Screening for gastrointestinal neoplasia: efficacy and cost of two different approaches in a clinical rehabilitation centre

Mortality from colorectal cancer (CRC) can be reduced by screening of asymptomatic individuals and by removal of colorectal adenomas (CRA). It is still under debate which screening method should be used. In a clinical rehabilitation centre we compared two widely different approaches: faecal occult blood testing (FOBT) with subsequent endoscopy of test-positives in an unselected patient group, and primary sigmoidoscopy of asymptomatic persons between 50 and 60 years of age. Between January 1988 and October 1991 a FOBT was offered to all--symptomatic and asymptomatic--6,500 in-patients of a clinical rehabilitation centre and lower/upper GI-endoscopy was suggested to test-positives (study A). In the latter half of this period 1,166 persons without bowel symptoms and/or disease and aged 50-60 years were invited to a screening sigmoidoscopy (study B). In study A 95% of the patients (n = 6,234) returned a complete FOBT, which was positive in 186 (2.98%). 126 of these 186 patients (68%) accepted further investigation, and a total of 78 sigmoidoscopies, 78 colonoscopies and 47 gastroscopies were performed. Six patients in whom a malignancy was detected (1 gastric, 1 rectal and 4 colonic; all in a curable stage) underwent surgery. In 28 patients CRA were identified and removed by snare excision. In study B 658/1,166 asymptomatic in-patients accepted the screening sigmoidoscopy (56%). Rectosigmoid adenomas were identified in 153 (23%). One rectal cancer was found. Of these cases, 116 underwent an additional colonoscopy, disclosing proximal adenomas in 39 patients (33.6%). The cost of identifying one CRA-bearer was $1,436 in study A and$271 in study B (assuming: FOBT = $3.00; sigmoidoscopy =$63.00; colonoscopy = $135; gastroscopy =$108). In study A, the cost of identifying one patient with cancer would have been $5,435, if the cost of identifying one CRA-bearer was set to$271 as in study B. Screening for CRC was well-accepted in the health-orientated environment of a rehabilitation centre. The cost of identifying a CRA-bearer with screening sigmoidoscopy was about one-fifth of that using preselection with a FOBT. However, with FOBT a higher number of cancers was found. For the discovery of CRA, mass-screening with sigmoidoscopy of persons above the age of 50 years can be advised. For the detection of both CRA and CRC, screening with FOBT and subsequent endoscopy is an acceptable and cost-effective method

Acceptance and outcome of endoscopic screening for colonic neoplasia in patients undergoing clinical rehabilitation for gastrointestinal and metabolic diseases

Acceptance and outcome of endoscopic screening for colonic neoplasia in patients undergoing clinical rehabilitation for gastrointestinal and metabolic diseases. Armbrecht U, Manus B, Bragelmann R, Stockbrugger RW, Stolte M. Marbachtalklinik, Bad Kissingen. Our purpose was to study the acceptance and the outcome of endoscopic screening investigations of the colon in patients between 50 and 60 years of age in a clinical rehabilitation center. A total of 1,166 patients (m = 691, f = 475) entered the study. After guaiac testing all patients for fecal occult blood loss (FOBT), 667 patients (57%; m = 407, 61%; f = 260, 39%; n.s.) accepted a sigmoidoscopy. Of 658 (m = 403, f = 255) patients with complete investigation, 153 (23%) (m = 104, 26%; f = 49, 19%; n.s.) had a total of 272 neoplastic polyps, including 1 carcinoma. Adenomas = /> 10 mm were found exclusively in male patients (n = 25, p 10 mm were 2%/10% (p 10 mm. In 5 cases with positive FOBT sigmoidoscopy and complementary colonoscopy did not reveal any patholog

The patient after total gastrectomy

The patient after total gastrectomy] [Article in German] Armbrecht U. Marbachtalklinik, Bad Kissingen

Acceptance and outcome of endoscopic screening for colonic neoplasia in patients undergoing clinical rehabilitation for gastrointestinal and metabolic diseases

