DDW 2015

Dr. Lin Chang at the University of California, Los Angeles, discussed how to work-up and manage functional abdominal pain. She reviewed a diagnostic algorithm that is evidence based and uses characteristics of the abdominal pain, coexisting warning signs, and a diagnostic work-up. A patient must be diagnosed with functional abdominal pain only after careful medical history, physical examination, and adequate consideration of competing etiologies.

Physical examination can be helpful in differentiating abdominal wall pain from that of visceral pain (Carnett’s sign) although some patients with functional abdominal pain may exhibit positive Carnett’s sign. Managing a patient with suspected functional abdominal pain includes careful attention to warning signs for organic disease (for example, unintended weight loss, hematochezia, abnormal labs, fever, or family history of serious GI disorders), avoiding unnecessary diagnostic testing, consideration of mental health consultation and pharmacotherapy as appropriate.

Dr. Chang reviewed the role of various pharmacologic agents for irritable bowel syndrome (IBS) with diarrhea (alosetron, rifaximin, and loperamide), IBS with constipation (linaclotide, lubiprostone, and polyethylene glycol) and agents such antispasmodics, tricyclic antidepressants, and SSRIs (reviewed extensively in the AGA Technical Review and Guidelines for Pharmacotherapy for IBS published in Gastroenterology. 2014 Nov;147[5]:1149-72.e2). It is important to establish a strong patient-provider relationship and to incorporate behavioral therapies into management of patients with recurrent or chronic functional abdominal pain.

Dr. Peter Gibson at Monash University in Melbourne discussed non–celiac gluten sensitivity and low-FODMAP diet in managing food sensitivity and functional bowel disorders. He pointed out that recent dietary strategies have changed from patient-initiated, whole-food strategies to avoiding specific dietary components such as FODMAPs and gluten and wheat products. FODMAPS (fermentable oligo-, di-, and monosaccharides and polyols) are foods that are generally high in fructose, lactose, oligosaccharides (e.g., beans, onions, garlic, complex carbohydrates) and polyols (e.g., mushrooms). FODMAPs are generally osmotic and lead to fermentation and diarrhea, bloating, and flatulence. General principles in offering a low-FODMAP diet are the selection of appropriate patients; correct education about FODMAP diets, preferably by a trained dietitian; and a step-down approach in which a strict diet is slowly liberalized. Dr. Gibson pointed out that there are a subset of IBS patients who are gluten sensitive but recent data suggest that wheat protein sensitivity may not be as common as it has been suggested and, in fact, FODMAPs may indeed be the major inducers of symptoms in individuals with supposed wheat intolerance. The potential risks of dietary manipulation such as creation of a dietary cripple or induction of an eating disorder should be kept in mind.

Dr. Anna Mae Diehl at Duke University Medical Center in Durham, N.C., spoke about the diagnosis, role of the microbiome, and the treatment of nonalcoholic fatty liver disease (NAFLD). It was pointed out that most patients with NAFLD have benign progression although individuals with nonalcoholic steatohepatitis (NASH), especially those with significant fibrosis, are at risk for developing cirrhosis, liver failure, and liver cancer. Therapeutic investigations undertaken to date have not sufficiently focused on improving fibrosis although several ongoing clinical trials are directed at this goal. Gut microbiome might be a new NAFLD diagnostic/therapeutic target because several recent animal studies have shown that gut microbiome may play a role in conferring susceptibility to liver injury, fibrosis, and cancer.

Dr. Lawrence J. Brandt at Albert Einstein College of Medicine, New York, gave an update on fecal microbiota therapy (FMT). He highlighted that FMT has historic roots going back to the 4^th century when Ge Hong described use of human fecal suspension to treat food poisoning or severe diarrhea. He made it clear that FMT should be offered only to those with recurrent Clostridium difficile infections (CDI), meeting selected criteria such as severe illness and prior treatment failures. The protocol for FMT in recurrent CDI includes careful selection of donor (may range from any healthy person, universal donor, or stool-bank product) and testing stool and blood of potential donors for any transmittable agents. A recent systematic review showed that the success rate for FMT in individuals with CDI is generally quite high (greater than 80%) but it may depend on the site of FMT – for example, if FMT is administered to duodenum/jejunum, the success rate is 86%, whereas if it is delivered to right colon/cecum, then the success rate can be as high as 93%. He highlighted the efficacy of FMT in severe, complicated CDI, which generally carries high morbidity and mortality. Practitioners offering FMT should carefully review the FDA guidance that was issued in March 2014. He noted that long-term consequences of FMT are not well understood and thus, risks versus benefits of FMT on a patient-by-patient basis must be carefully weighed.

Dr. Naga P. Chalasani is the David W. Crabb Professor and director of the division of gastroenterology and hepatology, Indiana University, Indianapolis. He has consulting agreements and receives research support from several pharmaceutical companies but none represent a conflict of interest for this activity.

This is a summary provided by the moderator of one of the spring postgraduate course sessions held at DDW 2015.

Dr. Lin Chang at the University of California, Los Angeles, discussed how to work-up and manage functional abdominal pain. She reviewed a diagnostic algorithm that is evidence based and uses characteristics of the abdominal pain, coexisting warning signs, and a diagnostic work-up. A patient must be diagnosed with functional abdominal pain only after careful medical history, physical examination, and adequate consideration of competing etiologies.

Physical examination can be helpful in differentiating abdominal wall pain from that of visceral pain (Carnett’s sign) although some patients with functional abdominal pain may exhibit positive Carnett’s sign. Managing a patient with suspected functional abdominal pain includes careful attention to warning signs for organic disease (for example, unintended weight loss, hematochezia, abnormal labs, fever, or family history of serious GI disorders), avoiding unnecessary diagnostic testing, consideration of mental health consultation and pharmacotherapy as appropriate.

Dr. Chang reviewed the role of various pharmacologic agents for irritable bowel syndrome (IBS) with diarrhea (alosetron, rifaximin, and loperamide), IBS with constipation (linaclotide, lubiprostone, and polyethylene glycol) and agents such antispasmodics, tricyclic antidepressants, and SSRIs (reviewed extensively in the AGA Technical Review and Guidelines for Pharmacotherapy for IBS published in Gastroenterology. 2014 Nov;147[5]:1149-72.e2). It is important to establish a strong patient-provider relationship and to incorporate behavioral therapies into management of patients with recurrent or chronic functional abdominal pain.

Dr. Peter Gibson at Monash University in Melbourne discussed non–celiac gluten sensitivity and low-FODMAP diet in managing food sensitivity and functional bowel disorders. He pointed out that recent dietary strategies have changed from patient-initiated, whole-food strategies to avoiding specific dietary components such as FODMAPs and gluten and wheat products. FODMAPS (fermentable oligo-, di-, and monosaccharides and polyols) are foods that are generally high in fructose, lactose, oligosaccharides (e.g., beans, onions, garlic, complex carbohydrates) and polyols (e.g., mushrooms). FODMAPs are generally osmotic and lead to fermentation and diarrhea, bloating, and flatulence. General principles in offering a low-FODMAP diet are the selection of appropriate patients; correct education about FODMAP diets, preferably by a trained dietitian; and a step-down approach in which a strict diet is slowly liberalized. Dr. Gibson pointed out that there are a subset of IBS patients who are gluten sensitive but recent data suggest that wheat protein sensitivity may not be as common as it has been suggested and, in fact, FODMAPs may indeed be the major inducers of symptoms in individuals with supposed wheat intolerance. The potential risks of dietary manipulation such as creation of a dietary cripple or induction of an eating disorder should be kept in mind.

Dr. Anna Mae Diehl at Duke University Medical Center in Durham, N.C., spoke about the diagnosis, role of the microbiome, and the treatment of nonalcoholic fatty liver disease (NAFLD). It was pointed out that most patients with NAFLD have benign progression although individuals with nonalcoholic steatohepatitis (NASH), especially those with significant fibrosis, are at risk for developing cirrhosis, liver failure, and liver cancer. Therapeutic investigations undertaken to date have not sufficiently focused on improving fibrosis although several ongoing clinical trials are directed at this goal. Gut microbiome might be a new NAFLD diagnostic/therapeutic target because several recent animal studies have shown that gut microbiome may play a role in conferring susceptibility to liver injury, fibrosis, and cancer.

Dr. Lawrence J. Brandt at Albert Einstein College of Medicine, New York, gave an update on fecal microbiota therapy (FMT). He highlighted that FMT has historic roots going back to the 4^th century when Ge Hong described use of human fecal suspension to treat food poisoning or severe diarrhea. He made it clear that FMT should be offered only to those with recurrent Clostridium difficile infections (CDI), meeting selected criteria such as severe illness and prior treatment failures. The protocol for FMT in recurrent CDI includes careful selection of donor (may range from any healthy person, universal donor, or stool-bank product) and testing stool and blood of potential donors for any transmittable agents. A recent systematic review showed that the success rate for FMT in individuals with CDI is generally quite high (greater than 80%) but it may depend on the site of FMT – for example, if FMT is administered to duodenum/jejunum, the success rate is 86%, whereas if it is delivered to right colon/cecum, then the success rate can be as high as 93%. He highlighted the efficacy of FMT in severe, complicated CDI, which generally carries high morbidity and mortality. Practitioners offering FMT should carefully review the FDA guidance that was issued in March 2014. He noted that long-term consequences of FMT are not well understood and thus, risks versus benefits of FMT on a patient-by-patient basis must be carefully weighed.

Dr. Naga P. Chalasani is the David W. Crabb Professor and director of the division of gastroenterology and hepatology, Indiana University, Indianapolis. He has consulting agreements and receives research support from several pharmaceutical companies but none represent a conflict of interest for this activity.

