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Background To demonstrate treatment efficacy in Crohn’s disease (CD), regulatory authorities require that trials include an endoscopic remission/response end point; however, standardized endoscopic assessment of disease activity, such as the Simple Endoscopic Score for Crohn’s Disease (SES-CD), is not typically recorded by clinicians in practice or outside of clinical trials. The novel Simplified Endoscopic Mucosal Assessment for Crohn’s Disease (SEMA-CD) was developed to be easy to use in routine clinical practice and as a trial end point. We conducted a study to assess and validate the reliability and feasibility of SEMA-CD as a measure of endoscopic disease activity. Methods Pre- and post-treatment ileocolonoscopy videos of pediatric (n = 36) and adult (n = 74) CD patients from 2 ustekinumab clinical trials were each scored with SEMA-CD by 2 to 3 professional central readers, blinded to clinical history and other video scorings; the correlation between SEMA-CD and SES-CD previously completed during the trials was assessed. Sensitivity to change, inter- and intrarater reliability, and comparative ease of scoring were also assessed. Results The SEMA-CD strongly correlated with SES-CD (Spearman ρ = 0.89; 95% confidence interval, 0.86-0.92). Pre- to post-treatment changes in SEMA-CD vs in SES-CD were strongly correlated, and the correlation remained strong between the scores when compared by study population (pediatric, adult), disease severity, and video quality. Intra- and inter-rater reliability were good, and SEMA-CD was rated easier than SES-CD to score 63.0% of the time, although slightly more difficult than SES-CD to score Conclusions The SEMA-CD is reliable, reproducible, sensitive to change, and easy to use in both pediatric and adult patients with CD.

Introduction Endoscopy education in the US traditionally follows the apprenticeship model, in which educators often have little formal training in education, and the acquisition of procedural skills by trainees relies heavily on procedure volume and learning by doing. A growing appreciation of the need to formally educate endoscopy trainers has led to the development of mandatory training curricula in other countries, but the implementation of such courses in the US has been limited. This 1-hour workshop aimed to provide educators the rationale and skills to offer a more standardized approach to procedural training. Methods We implemented a 1-hour interactive workshop designed for both gastroenterology faculty and trainees. The four sections of the workshop focused on: (1) rationale for standardized approach, (2) verbal and physical preparation for training, (3) training using standardized language and avoidance of cognitive overload, and (4) providing feedback. Four interactive video cases followed by large-group discussion were included. Results A total of 13 gastroenterology faculty and trainees attended the workshop. Eight additional members of the gastroenterology faculty watched an online video of the workshop. Survey data revealed that the workshop was effective in helping faculty set goals with trainees (Mpre = 2.4, Mpost = 3.6), identify standardized language to use during endoscopy (Mpre = 3.1, Mpost = 3.8), and give feedback after sessions (Mpre = 3.4, Mpost = 4.1). Discussion A 1-hour lecture-based interactive workshop with video cases was an engaging and effective introduction to formal endoscopy education techniques. The format was easy to incorporate into faculty conferences and can help bridge the current gap in formal endoscopy faculty training.

Background & Aims The prevalence and significance of digestive manifestations in coronavirus disease 2019 (COVID-19) remain uncertain. We aimed to assess the prevalence, spectrum, severity, and significance of digestive manifestations in patients hospitalized with COVID-19. Methods Consecutive patients hospitalized with COVID-19 were identified across a geographically diverse alliance of medical centers in North America. Data pertaining to baseline characteristics, symptomatology, laboratory assessment, imaging, and endoscopic findings from the time of symptom onset until discharge or death were abstracted manually from electronic health records to characterize the prevalence, spectrum, and severity of digestive manifestations. Regression analyses were performed to evaluate the association between digestive manifestations and severe outcomes related to COVID-19. Results A total of 1992 patients across 36 centers met eligibility criteria and were included. Overall, 53% of patients experienced at least 1 gastrointestinal symptom at any time during their illness, most commonly diarrhea (34%), nausea (27%), vomiting (16%), and abdominal pain (11%). In 74% of cases, gastrointestinal symptoms were judged to be mild. In total, 35% of patients developed an abnormal alanine aminotransferase or total bilirubin level; these were increased to less than 5 times the upper limit of normal in 77% of cases. After adjusting for potential confounders, the presence of gastrointestinal symptoms at any time (odds ratio, 0.93; 95% CI, 0.76–1.15) or liver test abnormalities on admission (odds ratio, 1.31; 95% CI, 0.80–2.12) were not associated independently with mechanical ventilation or death. Conclusions Among patients hospitalized with COVID-19, gastrointestinal symptoms and liver test abnormalities were common, but the majority were mild and their presence was not associated with a more severe clinical course.

