Prevention of Anastomotic Leakage in Ovarian Cancer Debulking Surgery and Its Impact on Overall Survival.

AIM: The aim of this retrospective study was to investigate the impact of anastomotic leakage on survival rate and to define potential factors of risk and protection from bowel anastomotic leakage in patients with bowel segment resection treated for epithelial ovarian cancer in an accredited high-volume center. PATIENTS AND METHODS: Data of 136 patients treated with bowel resection between 2010 and 2017 were collected. All operations were performed by three accredited gynecological oncologists and by two specialized colorectal surgeons. Survival and anastomotic leakage rates were analyzed as per preoperative treatment, number and localization of anastomoses, grading of ovarian cancer, and protective loop ileostomy. RESULTS: In total, anastomotic leakage was observed in 23 out of 165 anastomoses (13.9%), representing 23 anastomotic leakages in 136 patients (16.9%). The 30-day mortality rate was 0.73%. There was no statistically significant difference in anastomotic leakage rate depending on localization and number of anastomoses (p=0.634). Patients with a protective loop ileostomy (n=22/136 patients) had no anastomotic leakage (0.0%, p=0.021). The anastomotic leakage rate was significantly different in patients without protective loop ileostomy depending on bevacizumab administration [no bevacizumab: 15/111 (13.5%) vs. bevacizumab administration: 4/8 (50.0%), p=0.007]. Tumor-positive resection margins in bowel segments were an independent prognostic factor (relative risk=6.3; 95% confidence intervaI=3.1-12.9). CONCLUSION: In this data set, protective loop ileostomy likely reduced the anastomotic leakage rate after bowel resection in selected cases of ovarian cancer treated with debulking surgery. Especially in patients treated with bevacizumab, protective loop ileostomy should be considered. There was no significant impact of leakage rate on overall survival.

Irradiated breast cancer patients demonstrate subgroup-specific regularities in protein expression patterns of circulating leukocytes.

BACKGROUND: Breast cancer is one of the most frequent types of cancer with fatal outcome worldwide. The use of breast conserving lumpectomy followed by radiation therapy is common and has been shown to be a strategy competitive to mastectomy in preventing mortality caused by breast cancer. However, breast irradiation, particularly applied after pre-irradiation chemotherapy, frequently leads to serious short- and long-term side-effects, the prediction of which is highly desirable in terms of individual therapy planning. For these purposes, minimal-invasive molecular blood analysis is considered as a powerful diagnostic tool: molecular interplay in blood is highly informative and may predict individual side-effects of therapy. MATERIALS AND METHODS: Ex vivo comparative protein expression profiling was performed in circulating leukocytes isolated from fresh blood samples of seven breast cancer patients before lumpectomy and consequently at several checkpoints under radiation treatment (0-60 Gy). Protein expression patterns were investigated by two-dimensional polyacrylamide gel electrophoresis followed by protein spot identification using matrix assisted laser desorption/ ionisation -- time of flight. Specific expression levels of highly affected differentially expressed proteins were quantified by Western blotting. RESULTS: The radiation treatment caused individual extensive alterations in expression patterns of leukocytes in the patients tested. In particular, a key regulator of redox status, thioredoxin, and the free-radical detoxification cascade members, SOD-2 and catalase, were highly affected. In spite of the high diversity of individual expression levels, characteristic protein expression patterns were recognized and patients were grouped according to the similarities found. CONCLUSION: Characteristic expression patterns in circulating leukocytes might provide novel molecular targets for prediction of therapy side-effects and improve individual therapy planning for breast cancer patients, thus avoiding unnecessary and excessive treatment-related toxicity. Molecular candidates and specific patterns are demonstrated in this work.

Her-2/neu gene amplification and response to paclitaxel in patients with metastatic breast cancer.

BACKGROUND: HER-2/neu overexpression appears to be associated with improved response to anthracycline-based chemotherapy, but its association with response to taxane-based chemotherapy is unclear. In this retrospective subset analysis of patients with metastatic breast cancer enrolled in a randomized treatment trial, we investigated the response of patients with known HER-2/neu status to treatment with taxane-based epirubicin-paclitaxel (ET) chemotherapy compared with treatment with epirubicin-cyclophosphamide (EC) chemotherapy. METHODS: HER-2/neu status (positive [i.e., HER-2/neu amplification] or negative [i.e., no HER-2/neu amplification]) of archival specimens of primary tumors from 297 patients with metastatic breast cancer was determined by use of fluorescence in situ hybridization. Associations between HER-2/neu status and the efficacy of randomly assigned chemotherapy (ET versus EC) were investigated. All statistical tests were two-sided. RESULTS: Patients with HER-2/neu-positive tumors had a statistically significantly greater objective response rate than patients with HER-2/neu-negative tumors to treatment with ET (76% versus 50%, respectively; P =.005) but not to treatment with EC (46% versus 33%; P =.130). The objective response rate associated with ET was greater than that associated with EC for both HER-2/neu-positive tumors (76% versus 46%; P =.004) and HER-2/neu-negative tumors (50% versus 33%; P =.002). However, the improvement in the objective response rate associated with ET, compared with that associated with EC, was greater for patients with HER-2/neu-positive tumors (adjusted odds ratio [OR] = 3.64, 95% confidence interval [CI] = 1.48 to 8.92; P=.005) than for patients with HER-2/neu-negative tumors (adjusted OR = 1.92, 95% CI = 1.01 to 3.64; P=.046). Among patients with HER-2/neu-positive tumors, those who received ET had better progression-free survival and overall survival than those who received EC (for progression-free survival, adjusted relative risk [RR] = 0.65, 95% CI = 0.42 to 1.02; P=.062; for overall survival, adjusted RR = 0.60, 95% CI = 0.36 to 1.02; P=.059). However, among patients with HER-2/neu-negative tumors, those who received ET and those who received EC had similar progression-free survival and overall survival. CONCLUSIONS: HER-2/neu amplification does not adversely influence response to first-line chemotherapy with either ET or EC. Furthermore, a taxane-containing regimen such as ET may provide a preferential benefit to patients with HER-2/neu-positive tumors.

N-acetylcysteine in severe falciparum malaria in Thailand.

One hundred and eight patients with severe falciparum malaria underwent a placebo controlled trial with the antioxidant, N-acetylcysteine (NAC), as an adjunctive therapy along with standard intravenous artesunate therapy. Three NAC dosage regimens were used: an intravenous loading dose of 140 mg/kg followed by 70 mg/kg every four hours intravenously for up to 18 doses (Group 1); a single intravenous loading dose followed by oral NAC in the same amount as for Group 1 (Group 2); a regimen identical to Group 1 except that oral NAC was administered after the first 24 hours (Group 3). Fifty-four patients received placebo plus artesunate. Two critically ill patients died in Group 1. No patient sustained an adverse reaction to the NAC other than vomiting, and the deaths were attributed to severe disease with multiple organ involvement. The excellent results with NAC, the lack of adverse effects, and the rationale for NAC benefit supports the need for a large, double blind trial of NAC as an adjunctive therapy for severe malaria.