Extraperitoneal leakage as a possible explanation for failure of one-time intraperitoneal treatment in ovarian cancer.

Contains fulltext : 51784.pdf (publisher's version ) (Open Access)We conducted a single-arm study to determine the biodistribution of intraperitoneally (i.p.) administered 90yttrium-labeled murine monoclonal antibody HMFG1 (90Y-muHMFG1) in patients with advanced stage ovarian cancer. Seventeen (17) patients in complete clinical remission for epithelial ovarian cancer were included. After completion of chemotherapy, a mixture of 111indium-labeled muHMFG1 (imaging) and 90Y-muHMFG1 (therapy) was i.p. administered by a surgically placed, indwelling i.p. catheter. Planar and single-photon emission computed tomography images were recorded to determine the distribution of the study medication during the first 6 days postinjection. Of the first 3 patients, 2 patients had extraperitoneal leakage of up to 50% of the injected dose within 24 hours after injection of the study medication. Extraperitoneal leakage was mainly seen in the retroperitoneal spaces covering the upper and lower quadrant of the abdomen. After adjustments in the procedure, leakage was observed in 2 of the remaining 14 patients. Extraperitoneal leakage of i.p. administered therapy does occur. Such leakage would reduce the locally delivered dose of a drug and could potentially have a negative impact on therapeutic efficacy. Given the potential attraction of developing i.p. treatments for intra-abdominal cancer, the observations in this study need to be taken into consideration

Prognostic model on niche development after a first caesarean section:development and internal validation

Objective: To develop and internally validate a prognostic prediction model for development of a niche in the uterine scar after a first caesarean section (CS). Study design: Secondary analyses on data of a randomized controlled trial, performed in 32 hospitals in the Netherlands among women undergoing a first caesarean section. We used multivariable backward logistic regression. Missing data were handled using multiple imputation. Model performance was assessed by calibration and discrimination. Internal validation using bootstrapping techniques took place. The outcome was ‘development of a niche in the uterus’, defined as an indentation of = 2 mm in the myometrium. Results: We developed two models to predict niche development: in the total population and after elective CS. Patient related risk factors were: gestational age, twin pregnancy and smoking, and surgery related risk factors were double-layer closure and less surgical experience. Multiparity and Vicryl suture material were protective factors. The prediction model in women undergoing elective CS revealed similar results. After internal validation, Nagelkerke R2 ranged from 0.01 to 0.05 and was considered low; median area under the curve (AUC) ranged from 0.56 to 0.62, indicating failed to poor discriminative ability. Conclusions: The model cannot be used to accurately predict the development of a niche after a first CS. However, several factors seem to influence scar healing which indicates possibilities for future prevention such as surgical experience and suture material. The search for additional risk factors that play a role in development of a niche should be continued to improve the discriminative ability