BackgroundThe prevalence and significance of digestive manifestations in COVID-19 remain uncertain.MethodsConsecutive patients hospitalized with COVID-19 were identified across a geographically diverse alliance of medical centers in North America. Data pertaining to baseline characteristics, symptomatology, laboratory assessment, imaging, and endoscopic findings from the time of symptom onset until discharge or death were manually abstracted from electronic health records to characterize the prevalence, spectrum, and severity of digestive manifestations. Regression analyses were performed to evaluate the association between digestive manifestations and severe outcomes related to COVID-19.ResultsA total of 1992 patients across 36 centers met eligibility criteria and were included. Overall, 53% of patients experienced at least one gastrointestinal symptom at any time during their illness, most commonly diarrhea (34%), nausea (27%), vomiting (16%), and abdominal pain (11%). In 74% of cases, gastrointestinal symptoms were judged to be mild. In total, 35% of patients developed an abnormal alanine aminotransferase or total bilirubin level; these were elevated to less than 5 times the upper limit of normal in 77% of cases. After adjusting for potential confounders, the presence of gastrointestinal symptoms at any time (odds ratio 0.93, 95% confidence interval 0.76-1.15) or liver test abnormalities on admission (odds ratio 1.31, 95% confidence interval 0.80-2.12) were not independently associated with mechanical ventilation or death.ConclusionsAmong patients hospitalized with COVID-19, gastrointestinal symptoms and liver test abnormalities were common but the majority were mild and their presence was not associated with a more severe clinical course

// Mart Dela Cruz 1,* , Sarah Ledbetter 1,* , Sanjib Chowdhury 1,* , Ashish K. Tiwari 1 , Navneet Momi 1 , Ramesh K. Wali 1 , Charles Bliss 1 , Christopher Huang 1 , David Lichtenstein 1 , Swati Bhattacharya 1 , Anisha Varma-Wilson 1 , Vadim Backman 2 and Hemant K. Roy 1 1 Section of Gastroenterology, Boston University Medical Center, Boston, Massachusetts, USA 2 Department of Biomedical Engineering, Northwestern University, Evanston, Illinois, USA * These authors have contributed equally to this work Correspondence to: Hemant K. Roy, email: // Keywords : colorectal carcinoma, field carcinogenesis, metabolism, metabolic reprogramming, Warburg effect Received : December 08, 2016 Accepted : February 27, 2017 Published : March 11, 2017 Abstract Background: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in the United States. There is an increasing need for the identification of biomarkers of pre-malignant and early stage CRC to improve risk-stratification and screening recommendations. In this study, we investigated the possibility of metabolic and mitochondrial reprogramming early in the pre-malignant colorectal field. Methods: Rectal biopsies were taken from 81 patients undergoing screening colonoscopy, and gene expression of metabolic and mitochondrial markers were assessed using real time quantitative PCR. Validation studies were performed in two different animal models of colon carcinogenesis: Pirc rats and AOM-treated rats. Results: We found evidence of a Warburg effect in the normal-appearing rectal mucosa of patients harboring precancerous lesions elsewhere in the colon compared to control patients, with a significant increase in HIF1α , SLC2A1 (referred to as GLUT1) , PKM2 , and LDHA . We also found evidence of early mitochondrial changes in the colorectal field of patients harboring pre-cancerous lesions, with significantly increased mitochondrial gene expression of DRP1 (fission), OPA1 (fusion), PGC1 -α (biogenesis), UCP2 (uncoupling) and mtND1 (copy number). Similar results were observed in the two different animal models. Conclusions: These results demonstrate for the first time evidence of early Warburg-like metabolic changes as well as changes in mitochondrial function, dynamics and mtDNA copy number in endoscopically normal premalignant colorectal mucosal field. These findings provide an opportunity for the development of metabolic biomarkers that could be used for improving screening recommendations and risk-stratification. This also provides a potential target for novel chemopreventive strategies in the pre-malignant colorectal field.

