Human Epidermal Growth Factor Receptor-3 Expression Is Regulated at Transcriptional Level in Breast Cancer Settings by Junctional Adhesion Molecule-A via a Pathway Involving Beta-Catenin and FOXA1.

The success of breast cancer therapies targeting the human epidermal growth factor receptor-2 (HER2) is limited by the development of drug resistance by mechanisms including upregulation of HER3. Having reported that HER2 expression and resistance to HER2-targeted therapies can be regulated by Junctional Adhesion Molecule-A (JAM-A), this study investigated if JAM-A regulates HER3 expression. Expressional alteration of JAM-A in breast cancer cells was used to test expressional effects on HER3 and its effectors, alongside associated functional behaviors, in vitro and semi-in vivo.

Alpha-1 antitrypsin deficiency-associated panniculitis.

Background: Panniculitis represents a rare and potentially lethal manifestation of alpha-1 antitrypsin deficiency (AATD). Evidence regarding management is limited to case reports and small case series. We sought to clarify typical features and investigation of AATD-associated panniculitis and assess the evidence regarding therapeutic options.

Genital herpes - diagnosis, treatments, attitudes and response to disclosure amongst members of the UK Herpes Viruses Association.

A diagnosis of genital herpes may result in psychological as well as physical morbidity. Many patients require on-going help and contact the Herpes Viruses Association (HVA), a UK patient support organisation. The HVA conducts occasional questionnaires relating to various issues surrounding herpes and this study reports on a survey conducted amongst members in 2015.

Differential Expression Profiles of Oxidative Stress Levels, 8-oxo-dG and 4-HNE, in Barrett's Esophagus Compared to Esophageal Adenocarcinoma.

Barrett's esophagus (BE), a chronic inflammatory condition, is the leading risk factor for esophageal adenocarcinoma (EAC). In inflammation to cancer pathways, oxidative stress profiles have been linked to cancer progression. However, the relevance of oxidative stress profiles along the BE-disease sequence remains to be elucidated.

HLA-DR expression in tumor epithelium is an independent prognostic indicator in esophageal adenocarcinoma patients.

Esophageal adenocarcinoma (EAC) is an aggressive cancer with poor prognosis, and incidence is increasing rapidly in the Western world. Measurement of immune markers has been shown to have prognostic significance in a growing number of cancers, but whether this is true for EAC has yet to be evaluated. This study aimed to characterize HLA-DR expression in the esophagus across the inflammation to cancer progression sequence and to assess the prognostic significance of HLA-DR expression in EAC.

Metabolic tumor volume provides complementary prognostic information to EUS staging in esophageal and junctional cancer.

To determine the correlation between 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) derived esophageal tumor parameters [maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV)] and endoscopic ultrasound (EUS) derived tumor parameters (T stage, N stage) and their prognostic implications. 150 consecutive patients with cancer of the esophagus or esophagogastric junction underwent staging PET-CT and staging EUS. PET-CT derived SUVmax and MTV of the primary tumor was recorded.

Changes in mitochondrial stability during the progression of the Barrett's esophagus disease sequence.

Background: Barrett's esophagus follows the classic step-wise progression of metaplasia-dysplasia-adenocarcinoma. While Barrett's esophagus is a leading known risk factor for esophageal adenocarcinoma, the pathogenesis of this disease sequence is poorly understood. Mitochondria are highly susceptible to mutations due to high levels of reactive oxygen species (ROS) coupled with low levels of DNA repair.

2016 European guideline on donovanosis.

Donovanosis is a rare sexually transmitted infection now mainly seen in sporadic cases in Papua New Guinea, South Africa, India, Brazil and Australia. The causative organism is Calymmatobacterium granulomatis, though a proposal has been put forward that the organism be reclassified as Klebsiella granulomatis comb nov The incubation period is approximately 50 days with genital papules developing into ulcers that increase in size. Four types of lesions are described - ulcerogranulomatous, hypertrophic, necrotic and sclerotic.

2014 UK national guideline for the management of anogenital herpes.

These guidelines concern the management of anogenital herpes simplex virus infections in adults and give advice on diagnosis, management, and counselling of patients. This guideline replaces the 2007 BASHH herpes guidelines and includes new sections on herpes proctitis, key points to cover with patients regarding transmission and removal of advice on the management of HSV in pregnancy which now has a separate joint BASHH/RCOG guideline.

Excess visceral adiposity induces alterations in mitochondrial function and energy metabolism in esophageal adenocarcinoma.

Background: Visceral obesity has a strong association with both the incidence and mortality of esophageal adenocarcinoma (EAC). Alterations in mitochondrial function and energy metabolism is an emerging hallmark of cancer, however, the potential role that obesity plays in driving these alterations in EAC is currently unknown.

