Predisposing Role of Immunologic determinants in the Etiology of Barrett’s Esophagus

Gastroesophageal reflux disease (GERD) is defined as the presence of symptoms or lesions that can be attributed to reflux of gastric contents into the esophagus. In the Western world, GERD represent one of the most common gastrointestinal problems [1,2]. Cardinal manifestations of GERD are the presence of reflux symptoms such as heartburn, and the presence of gastroesophageal reflux. Heartburn is very common in Western populations with over 40% of the general population having monthly symptoms, and approximately 20% having symptoms on at least a weekly basis [1]. GERD is a spectrum encompassing a broad range of conditions. Of all patients referred for upper GI endoscopy for heartburn as their major symptom, 20-40 % have a reflux esophagitis, 6-12% have a Barrett’s esophagus (BE), and the remaining have endoscopynegative GERD [3-10]. The diagnosis of severe reflux esophagitis is important as treatment can prevent the development of reflux related complications such as bleeding, stricture, and ulcers. Another important complication of chronic exposure to gastroesophageal reflux is the development of esophageal adenocarcinoma (EAC). Gastroesophageal reflux is considered to be the key element in the development of EAC since severe, longstanding, and frequent episodes of gastroesophageal reflux is associated with a seven- to eightfold increased risk of EAC

Does CDX2 expression predict Barrett's metaplasia in oesophageal columnar epithelium without goblet cells?

Background: Intestinal metaplasia (Barrett's oesophagus), but not cardiac-type mucosa in columnar-lined oesophagus, is regarded as premalignant. As intestinal metaplasia and cardiac-type mucosa are endoscopically indiscernible, it is difficult to take targeted samples from columnar-lined oesophagus with consequently a risk of having undetected intestinal metaplasia. Aim: To investigate whether the intestinal markers CDX2, MUC2 and villin can predict the presence of undetected intestinal metaplasia in columnar-lined oesophagus. Methods: Presence of intestinal metaplasia or cardiac-type mucosa was identified in 122 biopsy sets of columnar-lined oesophagus from 61 patients, collected at two subsequent follow-up upper endoscopies. CDX2, MUC2 and villin expression were determined by immunohistochemistry. Results: All intestinal metaplasia samples (55) were positive for CDX2 and MUC2 and 32 of 55 for vil

Endoscopic mucosal resection (EMR) versus endoscopic submucosal dissection (ESD) for resection of large distal non-pedunculated colorectal adenomas (MATILDA-trial): Rationale and design of a multicenter randomized clinical trial

Background: Endoscopic mucosal resection (EMR) is currently the most used technique for resection of large distal colorectal polyps. However, in large lesions EMR can often only be performed in a piecemeal fashion resulting in relatively low radical (R0)-resection rates and high recurrence rates. Endoscopic submucosal dissection (ESD) is a newer procedure that is more difficult resulting in a longer procedural time, but is promising due to the high en-bloc resection rates and the very low recurrence rates. We aim to evaluate the (cost-)effectiveness of ESD against EMR on both short (i.e. 6 months) and long-term (i.e. 36 months). We hypothesize that in the short-run ESD is more time consuming resulting in higher healthcare costs, but is (cost-) effective on the long-term due to lower patients burden, a higher number of R0-resections and lower recurrence rates with less need for repeated procedures. Methods: This is a multicenter randomized clinical trial in patients with a non-pedunculated polyp larger than 20 mm in the rectum, sigmoid, or descending colon suspected to be an adenoma by means of endoscopic assessment. Primary endpoint is recurrence rate at follow-up colonoscopy at 6 months. Secondary endpoints are R0-resection rate, perceived burden and quality of life, healthcare resources utilization and costs, surgical referral rate, complication rate and recurrence rate at 36 months. Quality-adjusted-life-year (QALY) will be estimated taking an area under the curve approach and using EQ-5D-indexes. Healthcare costs will be calculated by multiplying used healthcare services with unit prices. The cost-effectiveness of ESD against EMR will be expressed as incremental cost-effectiveness ratios (ICER) showing additional costs per recurrence free patient and as ICER showing additional costs per QALY. Discussion: If this trial confirms ESD to be favorable on the long-term, the burden of extra colonoscopies and repeated procedures can be prevented for future patients. Trial registration:NCT02657044(Clinicaltrials.gov), registered January 8, 2016

