains a mainstay of EPI treatment and has shown improvements in steatorrhea, postprandial bloating and pain, nutrition, and unexplained weight loss. The Food and Drug Administration has approved several formulations in different strengths. The typical starting dose is based on age and weight, which is derived from guidelines for EPI treatment in patients with cystic fibrosis. However, the recommendations don’t consider many of the variables discussed above and simply provide an estimate for the average subject with severe EPI, so the dose should be titrated as needed based on age, weight, symptoms, and the holistic management plan.

For optimal results, regular follow-up is necessary to monitor compliance and treatment response. A reduction in symptoms can serve as a reliable indicator of effective EPI management, particularly weight stabilization, improved steatorrhea and diarrhea, and reduced postprandial bloating, pain, and flatulence. Physicians may provide patients with tracking tools to record their PERT compliance, symptom frequency, and lifestyle changes.

For patients with persistent concerns, PERT can be increased as needed. Although many PERT formulations are enteric coated, a proton pump inhibitor or H2 receptor agonist may improve their effectiveness. If EPI symptoms persist despite increased doses, other causes of malabsorption should be considered, such as the concomitant conditions mentioned above.

“As EPI escalates, a lower fat diet may become necessary to alleviate distressing gastrointestinal symptoms,” the authors wrote. “A close working relationship between the treating provider and the [registered dietician] is crucial so that barriers to optimum nutrient assimilation can be identified, communicated, and overcome. Frequent monitoring of the nutritional state with therapy is also imperative.”

PancreasFest 2021 received no specific funding for this event. The authors declared grant support, adviser roles, and speaking honoraria from several pharmaceutical and medical device companies and health care foundations, including the National Pancreas Foundation.

Dear colleagues,

Pancreas cysts have become almost ubiquitous in this era of high-resolution cross-sectional imaging. They are a common GI consult with patients and providers worried about the potential risk of malignant transformation. Despite significant research over the past few decades, predicting the natural history of these cysts, especially the side-branch intraductal papillary mucinous neoplasms (IPMNs), remains difficult. There have been a variety of expert recommendations and guidelines, but heterogeneity exists in management especially regarding timing of endoscopic ultrasound, imaging surveillance, and cessation of surveillance. Some centers will present these cysts at multidisciplinary conferences, while others will follow general or local algorithms. In this issue of Perspectives, Dr. Lauren G. Khanna, assistant professor of medicine at NYU Langone Health, New York, and Dr. Santhi Vege, professor of medicine at the Mayo Clinic, Rochester, Minn., present updated and differing approaches to managing these cysts. Which side of the debate are you on? We welcome your thoughts, questions and input– share with us on Twitter @AGA_GIHN

Continuing pancreas cyst surveillance indefinitely is reasonable

BY LAUREN G. KHANNA, MD, MS

Pancreas cysts remain a clinical challenge. The true incidence of pancreas cysts is unknown, but from MRI and autopsy series, may be up to 50%. Patients presenting with a pancreas cyst often have significant anxiety about their risk of pancreas cancer. We as a medical community initially did too; but over the past few decades as we have gathered more data, we have become more comfortable observing many pancreas cysts. Yet our recommendations for how, how often, and for how long to evaluate pancreas cysts are still very much under debate; there are multiple guidelines with discordant recommendations. In this article, I will discuss my approach to patients with a pancreas cyst.

NYU Langone Health

At the first evaluation, I review available imaging to see if there are characteristic features to determine the type of pancreas cyst: IPMN (including main duct, branch duct, or mixed type), serous cystic neoplasm (SCA), mucinous cystic neoplasm (MCN), solid pseudopapillary neoplasm (SPN), cystic neuroendocrine tumor (NET), or pseudocyst. I also review symptoms, including abdominal pain, weight loss, history of pancreatitis, and onset of diabetes, and check hemoglobin A1c and Ca19-9. I often recommend magnetic resonance cholangiopancreatography (MRCP) if it has not already been obtained and is feasible (that is, if a patient does not have severe claustrophobia or a medical device incompatible with MRI). If a patient is not a candidate for treatment should a pancreatic malignancy be identified, because of age, comorbidities, or preference, I recommend no further evaluation.

Where cyst type remains unclear despite MRCP, and for cysts over 2 cm, I recommend endoscopic ultrasound (EUS) for fluid sampling to assist in determining cyst type and to rule out any other high-risk features. In accordance with international guidelines, if a patient has any concerning imaging features, including main pancreatic duct dilation >5 mm, solid component or mural nodule, or thickened or enhancing duct walls, regardless of cyst size, I recommend EUS to assess for and biopsy any solid component and to sample cyst fluid to examine for dysplasia. Given the lower sensitivity of CT for high-risk features, if MRCP is not feasible, for cysts 1-2 cm, I recommend EUS for better evaluation.

If a cyst is determined to be a cystic NET; main duct or mixed-type IPMN; MCN; or SPN; or a branch duct IPMN with mural nodule, high-grade dysplasia, or adenocarcinoma, and the patient is a surgical candidate, I refer the patient for surgical evaluation. If a cyst is determined to be an SCA, the malignant potential is minimal, and patients do not require follow-up. Patients with a pseudocyst are managed according to their clinical scenario.

Many patients have a proven or suspected branch duct IPMN, an indeterminate cyst, or multiple cysts. Cyst management during surveillance is then determined by the size of the largest cyst and stability of the cyst(s). Of note, patients with an IPMN also have been shown to have an elevated risk of concurrent pancreas adenocarcinoma, which I believe is one of the strongest arguments for heightened surveillance of the entire pancreas in pancreas cyst patients. EUS in particular can identify small or subtle lesions that are not detected by cross-sectional imaging.

If a patient has no prior imaging, in accordance with international and European guidelines, I recommend the first surveillance MRCP at a 6-month interval for cysts <2 cm, which may offer the opportunity to identify rapidly progressing cysts. If a patient has previous imaging available demonstrating stability, I recommend surveillance on an annual basis for cysts <2 cm. For patients with a cyst >2 cm, as above, I recommend EUS, and if there are no concerning features on imaging or EUS, I then recommend annual surveillance.

While the patient is under surveillance, if there is more than minimal cyst growth, a change in cyst appearance, or development of any imaging high-risk feature, pancreatitis, new onset or worsening diabetes, or elevation of Ca19-9, I recommend EUS for further evaluation and consideration of surgery based on EUS findings. If an asymptomatic cyst <2 cm remains stable for 5 years, I offer patients the option to extend imaging to every 2 years, if they are comfortable. In my experience, though, many patients prefer to continue annual imaging. The American Gastroenterological Association guidelines promote stopping surveillance after 5 years of stability, however there are studies demonstrating development of malignancy in cysts that were initially stable over the first 5 years of surveillance. Therefore, I discuss with patients that it is reasonable to continue cyst surveillance indefinitely, until they would no longer be interested in pursuing treatment of any kind if a malignant lesion were to be identified.

There are two special groups of pancreas cyst patients who warrant specific attention. Patients who are at elevated risk of pancreas adenocarcinoma because of an associated genetic mutation or a family history of pancreatic cancer already may be undergoing annual pancreas cancer screening with either MRCP, EUS, or alternating MRCP and EUS. When these high-risk patients also have pancreas cysts, I utilize whichever strategy would image their pancreas most frequently and do not extend beyond 1-year intervals. Another special group is patients who have undergone partial pancreatectomy for IPMN. As discussed above, given the elevated risk of concurrent pancreas adenocarcinoma in IPMN patients, I recommend indefinite continued surveillance of the remaining pancreas parenchyma in these patients.

Given the prevalence of pancreas cysts, it certainly would be convenient if guidelines were straightforward enough for primary care physicians to manage pancreas cyst surveillance, as they do for breast cancer screening. However, the complexities of pancreas cysts necessitate the expertise of gastroenterologists and pancreas surgeons, and a multidisciplinary team approach is best where possible.

Dr. Khanna is chief, advanced endoscopy, Tisch Hospital; director, NYU Advanced Endoscopy Fellowship; assistant professor of medicine, NYU Langone Health. Email: Lauren.Khanna@nyulangone.org. There are no relevant conflicts to disclose.
 

References

Tanaka M et al. Pancreatology. 2017 Sep-Oct;17(5):738-75.

Sahora K et al. Eur J Surg Oncol. 2016 Feb;42(2):197-204.

Del Chiaro M et al. Gut. 2018 May;67(5):789-804

Vege SS et al. Gastroenterology. 2015 Apr;148(4):819-22

Petrone MC et al. Clin Transl Gastroenterol. 2018 Jun 13;9(6):158

Pancreas cysts: More is not necessarily better!

BY SANTHI SWAROOP VEGE, MD

Pancreas cysts (PC) are very common, incidental findings on cross-sectional imaging, performed for non–pancreas-related symptoms. The important issues in management of patients with PC in my practice are the prevalence, natural history, frequency of occurrence of high-grade dysplasia (HGD) and/or pancreatic cancer (PDAC), concerning clinical symptoms and imaging findings, indications for EUS and fine-needle aspiration cytology, ideal method and frequency of surveillance, indications for surgery (up front and during follow-up), follow-up after surgery, stopping surveillance, costs, and unintentional harms of management. Good population-based evidence regarding many of the issues described above does not exist, and all information is from selected clinic, radiology, EUS, and surgical cohorts (very important when trying to assess the publications). Cohort studies should start with all PC undergoing surveillance and assess various outcomes, rather than looking backward from EUS or surgical cohorts.

The 2015 American Gastroenterological Association guidelines on asymptomatic neoplastic pancreas cysts, which I coauthored, recommend, consistent with principles of High Value Care (minimal unintentional harms and cost effectiveness), that two of three high-risk features (mural nodule, cyst size greater than 3 cm, and dilated pancreatic duct) be present for EUS-guided fine-needle aspiration (EUS-FNA). By the same token, they advise surgery for those with two of three high-risk features and or concerning features on EUS and cytology. Finally, they suggest stopping surveillance at 5 years if there are no significant changes. Rigorous GRADE methodology along with systematic review of all relevant questions (rather than cohorts of 500 or fewer patients) formed the basis of the guidelines. Those meta-analyses showed that risk of PDAC in mural nodules, cyst size >3 cm, and dilated pancreatic duct, while elevated, still is very low in absolute terms. Less than 20% of resections for highly selected, high-risk cysts showed PDAC. The guidelines were met with a lot of resistance from several societies and physician groups. The recommendations for stopping surveillance after 5 years and no surveillance for absent or low-grade dysplasia after surgery are hotly contested, and these areas need larger, long-term studies.

The whole area of cyst fluid molecular markers that would suggest mucinous type (KRAS and GNAS mutations) and, more importantly, the presence or imminent development of PDAC (next-generation sequencing or NGS) is an exciting field. One sincerely hopes that there will be a breakthrough in this area to achieve the holy grail. Cost effectiveness studies demonstrate the futility of existing guidelines and favor a less intensive approach. Guidelines are only a general framework, and management of individual patients in the clinic is entirely at the discretion of the treating physician. One should make every attempt to detect advanced lesions in PC, but such effort should not subject a large majority of patients to unintentional harms by overtreatment and add further to the burgeoning health care costs in the country.

Mayo Clinic

PC are extremely common (10% of all abdominal imaging), increase with age, are seen in as many as 40%-50% of MRI examinations for nonpancreatic indications, and most (>50%) are IPMNs. Most of the debate centers around the concerns of PDAC and/or HGD associated with mucinous cysts (MCN, IPMN, side-branch, main duct, or mixed).

The various guidelines by multiple societies differ in some aspects, such as in selection of patients based on clinical, laboratory, and imaging findings for up-front surgery or surveillance, the frequency of surveillance based on the size of the cyst and the presence of other concerning cyst features (usually with MRCP), the indications for EUS (both initial and subsequent), importance of the magnitude of growth (most IPMNs slowly grow over a period of time), indications for surgery during surveillance and postsurgery surveillance, and the decision to stop surveillance at some point in time. The literature is replete with small case series reporting a proportion of cancers detected and often ignoring the harms of surgery. Incidence of and mortality caused by PDAC are very low (about 1% for both) in a large national cohort of VA pancreatic cyst patients with long-term follow-up and other studies.

Marcov modeling suggests that none of the guidelines would lead to cost-effective care with low mortality because of overtreatment of low-risk lesions, and a specificity of 67% or more for PDAC/HGB is required. AGA guidelines came close to it but with low sensitivity. Monte Carlo modeling suggests that less intensive strategies, compared with more intensive, result in a similar number of deaths at a much lower cost. While molecular markers in PC fluid are reported to increase the specificity of PDAC/HGD to greater than 70%, it should be observed that such validation was done in a small percentage of patients who had both those markers and resection.

The costs of expensive procedures like EUS, MRI, and surgery, the 3% complication rate with EUS-FNA (primarily acute pancreatitis), and the 1% mortality and approximately 20%-30% morbidity with surgery (bleeding, infection, fistula) and postpancreatectomy diabetes of approximately 30% in the long run need special attention.

In conclusion, one could say pancreas cysts are extremely frequent, most of the neoplastic cysts are mucinous (IPMN and MCN) and slowly growing over time without an associated cancer, and the greatest need at this time is to identify the small proportion of such cysts with PDAC and/or HGD. Until such time, judicious selection of patients for surveillance and reasonable intervals of such surveillance with selective use of EUS will help identify patients requiring resection. In our enthusiasm to detect every possible pancreatic cancer, we should not ignore the unintentional outcomes of surgery to a large majority of patients who would never develop PDAC and the astronomical costs associated with such practice.

Dr. Vege is professor of medicine at the Mayo Clinic. He reported having no conflicts of interest regarding this article.
 

References

Vege SS et al. Gastroenterology. 2015;148:819-22.

Lobo JM et al. Surgery. 2020;168:601-9.

Lennon AM and Vege SS. Clin Gastroenterol Hepatol. 2022;20:1663-7.

Harris RP. Ann Intern Med. 2015;162:787-9.