Methods: Adipose conditioned media (ACM) was prepared from visceral adipose tissue taken from computed tomography-determined viscerally-obese and non-obese EAC patients.

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.

Differential expression of mitochondrial energy metabolism profiles across the metaplasia-dysplasia-adenocarcinoma disease sequence in Barrett's oesophagus.

Contemporary clinical management of Barrett's oesophagus has highlighted the lack of accurate predictive markers of disease progression to oesophageal cancer. This study aims to examine alterations in mitochondrial energy metabolism profiles across the entire disease progression sequence in Barrett's oesophagus. An in-vitro model was used to screen 84 genes associated with mitochondrial energy metabolism.

Outcomes in gastric and junctional cancer using neoadjuvant and adjuvant chemotherapy (epirubicin, oxaliplatin, and capecitabine) and radical surgery.

Background: The MAGIC/UK Medical Research Council (MRC) trial set the standard of care for treatment of resectable gastric and junctional adenocarcinoma, demonstrating that perioperative chemotherapy with epirubicin, cisplatin and 5-fluorouracil (ECF) confers a survival benefit over surgery alone. The randomized ECF for advanced and locally advanced esophagogastric cancer (REAL-2) trial showed that, in the metastatic setting, the EOX regimen (epirubicin, oxaliplatin and capecitabine) is as effective as ECF, with a favourable toxicity profile.

Methods: Consecutive patients with resectable gastric or junctional adenocarcinoma treated with perioperative EOX, between 2007 and 2012, were retrospectively analysed.

Black stone - a natural remedy for premature ejaculation and performance enhancement, or maybe not?

We describe the use of a non-prescribed aid (Black stone) for premature ejaculation that resulted in a chemical burn on the penis with an appearance similar to severe balanitis.

A Barrett's esophagus registry of over 1000 patients from a specialist center highlights greater risk of progression than population-based registries and high risk of low grade dysplasia.

Barrett's esophagus (BE) arising from chronic gastro-oesophageal reflux (GERD) is the main pathologic precursor of esophageal adenocarcinoma (EAC). The risk of progression to high-grade dysplasia (HGD) and EAC is unclear, and recent population studies from Denmark and Northern Ireland suggest that this has been overestimated in the past. No data exist from the Republic of Ireland.

The role of obesity in gastrointestinal cancer: evidence and opinion.

There is increasing recognition of the impact of being overweight and obese on the development of cancers at diverse sites including the gastrointestinal tract. Large epidemiological studies indicate that up to 14% of tumours may be related to obesity. Pathophysiological mechanisms underpinning this association are not well understood and so are discussed in this review.

Defining esophageal landmarks, gastroesophageal reflux disease, and Barrett's esophagus.

The following paper on gastroesophageal reflux disease (GERD) and Barrett's esophagus (BE) includes commentaries on defining esophageal landmarks; new techniques for evaluating upper esophageal sphincter (UES) tone; differential diagnosis of GERD, BE, and hiatal hernia (HH); the use of high-resolution manometry for evaluation of reflux; the role of fundic relaxation in reflux; the use of 24-h esophageal pH-impedance testing in differentiating acid from nonacid reflux and its potential inclusion in future Rome criteria; classification of endoscopic findings in GERD; the search for the cell origin that generates BE; and the relationship between BE, Barrett's carcinoma, and obesity.

Cellular origins and molecular mechanisms of Barrett's esophagus and esophageal adenocarcinoma.

This paper presents commentaries on animal models used for Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) research; acid- and bile-induced chromosomal instability and clonal selection during the progression of BE to EAC; how the components of gastric refluxate, especially acid and bile salts, promote carcinogenesis in metaplastic BE; genome-wide changes in DNA methylation and transcription involved in BE carcinogenesis; the potential role of miRNA in the development of BE and EAC; the effect of inflammatory cytokines linked to obesity on the activation of cell-death pathways and cell survival in BE and esophageal cancer; and the role of autophagy in esophageal cancer development.

Classification of pathologic response to neoadjuvant therapy in esophageal and junctional cancer: assessment of existing measures and proposal of a novel 3-point standard.

Objective: To assess existing measures of pathologic response to neoadjuvant therapy in esophageal and junctional cancer, and to recommend an optimum classification.

Background: Multimodal therapy is increasingly the standard of care for locally advanced esophageal cancer. Numerous measures of pathologic response have been studied; however, no international standardization exists and no measure is incorporated into the current American Joint Committee on Cancer staging system.

Effect of Chlamydia diagnosis on heterosexual relationships.

This study investigated whether a Chlamydia diagnosis was associated with relationship breakup or physical violence from partners when compared to other attenders at a sexually transmitted infections (STIs) clinic. Patients diagnosed with Chlamydia and who had a regular partner at the time of diagnosis, were contacted 3-12 months later and completed a questionnaire on relationship history. A comparison group of gender-matched non-STI patients were also interviewed.