Dye-Based Chromoendoscopy in Patients With Lynch Syndrome: An Individual Patient Data Meta-Analysis of Randomized Trials.

INTRODUCTION: The additional diagnostic value of dye-based chromoendosocpy (CE) for surveillance of patients with Lynch syndrome is subject of debate. METHODS: To clarify this debate, we performed an individual patient data meta-analysis of randomized studies that compared CE with WLE for the detection of adenomas in patients with Lynch syndrome. RESULTS: Three randomized studies comprising 533 patients were included. The adenoma detection rate was 74/265 (28%) in patients randomized to WLE compared with 83/266 (31%) in patients randomized to CE (odds ratio 1.17; 95% confidence interval 0.81-1.70). DISCUSSION: Based on low-quality evidence, CE showed no apparent increase in adenoma detection compared to WLE during surveillance of patients with Lynch syndrome.

Associations of Height With the Risks of Colorectal and Endometrial Cancer in Persons With Lynch Syndrome.

People with Lynch syndrome (LS), who carry a pathogenic mutation in a DNA mismatch repair gene, have increased risks of colorectal cancer (CRC) and endometrial cancer (EC). A high reported variability in cancer risk suggests the existence of factors that modify cancer risk for persons with LS. We aimed to investigate the associations between height and CRC and EC risk for persons with LS using data from 2 large studies. Information on 1,115 men and 1,553 women with LS from the Colon Cancer Family Registry (1998-2007) and the GEOLynch Cohort Study (2006-2017) was harmonized. We used weighted Cox proportional hazards regression models with age on the time axis to estimate adjusted hazard ratios and 95% confidence intervals for each 5-cm increment in self-reported height. CRC was diagnosed in 947 persons during 65,369 person-years of observation, and 171 women were diagnosed with EC during 39,227 person-years. Height was not associated with CRC for either men (per 5-cm increment, hazard ratio (HR) = 1.00, 95% confidence interval (CI): 0.91, 1.11) or women (per 5-cm increment, HR = 1.01, 95% CI: 0.92, 1.11), nor was height associated with EC (per 5-cm increment, HR = 1.08, 95% CI: 0.94, 1.24). Hence, we observed no evidence for an association of height with either CRC or EC among persons with LS.

Diet quality and colorectal tumor risk in persons with Lynch syndrome.

BACKGROUND: Persons with Lynch syndrome (LS) have an increased risk of developing colorectal tumors (CRTs). Adherence to diet quality indices associated with colorectal cancer (CRC) risk in the general population has not been studied before in LS. METHODS: Dietary habits of 490 participants with LS from a prospective cohort study was collected using a food frequency questionnaire. The Dutch Healthy Diet index 2015 (DHD15-index) and Dietary Approaches to Stop Hypertension (DASH) were used to score food-based diet quality. Diet quality scores were divided into tertiles where a higher tertile reflects a higher diet quality. Multivariable Cox proportional hazard regression models were used to estimate the association between the DHD15-index, DASH score and CRT risk. RESULTS: During a median follow-up time of 53.4 months, 210 participants (42.9%) developed CRTs. The DHD-index and DASH score were not associated with CRT risk; hazard ratios for highest vs. lowest tertile were 1.00 (95% Confidence Interval (CI): 0.67-1.48) and 1.11 (95% CI: 0.74-1.69), respectively. No linear trends across the DHD-index and DASH score tertiles were observed (P-trend = 0.97 and 0.83 respectively). CONCLUSION: In contrast to observations in the general population, no evidence for an association between the food-based DHD15-index or DASH score and CRT risk was observed in persons with LS. Further studies are needed investigating the association between diet quality and mechanisms leading to the development of LS-associated tumors.

The Optimal Imaging Window for Dysplastic Colorectal Polyp Detection Using c-Met-Targeted Fluorescence Molecular Endoscopy.

