DRUG RESISTANCE-ASSOCIATED MARKER LRP FOR PREDICTION OF RESPONSE TO CHEMOTHERAPY AND PROGNOSES IN ADVANCED OVARIAN-CARCINOMA

Background: Drug resistance is a major impediment to the successful treatment of ovarian carcinoma. None of the earlier-identified resistance mechanisms, such as overexpression of the MDR1 gene product, P-glycoprotein (Pgp), has been shown to be a major determinant of clinical response to chemotherapy and survival for ovarian cancer patients. The multidrug resistance-associated protein (Mrp) and the lung resistance protein (Lrp, also called the p110 major vault protein), are newly described proteins associated with multidrug resistance in vitro. Purpose: The aim of this retrospective study was to investigate the expression of Mrp and Lrp, in addition to Pgp, in advanced ovarian carcinoma and to determine whether such expression was predictive of response to chemotherapy and survival. Methods: Fifty-seven banked frozen specimens, previously collected and frozen at the time of diagnosis from an equal number of patients with International Federation of Gynecology and Obstetrics (FIGO) stage III or IV ovarian carcinoma, were immunostained for Pgp (with monoclonal antibodies MAbs MRK-16 and JSB-1), Mrp (with MAb MRPrI), and Lrp (with MAb LRP-56). All patients had received platinum- or alkylating-based chemotherapy after debulking surgery. Clinicopathologic parameters determined at diagnosis were retrospectively assessed for their relationship with Pgp, Mrp, and Lrp expression. Response to treatment and survival were compared between Pgp, Mrp, and Lrp expression groups. Qualitative variables were analyzed using Fisher's exact test or the chi-squared test. All reported P values are two-tailed. Results: Nine (16%), 39 (68%), and 44 (77%) of the 57 tumor specimens examined showed positive immunostaining for Pgp, Mrp, and Lrp, respectively. Positive immunostaining for these proteins was not associated with any other prognostic factor examined. No association was found between Pgp and Mrp expression and response to chemotherapy and survival. In contrast, patients with Lrp-positive tumors had poorer response to chemotherapy (P = .004) and shorter progression-free (P = .003) and overall (P = .007) survival than Lrp-negative patients. Multivariate analysis of Lrp expression, FIGO stage, residual turner after initial surgery, tumor grade, and presence or absence of ascites showed that only Lrp status was independently related to both progression-free survival and overall survival. Conclusions: Positive Lrp immunostaining in advanced ovarian carcinoma appears to be an indicator of poor response to standard chemotherapy (platinum or alkylating agents) and of adverse prognoses. Implications: The functional characterization of Lrp and related proteins may reveal new approaches to modulate Lrp-associated drug resistance. A large prospective study is warranted to confirm the prognostic value of Lrp

Safety of hospital discharge before return of bowel function after elective colorectal surgery

Background: Ileus is common after colorectal surgery and is associated with an increased risk of postoperative complications. Identifying features of normal bowel recovery and the appropriateness for hospital discharge is challenging. This study explored the safety of hospital discharge before the return of bowel function.Methods: A prospective, multicentre cohort study was undertaken across an international collaborative network. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The main outcome of interest was readmission to hospital within 30 days of surgery. The impact of discharge timing according to the return of bowel function was explored using multivariable regression analysis. Other outcomes were postoperative complications within 30 days of surgery, measured using the Clavien-Dindo classification system.Results: A total of 3288 patients were included in the analysis, of whom 301 (9.2 per cent) were discharged before the return of bowel function. The median duration of hospital stay for patients discharged before and after return of bowel function was 5 (i.q.r. 4-7) and 7 (6-8) days respectively (P < 0.001). There were no significant differences in rates of readmission between these groups (6.6 versus 8.0 per cent; P = 0.499), and this remained the case after multivariable adjustment for baseline differences (odds ratio 0.90, 95 per cent c.i. 0.55 to 1.46; P = 0.659). Rates of postoperative complications were also similar in those discharged before versus after return of bowel function (minor: 34.7 versus 39.5 per cent; major 3.3 versus 3.4 per cent; P = 0.110).Conclusion: Discharge before return of bowel function after elective colorectal surgery appears to be safe in appropriately selected patients