Physical decline and its implications in the management of oesophageal and gastric cancer: a systematic review.

Purpose: The management of oesophageal and gastric cancer can cause significant physical decline, impacting on completion rates and outcomes. This systematic review aimed to (i) determine the impact of chemotherapy, chemoradiotherapy and surgery on physical function; (ii) identify associations between physical function and post-operative outcomes; and (iii) examine the effects of rehabilitation on physical function.

Methods: We included randomised controlled trials (RCT), non-RCTs of interventions and cohort studies that measured physical function by objective means in patients with oesophageal or gastric cancer.

Risks of breast or ovarian cancer in BRCA1 or BRCA2 predictive test negatives: findings from the EMBRACE study.

Purpose: BRCA1/BRCA2 predictive test negatives are proven noncarriers of a BRCA1/BRCA2 mutation that is carried by their relatives. The risk of developing breast cancer (BC) or epithelial ovarian cancer (EOC) in these women is uncertain. The study aimed to estimate risks of invasive BC and EOC in a large cohort of BRCA1/BRCA2 predictive test negatives.

Multimodality treatment for esophageal adenocarcinoma: multi-center propensity-score matched study.

Background: The primary aim of this study was to compare survival from neoadjuvant chemoradiotherapy plus surgery (NCRS) versus neoadjuvant chemotherapy plus surgery (NCS) for the treatment of esophageal or junctional adenocarcinoma. The secondary aims were to compare pathological effects, short-term mortality and morbidity, and to evaluate the effect of lymph node harvest upon survival in both treatment groups.

Methods: Data were collected from 10 European centers from 2001 to 2012.

Physiology, pathophysiology and therapeutic implications of enteroendocrine control of food intake.

With the increasing prevalence of obesity and its associated comorbidities, strides to improve treatment strategies have enhanced our understanding of the function of the gut in the regulation of food intake. The most successful intervention for obesity to date, bariatric surgery effectively manipulates enteroendocrine physiology to enhance satiety and reduce hunger. Areas covered: In the present article, we provide a detailed overview of the physiology of enteroendocrine control of food intake, and discuss its pathophysiologic correlates and therapeutic implications in both obesity and gastrointestinal disease.

Risk Factors for Anastomotic Stricture Post-esophagectomy with a Standardized Sutured Anastomosis.

Background: Benign anastomotic strictures occur frequently after esophagectomy, and impact on postoperative recovery, nutritional status, and quality of life. This large cohort study explored the incidence of stricture after transthoracic (2- and 3-stage) and transhiatal resections with uniform single-layer sutured anastomotic technique, and aimed to identify independent risk factors.

Methods: Patients undergoing esophagectomy with gastric conduit reconstruction between February 2001 and October 2014 were studied prospectively.

Weight Loss, Satiety, and the Postprandial Gut Hormone Response After Esophagectomy: A Prospective Study.

Objective: To prospectively characterize changes in body weight, satiety, and postprandial gut hormone profiles following esophagectomy.

Background: With improved oncologic outcomes in esophageal cancer, there is an increasing focus on functional status and health-related quality of life in survivorship. Early satiety and weight loss are common after esophagectomy, but the pathophysiology of these phenomena remains poorly understood.

Sharpening nature's tools for efficient tuberculosis control: A review of the potential role and development of host-directed therapies and strategies for targeted respiratory delivery.

Centuries since it was first described, tuberculosis (TB) remains a significant global public health issue. Despite ongoing holistic measures implemented by health authorities and a number of new oral treatments reaching the market, there is still a need for an advanced, efficient TB treatment. An adjunctive, host-directed therapy designed to enhance endogenous pathways and hence compliment current regimens could be the answer.

A Common Variant in the Adaptor Mal Regulates Interferon Gamma Signaling.

Humans that are heterozygous for the common S180L polymorphism in the Toll-like receptor (TLR) adaptor Mal (encoded by TIRAP) are protected from a number of infectious diseases, including tuberculosis (TB), whereas those homozygous for the allele are at increased risk. The reason for this difference in susceptibility is not clear. We report that Mal has a TLR-independent role in interferon-gamma (IFN-γ) receptor signaling.

Gut Hormone Suppression Increases Food Intake After Esophagectomy With Gastric Conduit Reconstruction.

Objectives: To characterize the gut hormone profile and determine the effect of satiety gut hormone blockade on food intake in disease-free postesophagectomy patients.

Background: Improved oncologic outcomes for esophageal cancer have resulted in increased survivorship and a focus on health-related quality of life. Anorexia and early satiety are common, but putative causative factors, in particular the gut-brain hormonal axis, have not been systematically studied.

Association of type and location of BRCA1 and BRCA2 mutations with risk of breast and ovarian cancer.

Importance: Limited information about the relationship between specific mutations in BRCA1 or BRCA2 (BRCA1/2) and cancer risk exists.