Fluorescence molecular endoscopy (FME) is an emerging technique that has the potential to improve the 22% colorectal polyp detection miss-rate. We determined the optimal dose-to-imaging interval and safety of FME using EMI-137, a c-Met-targeted fluorescent peptide, in a population at high risk for colorectal cancer. Methods: We performed in vivo FME and quantification of fluorescence by multidiameter single-fiber reflectance/single-fiber fluorescence spectroscopy in 15 patients with a dysplastic colorectal adenoma. EMI-137 was intravenously administered (0.13 mg/kg) at a 1-, 2- or 3-h dose-to-imaging interval (n = 3 patients per cohort). Two cohorts were expanded to 6 patients on the basis of target-to-background ratios. Fluorescence was correlated to histopathology and c-Met expression. EMI-137 binding specificity was assessed by fluorescence microscopy and in vitro experiments. Results: FME using EMI-137 appeared to be safe and well tolerated. All dose-to-imaging intervals showed significantly higher fluorescence in the colorectal lesions than in surrounding tissue, with a target-to-background ratio of 1.53, 1.66, and 1.74 for the 1-, 2-, and 3-h cohorts, respectively, and a mean intrinsic fluorescence of 0.035 vs. 0.023 mm-1 (P < 0.0003), 0.034 vs. 0.021 mm-1 (P < 0.0001), and 0.033 vs. 0.019 mm-1 (P < 0.0001), respectively. Fluorescence correlated with histopathology on a macroscopic and microscopic level, with significant c-Met overexpression in dysplastic mucosa. In vitro, a dose-dependent specific binding was confirmed. Conclusion: FME using EMI-137 appeared to be safe and feasible within a 1- to 3-h dose-to-imaging interval. No clinically significant differences were observed among the cohorts, although a 1-h dose-to-imaging interval was preferred from a clinical perspective. Future studies will investigate EMI-137 for improved colorectal polyp detection during screening colonoscopies.

Associations of Pathogenic Variants in MLH1, MSH2, and MSH6 With Risk of Colorectal Adenomas and Tumors and With Somatic Mutations in Patients With Lynch Syndrome.

BACKGROUND & AIMS: Lynch syndrome is caused by variants in DNA mismatch repair (MMR) genes and associated with an increased risk of colorectal cancer (CRC). In patients with Lynch syndrome, CRCs can develop via different pathways. We studied associations between Lynch syndrome-associated variants in MMR genes and risks of adenoma and CRC and somatic mutations in APC and CTNNB1 in tumors in an international cohort of patients. METHODS: We combined clinical and molecular data from 3 studies. We obtained clinical data from 2747 patients with Lynch syndrome associated with variants in MLH1, MSH2, or MSH6 from Germany, the Netherlands, and Finland who received at least 2 surveillance colonoscopies and were followed for a median time of 7.8 years for development of adenomas or CRC. We performed DNA sequence analyses of 48 colorectal tumors (from 16 patients with mutations in MLH1, 29 patients with mutations in MSH2, and 3 with mutations in MSH6) for somatic mutations in APC and CTNNB1. RESULTS: Risk of advanced adenoma in 10 years was 17.8% in patients with pathogenic variants in MSH2 vs 7.7% in MLH1 (P < .001). Higher proportions of patients with pathogenic variants in MLH1 or MSH2 developed CRC in 10 years (11.3% and 11.4%) than patients with pathogenic variants in MSH6 (4.7%) (P = .001 and P = .003 for MLH1 and MSH2 vs MSH6, respectively). Somatic mutations in APC were found in 75% of tumors from patients with pathogenic variants in MSH2 vs 11% in MLH1 (P = .015). Somatic mutations in CTNNB1 were found in 50% of tumors from patients with pathogenic variants in MLH1 vs 7% in MSH2 (P = .002). None of the 3 tumors with pathogenic variants in MSH6 had a mutation in CTNNB1, but all had mutations in APC. CONCLUSIONS: In an analysis of clinical and DNA sequence data from patients with Lynch syndrome from 3 countries, we associated pathogenic variants in MMR genes with risk of adenoma and CRC, and somatic mutations in APC and CTNNB1 in colorectal tumors. If these findings are confirmed, surveillance guidelines might be adjusted based on MMR gene variants.

Effect of chromoendoscopy in the proximal colon on colorectal neoplasia detection in Lynch syndrome: a multicenter randomized controlled trial.