Dear colleagues,

Pancreas cysts have become almost ubiquitous in this era of high-resolution cross-sectional imaging. They are a common GI consult with patients and providers worried about the potential risk of malignant transformation. Despite significant research over the past few decades, predicting the natural history of these cysts, especially the side-branch intraductal papillary mucinous neoplasms (IPMNs), remains difficult. There have been a variety of expert recommendations and guidelines, but heterogeneity exists in management especially regarding timing of endoscopic ultrasound, imaging surveillance, and cessation of surveillance. Some centers will present these cysts at multidisciplinary conferences, while others will follow general or local algorithms. In this issue of Perspectives, Dr. Lauren G. Khanna, assistant professor of medicine at NYU Langone Health, New York, and Dr. Santhi Vege, professor of medicine at the Mayo Clinic, Rochester, Minn., present updated and differing approaches to managing these cysts. Which side of the debate are you on? We welcome your thoughts, questions and input– share with us on Twitter @AGA_GIHN

Continuing pancreas cyst surveillance indefinitely is reasonable

BY LAUREN G. KHANNA, MD, MS

Pancreas cysts remain a clinical challenge. The true incidence of pancreas cysts is unknown, but from MRI and autopsy series, may be up to 50%. Patients presenting with a pancreas cyst often have significant anxiety about their risk of pancreas cancer. We as a medical community initially did too; but over the past few decades as we have gathered more data, we have become more comfortable observing many pancreas cysts. Yet our recommendations for how, how often, and for how long to evaluate pancreas cysts are still very much under debate; there are multiple guidelines with discordant recommendations. In this article, I will discuss my approach to patients with a pancreas cyst.

NYU Langone Health

At the first evaluation, I review available imaging to see if there are characteristic features to determine the type of pancreas cyst: IPMN (including main duct, branch duct, or mixed type), serous cystic neoplasm (SCA), mucinous cystic neoplasm (MCN), solid pseudopapillary neoplasm (SPN), cystic neuroendocrine tumor (NET), or pseudocyst. I also review symptoms, including abdominal pain, weight loss, history of pancreatitis, and onset of diabetes, and check hemoglobin A1c and Ca19-9. I often recommend magnetic resonance cholangiopancreatography (MRCP) if it has not already been obtained and is feasible (that is, if a patient does not have severe claustrophobia or a medical device incompatible with MRI). If a patient is not a candidate for treatment should a pancreatic malignancy be identified, because of age, comorbidities, or preference, I recommend no further evaluation.

Where cyst type remains unclear despite MRCP, and for cysts over 2 cm, I recommend endoscopic ultrasound (EUS) for fluid sampling to assist in determining cyst type and to rule out any other high-risk features. In accordance with international guidelines, if a patient has any concerning imaging features, including main pancreatic duct dilation >5 mm, solid component or mural nodule, or thickened or enhancing duct walls, regardless of cyst size, I recommend EUS to assess for and biopsy any solid component and to sample cyst fluid to examine for dysplasia. Given the lower sensitivity of CT for high-risk features, if MRCP is not feasible, for cysts 1-2 cm, I recommend EUS for better evaluation.

If a cyst is determined to be a cystic NET; main duct or mixed-type IPMN; MCN; or SPN; or a branch duct IPMN with mural nodule, high-grade dysplasia, or adenocarcinoma, and the patient is a surgical candidate, I refer the patient for surgical evaluation. If a cyst is determined to be an SCA, the malignant potential is minimal, and patients do not require follow-up. Patients with a pseudocyst are managed according to their clinical scenario.

Many patients have a proven or suspected branch duct IPMN, an indeterminate cyst, or multiple cysts. Cyst management during surveillance is then determined by the size of the largest cyst and stability of the cyst(s). Of note, patients with an IPMN also have been shown to have an elevated risk of concurrent pancreas adenocarcinoma, which I believe is one of the strongest arguments for heightened surveillance of the entire pancreas in pancreas cyst patients. EUS in particular can identify small or subtle lesions that are not detected by cross-sectional imaging.

If a patient has no prior imaging, in accordance with international and European guidelines, I recommend the first surveillance MRCP at a 6-month interval for cysts <2 cm, which may offer the opportunity to identify rapidly progressing cysts. If a patient has previous imaging available demonstrating stability, I recommend surveillance on an annual basis for cysts <2 cm. For patients with a cyst >2 cm, as above, I recommend EUS, and if there are no concerning features on imaging or EUS, I then recommend annual surveillance.

While the patient is under surveillance, if there is more than minimal cyst growth, a change in cyst appearance, or development of any imaging high-risk feature, pancreatitis, new onset or worsening diabetes, or elevation of Ca19-9, I recommend EUS for further evaluation and consideration of surgery based on EUS findings. If an asymptomatic cyst <2 cm remains stable for 5 years, I offer patients the option to extend imaging to every 2 years, if they are comfortable. In my experience, though, many patients prefer to continue annual imaging. The American Gastroenterological Association guidelines promote stopping surveillance after 5 years of stability, however there are studies demonstrating development of malignancy in cysts that were initially stable over the first 5 years of surveillance. Therefore, I discuss with patients that it is reasonable to continue cyst surveillance indefinitely, until they would no longer be interested in pursuing treatment of any kind if a malignant lesion were to be identified.

There are two special groups of pancreas cyst patients who warrant specific attention. Patients who are at elevated risk of pancreas adenocarcinoma because of an associated genetic mutation or a family history of pancreatic cancer already may be undergoing annual pancreas cancer screening with either MRCP, EUS, or alternating MRCP and EUS. When these high-risk patients also have pancreas cysts, I utilize whichever strategy would image their pancreas most frequently and do not extend beyond 1-year intervals. Another special group is patients who have undergone partial pancreatectomy for IPMN. As discussed above, given the elevated risk of concurrent pancreas adenocarcinoma in IPMN patients, I recommend indefinite continued surveillance of the remaining pancreas parenchyma in these patients.

Given the prevalence of pancreas cysts, it certainly would be convenient if guidelines were straightforward enough for primary care physicians to manage pancreas cyst surveillance, as they do for breast cancer screening. However, the complexities of pancreas cysts necessitate the expertise of gastroenterologists and pancreas surgeons, and a multidisciplinary team approach is best where possible.

Dr. Khanna is chief, advanced endoscopy, Tisch Hospital; director, NYU Advanced Endoscopy Fellowship; assistant professor of medicine, NYU Langone Health. Email: Lauren.Khanna@nyulangone.org. There are no relevant conflicts to disclose.
 

References

Tanaka M et al. Pancreatology. 2017 Sep-Oct;17(5):738-75.

Sahora K et al. Eur J Surg Oncol. 2016 Feb;42(2):197-204.

Del Chiaro M et al. Gut. 2018 May;67(5):789-804

Vege SS et al. Gastroenterology. 2015 Apr;148(4):819-22

Petrone MC et al. Clin Transl Gastroenterol. 2018 Jun 13;9(6):158

Pancreas cysts: More is not necessarily better!

BY SANTHI SWAROOP VEGE, MD

Pancreas cysts (PC) are very common, incidental findings on cross-sectional imaging, performed for non–pancreas-related symptoms. The important issues in management of patients with PC in my practice are the prevalence, natural history, frequency of occurrence of high-grade dysplasia (HGD) and/or pancreatic cancer (PDAC), concerning clinical symptoms and imaging findings, indications for EUS and fine-needle aspiration cytology, ideal method and frequency of surveillance, indications for surgery (up front and during follow-up), follow-up after surgery, stopping surveillance, costs, and unintentional harms of management. Good population-based evidence regarding many of the issues described above does not exist, and all information is from selected clinic, radiology, EUS, and surgical cohorts (very important when trying to assess the publications). Cohort studies should start with all PC undergoing surveillance and assess various outcomes, rather than looking backward from EUS or surgical cohorts.

The 2015 American Gastroenterological Association guidelines on asymptomatic neoplastic pancreas cysts, which I coauthored, recommend, consistent with principles of High Value Care (minimal unintentional harms and cost effectiveness), that two of three high-risk features (mural nodule, cyst size greater than 3 cm, and dilated pancreatic duct) be present for EUS-guided fine-needle aspiration (EUS-FNA). By the same token, they advise surgery for those with two of three high-risk features and or concerning features on EUS and cytology. Finally, they suggest stopping surveillance at 5 years if there are no significant changes. Rigorous GRADE methodology along with systematic review of all relevant questions (rather than cohorts of 500 or fewer patients) formed the basis of the guidelines. Those meta-analyses showed that risk of PDAC in mural nodules, cyst size >3 cm, and dilated pancreatic duct, while elevated, still is very low in absolute terms. Less than 20% of resections for highly selected, high-risk cysts showed PDAC. The guidelines were met with a lot of resistance from several societies and physician groups. The recommendations for stopping surveillance after 5 years and no surveillance for absent or low-grade dysplasia after surgery are hotly contested, and these areas need larger, long-term studies.

The whole area of cyst fluid molecular markers that would suggest mucinous type (KRAS and GNAS mutations) and, more importantly, the presence or imminent development of PDAC (next-generation sequencing or NGS) is an exciting field. One sincerely hopes that there will be a breakthrough in this area to achieve the holy grail. Cost effectiveness studies demonstrate the futility of existing guidelines and favor a less intensive approach. Guidelines are only a general framework, and management of individual patients in the clinic is entirely at the discretion of the treating physician. One should make every attempt to detect advanced lesions in PC, but such effort should not subject a large majority of patients to unintentional harms by overtreatment and add further to the burgeoning health care costs in the country.

Mayo Clinic

PC are extremely common (10% of all abdominal imaging), increase with age, are seen in as many as 40%-50% of MRI examinations for nonpancreatic indications, and most (>50%) are IPMNs. Most of the debate centers around the concerns of PDAC and/or HGD associated with mucinous cysts (MCN, IPMN, side-branch, main duct, or mixed).

The various guidelines by multiple societies differ in some aspects, such as in selection of patients based on clinical, laboratory, and imaging findings for up-front surgery or surveillance, the frequency of surveillance based on the size of the cyst and the presence of other concerning cyst features (usually with MRCP), the indications for EUS (both initial and subsequent), importance of the magnitude of growth (most IPMNs slowly grow over a period of time), indications for surgery during surveillance and postsurgery surveillance, and the decision to stop surveillance at some point in time. The literature is replete with small case series reporting a proportion of cancers detected and often ignoring the harms of surgery. Incidence of and mortality caused by PDAC are very low (about 1% for both) in a large national cohort of VA pancreatic cyst patients with long-term follow-up and other studies.

Marcov modeling suggests that none of the guidelines would lead to cost-effective care with low mortality because of overtreatment of low-risk lesions, and a specificity of 67% or more for PDAC/HGB is required. AGA guidelines came close to it but with low sensitivity. Monte Carlo modeling suggests that less intensive strategies, compared with more intensive, result in a similar number of deaths at a much lower cost. While molecular markers in PC fluid are reported to increase the specificity of PDAC/HGD to greater than 70%, it should be observed that such validation was done in a small percentage of patients who had both those markers and resection.

The costs of expensive procedures like EUS, MRI, and surgery, the 3% complication rate with EUS-FNA (primarily acute pancreatitis), and the 1% mortality and approximately 20%-30% morbidity with surgery (bleeding, infection, fistula) and postpancreatectomy diabetes of approximately 30% in the long run need special attention.

In conclusion, one could say pancreas cysts are extremely frequent, most of the neoplastic cysts are mucinous (IPMN and MCN) and slowly growing over time without an associated cancer, and the greatest need at this time is to identify the small proportion of such cysts with PDAC and/or HGD. Until such time, judicious selection of patients for surveillance and reasonable intervals of such surveillance with selective use of EUS will help identify patients requiring resection. In our enthusiasm to detect every possible pancreatic cancer, we should not ignore the unintentional outcomes of surgery to a large majority of patients who would never develop PDAC and the astronomical costs associated with such practice.

Dr. Vege is professor of medicine at the Mayo Clinic. He reported having no conflicts of interest regarding this article.
 

References

Vege SS et al. Gastroenterology. 2015;148:819-22.

Lobo JM et al. Surgery. 2020;168:601-9.

Lennon AM and Vege SS. Clin Gastroenterol Hepatol. 2022;20:1663-7.

Harris RP. Ann Intern Med. 2015;162:787-9.

Dear colleagues,

Pancreas cysts have become almost ubiquitous in this era of high-resolution cross-sectional imaging. They are a common GI consult with patients and providers worried about the potential risk of malignant transformation. Despite significant research over the past few decades, predicting the natural history of these cysts, especially the side-branch intraductal papillary mucinous neoplasms (IPMNs), remains difficult. There have been a variety of expert recommendations and guidelines, but heterogeneity exists in management especially regarding timing of endoscopic ultrasound, imaging surveillance, and cessation of surveillance. Some centers will present these cysts at multidisciplinary conferences, while others will follow general or local algorithms. In this issue of Perspectives, Dr. Lauren G. Khanna, assistant professor of medicine at NYU Langone Health, New York, and Dr. Santhi Vege, professor of medicine at the Mayo Clinic, Rochester, Minn., present updated and differing approaches to managing these cysts. Which side of the debate are you on? We welcome your thoughts, questions and input– share with us on Twitter @AGA_GIHN

Continuing pancreas cyst surveillance indefinitely is reasonable

BY LAUREN G. KHANNA, MD, MS

Pancreas cysts remain a clinical challenge. The true incidence of pancreas cysts is unknown, but from MRI and autopsy series, may be up to 50%. Patients presenting with a pancreas cyst often have significant anxiety about their risk of pancreas cancer. We as a medical community initially did too; but over the past few decades as we have gathered more data, we have become more comfortable observing many pancreas cysts. Yet our recommendations for how, how often, and for how long to evaluate pancreas cysts are still very much under debate; there are multiple guidelines with discordant recommendations. In this article, I will discuss my approach to patients with a pancreas cyst.

NYU Langone Health

At the first evaluation, I review available imaging to see if there are characteristic features to determine the type of pancreas cyst: IPMN (including main duct, branch duct, or mixed type), serous cystic neoplasm (SCA), mucinous cystic neoplasm (MCN), solid pseudopapillary neoplasm (SPN), cystic neuroendocrine tumor (NET), or pseudocyst. I also review symptoms, including abdominal pain, weight loss, history of pancreatitis, and onset of diabetes, and check hemoglobin A1c and Ca19-9. I often recommend magnetic resonance cholangiopancreatography (MRCP) if it has not already been obtained and is feasible (that is, if a patient does not have severe claustrophobia or a medical device incompatible with MRI). If a patient is not a candidate for treatment should a pancreatic malignancy be identified, because of age, comorbidities, or preference, I recommend no further evaluation.

Where cyst type remains unclear despite MRCP, and for cysts over 2 cm, I recommend endoscopic ultrasound (EUS) for fluid sampling to assist in determining cyst type and to rule out any other high-risk features. In accordance with international guidelines, if a patient has any concerning imaging features, including main pancreatic duct dilation >5 mm, solid component or mural nodule, or thickened or enhancing duct walls, regardless of cyst size, I recommend EUS to assess for and biopsy any solid component and to sample cyst fluid to examine for dysplasia. Given the lower sensitivity of CT for high-risk features, if MRCP is not feasible, for cysts 1-2 cm, I recommend EUS for better evaluation.