Objective: To identify mutation-specific cancer risks for carriers of BRCA1/2.

Design, Setting, And Participants: Observational study of women who were ascertained between 1937 and 2011 (median, 1999) and found to carry disease-associated BRCA1 or BRCA2 mutations.

Effect of BRCA Mutations on Metastatic Relapse and Cause-specific Survival After Radical Treatment for Localised Prostate Cancer.

Background: Germline BRCA mutations are associated with worse prostate cancer (PCa) outcomes; however, the most appropriate management for mutation carriers has not yet been investigated.

Objective: To evaluate the response of BRCA carriers to conventional treatments for localised PCa by analysing metastasis-free survival (MFS) and cause-specific survival (CSS) following radical prostatectomy (RP) or external-beam radiation therapy (RT).

Design, Setting, And Participants: Tumour features and outcomes of 1302 patients with local/locally advanced PCa (including 67 BRCA mutation carriers) were analysed.

Value of CT-PET after neoadjuvant chemoradiation in the prediction of histological tumour regression, nodal status and survival in oesophageal adenocarcinoma.

Background: The role of CT-PET after neoadjuvant chemoradiation (nCRT) for prediction of pathological response and oncological outcome in oesophageal and junctional adenocarcinoma (OAC) is unclear. The relationship between complete metabolic response (cMR), pathological complete response (pCR) and nodal status has not been clarified.

Methods: Patients with locally advanced OAC selected to receive nCRT and surgery with curative intent, on the basis of staging that included CT-PET positivity, were included.

DNA glycosylases involved in base excision repair may be associated with cancer risk in BRCA1 and BRCA2 mutation carriers.

Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2).

Basic concepts of inflammation and its role in carcinogenesis.

While the normal inflammatory cascade is self-limiting and crucial for host protection against invading pathogens and in the repair of damaged tissue, a wealth of evidence suggests that chronic inflammation is the engine driving carcinogenesis. Over a period of almost 150 years the link between inflammation and cancer development has been well established. In this chapter we discuss the fundamental concepts and mechanisms behind normal inflammation as it pertains to wound healing.

Autophagy in the immune response to tuberculosis: clinical perspectives.

A growing body of evidence points to autophagy as an essential component in the immune response to tuberculosis. Autophagy is a direct mechanism of killing intracellular Mycobacterium tuberculosis and also acts as a modulator of proinflammatory cytokine secretion. In addition, autophagy plays a key role in antigen processing and presentation.

Associations between leptin and adiponectin receptor upregulation, visceral obesity and tumour stage in oesophageal and junctional adenocarcinoma.

Background: Obesity is associated with oesophageal adenocarcinoma, but mechanisms linking fat and carcinogenesis remain poorly understood. Altered circulating adipocytokines may be important. This study aimed to identify pathways through which visceral fat impacts on tumour biology.

An unusual presentation of Boerhaave Syndrome: a case report.

We present a unique case of Boerhaave Syndrome that may highlight the spectrum of barotrauma from a Mallory-Weiss tear to full-thickness perforation. In this case, perforation only became evident following air insufflation at endoscopy.

Symposium on 'The challenge of translating nutrition research into public health nutrition'. Session 3: Joint Nutrition Society and Irish Nutrition and Dietetic Institute Symposium on 'Nutrition and autoimmune disease'. Recent advances in genetic understanding of coeliac disease.

Over the past 20 years major advances have been made in the diagnosis and understanding of pathogenic mechanisms relating to coeliac disease. Recently-identified genetic markers support the immunological-inflammatory nature of the disease. It is hoped that these newly-identified genes will assist further dissection of the inflammatory pathways in coeliac disease and give insight into why certain individuals develop intolerance to dietary gluten.

A caspase-independent pathway mediates macrophage cell death in response to Mycobacterium tuberculosis infection.

Macrophages can undergo apoptosis after infection with Mycobacterium tuberculosis. This macrophage response deprives the bacillus of its niche cell and supports the host response through better antigen presentation. The intracellular pathways of apoptosis that elaborate this macrophage response are not well understood.

Serum levels of soluble CD163 correlate with the inflammatory process in coeliac disease.

Background: In coeliac disease, following the introduction of a gluten-free diet, monitoring mucosal disease activity requires repeated small intestinal biopsies. If a test measuring a circulating inflammatory marker was available, this would be clinically valuable.

Aim: To determine if levels of soluble CD163, a scavenger receptor shed by tissue macrophages, correlated with the inflammatory lesion in coeliac disease.

Immunohistochemical analysis of coeliac mucosa following ingestion of oats.

There is now considerable clinical evidence that oats do not activate coeliac disease. Nonetheless, a reluctance to include oats in the gluten-free diet remains. Because gluten-induced damage is accompanied by activation of the gastrointestinal immune system, the purpose of this study was to investigate if similar changes were induced by oats ingestion.