The ideal technique for processing SpyBite tissue specimens: a prospective, single-blinded, pilot-study of histology and cytology techniques.

Background and study aims Diagnostic sensitivity for indeterminate biliary lesions remains suboptimal. Cytology techniques may mitigate the impediment of small cholangioscopic specimens. Our primary aim was to compare cell block cytology (CB) with standard histology for foregut SpyBite (SB) specimens. Our secondary aim was to assess CB in biliary SB biopsies. Patients and methods This was a two-phase prospective pilot study. In phase one, a prospective pilot study, foregut SB specimens from three sites (4 per site per patient per processing technique) were allocated to CB or histology, and assessed by a single, blinded pathologist. The gold standard comprised two standard forceps (CFB) histological specimens per site per patient. Specimen ease of processing, size and number, adequacy for diagnosis and artefact were evaluated. In phase two, CB was used for consecutive patients with indeterminate biliary lesions, and compared with phase one CB results. Results In phase one, 240 SB foregut biopsies were performed in 10 patients, 227 specimens recorded by pathologist. Specimen origin was identified in 100 % and 97 % of histology and CB batches respectively. Specimens were significantly larger in the histology group (2.02 mm vs 1.49 mm, P  < 0.05). There was a trend to less crush artifact with CB, and no difference in processing difficulty. In phase two, 11 patients (63.0 ±12.7 years, 91 % female) underwent SpyGlass (SG) assessment of suspected indeterminate stricture (n = 8) or mass (n = 3), and six underwent SB. All CB specimens were adequate for diagnosis. Specimen parameters were not significantly different from luminal CB outcomes. Conclusions In this pilot study, cell block cytology showed similar results as histological analysis of SpyBite specimens in the analysis of biliary stricture.

Spot diagnosis of intermittent gastrointestinal bleeding.

Background and study aims In this case report with video, we present a unique image of a rare, but important cause of gastrointestinal bleeding which often is missed due to its intermittent nature.

EUS-guided biliary drainage: A comprehensive review of the literature.

EUS-guided biliary drainage (EUS-BD) has emerged as a technique for gaining biliary access when ERCP fails. This article gives a comprehensive review on the role and technique of EUS-BD. Moreover, we propose an algorithm guiding the clinician when to consider EUS-BD after failed ERCP or in anticipated difficult cannulations.

Double-balloon enteroscopy-assisted dilatation avoids surgery for small bowel strictures: A systematic review.

AIM: To evaluate the therapeutic role of double-balloon enteroscopy (DBE) in small bowel strictures and to propose a standard approach to small bowel strictures. METHODS: Systematic review of studies involving DBE in patients with small bowel strictures. Only studies limited to small bowel strictures were included and those with ileo-colonic strictures were excluded. RESULTS: In total 13 studies were included, in which 310 patients were dilated. The average follow-up time was 31.8 mo per patient. The complication rate was 4.8% per patient and 2.6% per dilatation. Surgery was avoided in 80% of patients. After the first dilatation, 46% were treated with re-dilatation and only 17% required surgery. CONCLUSION: DBE-assisted dilatation avoids surgery in 80% of patients with small bowel strictures and is safe and effective. We propose a standardized approach to small bowel strictures.

Prevalence and outcomes of pancreatic cystic neoplasms in liver transplant recipients.

AIM: To determine the prevalence, characteristics and clinical course of pancreatic cystic neoplasms (PCNs) in liver transplantation (LT) recipients. METHODS: We retrospectively studied consecutive patients who underwent LT between January 1998 to April 2016. Clinical and laboratory data were obtained from patient medical records. Imaging findings on computed tomography and magnetic resonance cholangiopancreatography were reviewed by two radiologists. RESULTS: During the study period, 872 patients underwent cadaveric LT. Pancreatic cysts were identified in 53/872 (6.1%) and 31/53 (58.5%) were PCNs [28 intraductal papillary mucinous neoplasm (IPMN), 2 mucinous cystic neoplasm (MCN), 1 serous cystadenoma]. Patients with PCNs exhibited less male predominance (55% vs 73%, P = 0.03) compared to patients without pancreatic cysts. Thirteen patients (42%) were diagnosed with PCN pre-LT while 18 patients (58%) developed PCN post-LT. The median size of PCNs was 13mm [interquartile range (IQR) 10-20 mm]. All IPMNs were side-branch type. Most PCNs were found in the head and body of pancreas (37% each), followed by the tail (25%). Five patients underwent further evaluation with endoscopic ultrasound. Progress imaging was performed on 81% of patients. PCNs remained stable in size and number in all but 2 patients. During a median follow up of 39 mo (IQR 26-58 mo), the 2 (6%) patients with MCN underwent pancreatectomy. No PCN patient developed pancreatic adenocarcinoma, while 5 died from illnesses unrelated to the PCN. Among patients without PCN, 1/841 (0.1%) developed pancreatic adenocarcinoma. CONCLUSION: The prevalence of PCNs in LT recipients was similar to the general population (3.6%, 31/872). Side-branch IPMNs do not appear to have accelerated malignant potential in post-LT patients, indicating the current surveillance guidelines are applicable to this group.