If a cyst is determined to be a cystic NET; main duct or mixed-type IPMN; MCN; or SPN; or a branch duct IPMN with mural nodule, high-grade dysplasia, or adenocarcinoma, and the patient is a surgical candidate, I refer the patient for surgical evaluation. If a cyst is determined to be an SCA, the malignant potential is minimal, and patients do not require follow-up. Patients with a pseudocyst are managed according to their clinical scenario.

Many patients have a proven or suspected branch duct IPMN, an indeterminate cyst, or multiple cysts. Cyst management during surveillance is then determined by the size of the largest cyst and stability of the cyst(s). Of note, patients with an IPMN also have been shown to have an elevated risk of concurrent pancreas adenocarcinoma, which I believe is one of the strongest arguments for heightened surveillance of the entire pancreas in pancreas cyst patients. EUS in particular can identify small or subtle lesions that are not detected by cross-sectional imaging.

If a patient has no prior imaging, in accordance with international and European guidelines, I recommend the first surveillance MRCP at a 6-month interval for cysts <2 cm, which may offer the opportunity to identify rapidly progressing cysts. If a patient has previous imaging available demonstrating stability, I recommend surveillance on an annual basis for cysts <2 cm. For patients with a cyst >2 cm, as above, I recommend EUS, and if there are no concerning features on imaging or EUS, I then recommend annual surveillance.

While the patient is under surveillance, if there is more than minimal cyst growth, a change in cyst appearance, or development of any imaging high-risk feature, pancreatitis, new onset or worsening diabetes, or elevation of Ca19-9, I recommend EUS for further evaluation and consideration of surgery based on EUS findings. If an asymptomatic cyst <2 cm remains stable for 5 years, I offer patients the option to extend imaging to every 2 years, if they are comfortable. In my experience, though, many patients prefer to continue annual imaging. The American Gastroenterological Association guidelines promote stopping surveillance after 5 years of stability, however there are studies demonstrating development of malignancy in cysts that were initially stable over the first 5 years of surveillance. Therefore, I discuss with patients that it is reasonable to continue cyst surveillance indefinitely, until they would no longer be interested in pursuing treatment of any kind if a malignant lesion were to be identified.

There are two special groups of pancreas cyst patients who warrant specific attention. Patients who are at elevated risk of pancreas adenocarcinoma because of an associated genetic mutation or a family history of pancreatic cancer already may be undergoing annual pancreas cancer screening with either MRCP, EUS, or alternating MRCP and EUS. When these high-risk patients also have pancreas cysts, I utilize whichever strategy would image their pancreas most frequently and do not extend beyond 1-year intervals. Another special group is patients who have undergone partial pancreatectomy for IPMN. As discussed above, given the elevated risk of concurrent pancreas adenocarcinoma in IPMN patients, I recommend indefinite continued surveillance of the remaining pancreas parenchyma in these patients.

Given the prevalence of pancreas cysts, it certainly would be convenient if guidelines were straightforward enough for primary care physicians to manage pancreas cyst surveillance, as they do for breast cancer screening. However, the complexities of pancreas cysts necessitate the expertise of gastroenterologists and pancreas surgeons, and a multidisciplinary team approach is best where possible.

Dr. Khanna is chief, advanced endoscopy, Tisch Hospital; director, NYU Advanced Endoscopy Fellowship; assistant professor of medicine, NYU Langone Health. Email: Lauren.Khanna@nyulangone.org. There are no relevant conflicts to disclose.
 

References

Tanaka M et al. Pancreatology. 2017 Sep-Oct;17(5):738-75.

Sahora K et al. Eur J Surg Oncol. 2016 Feb;42(2):197-204.

Del Chiaro M et al. Gut. 2018 May;67(5):789-804

Vege SS et al. Gastroenterology. 2015 Apr;148(4):819-22

Petrone MC et al. Clin Transl Gastroenterol. 2018 Jun 13;9(6):158

Pancreas cysts: More is not necessarily better!

BY SANTHI SWAROOP VEGE, MD

Pancreas cysts (PC) are very common, incidental findings on cross-sectional imaging, performed for non–pancreas-related symptoms. The important issues in management of patients with PC in my practice are the prevalence, natural history, frequency of occurrence of high-grade dysplasia (HGD) and/or pancreatic cancer (PDAC), concerning clinical symptoms and imaging findings, indications for EUS and fine-needle aspiration cytology, ideal method and frequency of surveillance, indications for surgery (up front and during follow-up), follow-up after surgery, stopping surveillance, costs, and unintentional harms of management. Good population-based evidence regarding many of the issues described above does not exist, and all information is from selected clinic, radiology, EUS, and surgical cohorts (very important when trying to assess the publications). Cohort studies should start with all PC undergoing surveillance and assess various outcomes, rather than looking backward from EUS or surgical cohorts.

The 2015 American Gastroenterological Association guidelines on asymptomatic neoplastic pancreas cysts, which I coauthored, recommend, consistent with principles of High Value Care (minimal unintentional harms and cost effectiveness), that two of three high-risk features (mural nodule, cyst size greater than 3 cm, and dilated pancreatic duct) be present for EUS-guided fine-needle aspiration (EUS-FNA). By the same token, they advise surgery for those with two of three high-risk features and or concerning features on EUS and cytology. Finally, they suggest stopping surveillance at 5 years if there are no significant changes. Rigorous GRADE methodology along with systematic review of all relevant questions (rather than cohorts of 500 or fewer patients) formed the basis of the guidelines. Those meta-analyses showed that risk of PDAC in mural nodules, cyst size >3 cm, and dilated pancreatic duct, while elevated, still is very low in absolute terms. Less than 20% of resections for highly selected, high-risk cysts showed PDAC. The guidelines were met with a lot of resistance from several societies and physician groups. The recommendations for stopping surveillance after 5 years and no surveillance for absent or low-grade dysplasia after surgery are hotly contested, and these areas need larger, long-term studies.

The whole area of cyst fluid molecular markers that would suggest mucinous type (KRAS and GNAS mutations) and, more importantly, the presence or imminent development of PDAC (next-generation sequencing or NGS) is an exciting field. One sincerely hopes that there will be a breakthrough in this area to achieve the holy grail. Cost effectiveness studies demonstrate the futility of existing guidelines and favor a less intensive approach. Guidelines are only a general framework, and management of individual patients in the clinic is entirely at the discretion of the treating physician. One should make every attempt to detect advanced lesions in PC, but such effort should not subject a large majority of patients to unintentional harms by overtreatment and add further to the burgeoning health care costs in the country.

Mayo Clinic

PC are extremely common (10% of all abdominal imaging), increase with age, are seen in as many as 40%-50% of MRI examinations for nonpancreatic indications, and most (>50%) are IPMNs. Most of the debate centers around the concerns of PDAC and/or HGD associated with mucinous cysts (MCN, IPMN, side-branch, main duct, or mixed).

The various guidelines by multiple societies differ in some aspects, such as in selection of patients based on clinical, laboratory, and imaging findings for up-front surgery or surveillance, the frequency of surveillance based on the size of the cyst and the presence of other concerning cyst features (usually with MRCP), the indications for EUS (both initial and subsequent), importance of the magnitude of growth (most IPMNs slowly grow over a period of time), indications for surgery during surveillance and postsurgery surveillance, and the decision to stop surveillance at some point in time. The literature is replete with small case series reporting a proportion of cancers detected and often ignoring the harms of surgery. Incidence of and mortality caused by PDAC are very low (about 1% for both) in a large national cohort of VA pancreatic cyst patients with long-term follow-up and other studies.

Marcov modeling suggests that none of the guidelines would lead to cost-effective care with low mortality because of overtreatment of low-risk lesions, and a specificity of 67% or more for PDAC/HGB is required. AGA guidelines came close to it but with low sensitivity. Monte Carlo modeling suggests that less intensive strategies, compared with more intensive, result in a similar number of deaths at a much lower cost. While molecular markers in PC fluid are reported to increase the specificity of PDAC/HGD to greater than 70%, it should be observed that such validation was done in a small percentage of patients who had both those markers and resection.

The costs of expensive procedures like EUS, MRI, and surgery, the 3% complication rate with EUS-FNA (primarily acute pancreatitis), and the 1% mortality and approximately 20%-30% morbidity with surgery (bleeding, infection, fistula) and postpancreatectomy diabetes of approximately 30% in the long run need special attention.

In conclusion, one could say pancreas cysts are extremely frequent, most of the neoplastic cysts are mucinous (IPMN and MCN) and slowly growing over time without an associated cancer, and the greatest need at this time is to identify the small proportion of such cysts with PDAC and/or HGD. Until such time, judicious selection of patients for surveillance and reasonable intervals of such surveillance with selective use of EUS will help identify patients requiring resection. In our enthusiasm to detect every possible pancreatic cancer, we should not ignore the unintentional outcomes of surgery to a large majority of patients who would never develop PDAC and the astronomical costs associated with such practice.

Dr. Vege is professor of medicine at the Mayo Clinic. He reported having no conflicts of interest regarding this article.
 

References

Vege SS et al. Gastroenterology. 2015;148:819-22.

Lobo JM et al. Surgery. 2020;168:601-9.

Lennon AM and Vege SS. Clin Gastroenterol Hepatol. 2022;20:1663-7.

Harris RP. Ann Intern Med. 2015;162:787-9.

The American College of Gastroenterology (ACG) issued a clinical guideline for the diagnosis and management of biliary strictures, or abnormal narrowing in the liver’s ductal drainage system.

The recommendations provide guidance on the care of patients with extrahepatic and perihilar strictures, with a focus on diagnosis and drainage. Although some of the principles may apply to intrahepatic strictures, the guideline doesn’t specifically address them. The new guideline is considered separate from the 2015 ACG guideline related to primary sclerosing cholangitis.

“The appropriate diagnosis and management of biliary strictures is still a big clinical challenge and has important implications in endoscopic, surgical, and oncological decision-making,” co-author Jennifer Maranki, MD, a professor of medicine and director of endoscopy at Penn State Hershey Medical Center, said in an interview.

“We wanted to provide the best possible guidance to gastroenterologists based on the available body of literature, with key shifts in diagnosis and management based on currently available modalities and tools,” she said.

The guideline was published in the March issue of the American Journal of Gastroenterology.

The recommendations were developed by a diverse group of authors from across the United States in recognition of the potential influence of commercial and intellectual conflicts of interest. The panel used a systematic process that involved structured literature searches by librarians and independent appraisal of the quality of evidence by dedicated methodologists, the authors write.

Overall, the team outlined 11 recommendations and 12 key concepts. A strong recommendation was made when the benefits of the test or intervention clearly outweighed the potential disadvantages. A conditional recommendation was made when some uncertainty remained about the balance of benefits and harms. Key concepts address important clinical questions that lack adequate evidence to inform recommendations. They are based on indirect evidence and expert opinion.

Epidemiology and diagnosis

The burden of biliary strictures is difficult to estimate, owing to the lack of a specific administrative code. The estimated cost of caring for biliary disease in the United States is about $16.9 billion annually, although this figure includes costs associated with gallbladder disease, choledocholithiasis, and other (nonobstructive) biliary disorders, the authors write.

Among the 57,000 new cases of pancreatic cancer each year, at least 60% will cause obstructive jaundice, resulting in about 34,000 annual cases of malignant extrahepatic biliary stricture, the team notes. In addition, about 3,000 cases of malignant perihilar stricture are expected in the United States each year. Patients may also seek care for benign strictures associated with chronic pancreatitis, primary sclerosing cholangitis, autoimmune disease, and post-cholecystectomy injury.

Under the first key concept, the authors note that biliary strictures in adults are more likely to be malignant than benign, except in certain well-defined scenarios. This underscores the importance of having a high index of clinical suspicion during evaluation, they add.

In general, a definitive tissue diagnosis is necessary to guide oncologic and endoscopic care for most strictures that aren’t surgically resectable at the time of presentation. For patients with extrahepatic biliary stricture due to an apparent or suspected pancreatic mass, endoscopic ultrasound (EUS) with fine-needle sampling (aspiration or biopsy) is recommended over endoscopic retrograde cholangiopancreatography (ERCP) as the preferred method of evaluation for malignancy.

For patients with suspected malignant perihilar stricture, multimodality sampling is recommended over brush cytology alone at the time of the index ERCP.

Guidance on drainage

For management, the principal objective is to restore the physiologic flow of bile into the duodenum. Although there is wide variability in the difficulty and risk of drainage, depending on location and complexity, perihilar strictures are generally more challenging and are riskier to drain than extrahepatic strictures. The goals should be to alleviate symptoms, reduce serum bilirubin to a level such that chemotherapy can be safely administered, and optimize surgical outcomes.

For benign extrahepatic biliary strictures, ERCP is the preferred modality for durable treatment. Fully covered self-expanding metallic stent (SEMS) placement is recommended over multiple plastic stents to reduce the number of procedures required for long-term treatment.

For extrahepatic strictures due to resectable pancreatic cancer or cholangiocarcinoma, the authors recommend against routine preoperative biliary drainage. However, drainage is warranted for some patients, including those with acute cholangitis, severe pruritus, very high serum bilirubin levels, those undergoing neoadjuvant therapy, and those for whom surgery is delayed.

For malignant extrahepatic strictures that are unresectable or borderline resectable, SEMS placement is recommended over plastic stents. The evidence is insufficient to recommend for or against uncovered SEMS versus fully covered SEMS.

For perihilar strictures due to suspected malignancy, the evidence is insufficient to recommend for or against ERCP versus percutaneous transhepatic biliary drainage. In addition, for malignant perihilar strictures, the evidence is insufficient to recommend for or against plastic stents versus uncovered SEMS.

For perihilar strictures due to cholangiocarcinoma in cases in which resection or transplantation is not possible, adjuvant endobiliary ablation plus plastic stent placement is recommended over plastic stent placement alone.

Overall, for patients with a biliary stricture for which ERCP is indicated but is unsuccessful or impossible, EUS-guided biliary access and drainage is recommended over PTBD, because it is associated with fewer adverse events. However, these interventional EUS procedures should be performed by an endoscopist with substantial experience.

“The workup of biliary strictures is challenging, invasive, and costly, requiring multiple diagnostic tools with highly variable yields,” co-author Victoria Gomez, MD, associate professor of medicine and director of bariatric endoscopy at Mayo Clinic, Jacksonville, Fla., said in an interview.