This is a summary provided by the moderator of one of the spring postgraduate course sessions held at DDW 2015.

Dr. Lin Chang at the University of California, Los Angeles, discussed how to work-up and manage functional abdominal pain. She reviewed a diagnostic algorithm that is evidence based and uses characteristics of the abdominal pain, coexisting warning signs, and a diagnostic work-up. A patient must be diagnosed with functional abdominal pain only after careful medical history, physical examination, and adequate consideration of competing etiologies.

Physical examination can be helpful in differentiating abdominal wall pain from that of visceral pain (Carnett’s sign) although some patients with functional abdominal pain may exhibit positive Carnett’s sign. Managing a patient with suspected functional abdominal pain includes careful attention to warning signs for organic disease (for example, unintended weight loss, hematochezia, abnormal labs, fever, or family history of serious GI disorders), avoiding unnecessary diagnostic testing, consideration of mental health consultation and pharmacotherapy as appropriate.

Dr. Chang reviewed the role of various pharmacologic agents for irritable bowel syndrome (IBS) with diarrhea (alosetron, rifaximin, and loperamide), IBS with constipation (linaclotide, lubiprostone, and polyethylene glycol) and agents such antispasmodics, tricyclic antidepressants, and SSRIs (reviewed extensively in the AGA Technical Review and Guidelines for Pharmacotherapy for IBS published in Gastroenterology. 2014 Nov;147[5]:1149-72.e2). It is important to establish a strong patient-provider relationship and to incorporate behavioral therapies into management of patients with recurrent or chronic functional abdominal pain.

Dr. Peter Gibson at Monash University in Melbourne discussed non–celiac gluten sensitivity and low-FODMAP diet in managing food sensitivity and functional bowel disorders. He pointed out that recent dietary strategies have changed from patient-initiated, whole-food strategies to avoiding specific dietary components such as FODMAPs and gluten and wheat products. FODMAPS (fermentable oligo-, di-, and monosaccharides and polyols) are foods that are generally high in fructose, lactose, oligosaccharides (e.g., beans, onions, garlic, complex carbohydrates) and polyols (e.g., mushrooms). FODMAPs are generally osmotic and lead to fermentation and diarrhea, bloating, and flatulence. General principles in offering a low-FODMAP diet are the selection of appropriate patients; correct education about FODMAP diets, preferably by a trained dietitian; and a step-down approach in which a strict diet is slowly liberalized. Dr. Gibson pointed out that there are a subset of IBS patients who are gluten sensitive but recent data suggest that wheat protein sensitivity may not be as common as it has been suggested and, in fact, FODMAPs may indeed be the major inducers of symptoms in individuals with supposed wheat intolerance. The potential risks of dietary manipulation such as creation of a dietary cripple or induction of an eating disorder should be kept in mind.

Dr. Anna Mae Diehl at Duke University Medical Center in Durham, N.C., spoke about the diagnosis, role of the microbiome, and the treatment of nonalcoholic fatty liver disease (NAFLD). It was pointed out that most patients with NAFLD have benign progression although individuals with nonalcoholic steatohepatitis (NASH), especially those with significant fibrosis, are at risk for developing cirrhosis, liver failure, and liver cancer. Therapeutic investigations undertaken to date have not sufficiently focused on improving fibrosis although several ongoing clinical trials are directed at this goal. Gut microbiome might be a new NAFLD diagnostic/therapeutic target because several recent animal studies have shown that gut microbiome may play a role in conferring susceptibility to liver injury, fibrosis, and cancer.

Dr. Lawrence J. Brandt at Albert Einstein College of Medicine, New York, gave an update on fecal microbiota therapy (FMT). He highlighted that FMT has historic roots going back to the 4^th century when Ge Hong described use of human fecal suspension to treat food poisoning or severe diarrhea. He made it clear that FMT should be offered only to those with recurrent Clostridium difficile infections (CDI), meeting selected criteria such as severe illness and prior treatment failures. The protocol for FMT in recurrent CDI includes careful selection of donor (may range from any healthy person, universal donor, or stool-bank product) and testing stool and blood of potential donors for any transmittable agents. A recent systematic review showed that the success rate for FMT in individuals with CDI is generally quite high (greater than 80%) but it may depend on the site of FMT – for example, if FMT is administered to duodenum/jejunum, the success rate is 86%, whereas if it is delivered to right colon/cecum, then the success rate can be as high as 93%. He highlighted the efficacy of FMT in severe, complicated CDI, which generally carries high morbidity and mortality. Practitioners offering FMT should carefully review the FDA guidance that was issued in March 2014. He noted that long-term consequences of FMT are not well understood and thus, risks versus benefits of FMT on a patient-by-patient basis must be carefully weighed.

Dr. Naga P. Chalasani is the David W. Crabb Professor and director of the division of gastroenterology and hepatology, Indiana University, Indianapolis. He has consulting agreements and receives research support from several pharmaceutical companies but none represent a conflict of interest for this activity.

This is a summary provided by the moderator of one of the spring postgraduate course sessions held at DDW 2015.

Genetics in the context of disease causation refers to gene expression altered by DNA mutations. Epigenetics refers to gene expression altered without DNA mutations, but instead by other cellular mechanisms that will be described here. Together, genetic and epigenetic gene expression determine both physiologic and pathologic cellular processes and functions.

Many areas of gastroenterology are now known to involve these mechanisms as part of disease pathophysiology. The area most investigated in gastroenterology is perhaps colon cancer, which will be used as an example in describing clinically pertinent mechanisms and findings in both genetics and epigenetics.

Inherited DNA mutations of certain genes result in colon cancer susceptibility syndromes. Somatic mutations of many of the same genes are part of colon cancer pathogenesis in common or sporadic cases. Pertinent syndromes include familial adenomatous polyposis (APC gene), Lynch syndrome (mismatch repair genes [MMR]), MUTY-associated polyposis (MUTYH gene), Peutz-Jeghers syndrome (STK11 gene), juvenile polyposis (SMAD4 and BMPR1A genes), Cowden syndrome (PTEN gene), and variant polyposis (POLE, POLD1, and Gremm1 genes). For each of these syndromes, genetic testing is now an accepted part of clinical management for diagnosis and guidance as to who should receive more aggressive screening and surveillance for colon cancer prevention.

Acquired or somatic mutations of the same and other genes are involved in the process of benign to malignant transformation in the colon. Involved genes are often divided into three pathways, although there is much overlap between these pathways.

The first pathway is the chromosomal instability pathway that begins with acquired APC gene mutations of a colonocyte. These mutations are followed by the accumulation of additional mutations as normal cells progress to forming adenomatous polyps and then cancer. Such genes include KRAS, SMAD, TP53, PTEN, PI3KCA, and perhaps others. The second pathway involves acquired mutations of the mismatch repair genes early in the benign to malignant process, with mutations occurring especially in the MLH1 gene. It is called the microsatellite instability pathway. Different genes are then involved through mutation in this pathway to cancer. These include TGF beta, BAX, IGF2R, and others. The third pathway is called CIMP for “CpG island methylation phenotype.” It is actually an epigenetic pathway and involves the accumulation of mutations in yet other genes including MLH1, WRN, p16, RARB2, BRAF, and possibly many others, and gives rise to both adenomatous polyps and sessile serrated polyps.

Clinical relevance of somatic mutations of the genes in these three pathways is already informing clinical practice. Cancers with MMR gene mutations, for example, exhibit a better prognosis than other colon cancers but a decreased responsiveness to fluorouracil drugs. Tumors with KRAS or BRAF mutations have little or no response to EGFR-inhibitor drugs. Many of the genes in which acquired mutations occur are now interrogated as part of stool DNA screening tests.

Epigenetic processes change gene expression without DNA mutation and include three primary categories: DNA methylation, histone and chromatin changes, and microRNA changes.

Half of human genes have promotor regions rich in CpG islands. When methylation occurs in these CpG islands, gene expression is usually inhibited. This is the main mechanism of the CIMP pathway and in turn affects numerous cell functions important to cancer pathogenesis. Histones are proteins around which DNA coils. The proteins with coiled DNA are called chromatin units. Histones have protein tails that repress gene transcription when acetylation and specific methylations occur. Some histone proteins have already been observed to be overexpressed in colon cancer. MicroRNAs are short noncoding RNAs that induce gene repression in up to 30% of genes. Altered MicroRNA expression has been observed in many colon cancer–associated genes, and specific microRNA patterns have characterized certain colon cancers.

Epigenetic cancer markers are only beginning to be understood but are being examined for use in early detection and prognosis, tumor subclassifications, following the effectiveness of chemotherapy, and providing targets of intervention.

In summary, colon cancer genetics has provided genetic testing for inherited syndromes and guides to therapy with acquired mutations, while epigenetic mechanisms have the potential of being important to many areas of cancer diagnosis and treatment.

Dr. Burt is professor of medicine and holder of the Barnes Presidential Endowed Chair in Medicine at the Huntsman Cancer Institute and the University of Utah, Salt Lake City. He has consulted for Myriad Genetics. His comments were made during the ASGE and AGA joint Presidential Plenary at the annual Digestive Disease Week.

Genetics in the context of disease causation refers to gene expression altered by DNA mutations. Epigenetics refers to gene expression altered without DNA mutations, but instead by other cellular mechanisms that will be described here. Together, genetic and epigenetic gene expression determine both physiologic and pathologic cellular processes and functions.

