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BACKGROUND: Individuals with Lynch syndrome are at high risk for colorectal cancer (CRC). Regular colonoscopies have proven to decrease CRC incidence and mortality. However, colonoscopy is burdensome and interval CRCs still occur. Hence, an accurate, less-invasive screening method that guides the timing of colonoscopy would be of important value.AIM: To outline the performance of non-endoscopic screening modalities for Lynch-associated CRC and adenomas.METHODS: Systematic literature search in MEDLINE and EMBASE to identify studies investigating imaging techniques and biomarkers for detection of CRC and adenomas in Lynch syndrome. The QUADAS-2 tool was used for the quality assessment of included studies.RESULTS: Seven of 1332 screened articles fulfilled the inclusion criteria. Two studies evaluated either CT colonography or MR colonography; both techniques were unable to detect CRC and (advanced) adenomas CONCLUSIONS: Imaging techniques are unsuitable for colon surveillance in Lynch syndrome, whereas biomarkers are understudied. Having outlined biomarker research in Lynch-associated and sporadic CRC/adenomas, we believe that these non-invasive markers may hold potential (whether or not combined) for this population. As they could be of great value, (pre-)clinical studies in this field should be prioritised.

Background and Aims Percutaneous endoscopic gastrostomy (PEG) is indicated for prolonged enteral nutrition. This study aimed to analyze the outcome and to identify potential risk factors for complications in PEG procedures. Methods A single‐center retrospective analysis of the performed PEG procedures during the period January 2010 till January 2020. Results A PEG placement procedure was performed in 854 patients (64.1% male) and was successful in 833 (97.5%). In total, 513 push (61.6%) and 320 pull (38.6%) PEGs were placed. The mean age was 60.7 years, and the median follow‐up was 267 days. The push PEG was associated with peri‐procedural bleeding (P = 0.002) and tube dislodgements (P, Our study shows that the push and pull PEG placements are both safe and feasible procedures, with a low PEG‐related mortality.

Item does not contain fulltext Nodular regenerative hyperplasia (NRH) is a poorly understood liver condition, which is increasingly recognized in thiopurine-treated patients with inflammatory bowel disease (IBD).(1) It is difficult to establish an optimal approach to NRH patients, because its manifestations are highly variable (from asymptomatic to symptoms of noncirrhotic portal hypertension [NCPH]) and the prognosis is unknown.(2) The aim of this study was to identify NRH cases in IBD patients treated with azathioprine, mercaptopurine, and/or thioguanine, and to describe its clinical course.

Background Liver injury during inflammatory bowel disease (IBD) is primarily diagnosed by liver biopsy, which has a small but serious risk of severe complications. The aim of this study was to assess liver stiffness, and subsequently the prevalence and associations of liver fibrosis in IBD patients with thiopurine therapy and other clinical factors, by using transient elastography (TE). Methods In this prospective, international two-center study, included IBD-patients underwent TE measurements. Laboratory results and medication reports, radiology results and historical liver biopsy results were extracted from the patient charts. Results Transient elastography results of 168 patients were presented. Moderate and severe fibrosis were detected in 4% (7/168) and 1% (1/168) of the cohort, respectively. Factors contributing to lower liver stiffness were female gender and (historical) exposure to azathioprine. Further, there was a statistical trend towards lower liver stiffness in patients using thiopurines overall (4.7 vs. 5.2 kPa, p = 0.07). Liver stiffness correlated positively with waist circumference, liver enzyme tests, hemoglobin and 6-methylmercaptopurine concentration and negatively with platelet count. Conclusion Exposure to thiopurine therapy was not associated with higher liver stiffness, although no clinical difference in severity of fibrosis was detected. Further research should robustly determine the accuracy of TE as an evaluation of liver fibrosis in IBD patients.

Although early detection of Lynch syndrome (LS) is important, a considerable proportion of patients with LS remains unrecognized. We aimed to study the yield of LS detection by routine molecular analyses in colorectal cancer (CRC) patients until 70 years of age. We prospectively included consecutive CRC patients ≤70 years. Tumour specimens were analysed for microsatellite instability (MSI), immunohistochemical mismatch-repair protein expression and MLH1-promoter methylation. Tumours were classified as either: (a) likely caused by LS; (b) sporadic microsatellite-unstable (MSI-H); or (c) microsatellite-stable (MSS). Predictors of LS were determined by multivariable logistic regression. A total of 1117 CRC patients (57% males, median age 61 years) were included. Fifty patients (4.5%, 95% CI 3.4-5.9) were likely to have LS, and 71 had a sporadic MSI-H tumour (6.4%, 95% CI 5.1-8.0). Thirty-five patients likely to have LS (70%) were aged > 50 years. A molecular profile compatible with LS was detected in 10% (15/144) of patients aged ≤50, in 4% (15/377) of those aged 51-60 and in 3% (20/596) of patients > 61 years. Compared to MSS cases, patients likely to have LS were significantly younger (OR 3.9, 95% CI 1.7-8.7) and more often had right-sided CRCs (OR 14, 95% CI 6.0-34). In conclusion, molecular screening for LS in CRC patients ≤70 years leads to identification of a molecular profile compatible with LS in 4.5% of patients, with most of them not fulfilling the age criterion (≤50 years) routinely used for LS assessment. Routine use of MSI testing may be considered in CRC patients up to the age of 70 years, with a central role for the pathologist in the selection of patients.