BACKGROUND AND AIMS: Patients with Lynch syndrome (LS) undergo regular surveillance by colonoscopy because of an increased risk of colorectal neoplasia, particularly in the proximal colon. Chromoendoscopy (CE) has been reported to improve neoplasia detection compared with conventional white-light endoscopy (WLE), but evidence is limited. Our aim was to investigate the effect of CE in the proximal colon on detection of neoplastic lesions during surveillance in LS. METHODS: This was a multicenter prospective randomized controlled trial of 246 patients with LS who were randomly assigned (1:1) to conventional WLE (n = 123) or colonoscopy with CE in the proximal colon (n = 123), stratified for previous colorectal adenomas and enrolling center. Two years after baseline colonoscopy, patients underwent colonoscopy with CE in the proximal colon. The primary outcome was the proportion of patients with at least one neoplastic lesion at baseline and after 2 years. RESULTS: Neoplasia detection rates at baseline colonoscopy were 27% for WLE versus 30% for CE (odds ratio [OR], 1.23; 95% confidence interval [CI], 0.69-2.2; P = .56). In the proximal colon, neoplasia detection rates were 16% for WLE versus 24% for CE (OR, 1.6; 95% CI, 0.9-3.1; P = .13). Total procedure time was 9 minutes longer in the CE group. At follow-up after 2 years, neoplasia detection rates were similar in both groups: 26% for the original WLE group versus 28% for the CE group (OR, 1.1; P = .81). CONCLUSIONS: CE in the proximal colon for LS surveillance was not superior to WLE with respect to the initial detection of neoplasia, and not associated with reduced neoplasia detection rates after 2 years. The value of CE remains to be established. (Clinical trial registration number: NCT00905710.).

Features of incident colorectal cancer in Lynch syndrome.

BACKGROUND AND OBJECTIVE: Despite intensive colonoscopic surveillance, a substantial proportion of Lynch syndrome (LS) patients develop colorectal cancer (CRC). The aim of this study was to characterize incident CRC in LS patients. METHODS: All patients diagnosed with incident CRC after start of colonoscopic surveillance were identified in the Dutch LS Registry of 905 patients. A retrospective analysis of patient records was carried out for patient characteristics, survival, CRC characteristics and findings of previous colonoscopy. RESULTS: Seventy-one patients (7.8%) were diagnosed with incident CRC. Median interval between incident CRC diagnosis and previous colonoscopy was 23.8 (range 6.7-45.6) months. Median tumor diameter was 2.5 cm, and 17% of the tumors were sessile or flat. Most patients (83%) had no lymph node metastases. There was no association between tumor size and colonoscopy interval or lymph node status. Most patients (65%) had no adenomas during previous colonoscopy. Two patients (2.8%) eventually died from metastatic CRC. CONCLUSION: The high frequency of incident CRC in LS likely results from several factors. Our findings lend support to the hypothesis of fast conversion of adenomas to CRC, as 65% of patients had no report of polyps during previous colonoscopy. High-quality colonoscopies are essential, especially as tumors and adenomas are difficult to detect because of their frequent non-polypoid appearance. Early detection due to surveillance as well as the indolent growth of CRC, as demonstrated by the lack of lymph node metastases, contributes to the excellent survival observed.

Endoscopic versus percutaneous biliary drainage in patients with resectable perihilar cholangiocarcinoma: a multicentre, randomised controlled trial.

BACKGROUND: In patients with resectable perihilar cholangiocarcinoma, biliary drainage is recommended to treat obstructive jaundice and optimise the clinical condition before liver resection. Little evidence exists on the preferred initial method of biliary drainage. We therefore investigated the incidence of severe drainage-related complications of endoscopic biliary drainage or percutaneous transhepatic biliary drainage in patients with potentially resectable perihilar cholangiocarcinoma. METHODS: We did a multicentre, randomised controlled trial at four academic centres in the Netherlands. Patients who were aged at least 18 years with potentially resectable perihilar cholangiocarcinoma requiring major liver resection, and biliary obstruction of the future liver remnant (defined as a bilirubin concentration of >50 µmol/L [2·9 mg/dL]), were randomly assigned (1:1) to receive endoscopic biliary drainage or percutaneous transhepatic biliary drainage through the use of computer-generated allocation. Randomisation, done by the trial coordinator, was stratified for previous (attempted) biliary drainage, the extent of bile duct involvement, and enrolling centre. Patients were enrolled by clinicians of the participating centres. The primary outcome was the number of severe complications between randomisation and surgery in the intention-to-treat population. The trial was registered at the Netherlands National Trial Register, number NTR4243. FINDINGS: From Sept 26, 2013, to April 29, 2016, 261 patients were screened for participation, and 54 eligible patients were randomly assigned to endoscopic biliary drainage (n=27) or percutaneous transhepatic biliary drainage (n=27). The study was prematurely closed because of higher mortality in the percutaneous transhepatic biliary drainage group (11 [41%] of 27 patients) than in the endoscopic biliary drainage group (three [11%] of 27 patients; relative risk 3·67, 95% CI 1·15-11·69; p=0·03). Three of the 11 deaths among patients in the percutaneous transhepatic biliary drainage group occurred before surgery. The proportion of patients with severe preoperative drainage-related complications was similar between the groups (17 [63%] patients in the percutaneous transhepatic biliary drainage group vs 18 [67%] in the endoscopic biliary drainage group; relative risk 0·94, 95% CI 0·64-1·40). 16 (59%) patients in the percutaneous transhepatic biliary drainage group and ten (37%) patients in the endoscopic biliary drainage group developed preoperative cholangitis (p=0·1). 15 (56%) patients required additional percutaneous transhepatic biliary drainage after endoscopic biliary drainage, whereas only one (4%) patient required endoscopic biliary drainage after percutaneous transhepatic biliary drainage. INTERPRETATION: The study was prematurely stopped because of higher all-cause mortality in the percutaneous transhepatic biliary drainage group. Post-drainage complications were similar between groups, but the data should be interpreted with caution because of the small sample size. The results call for further prospective studies and reconsideration of indications and strategy towards biliary drainage in this complex disease. FUNDING: Dutch Cancer Foundation.

