Sex-specific risk factor profile in oesophageal adenocarcinoma

A nationwide Swedish case–control study of 388 men and 63 women with adenocarcinoma of the oesophagus and gastro-oesophageal function and 676 men controls and 140 women investigated whether sex differences in aetiology contribute to male predominance. Compared with men, women seemed more vulnerable to reflux (odds ratio (OR)=4.6, 95% confidence interval (CI)=2.0–10.5 vs OR=3.4, 95% CI=2.5–4.6), obesity (OR=10.3, 95% CI=2.6–42.3 vs OR=5.4, 95% CI=2.6–10.8) and smoking (OR=5.3, 95% CI=2.0–14.1 vs OR=2.8, 95% CI=1.9–4.2), less harmed by low intake of fruit and vegetables (OR=0.9, 95% CI 0.3–2.4 vs OR=1.6, 95% CI=1.1–2.2) and less protected by Helicobacter pylori infection (OR=0.5, 95% CI=0.3–0.8 vs OR=1.6, 95% CI=0.5–5.4)

Biologically-informed neural networks guide mechanistic modeling from sparse experimental data

Biologically-informed neural networks (BINNs), an extension of physics-informed neural networks [1], are introduced and used to discover the underlying dynamics of biological systems from sparse experimental data. In the present work, BINNs are trained in a supervised learning framework to approximate in vitro cell biology assay experiments while respecting a generalized form of the governing reaction-diffusion partial differential equation (PDE). By allowing the diffusion and reaction terms to be multilayer perceptrons (MLPs), the nonlinear forms of these terms can be learned while simultaneously converging to the solution of the governing PDE. Further, the trained MLPs are used to guide the selection of biologically interpretable mechanistic forms of the PDE terms which provides new insights into the biological and physical mechanisms that govern the dynamics of the observed system. The method is evaluated on sparse real-world data from wound healing assays with varying initial cell densities [2]

Hormone replacement therapy and risks of oesophageal and gastric adenocarcinomas

Oesophageal and gastric adenocarcinoma share an unexplained male predominance, which would be explained by the hypothesis that oestrogens are protective in this respect. We carried out a nested case–control study of hormone replacement therapy (HRT) among 299 women with oesophageal cancer, 313 with gastric cancer, and 3191 randomly selected control women, frequency matched by age and calendar year in the General Practitioners Research Database in the United Kingdom. Data were adjusted for age, calendar year, tobacco smoking, alcohol consumption, body mass index, hysterectomy, and upper gastrointestinal disorders. Among 1 619 563 person-years of follow-up, more than 50% reduced risk of gastric adenocarcinoma was found among users of HRT compared to nonusers (odds ratio (OR), 0.48, 95% confidence interval (CI) 0.29–0.79). This inverse association appeared to be stronger for gastric noncardia (OR 0.34, 95% CI 0.14–0.78) and weaker for gastric cardia tumours (OR 0.68, 95% CI 0.23–2.01). There was no association between HRT and oesophageal adenocarcinoma (OR 1.17, 95% CI 0.41–3.32)

Population‐based study of anastomotic stricture rates after minimally invasive and open oesophagectomy for cancer

Background The population‐based incidence of anastomotic stricture after minimally invasive oesophagectomy (MIO) and open oesophagectomy (OO) is not known. The aim of this study was to compare rates of anastomotic stricture requiring dilatation after the two approaches in an unselected cohort using nationwide data from Finland and Sweden. Methods All patients who had MIO or OO for oesophageal cancer between 2007 and 2014 were identified from nationwide registries in Finland and Sweden. Outcomes were the overall rate of anastomotic stricture and need for single or repeated (3 or more) dilatations for stricture within the first year after surgery. Multivariable Cox regression provided hazard ratios (HRs) with 95 per cent confidence intervals, adjusted for age, sex, co‐morbidity, histology, stage, year, country, hospital volume, length of hospital stay and readmissions. Results Some 239 patients underwent MIO and 1430 had an open procedure. The incidence of strictures requiring one dilatation was 16·7 per cent, and that for strictures requiring three or more dilatations was 6·6 per cent. The HR for strictures requiring one dilatation was not increased after MIO compared with that after OO (HR 1·19, 95 per cent c.i. 0·66 to 2·12), but was threefold higher for repeated dilatations (HR 3·25, 1·43 to 7·36). Of 18 strictures following MIO, 14 (78 per cent) occurred during the first 2 years after initiating this approach. Conclusion The need for endoscopic anastomotic dilatation after oesophagectomy was common, and the need for repeated dilatation was higher after MIO than following OO. The increased risk after MIO may reflect a learning curve. </div

Reproductive factors and oesophageal cancer in Chinese women: a case-control study

