GAPPS is a unique gastric polyposis syndrome with a significant risk of gastric adenocarcinoma. It is characterised by the autosomal dominant transmission of fundic gland polyposis, including areas of dysplasia or intestinal-type gastric adenocarcinoma, restricted to the proximal stomach, and with no evidence of colorectal or duodenal polyposis or other heritable gastrointestinal cancer syndromes.

Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is an autosomal-dominant cancer-predisposition syndrome with a significant risk of gastric, but not colorectal, adenocarcinoma. We mapped the gene to 5q22 and found loss of the wild-type allele on 5q in fundic gland polyps from affected individuals. Whole-exome and -genome sequencing failed to find causal mutations but, through Sanger sequencing, we identified point mutations in APC promoter 1B that co-segregated with disease in all six families. The mutations reduced binding of the YY1 transcription factor and impaired activity of the APC promoter 1B in luciferase assays. Analysis of blood and saliva from carriers showed allelic imbalance of APC, suggesting that these mutations lead to decreased allele-specific expression in vivo. Similar mutations in APC promoter 1B occur in rare families with familial adenomatous polyposis (FAP). Promoter 1A is methylated in GAPPS and sporadic FGPs and in normal stomach, which suggests that 1B transcripts are more important than 1A in gastric mucosa. This might explain why all known GAPPS-affected families carry promoter 1B point mutations but only rare FAP-affected families carry similar mutations, the colonic cells usually being protected by the expression of the 1A isoform. Gastric polyposis and cancer have been previously described in some FAP-affected individuals with large deletions around promoter 1B. Our finding that GAPPS is caused by point mutations in the same promoter suggests that families with mutations affecting the promoter 1B are at risk of gastric adenocarcinoma, regardless of whether or not colorectal polyps are present.

Barrett's esophagus (BE), a common condition, is the only known precursor to esophageal adenocarcinoma (EAC). There is uncertainty about the best way to manage BE as most people with BE never develop EAC and most patients diagnosed with EAC have no preceding diagnosis of BE. Moreover, there have been recent advances in knowledge and practice about the management of BE and early EAC. To aid clinical decision making in this rapidly moving field, Cancer Council Australia convened an expert working party to identify pertinent clinical questions. The questions covered a wide range of topics including endoscopic and histological definitions of BE and early EAC; prevalence, incidence, natural history, and risk factors for BE; and methods for managing BE and early EAC. The latter considered modification of lifestyle factors; screening and surveillance strategies; and medical, endoscopic, and surgical interventions. To answer each question, the working party systematically reviewed the literature and developed a set of recommendations through consensus. Evidence underpinning each recommendation was rated according to quality and applicability.

The gut microbiota is important in maintaining human health, but numerous factors have the potential to alter its composition. Our aim was to examine the impact of a standard bowel preparation on the intestinal microbiota using two different techniques. Fifteen subjects undergoing colonoscopy consumed a bowel preparation comprised of 10 mg bisacodyl and 2 L polyethylene glycol. The microbiota of stool samples, collected one month before, one week before (pre-colonoscopy), and one week, one month, and three to six months after colonoscopy (post-colonoscopy) was evaluated. Two samples were taken three to six months apart from five healthy subjects who did not undergo colonoscopy. Universal primers targeting the V2–V3 region of the 16S rRNA gene were used to PCR amplify all samples for denaturing gradient gel electrophoresis (PCR-DGGE). Pre- and post-colonoscopy samples were compared using Dice’s similarity coefficients. Three samples from ten subjects who underwent colonoscopy, and both samples from the five subjects who didn’t, were used for high-throughput sequencing of the V1–V3 region of the 16S rRNA gene. Samples were curated and analysed in Mothur. Results of the DGGE analyses show that the fecal microbiota of a small number of subjects had short-term changes. High-throughput sequencing results indicated that the variation between the samples of subjects who underwent colonoscopy was no greater than the variation observed between samples from subjects who did not. We conclude that bowel preparation does not have a lasting effect on the composition of the intestinal microbiota for the majority of subjects.

Endothelin-1 (ET-1), a potent vasoconstrictor, is released mainly by vascular endothelial cells under the influence of hypoxia and other stimuli. ET-1 is related to endothelial dysfunction, as well as arterial and pulmonary hypertension, all of which are thought to be associated with obstructive sleep apnoea (OSA).This study evaluated venous plasma concentrations of ET-1 and noradrenaline and 24-h systemic blood pressure in 29 patients with OSA (age=56.9 1.6 yrs; body mass index=29.5 0.7 kg . m -2 (mean SEM)). Blood samples were taken in the morning, evening and during sleep. In the same way, the patients were assessed during a night of continuous positive airway pressure (CPAP) and after 13.9 1.4 months while still on CPAP. ET-1 levels were compared to those of control subjects, who were selected from in-and outpatients and were matched to patients for age, sex, presence of arterial hypertension and coronary artery disease.ET-1 plasma levels were not elevated in the patients compared to the controls (41.6 2.2 and 44.9 1.3 pg . mL -1 , respectively, p=0.20). The ET-1 concentration did not change significantly, neither during sleep nor in the first night on CPAP therapy, nor under long-term treatment with CPAP. ET-1 neither correlated to the severity of OSA nor to that of systemic hypertension.The results suggest that endothelin-1 does not play a crucial role in the pathophysiology of obstructive sleep apnoea. Endothelins are peptides of 21 amino acids that are produced in a wide variety of cells. Endothelin-1 (ET-1) was isolated from vascular endothelial cells [1], whereas endothelin-2 (ET-2) and endothelin-3 (ET-3) are mainly produced within the kidney and intestine. ET-1 is released under the influence of chemical or physical stimuli, such as hypoxia or shear stress, as well as various receptor operated mechanisms. It is the most potent endogenous vasoconstrictor yet identified and seems to be intimately involved in the pathogenesis of pulmonary hypertension [2,3]. Whether ET-1 production is increased in arterial hypertension remains controversial though [4]. Patients with obstructive sleep apnoea (OSA) exhibit repetitive nocturnal apnoeas and hypopnoeas which result in oxygen desaturations and consecutive arousals. OSA can be successfully treated with continuous positive airway pressure (CPAP). The disease can be associated with pulmonary hypertension even in the absence of daytime hypoxaemia or concomitant lung disease [5,6]. In epidemiological and animal studies an association between systemic hypertension and OSA, independent of obesity, age and sex, was found [7,8]. It is therefore tempting to speculate that in OSA plasma ET-1 levels are elevated due to nocturnal desaturations and give rise to pulmonary as well as arterial hypertension. To further elucidate this hypothesis the authors' studied the influence of CPAP treatment on ET-1 plasma concentration in patients with OSA. Methods Subjects and protocolTwenty-nine consecutive subjects of both sexes that were referred to the authors' sleep labor...

We present three cases of the rare hepatosplenic T-cell lymphoma (HSTCL); two patients suffering from Crohn disease who developed HSTCL on azathioprine without exposure to biologicals, and a third patient who had psoriasis treated using etanercept, cyclosporine and methotrexate. The evidence for an association between HSTCL and immunosuppressive drugs and biologicals is reviewed. We argue for improved pharmacovigilance processes to help determine the benefit to risk ratios for the use of these and other new agents.

Using a simple cylindrical model for the colon and reducing drift by registering band images allows for the generation of visibility maps. The current results also suggest that the provided feedback through the visibility map could enhance clinicians' awareness of uncovered areas, which in return could reduce the probability of missing polyps.

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