Vitamin D Supplementation Regulates Postoperative Serum Levels of PD-L1 in Patients with Digestive Tract Cancer and Improves Survivals in the Highest Quintile of PD-L1: A Post Hoc Analysis of the AMATERASU Randomized Controlled Trial.

Because vitamin D responsive elements have been found to be located in the PD-L1 gene, vitamin D supplementation was hypothesized to regulate serum PD-L1 levels and thus alter survival time of cancer patients. A post hoc analysis of the AMATERASU randomized, double-blind, placebo-controlled trial of postoperative vitamin D3 supplementation (2000 IU/day) in 417 patients with stage I to stage III digestive tract cancer from the esophagus to the rectum was conducted. Postoperative serum PD-L1 levels were measured by ELISA and divided into quintiles (Q1-Q5). Serum samples were available for 396 (95.0%) of the original trial. Vitamin D supplementation significantly (p = 0.0008) up-regulated serum PD-L1 levels in the lowest quintile (Q1), whereas it significantly (p = 0.0001) down-regulated them in the highest quintile (Q5), and it did not either up- or down-regulate them in the middle quintiles (Q2-Q4). Significant effects of vitamin D supplementation, compared with placebo on death (HR, 0.34; 95% CI, 0.12-0.92) and relapse/death (HR, 0.37; 95% CI, 0.15-0.89) were observed in the highest quintile (Q5) of serum PD-L1, whereas significant effects were not observed in other quintiles (Pinteraction = 0.02 for death, Pinteraction = 0.04 for relapse/death). Vitamin D supplementation significantly reduced the risk of relapse/death to approximately one-third in the highest quintile of serum PD-L1.

Obesity is not associated with increased morbidity in patients undergoing cytoreductive surgery with intraperitoneal chemotherapy.

BACKGROUND AND OBJECTIVES: Recent single-institutional series have examined the relationship of body mass index (BMI) in patients undergoing cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) generally without significant increase in serious complications with increasing BMI. This study evaluates the impact of BMI on complication rates using a national cohort. METHODS: The ACS NSQIP database was queried for patients undergoing concurrent CRS with IPC (2005-2012). Death and serious morbidity (DSM) was the primary outcome. Statistical analyses were performed to determine significant associations between peri-operative factors and DSM. RESULTS: Of 1,085 patients, there were 30.4% (n = 330) obese (BMI >30) and 32.1% (n = 348) normal weight (BMI 18.5-24.9) patients. DSM rates did not differ between these groups (P = 0.853). Obese patients were more likely to experience post-operative wound (P = 0.017) and renal (P = 0.002) complications. Hypoalbuminemia (OR 7.34; 95% CI 2.27-23.73), prolonged operative time (OR 3.02; 95% CI 1.83-4.97) and concomitant liver resection (OR 3.29; 95% CI 1.31-8.28) were independent risk factors for DSM among obese patients. CONCLUSIONS: Obesity is not significantly associated with DSM in patients undergoing CRS/IPC, and should not be a major deterrence for surgery. However, obese patients are more likely to experience wound and renal complications and hypoalbuminemia is a strong preoperative risk factor. J. Surg. Oncol. 2016;114:619-624. © 2016 Wiley Periodicals, Inc.

The role of parenteral glutamine supplement for surgical patient perioperatively: result of a single center, prospective and controlled study.

