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Background and study aims: The clinical utility of narrow-band imaging (NBI) for Barrett's esophagus is limited by the multiplicity of classification schemes. We evaluated the interobserver agreement and accuracy of a new consensus-driven simplified binary classification of NBI surface patterns. Patients and methods: NBI images from macroscopically normal areas in patients with Barrett's esophagus were retrieved from endoscopy databases and were randomized for review by seven endoscopists (three experts, four nonexperts). A simplified binary classification of NBI mucosal and vascular patterns was used: (1) regular pattern (nondysplastic Barrett's esophagus); (2) irregular pattern (dysplastic Barrett's esophagus). Agreement in relation to surface patterns and predicted histology (dysplasia vs. no dysplasia) was calculated using κ statistics. Results: A total of 252 NBI images from 75 patients with Barrett's esophagus were assessed: 93 showed intestinal metaplasia, 91 low-grade dysplasia, and 68 high-grade dysplasia/esophageal adenocarcinoma. The median score for image quality was 4 (very good). Interobserver agreement for mucosal and vascular patterns and dysplasia prediction was fair: κ = 0.40 (95%CI: 0.37-0.42), 0.36 (95%CI: 0.33-0.38), and 0.39 (95%CI: 0.36-0.41) respectively, with comparable results for experts and nonexperts. Intraobserver agreement was substantially better among experts than among nonexperts, with mucosal κ = 0.63 vs. 0.49, vascular κ = 0.58 vs. 0.43, and predicted histology κ = 0.68 vs. 0.54 (all P < 0.005). Mean sensitivity and specificity of NBI surface patterns for predicting dysplasia were 47% (95%CI: 44%-55%) and 72% (95%CI: 69%-76%) respectively. Conclusions: Using a consensus-driven simplified classification of NBI surface patterns for Barrett's esophagus, the interobserver agreement was fair with suboptimal sensitivity and specificity. Significant improvements in NBI interpretation are needed prior to the routine use of NBI surface patterns for the assessment of Barrett's esophagus. [ABSTRACT FROM AUTHOR]

This review deals with the current, well-established indications for two-( 18 F)-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) scanning in patients with gastrointestinal cancers. FDG-PET is a non-invasive, functional imaging technique. FDG exploits the native glucose transporter to enter the cell. Since many tumours have enhanced glucose uptake, FDG is readily accumulated in malignant cells and can be detected by a PET camera. FDG-PET has been established as an important diagnostic tool in clinical oncology. This review deals with the current, well-established indications for FDG-PET scanning in patients with gastrointestinal cancers. In the current practice, FDG-PET is most commonly used to stage oesophageal carcinoma, to detect and stage recurrence of colorectal carcinoma and to differentiate between benign and malignant pancreatic lesions. The benefit of FDG-PET scanning in patients with oesophagus carcinoma is best established in stage IV disease, as the diagnostic accuracy to detect metastatic disease is higher compared to the combination of computed tomography (CT) and endoscopic ultrasound (EUS). In patients with a history of colorectal carcinoma, FDG-PET scanning is particularly effective in diagnosing recurrent disease, especially in those with a rising carcinoembryonic antigen without a suspect lesion on conventional imaging. Large series have indicated that the sensitivity and specificity for detecting recurrent colorectal carcinoma are in the range of 87%-100% and 66%-100%, respectively. Equally, FDG-PET has a high sensitivity (68%-96%) and specificity (78%-100%) in detecting pancreatic carcinoma in patients with a suspicious-looking pancreatic mass on CT scan. Lastly, we focus on the use of FDG-PET as a modality for early monitoring of treatment response in patients with gastrointestinal stromal cell tumours. Without doubt, future developments will further establish the diagnostic role of the FDG-PET scan in the care of patients with gastrointestinal cancers. [ABSTRACT FROM AUTHOR]