No Difference in Colorectal Cancer Incidence or Stage at Detection by Colonoscopy Among 3 Countries With Different Lynch Syndrome Surveillance Policies.

BACKGROUND & AIMS: Patients with Lynch syndrome are at high risk for developing colorectal cancer (CRC). Regular colonoscopic surveillance is recommended, but there is no international consensus on the appropriate interval. We investigated whether shorter intervals are associated with lower CRC incidence and detection at earlier stages by comparing the surveillance policies in Germany, which evaluates patients by colonoscopy annually, in the Netherlands (patients evaluated at 1-2-year intervals), and Finland (patients evaluated at 2-3-year intervals). METHODS: We collected data from 16,327 colonoscopic examinations (conducted from 1984 through 2015) of 2747 patients with Lynch syndrome (pathogenic variants in the MLH1, MSH2, or MSH6 genes) from the German HNPCC Consortium, the Dutch Lynch Syndrome Registry, and the Finnish Lynch Syndrome Registry. Our analysis included 23,309 person-years of cumulative observation time. Time from the index colonoscopy to incident CRC or adenoma was analyzed using the Kaplan-Meier method; groups were compared using the log-rank test. We performed multivariable Cox regression analyses to identify factors associated with CRC risk (diagnosis of CRC before the index colonoscopy, sex, mutation, age, and presence of adenoma at the index colonoscopy). RESULTS: The 10-year cumulative CRC incidence ranged from 4.1% to 18.4% in patients with low- and high-risk profiles, respectively, and varied with age, sex, mutation, and prior detection of CRC or adenoma. Observed colonoscopy intervals were largely in accordance with the country-specific recommendations. We found no significant differences in cumulative CRC incidence or CRC stage at detection among countries. There was no significant association between CRC stage and time since last colonoscopy. CONCLUSIONS: We did not find a significant reduction in CRC incidence or stage of detection in Germany (annual colonoscopic surveillance) than in countries with longer surveillance intervals (the Netherlands, with 1-2-year intervals, and Finland, with 2-3-year intervals). Overall, we did not find a significant association of the interval with CRC risk, although age, sex, mutation, and prior neoplasia were used to individually modify colonoscopy intervals. Studies are needed to develop and validate risk-adapted surveillance strategies and to identify patients who benefit from shorter surveillance intervals.

Extracolonic cancer risk in Dutch patients with APC (adenomatous polyposis coli)-associated polyposis.

