Search

Background: The faecal immunochemical test (FIT) suffers from suboptimal performance and participation in colorectal cancer (CRC) screening. Urinary volatile organic compounds (VOCs) may be a useful alternative. We aimed to determine the diagnostic potential of urinary VOCs for CRC/adenomas. By relating VOCs to known pathways, we aimed to gain insight into the pathophysiology of colorectal neoplasia. Methods: A systematic search was performed in PubMed, EMBASE and Web of Science. Original studies on urinary VOCs for CRC/adenoma detection with a control group were included. QUADAS-2 tool was used for quality assessment. Meta-analysis was performed by adopting a bivariate model for sensitivity/specificity. Fagan's nomogram estimated the performance of combined FIT-VOC. Neoplasm-associated VOCs were linked to pathways using the KEGG database. Results: Sixteen studies—involving 837 CRC patients and 1618 controls—were included; 11 performed chemical identification and 7 chemical fingerprinting. In all studies, urinary VOCs discriminated CRC from controls. Pooled sensitivity and specificity for CRC based on chemical fingerprinting were 84% (95% CI 73–91%) and 70% (95% CI 63–77%), respectively. The most distinctive individual VOC was butanal (AUC 0.98). The estimated probability of having CRC following negative FIT was 0.38%, whereas 0.09% following negative FIT-VOC. Combined FIT-VOC would detect 33% more CRCs. In total 100 CRC-associated urinary VOCs were identified; particularly hydrocarbons, carboxylic acids, aldehydes/ketones and amino acids, and predominantly involved in TCA-cycle or alanine/aspartate/glutamine/glutamate/phenylalanine/tyrosine/tryptophan metabolism, which is supported by previous research on (colorectal)cancer biology. The potential of urinary VOCs to detect precancerous adenomas or gain insight into their pathophysiology appeared understudied. Conclusion: Urinary VOCs hold potential for non-invasive CRC screening. Multicentre validation studies are needed, especially focusing on adenoma detection. Urinary VOCs elucidate underlying pathophysiologic processes.

The aim of this study was to evaluate the safety and efficacy of a modified CAL-WR.The use of segmental colectomy in patients with endoscopically unresectable colonic lesions results in significant morbidity and mortality. CAL-WR is an alternative procedure that may reduce morbidity.This prospective multicenter study was performed in 13 Dutch hospitals between January 2017 and December 2019. Inclusion criteria were (1) colonic lesions inaccessible using current endoscopic resection techniques (judged by an expert panel), (2) non-lifting residual/recurrent adenomatous tissue after previous polypectomy or (3) an undetermined resection margin after endoscopic removal of a low-risk pathological T1 (pT1) colon carcinoma. Thirty-day morbidity, technical success rate and radicality were evaluated.Of the 118 patients included (56% male, mean age 66 years, standard deviation ± 8 years), 66 (56%) had complex lesions unsuitable for endoscopic removal, 34 (29%) had non-lifting residual/recurrent adenoma after previous polypectomy and 18 (15%) had uncertain resection margins after polypectomy of a pT1 colon carcinoma. CAL-WR was technically successful in 93% and R0 resection was achieved in 91% of patients. Minor complications (Clavien-Dindo i-ii) were noted in 7 patients (6%) and an additional oncologic segmental resection was performed in 12 cases (11%). Residual tissue at the scar was observed in 5% of patients during endoscopic follow-up.CAL-WR is an effective, organ-preserving approach that results in minor complications and circumvents the need for major surgery. CAL-WR, therefore, deserves consideration when endoscopic excision of circumscribed lesions is impossible or incomplete.

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.

The prevalence and severity of non-alcoholic fatty liver disease (NAFLD) is increasing, yet adequately validated tests for care paths are limited and non-invasive markers of disease progression are urgently needed. The aim of this work was to summarize the performance of Pro-C3, a biomarker of active fibrogenesis, in detecting significant fibrosis (F ≥ 2), advanced fibrosis (F ≥ 3), cirrhosis (F4) and non-alcoholic steatohepatitis (NASH) in patients with NAFLD. A sensitive search of five databases was performed in July 2021. Studies reporting Pro-C3 measurements and liver histology in adults with NAFLD without co-existing liver diseases were eligible. Meta-analysis was conducted by applying a bivariate random effects model to produce summary estimates of Pro-C3 accuracy. From 35 evaluated reports, eight studies met our inclusion criteria; 1568 patients were included in our meta-analysis of significant fibrosis and 2058 in that of advanced fibrosis. The area under the summary curve was 0.81 (95% CI 0.77–0.84) in detecting significant fibrosis and 0.79 (95% CI 0.73–0.82) for advanced fibrosis. Our results support Pro-C3 as an important candidate biomarker for non-invasive assessment of liver fibrosis in NAFLD. Further direct comparisons with currently recommended non-invasive tests will demonstrate whether Pro-C3 panels can outperform these tests, and improve care paths for patients with NAFLD.

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.

This study evaluated the use of genetic testing and time trends in hereditary non-polyposis colorectal cancer (HNPCC), (attenuated) familial adenomatous polyposis [(A)FAP] and human MutY homolog (MUTYH) associated polyposis (MAP) families. Eighty-seven families, who were diagnosed with disease-causing mutations between 1995 and 2006, were included in this study. The families consisted of 1547 individuals at risk. Data of these individuals were collected from medical records and family pedigrees. There was considerable interest in genetic testing with test rates of 41% in HNPCC families, 42% in (A)FAP families and 53% in MAP families. The use of genetic testing was associated with age and parenthood. Despite the interest in genetic testing, many risk carriers do not apply for testing. Moreover, time trend analysis showed a decline in test rate in HNPCC families. Studies evaluating the reasons for not testing are needed. Furthermore, a better implementation of genetic testing in clinical practice is desirable.