“Providers caring for these patients must be up to date with the most current evidence so that they can make the safest and most well-informed decisions for their patients,” she said. “These include considerations such as limiting the use of anesthesia, using tests that will result in the highest diagnostic yield, and providing effective therapies to decompress biliary obstruction.”

Future questions

Additional research is needed in several areas to strengthen recommendations and advance the field, the study authors write.

“Biliary strictures without an associated mass are a diagnostic challenge, and there are exciting opportunities to understand how new technologies, such as artificial intelligence, can be used to improve our assessment,” co-author Anna Tavakkoli, MD, assistant professor of internal medicine in digestive and liver diseases at the University of Texas Southwestern Medical Center, Dallas, said in an interview.

“Also, we highlighted several controversies in the drainage of perihilar strictures, including whether to use ERCP versus percutaneous drainage, whether metallic or plastic stents are better, and what the optimal stent placement should be,” she said. “Future multicenter studies are needed to address these key controversies.”

Although fully covered SEMS placement remains effective for benign biliary strictures, multiple plastic stents may be a better alternative in some cases. Such cases include those in which the stricture is close to the hilum, those in which the gallbladder is intact and in which crossing the cystic duct orifice cannot be avoided, those in which a fully covered SEMS has previously migrated or was not well tolerated, and those in which stricture has recurred after removal of a fully covered SEMS.

‘Comprehensive list’

“Overall, the authors have done a commendable job putting together a comprehensive list of recommendations that will invariably alter the practice of many therapeutic endoscopists for the diagnosis and management of biliary strictures,” Matthew Fasullo, DO, an advanced endoscopy and gastroenterology fellow at New York University Medical Center, told this news organization.

Dr. Fasullo, who wasn’t involved with the guideline, has published on advances in pathophysiology, diagnosis, and treatment for post-transplant biliary complications.

“The fact that ... cholangioscopy-directed biopsies after an initial negative evaluation via ERCP reveal malignancy in 54% of cases underscores the need for best practice guidelines and supports advancements in diagnostics to confidently rule in or out cancer,” he said.

“The movement toward multimodality sampling at the time of initial evaluation with a combination of brushing, fluoroscopy-directed biopsies, cholangioscopy-directed biopsies, and fluorescence in situ hybridization should become universally adopted in those with an ambiguous diagnosis,” he added. “As technology continues to improve, next-generation sequencing will prove to be an invaluable adjunct to the current pathological evaluation.”

The authors received no financial support for the guideline. One author has a consultant role for Takeda Pharmaceuticals and is an advisory board member role for Advarra. The other authors and Dr. Fasullo have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

The American College of Gastroenterology (ACG) issued a clinical guideline for the diagnosis and management of biliary strictures, or abnormal narrowing in the liver’s ductal drainage system.

The recommendations provide guidance on the care of patients with extrahepatic and perihilar strictures, with a focus on diagnosis and drainage. Although some of the principles may apply to intrahepatic strictures, the guideline doesn’t specifically address them. The new guideline is considered separate from the 2015 ACG guideline related to primary sclerosing cholangitis.

“The appropriate diagnosis and management of biliary strictures is still a big clinical challenge and has important implications in endoscopic, surgical, and oncological decision-making,” co-author Jennifer Maranki, MD, a professor of medicine and director of endoscopy at Penn State Hershey Medical Center, said in an interview.

“We wanted to provide the best possible guidance to gastroenterologists based on the available body of literature, with key shifts in diagnosis and management based on currently available modalities and tools,” she said.

The guideline was published in the March issue of the American Journal of Gastroenterology.

The recommendations were developed by a diverse group of authors from across the United States in recognition of the potential influence of commercial and intellectual conflicts of interest. The panel used a systematic process that involved structured literature searches by librarians and independent appraisal of the quality of evidence by dedicated methodologists, the authors write.

Overall, the team outlined 11 recommendations and 12 key concepts. A strong recommendation was made when the benefits of the test or intervention clearly outweighed the potential disadvantages. A conditional recommendation was made when some uncertainty remained about the balance of benefits and harms. Key concepts address important clinical questions that lack adequate evidence to inform recommendations. They are based on indirect evidence and expert opinion.

Epidemiology and diagnosis

The burden of biliary strictures is difficult to estimate, owing to the lack of a specific administrative code. The estimated cost of caring for biliary disease in the United States is about $16.9 billion annually, although this figure includes costs associated with gallbladder disease, choledocholithiasis, and other (nonobstructive) biliary disorders, the authors write.

Among the 57,000 new cases of pancreatic cancer each year, at least 60% will cause obstructive jaundice, resulting in about 34,000 annual cases of malignant extrahepatic biliary stricture, the team notes. In addition, about 3,000 cases of malignant perihilar stricture are expected in the United States each year. Patients may also seek care for benign strictures associated with chronic pancreatitis, primary sclerosing cholangitis, autoimmune disease, and post-cholecystectomy injury.

Under the first key concept, the authors note that biliary strictures in adults are more likely to be malignant than benign, except in certain well-defined scenarios. This underscores the importance of having a high index of clinical suspicion during evaluation, they add.

In general, a definitive tissue diagnosis is necessary to guide oncologic and endoscopic care for most strictures that aren’t surgically resectable at the time of presentation. For patients with extrahepatic biliary stricture due to an apparent or suspected pancreatic mass, endoscopic ultrasound (EUS) with fine-needle sampling (aspiration or biopsy) is recommended over endoscopic retrograde cholangiopancreatography (ERCP) as the preferred method of evaluation for malignancy.

For patients with suspected malignant perihilar stricture, multimodality sampling is recommended over brush cytology alone at the time of the index ERCP.

Guidance on drainage

For management, the principal objective is to restore the physiologic flow of bile into the duodenum. Although there is wide variability in the difficulty and risk of drainage, depending on location and complexity, perihilar strictures are generally more challenging and are riskier to drain than extrahepatic strictures. The goals should be to alleviate symptoms, reduce serum bilirubin to a level such that chemotherapy can be safely administered, and optimize surgical outcomes.

For benign extrahepatic biliary strictures, ERCP is the preferred modality for durable treatment. Fully covered self-expanding metallic stent (SEMS) placement is recommended over multiple plastic stents to reduce the number of procedures required for long-term treatment.

For extrahepatic strictures due to resectable pancreatic cancer or cholangiocarcinoma, the authors recommend against routine preoperative biliary drainage. However, drainage is warranted for some patients, including those with acute cholangitis, severe pruritus, very high serum bilirubin levels, those undergoing neoadjuvant therapy, and those for whom surgery is delayed.

For malignant extrahepatic strictures that are unresectable or borderline resectable, SEMS placement is recommended over plastic stents. The evidence is insufficient to recommend for or against uncovered SEMS versus fully covered SEMS.

For perihilar strictures due to suspected malignancy, the evidence is insufficient to recommend for or against ERCP versus percutaneous transhepatic biliary drainage. In addition, for malignant perihilar strictures, the evidence is insufficient to recommend for or against plastic stents versus uncovered SEMS.

For perihilar strictures due to cholangiocarcinoma in cases in which resection or transplantation is not possible, adjuvant endobiliary ablation plus plastic stent placement is recommended over plastic stent placement alone.

Overall, for patients with a biliary stricture for which ERCP is indicated but is unsuccessful or impossible, EUS-guided biliary access and drainage is recommended over PTBD, because it is associated with fewer adverse events. However, these interventional EUS procedures should be performed by an endoscopist with substantial experience.

“The workup of biliary strictures is challenging, invasive, and costly, requiring multiple diagnostic tools with highly variable yields,” co-author Victoria Gomez, MD, associate professor of medicine and director of bariatric endoscopy at Mayo Clinic, Jacksonville, Fla., said in an interview.

“Providers caring for these patients must be up to date with the most current evidence so that they can make the safest and most well-informed decisions for their patients,” she said. “These include considerations such as limiting the use of anesthesia, using tests that will result in the highest diagnostic yield, and providing effective therapies to decompress biliary obstruction.”

Future questions

Additional research is needed in several areas to strengthen recommendations and advance the field, the study authors write.

“Biliary strictures without an associated mass are a diagnostic challenge, and there are exciting opportunities to understand how new technologies, such as artificial intelligence, can be used to improve our assessment,” co-author Anna Tavakkoli, MD, assistant professor of internal medicine in digestive and liver diseases at the University of Texas Southwestern Medical Center, Dallas, said in an interview.

“Also, we highlighted several controversies in the drainage of perihilar strictures, including whether to use ERCP versus percutaneous drainage, whether metallic or plastic stents are better, and what the optimal stent placement should be,” she said. “Future multicenter studies are needed to address these key controversies.”

Although fully covered SEMS placement remains effective for benign biliary strictures, multiple plastic stents may be a better alternative in some cases. Such cases include those in which the stricture is close to the hilum, those in which the gallbladder is intact and in which crossing the cystic duct orifice cannot be avoided, those in which a fully covered SEMS has previously migrated or was not well tolerated, and those in which stricture has recurred after removal of a fully covered SEMS.

‘Comprehensive list’

“Overall, the authors have done a commendable job putting together a comprehensive list of recommendations that will invariably alter the practice of many therapeutic endoscopists for the diagnosis and management of biliary strictures,” Matthew Fasullo, DO, an advanced endoscopy and gastroenterology fellow at New York University Medical Center, told this news organization.

Dr. Fasullo, who wasn’t involved with the guideline, has published on advances in pathophysiology, diagnosis, and treatment for post-transplant biliary complications.

“The fact that ... cholangioscopy-directed biopsies after an initial negative evaluation via ERCP reveal malignancy in 54% of cases underscores the need for best practice guidelines and supports advancements in diagnostics to confidently rule in or out cancer,” he said.

“The movement toward multimodality sampling at the time of initial evaluation with a combination of brushing, fluoroscopy-directed biopsies, cholangioscopy-directed biopsies, and fluorescence in situ hybridization should become universally adopted in those with an ambiguous diagnosis,” he added. “As technology continues to improve, next-generation sequencing will prove to be an invaluable adjunct to the current pathological evaluation.”

The authors received no financial support for the guideline. One author has a consultant role for Takeda Pharmaceuticals and is an advisory board member role for Advarra. The other authors and Dr. Fasullo have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

The American College of Gastroenterology (ACG) issued a clinical guideline for the diagnosis and management of biliary strictures, or abnormal narrowing in the liver’s ductal drainage system.

The recommendations provide guidance on the care of patients with extrahepatic and perihilar strictures, with a focus on diagnosis and drainage. Although some of the principles may apply to intrahepatic strictures, the guideline doesn’t specifically address them. The new guideline is considered separate from the 2015 ACG guideline related to primary sclerosing cholangitis.

“The appropriate diagnosis and management of biliary strictures is still a big clinical challenge and has important implications in endoscopic, surgical, and oncological decision-making,” co-author Jennifer Maranki, MD, a professor of medicine and director of endoscopy at Penn State Hershey Medical Center, said in an interview.

“We wanted to provide the best possible guidance to gastroenterologists based on the available body of literature, with key shifts in diagnosis and management based on currently available modalities and tools,” she said.

The guideline was published in the March issue of the American Journal of Gastroenterology.

The recommendations were developed by a diverse group of authors from across the United States in recognition of the potential influence of commercial and intellectual conflicts of interest. The panel used a systematic process that involved structured literature searches by librarians and independent appraisal of the quality of evidence by dedicated methodologists, the authors write.

Overall, the team outlined 11 recommendations and 12 key concepts. A strong recommendation was made when the benefits of the test or intervention clearly outweighed the potential disadvantages. A conditional recommendation was made when some uncertainty remained about the balance of benefits and harms. Key concepts address important clinical questions that lack adequate evidence to inform recommendations. They are based on indirect evidence and expert opinion.

Epidemiology and diagnosis

The burden of biliary strictures is difficult to estimate, owing to the lack of a specific administrative code. The estimated cost of caring for biliary disease in the United States is about $16.9 billion annually, although this figure includes costs associated with gallbladder disease, choledocholithiasis, and other (nonobstructive) biliary disorders, the authors write.

Among the 57,000 new cases of pancreatic cancer each year, at least 60% will cause obstructive jaundice, resulting in about 34,000 annual cases of malignant extrahepatic biliary stricture, the team notes. In addition, about 3,000 cases of malignant perihilar stricture are expected in the United States each year. Patients may also seek care for benign strictures associated with chronic pancreatitis, primary sclerosing cholangitis, autoimmune disease, and post-cholecystectomy injury.

Under the first key concept, the authors note that biliary strictures in adults are more likely to be malignant than benign, except in certain well-defined scenarios. This underscores the importance of having a high index of clinical suspicion during evaluation, they add.

In general, a definitive tissue diagnosis is necessary to guide oncologic and endoscopic care for most strictures that aren’t surgically resectable at the time of presentation. For patients with extrahepatic biliary stricture due to an apparent or suspected pancreatic mass, endoscopic ultrasound (EUS) with fine-needle sampling (aspiration or biopsy) is recommended over endoscopic retrograde cholangiopancreatography (ERCP) as the preferred method of evaluation for malignancy.

For patients with suspected malignant perihilar stricture, multimodality sampling is recommended over brush cytology alone at the time of the index ERCP.

Guidance on drainage

For management, the principal objective is to restore the physiologic flow of bile into the duodenum. Although there is wide variability in the difficulty and risk of drainage, depending on location and complexity, perihilar strictures are generally more challenging and are riskier to drain than extrahepatic strictures. The goals should be to alleviate symptoms, reduce serum bilirubin to a level such that chemotherapy can be safely administered, and optimize surgical outcomes.

For benign extrahepatic biliary strictures, ERCP is the preferred modality for durable treatment. Fully covered self-expanding metallic stent (SEMS) placement is recommended over multiple plastic stents to reduce the number of procedures required for long-term treatment.

For extrahepatic strictures due to resectable pancreatic cancer or cholangiocarcinoma, the authors recommend against routine preoperative biliary drainage. However, drainage is warranted for some patients, including those with acute cholangitis, severe pruritus, very high serum bilirubin levels, those undergoing neoadjuvant therapy, and those for whom surgery is delayed.

For malignant extrahepatic strictures that are unresectable or borderline resectable, SEMS placement is recommended over plastic stents. The evidence is insufficient to recommend for or against uncovered SEMS versus fully covered SEMS.

For perihilar strictures due to suspected malignancy, the evidence is insufficient to recommend for or against ERCP versus percutaneous transhepatic biliary drainage. In addition, for malignant perihilar strictures, the evidence is insufficient to recommend for or against plastic stents versus uncovered SEMS.