Increased suppressor of cytokine signaling-3 expression predicts mucosal relapse in ulcerative colitis.

BACKGROUND: Most biomarkers predicting mucosal relapse of ulcerative colitis (UC) patients in clinical remission represent low levels of mucosal inflammation. Since SOCS3 expression may increase the vulnerability of intestinal epithelial cells (IECs) to various insults, we investigated whether its expression predicts mucosal relapse in UC patients in clinical remission without any signs of mucosal inflammation. METHODS: UC patients (n = 32) in clinical, endoscopic, and histological remission were followed up for 9 years. IEC expression of SOCS3, p-STAT3, and p-STAT1 were assessed with biopsies from the baseline colonoscopy, last colonoscopy before relapse, and colonoscopy at relapse. Clinical data, endoscopy, and histology reports were collected from patient charts. RESULTS: Twenty-six (81%) patients had histological relapse, 19 (59%) developed an endoscopic relapse, and 17 (53%) had a clinical relapse during follow-up. SOCS3 expression at first colonoscopy during remission correlated with shorter time to histological, endoscopic, and clinical relapse. SOCS3 expression was increased at the last colonoscopy before relapse, approaching relapse levels, whereas p-STAT3 expression was low during the entire remission. A positive correlation between IEC SOCS3 and its inducer p-STAT1 was shown. CONCLUSIONS: SOCS3 IEC expression during remission may be useful in predicting mucosal relapse in patients without any signs of mucosal inflammation. These data strengthen our hypothesis that SOCS3 contributes to enhanced vulnerability of IEC during remission. Thus, SOCS3 levels during remission may function as a therapeutic target for clinical monitoring and early induction of mucosal healing.

Disease severity does not affect the interval between IBD diagnosis and the development of CRC: results from two large, Dutch case series.

BACKGROUND: The increased risk of colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD) is well established. The incidence of IBD-related CRC however, differs markedly between cohorts from referral centers and population-based studies. In the present study we aimed to identify characteristics potentially explaining these differences in two cohorts of patients with IBD-related CRC. METHODS: PALGA, a nationwide pathology network and registry in The Netherlands, was used to search for patients with IBD-associated CRC between 1990 and 2006. Patients from 7 referral hospitals and 78 general hospitals were included. Demographic and disease specific parameters were collected retrospectively using patient charts. RESULTS: A total of 281 patients with IBD-associated CRC were identified. Patients from referral hospitals had a lower median age at IBD diagnosis (26 years vs. 28 years (p=0.02)), while having more IBD-relapses before CRC diagnosis than patients from general hospitals (3.8 vs. 1.5 (p<0.01)). In patients from referral hospitals, CRC was diagnosed at a younger age (47 years vs. 51 years (p=0.01)). However, the median interval between IBD diagnosis and diagnosis of CRC was similar in both cohorts (19 years in referral hospitals vs. 17 years in general hospitals (p=0.13)). CONCLUSIONS: IBD patients diagnosed with CRC treated in referral hospitals in The Netherlands are younger at both the diagnosis of IBD and CRC than IBD patients with CRC treated in general hospitals. Although patients from referral centers appeared to have a more severe course of IBD, the interval between IBD and CRC diagnosis was similar.

Majority of patients with inflammatory bowel disease in clinical remission have mucosal inflammation.