Quality of life and fear of cancer recurrence in T1 colorectal cancer patients treated with endoscopic or surgical tumor resection

Surgical oncolog

Clinicopathological features and risk factors for developing colorectal neoplasia in Hodgkin's lymphoma survivors

Background Hodgkin's lymphoma (HL) survivors treated with abdominal radiotherapy and/or procarbazine have an increased risk of developing colorectal neoplasia.Aims We evaluated the clinicopathological characteristics and risk factors for developing (advanced) neoplasia (AN) in HL survivors.Methods In all, 101 HL survivors (median age 51 years, median age of HL diagnosis 25 years) underwent colonoscopy and 350 neoplasia and 44 AN (classified as advanced adenomas/serrated lesions or colorectal cancer), mostly right-sided, were detected, as published previously. An average-risk asymptomatic cohort who underwent screening colonoscopy were controls (median age 60 years). Clinicopathological characteristics of AN were evaluated in both groups. Mismatch repair (MMR) status was assessed using immunohistochemistry (MLH1/MSH2/MSH6/PMS2). Logistic regression analysis was performed to evaluate the risk factors for AN in HL survivors, including age at HL diagnosis and interval between HL and colonoscopy.Results In 101 colonoscopies in HL survivors, AN was primarily classified based on polyp size >= 10 mm, whereas (high-grade)dysplasia was more often seen in AN in controls. An interval between HL diagnosis and colonoscopy >26 years was associated with more AN compared with an interval of = 10 mm) in HL survivors. Longer follow-up between HL diagnosis and colonoscopy was associated with a higher prevalence of AN in HL survivors.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Diagnostic value of radiological staging and surveillance for T1 colorectal carcinomas: a multicenter cohort study

Background: The role of radiological staging and surveillance imaging is under debate for T1 colorectal cancer (CRC) as the risk of distant metastases is low and imaging may lead to the detection of incidental findings. Objective: The aim of this study was to evaluate the yield of radiological staging and surveillance imaging for T1 CRC. Methods: In this retrospective multicenter cohort study, all patients of 10 Dutch hospitals with histologically proven T1 CRC who underwent radiological staging in the period 2000-2014 were included. Clinical characteristics, pathological, endoscopic, surgical and imaging reports at baseline and during follow-up were recorded and analyzed. Patients were classified as high-risk T1 CRC if at least one of the histological risk factors (lymphovascular invasion, poor tumor differentiation, deep submucosal invasion or positive resection margins) was present and as low-risk when all risk factors were absent. Results: Of the 628 included patients, 3 (0.5%) had synchronous distant metastases, 13 (2.1%) malignant incidental findings and 129 (20.5%) benign incidental findings at baseline staging. Radiological surveillance was performed among 336 (53.5%) patients. The 5-year cumulative incidence of distant recurrence, malignant and benign incidental findings were 2.4% (95% confidence interval (CI): 1.1%-5.4%), 2.5% (95% CI: 0.6%-10.4%) and 18.3% (95% CI: 13.4%-24.7%), respectively. No distant metastatic events occurred among low-risk T1 CRC patients. Conclusion: The risk of synchronous distant metastases and distant recurrence in T1 CRC is low, while there is a substantial risk of detecting incidental findings. Radiological staging seems unnecessary prior to local excision of suspected T1 CRC and after local excision of low-risk T1 CRC. Radiological surveillance should not be performed in patients with low-risk T1 CRC.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Periprocedural adverse events after endoscopic resection of T1 colorectal carcinomas

Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Diagnostic yield of colonoscopy surveillance in testicular cancer survivors treated with platinum-based chemotherapy: study protocol of a prospective cross-sectional cohort study

