Sexual function following trocar-guided mesh or vaginal native tissue repair in recurrent prolapse: a randomized controlled trial.

INTRODUCTION: Surgical treatment of pelvic organ prolapse (POP) affects sexual function. Generally, this results in improved sexual function, but deterioration is reported also. AIM: The purpose of this study was to evaluate and compare sexual function in patients with recurrent POP undergoing either a vaginal surgical repair with native tissue or a trocar-guided mesh insertion. METHODS: Sexually active patients randomly assigned to either native tissue repair or trocar-guided mesh insertion, which had completed the pelvic organ prolapse (POP)/urinary incontinence sexual questionnaire (PISQ-12) both at baseline and at 12 months, were included. Total, subscale, and individual question analysis were performed. Logistic regression was used to identify factors that were independently associated with improvement/deterioration in total PISQ-12 scores. MAIN OUTCOME MEASURES: Primary outcome was sexual function at 12 months following surgery, measured by the short form of the pelvic organ prolapse/urinary incontinence sexual questionnaire (PISQ-12). Secondary outcomes were the identification of factors independently associated with change in PISQ-12 scores and changes in individual PISQ-12 question scores. RESULTS: Sixty patients were included; 32 in the mesh arm and 28 in the native tissue arm. At 12 months, PISQ-12 scores were not different in both treatment arms (34.3, standard deviation [SD] 6.7 vs. 34.7, SD 5.7), but improvement was detected in the native tissue arm, whereas PISQ-12 total score remained unchanged in the mesh arm. Deteriorations were observed in the behavioral/emotive subscale and partner-related items in the mesh arm. In the native tissue arm, significant improvements in the physical and partner-related subscales were observed. The presence of mesh exposure was independently associated with deterioration in total PISQ-12 score. CONCLUSION: At 12 months, PISQ-12 scores were not different in either treatment arm, but were affected differently by trocar-guided mesh insertion or by native tissue repair. Mesh exposure was independently associated with deterioration in sexual function.

Molecular specific and cell selective cytotoxicity induced by a novel synthetic HLA-DR antibody mimic for lymphoma and leukemia.

Like rituximab, monoclonal antibodies reactive with human leukocyte antigen have potent antilymphoma activity. However, size limits their vascular and tissue penetration. To mimic monoclonal antibody binding, nanomolecules have been synthesized, shown specific for the beta subunit of HLA-DR10, and selective for cells expressing this protein. Selective high affinity ligands (SHALs) containing the 3-(2-([3-chloro-5-trifluoromethyl)-2-pyridinyl]oxy)-anilino)-3-oxopropanionic acid (Ct) ligand residualized and had antilymphoma activity against expressing cells. Herein, we show the extraordinary potency in mice with human lymphoma xenografts of a tridentate SHAL containing this ligand. After titrating antilymphoma activity in cell culture, a randomized preclinical study of a tridentate SHAL containing the Ct ligand was conducted in mice with established and aggressive human lymphoma xenografts. Mice having HLA-DR10 expressing Raji B- or Jurkat's T-lymphoma xenografts were randomly assigned to receive either treatment with SHAL at a dose of 100 ng i.p. weekly for 3 consecutive weeks, or to be untreated. Primary end-points were cure, overall response rates and survival. Toxicity was also evaluated in these mice, and a USFDA general safety study was conducted in healthy Balb/c mice. In Raji cell culture, the threshold and IC50 concentrations for cytotoxic activity were 0.7 and 2.5 nmol (pm/ml media), respectively. When compared to treated Jurkat's xenografts or untreated xenografts, Raji xenografts treated with the SHAL showed an 85% reduction in hazard of death (P=0.014; 95% confidence interval 32-95% reduction). There was no evidence for toxicity even after i.p. doses 2000 times greater than the treatment dose associated with cure of a majority of the mice with Raji xenografts. When compared with control groups, treatment selectively improved response rates and survival in mice with HLA-DR10 expressing human lymphoma xenografts at doses not associated with adverse events and readily achievable in patients.