Repeated cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy in patients with peritoneal carcinomatosis: A retrospective cohort study.

INTRODUCTION: The prognosis of abdominal cancer with peritoneal carcinomatosis (PC) is poor. In literature, some authors described a repeated Cytoreductive Surgery (CRS) with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in patients with recurrent PC as feasible for overall survival improvement. Hence, we implemented this approach at our hospital and analyzed our cases. METHODS: A unicentric retrospective observational study took place at the Helios hospital Berlin-Buch in 2020. The data of individuals who received a HIPEC in the time of 2007-2019 were extracted. The data were entered in the HIPEC database of the German Society of General and Visceral Surgery (StuDoQ|HIPEC, German society for general and visceral surgery). The primary objective was the overall survival after first HIPEC procedure. RESULTS: A total of 292 data files from were extracted and 14 patients were identified as eligible for further analysis (7× colorectal, 3x gastric, 1× appendix cancer, 1× cancer of unknown primary, 1× Mesothelioma, 1× Pseudomyxoma peritonei). The mean age was 57 (8) years. The BMI was on average 23.5 (3.5) kg/m2. A total of 8 individuals were female and 6 male (6xASA-Score I, 8xASA-Score II). The initial Peritoneal Cancer Index (PCI) was on average 11.5 (9.1). The average overall survival after 1. HIPEC for colonic cancer was 74 months (n = 3; 43, 70 and 90 month), for gastric cancer 29 months (n = 2; 19 and 39 month) and for mesothelioma 44 months (n = 1). CONCLUSIONS: Based on our findings Repeated Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy may improve overall survival of selected patients suffering from peritoneal carcinomatosis.

Defective gammadelta T-cell function and granzyme B gene polymorphism in a cohort of newly diagnosed breast cancer patients.

OBJECTIVE: The purpose of this study was to examine the antitumor immune function of gammadelta T cells and to scan the granzyme B gene for the known single nucleotide polymorphism in breast cancer patients and normal controls. MATERIALS AND METHODS: Levels, cytotoxicity, and functional capacity of gammadelta T cells in peripheral blood mononuclear cells were assessed by flow cytometry, (51)Cr release, and ELISpot assays, respectively. Furthermore, sequence based typing was adopted to screen for granzyme B gene polymorphism. RESULTS: We have found that the frequency and function of gammadelta T cells are reduced both in peripheral blood mononuclear cells of 30 newly diagnosed breast cancer patients (2 [1.2, 3]), compared with 38 normal controls (3.2 [2.5, 5.7]) (p=0.02). In addition, resting gammadelta T cells from breast cancer patients produced significantly more interleukin-6 and tumor necrosis factor-alpha than normal controls. Moreover, ex vivo stimulation of gammadelta T cells with zoledronic acid and interleukin-2 compensated in part for this deficiency, as it stimulated the proliferation, cytokine production, and enhanced the expression of messenger RNA of granzyme B. Interestingly, when the known granzyme B gene polymorphism was screened, we found the prevalence of the mutated genotype RAH/RAH to be significantly (p<0.017) associated with breast cancer patients (14.30%) compared with normal donors (1.40%). Cytotoxicity exerted by gammadelta T cells on Daudi and MCF-7 was significantly higher in donors with the wild-type QPY/QPY (50%) compared with donors with RAH/RAH (21%). CONCLUSIONS: Our data suggest that reduction in the proportion of gammadelta T cells and granzyme B gene polymorphism leads to defective immune function in breast cancer patients. Treatment with zoledronic acid amend partially this fault. Further studies of gammadelta T cells function and granzyme B gene polymorphism in cancers, as well as the potential therapeutic use of zoledronic acid are warranted.

The toxic pathophysiology of retinol hypervitaminosis and norethisterone enantate in rats.

The use of the long acting contraceptive was accompanied by clinically overt toxic manifestations on the liver, glucose tolerance, in addition to the danger of carcinogenicity. Also chronic hypervitaminosis "A" leads to a variety of toxic manifestations of obscure mechanism. The objective of this experimental work was directed to study the toxicity of the isolated and combined augmented doses of the two therapeutic agents on the female albino rat. The results of the present study evidenced that the long acting contraceptive norethisterone enantate is potentially hepato- and nephro-toxic. More damage to the liver; and luteinization of theca and stroma cells of the ovaries occurred as a result of retinol hypervitaminosis. The brunt of toxicity and damage on the test organs after coadministration of both chemicals proved to be synergetic except on the ovarian tissues.