Background: Testicular cancer (TC) survivors have an increased risk of various second primary malignancies. A recent cohort study detected an increased risk of colorectal cancer (CRC) in TC survivors treated with platinum-based chemotherapy with a hazard ratio of 3.9. CRC risk increased with higher cisplatin-dose. We know that colonoscopy surveillance in high-risk populations results in reduced incidence and mortality of CRC. TC survivors treated with platinum-based chemotherapy can potentially benefit from colonoscopy surveillance; however, to which extent is unknown. Furthermore, the pathogenesis of these secondary CRCs is unknown, and better insights into the carcinogenesis may affect surveillance decisions. Methods: This prospective multicenter study will be performed in four Dutch hospitals. TC survivors are eligible if treated with ≥ 3 cycles of cisplatin before age 50. Colonoscopy will be performed ≥ 8 years after initial treatment (minimum and maximum ages at colonoscopy, 35 and 75 years, respectively). The primary aim of the study is the diagnostic yield of advanced neoplasia detected during colonoscopy. As secondary aim, we will evaluate the molecular profile of advanced colorectal neoplasia and will assess current platinum levels in blood and urine and correlate blood-platinum levels with prevalence of colorectal lesions. Furthermore, we will investigate effectiveness of fecal immunochemical testing (FIT) and burden of colonoscopy by two questionnaires. Demographic data, previous history, results of colonoscopy, hemoglobin level of FIT and results of molecular and platinum levels will be obtained. Yield of colonoscopy will be determined by detection rate of adenoma and serrated lesions, advanced adenoma detection rate and CRC detection rate. The MISCAN model will be used for cost-effectiveness analyses of CRC surveillance. With 234 participants undergoing colonoscopy, we can detect an absolute difference of 6% of advanced neoplasia with 80% power. Discussion: TC survivors treated with cisplatin-based chemotherapy can benefit from CRC surveillance. Evaluation of the diagnostic performance and patient acceptance of CRC surveillance is of importance to develop surveillance recommendations. Insight into the carcinogenesis of cisplatin-related advanced colorectal lesions will contribute to CRC prevention in the increasing number of TC survivors. The results may also be important for the many other cancer survivors treated with platinum-based chemotherapy. Trial registration: Clinical Trials: NCT04180033, November 27, 2019, https://clinicaltrials.gov/ct2/sh

Pedunculated Morphology of T1 Colorectal Tumors Associates With Reduced Risk of Adverse Outcome

Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Towards Response ADAptive Radiotherapy for organ preservation for intermediate-risk rectal cancer (preRADAR): protocol of a phase I dose-escalation trial

Introduction Organ preservation is associated with superior functional outcome and quality of life (QoL) compared with total mesorectal excision (TME) for rectal cancer. Only 10% of patients are eligible for organ preservation following short-course radiotherapy (SCRT, 25 Gy in five fractions) and a prolonged interval (4–8 weeks) to response evaluation. The organ preservation rate could potentially be increased by dose-escalated radiotherapy. Online adaptive magnetic resonance-guided radiotherapy (MRgRT) is anticipated to reduce radiation-induced toxicity and enable radiotherapy dose escalation. This trial aims to establish the maximum tolerated dose (MTD) of dose-escalated SCRT using online adaptive MRgRT.Methods and analysis The preRADAR is a multicentre phase I trial with a 6+3 dose-escalation design. Patients with intermediate-risk rectal cancer (cT3c-d(MRF-)N1M0 or cT1-3(MRF-)N1M0) interested in organ preservation are eligible. Patients are treated with a radiotherapy boost of 2×5 Gy (level 0), 3×5 Gy (level 1), 4×5 Gy (level 2) or 5×5 Gy (level 3) on the gross tumour volume in the week following standard SCRT using online adaptive MRgRT. The trial starts on dose level 1. The primary endpoint is the MTD based on the incidence of dose-limiting toxicity (DLT) per dose level. DLT is a composite of maximum one in nine severe radiation-induced toxicities and maximum one in three severe postoperative complications, in patients treated with TME or local excision within 26 weeks following start of treatment. Secondary endpoints include the organ preservation rate, non-DLT, oncological outcomes, patient-reported QoL and functional outcomes up to 2 years following start of treatment. Imaging and laboratory biomarkers are explored for early response prediction.Ethics and dissemination The trial protocol has been approved by the Medical Ethics Committee of the University Medical Centre Utrecht. The primary and secondary trial results will be published in international peer-reviewed journals.Biological, physical and clinical aspects of cancer treatment with ionising radiatio