Objective To compare the sensitivity of autofluorescence endoscopy (AFE) and white light video endoscopy (WLE) for the detection of colorectal adenomas in high-risk patients belonging to Lynch syndrome (LS) or familial colorectal cancer (CRC) families. Methods This was a prospective single-centre study carried out in a tertiary referral centre. The subjects were 75 asymptomatic patients originating from LS or familial CRC families. Patients were examined with either WLE followed by AFE or AFE followed by WLE. Back-to-back colonoscopy was performed by two blinded endoscopists. All lesions were removed during the second endoscopic procedure. Lesions missed during the second procedure were identified and removed on third pass. The sensitivity calculations for colorectal adenomas were based on histology results. The main outcome measures were the difference in sensitivity between WLE and AFE for the detection of adenomas in patients with LS or familial CRC. Results At least one adenoma was detected in 41 (55%) patients. WLE identified adenomas in 28/41 patients and AFE in 37/41 patients, corresponding to a 32% increase. In total 95 adenomas were detected, 65 by WLE and 87 by AFE, resulting in a significantly higher sensitivity of AFE compared with WLE (92% vs 68%; p=0.001). The additionally detected adenomas with AFE were significantly smaller than the adenomas detected by WLE (mean 3.0 mm vs 4.9 mm, p

Background and aims: In Lynch syndrome, the clinical phenotype in MSH6 mutation families differs from that in MLH1 and MSH2 families. Therefore, MSH6 mutation families are less likely to fulfil diagnostic criteria such as the Amsterdam II criteria (AC II) and the revised Bethesda guidelines (rBG), and will be underdiagnosed. The aim of the present study was to evaluate the contribution of MSH6 gene mutations in families that were analysed for Lynch syndrome in a diagnostic setting. Methods: Families that had molecular analysis for Lynch syndrome were included in this study. Complete molecular screening of the MLH1 , MSH2 and MSH6 genes was performed in all families. Microsatellite instability (MSI) and immunohistochemical (IHC) analysis was performed in almost all families. Clinical data were collected from medical records and family pedigrees. Results: A total of 108 families were included. MSI and IHC analysis was performed in 97 families, and in 40 an MSI-high phenotype with absent protein expression was found. Germline mutation analysis detected mutations in 23 families (7 MLH1 , 4 MSH2 and 12 MSH6 ). The majority of MSH6 families were AC II negative, but fulfilled the rBG. Conclusions: There is a high incidence of MSH6 mutations in families tested for Lynch syndrome in a diagnostic setting. Many of these families remain underdiagnosed using the AC II. The rBG are more useful to select these families for further analysis. However, to optimise the detection of MSH6 families, MSI and IHC analysis should also be performed in families with clustering of late-onset endometrial carcinoma.

Background The most common hereditary colorectal cancer syndrome is hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome. Diagnosis of this syndrome is difficult, because of lack of specific diagnostic fatures. Aim To discuss the diagnostic criteria and laboratory work up for HNPCC. Furthermore, survelillance programs for HNPCC and treatment of HNPCC associated colorectal cancer are discussed. Results Current diagnostic criteria, including the Amsterdam II and Bethesda criteria, are suboptimal for the detection of HNPCC. Molecular screening by microsatellite instability (MSI) and immunohistochemistry (IHC) is useful in the diagnosis of HNPCC. Both techniques have a higher sensitivity compared to the Amsterdam II and Bethesda criteria. A combination of both MSI and IHC provides the most optimal selection for mutation analysis. After identification of a mutation in an affected individual, genetic counselling and presymptomatic mutation analysis should be offered to relatives. Furthermore, colonoscopic surveillance should be performed in proven mutation carriers. Conclusions Identification of HNPCC is a clinical challenge involving many clinicians. Identification of persons at risk can be achieved by a combination of a detailed family history, testing with molecular and mutation analysis.

Colorectal carcinoma (CRC) is a common cancer and the second most common cause of death. The therapeutic costs for this disease will continue to rise due to an increasing incidence and the introduction of new chemotherapeutic modalities. Colorectal carcinoma is preceded by precursor lesions, which can be used as a target for early detection and therapy. Biennial population screening with faecal occult blood tests (FOBT) lowers CRC mortality with 14–18%. Five year screening with flexible sigmoidoscopy is a cost-effective alternative, which yields a higher preventive effect when similar participation rates are achieved. Screening colonoscopy has the advantage of examination of the complete colon but disadvantages are the high participant burden and the higher demand for endoscopic personnel and endoscopy units. Future screening modalities like faecal DNA markers and CT colonography are promising but need further improvement. In Europe, faecal occult blood testing and flexible sigmoidoscopy are currently the most suitable screening modalities for colorectal cancer screening.