For perihilar strictures due to cholangiocarcinoma in cases in which resection or transplantation is not possible, adjuvant endobiliary ablation plus plastic stent placement is recommended over plastic stent placement alone.

Overall, for patients with a biliary stricture for which ERCP is indicated but is unsuccessful or impossible, EUS-guided biliary access and drainage is recommended over PTBD, because it is associated with fewer adverse events. However, these interventional EUS procedures should be performed by an endoscopist with substantial experience.

“The workup of biliary strictures is challenging, invasive, and costly, requiring multiple diagnostic tools with highly variable yields,” co-author Victoria Gomez, MD, associate professor of medicine and director of bariatric endoscopy at Mayo Clinic, Jacksonville, Fla., said in an interview.

“Providers caring for these patients must be up to date with the most current evidence so that they can make the safest and most well-informed decisions for their patients,” she said. “These include considerations such as limiting the use of anesthesia, using tests that will result in the highest diagnostic yield, and providing effective therapies to decompress biliary obstruction.”

Future questions

Additional research is needed in several areas to strengthen recommendations and advance the field, the study authors write.

“Biliary strictures without an associated mass are a diagnostic challenge, and there are exciting opportunities to understand how new technologies, such as artificial intelligence, can be used to improve our assessment,” co-author Anna Tavakkoli, MD, assistant professor of internal medicine in digestive and liver diseases at the University of Texas Southwestern Medical Center, Dallas, said in an interview.

“Also, we highlighted several controversies in the drainage of perihilar strictures, including whether to use ERCP versus percutaneous drainage, whether metallic or plastic stents are better, and what the optimal stent placement should be,” she said. “Future multicenter studies are needed to address these key controversies.”

Although fully covered SEMS placement remains effective for benign biliary strictures, multiple plastic stents may be a better alternative in some cases. Such cases include those in which the stricture is close to the hilum, those in which the gallbladder is intact and in which crossing the cystic duct orifice cannot be avoided, those in which a fully covered SEMS has previously migrated or was not well tolerated, and those in which stricture has recurred after removal of a fully covered SEMS.

‘Comprehensive list’

“Overall, the authors have done a commendable job putting together a comprehensive list of recommendations that will invariably alter the practice of many therapeutic endoscopists for the diagnosis and management of biliary strictures,” Matthew Fasullo, DO, an advanced endoscopy and gastroenterology fellow at New York University Medical Center, told this news organization.

Dr. Fasullo, who wasn’t involved with the guideline, has published on advances in pathophysiology, diagnosis, and treatment for post-transplant biliary complications.

“The fact that ... cholangioscopy-directed biopsies after an initial negative evaluation via ERCP reveal malignancy in 54% of cases underscores the need for best practice guidelines and supports advancements in diagnostics to confidently rule in or out cancer,” he said.

“The movement toward multimodality sampling at the time of initial evaluation with a combination of brushing, fluoroscopy-directed biopsies, cholangioscopy-directed biopsies, and fluorescence in situ hybridization should become universally adopted in those with an ambiguous diagnosis,” he added. “As technology continues to improve, next-generation sequencing will prove to be an invaluable adjunct to the current pathological evaluation.”

The authors received no financial support for the guideline. One author has a consultant role for Takeda Pharmaceuticals and is an advisory board member role for Advarra. The other authors and Dr. Fasullo have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

People who have had COVID-19 have a 36% overall higher risk of developing gastrointestinal problems in the year after infection than people who have not had the illness, a large new study indicates.

The researchers estimate that, so far, SARS-CoV-2 infections have contributed to more than 6 million new cases of GI disorders in the United States and 42 million new cases worldwide.

The diagnoses more common among patients who’ve had COVID ranged from stomach upset to acute pancreatitis, say the researchers, led by Evan Xu, a data analyst at the Clinical Epidemiology Center, Research and Development Service, VA St. Louis Health Care System.

Signs and symptoms of GI problems, such as constipation and diarrhea, also were more common among patients who had had the virus, the study found.

“Altogether, our results show that people with SARS-CoV-2 infection are at increased risk of gastrointestinal disorders in the post-acute phase of COVID-19,” the researchers write. “Post-COVID care should involve attention to gastrointestinal health and disease.”

The results were published online in Nature Communications.
 

Disease risks jump

The researchers used data from the U.S. Department of Veterans Affairs national health care databases to identify 154,068 people with confirmed COVID-19 from March 1, 2020, through Jan. 15, 2021. They used statistical modeling to compare those patients with 5.6 million patients with similar characteristics who had not been infected during the same period and an historical control group of 5.9 million patients from March 1, 2018, to Dec. 31, 2019, before the virus began to spread across the globe.

The study included hospitalized and nonhospitalized COVID patients. The majority of the study population was male, but the study included almost 1.2 million female patients.

Compared with control persons, post-COVID patients’ increased risk of a GI diagnosis and the excess disease burden at 1 year, respectively, were as follows.

• 102% for cholangitis; 0.22 per 1,000 persons
• 62% for peptic ulcer disease; 1.57 per 1,000 persons
• 54% for irritable bowel syndrome; 0.44 per 1,000 persons
• 47% for acute gastritis; 0.47 per 1,000 persons
• 46% for acute pancreatitis; 0.6 per 1,000 persons
• 36% for functional dyspepsia; 0.63 per 1,000 persons
• 35% for gastroesophageal reflux disease; 15.5 per 1,000 persons

Patients who’d had the virus were also at higher risk for GI symptoms than their COVID-free peers. Their risk was 60% higher for constipation, 58% for diarrhea, 52% for vomiting, 46% for bloating, and 44% for abdominal pain, the investigators found.

The risk of developing GI symptoms increased with COVID-19 severity and was highest for those who received intensive care because of the virus, the researchers note.

Subgroup analyses found that the risks of composite gastrointestinal outcome were evident in all subgroups based on age, race, sex, obesity, smoking, cardiovascular disease, chronic kidney disease, diabetes, hyperlipidemia, and hypertension, the authors write.
 

Disease burden rises

The increased numbers of GI patients with prior SARS-CoV-2 infection are altering the burden on the health care system, senior author Ziyad Al-Aly, MD, a clinical epidemiologist at Washington University, St. Louis, said in an interview.

The shift may be pronounced in primary care, where GI concerns should be seen as a trigger for questions about prior SARS-CoV-2 infection, Dr. Al-Aly said.

Patients may encounter longer wait times at GI clinics or may give up on trying to schedule appointments if waits become too long, he said. They may also present to emergency departments if they can’t get an outpatient appointment, he added.

Simon C. Mathews, MD, assistant professor of medicine, division of gastroenterology, Johns Hopkins Medicine, Baltimore, told this news organization that he’s seeing increased wait times since COVID emerged.

“We know that the pandemic impacted patients’ ability and willingness to seek GI care. There continues to be a long backlog for patients who are only now getting reconnected to care. As a result, our clinics are busier than ever, and our wait times for appointments are unfortunately longer than we would like,” said Dr. Mathews, who was not involved in the research.

Abdominal pain, bloating, diarrhea, and constipation continue to be among the most common symptoms Dr. Mathews sees in clinic, he said.

Kyle Staller, MD, a Massachusetts General Brigham gastroenterologist, said in an interview that it’s important to distinguish symptoms from eventual diagnoses, which lag behind.

“Are patients attributing their symptoms to COVID, or is COVID itself creating a background of inflammation or changes in the nerves that are making these symptoms more common? My suspicion is a little bit of both,” said Dr. Staller, who is director of the Gastrointestinal Motility Laboratory at Mass General, Boston.

Although his clinic is seeing patients with the GI signs and symptoms listed in the article, “we’re not seeing as much of some of the diagnoses, like peptic ulcer disease and pancreatitis,” he said. “I wonder if those may be related to some of the consequences of being critically ill in general, rather than COVID specifically. Those diagnoses I would be more skeptical about.”
 

Duration of symptoms unclear

It’s hard to tell patients how long their GI symptoms might last after COVID, given the relatively short time researchers have had to study the virus, said Dr. Staller, who was not involved in the research.

The symptoms he’s seeing in patients after COVID mimic those of postinfectious IBS, which literature says could last for months or years, Dr. Staller said. “But they should improve over time,” he added.

Senior author Dr. Al-Aly agreed that the duration of post-COVID GI symptoms is unclear.

“What I can tell you is that even people who got SARS-CoV-2 infection from March 2020 are still coming back for GI problems,” he said.

Unlike other symptoms of long COVID, such as brain fog, gastroenterologists fortunately know how to treat the GI disorders that evolve from SARS-CoV-2 infection, said Dr. Al-Aly, who has studied the long-term effects of the virus on the brain, kidneys, heart, and other organs.

All health care providers “need to be thinking about COVID as a risk factor for all these diseases” and should ask patients about SARS-CoV-2 infection when they take their histories, he said.

The authors, Dr. Staller, and Dr. Mathews report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

People who have had COVID-19 have a 36% overall higher risk of developing gastrointestinal problems in the year after infection than people who have not had the illness, a large new study indicates.

The researchers estimate that, so far, SARS-CoV-2 infections have contributed to more than 6 million new cases of GI disorders in the United States and 42 million new cases worldwide.

The diagnoses more common among patients who’ve had COVID ranged from stomach upset to acute pancreatitis, say the researchers, led by Evan Xu, a data analyst at the Clinical Epidemiology Center, Research and Development Service, VA St. Louis Health Care System.

Signs and symptoms of GI problems, such as constipation and diarrhea, also were more common among patients who had had the virus, the study found.

“Altogether, our results show that people with SARS-CoV-2 infection are at increased risk of gastrointestinal disorders in the post-acute phase of COVID-19,” the researchers write. “Post-COVID care should involve attention to gastrointestinal health and disease.”

The results were published online in Nature Communications.
 

Disease risks jump

The researchers used data from the U.S. Department of Veterans Affairs national health care databases to identify 154,068 people with confirmed COVID-19 from March 1, 2020, through Jan. 15, 2021. They used statistical modeling to compare those patients with 5.6 million patients with similar characteristics who had not been infected during the same period and an historical control group of 5.9 million patients from March 1, 2018, to Dec. 31, 2019, before the virus began to spread across the globe.

The study included hospitalized and nonhospitalized COVID patients. The majority of the study population was male, but the study included almost 1.2 million female patients.

Compared with control persons, post-COVID patients’ increased risk of a GI diagnosis and the excess disease burden at 1 year, respectively, were as follows.

• 102% for cholangitis; 0.22 per 1,000 persons
• 62% for peptic ulcer disease; 1.57 per 1,000 persons
• 54% for irritable bowel syndrome; 0.44 per 1,000 persons
• 47% for acute gastritis; 0.47 per 1,000 persons
• 46% for acute pancreatitis; 0.6 per 1,000 persons
• 36% for functional dyspepsia; 0.63 per 1,000 persons
• 35% for gastroesophageal reflux disease; 15.5 per 1,000 persons

Patients who’d had the virus were also at higher risk for GI symptoms than their COVID-free peers. Their risk was 60% higher for constipation, 58% for diarrhea, 52% for vomiting, 46% for bloating, and 44% for abdominal pain, the investigators found.

The risk of developing GI symptoms increased with COVID-19 severity and was highest for those who received intensive care because of the virus, the researchers note.

Subgroup analyses found that the risks of composite gastrointestinal outcome were evident in all subgroups based on age, race, sex, obesity, smoking, cardiovascular disease, chronic kidney disease, diabetes, hyperlipidemia, and hypertension, the authors write.
 

Disease burden rises

The increased numbers of GI patients with prior SARS-CoV-2 infection are altering the burden on the health care system, senior author Ziyad Al-Aly, MD, a clinical epidemiologist at Washington University, St. Louis, said in an interview.

The shift may be pronounced in primary care, where GI concerns should be seen as a trigger for questions about prior SARS-CoV-2 infection, Dr. Al-Aly said.

Patients may encounter longer wait times at GI clinics or may give up on trying to schedule appointments if waits become too long, he said. They may also present to emergency departments if they can’t get an outpatient appointment, he added.

Simon C. Mathews, MD, assistant professor of medicine, division of gastroenterology, Johns Hopkins Medicine, Baltimore, told this news organization that he’s seeing increased wait times since COVID emerged.

“We know that the pandemic impacted patients’ ability and willingness to seek GI care. There continues to be a long backlog for patients who are only now getting reconnected to care. As a result, our clinics are busier than ever, and our wait times for appointments are unfortunately longer than we would like,” said Dr. Mathews, who was not involved in the research.

Abdominal pain, bloating, diarrhea, and constipation continue to be among the most common symptoms Dr. Mathews sees in clinic, he said.

Kyle Staller, MD, a Massachusetts General Brigham gastroenterologist, said in an interview that it’s important to distinguish symptoms from eventual diagnoses, which lag behind.

“Are patients attributing their symptoms to COVID, or is COVID itself creating a background of inflammation or changes in the nerves that are making these symptoms more common? My suspicion is a little bit of both,” said Dr. Staller, who is director of the Gastrointestinal Motility Laboratory at Mass General, Boston.

Although his clinic is seeing patients with the GI signs and symptoms listed in the article, “we’re not seeing as much of some of the diagnoses, like peptic ulcer disease and pancreatitis,” he said. “I wonder if those may be related to some of the consequences of being critically ill in general, rather than COVID specifically. Those diagnoses I would be more skeptical about.”
 

Duration of symptoms unclear

It’s hard to tell patients how long their GI symptoms might last after COVID, given the relatively short time researchers have had to study the virus, said Dr. Staller, who was not involved in the research.

The symptoms he’s seeing in patients after COVID mimic those of postinfectious IBS, which literature says could last for months or years, Dr. Staller said. “But they should improve over time,” he added.

Senior author Dr. Al-Aly agreed that the duration of post-COVID GI symptoms is unclear.

“What I can tell you is that even people who got SARS-CoV-2 infection from March 2020 are still coming back for GI problems,” he said.

Unlike other symptoms of long COVID, such as brain fog, gastroenterologists fortunately know how to treat the GI disorders that evolve from SARS-CoV-2 infection, said Dr. Al-Aly, who has studied the long-term effects of the virus on the brain, kidneys, heart, and other organs.

All health care providers “need to be thinking about COVID as a risk factor for all these diseases” and should ask patients about SARS-CoV-2 infection when they take their histories, he said.

The authors, Dr. Staller, and Dr. Mathews report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

People who have had COVID-19 have a 36% overall higher risk of developing gastrointestinal problems in the year after infection than people who have not had the illness, a large new study indicates.