BACKGROUND: We conducted a prospective and case-controlled study to evaluate the impact of supplement of alanyl-glutamine dipeptide (Gln) in parenteral nutrition on perioperative immune and nutritional changes and clinical outcomes for patients undergoing gastrointestinal (GI) operations. MATERIALS AND METHODS: During 2006, 70 patients undergoing GI surgeries were allocated equally into two groups. One group received regular parenteral nutrition and the other received the same formulation and supplemented with the Gln; the two groups were isonitrogenous. The infusion was started from 1 day before operation to the sixth day after operation for 7 days. Blood samples were collected on the morning of the day before the operation and on the morning 6 days after the operation and analyzed for immune and nutrition parameters. RESULTS: There were no differences between the two groups in terms of clinical characteristics, operative procedures, biochemistry, nutritional status, and immune status preoperatively. After GI surgery, significant reduction in nutritional and immune parameters were observed in both groups, demonstrated by significant difference of albumin, C-reactive protein (CRP), lymphocyte count, T cell, and CD8 cell. The length of hospital stay is slightly longer in the control group patients, but not to statistical significance (16.3 +/- 21.3 versus 12.2 +/- 6.8 days, p = 0.299). In terms of morbidity, there was no difference between the two groups, but two patients in the control group had wound infection; none was noted in the Gln group (p = 1.0). No surgical mortality was noted in this study. CONCLUSIONS: Perioperative parenteral nutrition supplemented with Gln is beneficial for patients undergoing GI surgery. Gln supplementation significantly attenuated postoperative inflammation and ameliorated postoperative immunodepression as well as nutritional depression in GI surgery.

Cancer risk in nuclear workers occupationally exposed to uranium-emphasis on internal exposure.

Workers involved in the nuclear fuel cycle have a potential for internal exposure to uranium. The present review of epidemiological studies of these workers aims to elucidate the relationship between occupational internal uranium exposure and cancer risk. Eighteen cohort and 5 nested case-control studies published since 1980 are reviewed. Workers occupationally exposed to uranium appear to be at increased risk of mortality from neoplasms of the lung, larynx, and lymphatic and haematopoietic tissue. Currently available evidence for a positive association between internal exposure to uranium and the risk of cancer is limited. The common weaknesses in reviewed studies include low statistical power and inaccurate assessment of internal exposure to uranium. Further investigations should focus on precise assessment of occupational exposure and address the issue of potential confounders.

N-3 fatty acids, cancer and cachexia: a systematic review of the literature.

Use of n-3 fatty acids (FA) has been reported to be beneficial for cancer patients. We performed a systematic review of the literature in order to issue recommendations on the clinical use of n-3 FA in the cancer setting. A systematic search was performed in MEDLINE, EMBASE, Cochrane and Healthstar databases. We selected clinical trials or prospective observational studies including patients with cancer and life expectancy >2 months, in which enteral supplements with n-3 FA were administered. Parameters evaluated individually were clinical (nutritional status, tolerance, survival and hospital stays), biochemical (inflammatory mediators), and functional (functional status, appetite and quality of life (QoL)). Seventeen studies met the inclusion criteria; eight were of high quality. The panel of experts established the following evidence: (1) oral supplements with n-3 FA benefit patients with advanced cancer and weight loss, and are indicated in tumours of the upper digestive tract and pancreas; (2) the advantages observed were: increased weight and appetite, improved QoL, and reduced post-surgical morbidity; (3) there is no defined pattern for combining different n-3 FA, and it is recommended to administer > 1.5 g/day; and (4) better tolerance is obtained administering low-fat formulas for a period of at least 8 weeks. All the evidences were grade B but for 'length of treatment' and 'advantage of survival' it was grade C. Our findings suggest that administration of n-3 FA (EPA and DHA) in doses of at least 1.5 g/day for a prolonged period of time to patients with advanced cancer is associated with an improvement in clinical, biological and QoL parameters.

Reoperative pancreaticoduodenectomy for periampullary carcinoma.