BACKGROUND: Screening of patients with familial adenomatous polyposis (FAP) have led to a substantial reduction in mortality due to colorectal cancer (CRC). Recent guidelines suggest that surveillance of non-intestinal malignancies should also be considered in those patients. However, the value of these surveillance programmes is unknown. The aims of this study were (1) to assess the occurrence of extracolonic malignancies in a large series of adenomatous polyposis coli (APC) mutation carriers and (2) to evaluate the causes of death. METHODS: All APC mutation carriers were selected from the Dutch polyposis registry. Data on causes of death were collected. Pathology reports were retrieved from the Dutch Pathology Registry. RESULTS: A total of 85 extracolonic malignancies were diagnosed in 74 of 582 APC mutation carriers. Duodenal and skin cancers were the most prevalent cancers. Thyroid cancer was observed in only 1.5% of the cases. The main cause of death was cancer (59% of all deaths), with 42% due to CRC and 21% due to duodenal cancer. One patient died from thyroid cancer. The second and third most common causes of death were cardiovascular disease (13% of all deaths) and desmoid tumours (11% of all deaths), respectively. CONCLUSION: Extending surveillance programmes to other cancers will not contribute significantly to the survival of patients with FAP.

Incidence of small bowel neoplasia in Lynch syndrome assessed by video capsule endoscopy.

BACKGROUND AND STUDY AIMS: Lynch syndrome (LS) patients have an increased risk of small bowel cancer. The question is whether surveillance will lead to early detection of (pre)malignant lesions. We recently reported on prevalence of small bowel neoplasia (SBN) in LS patients as assessed by video capsule endoscopy (VCE). The aim of this prospective study was to determine the incidence of SBN. PATIENTS AND METHODS: Asymptomatic LS patients who underwent a VCE were invited to undergo a second VCE procedure 2 years later. If abnormalities or polypoid lesions larger than 1 cm were detected, subsequent endoscopic procedures were performed. RESULTS: A total of 155 (78 %) of the initial 200 patients underwent a second VCE procedure after a mean of 2.2 (range 1 - 6) years. In 17 of the 155 (11 %) patients possibly significant lesions were detected, which required further investigation by means of gastroduodenoscopy (n = 8) or balloon-assisted endoscopy (n = 9). These procedures revealed no SBN. CONCLUSION: No SBN was found after 2 years. Surveillance of the small bowel by VCE does not seem to be warranted in asymptomatic LS patients.

Impact of non-anastomotic biliary strictures after liver transplantation on healthcare consumption, use of ionizing radiation and infectious events.

BACKGROUND: Non-anastomotic biliary strictures (NAS) after orthotopic liver transplantation (OLT) have a negative influence on graft survival. Expert opinion suggests a negative effect of NAS on other important aspects of post-transplant care, although its impact is largely unknown as data are scarce. METHODS: This retrospective single center study analyzed data on healthcare consumption, use of ionizing radiation, infectious complications and development of highly resistant microorganisms (HRMO) in adult patients with NAS. A comparison with a matched control group was made. RESULTS: Forty-three liver recipients with NAS and 43 controls were included. Hospital admissions were higher in patients with NAS. Most common reason for admission was bacterial cholangitis (BC), with 70% of the patients having at least one episode compared to 9% in the control group. In patients with NAS, 67% received at least one ERCP compared to 21% in the control group (p = 0.001). This resulted in a larger yearly received radiation dose for patients with NAS (p = 0.001). Frequency of intravenous antibiotic therapy was higher (p = 0.001) for patients with NAS, consistently resulting in a higher number of cultures found with HRMO (p = 0.012). CONCLUSION: NAS after OLT have a negative effect on post-transplant care, increasing readmission rates, interventional procedures, exposure to ionizing radiation, use of antibiotics, and development of HRMO.

Adherence to surveillance guidelines after removal of colorectal adenomas: a large, community-based study.

OBJECTIVE: To determine adherence to recommended surveillance intervals in clinical practice. DESIGN: 2997 successive patients with a first adenoma diagnosis (57% male, mean age 59 years) from 10 hospitals, who underwent colonoscopy between 1998 and 2002, were identified via Pathologisch Anatomisch Landelijk Geautomatiseerd Archief: Dutch Pathology Registry. Their medical records were reviewed until 1 December 2008. Time to and findings at first surveillance colonoscopy were assessed. A surveillance colonoscopy occurring within ± 3 months of a 1-year recommended interval and ± 6 months of a recommended interval of 2 years or longer was considered appropriate. The analysis was stratified by period per change in guideline (before 2002: 2-3 years for patients with 1 adenoma, annually otherwise; in 2002: 6 years for 1-2 adenomas, 3 years otherwise). We also assessed differences in adenoma and colorectal cancer recurrence rates by surveillance timing. RESULTS: Surveillance was inappropriate in 76% and 89% of patients diagnosed before 2002 and in 2002, respectively. Patients eligible under the pre-2002 guideline mainly received surveillance too late or were absent (57% of cases). For patients eligible under the 2002 guideline surveillance occurred mainly too early (48%). The rate of advanced neoplasia at surveillance was higher in patients with delayed surveillance compared with those with too early or appropriate timed surveillance (8% vs 4-5%, p<0.01). CONCLUSIONS: There is much room for improving surveillance practice. Less than 25% of patients with adenoma receive appropriate surveillance. Such practice seriously hampers the effectiveness and efficiency of surveillance, as too early surveillance poses a considerable burden on available resources while delayed surveillance is associated with an increased rate of advanced adenoma and especially colorectal cancer.