The AspireAssist System (AspireAssist) is an endoscopic weight loss device that is comprised of an endoscopically placed percutaneous gastrostomy tube and an external device to facilitate drainage of about 30% of the calories consumed in a meal, in conjunction with lifestyle (diet and exercise) counseling.In this 52-week clinical trial, 207 participants with a body-mass index (BMI) of 35.0-55.0 kg/mAt 52 weeks, participants in the AspireAssist group, on a modified intent-to-treat basis, had lost a mean (±s.d.) of 31.5±26.7% of their excess body weight (12.1±9.6% total body weight), whereas those in the Lifestyle Counseling group had lost a mean of 9.8±15.5% of their excess body weight (3.5±6.0% total body weight) (P0.001). A total of 58.6% of participants in the AspireAssist group and 15.3% of participants in the Lifestyle Counseling group lost at least 25% of their excess body weight (P0.001). The most frequently reported adverse events were abdominal pain and discomfort in the perioperative period and peristomal granulation tissue and peristomal irritation in the postoperative period. Serious adverse events were reported in 3.6% of participants in the AspireAssist group.The AspireAssist System was associated with greater weight loss than Lifestyle Counseling alone.

BackgroundPancreatic cystic lesions (PCLs) are a heterogenous group of lesions with varying degrees of malignant potential. PCLs are often incidentally detected on imaging. Management for patients without an immediate indication for resection or tissue sampling entails radiographic surveillance to assess for features concerning for malignant transformation. This study aims to determine the rates of adherence to surveillance recommendations for incidental PCLs, and identify factors associated with adherence or loss of follow-up.MethodsWe conducted a single-centre retrospective study of patients at a tertiary safety net hospital with incidentally discovered asymptomatic PCLs. Follow-up was defined as having undergone repeat imaging as recommended in the radiology report. Data were analysed using logistic regression.ResultsWithin our cohort (n=172), 123 (71.5%) subjects completed follow-up imaging. Attending a gastroenterology appointment was most strongly associated with completing follow-up for PCLs and remained significant (p=0.001) in a multivariate logistic regression model. Subjects without a documented primary care provider were less likely to have follow-up (p=0.028). Larger cyst size was associated with completion of follow-up in univariate only (p=0.067).ConclusionWe found that follow-up of an incidentally discovered PCLs was completed in the majority of our subjects. Incomplete follow-up for PCLs occurred in up to one in three to four patients in our cohort. Access to primary care and utilisation of subspecialty gastroenterology care are associated with completion of follow-up for PCLs. If validated, our findings can guide potential interventions to improve follow-up rates for PCLs.

Serrated polyps are precursors in an alternative pathway to colon cancer. These polyps are frequently sessile or flat, located in the proximal colon, and may be overlooked during colonoscopy. Histological criteria to classify these polyps have only recently been described. This study assessed the variation of serrated polyp detection among endoscopists and pathologists in an average risk-screening cohort and trends in detection over time.Endoscopy and pathology reports were reviewed from all average risk-screening colonoscopies at an urban academic medical center from 2006 through 2008. Polyps were classified as adenoma (tubular, tubulovillous, or villous), serrated polyp (hyperplastic polyp (HP), sessile serrated adenoma (SSA), or dysplastic serrated polyp (DSP)), adenocarcinoma, or other. Differences in polyp detection among endoscopists and pathologists were tested with χ(2)-tests. Potential predictors of polyp detection were modeled with Poisson regression.Included in the study were 4,335 polyps from 7,192 colonoscopies. Detection prevalence (patients with at least one polyp per 100 colonoscopies) was 22.2 for adenomas, 11.7 for HP, 0.6 for SSA, and 0.2 for DSP. Detection prevalence of proximal SSAs increased from 0.2 in 2006 to 4.4 in 2008 (P0.001). Detection prevalences among endoscopists differed significantly for adenomas, HP, and SSA. Classification rates among pathologists differed significantly for HP and SSA, but not for adenoma or DSP. On multivariate analysis, endoscopist was a significant predictor of adenoma, HP, and SSA. Pathologist was a significant predictor of HP, SSA, and DSP, but not adenoma.This study describes the detection of colorectal polyps in an average risk-screening cohort at an urban academic medical center. Detection of proximal SSAs increased during the study period. Detection of adenoma, HP, and SSA differed significantly by endoscopist. Classification of HP and SSA differed significantly by pathologist. Endoscopy and pathology practices should consider educational interventions to improve serrated polyp detection and standardize classification.