The researchers estimate that, so far, SARS-CoV-2 infections have contributed to more than 6 million new cases of GI disorders in the United States and 42 million new cases worldwide.

The diagnoses more common among patients who’ve had COVID ranged from stomach upset to acute pancreatitis, say the researchers, led by Evan Xu, a data analyst at the Clinical Epidemiology Center, Research and Development Service, VA St. Louis Health Care System.

Signs and symptoms of GI problems, such as constipation and diarrhea, also were more common among patients who had had the virus, the study found.

“Altogether, our results show that people with SARS-CoV-2 infection are at increased risk of gastrointestinal disorders in the post-acute phase of COVID-19,” the researchers write. “Post-COVID care should involve attention to gastrointestinal health and disease.”

The results were published online in Nature Communications.
 

Disease risks jump

The researchers used data from the U.S. Department of Veterans Affairs national health care databases to identify 154,068 people with confirmed COVID-19 from March 1, 2020, through Jan. 15, 2021. They used statistical modeling to compare those patients with 5.6 million patients with similar characteristics who had not been infected during the same period and an historical control group of 5.9 million patients from March 1, 2018, to Dec. 31, 2019, before the virus began to spread across the globe.

The study included hospitalized and nonhospitalized COVID patients. The majority of the study population was male, but the study included almost 1.2 million female patients.

Compared with control persons, post-COVID patients’ increased risk of a GI diagnosis and the excess disease burden at 1 year, respectively, were as follows.

• 102% for cholangitis; 0.22 per 1,000 persons
• 62% for peptic ulcer disease; 1.57 per 1,000 persons
• 54% for irritable bowel syndrome; 0.44 per 1,000 persons
• 47% for acute gastritis; 0.47 per 1,000 persons
• 46% for acute pancreatitis; 0.6 per 1,000 persons
• 36% for functional dyspepsia; 0.63 per 1,000 persons
• 35% for gastroesophageal reflux disease; 15.5 per 1,000 persons

Patients who’d had the virus were also at higher risk for GI symptoms than their COVID-free peers. Their risk was 60% higher for constipation, 58% for diarrhea, 52% for vomiting, 46% for bloating, and 44% for abdominal pain, the investigators found.

The risk of developing GI symptoms increased with COVID-19 severity and was highest for those who received intensive care because of the virus, the researchers note.

Subgroup analyses found that the risks of composite gastrointestinal outcome were evident in all subgroups based on age, race, sex, obesity, smoking, cardiovascular disease, chronic kidney disease, diabetes, hyperlipidemia, and hypertension, the authors write.
 

Disease burden rises

The increased numbers of GI patients with prior SARS-CoV-2 infection are altering the burden on the health care system, senior author Ziyad Al-Aly, MD, a clinical epidemiologist at Washington University, St. Louis, said in an interview.

The shift may be pronounced in primary care, where GI concerns should be seen as a trigger for questions about prior SARS-CoV-2 infection, Dr. Al-Aly said.

Patients may encounter longer wait times at GI clinics or may give up on trying to schedule appointments if waits become too long, he said. They may also present to emergency departments if they can’t get an outpatient appointment, he added.

Simon C. Mathews, MD, assistant professor of medicine, division of gastroenterology, Johns Hopkins Medicine, Baltimore, told this news organization that he’s seeing increased wait times since COVID emerged.

“We know that the pandemic impacted patients’ ability and willingness to seek GI care. There continues to be a long backlog for patients who are only now getting reconnected to care. As a result, our clinics are busier than ever, and our wait times for appointments are unfortunately longer than we would like,” said Dr. Mathews, who was not involved in the research.

Abdominal pain, bloating, diarrhea, and constipation continue to be among the most common symptoms Dr. Mathews sees in clinic, he said.

Kyle Staller, MD, a Massachusetts General Brigham gastroenterologist, said in an interview that it’s important to distinguish symptoms from eventual diagnoses, which lag behind.

“Are patients attributing their symptoms to COVID, or is COVID itself creating a background of inflammation or changes in the nerves that are making these symptoms more common? My suspicion is a little bit of both,” said Dr. Staller, who is director of the Gastrointestinal Motility Laboratory at Mass General, Boston.

Although his clinic is seeing patients with the GI signs and symptoms listed in the article, “we’re not seeing as much of some of the diagnoses, like peptic ulcer disease and pancreatitis,” he said. “I wonder if those may be related to some of the consequences of being critically ill in general, rather than COVID specifically. Those diagnoses I would be more skeptical about.”
 

Duration of symptoms unclear

It’s hard to tell patients how long their GI symptoms might last after COVID, given the relatively short time researchers have had to study the virus, said Dr. Staller, who was not involved in the research.

The symptoms he’s seeing in patients after COVID mimic those of postinfectious IBS, which literature says could last for months or years, Dr. Staller said. “But they should improve over time,” he added.

Senior author Dr. Al-Aly agreed that the duration of post-COVID GI symptoms is unclear.

“What I can tell you is that even people who got SARS-CoV-2 infection from March 2020 are still coming back for GI problems,” he said.

Unlike other symptoms of long COVID, such as brain fog, gastroenterologists fortunately know how to treat the GI disorders that evolve from SARS-CoV-2 infection, said Dr. Al-Aly, who has studied the long-term effects of the virus on the brain, kidneys, heart, and other organs.

All health care providers “need to be thinking about COVID as a risk factor for all these diseases” and should ask patients about SARS-CoV-2 infection when they take their histories, he said.

The authors, Dr. Staller, and Dr. Mathews report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

An investigation of genomics data related to primary sclerosing cholangitis (PSC) in published medical literature revealed several genes likely involved in the pathogenesis of this autoimmune diseases, according to a study published in Gastro Hep Advances.

PSC is very rare, with an incidence of 0-1.3 cases per 100,000 people per year. Because up to 80% of patients with PSC also have inflammatory bowel disease (IBD), a link along the gut-liver axis is suspected. So far, scientists have not understood the causes of PSC, the main complications of which include biliary cirrhosis, bacterial cholangitis, and cholangiocarcinoma.

No treatment is currently available for PSC, but the findings of this genomics study suggest several targets that may be worth pursuing, particularly the gene NR0B2.

“The therapeutic targeting of NR0B2 may potentiate that of FXR [farnesoid X receptor] and enable action on early events of the disease and prevent its progression,” wrote Christophe Desterke, PhD, of the Paul-Brousse Hospital, the French National Institute of Health and Medical Research, and the University of Paris-Saclay in Villejuif, France, and his associates.

The researchers used an algorithmic tool to mine the MEDLINE/PubMed/NCBI database using the three key symptoms of PSC – biliary fibrosis, biliary inflammation, and biliary stasis – as their keywords. This approach allowed them to discover the genes and potential pathways related to PSC in published research text or in clinical, animal, and cellular models.

The researchers initially found 525 genes linked to PSC and then compared them to RNA data from liver biopsies taken from patients with liver disease from various causes. This process led to a ranking of the 10 best markers of PSC, based on the data-mining method and the genes’ association with one or more of the three PSC symptoms.

At the top of the list is NR1H4, also called FXR, which ranks most highly with biliary fibrosis and biliary stasis. NR1H4 is already a clear target for cholestatic and fatty liver diseases, the authors noted. The other genes, in descending order of relevance, are: ABCB4, ABCB11, TGFB1, IFNL3, PNPLA3, IL6, TLR4, GPBAR1, and IL17A. In addition, complications of PSC were significantly associated with upregulation of TNFRS12A, SOX9, ANXA2, MMP7, and LCN2.

Separately, investigation of the 525 initially identified genes in mouse models of PSC revealed that NR0B2 is also a key player in the pathogenesis of PSC.

"NR0B2 was upregulated in PSC livers independent of gender, age, and body mass index,” the authors reported. “Importantly, it was not dependent on the severity of PSC in the prognostic cohort, suggesting that this may be an early event during the disease.”

The researchers also found a possible pathway explaining the autoimmunity of PSC – the involvement of CD274, also known as the PDL1 immune checkpoint. The authors noted that the PDL1 inhibitor pembrolizumab has previously been reported as a cause of sclerosing cholangitis.

Further, the researchers discovered overexpression of FOXP3 in the livers of patients with PSC. Because FOXP3 determines what T-cell subtypes look like, the finding suggests that an “imbalance between Foxp3þ regulatory T cells and Th17 cells may be involved in IBD and PSC,” they wrote.

Also of note was the overexpression of SOX9 in the livers of patients with PSC whose profiles suggested the worst clinical prognoses.

Finally, the researchers identified three genes as potentially involved in development of cholangiocarcinoma: GSTA3, ID2 (which is overexpressed in biliary tract cancer), and especially TMEM45A, a protein in cells’ Golgi apparatus that is already known to be involved in the development of several other cancers.

The research was funded by the French National Institute of Health and Medical Research. The authors reported no conflicts of interest.

An investigation of genomics data related to primary sclerosing cholangitis (PSC) in published medical literature revealed several genes likely involved in the pathogenesis of this autoimmune diseases, according to a study published in Gastro Hep Advances.

PSC is very rare, with an incidence of 0-1.3 cases per 100,000 people per year. Because up to 80% of patients with PSC also have inflammatory bowel disease (IBD), a link along the gut-liver axis is suspected. So far, scientists have not understood the causes of PSC, the main complications of which include biliary cirrhosis, bacterial cholangitis, and cholangiocarcinoma.

No treatment is currently available for PSC, but the findings of this genomics study suggest several targets that may be worth pursuing, particularly the gene NR0B2.

“The therapeutic targeting of NR0B2 may potentiate that of FXR [farnesoid X receptor] and enable action on early events of the disease and prevent its progression,” wrote Christophe Desterke, PhD, of the Paul-Brousse Hospital, the French National Institute of Health and Medical Research, and the University of Paris-Saclay in Villejuif, France, and his associates.

The researchers used an algorithmic tool to mine the MEDLINE/PubMed/NCBI database using the three key symptoms of PSC – biliary fibrosis, biliary inflammation, and biliary stasis – as their keywords. This approach allowed them to discover the genes and potential pathways related to PSC in published research text or in clinical, animal, and cellular models.

The researchers initially found 525 genes linked to PSC and then compared them to RNA data from liver biopsies taken from patients with liver disease from various causes. This process led to a ranking of the 10 best markers of PSC, based on the data-mining method and the genes’ association with one or more of the three PSC symptoms.

At the top of the list is NR1H4, also called FXR, which ranks most highly with biliary fibrosis and biliary stasis. NR1H4 is already a clear target for cholestatic and fatty liver diseases, the authors noted. The other genes, in descending order of relevance, are: ABCB4, ABCB11, TGFB1, IFNL3, PNPLA3, IL6, TLR4, GPBAR1, and IL17A. In addition, complications of PSC were significantly associated with upregulation of TNFRS12A, SOX9, ANXA2, MMP7, and LCN2.

Separately, investigation of the 525 initially identified genes in mouse models of PSC revealed that NR0B2 is also a key player in the pathogenesis of PSC.

"NR0B2 was upregulated in PSC livers independent of gender, age, and body mass index,” the authors reported. “Importantly, it was not dependent on the severity of PSC in the prognostic cohort, suggesting that this may be an early event during the disease.”

The researchers also found a possible pathway explaining the autoimmunity of PSC – the involvement of CD274, also known as the PDL1 immune checkpoint. The authors noted that the PDL1 inhibitor pembrolizumab has previously been reported as a cause of sclerosing cholangitis.

Further, the researchers discovered overexpression of FOXP3 in the livers of patients with PSC. Because FOXP3 determines what T-cell subtypes look like, the finding suggests that an “imbalance between Foxp3þ regulatory T cells and Th17 cells may be involved in IBD and PSC,” they wrote.

Also of note was the overexpression of SOX9 in the livers of patients with PSC whose profiles suggested the worst clinical prognoses.

Finally, the researchers identified three genes as potentially involved in development of cholangiocarcinoma: GSTA3, ID2 (which is overexpressed in biliary tract cancer), and especially TMEM45A, a protein in cells’ Golgi apparatus that is already known to be involved in the development of several other cancers.

The research was funded by the French National Institute of Health and Medical Research. The authors reported no conflicts of interest.

An investigation of genomics data related to primary sclerosing cholangitis (PSC) in published medical literature revealed several genes likely involved in the pathogenesis of this autoimmune diseases, according to a study published in Gastro Hep Advances.

PSC is very rare, with an incidence of 0-1.3 cases per 100,000 people per year. Because up to 80% of patients with PSC also have inflammatory bowel disease (IBD), a link along the gut-liver axis is suspected. So far, scientists have not understood the causes of PSC, the main complications of which include biliary cirrhosis, bacterial cholangitis, and cholangiocarcinoma.

No treatment is currently available for PSC, but the findings of this genomics study suggest several targets that may be worth pursuing, particularly the gene NR0B2.

“The therapeutic targeting of NR0B2 may potentiate that of FXR [farnesoid X receptor] and enable action on early events of the disease and prevent its progression,” wrote Christophe Desterke, PhD, of the Paul-Brousse Hospital, the French National Institute of Health and Medical Research, and the University of Paris-Saclay in Villejuif, France, and his associates.

The researchers used an algorithmic tool to mine the MEDLINE/PubMed/NCBI database using the three key symptoms of PSC – biliary fibrosis, biliary inflammation, and biliary stasis – as their keywords. This approach allowed them to discover the genes and potential pathways related to PSC in published research text or in clinical, animal, and cellular models.

The researchers initially found 525 genes linked to PSC and then compared them to RNA data from liver biopsies taken from patients with liver disease from various causes. This process led to a ranking of the 10 best markers of PSC, based on the data-mining method and the genes’ association with one or more of the three PSC symptoms.

At the top of the list is NR1H4, also called FXR, which ranks most highly with biliary fibrosis and biliary stasis. NR1H4 is already a clear target for cholestatic and fatty liver diseases, the authors noted. The other genes, in descending order of relevance, are: ABCB4, ABCB11, TGFB1, IFNL3, PNPLA3, IL6, TLR4, GPBAR1, and IL17A. In addition, complications of PSC were significantly associated with upregulation of TNFRS12A, SOX9, ANXA2, MMP7, and LCN2.

Separately, investigation of the 525 initially identified genes in mouse models of PSC revealed that NR0B2 is also a key player in the pathogenesis of PSC.

"NR0B2 was upregulated in PSC livers independent of gender, age, and body mass index,” the authors reported. “Importantly, it was not dependent on the severity of PSC in the prognostic cohort, suggesting that this may be an early event during the disease.”