Prevalence of small-bowel neoplasia in Lynch syndrome assessed by video capsule endoscopy.

OBJECTIVE: The aim was to determine the prevalence of small-bowel neoplasia in asymptomatic patients with Lynch syndrome (LS) by video capsule endoscopy (VCE). DESIGN: After obtaining informed consent, asymptomatic proven gene mutation carriers aged 35-70 years were included in this prospective multicentre study in the Netherlands. Patients with previous small-bowel surgery were excluded. After bowel preparation, VCE was performed. The videos were read by two independent investigators. If significant lesions were detected, an endoscopic procedure was subsequently performed to obtain histology and, if possible, remove the lesion. RESULTS: In total, 200 patients (mean age 50 years (range 35-69), M/F 88/112), with proven mutations were included. These concerned MLH1 (n = 50), MSH2 (n = 68), MSH6 (n = 76), PMS2 (n = 3) and Epcam (n = 3) mutation carriers. In 95% of the procedures, caecal visualisation was achieved. Small-bowel neoplasia was detected in two patients: one adenocarcinoma (TisN0Mx) and one adenoma, both located in the duodenum. In another patient, a duodenal cancer (T2N0Mx) was diagnosed 7 months after a negative VCE. This was considered a lesion missed by VCE. All three neoplastic lesions were within reach of a conventional gastroduodenoscope. All patients with neoplasia were men, over 50 years of age and without a family history of small-bowel cancer. CONCLUSIONS: The prevalence of small-bowel neoplasia in asymptomatic patients with LS was 1.5%. All neoplastic lesions were located in the duodenum and within reach of conventional gastroduodenoscopy. Although VCE has the potential to detect these neoplastic lesions, small-bowel neoplasia may be missed. TRIAL REGISTRATION NUMBER: NCT00898768.

Completion rate of small bowel capsule endoscopy is higher after erythromycin compared to domperidone.

BACKGROUND: In up to 30 percent of small bowel capsule endoscopy procedures, the capsule does not reach the cecum within recording time. A prolonged gastric transit time has been recognized as a risk factor for incomplete capsule endoscopy. The aim of this study was to analyze if a single dose of orally administered erythromycin prior to capsule endoscopy results in a higher completion rate compared to orally administered domperidone. METHODS: Single centre, non-concurrent prospective cohort study, 649 capsule endoscopy procedures were included. Cecal completion rates, gastric and small bowel transit times and diagnostic yield were analyzed. RESULTS: 239 patients received erythromycin, 410 patients received domperidone. The cecal completion rate was 86% after erythromycin versus 80% after domperidone (p = 0.03). After excluding known risk factors for incomplete capsule endoscopy such as hospitalization and previous abdominal surgery, erythromycin still resulted in an increased completion rate (p = 0.04). Median gastric transit time was lower after erythromycin compared to domperidone (13 min versus 22 min, p < 0.001). Median small bowel transit times were similar in both groups (236 min versus 248 min, p = 0.21). CONCLUSIONS: In this study, the largest to date on this subject, the cecal completion rate was higher with erythromycin than with domperidone, but there was no difference in the diagnostic yield.

Non-small-bowel abnormalities identified during small bowel capsule endoscopy.

