The hyperthermic intraoperative intraperitoneal chemotherapy in the treatment of advanced abdominopelvic cancer. Personal experience on 103 procedures during a seventeen year period in a single Italian center.

OBJECTIVE: Integration of different therapeutic strategies in cancer surgery in the last years has led from treating primary lesions to the surgical treatment of metastases. The purpose of this paper is to report a single Italian center experience of treatment of peritoneal carcinosis of the abdominopelvic malignancies. PATIENTS AND METHODS: 103 HIPEC procedures were performed in 17 years on 94 selected patients affected by abdominopelvic cancer. The PCI score was calculated at laparotomy. The CC score was calculated before doing HIPEC. HIPEC was carried out according to the Coliseum technique. RESULTS: The surgical cytoreduction allowed 89 patients to be subjected to HIPEC treatment with a CC score 0; 9 patients with a CC 1; 3 patients with a CC 2 and 2 patients with a CC 3. In 22 patients postoperative complications were recorded. No operative mortality occurred. The median follow-up of 53 months shows a rate of survival equivalent to 49 %, with a relapse in 46 patients, 29 of them reached exitus. CONCLUSIONS: The surgical resection alone for patients affected by advanced cancer with peritoneal carcinomatosis cannot be considered a sufficient treatment any longer and HIPEC would help to prolong survival in these patients.

A randomized, double-blind, placebo-controlled, multicenter study of a ginger extract in the management of chemotherapy-induced nausea and vomiting (CINV) in patients receiving high-dose cisplatin.

BACKGROUND: The activity of ginger in the management of chemotherapy-induced nausea and vomiting (CINV) has been suggested, but design inadequacies, heterogeneity of the population, small numbers and poor quality of tested products limit the possibility to offer generalizable results. PATIENTS AND METHODS: We conducted a randomized, double-blind, placebo-controlled, multicenter study in patients planned to receive ≥2 chemotherapy cycles with high dose (>50 mg/m2) cisplatin. Patients received ginger 160 mg/day (with standardized dose of bioactive compounds) or placebo in addition to the standard antiemetic prophylaxis for CINV, starting from the day after cisplatin administration. CINV was assessed through daily visual-analogue scale and Functional Living Index Emesis questionnaires. The main objective was protection from delayed nausea; secondary end points included intercycle nausea and nausea anticipatory symptoms. RESULTS: In total, 121 patients received ginger and 123 placebo. Lung (49%) and head and neck cancer (HNC; 35%) were the most represented tumors. No differences were reported in terms of safety profile or compliance. The incidence of delayed, intercycle and anticipatory nausea did not differ between the two arms in the first cycle and second cycle. A benefit of ginger over placebo in Functional Living Index Emesis nausea score differences (day 6-day 1) was identified for females (P = 0.048) and HNC patients (P = 0.038). CONCLUSIONS: In patients treated with high-dose cisplatin, the daily addition of ginger, even if safe, did not result in a protective effect on CINV. The favorable effect observed on nausea in subgroups at particular risk of nausea (females; HNC) deserves specific investigation.

A phase II study of sorafenib in recurrent and/or metastatic salivary gland carcinomas: Translational analyses and clinical impact.

BACKGROUND: Pre-clinical and clinical evidence suggests a rationale for the use of anti-angiogenic agents, including sorafenib, in recurrent and/or metastatic salivary gland carcinomas (RMSGCs). This study evaluates the activity of sorafenib in patients with RMSGCs and also investigates whether the activity of sorafenib could be related to its main tailored targets (i.e. BRAF, vascular endothelial growth factor receptor 2 [VEGFR2], platelet-derived growth factor receptor α [PDGFRα] and ß, RET, KIT). PATIENTS AND METHODS: Patients received sorafenib at 400 mg BID. The primary end-point was response rate (RR) including complete response or partial response (PR); secondary end-points included RR according to Choi criteria, disease control rate (DCR), overall survival (OS), and progression-free survival (PFS). RESULTS: Thirty-seven patients (19 adenoid cystic cancers, ACC) were enrolled. Six PRs were recorded. RR was 16% (95% confidence interval [CI]: 6-32; 11% in ACC and 22% in non-ACC). Choi criteria could be applied in 30 out of 37 cases with a RR of 50% (95% CI: 31-69%); DCR was 76% (95% CI: 59-88%). Incidence of ≥G3 adverse events was 29.7%. Median PFS and OS for the entire population were 5.9 months and 23.4 months, respectively. Median PFS and OS were 8.9 and 26.4 months for ACC versus 4.2 and 12.3 months for non-ACC patients. All the cases showed expression of PDGFRß in the stroma and VEGFR2 in endothelial cells; PDGFRα positivity was found in the stroma of four (27%) cases. All except for two cases showed no PDGFRß, VEGFR2 and PDGFRα expression in the tumour cells. KIT expression was restricted to ACC and a weak RET expression was limited to one adenocarcinoma, not otherwise specified (NOS). No BRAF mutation was found. No correlation was observed between the sorafenib activity and the expression of its markers although all six responders (two ACC, one adenocarcinoma, NOS, one salivary duct cancer [SDC], one high-grade mucoepidermoid [HG-MEC] and one poorly-differentiated cancer) are enriched in the stromal component showing a PDGFRß immunodecoration. In ACCs, immunohistochemistry revealed MYB protein expression in 15/16 cases (94%) and the MYB-NFIB fusion oncogene was observed in 9/14 (64%). CONCLUSIONS: Sorafenib is the first anti-angiogenic agent to demonstrate activity in RMSGC patients, particularly in some histotypes such as HG-MEC, SDC and adenocarcinoma, NOS. The PDGFRß-positive rich stromal component characterising these histotypes and the lack of correlation between the activity of sorafenib and its targets suggests anti-angiogenic effect as the prevalent mechanism of action of sorafenib in SGCs.