Many areas of gastroenterology are now known to involve these mechanisms as part of disease pathophysiology. The area most investigated in gastroenterology is perhaps colon cancer, which will be used as an example in describing clinically pertinent mechanisms and findings in both genetics and epigenetics.

Inherited DNA mutations of certain genes result in colon cancer susceptibility syndromes. Somatic mutations of many of the same genes are part of colon cancer pathogenesis in common or sporadic cases. Pertinent syndromes include familial adenomatous polyposis (APC gene), Lynch syndrome (mismatch repair genes [MMR]), MUTY-associated polyposis (MUTYH gene), Peutz-Jeghers syndrome (STK11 gene), juvenile polyposis (SMAD4 and BMPR1A genes), Cowden syndrome (PTEN gene), and variant polyposis (POLE, POLD1, and Gremm1 genes). For each of these syndromes, genetic testing is now an accepted part of clinical management for diagnosis and guidance as to who should receive more aggressive screening and surveillance for colon cancer prevention.

Acquired or somatic mutations of the same and other genes are involved in the process of benign to malignant transformation in the colon. Involved genes are often divided into three pathways, although there is much overlap between these pathways.

The first pathway is the chromosomal instability pathway that begins with acquired APC gene mutations of a colonocyte. These mutations are followed by the accumulation of additional mutations as normal cells progress to forming adenomatous polyps and then cancer. Such genes include KRAS, SMAD, TP53, PTEN, PI3KCA, and perhaps others. The second pathway involves acquired mutations of the mismatch repair genes early in the benign to malignant process, with mutations occurring especially in the MLH1 gene. It is called the microsatellite instability pathway. Different genes are then involved through mutation in this pathway to cancer. These include TGF beta, BAX, IGF2R, and others. The third pathway is called CIMP for “CpG island methylation phenotype.” It is actually an epigenetic pathway and involves the accumulation of mutations in yet other genes including MLH1, WRN, p16, RARB2, BRAF, and possibly many others, and gives rise to both adenomatous polyps and sessile serrated polyps.

Clinical relevance of somatic mutations of the genes in these three pathways is already informing clinical practice. Cancers with MMR gene mutations, for example, exhibit a better prognosis than other colon cancers but a decreased responsiveness to fluorouracil drugs. Tumors with KRAS or BRAF mutations have little or no response to EGFR-inhibitor drugs. Many of the genes in which acquired mutations occur are now interrogated as part of stool DNA screening tests.

Epigenetic processes change gene expression without DNA mutation and include three primary categories: DNA methylation, histone and chromatin changes, and microRNA changes.

Half of human genes have promotor regions rich in CpG islands. When methylation occurs in these CpG islands, gene expression is usually inhibited. This is the main mechanism of the CIMP pathway and in turn affects numerous cell functions important to cancer pathogenesis. Histones are proteins around which DNA coils. The proteins with coiled DNA are called chromatin units. Histones have protein tails that repress gene transcription when acetylation and specific methylations occur. Some histone proteins have already been observed to be overexpressed in colon cancer. MicroRNAs are short noncoding RNAs that induce gene repression in up to 30% of genes. Altered MicroRNA expression has been observed in many colon cancer–associated genes, and specific microRNA patterns have characterized certain colon cancers.

Epigenetic cancer markers are only beginning to be understood but are being examined for use in early detection and prognosis, tumor subclassifications, following the effectiveness of chemotherapy, and providing targets of intervention.

In summary, colon cancer genetics has provided genetic testing for inherited syndromes and guides to therapy with acquired mutations, while epigenetic mechanisms have the potential of being important to many areas of cancer diagnosis and treatment.

Dr. Burt is professor of medicine and holder of the Barnes Presidential Endowed Chair in Medicine at the Huntsman Cancer Institute and the University of Utah, Salt Lake City. He has consulted for Myriad Genetics. His comments were made during the ASGE and AGA joint Presidential Plenary at the annual Digestive Disease Week.

Genetics in the context of disease causation refers to gene expression altered by DNA mutations. Epigenetics refers to gene expression altered without DNA mutations, but instead by other cellular mechanisms that will be described here. Together, genetic and epigenetic gene expression determine both physiologic and pathologic cellular processes and functions.

Many areas of gastroenterology are now known to involve these mechanisms as part of disease pathophysiology. The area most investigated in gastroenterology is perhaps colon cancer, which will be used as an example in describing clinically pertinent mechanisms and findings in both genetics and epigenetics.

Inherited DNA mutations of certain genes result in colon cancer susceptibility syndromes. Somatic mutations of many of the same genes are part of colon cancer pathogenesis in common or sporadic cases. Pertinent syndromes include familial adenomatous polyposis (APC gene), Lynch syndrome (mismatch repair genes [MMR]), MUTY-associated polyposis (MUTYH gene), Peutz-Jeghers syndrome (STK11 gene), juvenile polyposis (SMAD4 and BMPR1A genes), Cowden syndrome (PTEN gene), and variant polyposis (POLE, POLD1, and Gremm1 genes). For each of these syndromes, genetic testing is now an accepted part of clinical management for diagnosis and guidance as to who should receive more aggressive screening and surveillance for colon cancer prevention.

Acquired or somatic mutations of the same and other genes are involved in the process of benign to malignant transformation in the colon. Involved genes are often divided into three pathways, although there is much overlap between these pathways.

The first pathway is the chromosomal instability pathway that begins with acquired APC gene mutations of a colonocyte. These mutations are followed by the accumulation of additional mutations as normal cells progress to forming adenomatous polyps and then cancer. Such genes include KRAS, SMAD, TP53, PTEN, PI3KCA, and perhaps others. The second pathway involves acquired mutations of the mismatch repair genes early in the benign to malignant process, with mutations occurring especially in the MLH1 gene. It is called the microsatellite instability pathway. Different genes are then involved through mutation in this pathway to cancer. These include TGF beta, BAX, IGF2R, and others. The third pathway is called CIMP for “CpG island methylation phenotype.” It is actually an epigenetic pathway and involves the accumulation of mutations in yet other genes including MLH1, WRN, p16, RARB2, BRAF, and possibly many others, and gives rise to both adenomatous polyps and sessile serrated polyps.

Clinical relevance of somatic mutations of the genes in these three pathways is already informing clinical practice. Cancers with MMR gene mutations, for example, exhibit a better prognosis than other colon cancers but a decreased responsiveness to fluorouracil drugs. Tumors with KRAS or BRAF mutations have little or no response to EGFR-inhibitor drugs. Many of the genes in which acquired mutations occur are now interrogated as part of stool DNA screening tests.

Epigenetic processes change gene expression without DNA mutation and include three primary categories: DNA methylation, histone and chromatin changes, and microRNA changes.

Half of human genes have promotor regions rich in CpG islands. When methylation occurs in these CpG islands, gene expression is usually inhibited. This is the main mechanism of the CIMP pathway and in turn affects numerous cell functions important to cancer pathogenesis. Histones are proteins around which DNA coils. The proteins with coiled DNA are called chromatin units. Histones have protein tails that repress gene transcription when acetylation and specific methylations occur. Some histone proteins have already been observed to be overexpressed in colon cancer. MicroRNAs are short noncoding RNAs that induce gene repression in up to 30% of genes. Altered MicroRNA expression has been observed in many colon cancer–associated genes, and specific microRNA patterns have characterized certain colon cancers.

Epigenetic cancer markers are only beginning to be understood but are being examined for use in early detection and prognosis, tumor subclassifications, following the effectiveness of chemotherapy, and providing targets of intervention.

In summary, colon cancer genetics has provided genetic testing for inherited syndromes and guides to therapy with acquired mutations, while epigenetic mechanisms have the potential of being important to many areas of cancer diagnosis and treatment.

Dr. Burt is professor of medicine and holder of the Barnes Presidential Endowed Chair in Medicine at the Huntsman Cancer Institute and the University of Utah, Salt Lake City. He has consulted for Myriad Genetics. His comments were made during the ASGE and AGA joint Presidential Plenary at the annual Digestive Disease Week.

Optimizing colonoscopy quality in patients with ulcerative colitis or Crohn’s disease involving the colon is important. Their risk for the development of colorectal cancer (CRC) and of interval CRC is significantly higher compared with the non–inflammatory bowel disease (IBD) population.

Most CRC cases in IBD are believed to arise from dysplasia, and thus, surveillance colonoscopy is recommended to detect dysplasia. Key factors that influence the success of surveillance colonoscopy in IBD patients include: 1) endoscopic recognition of dysplasia, 2) adequacy of mucosal sampling, 3) awareness of interfering anatomy, such as strictures and pseudopolyps, 4) appropriate differentiation of dysplastic lesions as endoscopically resectable, 5) complete removal of endoscopically resectable dysplasia, and 6) patient compliance.

Over a decade ago, we learned that most dysplasia discovered in patients with IBD is actually visible. The use of high-definition video-endoscopy and newer methods, such as chromoendoscopy with mucosal dye spraying, enhance the detection of dysplasia. Today, with the widespread use of newer technologies and techniques, the literature indicates that targeted biopsies of visible lesions account for approximately 90% of cases, whereas random biopsy (resulting in detection of an endoscopically invisible lesion) accounts for only 10% of cases of identified dysplasia.

The endoscopic recognition of dysplastic colorectal lesions may have important implications for the surveillance and management of dysplasia, and shift it away from the traditional random biopsy technique, where less than 0.1% of the colonic mucosal surface area is sampled, and from colectomy for any diagnosis of dysplasia.

