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Background: Altered enteroendocrine hormone responses are widely believed to underlie the beneficial effects of bariatric surgery in type 2 diabetes. While elevated postprandial glucagon-like peptide-1 (GLP-1) is considered one of the mediators, increased postprandial glucagon levels have recently been implicated., Objectives: We investigated hormonal responses in lean patients after prophylactic total gastrectomy (PTG), as a model of Roux-en-Y gastric bypass without the confounding effects of obesity or massive weight loss., Setting: University hospital, United Kingdom., Methods: Ten participants after PTG and 9 healthy volunteers were recruited for oral glucose tolerance tests. Plasma glucose, insulin, GLP-1, peptide YY, glucose-dependent insulinotropic-polypeptide, glucagon, oxyntomodulin, glucagon (1-61) , and glicentin levels were assessed using immunoassays and/or mass spectrometry., Results: PTG participants exhibited accelerated plasma glucose appearance, followed, in 3 of 10 cases, by hypoglycemia (<3 mM glucose). Plasma GLP-1, peptide YY, glucose-dependent insulinotropic-polypeptide, glicentin, and oxyntomodulin responses were elevated, and glucagon appeared to rise in PTG participants when measured with a glucagon-specific enzyme-linked immunosorbent assay. We revisited the specificity of this assay, and demonstrated significant cross-reactivity with glicentin and oxyntomodulin at concentrations observed in PTG plasma. Reassessment of glucagon with the same assay using a modified protocol, and by liquid chromatography-mass spectrometry, demonstrated suppression of glucagon secretion after oral glucose tolerance tests in both PTG and control cohorts., Conclusions: Care should be taken when assessing glucagon levels in the presence of elevated plasma levels of other proglucagon products. Substantial elevation of GLP-1 and insulin responses after PTG likely contribute to the observed hypoglycemia, and mirror similar hormone levels and complications observed in bariatric weight loss patients., (Copyright © 2018 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Individuals identified as at high risk of developing Hereditary Diffuse Gastric Cancer (HDGC) are advised to undergo prophylactic surgery - have their stomach removed - in their early twenties. Research with (older) cancer patients who undergo gastrectomy for curative reasons suggests that gastric resection has a number of physical and psychosocial sequelae. Because it is difficult to extrapolate the findings of studies of older cancer patients to younger healthy patients who are considering prophylactic total gastrectomy (PTG), the aim of this qualitative interview study was to determine the psychosocial implications of undergoing prophylactic surgery to manage genetic risk. Fourteen men and 13 women from the UK's Familial Gastric Cancer study who had undergone PTG were invited to participate in qualitative interviews. Most reported that undergoing surgery and convalescence was easier than anticipated. There was evidence that age affected experiences of PTG, with younger patients tending to report faster recovery times and more transient aftereffects. All saw the benefits of risk reduction as outweighing the costs of surgery. Surgery was described as having a range of physical impacts (disrupted appetite, weight loss, fatigue, GI symptoms) that had related psychological, social and economic implications. Those considering PTG need to be aware that its impact on quality of life is difficult to predict and negative sequelae may be ongoing for some individuals.

Hereditary diffuse gastric cancer has an early onset and poor prognosis, therefore, individuals who carry a pathogenic (CDH1) mutation in the E-cadherin gene (CDH1) are offered endoscopic surveillance and advised to undergo prophylactic total gastrectomy (PTG) in their early to mid-twenties. Patients not ready or fit to undergo gastrectomy, or in whom the genetic testing result is unknown or ambiguous, are offered surveillance. Little is known about the factors that influence decisions to undergo or decline PTG, making it difficult to provide optimal support for those facing these decisions. Qualitative interviews were carried out with 35 high-risk individuals from the Familial Gastric Cancer Study in the UK. Twenty-seven had previously undergone PTG and eight had been identified as carrying a pathogenic CDH1 mutation but had declined surgery at the time of interview. The interviews explored the experience of decision-making and factors influencing risk-management decisions. The data suggest that decisions to proceed with PTG are influenced by a number of potentially competing factors: objective risk confirmation by genetic testing and/or receiving a positive biopsy; perceived familial cancer burden and associated risk perceptions; perceptions of post-surgical life; an increasing inability to tolerate endoscopic procedures; a concern that surveillance could miss a cancer developing and individual's life stage. These findings have implications for advising this patient group.

Background: The advice to individuals with identified CDH1 mutations is generally to undertake prophylactic total gastrectomy (PTG). This study evaluated the effect of PTG on health-related quality of life (HRQL) in asymptomatic individuals with identified CDH1 mutations at high risk for gastric cancer., Methods: Individuals with hereditary diffuse gastric cancer (HDGC) were recruited to a prospective, multicenter UK study. Questionnaires, including the European Organization for Research and Treatment for Cancer core Quality-of-Life Questionnaire (EORTC QLQ C30); the gastric cancer specific module (EORTC QLQ STO22); and the 36-item short form health survey version 2.0, were completed before and at regular intervals after surgery., Results: Sixty individuals fulfilled HDGC criteria; 38 (63%) had a CDH1 mutation and 32 (53%) underwent PTG. At baseline, there was no significant difference in mental health depending on CDH1 mutation status and treatment preference. Physical functioning reduced in the first month after surgery but recovered to baseline by 12 months. Similarly mental functioning reduced in the first month after surgery but recovered by 3 to 9 months. However, specific symptoms were identified, such as diarrhoea (70%), fatigue (63%), discomfort when eating (81%), reflux (63%), eating restrictions (45%), and body image (44%), which persisted after PTG., Conclusions: Patients contemplating prophylactic gastrectomy can be reassured about the long-term HRQL outcomes, but some residual symptoms require adjustment.

Venous thromboembolism (VTE) is a frequent cause of morbidity and mortality in patients with cancer and those having chemotherapy. However, the incidence of VTE during radical treatment for patients with oesophago-gastric cancer is poorly documented. The incidence of VTE was assessed in 200 consecutive patients with oesophago-gastric cancer having surgery with curative intent; 132 (66%) had neo-adjuvant chemotherapy, 37 (18.5%) had adjuvant chemotherapy and 64 (32%) had no chemotherapy. Patients received 40 mg of Enoxaparin subcutaneously daily during the peri-operative hospital stay. Asymptomatic VTE were detected by routine chest computed tomography (CT) pre and post surgery. Symptomatic patients with suspected VTE were investigated and treated as clinically appropriate. Twenty six patients (13%) developed VTE of which 14 (54%) were symptomatic; 12/26 (46%) VTE were detected pre-operatively, all during or after neo-adjuvant chemotherapy, and 14/26 (54%) post-operatively. There were two post-operative deaths caused by pulmonary emboli occurring at days 24 and 56 respectively despite peri-operative VTE prophylaxis. Multivariate analysis demonstrated that neo-adjuvant chemotherapy was the only factor that predicted pre-operative VTE (p = 0.073) and any VTE (p = 0.045). This study found a 13% incidence of VTE in patients undergoing therapy with curative intent for oesophago-gastric cancer and a statistically significant association between neo-adjuvant chemotherapy and VTE. Half of the patients with VTE were asymptomatic but two had fatal PE's. Current VTE prophylaxis regimens for this patient group may be inadequate., (Copyright © 2011 Elsevier Ltd. All rights reserved.)