Anthropometric and reproductive factors and risk of esophageal and gastric cancer by subtype and subsite: Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Obesity has been associated with upper gastrointestinal cancers; however, there are limited prospective data on associations by subtype/subsite. Obesity can impact hormonal factors, which have been hypothesized to play a role in these cancers. We investigated anthropometric and reproductive factors in relation to esophageal and gastric cancer by subtype and subsite for 476,160 participants from the European Prospective Investigation into Cancer and Nutrition cohort. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models. During a mean follow-up of 14 years, 220 esophageal adenocarcinomas (EA), 195 esophageal squamous cell carcinomas, 243 gastric cardia (GC) and 373 gastric noncardia (GNC) cancers were diagnosed. Body mass index (BMI) was associated with EA in men (BMI ≥30 vs. 18.5–25 kg/m²: HR = 1.94, 95% CI: 1.25–3.03) and women (HR = 2.66, 95% CI: 1.15–6.19); however, adjustment for waist-to-hip ratio (WHR) attenuated these associations. After mutual adjustment for BMI and HC, respectively, WHR and waist circumference (WC) were associated with EA in men (HR = 3.47, 95% CI: 1.99–6.06 for WHR >0.96 vs. <0.91; HR = 2.67, 95% CI: 1.52–4.72 for WC >98 vs. <90 cm) and women (HR = 4.40, 95% CI: 1.35–14.33 for WHR >0.82 vs. <0.76; HR = 5.67, 95% CI: 1.76–18.26 for WC >84 vs. <74 cm). WHR was also positively associated with GC in women, and WC was positively associated with GC in men. Inverse associations were observed between parity and EA (HR = 0.38, 95% CI: 0.14–0.99; >2 vs. 0) and age at first pregnancy and GNC (HR = 0.54, 95% CI: 0.32–0.91; >26 vs. <22 years); whereas bilateral ovariectomy was positively associated with GNC (HR = 1.87, 95% CI: 1.04–3.36). These findings support a role for hormonal pathways in upper gastrointestinal cancers.     

Immunohistochemical and molecular analysis of PI3K/AKT/mTOR pathway in esophageal carcinoma

Among the numerous signaling pathways involved in tumorigenesis, PI3K‐AKT‐mTOR is a key one that regulates diverse cellular functions. However, its prognostic value in esophageal carcinoma remains unclear. In our study, we examined the immunohistochemical expression of phosphorylated (p‐) AKT, mTOR, p70S6K and 4E‐BP1 along with the mutational status of PIK3CA and AKT1 genes by High Resolution Melting Analysis and Pyrosequencing in 44 esophageal carcinomas. The results were correlated with the clinicopathological characteristics of the patients in an effort to define their possible prognostic significance. Total p‐mTOR cytoplasmic expression, assessed in 10 random areas, was positively correlated with tumor stage (Kruskal–Wallis ANOVA, I/II vs III/IV, p = 0.0500). Μoreover, maximum p‐mTOR cytoplasmic immunoexpression, estimated in hot spot areas, was positively associated with tumor grade (Mann–Whitney U test, I/II vs III, p = 0.0565). Interestingly, p‐4E‐BP1 immunoreactivity was negatively correlated with tumor histological grade (Mann–Whitney U test, I/II vs III, p = 0.0427). No mutation was observed in exons 9 and 20 of PIK3CA gene and in exon 4 of AKT1 gene. In conclusion, our findings depict the presence of activated PI3K/AKT/mTOR pathway in esophageal cancer bringing forward p‐mTOR and p‐4E‐BP1 for their potential role in esophageal carcinogenesis. Additional studies are warranted to validate our findings.     

Ductal Carcinoma In Situ with Microinvasion on Core Biopsy: Evaluating Tumor Upstaging Rate,Lymph Node Metastasis Rate,and Associated Predictive Variables

Annals of Surgical Oncology - The role of sentinel lymph node biopsy (SLNB) when ductal carcinoma in situ with microinvasion (DCISM) is identified on core biopsy is unclear. Our aim was to assess...     

The importance of two-step tuberculin skin testing for newly employed healthcare workers.

At the time of hire, 4059 of 6522 healthcare workers required a 2-step tuberculin skin test; 114 workers (2.8%) demonstrated a boosted reaction after the second step. Boosted reactions were significantly associated with male sex and older age. A verbal history of previous tuberculin skin test results was not a reliable indicator of baseline tuberculin skin test status at the time of hire.     

Lipid-lowering diets in patients taking pravastatin, a new HMG-CoA reductase inhibitor: compliance and adequacy

We examined seven 1-d diet records kept during 1 y by 272 men and women instructed to follow a lipid-lowering diet while participating in a clinical trial of pravastatin, a new 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor. The mean percentage of calories from total fat and saturated, unsaturated, and monounsaturated fatty acids was similar throughout the year even though the patients knew they were taking an effective lipid-lowering agent. However, the diets of greater than 40% of women included less than two-thirds of the recommended dietary allowance (RDA) of folic acid, vitamins B-6 and D, and calcium and zinc; in men, folic acid and zinc intakes were low. We conclude that patients comply with lipid-lowering diets even when they know that they are receiving an effective serum lipid-lowering agent. However, for both men and women special attention should be given to the intake of several nutrients.     

Antiulcer activity of Tinospora cordifolia Miers and Centella asiatica linn extracts

The ethanol extracts of the roots of T. cordifolia Miers and C. asiatica Linn were observed to induce a marked protective action against an 8 h restraint stress induced ulcerization, the activity being comparable to that of diazepam.     

Transplantation of normal hepatocytes modulates the development of chronic liver lesions induced by a pyrrolizidine alkaloid, lasiocarpinet

Laipcarpine (LC), a pyorrolizidine alkaloid, is able to inducea series of chronic and progressive lesions in rat liver, includingalong-lasting block in the cell cycle, the appearance of enlargedhepatocytes (megalocytosis), fibrosis, cirrhosis and malignantneoplasms. In this study the effect of transplantation of normalhepatocytes on the development of LC (80 µmol/kg i.p.).Four weeks later all animals were subjected to 2/3 paroticlhepatectomy (PH). In addition, at the time of PH one group ofrats were transplanted with normal hepatocytes isolated froma syngeneic donor (10⁶ cells/rat via the portal vein), whilethe other group received only the culture medium. All rats werekilled 14 weeks after the operation. Grossly, the liver of ratsexposed to LC followed by PH with no transplantation of normalhepatocytes was small in size (% liver wt/body wt 1.66 ±0.08) and exhibited a few whitish nodules. Histologically,