Enhanced endoscopy techniques such as chromoendoscopy can have a substantial impact upon IBD surveillance, increasing the dysplasia detection rates, as well as informing management decisions. Chromoendoscopy, using a dye solution of either methylene blue or indigo carmine applied onto the colonic mucosa to enhance contrast during surveillance colonoscopy, is performed either in a pancolonic fashion to detect lesions or in a targeted fashion to allow for detailed viewing of an identified lesion (Figure 1).

Additional resources are freely available detailing the technique and suggested steps to implement chromoendoscopy into practice. (See additional resources on chromoendoscopy and targeted biopsy techniques.)

An international multidisciplinary group, SCENIC (Surveillance for Colorectal Endoscopic Neoplasia Detection and Management in Inflammatory Bowel Disease Patients: International Consensus), which represents a wide spectrum of stakeholders and attitudes regarding IBD surveillance, sought to develop unifying consensus recommendations addressing two issues: 1) how should surveillance colonoscopy to detect dysplasia be performed, and 2) how should dysplasia identified at colonoscopy be managed. The SCENIC group adhered to suggested standards for guideline development from the Institute of Medicine and others and that incorporated the GRADE methodology. A systematic review was performed for each focused clinical question, followed by a review of a full synthesis of evidence by panelists.

SCENIC key summary recommendations

Detection

• High definition is recommended over standard definition for performance of surveillance colonoscopy.

• Routine performance of chromoendoscopy during IBD surveillance is suggested as an adjunct to high-definition colonoscopy.

• Narrowband imaging is not recommended as an alternative for high-definition, white-light colonoscopy or chromoendoscopy.

• No specific recommendation on performance of random biopsies was made in patients undergoing high-definition, white-light colonoscopy plus chromoendoscopy. The panel did not reach consensus on this topic because 60% of the panel members disagreed with performing random biopsies during chromoendoscopy, and a recommendation required 80% agreement or disagreement.

Management

• When dysplasia is detected, it should be characterized as “endoscopically resectable” or “nonendoscopically resectable” (The terms “dysplasia-associated lesion or mass (DALM),” “adenoma-like,” and “nonadenoma-like” should be abandoned).

• Visible dysplasia should be characterized according to the Paris classification polypoid or nonpolypoid, with modifications including the addition of terms for ulceration and border of the lesion.

• The term endoscopically resectable indicates that 1) distinct margins of the lesion could be identified, 2) the lesion appears to be completely removed on visual inspection after endoscopic resection, 3) histologic examination of the resected specimen is consistent with complete removal, and 4) biopsy specimens taken from mucosa immediately adjacent to the resection site are free of dysplasia on histologic examination.

• After complete removal of endoscopically resectable polypoid or nonpolypoid dysplasia, surveillance colonoscopy is recommended rather than colectomy.

• For patients with endoscopically invisible dysplasia (confirmed by a GI pathologist), referral is suggested to an endoscopist with expertise in IBD surveillance using chromoendoscopy with high-definition colonoscopy.

The SCENIC recommendations aim to optimize the detection and management of dysplasia in IBD patients. Future research in IBD surveillance should assess the potential for chromoendoscopy to improve risk stratification to elucidate optimal surveillance intervals, and the impact on CRC incidence and mortality. In addition, the role of resection of nonpolypoid dysplasia in the reduction in CRC incidence or need for colectomy requires further investigation.

Dr. Kaltenbach is a gastroenterologist at Veterans Affairs, and a clinical assistant professor of medicine at Stanford (Calif.) University. She has no conflicts of interest. Her comments were made during the ASGE and AGA joint Presidential Plenary at the annual Digestive Disease Week.

[email protected]

Optimizing colonoscopy quality in patients with ulcerative colitis or Crohn’s disease involving the colon is important. Their risk for the development of colorectal cancer (CRC) and of interval CRC is significantly higher compared with the non–inflammatory bowel disease (IBD) population.

Most CRC cases in IBD are believed to arise from dysplasia, and thus, surveillance colonoscopy is recommended to detect dysplasia. Key factors that influence the success of surveillance colonoscopy in IBD patients include: 1) endoscopic recognition of dysplasia, 2) adequacy of mucosal sampling, 3) awareness of interfering anatomy, such as strictures and pseudopolyps, 4) appropriate differentiation of dysplastic lesions as endoscopically resectable, 5) complete removal of endoscopically resectable dysplasia, and 6) patient compliance.

Over a decade ago, we learned that most dysplasia discovered in patients with IBD is actually visible. The use of high-definition video-endoscopy and newer methods, such as chromoendoscopy with mucosal dye spraying, enhance the detection of dysplasia. Today, with the widespread use of newer technologies and techniques, the literature indicates that targeted biopsies of visible lesions account for approximately 90% of cases, whereas random biopsy (resulting in detection of an endoscopically invisible lesion) accounts for only 10% of cases of identified dysplasia.

The endoscopic recognition of dysplastic colorectal lesions may have important implications for the surveillance and management of dysplasia, and shift it away from the traditional random biopsy technique, where less than 0.1% of the colonic mucosal surface area is sampled, and from colectomy for any diagnosis of dysplasia.

Enhanced endoscopy techniques such as chromoendoscopy can have a substantial impact upon IBD surveillance, increasing the dysplasia detection rates, as well as informing management decisions. Chromoendoscopy, using a dye solution of either methylene blue or indigo carmine applied onto the colonic mucosa to enhance contrast during surveillance colonoscopy, is performed either in a pancolonic fashion to detect lesions or in a targeted fashion to allow for detailed viewing of an identified lesion (Figure 1).

Additional resources are freely available detailing the technique and suggested steps to implement chromoendoscopy into practice. (See additional resources on chromoendoscopy and targeted biopsy techniques.)

An international multidisciplinary group, SCENIC (Surveillance for Colorectal Endoscopic Neoplasia Detection and Management in Inflammatory Bowel Disease Patients: International Consensus), which represents a wide spectrum of stakeholders and attitudes regarding IBD surveillance, sought to develop unifying consensus recommendations addressing two issues: 1) how should surveillance colonoscopy to detect dysplasia be performed, and 2) how should dysplasia identified at colonoscopy be managed. The SCENIC group adhered to suggested standards for guideline development from the Institute of Medicine and others and that incorporated the GRADE methodology. A systematic review was performed for each focused clinical question, followed by a review of a full synthesis of evidence by panelists.

SCENIC key summary recommendations

Detection

• High definition is recommended over standard definition for performance of surveillance colonoscopy.

• Routine performance of chromoendoscopy during IBD surveillance is suggested as an adjunct to high-definition colonoscopy.

• Narrowband imaging is not recommended as an alternative for high-definition, white-light colonoscopy or chromoendoscopy.

• No specific recommendation on performance of random biopsies was made in patients undergoing high-definition, white-light colonoscopy plus chromoendoscopy. The panel did not reach consensus on this topic because 60% of the panel members disagreed with performing random biopsies during chromoendoscopy, and a recommendation required 80% agreement or disagreement.

Management

• When dysplasia is detected, it should be characterized as “endoscopically resectable” or “nonendoscopically resectable” (The terms “dysplasia-associated lesion or mass (DALM),” “adenoma-like,” and “nonadenoma-like” should be abandoned).

• Visible dysplasia should be characterized according to the Paris classification polypoid or nonpolypoid, with modifications including the addition of terms for ulceration and border of the lesion.

• The term endoscopically resectable indicates that 1) distinct margins of the lesion could be identified, 2) the lesion appears to be completely removed on visual inspection after endoscopic resection, 3) histologic examination of the resected specimen is consistent with complete removal, and 4) biopsy specimens taken from mucosa immediately adjacent to the resection site are free of dysplasia on histologic examination.

• After complete removal of endoscopically resectable polypoid or nonpolypoid dysplasia, surveillance colonoscopy is recommended rather than colectomy.

• For patients with endoscopically invisible dysplasia (confirmed by a GI pathologist), referral is suggested to an endoscopist with expertise in IBD surveillance using chromoendoscopy with high-definition colonoscopy.

The SCENIC recommendations aim to optimize the detection and management of dysplasia in IBD patients. Future research in IBD surveillance should assess the potential for chromoendoscopy to improve risk stratification to elucidate optimal surveillance intervals, and the impact on CRC incidence and mortality. In addition, the role of resection of nonpolypoid dysplasia in the reduction in CRC incidence or need for colectomy requires further investigation.

Dr. Kaltenbach is a gastroenterologist at Veterans Affairs, and a clinical assistant professor of medicine at Stanford (Calif.) University. She has no conflicts of interest. Her comments were made during the ASGE and AGA joint Presidential Plenary at the annual Digestive Disease Week.

[email protected]

Optimizing colonoscopy quality in patients with ulcerative colitis or Crohn’s disease involving the colon is important. Their risk for the development of colorectal cancer (CRC) and of interval CRC is significantly higher compared with the non–inflammatory bowel disease (IBD) population.

Most CRC cases in IBD are believed to arise from dysplasia, and thus, surveillance colonoscopy is recommended to detect dysplasia. Key factors that influence the success of surveillance colonoscopy in IBD patients include: 1) endoscopic recognition of dysplasia, 2) adequacy of mucosal sampling, 3) awareness of interfering anatomy, such as strictures and pseudopolyps, 4) appropriate differentiation of dysplastic lesions as endoscopically resectable, 5) complete removal of endoscopically resectable dysplasia, and 6) patient compliance.

Over a decade ago, we learned that most dysplasia discovered in patients with IBD is actually visible. The use of high-definition video-endoscopy and newer methods, such as chromoendoscopy with mucosal dye spraying, enhance the detection of dysplasia. Today, with the widespread use of newer technologies and techniques, the literature indicates that targeted biopsies of visible lesions account for approximately 90% of cases, whereas random biopsy (resulting in detection of an endoscopically invisible lesion) accounts for only 10% of cases of identified dysplasia.