BACKGROUND: Potentially resectable periampullary tumours may not be treated appropriately due to lack of local expertise in both assessment of resectability and resection in referring centres. Tata Memorial Hospital is a major referral centre for oncology and these patients are finally referred to this institution. In carefully selected patients, resection can be accomplished. The purpose of the present paper was to determine the perioperative morbidity and mortality for patients undergoing reoperative pancreaticoduodenectomy at a major comprehensive cancer centre. METHODS: Between January 1991 and December 2001 15 patients, who had undergone previous non-resectional surgery for operable periampullary carcinoma, underwent re-exploration. The perioperative morbidity and mortality were analysed and compared with that of the group of patients undergoing primary pancreaticoduodenectomy (143 patients) in the same period. RESULTS: All the 15 patients undergoing re-exploration had a successful resection by pancreaticoduodenectomy. In the reoperative group eight patients (53%) underwent classic pancreaticoduodenectomy and seven patients (46%) had a pylorus-preserving pancreaticoduodenectomy, as compared to 102 (71%) and 41 (29%) patients in the primary surgery group, respectively. Although the mean operative time and the estimated blood loss were higher in the reoperative group, the morbidity and mortality rates were similar in the two groups. The overall 30-day mortality rate was 6.6% and 6.9% in the reoperative and the primary surgery group, respectively. Major morbidity occurred in two of the 15 patients (13.3%), and one patient (6.6%) died following surgery in the reoperative group. CONCLUSION: Reoperative pancreaticoduodenectomy can be performed safely in carefully selected patients with resectable, localized periampullary tumours with similar morbidity and mortality to patients undergoing primary surgery.

Peritonectomy combined with intraperitoneal chemohyperthermia in abdominal cancer with peritoneal carcinomatosis: phase I-II study.

OBJECTIVE: To evaluate the feasibility and the tolerance of Peritonectomy Procedure (PP) combined with Intraperitoneal Chemohyperthermia (IPCH) in patients with peritoneal carcinomatosis, a phase I-II study has been realised from January 1997 to September 1998. METHODS: Eighteen patients were included for peritoneal carcinomatosis from colorectal cancer (13), ovarian cancer (2), gallbladder cancer (1), gastric cancer (1) and peritoneal mesothelioma (1). Peritoneal carcinomatosis were mainly advanced disease (16 stage 3 and 4, 2 stage 2). All the patients underwent surgical resection of their primary tumor with PP as described by Sugarbaker and IPCH (with Mitomycin C, Cisplatinum or both). IPCH used in this study was a "closed sterile circuit" device with inflow temperatures ranging from 46 to 48 degrees C. IPCH was performed on the same day as PP (8118) or delayed (10/18). RESULTS: Significant down-staging of peritoneal carcinomatosis was achieved for 16 patients. One patient died postoperatively, while the morbidity rate was 6/18 (long postoperative ileus, grade 3 leucopenia and anastomotic leakage). CONCLUSIONS: Combination of PP and IPCH could achieve significant tumoral volume reduction in peritoneal carcinomatosis. This aggressive treatment must be employed selectively because of its morbidity. Larger phase III studies are now needed.

[Surgery associated with intraoperative hyperthermia-chemotherapy in the treatment of malignant tumors of the digestive system with peritoneal carcinosis]. / Chirurgia associata ad ipertermochemioterapia intraoperatoria nel trattamento dei tumori maligni dell'apparato digerente con carcinosi peritoneale.

In the last two years the authors have treated 4 patients affected with malignant tumors of large bowel with very poor prognosis. In every cases they found large spreading to peritoneal cavity. These patients underwent to intraperitoneal hyperthermia-chemotherapy using a special device conceived by authors. This treatment produced promising results as related to life quality in these cases.

Mediterranean epidemiological evidence on tomatoes and the prevention of digestive-tract cancers.

Tomatoes have been estimated as the second most important source of vitamin C, after oranges, in an Italian population. We have therefore considered the relationship between tomato intake and the risk of digestive tract cancers using data from a series of case-control studies conducted in Italy between 1983 and 1992, and including 317 histologically confirmed, incident cases of cancer of the oral cavity and pharynx, 85 of the esophagus, 723 of the stomach, 955 of the colon, and 629 of the rectum, and a total of 2879 controls admitted for acute, non-neoplastic conditions, unrelated to long-term modifications of diet. Multivariate odds ratios (OR) and 95% confidence intervals (CI) for subsequent quartiles of intake of tomatoes were derived, after allowance for age, sex, study center, education, smoking, alcohol drinking, and total calorie intake. There was a consistent pattern of protection for all sites. The ORs for the highest consumption quartile were 0.65 (95% CI 0.4-1.0) for oral cavity, pharynx, and esophagus, 0.43 (95% CI 0.3-0.6) for stomach, 0.39 (95% CI 0.3-0.5) for colon, and 0.42 (95% CI 0.3-0.6) for rectum. Another study of colorectal cancer, based on 1,953 cases and 4,154 controls, conducted between 1992 and 1996 and using a more detailed food frequency questionnaire, confirmed that tomato intake was significantly protective on colorectal cancer risk, even after allowance for several potential confounding factors, including measures of body mass index, calorie intake, and physical activity. The ORs for the highest consumption quintile were 0.79 (95% CI 0.6-0.9) for colon, and 0.71 (95% CI 0.5-0.9) for rectal cancer. The beneficial effect of tomatoes observed in these epidemiological studies may be due to the fact that they constitute one of the most specific features of the Mediterranean diet. This has both a scientific and a public health relevance.

