Robotic Versus Laparoscopic Hysterectomy for Benign Disease: A Systematic Review and Meta-Analysis of Randomized Trials.

We conducted a systematic review and meta-analysis to assess the safety and effectiveness of robotic vs laparoscopic hysterectomy in women with benign uterine disease, as determined by randomized studies. We searched MEDLINE, EMBASE, the Cochrane Library, ClinicalTrials.gov, and Controlled-Trials.com from study inception to October 9, 2014, using the intersection of the themes "robotic" and "hysterectomy." We included only randomized and quasi-randomized controlled trials of robotic vs laparoscopic hysterectomy in women for benign disease. Four trials met our inclusion criteria and were included in the analyses. We extracted data, and assessed the studies for methodological quality in duplicate. For meta-analysis, we used random effects to calculate pooled risk ratios (RRs) and weighted mean differences. For our primary outcome, we used a modified version of the Expanded Accordion Severity Grading System to classify perioperative complications. We identified 41 complications among 326 patients. Comparing robotic and laparoscopic hysterectomy, revealed no statistically significant differences in the rate of class 1 and 2 complications (RR, 0.66; 95% confidence interval [CI], 0.23-1.89) or in the rate of class 3 and 4 complications (RR, 0.99; 95% CI, 0.22-4.40). Analyses of secondary outcomes were limited owing to heterogeneity, but showed no significant benefit of the robotic technique over the laparoscopic technique in terms of length of hospital stay (weighted mean difference, -0.39 day; 95% CI, -0.92 to 0.14 day), total operating time (weighted mean difference, 9.0 minutes; 95% CI, -31.27 to 47.26 minutes), conversions to laparotomy, or blood loss. Outcomes of cost, pain, and quality of life were reported inconsistently and were not amenable to pooling. Current evidence demonstrates neither statistically significant nor clinically meaningful differences in surgical outcomes between robotic and laparoscopic hysterectomy for benign disease. The role of robotic surgery in benign gynecology remains unclear.

53BP1 is limiting for NHEJ repair in ATM-deficient model systems that are subjected to oncogenic stress or radiation.

UNLABELLED: The DNA damage response (DDR) factors ataxia telangiectasia mutated (ATM) and p53 binding protein 1 (53BP1) function as tumor suppressors in humans and mice, but the significance of their mutual interaction to the suppression of oncogenic translocations in vivo has not been investigated. To address this question, the phenotypes of compound mutant mice lacking 53BP1 and ATM (Trp53bp1(-/-)/Atm(-/-)), relative to single mutants, were examined. These analyses revealed that loss of 53BP1 markedly decreased the latency of T-lineage lymphomas driven by RAG-dependent oncogenic translocations in Atm(-/-) mice (average survival, 14 and 23 weeks for Trp53bp1(-/-)/Atm(-/-) and Atm(-/-) mice, respectively). Mechanistically, 53BP1 deficiency aggravated the deleterious effect of ATM deficiency on nonhomologous end-joining (NHEJ)-mediated double-strand break repair. Analysis of V(D)J recombinase-mediated coding joints and signal joints in Trp53bp1(-/-)/Atm(-/-) primary thymocytes is, however, consistent with canonical NHEJ-mediated repair. Together, these findings indicate that the greater NHEJ defect in the double mutant mice resulted from decreased efficiency of rejoining rather than switching to an alternative NHEJ-mediated repair mechanism. Complementary analyses of irradiated primary cells indicated that defects in cell-cycle checkpoints subsequently function to amplify the NHEJ defect, resulting in more frequent chromosomal breaks and translocations in double mutant cells throughout the cell cycle. Finally, it was determined that 53BP1 is dispensable for the formation of RAG-mediated hybrid joints in Atm(-/-) thymocytes but is required to suppress large deletions in a subset of hybrid joints. IMPLICATIONS: The current study uncovers novel ATM-independent functions for 53BP1 in the suppression of oncogenic translocations and in radioprotection.