The endoscopic recognition of dysplastic colorectal lesions may have important implications for the surveillance and management of dysplasia, and shift it away from the traditional random biopsy technique, where less than 0.1% of the colonic mucosal surface area is sampled, and from colectomy for any diagnosis of dysplasia.

Enhanced endoscopy techniques such as chromoendoscopy can have a substantial impact upon IBD surveillance, increasing the dysplasia detection rates, as well as informing management decisions. Chromoendoscopy, using a dye solution of either methylene blue or indigo carmine applied onto the colonic mucosa to enhance contrast during surveillance colonoscopy, is performed either in a pancolonic fashion to detect lesions or in a targeted fashion to allow for detailed viewing of an identified lesion (Figure 1).

Additional resources are freely available detailing the technique and suggested steps to implement chromoendoscopy into practice. (See additional resources on chromoendoscopy and targeted biopsy techniques.)

An international multidisciplinary group, SCENIC (Surveillance for Colorectal Endoscopic Neoplasia Detection and Management in Inflammatory Bowel Disease Patients: International Consensus), which represents a wide spectrum of stakeholders and attitudes regarding IBD surveillance, sought to develop unifying consensus recommendations addressing two issues: 1) how should surveillance colonoscopy to detect dysplasia be performed, and 2) how should dysplasia identified at colonoscopy be managed. The SCENIC group adhered to suggested standards for guideline development from the Institute of Medicine and others and that incorporated the GRADE methodology. A systematic review was performed for each focused clinical question, followed by a review of a full synthesis of evidence by panelists.

SCENIC key summary recommendations

Detection

• High definition is recommended over standard definition for performance of surveillance colonoscopy.

• Routine performance of chromoendoscopy during IBD surveillance is suggested as an adjunct to high-definition colonoscopy.

• Narrowband imaging is not recommended as an alternative for high-definition, white-light colonoscopy or chromoendoscopy.

• No specific recommendation on performance of random biopsies was made in patients undergoing high-definition, white-light colonoscopy plus chromoendoscopy. The panel did not reach consensus on this topic because 60% of the panel members disagreed with performing random biopsies during chromoendoscopy, and a recommendation required 80% agreement or disagreement.

Management

• When dysplasia is detected, it should be characterized as “endoscopically resectable” or “nonendoscopically resectable” (The terms “dysplasia-associated lesion or mass (DALM),” “adenoma-like,” and “nonadenoma-like” should be abandoned).

• Visible dysplasia should be characterized according to the Paris classification polypoid or nonpolypoid, with modifications including the addition of terms for ulceration and border of the lesion.

• The term endoscopically resectable indicates that 1) distinct margins of the lesion could be identified, 2) the lesion appears to be completely removed on visual inspection after endoscopic resection, 3) histologic examination of the resected specimen is consistent with complete removal, and 4) biopsy specimens taken from mucosa immediately adjacent to the resection site are free of dysplasia on histologic examination.

• After complete removal of endoscopically resectable polypoid or nonpolypoid dysplasia, surveillance colonoscopy is recommended rather than colectomy.

• For patients with endoscopically invisible dysplasia (confirmed by a GI pathologist), referral is suggested to an endoscopist with expertise in IBD surveillance using chromoendoscopy with high-definition colonoscopy.

The SCENIC recommendations aim to optimize the detection and management of dysplasia in IBD patients. Future research in IBD surveillance should assess the potential for chromoendoscopy to improve risk stratification to elucidate optimal surveillance intervals, and the impact on CRC incidence and mortality. In addition, the role of resection of nonpolypoid dysplasia in the reduction in CRC incidence or need for colectomy requires further investigation.

Dr. Kaltenbach is a gastroenterologist at Veterans Affairs, and a clinical assistant professor of medicine at Stanford (Calif.) University. She has no conflicts of interest. Her comments were made during the ASGE and AGA joint Presidential Plenary at the annual Digestive Disease Week.

[email protected]

Important new themes are whether we can actually find a cure for inflammatory bowel disease and, in particular, whether there are common pathogenetic mechanisms leading to Crohn’s disease and ulcerative colitis. Are Crohn’s and ulcerative colitis infectious diseases? If the answer to that question is ‘yes,’ then eliminating that “pathogen” would turn off the immune response. Crohn’s disease and ulcerative colitis share common genetic origins with the majority of genes shared between both disorders. Indeed, 110 of the 163 confirmed loci in IBD are common between the two disorders ⁽Nature 2012;491:119–24).

In addition to there being many genes contributing even a small amount to the development of IBD, there are also some genetic pathways that have a far more impactful role in IBD. By studying very-early-onset IBD, we have discovered that the IL-10 receptor pathway is very important in controlling intestinal inflammation, such that if you have a mutation in the receptor for IL-10 it can lead to very-early-onset IBD. Children who are born with these disorders can be treated with a hematopoietic bone marrow transplant. At this year’s Digestive Disease Week (DDW⁾ in fact, there was the presentation of the ASTIC trial; it described patients having a prolonged remission after an autologous hematopoietic stem cell transplant.

One of the big advances that has been made in terms of the treatment of IBD is based on an understanding of the pathogenetic pathways; in particular, there has been an increase in the number of medications that are currently available to treat IBD from a variety of different avenues. There was a recent publication describing an anti-sense treatment against SMAD7 in restoring TGF-beta signaling that produced a very rapid and profound improvement in the clinical symptoms of Crohn’s disease. We await more data on that particular compound.

We now know that an antibody against P40, which is the common subunit between IL-12 and IL-23, is effective in the treatment of Crohn’s disease and is commercially available as ustekinumab. At this year’s DDW we heard about an antibody that is specific for anti-IL-23 since it only antagonizes the P19 subunit of the cytokine; it also shows great promise for treating IBD. At DDW 2014, vedolizumab had just obtained approval for the treatment of ulcerative colitis and Crohn’s disease and that has been a big advance in treating patients. On its heels are a variety of other compounds that work by a similar mechanism by inhibiting the trafficking of effector lymphocytes to the intestine; these include anti-beta7 strategies and anti-MAdCAM. Both of these have been shown to be more effective in ulcerative colitis than in Crohn’s disease, as has been a common theme.

The other important presentation that took place at DDW 2015 is the use of ozanimod to treat ulcerative colitis; again, this is an oral agent that has a very dramatic effect in treating ulcerative colitis in a very short period of time by inhibiting the exit of effector T cells from lymph nodes. This tells us about the host immune response. We can now sequence all the bacteria that are present in the gut and using that approach we have found broad patterns of decreased diversity in patients who have IBD, although we have not identified a particular pathogen or pathogens.

The laboratory of Dr. Richard Flavell used a strategy in which they identified bacteria that were IgA coated and reasoned that IgA-coated bacteria were more likely to be pathogens (Cell. 2014 Aug 28;158(5):1000-1010). Indeed, by giving mice these IgA-coated bacteria found in IBD patients, the mice were more likely to develop colitis than if you gave non–IgA-coated bacteria to the same mice.

Another very important observation was in a study that was published in Nature, which demonstrated that emulsifiers really changed the relationship between the host and the microbiome. In particular, the investigators found that interactions with the microbiota led to metabolic syndrome. They also found that with dietary emulsifiers there is encroachment of the epithelium because of a thinning of the mucous layer and the study animals were more susceptible to developing colitis. I think that this is a sign to our patients that it is better to avoid processed foods.

Dr. Abreu is professor of medicine, professor of microbiology and immunology, chief of the division of gastroenterology, the Martin Kalser Chair in gastroenterology, and the director, Crohn’s & Colitis Center at the University of Miami Miller School of Medicine. She consults for AbbVie, Focus Medical Communications, GSK, and many other biopharmaceutical companies. Her comments were made during the ASGE and AGA joint Presidential Plenary at the annual Digestive Disease Week.

Important new themes are whether we can actually find a cure for inflammatory bowel disease and, in particular, whether there are common pathogenetic mechanisms leading to Crohn’s disease and ulcerative colitis. Are Crohn’s and ulcerative colitis infectious diseases? If the answer to that question is ‘yes,’ then eliminating that “pathogen” would turn off the immune response. Crohn’s disease and ulcerative colitis share common genetic origins with the majority of genes shared between both disorders. Indeed, 110 of the 163 confirmed loci in IBD are common between the two disorders ⁽Nature 2012;491:119–24).

In addition to there being many genes contributing even a small amount to the development of IBD, there are also some genetic pathways that have a far more impactful role in IBD. By studying very-early-onset IBD, we have discovered that the IL-10 receptor pathway is very important in controlling intestinal inflammation, such that if you have a mutation in the receptor for IL-10 it can lead to very-early-onset IBD. Children who are born with these disorders can be treated with a hematopoietic bone marrow transplant. At this year’s Digestive Disease Week (DDW⁾ in fact, there was the presentation of the ASTIC trial; it described patients having a prolonged remission after an autologous hematopoietic stem cell transplant.

One of the big advances that has been made in terms of the treatment of IBD is based on an understanding of the pathogenetic pathways; in particular, there has been an increase in the number of medications that are currently available to treat IBD from a variety of different avenues. There was a recent publication describing an anti-sense treatment against SMAD7 in restoring TGF-beta signaling that produced a very rapid and profound improvement in the clinical symptoms of Crohn’s disease. We await more data on that particular compound.