Acceptance and outcome of endoscopic screening for colonic neoplasia in patients undergoing clinical rehabilitation for gastrointestinal and metabolic diseases. Armbrecht U, Manus B, Bragelmann R, Stockbrugger RW, Stolte M. Marbachtalklinik, Bad Kissingen. Our purpose was to study the acceptance and the outcome of endoscopic screening investigations of the colon in patients between 50 and 60 years of age in a clinical rehabilitation center. A total of 1,166 patients (m = 691, f = 475) entered the study. After guaiac testing all patients for fecal occult blood loss (FOBT), 667 patients (57%; m = 407, 61%; f = 260, 39%; n.s.) accepted a sigmoidoscopy. Of 658 (m = 403, f = 255) patients with complete investigation, 153 (23%) (m = 104, 26%; f = 49, 19%; n.s.) had a total of 272 neoplastic polyps, including 1 carcinoma. Adenomas = /> 10 mm were found exclusively in male patients (n = 25, p 10 mm were 2%/10% (p 10 mm. In 5 cases with positive FOBT sigmoidoscopy and complementary colonoscopy did not reveal any patholog

Nutrient malassimilation following total gastrectomy.

Nutrient malassimilation following total gastrectomy. Bragelmann R, Armbrecht U, Rosemeyer D, Schneider B, Zilly W, Stockbrugger RW. Dept. of Gastroenterology, Academisch Hospital Maastricht, The Netherlands. BACKGROUND: The aim of the study was to elucidate the degree and the pathophysiology of abdominal symptoms, malnutrition and malassimilation after total gastrectomy. METHODS: In 174 consecutive patients, with potentially curative total gastrectomy for gastric malignancy, subjective symptoms and objective parameters of malassimilation were evaluated. RESULTS: Abdominal symptoms were present in 86% of the patients. In spite of a high daily calorie intake (median 37.8 kcal/kg body weight) mean body mass index had been decreasing since good health. Anaemia was found in 46%, sideropenia in 31% and oesophagitis in 26%. Mean faecal fat excretion was 17.4 (1.4) g/day and mean fat malassimilation 14.8% (1.1) of the intake. A shortened small-bowel transit was measured in 21.7% of the patients, and bacterial overgrowth was present in 37.7%. CONCLUSIONS: Malassimilation post total gastrectomy seems to be multifactorial. Shortened small-bowel transit and subsequent dyssynchrony of pancreatic enzyme supply seem to be of major importance

The effect of pancreatic enzyme supplementation in patients with steatorrhoea after total gastrectomy.

Department of Gastroenterology, Academisch Ziekenhuis, Maastricht, The Netherlands.OBJECTIVE: To assess the influence of pancreatic enzyme supplementation on symptoms, energy intake, bowel habits, and fat malassimilation in patients after total gastrectomy. DESIGN: A prospective, double-blind, randomized, parallel, placebo-controlled, multi-centre trial. SETTING: Institutionalized patients in three gastroenterological rehabilitation clinics. PARTICIPANTS: 52 institutionalized patients with a faecal fat output > or = 14 g/day, operated on for malignant gastric disease a median of 198 days (interquartile range (IQR) 47-608) previously, and free from recurrence and/or metastasis. INTERVENTIONS: Nine sachets of pancreatic enzymes per day (each containing lipase 36,000, amylase 27,000, protease 2400 FIP (Federation International Pharmaceutique)) or identical-looking placebo were given for 14 days. MAIN OUTCOME MEASURES: Abdominal symptoms, energy intake, bowel habits and fat malassimilation. RESULTS: After treatment, patients on enzyme therapy felt better overall (P = 0.006), but no improvement of a specific symptom could be identified. During the intervention, the median kilojoule intake per kilogram body weight was 9% higher in the placebo group (170.8 (IQR 146.9-202.6)) than in the enzyme-treated group (157.0 (IQR 134.8-170.4)) (P = 0.03). Enzyme treatment did not result in a significant difference between the placebo and the enzyme-treated group regarding bowel habits or fat malassimilation. CONCLUSIONS: The effect of high-dose pancreatic enzymes supplementation on symptoms and steatorrhoea after total gastrectomy is marginal and does not justify its routine use.Publication Types: Clinical Trial Multicenter Study Randomized Controlled Tria

Determinants of medico-social functioning after total gastrectomy.

