Management of Barrett’s Esophagus: Practice-Oriented Answers to Clinical Questions

Barrett's esophagus is the most important complication of gastro-esophageal reflux disease and the only known precursor of esophageal adenocarcinoma. The diagnosis and treatment of Barrett's esophagus are clinically challenging as it requires a high level of knowledge and competence in upper gastrointestinal endoscopy. For instance, endoscopists should know when and how to perform biopsies when Barrett's esophagus is suspected. Furthermore, the correct identification and treatment of dysplastic Barrett's esophagus is crucial to prevent progression to cancer as well as it is the endoscopic surveillance of treated patients. Herein, we report practice-oriented answers to clinical questions that clinicians should be aware of when approaching patients with Barrett's esophagus

Leakage Current Mechanisms in SiGe HBTs Fabricated Using Selective and Nonselective Epitaxy

SiGe heterojunction bipolar transistors (HTBs) have been fabricated using selective epitaxy for the Si collector, followed in the same growth step by nonselective epitaxy for the p+ SiGe base and n-Si emitter cap. DC electrical characteristics are compared with cross-section TEM images to identify the mechanisms and origins of leakage currents associated with the epitaxy in two different types of transistor . In the first type, the polysilicon emitter is smaller than the collector active area, so that the extrinsic base implant penetrates into the single-crystal Si and SiGe around the perimeter of the emitter and the polycrystalline Si and SiGe exrtrinsic base. In these transistors, the Bummel plots are near-ideal and there is no evidence of emitter/collector leakage. In the second type, the collector active area is smaller than the polysilicon emitter, so the extrinsic base implant only penetrates into the polysilicon extrinsic base. In these transistors, the leakage currents observed depend on the base doping level. In transistors with a low doped base, emitter/collector and emitter/base leakage is observed, whereas in transistors with a high doped base only emitter/base leakage is observed. The emitter/collector leakage is explained by punch through o fhte base caused by thinning of the SiGe base at the emitter perimeter. The emitter/base leakeage is shown to be due to Poole-Frenkel mechanism and is explained by penetration of the emitter/base depletion region into the p+ polysilicon extrinsic base at the emitter periphery. Variable collector/base reverse leakage currents are observed and a variety of mechanisms are observed, including Shockley-Read-Hall recombination, trap assisted tunneling, Poole Frenkel and band to band tunneling. These result s are explained by the presence of polysilicon grains on the sidewalls of the field oxide at the collector perimeter

Characterization of Early and Late Damage in a Mouse Model of Pelvic Radiation Disease

Pelvic radiation disease (PRD), a frequent side effect in patients with abdominal/pelvic cancers treated with radiotherapy, remains an unmet medical need. Currently available preclinical models have limited applications for the investigation of PRD pathogenesis and possible therapeutic strategies. In order to select the most effective irradiation protocol for PRD induction in mice, we evaluated the efficacy of three different locally and fractionated X-ray exposures. Using the selected protocol (10 Gy/day x 4 days), we assessed PRD through tissue (number and length of colon crypts) and molecular (expression of genes involved in oxidative stress, cell damage, inflammation, and stem cell markers) analyses at short (3 h or 3 days after X-ray) and long (38 days after X-rays) post-irradiation times. The results show that a primary damage response in term of apoptosis, inflammation, and surrogate markers of oxidative stress was found, thus determining a consequent impairment of cell crypts differentiation and proliferation as well as a local inflammation and a bacterial translocation to mesenteric lymph nodes after several weeks post-irradiation. Changes were also found in microbiota composition, particularly in the relative abundance of dominant phyla, related families, and in alpha diversity indices, as an indication of dysbiotic conditions induced by irradiation. Fecal markers of intestinal inflammation, measured during the experimental timeline, identified lactoferrin, along with elastase, as useful non-invasive tools to monitor disease progression. Thus, our preclinical model may be useful to develop new therapeutic strategies for PRD treatment

Endoscopic palliation in patients with incurable malignant colorectal obstruction by means of self-expanding metal stent: analysis of results and predictors of outcomes in a large multicenter series

Objectives: To evaluate the short- and long-term efficacy of self-expanding metal stents (SEMSs) in patients with colorectal obstruction and incurable cancer and the related factors that affect outcomes. Design: Retrospective analysis of SEMS placement for incurable colorectal obstruction in a 3-year period. Setting: Five tertiary care endoscopic centers. Patients and Intervention: Consecutive patients (N=201) undergoing stenting for incurable malignant obstruction. Main Outcome Measurements: Clinical and technical success of stenting, complications rate, and factors affecting outcomes. Results: Technical success was achieved in 184 of 201 patients (91.5%) and clinical success occurred in 165 of 184 patients (89.7%; 82.1% of 201 patients). Technicaland clinical failures were more frequent in extrinsic and long colorectal stenoses. Overall, 165 patients had normal bowel movements during follow-up (mean [SD], 115.5 [100.3] days; range, 1-500 days), 15 developed complications, 127 had a functioning SEMS at the time of death, and 23 were alive at completion of the study. Twenty-four (11.9%) major complications occurred: 11 migrations, 12 perforations, and 1 reobstruction. Migration of SEMSs was associated with stent diameter less than 25 mm. Bevacizumab therapy increased the risk of perforation by 19.6-fold. Karnofsky performance status of 50 or less was associated with shorter survival and a 3.7- fold higher risk of death within 6 months after the stent was placed. Conclusions: The use of SEMSs is safe and effective for palliation of incurable malignant colonic obstruction; approximately 75% of patients with SEMSs are able to avoid colostomy