We now know that an antibody against P40, which is the common subunit between IL-12 and IL-23, is effective in the treatment of Crohn’s disease and is commercially available as ustekinumab. At this year’s DDW we heard about an antibody that is specific for anti-IL-23 since it only antagonizes the P19 subunit of the cytokine; it also shows great promise for treating IBD. At DDW 2014, vedolizumab had just obtained approval for the treatment of ulcerative colitis and Crohn’s disease and that has been a big advance in treating patients. On its heels are a variety of other compounds that work by a similar mechanism by inhibiting the trafficking of effector lymphocytes to the intestine; these include anti-beta7 strategies and anti-MAdCAM. Both of these have been shown to be more effective in ulcerative colitis than in Crohn’s disease, as has been a common theme.

The other important presentation that took place at DDW 2015 is the use of ozanimod to treat ulcerative colitis; again, this is an oral agent that has a very dramatic effect in treating ulcerative colitis in a very short period of time by inhibiting the exit of effector T cells from lymph nodes. This tells us about the host immune response. We can now sequence all the bacteria that are present in the gut and using that approach we have found broad patterns of decreased diversity in patients who have IBD, although we have not identified a particular pathogen or pathogens.

The laboratory of Dr. Richard Flavell used a strategy in which they identified bacteria that were IgA coated and reasoned that IgA-coated bacteria were more likely to be pathogens (Cell. 2014 Aug 28;158(5):1000-1010). Indeed, by giving mice these IgA-coated bacteria found in IBD patients, the mice were more likely to develop colitis than if you gave non–IgA-coated bacteria to the same mice.

Another very important observation was in a study that was published in Nature, which demonstrated that emulsifiers really changed the relationship between the host and the microbiome. In particular, the investigators found that interactions with the microbiota led to metabolic syndrome. They also found that with dietary emulsifiers there is encroachment of the epithelium because of a thinning of the mucous layer and the study animals were more susceptible to developing colitis. I think that this is a sign to our patients that it is better to avoid processed foods.

Dr. Abreu is professor of medicine, professor of microbiology and immunology, chief of the division of gastroenterology, the Martin Kalser Chair in gastroenterology, and the director, Crohn’s & Colitis Center at the University of Miami Miller School of Medicine. She consults for AbbVie, Focus Medical Communications, GSK, and many other biopharmaceutical companies. Her comments were made during the ASGE and AGA joint Presidential Plenary at the annual Digestive Disease Week.

Important new themes are whether we can actually find a cure for inflammatory bowel disease and, in particular, whether there are common pathogenetic mechanisms leading to Crohn’s disease and ulcerative colitis. Are Crohn’s and ulcerative colitis infectious diseases? If the answer to that question is ‘yes,’ then eliminating that “pathogen” would turn off the immune response. Crohn’s disease and ulcerative colitis share common genetic origins with the majority of genes shared between both disorders. Indeed, 110 of the 163 confirmed loci in IBD are common between the two disorders ⁽Nature 2012;491:119–24).

In addition to there being many genes contributing even a small amount to the development of IBD, there are also some genetic pathways that have a far more impactful role in IBD. By studying very-early-onset IBD, we have discovered that the IL-10 receptor pathway is very important in controlling intestinal inflammation, such that if you have a mutation in the receptor for IL-10 it can lead to very-early-onset IBD. Children who are born with these disorders can be treated with a hematopoietic bone marrow transplant. At this year’s Digestive Disease Week (DDW⁾ in fact, there was the presentation of the ASTIC trial; it described patients having a prolonged remission after an autologous hematopoietic stem cell transplant.

One of the big advances that has been made in terms of the treatment of IBD is based on an understanding of the pathogenetic pathways; in particular, there has been an increase in the number of medications that are currently available to treat IBD from a variety of different avenues. There was a recent publication describing an anti-sense treatment against SMAD7 in restoring TGF-beta signaling that produced a very rapid and profound improvement in the clinical symptoms of Crohn’s disease. We await more data on that particular compound.

We now know that an antibody against P40, which is the common subunit between IL-12 and IL-23, is effective in the treatment of Crohn’s disease and is commercially available as ustekinumab. At this year’s DDW we heard about an antibody that is specific for anti-IL-23 since it only antagonizes the P19 subunit of the cytokine; it also shows great promise for treating IBD. At DDW 2014, vedolizumab had just obtained approval for the treatment of ulcerative colitis and Crohn’s disease and that has been a big advance in treating patients. On its heels are a variety of other compounds that work by a similar mechanism by inhibiting the trafficking of effector lymphocytes to the intestine; these include anti-beta7 strategies and anti-MAdCAM. Both of these have been shown to be more effective in ulcerative colitis than in Crohn’s disease, as has been a common theme.

The other important presentation that took place at DDW 2015 is the use of ozanimod to treat ulcerative colitis; again, this is an oral agent that has a very dramatic effect in treating ulcerative colitis in a very short period of time by inhibiting the exit of effector T cells from lymph nodes. This tells us about the host immune response. We can now sequence all the bacteria that are present in the gut and using that approach we have found broad patterns of decreased diversity in patients who have IBD, although we have not identified a particular pathogen or pathogens.

The laboratory of Dr. Richard Flavell used a strategy in which they identified bacteria that were IgA coated and reasoned that IgA-coated bacteria were more likely to be pathogens (Cell. 2014 Aug 28;158(5):1000-1010). Indeed, by giving mice these IgA-coated bacteria found in IBD patients, the mice were more likely to develop colitis than if you gave non–IgA-coated bacteria to the same mice.

Another very important observation was in a study that was published in Nature, which demonstrated that emulsifiers really changed the relationship between the host and the microbiome. In particular, the investigators found that interactions with the microbiota led to metabolic syndrome. They also found that with dietary emulsifiers there is encroachment of the epithelium because of a thinning of the mucous layer and the study animals were more susceptible to developing colitis. I think that this is a sign to our patients that it is better to avoid processed foods.

Dr. Abreu is professor of medicine, professor of microbiology and immunology, chief of the division of gastroenterology, the Martin Kalser Chair in gastroenterology, and the director, Crohn’s & Colitis Center at the University of Miami Miller School of Medicine. She consults for AbbVie, Focus Medical Communications, GSK, and many other biopharmaceutical companies. Her comments were made during the ASGE and AGA joint Presidential Plenary at the annual Digestive Disease Week.

Value in health care is often defined as “health outcomes achieved per dollar spent,” or “outcomes/costs.” Value encompasses efficiency, but is primarily results oriented and not based on volume. For purposes of comparison and assessment, value assessments apply to patient- and condition-specific episodes of care.

As the dominant driver of value-based reimbursement (VBR), the Center for Medicare & Medicaid Services, has defined a payment taxonomy for coming years based upon the degree of linkage between quality and reimbursement (JAMA 2014;311:1967-8). Four categories of reimbursement extend from traditional fee for service (FFS; Category 1) to FFS with significant reliance on quality measures and outcome (Cat. 2), entirely population-based models with payments stimulated by delivery of care (Cat. 3), and payment based entirely on capitated coverage of individuals over time (Cat. 4).

Category 2 reimbursement for physicians is largely based upon the Physicians Quality Reporting System (PQRS) with Value-Based Payment Modifiers (VBPM). Incentives for participation in PQRS ended in 2014. For select groups of more than 100 physicians, 2015 payments will be based on 2013 PQRS submissions, with a 1% cut for groups that didn’t submit data in 2013. For all physicians, failure to participate in 2015 will result in a downward adjustment of 2% in 2017. Participation will generate bonuses or penalties of 1%-4% in 2017, based on group size, claims-based cost data, and submission of PQRS quality data, via one of three mechanisms. The most attractive option for many groups will be submission of data for 50% of applicable patients via a Qualified Clinical Data Registry, such as the ASGE & ACG’s GI Quality Improvement Consortium (GIQUIC) or the AGA’s Digestive Health Registry (DHR).

Category 3 in the CMS payment taxonomy triggers reimbursement by delivery of care, but links it to episodes of care or to population management, with varied mechanisms for providers to share in the potential benefits and risks of cost extremes. Programs include Accountable Care Organizations (ACOs), medical homes for specified conditions, and shared savings for comprehensive primary care and end-stage renal disease. Presently, most employ a modest potential upside in reimbursement for savings but only limited downside risk. In 2015, ACOs cover about 23 million lives, or 7% of the population of the United States. Estimates suggest coverage of 72 million (22%) by 2020 (Leavitt Partners, Salt Lake, 2015).

In Category 4 of the CMS taxonomy, the Next Generation ACO Model drops all links between reimbursement and actual delivery of care, in favor of reimbursement for the assumption of care of individuals over time frames greater than 1 year, with greater participation in savings and risk. Several inducements and tools are included to enhance participation and the management of care, including: 1) reward to beneficiaries for participation, 2) reimbursement for skilled nursing care without prior hospitalization, and 3) expanded coverage for tele-health and home services. CMS aims to increase Categories 3 (alternative FFS) and 4 (population-based payment models) to 50% of covered individuals by 2018.

VBR by nongovernmental payers lags behind that of federal and state programs. CMS is currently testing more than 20 models for care and reimbursement, with aims to pull private payers into VBR and the final common pathway of management of populations while conserving health care resources (JAMA 2014;311:1967-8).

For gastroenterology, VBR will require practice redesign, with the expectation that physicians will focus their care toward their maximal level of licensure and privileging, while enabling employed advanced practice R.N.’s (certified nurse practitioner, or CNP) and physician assistants to do the same (Clin. Gastroenterol. Hepatol. 2014;12:1584-6 ).