Department of Gastroenterology, University Hospital Maastricht, Netherlands. AIM: To describe medico-social functioning after total gastrectomy and the factors determining it. PATIENTS AND METHODS: In three medical rehabilitation centres, 173 consecutive patients (female/male = 62/111) after potentially curative total gastrectomy for gastric malignancy 206 days earlier (median, interquartile range = IQR 56-644) were evaluated for different pre- and post-operative parameters with potential influence on post-operative medico-social functioning as measured with the Edinburgh Rehabilitation Status Scale (ERSS). Parameters evaluated were: gender, age, time since operation, tumour stage, type of operation, clinical centre of admittance, haemoglobin, ferritin, albumin, presence of small bowel bacterial overgrowth, rapid oro-coecal transit, dyspepsia, early satiety, reflux, dysphagia, vomiting, a symptom based score, body mass index in health, at operation and on admission, weight loss since operation, calorie intake, bowel habits, and fat malassimilation. Independent influential factors for the ERSS were identified in a linear regression analysis. RESULTS: The median ERSS-score was 4 (IQR 2-6) on a scale from 0 (best) to 28 (worst). There was a significant difference in the ERSS-scores between the three different clinics. The ERSS-scores improved significantly with time since operation (ca. 22% per year). ERSS-scores were higher in patients with intestino-oesophageal reflux (+71%), with dyspepsia (+65%), or with dysphagia (+62%). CONCLUSION: Medico-social functioning was acceptable in this patient population. After total gastrectomy, dyspepsia, dysphagia, and intestinal reflux into the oesophagus need special attention

CD74-NRG1 fusions are oncogenic in vivo and induce therapeutically tractable ERBB2:ERBB3 heterodimerization

NRG1 fusions are recurrent somatic genome alterations occurring across several tumor types, including invasive mucinous lung adenocarcinomas and pancreatic ductal adenocarcinomas and are potentially actionable genetic alterations in these cancers. We initially discovered CD74-NRG1 as the first NRG1 fusion in lung adenocarcinomas, and many additional fusion partners have since been identified. Here, we present the first CD74-NRG1 transgenic mouse model and provide evidence that ubiquitous expression of the CD74-NRG1 fusion protein in vivo leads to tumor development at high frequency. Furthermore, we show that ERBB2:ERBB3 heterodimerization is a mechanistic event in transformation by CD74-NRG1 binding physically to ERBB3 and that CD74-NRG1–expressing cells proliferate independent of supplemented NRG1 ligand. Thus, NRG1 gene fusions are recurrent driver oncogenes that cause oncogene dependency. Consistent with these findings, patients with NRG1 fusion-positive cancers respond to therapy targeting the ERBB2:ERBB3 receptors

MYC paralog-dependent apoptotic priming orchestrates a spectrum of vulnerabilities in small cell lung cancer

MYC paralogs are frequently activated in small cell lung cancer (SCLC) but represent poor drug targets. Thus, a detailed mapping of MYC-paralog-specific vulnerabilities may help to develop effective therapies for SCLC patients. Using a unique cellular CRISPR activation model, we uncover that, in contrast to MYCN and MYCL, MYC represses BCL2 transcription via interaction with MIZ1 and DNMT3a. The resulting lack of BCL2 expression promotes sensitivity to cell cycle control inhibition and dependency on MCL1. Furthermore, MYC activation leads to heightened apoptotic priming, intrinsic genotoxic stress and susceptibility to DNA damage checkpoint inhibitors. Finally, combined AURK and CHK1 inhibition substantially prolongs the survival of mice bearing MYC-driven SCLC beyond that of combination chemotherapy. These analyses uncover MYC-paralog-specific regulation of the apoptotic machinery with implications for genotype-based selection of targeted therapeutics in SCLC patients