Development of chemopreventive agents for lung and upper aerodigestive tract cancers.

The lung and upper aerodigestive tract (oral cavity, larynx, pharynx, upper esophagus) will harbor the greatest proportion (approximately 20%) of estimated new cancer cases in 1992. The estimated mortality rate is even higher (32%), which is reflected in a 5-year survival rate of only 7% and 12% for esophageal and lung cancer, respectively. Tobacco use appears to remain the major cause of aerodigestive cancers despite efforts at primary prevention--cessation of exposure. Another strategy to decrease this public health problem is secondary prevention or chemoprevention. Cancer chemoprevention is defined as intervention with chemical agents before invasion to halt or slow the carcinogenic process; potential agents may include minor dietary constituents and pharmaceuticals. The main objective of the Division of Cancer Prevention and Control (DCPC), National Cancer Institute, is to develop promising chemopreventive drugs for use in humans. The testing of cancer chemopreventives for efficacy in the clinic differs from that of cancer treatment drugs. Chemopreventive drug trials involve healthy target populations, and the endpoints are reduced cancer incidence or mortality, or increased latency, with no to minimal toxicity. The lung and upper aerodigestive tract represent a unique opportunity for intervention in this setting. Even with cessation of tobacco exposure, the risk of cancer in the entire epithelium remains high for years due to the "field cancerization" effect. Some of the first chemopreventive trials made use of this system due to the availability of a study population with a tissue at demonstrably high risk for malignant progression. Much of the evidence for chemopreventive efficacy is in the oral cavity because of the well-defined epithelial neoplastic progression, the existence of well-established preclinical models, and relative ease of tissue monitoring and sampling. In one of the first randomized trials, Hong and co-workers demonstrated that 13-cis-retinoic acid prevents the appearance of second primary tumors in patients previously treated for squamous cell carcinomas of the oral cavity and upper respiratory tract. Even using a high risk population, chemoprevention trials involve large sample sizes, lengthy duration and follow-up, and high cost. To circumvent these problems, the use of intermediate biomarkers as surrogate endpoints is being explored. Intermediate biomarkers are defined as biological alterations in tissue (histological, genetic, biochemical, proliferative, differentiation-related) occurring prior to cancer development. In the oral cavity, studies using modulation of a histological intermediate biomarker, dysplastic leukoplakia, as the endpoint have demonstrated response to a retinoid.(ABSTRACT TRUNCATED AT 400 WORDS)

Causes of death among employees of a synthetic abrasive product manufacturing company.

Analysis of the causes of death among workers employed in the manufacture of synthetic abrasive products was performed using data from death certificates and employment records. The subjects were 1,030 white male workers who had been employed by a single manufacturer and who were identified through a review of death certificates issued during a 20-year period. Proportional mortality analysis revealed excess digestive cancer and respiratory disease deaths. Personnel records permitted refinement of the study population to 968 with classification of each individual into one of seven employment categories. Case-control analysis of workers ever employed in the individual categories revealed elevated odds ratios for respiratory disease deaths among those most exposed to the synthetic abrasive dust. The excesses were greatest in those exposed 20 or more years. Excesses of esophageal and rectal cancers were noted in two manufacturing areas although the numbers were small. Review of the literature further supports the findings that synthetic abrasive exposures may be associated with elevated respiratory morbidity and mortality.