This trend is already well established in many environments. Redesign is also stimulating consolidation of practices to better enable contracts for population management by the group. A second development will be increasing use of risk-bearing contracts for episodes of care, particularly for colorectal cancer surveillance and liver transplantation. Specialty medical homes, as opposed to primary care medical homes, will grow for care of inflammatory bowel disease and perhaps for chronic liver disease patients. Success with these initiatives, with both preservation of adequate reimbursement and appropriate constraint in delivery of care, will require extensive reliance on big data for demonstration of quality and patient engagement for optimizing the frequency and intensity of care.

Dr. Petersen is professor of medicine, Mayo Graduate School of Medicine, Mayo Clinic College of Medicine, Rochester, Minn. He has no conflicts of interest. His comments were made during the ASGE and AGA joint Presidential Plenary at the annual Digestive Disease Week.

Value in health care is often defined as “health outcomes achieved per dollar spent,” or “outcomes/costs.” Value encompasses efficiency, but is primarily results oriented and not based on volume. For purposes of comparison and assessment, value assessments apply to patient- and condition-specific episodes of care.

As the dominant driver of value-based reimbursement (VBR), the Center for Medicare & Medicaid Services, has defined a payment taxonomy for coming years based upon the degree of linkage between quality and reimbursement (JAMA 2014;311:1967-8). Four categories of reimbursement extend from traditional fee for service (FFS; Category 1) to FFS with significant reliance on quality measures and outcome (Cat. 2), entirely population-based models with payments stimulated by delivery of care (Cat. 3), and payment based entirely on capitated coverage of individuals over time (Cat. 4).

Category 2 reimbursement for physicians is largely based upon the Physicians Quality Reporting System (PQRS) with Value-Based Payment Modifiers (VBPM). Incentives for participation in PQRS ended in 2014. For select groups of more than 100 physicians, 2015 payments will be based on 2013 PQRS submissions, with a 1% cut for groups that didn’t submit data in 2013. For all physicians, failure to participate in 2015 will result in a downward adjustment of 2% in 2017. Participation will generate bonuses or penalties of 1%-4% in 2017, based on group size, claims-based cost data, and submission of PQRS quality data, via one of three mechanisms. The most attractive option for many groups will be submission of data for 50% of applicable patients via a Qualified Clinical Data Registry, such as the ASGE & ACG’s GI Quality Improvement Consortium (GIQUIC) or the AGA’s Digestive Health Registry (DHR).

Category 3 in the CMS payment taxonomy triggers reimbursement by delivery of care, but links it to episodes of care or to population management, with varied mechanisms for providers to share in the potential benefits and risks of cost extremes. Programs include Accountable Care Organizations (ACOs), medical homes for specified conditions, and shared savings for comprehensive primary care and end-stage renal disease. Presently, most employ a modest potential upside in reimbursement for savings but only limited downside risk. In 2015, ACOs cover about 23 million lives, or 7% of the population of the United States. Estimates suggest coverage of 72 million (22%) by 2020 (Leavitt Partners, Salt Lake, 2015).

In Category 4 of the CMS taxonomy, the Next Generation ACO Model drops all links between reimbursement and actual delivery of care, in favor of reimbursement for the assumption of care of individuals over time frames greater than 1 year, with greater participation in savings and risk. Several inducements and tools are included to enhance participation and the management of care, including: 1) reward to beneficiaries for participation, 2) reimbursement for skilled nursing care without prior hospitalization, and 3) expanded coverage for tele-health and home services. CMS aims to increase Categories 3 (alternative FFS) and 4 (population-based payment models) to 50% of covered individuals by 2018.

VBR by nongovernmental payers lags behind that of federal and state programs. CMS is currently testing more than 20 models for care and reimbursement, with aims to pull private payers into VBR and the final common pathway of management of populations while conserving health care resources (JAMA 2014;311:1967-8).

For gastroenterology, VBR will require practice redesign, with the expectation that physicians will focus their care toward their maximal level of licensure and privileging, while enabling employed advanced practice R.N.’s (certified nurse practitioner, or CNP) and physician assistants to do the same (Clin. Gastroenterol. Hepatol. 2014;12:1584-6 ).

This trend is already well established in many environments. Redesign is also stimulating consolidation of practices to better enable contracts for population management by the group. A second development will be increasing use of risk-bearing contracts for episodes of care, particularly for colorectal cancer surveillance and liver transplantation. Specialty medical homes, as opposed to primary care medical homes, will grow for care of inflammatory bowel disease and perhaps for chronic liver disease patients. Success with these initiatives, with both preservation of adequate reimbursement and appropriate constraint in delivery of care, will require extensive reliance on big data for demonstration of quality and patient engagement for optimizing the frequency and intensity of care.

Dr. Petersen is professor of medicine, Mayo Graduate School of Medicine, Mayo Clinic College of Medicine, Rochester, Minn. He has no conflicts of interest. His comments were made during the ASGE and AGA joint Presidential Plenary at the annual Digestive Disease Week.

Value in health care is often defined as “health outcomes achieved per dollar spent,” or “outcomes/costs.” Value encompasses efficiency, but is primarily results oriented and not based on volume. For purposes of comparison and assessment, value assessments apply to patient- and condition-specific episodes of care.

As the dominant driver of value-based reimbursement (VBR), the Center for Medicare & Medicaid Services, has defined a payment taxonomy for coming years based upon the degree of linkage between quality and reimbursement (JAMA 2014;311:1967-8). Four categories of reimbursement extend from traditional fee for service (FFS; Category 1) to FFS with significant reliance on quality measures and outcome (Cat. 2), entirely population-based models with payments stimulated by delivery of care (Cat. 3), and payment based entirely on capitated coverage of individuals over time (Cat. 4).

Category 2 reimbursement for physicians is largely based upon the Physicians Quality Reporting System (PQRS) with Value-Based Payment Modifiers (VBPM). Incentives for participation in PQRS ended in 2014. For select groups of more than 100 physicians, 2015 payments will be based on 2013 PQRS submissions, with a 1% cut for groups that didn’t submit data in 2013. For all physicians, failure to participate in 2015 will result in a downward adjustment of 2% in 2017. Participation will generate bonuses or penalties of 1%-4% in 2017, based on group size, claims-based cost data, and submission of PQRS quality data, via one of three mechanisms. The most attractive option for many groups will be submission of data for 50% of applicable patients via a Qualified Clinical Data Registry, such as the ASGE & ACG’s GI Quality Improvement Consortium (GIQUIC) or the AGA’s Digestive Health Registry (DHR).

Category 3 in the CMS payment taxonomy triggers reimbursement by delivery of care, but links it to episodes of care or to population management, with varied mechanisms for providers to share in the potential benefits and risks of cost extremes. Programs include Accountable Care Organizations (ACOs), medical homes for specified conditions, and shared savings for comprehensive primary care and end-stage renal disease. Presently, most employ a modest potential upside in reimbursement for savings but only limited downside risk. In 2015, ACOs cover about 23 million lives, or 7% of the population of the United States. Estimates suggest coverage of 72 million (22%) by 2020 (Leavitt Partners, Salt Lake, 2015).

In Category 4 of the CMS taxonomy, the Next Generation ACO Model drops all links between reimbursement and actual delivery of care, in favor of reimbursement for the assumption of care of individuals over time frames greater than 1 year, with greater participation in savings and risk. Several inducements and tools are included to enhance participation and the management of care, including: 1) reward to beneficiaries for participation, 2) reimbursement for skilled nursing care without prior hospitalization, and 3) expanded coverage for tele-health and home services. CMS aims to increase Categories 3 (alternative FFS) and 4 (population-based payment models) to 50% of covered individuals by 2018.

VBR by nongovernmental payers lags behind that of federal and state programs. CMS is currently testing more than 20 models for care and reimbursement, with aims to pull private payers into VBR and the final common pathway of management of populations while conserving health care resources (JAMA 2014;311:1967-8).

For gastroenterology, VBR will require practice redesign, with the expectation that physicians will focus their care toward their maximal level of licensure and privileging, while enabling employed advanced practice R.N.’s (certified nurse practitioner, or CNP) and physician assistants to do the same (Clin. Gastroenterol. Hepatol. 2014;12:1584-6 ).

This trend is already well established in many environments. Redesign is also stimulating consolidation of practices to better enable contracts for population management by the group. A second development will be increasing use of risk-bearing contracts for episodes of care, particularly for colorectal cancer surveillance and liver transplantation. Specialty medical homes, as opposed to primary care medical homes, will grow for care of inflammatory bowel disease and perhaps for chronic liver disease patients. Success with these initiatives, with both preservation of adequate reimbursement and appropriate constraint in delivery of care, will require extensive reliance on big data for demonstration of quality and patient engagement for optimizing the frequency and intensity of care.

Dr. Petersen is professor of medicine, Mayo Graduate School of Medicine, Mayo Clinic College of Medicine, Rochester, Minn. He has no conflicts of interest. His comments were made during the ASGE and AGA joint Presidential Plenary at the annual Digestive Disease Week.

WASHINGTON – Initial misdiagnoses were common and were associated with a later disease stage at diagnosis, in a study of 313 patients diagnosed with pancreatic cancer, Dr. Douglas Swords said at the annual Digestive Disease Week.

“By far, the most common misdiagnosis was gallbladder disease,” and there was about a 3-month longer time period, on average, from the first visit to a physician to the actual cancer diagnosis, in patients who were initially misdiagnosed, said Dr. Swords, a surgery resident at the University of Utah, Salt Lake City.