BACKGROUND: Management of inflammatory bowel disease (IBD) is increasingly focused on mucosal remission. We assessed the prevalence of mucosal inflammation during clinical remission, the clinical consequences, and the impact on disease course. METHODS: IBD patients from two referral centers who underwent a surveillance colonoscopy while clinically in remission between January 2001 and December 2003 were included. Follow-up ended May 1, 2009. Clinical data were collected from patient charts. Statistical analysis was performed using independent t-tests and nonparametric tests. RESULTS: In total, 152 IBD patients were included (98 [65%] ulcerative colitis, 46 [30%] Crohn's disease; 85 [56%] males). Median follow-up was 6.8 years (interquartile range [IQR] 6-8). Forty-seven (31%) patients had no signs of inflammation during endoscopy (group A). Of the remaining 105 (68%) patients, 51 (49%) had both endoscopic and histological inflammation (group B), 51 (49%) histological inflammation only (group C), two (2%) endoscopic lesions only (group D). Two years later, 29% of all patients had endoscopic inflammation and another 27% had only microscopic inflammation. In 39% the inflammation had resolved spontaneously. Inflammation was more often found in group B+C (n = 62/102; 61%) than in group A (n = 17/47; 36%; P = 0.21). Inflammation was not associated with more frequent clinical relapses nor with stricture formation, nor with the need for surgery. CONCLUSIONS: A large proportion of IBD patients have mucosal inflammation without clinical symptoms. Although one-third recover spontaneously, mucosal inflammation in patients who are clinically in remission is associated with more severe mucosal disease activity, but not with more complications or symptomatic flares during follow-up.

Malignant transformation of perianal and enterocutaneous fistulas is rare: results of 17 years of follow-up from The Netherlands.

OBJECTIVE: Malignant transformation of fistulas has been observed, particularly in perianal fistulas in Crohn's disease (CD) patients. The prevalence of adenocarcinoma in enterocutaneous fistulas and non-CD-related fistulas, however, is unknown. We investigated adenocarcinoma originating from perianal and enterocutaneous fistulas in both CD patients and non-CD patients from nine large, mostly tertiary referral, hospitals in The Netherlands. METHODS: Patients suffering from fistulizing disease and either dysplasia or adenocarcinoma between January 1990 and January 2007 were identified using the nationwide automated pathology database (PALGA). Clinical and histopathological data were collected and verified using hospital patient-charts and reported by descriptive statistics. The total CD-population comprised 6058 patients. RESULTS: In a study-period of 17 years, 2324 patients with any fistula were reported in PALGA. In 542 patients, dysplasia or adenocarcinoma was also mentioned. After initial review and additional detailed chart review, 538 patients were excluded, mainly because the adenocarcinoma was not related to the fistula. In the remaining four patients, all suffering from CD, adenocarcinoma originating from the fistula-tract was confirmed. The malignancies developed 25 years (IQR 10-38) after CD diagnosis, and 10 years (IQR 6-22) after fistula diagnosis. Median age at time of adenocarcinoma diagnosis was 48.3 years (IQR 43-58). Only one patient had clinical symptoms indicative for adenocarcinoma. In three other patients, the adenocarcinoma was found coincidently. CONCLUSIONS: Adenocarcinoma complicating perianal or enterocutaneous fistula-tracts is a rare finding. Only 4 out of 6058 CD patients developed a fistula-associated adenocarcinoma. We could not identify any malignant transformations in non-CD-related fistulas in our 17 years study-period.

The risk of inflammatory bowel disease-related colorectal carcinoma is limited: results from a nationwide nested case-control study.