Background The most common complication of uncovered biliary self-expandable metal stents (SEMSs) is tumor ingrowth. The addition of an impenetrable covering may prolong stent patency. Objective To compare stent patency between uncovered and partially covered SEMSs in malignant biliary obstruction. Design Multicenter randomized trial. Setting Four teaching hospitals. Patients Adults with inoperable distal malignant biliary obstruction. Interventions Uncovered or partially covered SEMS insertion. Main outcome measures Time to recurrent biliary obstruction, patient survival, serious adverse events, and mechanism of recurrent biliary obstruction. Results From October 2002 to May 2008, 129 patients were randomized. Recurrent biliary obstruction was observed in 11 of 61 uncovered SEMSs (18%) and 20 of 68 partially covered SEMSs (29%). The median times to recurrent biliary obstruction were 711 days and 357 days for the uncovered and partially covered SEMS groups, respectively ( P = .530). Median patient survival was 239 days for the uncovered SEMS and 227 days for the partially covered SEMS groups ( P = .997). Serious adverse events occurred in 27 (44%) and 42 (62%) patients in the uncovered and partially covered SEMS groups, respectively ( P = .046). None of the uncovered and 8 (12%) of the partially covered SEMSs migrated ( P = .0061). Limitations Intended sample size was not reached. Allocation to treatment groups was unequal. Conclusions There was no significant difference in time to recurrent biliary obstruction or patient survival between the partially covered and uncovered SEMS groups. Partially covered SEMSs were associated with more serious adverse events, particularly migration. (Clinical trial registration number: NCT01047332.)

In recent years, the number of bariatric operations performed annually in the United States has increased dramatically, giving rise to a new set of challenges and postoperative complications that endoscopists will face. To perform endoscopy successfully and safely in these patients, gastroenterologists must become familiar with anatomic alterations created by bariatric surgery and the common adverse gastrointestinal symptoms and structural complications that can arise. This article will review the major bariatric operations, their postoperative complications, and techniques of diagnostic and therapeutic upper endoscopy in bariatric surgery patients.

Colorectal cancer is the third leading type of cancer, and the second leading cause of cancer-related death in the United States. Prevention of colorectal cancer should be achievable by screening programs that detect adenomas in asymptomatic patients and lead to their removal. In this manuscript, we review the major screening modalities, the advantages and disadvantages of each approach, the data supporting their use, and various issues affecting the implementation of each test. Screening guidelines will be reviewed, and future techniques for colorectal cancer screening examined.

Endoscopy in the bariatric surgical patient presents a new challenge for gastroenterologists, one that will be encountered with increasing frequency as the problem of obesity grows and performance of bariatric surgery rises. To ensure a safe, successful, and useful endoscopy, it is important to be familiar with the expected postsurgical anatomy and endoscopic appearance after the various bariatric operations, and the common complications that can arise. This article discusses various aspects of performing endoscopy in patients following bariatric surgery, with a focus on the gastric bypass and vertical banded gastroplasty.

Nonvariceal UGI bleeding is one of the most common emergencies that gastroenterologists encounter, and continues to be a significant cause of morbidity and mortality. The keys to management are rapid resuscitation and stabilization; appropriate triage based on pre-endoscopic risk factors; early endoscopy to achieve prompt diagnosis and implement hemostatic therapy to high-risk lesions; and aggressive antisecretory therapy (in the case of peptic ulcer bleeding) to reduce the risk of continued or recurrent bleeding.