Background: Constitutional mismatch repair deficiency (CMMRD) is a rare autosomal recessively inherited syndrome that is caused by biallelic pathogenic variants of the mismatch repair genes. It is characterised by the development of multiple tumours in the first and second decade of life including brain, gastrointestinal and haematological tumours often resulting in early death. In order to improve the prognosis of these patients, the European collaborative group 'care for CMMRD' developed a surveillance programme in 2014 and established a registry of patients with CMMRD in Paris. The aim of the study was to evaluate the outcome of this programme., Methods: Twenty-two patients with a definitive diagnosis of CMMRD and with at least one follow-up study were selected from the registry. Medical data on the outcome of surveillance were collected from these patients., Results: During a mean follow-up of 4 years, the programme detected eight malignant tumours including three brain tumours, three upper gastrointestinal cancers and two colorectal cancers. Most tumours could successfully be treated. In addition, many adenomas were detected in the duodenum, and colorectum and subsequently removed. Seven patients developed a symptomatic malignancy, including two brain tumours, one small bowel cancer and four haematological malignancies. At the end of the follow-up, 16 out of 22 patients (73%) who participated in the surveillance programme were still alive., Conclusion: The study suggests a beneficial effect of surveillance of the digestive tract and brains., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Constitutional mismatch repair deficiency (CMMRD) is a rare childhood cancer predisposition syndrome caused by biallelic germline mutations in one of four mismatch-repair genes. Besides very high tumour risks, CMMRD phenotypes are often characterised by the presence of signs reminiscent of neurofibromatosis type 1 (NF1). Because NF1 signs may be present prior to tumour onset, CMMRD is a legitimate differential diagnosis in an otherwise healthy child suspected to have NF1/Legius syndrome without a detectable underlying NF1 / SPRED1 germline mutation. However, no guidelines indicate when to counsel and test for CMMRD in this setting. Assuming that CMMRD is rare in these patients and that expected benefits of identifying CMMRD prior to tumour onset should outweigh potential harms associated with CMMRD counselling and testing in this setting, we aimed at elaborating a strategy to preselect, among children suspected to have NF1/Legius syndrome without a causative NF1 / SPRED1  mutation and no overt malignancy, those children who have a higher probability of having CMMRD. At an interdisciplinary workshop, we discussed estimations of the frequency of CMMRD as a differential diagnosis of NF1 and potential benefits and harms of CMMRD counselling and testing in a healthy child with no malignancy. Preselection criteria and strategies for counselling and testing were developed and reviewed in two rounds of critical revisions. Existing diagnostic CMMRD criteria were adapted to serve as a guideline as to when to consider CMMRD as differential diagnosis of NF1/Legius syndrome. In addition, counselling and testing strategies are suggested to minimise potential harms., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

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.

Background & Aims: Two percent to 4% of all cases of colorectal cancer (CRC) are associated with Lynch syndrome. Dominant clustering of CRC (non-Lynch syndrome) accounts for 1%-3% of the cases. Because carcinogenesis is accelerated in Lynch syndrome, an intensive colonoscopic surveillance program has been recommended since 1995. The aim of the study was to evaluate the effectiveness of this program., Methods: The study included 205 Lynch syndrome families with identified mutations in one of the mismatch repair genes (745 mutation carriers). We also analyzed data from non-Lynch syndrome families (46 families, 344 relatives). Patients were observed from January 1, 1995, until January 1, 2009. End points of the study were CRC or date of the last colonoscopy., Results: After a mean follow-up of 7.2 years, 33 patients developed CRC under surveillance. The cumulative risk of CRC was 6% after the 10-year follow-up period. The risk of CRC was higher in carriers older than 40 years and in carriers of MLH1 and MSH2 mutations. After a mean follow-up of 7.0 years, 6 cases of CRC were detected among non-Lynch syndrome families. The risk of CRC was significantly higher among families with Lynch syndrome, compared with those without., Conclusions: With surveillance intervals of 1-2 years, members of families with Lynch syndrome have a lower risk of developing CRC than with surveillance intervals of 2-3 years. Because of the low risk of CRC in non-Lynch syndrome families, a less intensive surveillance protocol can be recommended., (Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.)

We report reproducible fabrication of InP-InAsP nanowire light-emitting diodes in which electron-hole recombination is restricted to a quantum-dot-sized InAsP section. The nanowire geometry naturally self-aligns the quantum dot with the n-InP and p-InP ends of the wire, making these devices promising candidates for electrically driven quantum optics experiments. We have investigated the operation of these nanoLEDs with a consistent series of experiments at room temperature and at 10 K, demonstrating the potential of this system for single photon applications.

A 21-year-old man was admitted because of upper abdominal pain and cholestasis. Endoscopic retrograde cholangiopancreatography was suggestive of primary sclerosing cholangitis. During follow-up the patient developed symptoms which were not compatible with primary sclerosing cholangitis, i.e. icterus and weight loss. Finally the patient died, almost three years after presentation, because of a metastatic adenocarcinoma which had arisen from biliary papillomatosis. Biliary papillomatosis is characterised by papillary adenomatous proliferation of the bile duct epithelium. It has a high chance of malignant degeneration. The only curative option would have been transplantation of the liver and biliary system, but this ought to have happened at an early stage before malignant degeneration had occurred.