Elizabeth Mechcatie/Frontline Medical News

In the series of 313 patients diagnosed with pancreatic cancer, 98 (31.3%) were initially misdiagnosed, with a total of 119 diagnoses other than pancreatic cancer, he said. The most common misdiagnosis was gallbladder disease, which led to a cholecystectomy in 38 cases, followed by gastroesophageal reflux disease in 15 cases, and peptic ulcer disease in 11 cases. Those initially misdiagnosed were an average of about 5 years younger.

Patients with an initial misdiagnosis had significantly greater rates of abdominal pain (about 85% vs. about 60%), weight loss (about 85% vs. about 75%), nausea/vomiting (50% vs. almost 40%), and pancreatitis (almost 30% vs. less than 5%), Dr. Swords said. In addition, patients with an initial misdiagnosis had significantly lower rates of jaundice (about 50% vs. almost 80%). The rates of diarrhea and anorexia were not significantly different between the two groups.

The study also looked at the time intervals from when the patient developed symptoms to the physician visit, from the physician visit to the cancer diagnosis, and from the physician visit to the performance of axial imaging. There was no difference in the time of symptom onset to the first visit with a physician in the two groups (0.5 month among those initially misdiagnosed and 0.7 month among those correctly diagnosed).

©decade3d/Thinkstock.com

However, the time from the physician visit to the cancer diagnosis was 3.5 months among those initially misdiagnosed, vs. less than a month (0.6 month) among those who were correctly diagnosed, a statistically significant difference (P <.001), he said.

In addition, for those patients initially misdiagnosed, it took about 1 month longer from the physician visit to the time a CT scan or other type of axial imaging was ordered (an average of 1.1 months vs. 0.1 month, P <.001).

There was also a statistically significant association between a more advanced stage and initial misdiagnosis. Patients who were initially misdiagnosed had a 1.4-fold greater risk of having stage III or IV disease at the time of the pancreatic cancer diagnosis, Dr. Swords said.

Almost 40% (39) of those who were initially misdiagnosed were diagnosed with stage IV disease when they were correctly diagnosed, compared with 23.7% (51 patients) of those who were correctly diagnosed. The proportion diagnosed with stage III disease was similar, 21.4% among those initially misdiagnosed and 20% of those correctly diagnosed. Almost 51% of those correctly diagnosed were diagnosed with stage II disease, vs. 33.7% of those who were initially misdiagnosed. Of those initially misdiagnosed, 5.1% were diagnosed with stage I disease, compared with 5.6% of those correctly diagnosed.

However, the earlier stage at diagnosis for those with an initial correct diagnosis “did not translate into a survival difference,” Dr. Swords said, noting that there was a trend toward shorter survival among those who were initially misdiagnosed (median overall survival of 9.6 vs. 10.3 months).

Based on these results, Dr. Swords said, “surgeons should consider the diagnosis of pancreatic cancer when a patient referred for cholecystectomy has vague or atypical symptoms.”

He said he had no relevant financial disclosures.

[email protected]

WASHINGTON – Initial misdiagnoses were common and were associated with a later disease stage at diagnosis, in a study of 313 patients diagnosed with pancreatic cancer, Dr. Douglas Swords said at the annual Digestive Disease Week.

“By far, the most common misdiagnosis was gallbladder disease,” and there was about a 3-month longer time period, on average, from the first visit to a physician to the actual cancer diagnosis, in patients who were initially misdiagnosed, said Dr. Swords, a surgery resident at the University of Utah, Salt Lake City.

Elizabeth Mechcatie/Frontline Medical News

In the series of 313 patients diagnosed with pancreatic cancer, 98 (31.3%) were initially misdiagnosed, with a total of 119 diagnoses other than pancreatic cancer, he said. The most common misdiagnosis was gallbladder disease, which led to a cholecystectomy in 38 cases, followed by gastroesophageal reflux disease in 15 cases, and peptic ulcer disease in 11 cases. Those initially misdiagnosed were an average of about 5 years younger.

Patients with an initial misdiagnosis had significantly greater rates of abdominal pain (about 85% vs. about 60%), weight loss (about 85% vs. about 75%), nausea/vomiting (50% vs. almost 40%), and pancreatitis (almost 30% vs. less than 5%), Dr. Swords said. In addition, patients with an initial misdiagnosis had significantly lower rates of jaundice (about 50% vs. almost 80%). The rates of diarrhea and anorexia were not significantly different between the two groups.

The study also looked at the time intervals from when the patient developed symptoms to the physician visit, from the physician visit to the cancer diagnosis, and from the physician visit to the performance of axial imaging. There was no difference in the time of symptom onset to the first visit with a physician in the two groups (0.5 month among those initially misdiagnosed and 0.7 month among those correctly diagnosed).

©decade3d/Thinkstock.com

However, the time from the physician visit to the cancer diagnosis was 3.5 months among those initially misdiagnosed, vs. less than a month (0.6 month) among those who were correctly diagnosed, a statistically significant difference (P <.001), he said.

In addition, for those patients initially misdiagnosed, it took about 1 month longer from the physician visit to the time a CT scan or other type of axial imaging was ordered (an average of 1.1 months vs. 0.1 month, P <.001).

There was also a statistically significant association between a more advanced stage and initial misdiagnosis. Patients who were initially misdiagnosed had a 1.4-fold greater risk of having stage III or IV disease at the time of the pancreatic cancer diagnosis, Dr. Swords said.

Almost 40% (39) of those who were initially misdiagnosed were diagnosed with stage IV disease when they were correctly diagnosed, compared with 23.7% (51 patients) of those who were correctly diagnosed. The proportion diagnosed with stage III disease was similar, 21.4% among those initially misdiagnosed and 20% of those correctly diagnosed. Almost 51% of those correctly diagnosed were diagnosed with stage II disease, vs. 33.7% of those who were initially misdiagnosed. Of those initially misdiagnosed, 5.1% were diagnosed with stage I disease, compared with 5.6% of those correctly diagnosed.

However, the earlier stage at diagnosis for those with an initial correct diagnosis “did not translate into a survival difference,” Dr. Swords said, noting that there was a trend toward shorter survival among those who were initially misdiagnosed (median overall survival of 9.6 vs. 10.3 months).

Based on these results, Dr. Swords said, “surgeons should consider the diagnosis of pancreatic cancer when a patient referred for cholecystectomy has vague or atypical symptoms.”

He said he had no relevant financial disclosures.

[email protected]

WASHINGTON – Initial misdiagnoses were common and were associated with a later disease stage at diagnosis, in a study of 313 patients diagnosed with pancreatic cancer, Dr. Douglas Swords said at the annual Digestive Disease Week.

“By far, the most common misdiagnosis was gallbladder disease,” and there was about a 3-month longer time period, on average, from the first visit to a physician to the actual cancer diagnosis, in patients who were initially misdiagnosed, said Dr. Swords, a surgery resident at the University of Utah, Salt Lake City.

Elizabeth Mechcatie/Frontline Medical News

In the series of 313 patients diagnosed with pancreatic cancer, 98 (31.3%) were initially misdiagnosed, with a total of 119 diagnoses other than pancreatic cancer, he said. The most common misdiagnosis was gallbladder disease, which led to a cholecystectomy in 38 cases, followed by gastroesophageal reflux disease in 15 cases, and peptic ulcer disease in 11 cases. Those initially misdiagnosed were an average of about 5 years younger.

Patients with an initial misdiagnosis had significantly greater rates of abdominal pain (about 85% vs. about 60%), weight loss (about 85% vs. about 75%), nausea/vomiting (50% vs. almost 40%), and pancreatitis (almost 30% vs. less than 5%), Dr. Swords said. In addition, patients with an initial misdiagnosis had significantly lower rates of jaundice (about 50% vs. almost 80%). The rates of diarrhea and anorexia were not significantly different between the two groups.

The study also looked at the time intervals from when the patient developed symptoms to the physician visit, from the physician visit to the cancer diagnosis, and from the physician visit to the performance of axial imaging. There was no difference in the time of symptom onset to the first visit with a physician in the two groups (0.5 month among those initially misdiagnosed and 0.7 month among those correctly diagnosed).

©decade3d/Thinkstock.com

However, the time from the physician visit to the cancer diagnosis was 3.5 months among those initially misdiagnosed, vs. less than a month (0.6 month) among those who were correctly diagnosed, a statistically significant difference (P <.001), he said.

In addition, for those patients initially misdiagnosed, it took about 1 month longer from the physician visit to the time a CT scan or other type of axial imaging was ordered (an average of 1.1 months vs. 0.1 month, P <.001).

There was also a statistically significant association between a more advanced stage and initial misdiagnosis. Patients who were initially misdiagnosed had a 1.4-fold greater risk of having stage III or IV disease at the time of the pancreatic cancer diagnosis, Dr. Swords said.

Almost 40% (39) of those who were initially misdiagnosed were diagnosed with stage IV disease when they were correctly diagnosed, compared with 23.7% (51 patients) of those who were correctly diagnosed. The proportion diagnosed with stage III disease was similar, 21.4% among those initially misdiagnosed and 20% of those correctly diagnosed. Almost 51% of those correctly diagnosed were diagnosed with stage II disease, vs. 33.7% of those who were initially misdiagnosed. Of those initially misdiagnosed, 5.1% were diagnosed with stage I disease, compared with 5.6% of those correctly diagnosed.

However, the earlier stage at diagnosis for those with an initial correct diagnosis “did not translate into a survival difference,” Dr. Swords said, noting that there was a trend toward shorter survival among those who were initially misdiagnosed (median overall survival of 9.6 vs. 10.3 months).

Based on these results, Dr. Swords said, “surgeons should consider the diagnosis of pancreatic cancer when a patient referred for cholecystectomy has vague or atypical symptoms.”

He said he had no relevant financial disclosures.

[email protected]