Background The aim of this study was to describe the endoscopic findings in patients with upper GI symptoms after Roux-en-Y gastric bypass surgery and to correlate clinical features with endoscopic findings. Methods Patients with symptoms after Roux-en-Y gastric bypass referred for endoscopy were studied. Endoscopy was performed in standard fashion with a 9.8-mm diameter endoscope. Results Forty-nine patients underwent a total of 69 upper endoscopy procedures between January 2001 and February 2003. The most common endoscopic findings were the following: normal post-surgical anatomy (21 patients, 43%), marginal ulcer (13 patients, 27%), stomal stenosis (9 patients [19%], including 5 with a concomitant marginal ulcer), and staple-line dehiscence (8 patients [16%], including one with a marginal ulcer). Abdominal pain was the most common symptom (26 patients, 53%) and was more frequent among patients with a normal endoscopy compared with those with an abnormal endoscopy ( p =0.04). Stomal stenosis was present in 39% of patients with nausea, vomiting, or dysphagia; it was not present in any patient without these symptoms ( p =0.001). Fifteen percent of procedures performed within the first 6 postoperative months were normal, compared with 53% of those performed beyond 6 months ( p =0.02). There was no complication of endoscopy. Conclusions Among patients with symptoms after Roux-en-Y gastric bypass presenting for endoscopy, normal post-surgical anatomy was the most common finding. Marginal ulcer was the most common abnormality. Presentation with abdominal pain and performance of endoscopy beyond the 6th post-operative month were predictive of a normal endoscopy, and lack of nausea, vomiting, and dysphagia predicted the absence of stomal stenosis.

Hepatobiliary disorders occur frequently in patients with IBD, with PSC and cholangiocarcinoma being the most clinically significant for endoscopists. Endoscopic therapy for PSC is effective in improving symptoms, biochemical parameters, and radiographic abnormalities. Endoscopic therapy may also confer survival benefit, but this has yet to be confirmed in randomized, controlled trials. Treatment should be restricted to those individuals with a rapid decline in liver function testing or those with recurrent cholangitis. Cholangiocarcinoma is a serious complication of PSC and carries an extremely poor prognosis. ERCP with brush cytology has a relatively low sensitivity and the diagnosis is usually made after the disease has become metastatic. Malignant biliary obstruction can be palliated by endoscopic stenting. Photodynamic therapy is a promising experimental technique that may confer symptomatic and survival benefit in patients with nonresectable, advanced cholangiocarcinoma. IBD patients also have an elevated risk for developing acute and chronic pancreatitis as well as pancreatic insufficiency. The majority of cases of acute pancreatitis are likely due to medication side effects and local structural complications of IBD. The remainder may possibly represent true extraintestinal manifestations of IBD. Chronic pancreatitis is frequently subclinical, but may be accompanied by clinically relevant exocrine insufficiency. ERCP is the test of choice for the diagnosis of chronic pancreatitis, but the role of endoscopy in the therapeutic management of IBD-associated chronic pancreatitis remains to be defined.

Clinical trials in inflammatory bowel disease (IBD) are evolving at a rapid pace by employing central reading for endoscopic mucosal assessment in a field that was, historically, largely based on assessments by local physicians. This transition from local to central reading carries with it numerous technical, operational, and scientific challenges, many of which can be resolved by imaging core laboratories (ICLs), a concept that has a longer history in clinical trials in a number of diseases outside the realm of gastroenterology. For IBD trials, ICLs have the dual goals of providing objective, consistent assessments of endoscopic findings using central-reading paradigms whilst providing important expertise with regard to operational issues and regulatory expectations. This review focuses on current approaches to using ICLs for central endoscopic reading in IBD trials.

