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.     

Amisulpride in the short-term treatment of depressive and physical symptoms in cancer patients during chemotherapies

Introduction Amisulpride is a substituted benzamide that, at low doses, selectively blocks D2 and D3 presynaptic dopamine receptors, enhancing dopaminergic transmission in frontal cortex and limbic areas. Many clinical studies versus placebo, tricyclic antidepressants and selective serotonin reuptake inhibitors showed amisulpride antidepressant effect, supporting its safety and rapid onset of action. In oncological population, depression is quite frequent and difficult to treat because of the particular sensitivity of cancer patients to the antidepressants’ side effects. Goals of work The aims of this study were to evaluate efficacy, safety and tolerability of low doses of amisulpride (50 mg) in oncological, depressed patients during chemotheraphy. Materials and methods One hundred six consecutive cancer outpatients with depressive symptoms were treated in a prospective, intention to treat, 4-week study, and were evaluated in single-blind with Montgomery Asberg rating scale for depression (MADRS), clinical global impression (CGI) and dosage record treatment emergent symptom scale (DOTES) to assess side effects of treatment. Main results After 4 weeks of treatment, scores of MADRS and CGI significantly improved (p < 0.002; p < 0.001, respectively), with a reduction of depressive symptoms concerning both emotional (such as apparent sadness, reported sadness, inner tension, etc.) and physical cluster (such as lack of appetite, reduction in weight, tiredness and insomnia) with good tolerability (only two patients dropped out). Conclusions This study is the first trial on the use of amisulpride in a cohort of oncological, depressed patients during chemotherapy. Amisulpride demonstrated high efficacy and safety. Controlled studies are needed to confirm these preliminary data.     

The prevention of deep venous thromboses after radical or modified mastectomy interventions

With the aim of preventing deep vein thrombosis after radical or modified mastectomy, 100 patients were randomly assigned to one of two different groups: the first group was treated with defibrotide (400 mg b.i.d. e.v.) starting from the day before the operation and continuing for the following seven days. The second group was given calcium heparin (5,000 IU b.i.d. by s.c. route) from day 0 to the 7th post-operative day. Neither side effects nor DVT or PE were observed. The quantity of fluids from the drainages rapidly decreased in both groups from the first day to the third one, while the quantity of blood cells was negligible starting from the second post-operative day. On this basis defibrotide may be considered an effective and well tolerated drug for the prevention of DVT.     

Characterization of T-cell subsets infiltrating post-burn hypertrophic scar tissues

In this study, skin-infiltrating cells were characterized in both the active and remission phases of post-burn hypertrophic scar biopstes. Immunohistochemistry examination of active phase samples showed an abundant presence of Langerhans cells, T cells, macrophages, a low presence of natural killer cells and the lack of B lymphocytes. In active hypertrophic scars T lymphocytes infiltrate deep into the superficial dermis and are also observed in the epidermis: CD3⁺ cells were present at about 222±107 per 0.25 mm². In particular the analysis of lymphocyte subpopulations showed that CD4⁺ T cells predominate in the dermis as well as in the epidermis of active hypertrophic scars whereas CD8⁺ cells were less well represented (CD4/CD8 ratio is 2.06). This distribution was also shown in remission phase samples and in normotrophic scar specimens, although the lymphocyte number was significantly lower. Approximately 70 per cent of T lymphocytes present in the tissue involved in active phase hypertrophic scar samples were activated (positive with anti-HLA-DR and IL-2 receptor antibodies) which is significantly higher than remission phase hypertrophic and normotrophic scars, in which positivity was 40 and 38 per cent, respectively. Upon activation, the lesional lymphocytes release several cytokines, locally and transiently, that interact with specific receptors in response to different stimulation. Central to the immune hypothesis of hypertrophic scars is that some of the T-cell lymphokines act on keratinocytes, fibroblasts and other cell types to induce changes characteristic of these scars. The presence and close proximity of activated T lymphocytes and antigen-presenting cells of various phenotypes in both the epidermis and dermis of hypertrophic tissues provides strong circumstantial evidence of a local immune response. However, the manner in which T cells achieve and maintain their activated state in hypertrophic tissues in not yet known, and both antigen-dependent and independent mechanisms may contribute.     