Adjuvant chemoradiation in pancreatic cancer: Impact of radiotherapy dose on survival

BackgroundTo evaluate the impact of radiation dose on overall survival (OS) in patients treated with adjuvant chemoradiation (CRT) for pancreatic ductal adenocarcinoma (PDAC).MethodsA multicenter retrospective analysis on 514 patients with PDAC (T1-4; N0-1; M0) treated with surgical resection with macroscopically negative margins (R0-1) followed by adjuvant CRT was performed. Patients were stratified into 4 groups based on radiotherapy doses (group 1: <45Gy, group 2: 45 and<50Gy, group 3: 50 and<55Gy, group 4: 55Gy). Adjuvant chemotherapy was prescribed to 141 patients. Survival functions were plotted using the Kaplan-Meier method and compared through the log-rank test.ResultsMedian follow-up was 35months (range: 3-120months). At univariate analysis, a worse OS was recorded in patients with higher preoperative Ca 19.9 levels (90U/ml; p<0.001), higher tumor grade (G3-4, p=0.004), R1 resection (p=0.004), higher pT stage (pT3-4, p=0.002) and positive nodes (p<0.001). Furthermore, patients receiving increasing doses of CRT showed a significantly improved OS. In groups 1, 2, 3, and 4, median OS was 13.0months, 21.0months, 22.0months, and 28.0months, respectively (p=0.004). The significant impact of higher dose was confirmed by multivariate analysis.ConclusionsIncreasing doses of CRT seems to favorably impact on OS in adjuvant setting. The conflicting results of randomized trials on adjuvant CRT in PDAC could be due to <45Gy dose generally used

Systematic investigation of gastrointestinal diseases in China (SILC): validation of survey methodology

Background: Symptom-based surveys suggest that the prevalence of gastrointestinal diseases is lower in China than in Western countries. The aim of this study was to validate a methodology for the epidemiological investigation of gastrointestinal symptoms and endoscopic findings in China. Methods: A randomized, stratified, multi-stage sampling methodology was used to select 18 000 adults aged 18-80 years from Shanghai, Beijing, Xi'an, Wuhan and Guangzhou. Participants from Shanghai were invited to provide blood samples and undergo upper gastrointestinal endoscopy. All participants completed Chinese versions of the Reflux Disease Questionnaire (RDQ) and the modified Rome II questionnaire; 20% were also invited to complete the 36-item Short Form Health Survey (SF-36) and Epworth Sleepiness Scale (ESS). The psychometric properties of the questionnaires were evaluated statistically. Results: The study was completed by 16 091 individuals (response rate: 89.4%), with 3219 (89.4% of those invited) completing the SF-36 and ESS. All 3153 participants in Shanghai provided blood samples and 1030 (32.7%) underwent endoscopy. Cronbach's alpha coefficients were 0.89, 0.89, 0.80 and 0.91, respectively, for the RDQ, modified Rome II questionnaire, ESS and SF-36, supporting internal consistency. Factor analysis supported construct validity of all questionnaire dimensions except SF-36 psychosocial dimensions. Conclusion: This population-based study has great potential to characterize the relationship between gastrointestinal symptoms and endoscopic findings in China.Xiaoyan Yan, Rui Wang, Yanfang Zhao, Xiuqiang Ma, Jiqian Fang, Hong Yan, Xiaoping Kang, Ping Yin, Yuantao Hao, Qiang Li, John Dent, Joseph Sung, Duowu Zou, Saga Johansson, Katarina Halling, Wenbin Liu and Jia H

Colonoscopy quality across Europe : a report of the European Colonoscopy Quality Investigation (ECQI) Group

publishedVersionPeer reviewe

Dual-Phase PET-CT to Differentiate [F-18]Fluoromethylcholine Uptake in Reactive and Malignant Lymph Nodes in Patients with Prostate Cancer

PURPOSE: To investigate whether time-trends of enhanced [(18)F]Fluoromethylcholine ([(18)F]FCH) in lymph nodes (LN) of prostate cancer (PCa) patients can help to discriminate reactive from malignant ones, and whether single time point standardized uptake value (SUV) measurements also suffice. PROCEDURES: 25 PCa patients with inguinal (presumed benign) and enlarged pelvic LN (presumed malignant) showing enhanced [(18)F]FCH uptake at dual-phase PET-CT were analyzed. Associations between LN status (benign versus malignant) and SUV(max) and SUV(meanA50), determined at 2 min (early) and 30 min (late) post injection, were assessed. We considered two time-trends of [(18)F]FCH uptake: type A (SUV early > SUV late) and type B (SUV late ≥ SUV early). Histopathology and/or follow-up were used to confirm the assumption that LN with type A pattern are benign, and LN with type B pattern malignant. RESULTS: Analysis of 54 nodes showed that LN status, time-trends, and 'late' (30 min p.i.) SUV(max) and SUV(meanA50) parameters were strongly associated (P<0.0001). SUV(max) relative difference was the best LN status predictor. All but one inguinal LN showed a decreasing [(18)F]FCH uptake over time (pattern A), while 95% of the pelvic nodes presented a stable or increasing uptake (pattern B) type. CONCLUSIONS: Time-trends of enhanced [(18)F]FCH uptake can help to characterize lymph nodes in prostate cancer patients. Single time-point SUV measurements, 30 min p.i., may be a reasonable alternative for predicting benign versus malignant status of lymph nodes, but this remains to be validated in non-enlarged pelvic lymph nodes