Mildly elevated transaminases are often observed in anorexia nervosa patients, but severe hepatitis is less common. We suggest that hypoperfusion is the pathogenetic factor that causes severe hepatitis in a patient with a very poor nutritional status and present an overview of previous case reports. In our patient, early initiation of intravenous fluids resulted in rapid recovery of the liver test abnormalities, despite minimal oral caloric intake, the refusal of enteral feeding and the development of a hypoglycemic coma. Two months after admission, transaminases had normalized. Reversible severe hepatitis has been described in most of the cases, with only one anorexia nervosa-related fatal hepatitis. In general, both adequate hydration and gradual enteral feeding with monitoring of electrolytes are essential in the management of anorexia patients with severe hepatitis.

OBJECTIVES: Sporadic duodenal adenomas are an uncommon finding. It is not clear whether patients with sporadic duodenal adenoma have a greater risk for colorectal neoplasia and should undergo colonoscopy. The aims of the present study were to estimate the prevalence of colorectal neoplasia in patients with sporadic duodenal adenoma, and to compare colorectal neoplasia rates in patients with sporadic duodenal adenomas versus those without them. METHODS: A retrospective case-control study was conducted to identify sporadic duodenal adenoma patients using the databases of two academic and one regional hospital in the Netherlands. Colonoscopic findings in the sporadic duodenal adenoma patients were compared with those of a control group of patients who underwent both gastroduodenoscopy and colonoscopy. Furthermore, the frequency of colorectal cancer in the sporadic duodenal adenoma patients was compared with the population incidence of colorectal cancer. RESULTS: During the period 1991-2006, 102 patients in total with sporadic duodenal adenomas were identified. Colonoscopy was performed in 49 patients (48%), and colorectal neoplasia was present in 21 of these patients (43%). There was a significantly higher rate of both colorectal neoplasia (43% vs 17%, odds ratio [OR] 3.6, 95% confidence interval [CI] 1.7-7.4) and advanced colorectal adenoma (18% vs 3%, OR 7.8, 95% CI 2.1-29.4) in the patients with sporadic duodenal adenoma compared to that in the control group. Also, the incidence of colorectal cancer was higher in sporadic duodenal adenoma patients compared to that in the population (P = 0.02). CONCLUSIONS: Individuals with sporadic duodenal adenomas appear to be at a significantly higher risk of colorectal neoplasia, and therefore should undergo colonoscopy.

Background: The duodenal adenomas as seen in familial adenomatous polyposis (FAP) are likely to develop through the classical adenoma-carcinoma pathway as they exhibit mutations in the APC gene, KRAS mutations, p53 dysfunction, and loss of E-cadherin expression. However, it is unknown whether sporadic duodenal adenomas also develop into duodenal carcinoma through the classical adenoma carcinoma sequence. Limited data suggest that sporadic adenomas show similar molecular features as colorectal adenomas, harboring APC and KRAS mutations. Therefore, the aim of the present study was to evaluate the molecular changes of sporadic duodenal adenomas. Methods: Tissue samples of 64 sporadic duodenal adenomas were available from the pathology archives of two academic hospitals. Tissue samples of patients with duodenal carcinoma or patients with FAP were excluded. None of the patients belonged to a known Lynch syndrome family. DNA was extracted from paraffin sections of the adenoma and analyzed for the presence of microsatellite instability. Also, mutation analysis using polymerase chain reaction followed by direct-sequencing was performed. The mutation analysis included mutational hotspots of the Wnt signaling pathway (APC, β-catenin), the MAP kinase pathway (KRAS and BRAF) and the del1100c mutation within the CHK2 gene. Results: Two (3%) of the 64 adenomas showed a high level of MSI (MSI-H). APC mutation analysis was possible in 52 adenomas and revealed a mutation in thirteen (24%), including seven duodenal adenomas with a recurrent 4684insA (K1555fsX1557)mutation. KRASmutation analysis was possible in 52 adenomas and revealed one (2%) mutation (34GGT>TGT (G12C)). β-catenin mutation analysis was possible in 48 adenomas and revealed one (2%) mutation (121ACC>GCC(T41A)). BRAF (58 adenomas) and CHK2 (53 adenomas) mutation analysis did not reveal any mutation. Conclusions: In our cohort of sporadic duodenal adenomas the frequency of Wnt signaling pathway abnormalities is low, most adenomas are microsatellite stable and the number of MAP kinase pathway abnormalities is negligible. In addition, CHK2 mutations seem not to be present in sporadic duodenal adenomas. These findings suggest that a proportion of sporadic duodenal adenomas develop via the same mechanisms (the adenoma-carcinoma sequence) as colorectal adenomas, but it is possible that other molecular changes may also underlie the development of sporadic duodenal adenomas.