OBJECTIVES: The risk for inflammatory bowel disease (IBD)-related colorectal cancer (CRC) remains a matter of debate. Initial reports mainly originate from tertiary referral centers, and conflict with more recent studies. Overall, epidemiology of IBD-related CRC is relevant to strengthen the basis of surveillance guidelines. We performed a nationwide nested case-control study to assess the risk for IBD-related CRC and associated prognostic factors in general hospitals. METHODS: IBD patients diagnosed with CRC between January 1990 and July 2006 in 78 Dutch general hospitals were identified as cases, using a nationwide automated pathology database. Control IBD patients without CRC were randomly selected. Clinical data were collected from detailed chart review. Poisson regression analysis was used for univariable and multivariable analyses. RESULTS: A total of 173 cases were identified through pathology and chart review and compared with 393 controls. The incidence rate of IBD-related CRC was 0.04%. Risk factors for IBD-related CRC were older age, concomitant primary sclerosing cholangitis (PSC, relative ratio (RR) per year duration 1.05; 95% confidence interval (CI) 1.01-1.10), pseudopolyps (RR 1.92; 95% CI 1.28-2.88), and duration of IBD (RR per year 1.04; 95% CI 1.02-1.05). Using immunosuppressive therapy (odds ratio (OR) 0.3; 95% CI 0.16-0.56, P<0.001) or anti-tumor necrosis factor (TNF) (OR 0.09; 95% CI 0.01-0.68, P<0.02) was protective. CONCLUSIONS: We found a limited risk for developing IBD-related CRC in The Netherlands. Age, duration of PSC and IBD, concomitant pseudopolyps, and use immunosuppressives or anti-TNF were strong prognostic factors in general hospitals.

A short course of corticosteroids prior to surveillance colonoscopy to decrease mucosal inflammation in inflammatory bowel disease patients: results from a randomized controlled trial.

BACKGROUND: Inflammation is a known pitfall of surveillance colonoscopy for inflammatory bowel disease (IBD) as it is difficult to differentiate between inflammation and true dysplasia. This randomized controlled trial assessed the effectiveness of a low dose of corticosteroids prior to surveillance colonoscopy to decrease mucosal inflammation. METHODS: IBD-patients scheduled for surveillance colonoscopy between July 2008-January 2010 were eligible to participate. Patients were randomized to either two weeks daily 20mg prednisone and calcium plus vitamin D prior to surveillance colonoscopy or no treatment. All biopsies were reviewed by an expert gastrointestinal pathologist who was blinded for medication-use. Statistics were performed using chi-square tests, non-parametric tests and binary logistic regression. RESULTS: Sixty patients (M/F 30/30, UC/CD 31/29) participated: 31 (52%) in the treatment arm and 29 (48%) in the control group. In the treatment arm, 247 biopsies were scored against 262 in the control group. In the treatment arm 27 out of 247 biopsies (10.9%) had a score >1 on the Geboes scale, against 50 out of 262 biopsies (19.1%) in the control group, p=0.013. In total, 58% of the treatment arm against 66% of the control group had endoscopic or histological mucosal inflammation (p=0.6). There was a trend for patients in the treatment arm to have less severe inflammation compared with the control group, however this was not significant (p=0.12). CONCLUSIONS: In our cohort, a short course of corticosteroids decreases the overall histological disease activity in individual biopsies without major side-effects. Moreover, there is a trend for corticosteroids to decrease the maximum severity of both endoscopic and histological disease activity per patient.

Inflammatory bowel disease-patients are insufficiently educated about the basic characteristics of their disease and the associated risk of colorectal cancer.

BACKGROUND/AIM: Limited data are available about inflammatory bowel disease-patients' knowledge of disease and associated risks. We assessed patients' knowledge of disease and its associated risks/complications, and their perspectives on current recommendations for colectomy when low-grade dysplasia is found. METHODS: Inflammatory bowel disease-patients at a regional patient-information-day were asked to anonymously complete a survey (group-A). A 2nd group was recruited online through the Dutch inflammatory bowel disease-patients' association (group-B). RESULTS: In group-A, 109 inflammatory bowel disease-patients completed the survey (76% Crohn's disease, 24% ulcerative colitis, 78% female). Thirty-three patients (30%) were unaware of their disease-localization; 30% thought inflammatory bowel disease shortened their life-expectancy; 26% thought it was likely for a severe complication to occur during colonoscopy. Patients estimated their 10-year colorectal carcinoma-risk at 25%. Mean perceived colorectal carcinoma-associated mortality-risk was 13%. Patients would agree to colectomy if their current colorectal carcinoma-risk was at least 53% and 70% would refuse physicians' recommendation for colectomy if dysplasia were detected with a 20% risk of concomitant colorectal carcinoma. Group-B (n=393 inflammatory bowel disease-patients) verified the results above. However, fewer patients (52%) would refuse physicians' recommendation for colectomy, p=0.01. CONCLUSION: Inflammatory bowel disease-patients are ill-informed about their disease and its associated risks. Improvement of patient-education is necessary to appropriately involve patients in the decision-making process.