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.

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 aged50 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 patients61 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.

Background Lynch syndrome (LS) is associated with a high risk for colorectal cancer (CRC) and extracolonic malignancies, such as endometrial carcinoma (EC). The risk is dependent of the affected mismatch repair gene. The aim of the present study was to calculate the cumulative risk of LS related cancers in proven MLH1, MSH2 and MSH6 mutation carriers. Methods The studypopulation consisted out of 67 proven LS families. Clinical information including mutation status and tumour diagnosis was collected. Cumulative risks were calculated and compared using Kaplan Meier survival analysis. Results MSH6 mutation carriers, both males and females had the lowest risk for developing CRC at age 70 years, 54% and 30% respectively and the age of onset was delayed by 3-5 years in males. With respect to endometrial carcinoma, female MSH6 mutation carriers had the highest risk at age 70 years (61%) compared to MLH1 (25%) and MSH2 (49%). Also, the age of EC onset was delayed by 5-10 years in comparison with MLH1 and MSH2. Conclusions Although the cumulative lifetime risk of LS related cancer is similar, MLH1, MSH2 and MSH6 mutations seem to cause distinguishable cancer risk profiles. Female MSH6 mutation carriers have a lower CRC risk and a higher risk for developing endometrial carcinoma. As a consequence, surveillance colonoscopy starting at age 30 years instead of 20-25 years is more suitable. Also, prophylactic hysterectomy may be more indicated in female MSH6 mutation carriers compared to MLH1 and MSH2 mutation carriers.

Aims: To investigate post-operative capillary density regeneration in healing mucoperiosteal flaps at guided bone regeneration-treated implant sites.Material and Methods: A non-invasive post-operative investigation was performed in 10 patients using orthogonal polarization spectral (OPS) imaging for assessment of capillary density during the course of mucoperiosteal flap wound healing for 6 weeks in patients receiving dental implants.Results: The greatest increase in capillary regeneration occurred in the early wound-healing phase, during weeks 1 and 2, and recovery to baseline was achieved between weeks 4 and 5. A comparison of adjacent OPS measurements indicated that differences between the time point immediately following administration of local anaesthesia and directly post-operatively ( p=0.002), between a directly post-operative time point and after 1 week (p=0.009), and between post-operative weeks 1 and 2 (p=0.036) were statistically significant.Conclusions: The early healing phase of mucoperiosteal flaps is characterized by rapid capillary regeneration. OPS imaging enabled the possibility to monitor and quantify the temporal development of mucoperiosteal flap revascularization following periodontal surgery.

Background/aims: The identification of Lynch syndrome is hampered by the absence of specific diagnostic features and underutilisation of genetic testing. Prediction models have therefore been developed, but they have not been validated for a clinical genetic setting. The aim of the present study was to evaluate the usefulness of currently available prediction models. Methods: The authors collected data of 321 index probands who were referred to the department of clinical genetics of the Erasmus Medical Center because of a family history of colorectal cancer. These data were used as input for five previously published models. External validity was assessed by discriminative ability (AUC: area under the receiver operating characteristic curve) and calibration. For further insight, predicted probabilities were categorised with cut-offs of 5%, 10%, 20% and 40%. Furthermore, costs of different testing strategies were related to the number of extra detected mutation carriers. Results: Of the 321 index probands, 66 harboured a germline mutation. All models discriminated well between high risk and low risk index probands (AUC 0.82-0.84). Calibration was well for the Premm(1,2) and Edinburgh model, but poor for the other models. Cut-offs could be found for the prediction models where costs could be saved while missing only few mutations. Conclusions: The Edinburgh and Premm(1,2) model were the models with the best performance for an intermediate to high risk setting. These models may well be of use in clinical practice to select patients for further testing of mismatch repair gene mutations.

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.

NSAIDs and Helicobacter pylori are risk factors for the development of peptic ulcers. A prospective study was conducted to determine prevalence of NSAID use, H pylori infection, and outcome of peptic ulcer bleeding.In 2000, data of all 361 patients presenting with peptic ulcer bleeding were prospectively collected in a defined geographical area, including 14 hospitals, and serving a catch area of 1.68 million persons. Follow-up data after a mean of 31 months were obtained from 211 patients.The overall incidence was 21.5 cases per 100,000 persons. Mean age of the group was 70.9 years, 55% were male, and 41% had severe or life-threatening comorbidity. NSAIDs were used by 52%, and in only 17% concomitant acid suppressive therapy was given. H pylori infection was tested in 64%. Of the patients tested for H pylori, 43% were positive. Twenty-three percent were H pylori negative and not using NSAIDs. Rebleeding during initial admission occurred in 19%. Mortality during initial admission was 14%. During follow-up mortality was high, 29%.Half of all ulcer bleeding was associated with NSAID use. Only a minority of NSAID users used concomitant acid suppressive therapy. H pylori is not assessed systematically in all patients with ulcer bleeding. Almost a quarter of the ulcers were associated with neither H pylori infection nor NSAID use. Mortality, both during hospitalization and follow-up, was substantial.

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.