The researchers also found a possible pathway explaining the autoimmunity of PSC – the involvement of CD274, also known as the PDL1 immune checkpoint. The authors noted that the PDL1 inhibitor pembrolizumab has previously been reported as a cause of sclerosing cholangitis.

Further, the researchers discovered overexpression of FOXP3 in the livers of patients with PSC. Because FOXP3 determines what T-cell subtypes look like, the finding suggests that an “imbalance between Foxp3þ regulatory T cells and Th17 cells may be involved in IBD and PSC,” they wrote.

Also of note was the overexpression of SOX9 in the livers of patients with PSC whose profiles suggested the worst clinical prognoses.

Finally, the researchers identified three genes as potentially involved in development of cholangiocarcinoma: GSTA3, ID2 (which is overexpressed in biliary tract cancer), and especially TMEM45A, a protein in cells’ Golgi apparatus that is already known to be involved in the development of several other cancers.

The research was funded by the French National Institute of Health and Medical Research. The authors reported no conflicts of interest.

Pancreatic cancer screening appears to be safe and effective for certain patients with high-risk indications due to genetic susceptibility, according to a prospective multicenter study presented at the annual meeting of the American College of Gastroenterology.

Screening in high-risk patients detected high-risk lesions in 0.8% of patients, which was lower than the typical range found in the literature, at 3%, said Andy Silva-Santisteban, MD, a research fellow at Beth Israel Deaconess Medical Center at Harvard Medical School in Boston.

Pancreatic cancer is the third leading cause of cancer death in the U.S., which is estimated to become the second leading cause by 2030. About 15%-20% of patients are candidates for surgical resection at the time of diagnosis, with survival rates below 10%.

“These statistics have led pancreatic cancer screening to be studied with the goal of detecting earlier stages of the disease to improve survival,” Dr. Silva-Santisteban said. “However, pancreatic cancer screening is not recommended for the general population.”

Pancreatic cancer screening is recommended for patients with increased risk due to genetic susceptibility, yet recent studies have found that screening studies face limitations from factors like small sample sizes, single-center focus, retrospective nature, nonconsecutive accrual of patients, varied inclusion criteria, and use of nonstandardized screening protocols.

To overcome these limitations, Dr. Silva-Santisteban and colleagues conducted a prospective multicenter study of pancreatic cancer screening in consecutive high-risk patients at five centers in the United States between 2020 and 2022, also called the Pancreas Scan Study. Dr. Silva-Santisteban presented results from the first round of enrollment, which was awarded the Outstanding Research Award in the Biliary/Pancreas Category for Trainee.

The research team evaluated the yield (low-, moderate-, and high-risk pancreatic pathology), safety, and outcomes of screening. Low-risk pancreas pathology was categorized as fatty pancreas and chronic pancreatitis-like changes. Intermediate-risk was categorized as branch duct–intraductal papillary mucinous neoplasm or neuroendocrine tumor under 2 cm. High-risk was categorized as main duct–intraductal papillary mucinous neoplasm (MD-IPMN), pancreatic intraepithelial neoplasia grade III (PanIN-III)/dysplasia, neuroendocrine tumor over 2 cm, or pancreatic cancer.

Patients were included if they were 18 years or older and had at least one of the following: BRCA1, BRCA2, or PALB2 plus a family history of pancreatic cancer; Lynch syndrome plus a family history of pancreatic cancer; Peutz-Jeghers syndrome; familial atypical multiple mole melanoma (FAMMM); ataxia telangiectasia mutated plus family history of pancreatic cancer; hereditary pancreatitis; or familial pancreatic cancer (FPC) syndrome.

Pancreatic cancer screening appears to be safe and effective for certain patients with high-risk indications due to genetic susceptibility, according to a prospective multicenter study presented at the annual meeting of the American College of Gastroenterology.

Screening in high-risk patients detected high-risk lesions in 0.8% of patients, which was lower than the typical range found in the literature, at 3%, said Andy Silva-Santisteban, MD, a research fellow at Beth Israel Deaconess Medical Center at Harvard Medical School in Boston.

Pancreatic cancer is the third leading cause of cancer death in the U.S., which is estimated to become the second leading cause by 2030. About 15%-20% of patients are candidates for surgical resection at the time of diagnosis, with survival rates below 10%.

“These statistics have led pancreatic cancer screening to be studied with the goal of detecting earlier stages of the disease to improve survival,” Dr. Silva-Santisteban said. “However, pancreatic cancer screening is not recommended for the general population.”

Pancreatic cancer screening is recommended for patients with increased risk due to genetic susceptibility, yet recent studies have found that screening studies face limitations from factors like small sample sizes, single-center focus, retrospective nature, nonconsecutive accrual of patients, varied inclusion criteria, and use of nonstandardized screening protocols.

To overcome these limitations, Dr. Silva-Santisteban and colleagues conducted a prospective multicenter study of pancreatic cancer screening in consecutive high-risk patients at five centers in the United States between 2020 and 2022, also called the Pancreas Scan Study. Dr. Silva-Santisteban presented results from the first round of enrollment, which was awarded the Outstanding Research Award in the Biliary/Pancreas Category for Trainee.

The research team evaluated the yield (low-, moderate-, and high-risk pancreatic pathology), safety, and outcomes of screening. Low-risk pancreas pathology was categorized as fatty pancreas and chronic pancreatitis-like changes. Intermediate-risk was categorized as branch duct–intraductal papillary mucinous neoplasm or neuroendocrine tumor under 2 cm. High-risk was categorized as main duct–intraductal papillary mucinous neoplasm (MD-IPMN), pancreatic intraepithelial neoplasia grade III (PanIN-III)/dysplasia, neuroendocrine tumor over 2 cm, or pancreatic cancer.

Patients were included if they were 18 years or older and had at least one of the following: BRCA1, BRCA2, or PALB2 plus a family history of pancreatic cancer; Lynch syndrome plus a family history of pancreatic cancer; Peutz-Jeghers syndrome; familial atypical multiple mole melanoma (FAMMM); ataxia telangiectasia mutated plus family history of pancreatic cancer; hereditary pancreatitis; or familial pancreatic cancer (FPC) syndrome.

Pancreatic cancer screening appears to be safe and effective for certain patients with high-risk indications due to genetic susceptibility, according to a prospective multicenter study presented at the annual meeting of the American College of Gastroenterology.

Screening in high-risk patients detected high-risk lesions in 0.8% of patients, which was lower than the typical range found in the literature, at 3%, said Andy Silva-Santisteban, MD, a research fellow at Beth Israel Deaconess Medical Center at Harvard Medical School in Boston.

Pancreatic cancer is the third leading cause of cancer death in the U.S., which is estimated to become the second leading cause by 2030. About 15%-20% of patients are candidates for surgical resection at the time of diagnosis, with survival rates below 10%.

“These statistics have led pancreatic cancer screening to be studied with the goal of detecting earlier stages of the disease to improve survival,” Dr. Silva-Santisteban said. “However, pancreatic cancer screening is not recommended for the general population.”

Pancreatic cancer screening is recommended for patients with increased risk due to genetic susceptibility, yet recent studies have found that screening studies face limitations from factors like small sample sizes, single-center focus, retrospective nature, nonconsecutive accrual of patients, varied inclusion criteria, and use of nonstandardized screening protocols.

To overcome these limitations, Dr. Silva-Santisteban and colleagues conducted a prospective multicenter study of pancreatic cancer screening in consecutive high-risk patients at five centers in the United States between 2020 and 2022, also called the Pancreas Scan Study. Dr. Silva-Santisteban presented results from the first round of enrollment, which was awarded the Outstanding Research Award in the Biliary/Pancreas Category for Trainee.

The research team evaluated the yield (low-, moderate-, and high-risk pancreatic pathology), safety, and outcomes of screening. Low-risk pancreas pathology was categorized as fatty pancreas and chronic pancreatitis-like changes. Intermediate-risk was categorized as branch duct–intraductal papillary mucinous neoplasm or neuroendocrine tumor under 2 cm. High-risk was categorized as main duct–intraductal papillary mucinous neoplasm (MD-IPMN), pancreatic intraepithelial neoplasia grade III (PanIN-III)/dysplasia, neuroendocrine tumor over 2 cm, or pancreatic cancer.

Patients were included if they were 18 years or older and had at least one of the following: BRCA1, BRCA2, or PALB2 plus a family history of pancreatic cancer; Lynch syndrome plus a family history of pancreatic cancer; Peutz-Jeghers syndrome; familial atypical multiple mole melanoma (FAMMM); ataxia telangiectasia mutated plus family history of pancreatic cancer; hereditary pancreatitis; or familial pancreatic cancer (FPC) syndrome.

Signs of pancreatic cancer that were missed on earlier imaging scans represent a “huge window of lost opportunity,” say United Kingdom researchers who report a novel analysis. 

The study set out to identify the incidence and root causes of missed pancreatic cancer diagnoses on CT and MRI scans, the investigators explained at the United European Gastroenterology Week 2022.

The team studied 600 pancreatic cancer cases, including 46 cases (7.7%) categorized as postimaging pancreatic cancer (PIPC) – cases not detected on imaging performed 3-18 months prior to diagnosis.

They also reviewed 46 CT scans and 4 MRI scans performed in PIPC patients.

The detailed analysis showed that 36% of cases of PIPC were potentially avoidable, reported first author Nosheen Umar, MD, a gastroenterology research fellow at the University of Birmingham (England).

In 10% of PIPC patients, imaging signs associated with pancreatic cancer, such as dilated bile or pancreatic ducts, were not recognized as such and were not investigated further. In 26% of scans, the signs of a mass lesion were not picked up by the radiologist.

The findings are notable as the time window for curative PC surgery is often short, and missing the diagnosis on cross-sectional imaging can result in worse clinical outcomes for patients already dealing with a challenging cancer that has generally poor outcomes, Dr. Umar said in an interview.

In fact, pancreatic cancer has the lowest survival rate of all cancers in Europe, the UEG noted in a press release. Life expectancy at the time of diagnosis is just 4.6 months, and 5-year survival is less than 10%, Dr. Umar said.

Pancreatic cancer causes 95,000 deaths in the European Union each year, the UEG noted, adding that by 2035 the number of cases is predicted to rise by almost 40%.
 

Details of missed imaging signs

The aim of this study was to establish the most plausible explanations for missed imaging signs of PC, Dr. Umar explained, adding that early diagnosis is vitally important for offering patients the best chance of survival.

Cases analyzed for the study were identified from electronic medical records of adults diagnosed with PC between 2016 and 2021 at two National Health Service providers. An algorithm was developed to categorize PIPC and assess potential causes of the missed diagnoses.

The PIPC cases were categorized by type:

• Type 1 – A focal lesion on previous imaging reported in the same pancreatic segment as PIPC (0% of cases)
• Type 2 – Imaging changes that can be associated with PC reported on previous imaging (20% of cases)
• Type 3 – No lesion or imaging changes that can be associated with PC reported on previous imaging in the same pancreatic segment as PIPC, but lesion or imaging changes noted on review after PIPC diagnosis (26% of cases)
• Type 4 – No lesion or imaging changes that can be associated with PC reported on previous imaging in the same pancreatic segment as PIPC and no lesion or imaging changes on review after PIPC diagnosis (54% of cases)

“We hope this study will raise awareness of the issue of postimaging pancreatic cancer and common reasons why pancreatic cancer can be initially missed,” Dr. Umar stated in the UEG press release. “This will help to standardize future studies of this issue and guide quality improvement efforts so we can increase the likelihood of an early diagnosis of pancreatic cancer, increase the chances of patient survival and, ultimately, save lives.”

The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Signs of pancreatic cancer that were missed on earlier imaging scans represent a “huge window of lost opportunity,” say United Kingdom researchers who report a novel analysis. 

The study set out to identify the incidence and root causes of missed pancreatic cancer diagnoses on CT and MRI scans, the investigators explained at the United European Gastroenterology Week 2022.

The team studied 600 pancreatic cancer cases, including 46 cases (7.7%) categorized as postimaging pancreatic cancer (PIPC) – cases not detected on imaging performed 3-18 months prior to diagnosis.

They also reviewed 46 CT scans and 4 MRI scans performed in PIPC patients.

The detailed analysis showed that 36% of cases of PIPC were potentially avoidable, reported first author Nosheen Umar, MD, a gastroenterology research fellow at the University of Birmingham (England).

In 10% of PIPC patients, imaging signs associated with pancreatic cancer, such as dilated bile or pancreatic ducts, were not recognized as such and were not investigated further. In 26% of scans, the signs of a mass lesion were not picked up by the radiologist.

The findings are notable as the time window for curative PC surgery is often short, and missing the diagnosis on cross-sectional imaging can result in worse clinical outcomes for patients already dealing with a challenging cancer that has generally poor outcomes, Dr. Umar said in an interview.

In fact, pancreatic cancer has the lowest survival rate of all cancers in Europe, the UEG noted in a press release. Life expectancy at the time of diagnosis is just 4.6 months, and 5-year survival is less than 10%, Dr. Umar said.

Pancreatic cancer causes 95,000 deaths in the European Union each year, the UEG noted, adding that by 2035 the number of cases is predicted to rise by almost 40%.
 

Details of missed imaging signs

The aim of this study was to establish the most plausible explanations for missed imaging signs of PC, Dr. Umar explained, adding that early diagnosis is vitally important for offering patients the best chance of survival.

Cases analyzed for the study were identified from electronic medical records of adults diagnosed with PC between 2016 and 2021 at two National Health Service providers. An algorithm was developed to categorize PIPC and assess potential causes of the missed diagnoses.

The PIPC cases were categorized by type:

• Type 1 – A focal lesion on previous imaging reported in the same pancreatic segment as PIPC (0% of cases)
• Type 2 – Imaging changes that can be associated with PC reported on previous imaging (20% of cases)
• Type 3 – No lesion or imaging changes that can be associated with PC reported on previous imaging in the same pancreatic segment as PIPC, but lesion or imaging changes noted on review after PIPC diagnosis (26% of cases)
• Type 4 – No lesion or imaging changes that can be associated with PC reported on previous imaging in the same pancreatic segment as PIPC and no lesion or imaging changes on review after PIPC diagnosis (54% of cases)

“We hope this study will raise awareness of the issue of postimaging pancreatic cancer and common reasons why pancreatic cancer can be initially missed,” Dr. Umar stated in the UEG press release. “This will help to standardize future studies of this issue and guide quality improvement efforts so we can increase the likelihood of an early diagnosis of pancreatic cancer, increase the chances of patient survival and, ultimately, save lives.”