Inflammatory bowel disease (IBD) is a spectrum of disorders that leads to inflammation of the intestinal mucosa, classified clinically as ulcerative colitis (UC) or Crohn’s disease (CD). UC involves the large intestine and causes inflammation in a continuous pattern from the rectum to the cecum. CD, however, can involve the large or small intestines, generally spares the rectum, and can lead to fistulas, abscesses, and/or strictures. In the United States, it is estimated that between 1 million and 1.5 million people have IBD.1–3 There is no gold standard for classifying IBD as UC or CD, although this is crucial for prognostic and therapeutic reasons. In the majority of cases, UC can be distinguished from CD using clinical features, laboratory testing, routine white light endoscopy with associated biopsy histopathology, and radiological imaging. However, in approximately 10% to 15% of patients with disease limited to the colon, a definitive diagnosis can be difficult.4 IBD restricted to the colon that cannot be further classified as CD or UC is termed as IBD unclassified (IBD-U).5 Laboratory markers, such as fecal markers and serological antibody testing, may be used to aid in the diagnosis of IBD,6,7 and, in cases of IBD-U, to help and distinguish between IBD subtypes and identify high-risk individuals, which may have treatment implications.8,9 Although serological biomarkers alone are not useful in diagnosing IBD,10,11 they may have an adjunctive role in cases of IBD-U and in stratifying those at high-risk for disease-related complications. Optical spectroscopy has been suggested as a promising tool for the management of IBD.12–14 Fluorescence spectroscopy has been reported to differentiate normal colon from IBD ex vivo in murine models15 and to increase the detection of invisible flat intraepithelial neoplasia.16 Recently, Raman spectroscopy has been proposed as an optical biomarker for distinguishing CD from UC in vitro in ex vivo tissue samples from patients with IBD.17 Elastic scattering spectroscopy (ESS) and related reflectance spectroscopies have shown promise in vivo in the gastrointestinal tract for detecting neoplasia in the colon,18–22 dysplasia in the esophagus,21,23–27 and colitis and dysplasia in patients with IBD.18,19 ESS has also been used to distinguish pathologies in other epithelially lined hollow organs, such as the urinary bladder,28 and in cystic and solid tissues, including breast and associated lymph nodes,29,30 pancreas,31 and thyroid.32,33 ESS, mediated by application-specific fiberoptic probes with specialized optical geometries, is sensitive to the absorption spectra of major chromophores (e.g., oxy-/deoxy-hemoglobin) and, more importantly, to the scattering spectra related to micromorphological features of tissues that are in contact with the tip of the probe. ESS spectra derive from the wavelength-dependent optical scattering efficiency (and the effects of changes in the scattering angular probability) caused by optical index gradients because of cellular and subcellular structures. Thus, unlike Raman and fluorescence spectroscopy, ESS provides largely microstructural, not biochemical, information. As such, ESS is sensitive to structural features such as nuclear size, crowding, chromaticity, and chromatin granularity, as well as to mitochondrial and organellar size and density. Such features are, to varying degrees, components of a histopathological assessment. ESS, however, is a real-time, point-source measurement that senses these types of morphological changes semiquantitatively without actually rendering a microscopic image, per se. In addition, because of its inherent simplicity and miniaturizability, ESS is extremely low cost, clinically robust, and impacts procedure flow minimally, especially when integrated into standard endoscopic biopsy tools.21 In this article, we investigate whether ESS has utility as an in vivo real-time endoscopic reporter of disease activity and an optical biomarker for distinguishing CD from UC.

Colorectal cancer (CRC) is a heterogeneous disorder than arises via multiple distinct pathways, such as the serrated pathway, in which serrated polyps (including variants of hyperplastic polyps) are the precursor lesions. Approximately 15-20% of all CRCs arise via the serrated pathway, and these serrated carcinomas are clinically, morphologically, and molecularly distinct from conventional CRCs. The prevention of serrated carcinomas represents an important clinical challenge. Gastroenterologists need to recognize and remove potential precursor lesions and implement a post-polypectomy surveillance program when appropriate. This article focuses on the characteristics and significance of clinically relevant serrated polyps and addresses implications for CRC prevention practices.

GI endoscopists now have an integral role in the multidisciplinary treatment of obese patients undergoing bariatric surgery, particularly in the prevention and treatment of postoperative complications. Although it is controversial, routine preoperative upper endoscopy should be considered in all bariatric patients, especially those undergoing Roux-en-Y gastric bypass (RYGB) surgery. Endoscopists need to work in close coordination with their bariatric surgery colleagues in all phases of care in order to maximize the yield and safety of endoscopy in this patient population. The purpose of this article is to review the role of the endoscopist in a multidisciplinary obesity center as it pertains to the preoperative, intraoperative, and postoperative management of bariatric surgery patients. As the performance of bariatric surgery continues to rise in response to the obesity epidemic, GI endoscopists are becoming increasingly involved in the preoperative and postoperative care of patients who had bariatric surgery. The American Society for Gastrointestinal Endoscopy (ASGE) Standards of Practice Committee recently published its guidelines on the role of endoscopy in this patient population. 1 The purpose of this article is to complement those guidelines and to highlight the role of the endoscopist in a multidisciplinary obesity center as it pertains to the preoperative, intraoperative, and postoperative management of patients for bariatric surgery. THE ROLE OF PREOPERATIVE ENDOSCOPY