AIM: To investigate the incidence of non-small-bowel abnormalities in patients referred for small bowel capsule endoscopy, this single center study was performed. METHODS: Small bowel capsule endoscopy is an accepted technique to investigate obscure gastrointestinal bleeding. This is defined as bleeding from the digestive tract that persists or recurs without an obvious etiology after a normal gastroduodenoscopy and colonoscopy. Nevertheless, capsule endoscopy sometimes reveals findings outside the small bowel, i.e., within reach of conventional endoscopes. In this retrospective single center study, 595 patients undergoing capsule endoscopy between 2003 and 2009 were studied. The incidence of non-small bowel abnormalities was defined as visible abnormalities detected by capsule endoscopy that are located within reach of conventional endoscopes. RESULTS: In 595 patients, referred for obscure gastrointestinal bleeding or for suspected Crohn's disease, abnormalities were found in 306 (51.4%). Of these 306 patients, 85 (27.7%) had abnormalities within reach of conventional endoscopes; 63 had abnormalities apparently overlooked at previous conventional endoscopies, 10 patients had not undergone upper and lower endoscopy prior to capsule endoscopy and 12 had abnormalities that were already known prior to capsule endoscopy. The most common type of missed lesions were vascular lesions (n = 47). Non-small-bowel abnormalities were located in the stomach (n = 15), proximal small bowel (n = 22), terminal ileum (n = 21), colon (n = 19) or at other or multiple locations (n = 8). Ten patients with abnormal findings in the terminal ileum had not undergone examination of the ileum during colonoscopy. CONCLUSION: A significant proportion of patients undergoing small bowel capsule endoscopy had lesions within reach of conventional endoscopes, indicating that capsule endoscopy was unnecessarily performed.

Ursodeoxycholic acid counteracts celecoxib in reduction of duodenal polyps in patients with familial adenomatous polyposis: a multicentre, randomized controlled trial.

BACKGROUND: Due to prophylactic colectomy, mortality in patients with familial adenomatous polyposis (FAP) has changed, with duodenal cancer currently being the main cause of death. Although celecoxib reduces duodenal polyp density in patients with FAP, its long-term use may increase the risk of cardiovascular events and alternatives need to be explored. Preclinical studies suggest that the combination of celecoxib with ursodeoxycholic acid (UDCA) is a potentially effective strategy. We performed a randomized, double-blind, placebo-controlled trial to investigate the effect of celecoxib and UDCA co-treatment on duodenal adenomatosis in patients with FAP. METHODS: Patients with FAP received celecoxib (400 mg twice daily) and UDCA (1000-2000 mg daily, ~20-30 mg/kg/day, n=19) or celecoxib and placebo (n=18) orally for 6 months. Primary outcome was drug efficacy, assessed by comparing duodenal polyp density at pre- and post-intervention by blinded review of endoscopic recordings. As secondary outcomes, cell proliferation, apoptosis, and COX-2 levels in normal duodenal mucosa were assessed by immunohistochemistry or real-time quantitative polymerase chain reaction. RESULTS: In intention-to-treat analysis, deceased polyp density was observed after celecoxib/placebo treatment (p=0.029), whereas increased polyp density was observed after celecoxib/UDCA treatment (p=0.014). The difference in change in duodenal polyp density was statistically significant between the groups (p=0.011). No changes in secondary outcomes were observed. Thirty patients (81%) reported one or more adverse events, 16 patients (84%, Common Toxicity Criteria for Adverse Events version 3.0 (CTCAE) grade 1-3) treated with celecoxib/UDCA and 14 patients (78%, CTCAE grade 1-2) treated with celecoxib/placebo. Nine patients (24%) discontinued intervention prematurely, 5 patients (26%) treated with celecoxib/UDCA and 4 patients (22%) treated with celecoxib/placebo. CONCLUSIONS: Celecoxib reduces duodenal polyp density in patients with FAP, and unexpectedly, high dose UDCA co-treatment counteracts this effect. The benefit of long term use of celecoxib for duodenal cancer prevention needs to be weighed against the (risk of) adverse events. TRIAL REGISTRATION: http://ClinicalTrials.gov, identifier NCT00808743.

Features of adenoma and colonoscopy associated with recurrent colorectal neoplasia based on a large community-based study.