The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Signs of pancreatic cancer that were missed on earlier imaging scans represent a “huge window of lost opportunity,” say United Kingdom researchers who report a novel analysis. 

The study set out to identify the incidence and root causes of missed pancreatic cancer diagnoses on CT and MRI scans, the investigators explained at the United European Gastroenterology Week 2022.

The team studied 600 pancreatic cancer cases, including 46 cases (7.7%) categorized as postimaging pancreatic cancer (PIPC) – cases not detected on imaging performed 3-18 months prior to diagnosis.

They also reviewed 46 CT scans and 4 MRI scans performed in PIPC patients.

The detailed analysis showed that 36% of cases of PIPC were potentially avoidable, reported first author Nosheen Umar, MD, a gastroenterology research fellow at the University of Birmingham (England).

In 10% of PIPC patients, imaging signs associated with pancreatic cancer, such as dilated bile or pancreatic ducts, were not recognized as such and were not investigated further. In 26% of scans, the signs of a mass lesion were not picked up by the radiologist.

The findings are notable as the time window for curative PC surgery is often short, and missing the diagnosis on cross-sectional imaging can result in worse clinical outcomes for patients already dealing with a challenging cancer that has generally poor outcomes, Dr. Umar said in an interview.

In fact, pancreatic cancer has the lowest survival rate of all cancers in Europe, the UEG noted in a press release. Life expectancy at the time of diagnosis is just 4.6 months, and 5-year survival is less than 10%, Dr. Umar said.

Pancreatic cancer causes 95,000 deaths in the European Union each year, the UEG noted, adding that by 2035 the number of cases is predicted to rise by almost 40%.
 

Details of missed imaging signs

The aim of this study was to establish the most plausible explanations for missed imaging signs of PC, Dr. Umar explained, adding that early diagnosis is vitally important for offering patients the best chance of survival.

Cases analyzed for the study were identified from electronic medical records of adults diagnosed with PC between 2016 and 2021 at two National Health Service providers. An algorithm was developed to categorize PIPC and assess potential causes of the missed diagnoses.

The PIPC cases were categorized by type:

• Type 1 – A focal lesion on previous imaging reported in the same pancreatic segment as PIPC (0% of cases)
• Type 2 – Imaging changes that can be associated with PC reported on previous imaging (20% of cases)
• Type 3 – No lesion or imaging changes that can be associated with PC reported on previous imaging in the same pancreatic segment as PIPC, but lesion or imaging changes noted on review after PIPC diagnosis (26% of cases)
• Type 4 – No lesion or imaging changes that can be associated with PC reported on previous imaging in the same pancreatic segment as PIPC and no lesion or imaging changes on review after PIPC diagnosis (54% of cases)

“We hope this study will raise awareness of the issue of postimaging pancreatic cancer and common reasons why pancreatic cancer can be initially missed,” Dr. Umar stated in the UEG press release. “This will help to standardize future studies of this issue and guide quality improvement efforts so we can increase the likelihood of an early diagnosis of pancreatic cancer, increase the chances of patient survival and, ultimately, save lives.”

The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A real-world analysis in the United Kingdom found that a fully covered metal stent is safe and effective at controlling anastomotic strictures (AS) following liver transplants.

Biliary AS occurs in an estimated 5%-32% of patients following a liver transplant. Generally, these have been managed by insertion of side-by-side plastic stents to remodel the stricture, but this often required multiple procedures to resolve the problem. More recently, transpapillary fully covered self-expanding metallic stents (FCSEMSs) have been introduced and they appear to perform equivalently to their plastic counterparts while requiring fewer procedures.

The new study “is yet another large experience demonstrating that use of fully covered metal stents for treating anastomotic biliary strictures is highly effective and also cost-effective because you really decrease the number of ERCPs [endoscopic retrograde cholangiopancreatographies] that are required to treat an anastomotic stricture,” said Vladimir Kushnir, MD, who was asked to comment on the study, which was published in Therapeutic Advances in Gastroenterology.

The researchers analyzed retrospective data from 162 consecutive patients who underwent ERCP with intraductal self-expanding metal stent (IDSEMS) insertion at nine tertiary centers. The procedures employed the Kaffes (Taewoong Niti-S) biliary covered stent, which is not available in the United States. Unlike conventional FCSEMSs, the device does not have to traverse the papilla. It is also shorter and includes an antimigration waist and removal wires that may reduce the risk of silent migration. Small case series suggested efficacy in the treatment of post–liver transplant AS.

There were 176 episodes of stent insertion among the 162 included patients; 62% of patients were male, and the median age at transplant was 54 years. Etiologies included hepatocellular carcinoma (22%), alcohol-related liver disease (18%), and nonalcoholic fatty liver disease (12%). The median time to development of a stricture was 24.9 weeks. Among all patients, 35% had previously received stents; 75% of those were plastic stents.

Overall, 10% of patients experienced stricture recurrence at a median interval of 19 weeks following stent removal. Median stent emplacement was 15 weeks, and 81% of patients had a resolution of their strictures.

Dr. Kushnir, from Washington University in St. Louis, highlighted the differences between the stent used in the study and those currently available in the United States. “This type of stent is a self-expanding metal stent that’s covered, but what’s different about it is that it’s designed to go completely within the bile duct, whereas a traditional fully covered metal stent traverses the major duodenal papilla.”

Despite those differences, he believes that the study can inform current practice in the United States. “In situations where you’re faced with a question of whether or not you leave multiple plastic stents in, or you put a full metal stent in that’s going to be fully within the bile duct, I think this data does provide some reassurance. If you’re using one of the traditional stents that we have in the United States and putting it fully within the bile duct, you do need to be prepared to have a little bit of a harder time removing the stent when the time comes for the removal procedure, which could require cholangioscopy. But this does provide some evidence to back up the practice of using fully covered metal stents fully within the bile duct to remediate anastomotic strictures that may be just a little too high up to treat traditionally with a stent that remains transpapillary,” said Dr. Kushnir.

The study also suggests an avenue for further research. “What’s also interesting about this study is that they only left the stents in for 3 months. In most clinical trials, where we’ve used fully covered metal stents for treating anastomotic biliary strictures, you leave the stent in from anywhere from 6 to 12 months. So with only 3 months dwell time they were able to get pretty impressive results, at least in the short term, in a retrospective study, so it does raise the question of should we be evaluating shorter dwell times for stents in treating anastomotic strictures when we’re using a fully covered metal stent that’s a larger diameter?” said Dr. Kushnir.

The authors noted some limitations, such as the retrospective design, small sample size, and lack of control group. They also noted that the multicenter design may have introduced heterogeneity in patient management and follow-up.

“In conclusion, IDSEMS appear to be safe and highly efficacious in the management of [post–liver transplant] AS,” concluded the authors. “Long-term outcomes appear good with low rates of AS recurrence.”

The authors declare no conflicts of interest. Dr. Kushnir is a consultant for ConMed and Boston Scientific.

A real-world analysis in the United Kingdom found that a fully covered metal stent is safe and effective at controlling anastomotic strictures (AS) following liver transplants.

Biliary AS occurs in an estimated 5%-32% of patients following a liver transplant. Generally, these have been managed by insertion of side-by-side plastic stents to remodel the stricture, but this often required multiple procedures to resolve the problem. More recently, transpapillary fully covered self-expanding metallic stents (FCSEMSs) have been introduced and they appear to perform equivalently to their plastic counterparts while requiring fewer procedures.

The new study “is yet another large experience demonstrating that use of fully covered metal stents for treating anastomotic biliary strictures is highly effective and also cost-effective because you really decrease the number of ERCPs [endoscopic retrograde cholangiopancreatographies] that are required to treat an anastomotic stricture,” said Vladimir Kushnir, MD, who was asked to comment on the study, which was published in Therapeutic Advances in Gastroenterology.

The researchers analyzed retrospective data from 162 consecutive patients who underwent ERCP with intraductal self-expanding metal stent (IDSEMS) insertion at nine tertiary centers. The procedures employed the Kaffes (Taewoong Niti-S) biliary covered stent, which is not available in the United States. Unlike conventional FCSEMSs, the device does not have to traverse the papilla. It is also shorter and includes an antimigration waist and removal wires that may reduce the risk of silent migration. Small case series suggested efficacy in the treatment of post–liver transplant AS.

There were 176 episodes of stent insertion among the 162 included patients; 62% of patients were male, and the median age at transplant was 54 years. Etiologies included hepatocellular carcinoma (22%), alcohol-related liver disease (18%), and nonalcoholic fatty liver disease (12%). The median time to development of a stricture was 24.9 weeks. Among all patients, 35% had previously received stents; 75% of those were plastic stents.

Overall, 10% of patients experienced stricture recurrence at a median interval of 19 weeks following stent removal. Median stent emplacement was 15 weeks, and 81% of patients had a resolution of their strictures.

Dr. Kushnir, from Washington University in St. Louis, highlighted the differences between the stent used in the study and those currently available in the United States. “This type of stent is a self-expanding metal stent that’s covered, but what’s different about it is that it’s designed to go completely within the bile duct, whereas a traditional fully covered metal stent traverses the major duodenal papilla.”

Despite those differences, he believes that the study can inform current practice in the United States. “In situations where you’re faced with a question of whether or not you leave multiple plastic stents in, or you put a full metal stent in that’s going to be fully within the bile duct, I think this data does provide some reassurance. If you’re using one of the traditional stents that we have in the United States and putting it fully within the bile duct, you do need to be prepared to have a little bit of a harder time removing the stent when the time comes for the removal procedure, which could require cholangioscopy. But this does provide some evidence to back up the practice of using fully covered metal stents fully within the bile duct to remediate anastomotic strictures that may be just a little too high up to treat traditionally with a stent that remains transpapillary,” said Dr. Kushnir.

The study also suggests an avenue for further research. “What’s also interesting about this study is that they only left the stents in for 3 months. In most clinical trials, where we’ve used fully covered metal stents for treating anastomotic biliary strictures, you leave the stent in from anywhere from 6 to 12 months. So with only 3 months dwell time they were able to get pretty impressive results, at least in the short term, in a retrospective study, so it does raise the question of should we be evaluating shorter dwell times for stents in treating anastomotic strictures when we’re using a fully covered metal stent that’s a larger diameter?” said Dr. Kushnir.

The authors noted some limitations, such as the retrospective design, small sample size, and lack of control group. They also noted that the multicenter design may have introduced heterogeneity in patient management and follow-up.

“In conclusion, IDSEMS appear to be safe and highly efficacious in the management of [post–liver transplant] AS,” concluded the authors. “Long-term outcomes appear good with low rates of AS recurrence.”

The authors declare no conflicts of interest. Dr. Kushnir is a consultant for ConMed and Boston Scientific.

A real-world analysis in the United Kingdom found that a fully covered metal stent is safe and effective at controlling anastomotic strictures (AS) following liver transplants.

Biliary AS occurs in an estimated 5%-32% of patients following a liver transplant. Generally, these have been managed by insertion of side-by-side plastic stents to remodel the stricture, but this often required multiple procedures to resolve the problem. More recently, transpapillary fully covered self-expanding metallic stents (FCSEMSs) have been introduced and they appear to perform equivalently to their plastic counterparts while requiring fewer procedures.

The new study “is yet another large experience demonstrating that use of fully covered metal stents for treating anastomotic biliary strictures is highly effective and also cost-effective because you really decrease the number of ERCPs [endoscopic retrograde cholangiopancreatographies] that are required to treat an anastomotic stricture,” said Vladimir Kushnir, MD, who was asked to comment on the study, which was published in Therapeutic Advances in Gastroenterology.

The researchers analyzed retrospective data from 162 consecutive patients who underwent ERCP with intraductal self-expanding metal stent (IDSEMS) insertion at nine tertiary centers. The procedures employed the Kaffes (Taewoong Niti-S) biliary covered stent, which is not available in the United States. Unlike conventional FCSEMSs, the device does not have to traverse the papilla. It is also shorter and includes an antimigration waist and removal wires that may reduce the risk of silent migration. Small case series suggested efficacy in the treatment of post–liver transplant AS.

There were 176 episodes of stent insertion among the 162 included patients; 62% of patients were male, and the median age at transplant was 54 years. Etiologies included hepatocellular carcinoma (22%), alcohol-related liver disease (18%), and nonalcoholic fatty liver disease (12%). The median time to development of a stricture was 24.9 weeks. Among all patients, 35% had previously received stents; 75% of those were plastic stents.

Overall, 10% of patients experienced stricture recurrence at a median interval of 19 weeks following stent removal. Median stent emplacement was 15 weeks, and 81% of patients had a resolution of their strictures.

Dr. Kushnir, from Washington University in St. Louis, highlighted the differences between the stent used in the study and those currently available in the United States. “This type of stent is a self-expanding metal stent that’s covered, but what’s different about it is that it’s designed to go completely within the bile duct, whereas a traditional fully covered metal stent traverses the major duodenal papilla.”

Despite those differences, he believes that the study can inform current practice in the United States. “In situations where you’re faced with a question of whether or not you leave multiple plastic stents in, or you put a full metal stent in that’s going to be fully within the bile duct, I think this data does provide some reassurance. If you’re using one of the traditional stents that we have in the United States and putting it fully within the bile duct, you do need to be prepared to have a little bit of a harder time removing the stent when the time comes for the removal procedure, which could require cholangioscopy. But this does provide some evidence to back up the practice of using fully covered metal stents fully within the bile duct to remediate anastomotic strictures that may be just a little too high up to treat traditionally with a stent that remains transpapillary,” said Dr. Kushnir.

The study also suggests an avenue for further research. “What’s also interesting about this study is that they only left the stents in for 3 months. In most clinical trials, where we’ve used fully covered metal stents for treating anastomotic biliary strictures, you leave the stent in from anywhere from 6 to 12 months. So with only 3 months dwell time they were able to get pretty impressive results, at least in the short term, in a retrospective study, so it does raise the question of should we be evaluating shorter dwell times for stents in treating anastomotic strictures when we’re using a fully covered metal stent that’s a larger diameter?” said Dr. Kushnir.

The authors noted some limitations, such as the retrospective design, small sample size, and lack of control group. They also noted that the multicenter design may have introduced heterogeneity in patient management and follow-up.

“In conclusion, IDSEMS appear to be safe and highly efficacious in the management of [post–liver transplant] AS,” concluded the authors. “Long-term outcomes appear good with low rates of AS recurrence.”

The authors declare no conflicts of interest. Dr. Kushnir is a consultant for ConMed and Boston Scientific.