The aim of this study was to compare BRAF and KRAS, CpG island methylator phenotype (CIMP), and microsatellite instability (MSI) status in each of the histologic categories, including end-point carcinomas with residual adenoma, of the serrated polyp neoplasia pathway and the traditional (nonserrated) adenoma-carcinoma sequence. Deoxyribonucleic acid (DNA) was extracted from the selected samples and assayed for BRAF, KRAS2 codon12, 13, CIMP using markers hMLH1, MGMT, MINT1, MINT2, p16, and MSI using an assay for BAT25 and BAT26. A BRAF mutation was present in 82% of serrated carcinomas (SCas), 62% of serrated adenomas (SAs), 83% of serrated polyps with abnormal proliferation (SPAPs-syn. sessile serrated adenoma [SSA]), 76% of microvesicular serrated polyps (MVSPs), and was not found in any of the histologic categories of the traditional adenoma-carcinoma sequence. KRAS2 mutations were found in 43% of the goblet cell serrated polyp (GCSP) category, 13% of MVSPs, 7% of SPAPs, and 24% of SAs; in 26% of large traditional adenoma (lTAs) compared with small traditional adenomas (sTAs) (0/30; P0.005) and in 37.3% of traditional carcinomas (TCa). CIMP-H (1 marker positive) was significantly more frequent in SPAP, SA, and SCa compared with MVSP (P0.05); CIMP-H was present in 10% of sTAs but was found more frequently in lTA (44.4%; OR 7.2; P=0.007) and TCa (38.9%; OR 5.8; P=0.007). Higher CIMP levels (4 or more markers positive) were significantly more frequent in advanced categories of the serrated pathway (SAs [31%] and SCas [30%]) compared with lTAs [0%] and TCAs [3.4%] (OR 12.2; P=0.02). MSI-H was identified only in the adenocarcinoma component of SCas (9/11) or in the contiguous SAs (3/7). The findings indicate that a BRAF mutation is a specific marker for a serrated polyp pathway that has its origin in a hyperplastic polyp (MVSP) and a potential end point as MSI carcinoma. CIMP-High (CIMP-H) develops early in this sequence and MSI-H develops late. The data provided a less complete picture of a second serrated pathway, identified by a KRAS2 mutation in SAs, but showed that the progressive stages of both iterations of the serrated neoplasia pathway are separate and distinct from those of the traditional adenoma-carcinoma sequence.

The most common biliary problem in patients with inflammatory bowel disease is primary sclerosing cholangitis (PSC). The treatment of this disease is multifaceted and frequently requires a multidisciplinary approach involving internists, nutritionists, gastroenterologists, and surgeons. Unfortunately, other than liver transplantation, no therapy that is currently available has been proven to alter the natural history of PSC or prolong survival. Ursodeoxycholic acid is currently the most promising pharmacologic treatment option for slowing disease progression and should be used in higher than usual doses (20 to 30 mg/kg/d). Treatment of symptoms due to cholestasis, such as pruritis and steatorrhea, is an important aspect of the medical care of patients with PSC. Our preferred treatment of pruritis due to cholestasis is with bile acid binding exchange resins such as cholestyramine or colestipol (which is generally better tolerated than cholestyramine). Endoscopic therapy should be reserved for patients with obstructive jaundice, cholangitis, or symptomatic dominant biliary strictures. We recommend dilation of dominant strictures with graduated or balloon dilators followed by temporary stenting if the postdilation cholangiographic appearance is not improved or adequate biliary drainage cannot be assured. There is indirect evidence that the combination of ursodeoxycholic acid and endoscopic therapy to maintain biliary patency may improve transplant-free survival in patients with PSC, although this remains to be proven. Liver transplantation remains the only effective treatment of advanced PSC, and should be considered in patients with complications of cirrhosis or intractable pruritis or fatigue.