The effectiveness of oral goat colostrum in the treatment of patients with type 2 diabetes mellitus: our preliminary experience.

INTRODUCTION: The properties of colostrum were recognized and investigated more thoroughly in the first half of the eighties, when the immune factors and growth factors it contains were pointed out. Numerous studies show that the administration of colostrum benefits the subjects with type 2 diabetes mellitus as it gradually regulates appetite, improves utilization of nutrients, especially glucose, and leads to a significant decrease in body fat. MATERIALS AND METHODS: The following study is aimed at verifying a possible reduction in the use of insulin in 27 subjects with type 2 diabetes, treated with goat colostrum in the form gastro-resistant tablets of 300 mg (4/die). RESULTS: In subjects with type 2 diabetes treated with insulin, the administration of colostrum has obtained a significant reduction of insulin dosage and normalization of blood glucose levels. CONCLUSIONS: The effects of colostrum are presumably linked to increased levels of IGF-1 that improves the utilization of glucose, stimulates glycogen and protein synthesis.

Complications related to hyperthermia during hypertermic intraoperative intraperitoneal chemiotherapy (HIPEC) treatment. Do they exist?

BACKGROUND AND OBJECTIVES: Hyperthermia, either alone or in combination with anticancer drugs, is becoming more and more a clinical reality for the treatment of far advanced gastrointestinal cancers, acting as a cytotoxic agent at a temperature between 40-42.5 degrees C. Although hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) is demonstrated to have some benefit in selected patients with peritoneal seeding, there are not enough data on the risk of damage of normal tissue that increases as the temperature rises, with possible serious and, sometimes, lethal complications. MATERIALS AND METHODS: We searched on medline words like "intraoperative intraperitoneal chemohyperthermia and morbidity", focusing our attention on studies (published since 1990) which reported morbidity as bowel obstruction, bowel perforation or anastomic leak, during intraoperative intraoperitoneal chemotherapy in hyperthermia (HIPEC). RESULTS: Heat acts increasing cancer cell killing after exposure to ionizing radiation, inhibiting repairing processes of radiation-induced DNA lesions (radiosensitization), and also sensitizing cancer cells to chemotherapeutic drugs, particularly to alkylating agents (chemosensitization). The peritoneal carcinomatosis (a frequent evolution of advanced digestive cancer) represents one of the main indication to hypertermic treatment. In the last fifteen years, in fact, different methods were developed for the surgery treatment (peritonectomy) and for loco-regional chemotherapic treatment of the carcinomatosis (intraperitoneal intra/post-operative iper/normothermic chemotherapy) to act directly on neoplastic seeding. We found, as result of different studies, 9 articles, written about perforation after HIPEC. CONCLUSION: The aim of the present study is to present the review of the literature in terms of peri-operative complications related to the hyperthermia during intraoperative chemohyperthermia procedure.

Bioactivity of crude extracts and some constituents of Blutaparon portulacoides (Amaranthaceae).

Crude extracts (aerial parts and roots, both dried), methylenedioxyflavonol, and a mixture of acyl steryl glycosides isolated from Blutaparon portulacoides, were assayed for their toxicity against Trypanosoma cruzi trypomastigotes and Leishmania amazonensis amastigotes from axenic cultures. The antimicrobial activity was also investigated, in a screening conducted using fifteen strains of Gram-positive and Gram-negative bacteria, along with the yeasts, Candida albicans and Candida tropicalis. To assess the antibacterial activity of the isolated compounds, the minimum inhibitory concentrations (MICs) were determined. There are no reports of acyl steryl glycosides in the genus Blutaparon and their biological activities are being evaluated for the first time.