Predictive indices for the identification of high-risk patients

In this article, the predictive indices which have been developed during the last decade to assess the risk of complications during hospitalization are reviewed. These indices are based on the evaluation of nutritional and immunological parameters and are particularly suitable for the identification of the surgical patient at risk for postoperative septic complications. The authors also review the methods which have been proposed for the classification of the severity of disease in critically ill subjects and the sepsis score method for the prediction of clinical outcome in severely septic surgical patients.     

Immunohistochemical pattern of hMSH2/hMLH1 in familial and sporadic colorectal, gastric, endometrial and ovarian carcinomas with instability in microsatellite sequences

Alterations of DNA mismatch repair (MMR) genes are involved in carcinogenesis of sporadic and inherited human cancers characterised by instability of DNA microsatellite sequences (MSI). MSI tumours are usually identified using molecular analysis. In the present investigation, hMLH1 and hMSH2 immunohistochemistry was tested in order to evaluate the utility of this method in predicting MMR deficiency. Colorectal (72), gastric (68), endometrial (44) and ovarian (17) carcinomas were independently evaluated for familial history, histological type of tumour, MSI status and immunohistochemical results. Loss of expression of either hMLH1 or hMSH2 was observed in 51 of 55 (92.8%) MSI tumours, while 145 of 146 microsatellite stable (MSS) tumours expressed both the hMLH1 and hMSH2 gene products. Independently of tumour site, an overall agreement between immunohistochemical and molecular results was observed in 15 hereditary non-polyposis colorectal cancer-related tumours. Among sporadic tumours, only 2 of 60 colorectal and 2 of 66 gastric carcinomas, displaying MSI, expressed both hMLH1 and hMSH2 gene products. All 39 endometrial and 16 ovarian tumours presented a concordant molecular and immunohistochemical profile. These data show that immunohistochemistry is an accurate and rapid method to predict the presence of defective DNA MMR genes and to identify both sporadic and familial MSI tumours.     

Effect of Intralipid on some immunological parameters and leukocyte functions in patients with esophageal and gastric cancer

This study has been undertaken to investigate if the intravenous (i.v.) infusion of fat emulsions may be associated with impairment of some immunological functions thus increasing the risk of septic complications. Fifteen malnourished patients with advanced gastric or esophageal cancer received for 2 weeks preoperatively and 1 week after surgery an isocaloric and isonitrogenous TPN treatment with Intralipid (group A: n=8) or glucose alone (group B: n=7) as energy substrate. Cluster analysis of 11 nutritional parameters and some tests of the humoral and cellular immunity (IgG, IgM, C3c, Factor B; polymorphonuclear (PMN) cells, total lymphocytes, T and B lymphocyte counts; 'in vitro' PMN chemotaxis, adherence to nylon fibers, phagocytosis of latex particles) were sequentially determined. The incidence and severity of post-operative infections were investigated and a 'sepsis score' was calculated for each patient. Pre- and postoperative TPN were not associated with an improvement of the nutritional status. The humoral and cellular immune parameters showed the same behaviour in patients receiving Intralipid and in controls. The chemotactic activity of PMN cells was constantly normal, granulocyte adherence fluctuated below the normality range in controls, whereas phagocytosis of latex was similar in both groups. Post-operative infectious episodes were less severe in patients receiving Intralipid. Our results do not confirm that Intralipid adversely affects some aspects of the humoral and cellular immune response.     

Trans-Epithelial Transport,Metabolism, and Biological Activity Assessment of the Multi-Target Lupin Peptide LILPKHSDAD (P5) and Its Metabolite LPKHSDAD (P5-Met)

P5 (LILPKHSDAD) is a hypocholesterolemic peptide from lupin protein with a multi-target activity, since it inhibits both 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoAR) and proprotein convertase subtilisin/kexin type-9 (PCSK9). This work shows that, during epithelial transport experiments, the metabolic transformation mediated by intestinal peptidases produces two main detected peptides, ILPKHSDAD (P5-frag) and LPKHSDAD (P5-met), and that both P5 and P5-met are linearly absorbed by differentiated human intestinal Caco-2 cells. Extensive comparative structural, biochemical, and cellular characterizations of P5-met and the parent peptide P5 demonstrate that both peptides have unique characteristics and share the same mechanisms of action. In fact, they exert an intrinsically multi-target behavior being able to regulate cholesterol metabolism by modulating different pathways. The results of this study also highlight the dynamic nature of bioactive peptides that may be modulated by the biological systems they get in contact with.