<p/> <p>Background</p> <p>Previous studies showed that sex hormone might play a role in the development of oesophageal cancer in Western countries. However, evidence from Chinese populations is still lacking.</p> <p>Methods</p> <p>We performed a hospital-based case-control study in Guangzhou, China. From June 2006 to May 2009, face-to-face interviews were conducted on 73 cases and 157 controls. Cases were Chinese females with newly diagnosed primary oesophageal cancer. Controls were hospitalized individuals without cancer and frequency matched by age groups. The interviews included questions about childbearing and menarche history, together with potential confounders. Unconditional logistic regression was used to estimate the risk of factors.</p> <p>Results</p> <p>Women who had given birth before were not at increased risk compared to childless women (adjusted OR = 1.17, 95% CI: 0.48 ~ 2.85). The risk of oesophageal cancer increased with age at first birth: the adjusted OR for women first giving birth at age 25 or later was 2.02 (95% CI: 1.01 ~ 4.04) compared with those reporting their first birth before age 22. History of spontaneous abortion was not significantly associated with increased risk (adjusted OR = 1.37, 95% CI: 0.49 ~ 3.83). No significant association was observed between menstrual variables (age at menarche, age at menopause, and years of menstruation) and risk of oesophageal cancer.</p> <p>Conclusions</p> <p>Giving birth at later age may increase the risk of oesophageal cancer in women. Further studies in Chinese populations with larger sample sizes are still needed.</p

Orbifold projection in supersymmetric QCD at N_f\leq N_c

Supersymmetric orbifold projection of N=1 SQCD with relatively small number of flavors (not larger than the number of colors) is considered. The purpose is to check whether orbifolding commutes with the infrared limit. On the one hand, one considers the orbifold projection of SQCD and obtains the low-energy description of the resulting theory. On the other hand, one starts with the low-energy effective theory of the original SQCD, and only then perfoms orbifolding. It is shown that at finite N_c the two low-energy theories obtained in these ways are different. However, in the case of stabilized run-away vacuum these two theories are shown to coincide in the large N_c limit. In the case of quantum modified moduli space, topological solitons carrying baryonic charges are present in the orbifolded low-energy theory. These solitons may restore the correspondence between the two theories provided that the soliton mass tends to zero in the large N_c limit.Comment: 10 pages; misprint corrected, reference adde

Polymorphisms in Genes of Relevance for Oestrogen and Oxytocin Pathways and Risk of Barrett's Oesophagus and Oesophageal Adenocarcinoma: A Pooled Analysis from the BEACON Consortium.

BACKGROUND: The strong male predominance in oesophageal adenocarcinoma (OAC) and Barrett's oesophagus (BO) continues to puzzle. Hormonal influence, e.g. oestrogen or oxytocin, might contribute. METHODS: This genetic-epidemiological study pooled 14 studies from three continents, Australia, Europe, and North America. Polymorphisms in 3 key genes coding for the oestrogen pathway (receptor alpha (ESR1), receptor beta (ESR2), and aromatase (CYP19A1)), and 3 key genes of the oxytocin pathway (the oxytocin receptor (OXTR), oxytocin protein (OXT), and cyclic ADP ribose hydrolase glycoprotein (CD38)), were analysed using a gene-based approach, versatile gene-based test association study (VEGAS). RESULTS: Among 1508 OAC patients, 2383 BO patients, and 2170 controls, genetic variants within ESR1 were associated with BO in males (p = 0.0058) and an increased risk of OAC and BO combined in males (p = 0.0023). Genetic variants within OXTR were associated with an increased risk of BO in both sexes combined (p = 0.0035) and in males (p = 0.0012). We followed up these suggestive findings in a further smaller data set, but found no replication. There were no significant associations between the other 4 genes studied and risk of OAC, BO, separately on in combination, in males and females combined or in males only. CONCLUSION: Genetic variants in the oestrogen receptor alpha and the oxytocin receptor may be associated with an increased risk of BO or OAC, but replication in other large samples are needed

Incidence and survival of oesophageal and gastric cancer in England between 1998 and 2007, a population-based study

BACKGROUND: Major changes in the incidence of oesophageal and gastric cancers have been reported internationally. This study describes recent trends in incidence and survival of subgroups of oesophageal and gastric cancer in England between 1998 and 2007 and considers the implications for cancer services and policy. METHODS: Data on 133,804 English patients diagnosed with oesophageal and gastric cancer between 1998 and 2007 were extracted from the National Cancer Data Repository. Using information on anatomical site and tumour morphology, data were divided into six groups; upper and middle oesophagus, lower oesophagus, oesophagus with an unspecified anatomical site, cardia, non-cardia stomach, and stomach with an unspecified anatomical site. Age-standardised incidence rates (per 100,000 European standard population) were calculated for each group by year of diagnosis and by socioeconomic deprivation. Survival was estimated using the Kaplan-Meier method. RESULTS: The majority of oesophageal cancers were in the lower third of the oesophagus (58%). Stomach with an unspecified anatomical site was the largest gastric cancer group (53%). The incidence of lower oesophageal cancer increased between 1998 and 2002 and remained stable thereafter. The incidence of cancer of the cardia, non-cardia stomach, and stomach with an unspecified anatomical site declined over the 10 year period. Both lower oesophageal and cardia cancers had a much higher incidence in males compared with females (M:F 4:1). The incidence was also higher in the most deprived quintiles for all six cancer groups. Survival was poor in all sub-groups with 1 year survival ranging from 14.8-40.8% and 5 year survival ranging from 3.7-15.6%. CONCLUSIONS: An increased focus on prevention and early diagnosis, especially in deprived areas and in males, is required to improve outcomes for these cancers. Improved recording of tumour site, stage and morphology and the evaluation of focused early diagnosis programmes are also needed. The poor long-term survival reinforces the need for early detection and multidisciplinary care