BACKGROUND & AIMS: We investigated adenoma and colonoscopy characteristics that are associated with recurrent colorectal neoplasia based on data from community-based surveillance practice. METHODS: We analyzed data of 2990 consecutive patients (55% male; mean age 61 years) newly diagnosed with adenomas from 1988 to 2002 at 10 hospitals throughout The Netherlands. Medical records were reviewed until December 1, 2008. We excluded patients with hereditary colorectal cancer (CRC) syndromes, a history of CRC, inflammatory bowel disease, or without surveillance data. We analyzed associations among adenoma number, size, grade of dysplasia, villous histology, and location with recurrence of advanced adenoma (AA) and nonadvanced adenoma (NAA). We performed a multivariable multinomial logistic regression analysis to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: During the surveillance period, 203 (7%) patients were diagnosed with AA and 954 (32%) patients with NAA. The remaining 1833 (61%) patients had no adenomas during a median follow-up of 48 months. Factors associated with AA during the surveillance period included baseline number of adenomas (ORs ranging from 1.6 for 2 adenomas; 95% CI: 1.1-2.4 to 3.3 for ≥5 adenomas; 95% CI: 1.7-6.6), adenoma size ≥10 mm (OR = 1.7; 95% CI: 1.2-2.3), villous histology (OR = 2.0; 95% CI: 1.2-3.2), proximal location (OR = 1.6; 95% CI: 1.2-2.3), insufficient bowel preparation (OR = 3.4; 95% CI: 1.6-7.4), and only distal colonoscopy reach (OR = 3.2; 95% CI: 1.2-8.5). Adenoma number had the greatest association with NAA. High-grade dysplasia was not associated with AA or NAA. CONCLUSIONS: Large size and number, villous histology, proximal location of adenomas, insufficient bowel preparation, and poor colonoscopy reach were associated with detection of AA during surveillance based on data from community-based practice. These characteristics should be used jointly to develop surveillance policies for adenoma patients.

Endoscopic corticosteroid injections do not reduce dysphagia after endoscopic dilation therapy in patients with benign esophagogastric anastomotic strictures.

BACKGROUND & AIMS: Benign anastomotic strictures are often difficult to treat. We assessed the efficacy of adding corticosteroid injections to endoscopic dilation therapy with Savary bougienage. METHODS: In a multicenter, double-blind trial, 60 patients (mean age, 63 ± 9 years; 78% male) with an untreated cervical anastomotic stricture after esophagectomy with gastric tube reconstruction and dysphagia for at least solid food were randomly assigned to groups given 4 quadrant injections of 0.5 mL triamcinolone (40 mg/mL, n = 29) or saline (controls, n = 31) into the stricture, followed by Savary dilation to 16 mm. Dysphagia, complications, and quality of life were assessed after 1 and 2 weeks and 1, 3, and 6 months. The primary end point was a dysphagia-free period of 6 months. RESULTS: In the corticosteroid group, 45% of the patients remained dysphagia-free for 6 months, compared with 36% of controls (relative risk, 1.26; 95% confidence interval, 0.68-2.36; P = .46). Median time to repeat dilation was 108 days (range, 15-180 days) in the corticosteroid group vs 42 days (range, 17-180 days) for controls (P = .11). A median number of 2 dilations (range, 1-7) was performed in the corticosteroid group vs 3 dilations (range, 1-9) in controls (relative risk, 0.76; 95% confidence interval, 0.42-1.38; P = .36). Two major intervention-related complications occurred, 1 submucosal laceration in the corticosteroid group and 1 hemorrhage in the control group. Four patients in the corticosteroid group, but none of the controls, developed Candida esophagitis (P = .03). CONCLUSIONS: Corticosteroid injections do not provide a statistically significant decrease in frequency of repeat dilations or prolongation of the dysphagia-free period in patients with benign anastomotic esophagogastric strictures. Dutch Trial Registration Number 2236.

Role of new endoscopic techniques in Lynch syndrome.

Lynch syndrome, or hereditary nonpolyposis colorectal cancer (HNPCC), is the most common hereditary condition predisposing for colorectal cancer. International guidelines recommend surveillance of the colorectum by colonoscopy every 1-2 years starting at the age of 20-25 years. This has been shown to reduce the incidence of, and mortality due to colorectal cancer. Aim of this review was to determine the current role of new endoscopic techniques, such as narrow-band imaging, autofluorescence endoscopy and chromoendoscopy in the surveillance of Lynch syndrome. So far, six studies have been published in which the new endoscopic techniques were investigated in Lynch syndrome: narrow-band imaging (n = 1), autofluorescence endoscopy (n = 1) and chromoendoscopy (n = 4). At this moment, none of the new endoscopic techniques have shown clear and convincing superiority over conventional white light colonoscopy in Lynch syndrome subjects. Of these three techniques, chromoendoscopy appears to be the most promising new endoscopic technique in aiding in the detection of neoplastic lesions in Lynch syndrome, although further prospective studies are needed.