When should ulcerative colitis patients undergo colectomy for dysplasia? Mismatch between patient preferences and physician recommendations.

BACKGROUND: If dysplasia is found on biopsies during surveillance colonoscopy for ulcerative colitis (UC), many experts recommend colectomy given the substantial risk of synchronous colon cancer. The objective was to learn if UC patients' perceptions of their colon cancer risk and if their preferences for elective colectomy match with physicians' recommendations if dysplasia was found. METHODS: A self-administered written survey included 199 patients with UC for at least 8 years (mean age 49 years, 52% female) who were recruited from Dartmouth-Hitchcock (n = 104) and the University of Chicago (n = 95). The main outcome was the proportion of patients who disagree with physicians' recommendations for colectomy because of dysplasia. RESULTS: Almost all respondents recognized that UC raised their chance of getting colon cancer. In all, 74% thought it was "unlikely" or "very unlikely" to get colon cancer within the next 10 years and they quantified this risk to be 23%; 60% of patients would refuse a physician's recommendation for elective colectomy if dysplasia was detected, despite being told that they had a 20% risk of having cancer now. On average, these patients would only agree to colectomy if their risk of colon cancer "right now" were at least 73%. CONCLUSIONS: UC patients recognize their increased risk of colon cancer and undergo frequent surveillance to reduce their risk. Nonetheless, few seem prepared to follow standard recommendations for elective colectomy if dysplasia is found. This may reflect the belief that surveillance alone is sufficient to reduce their colon cancer risk or genuine disagreement about when it is worth undergoing colectomy.

Patients' preferences regarding shared decision-making in the treatment of inflammatory bowel disease: results from a patient-empowerment study.

BACKGROUND: Shared decision-making is gaining favor in clinical practice, although the extent to which patients want to be involved in choosing their treatment varies substantially. Because data are lacking on the preferences of patients with chronic diseases such as inflammatory bowel disease (IBD), we wanted to assess IBD patients' preferences about being involved in such decisions. METHODS: Adult IBD patients were asked to anonymously complete an online survey on their preferences. Non-parametric tests (chi(2)) were used to determine the relationship between responses and respondents. RESULTS: The questionnaire was completed by 1,067 patients, 617 with Crohn's disease and 450 with ulcerative colitis. Patients' mean age was 43 (SD 13.7) years; the majority were female (66%). In total, 866 patients (81%) reported it as 'very important' to be actively involved in the decision-making process, and another 177 (17%) rated it as 'quite important'. When asked how their treatment could be improved, 537 patients (50%) wanted close, equitable collaboration with their physician. This preference was significantly associated with a disease duration of

Patient's perspectives important for early anti-tumor necrosis factor treatment in inflammatory bowel disease.

BACKGROUND/AIM: We hypothesized that limited information is given to patients on the risks and benefits of individual therapy, and feedback is lacking to verify if patients correctly interpreted the given information. We assessed the perspectives of patients with inflammatory bowel disease (IBD) concerning the treatment-associated risks/benefits of infliximab. METHODS: Patients were asked to complete a survey regarding the benefits and risks of infliximab. Results are reported as descriptive statistics. Comparisons between groups were analyzed using independent t tests and the Kruskal-Wallis test. RESULTS: In total, 152 IBD patients completed the questionnaire. Fifty-seven percent (78/138) estimated the 1-year remission rate from infliximab to be >50%. Seventy-one percent (104/146) indicated they would not take a drug with risks reflecting those estimated for infliximab if the 1-year remission rate was <75%. Crohn's disease patients and those recalling a discussion regarding the risks/benefits of infliximab treatment had higher estimates of the 1-year remission rate with infliximab than ulcerative colitis patients (p = 0.03) and patients who did not recall previous information (p = 0.03). Perceptions were independent of age and disease duration. CONCLUSION: IBD patients misperceive the risks and benefits of infliximab. The majority of patients would not accept treatment-related risks if the 1-year remission rate was <75%. Counseling on treatment-associated risks and benefits should be ameliorated.