Outcome trends and safety measures after 30 years of laparoscopic cholecystectomy:a systematic review and pooled data analysis

BACKGROUND: Laparoscopic cholecystectomy (LC), one of the most commonly performed surgical procedures, remains associated with significant major morbidity including bile leak and bile duct injury (BDI). The effect of changes in practice over time, and of interventions to improve patient safety, on morbidity rates is not well understood. The aim of this review was to describe current incidence rates and trends for BDI and other complications during and after LC, and to identify risk factors and preventative measures associated with morbidity and BDI. METHODS: PubMed, MEDLINE, and Web of Science database searches and data extraction were conducted for studies which reported individual complications and complication rates following laparoscopic cholecystectomy in a representative population. Outcomes data were pooled. Meta-regression analysis was performed to assess factors associated with conversion, morbidity, and BDI rates. RESULTS: One hundred and fifty-one studies reporting outcomes for 505,292 patients were included in the final quantitative synthesis. Overall morbidity, BDI, and mortality rates were 1.6-5.3%, 0.32-0.52%, and 0.08-0.14%, respectively. Reported BDI rates reduced over time (1994-1999: 0.69(0.52-0.84)% versus 2010-2015 0.22(0.02-0.40)%, p = 0.011). Meta-regression analysis suggested higher conversion rates in developed versus developing countries (4.7 vs. 3.4%), though a greater degree of reporting bias was present in these studies, with no other significant associations identified. CONCLUSIONS: Overall, trends suggest a reduction in BDI over time with unchanged morbidity and mortality rates. However, data and reporting are heterogenous. Establishment of international outcomes registries should be considered

Estrogen Receptor Positive Breast Cancer with High Expression of Androgen Receptor has Less Cytolytic Activity and Worse Response to Neoadjuvant Chemotherapy but Better Survival

Estrogen receptor (ER) positive breast cancer (BC), the most abundant BC subtype, is notorious for poor response to neoadjuvant chemotherapy (NAC). The androgen receptor (AR) was reported to support estradiol-mediated ER activity in an in vitro system. Recently, ER-positive BC with fewer tumor infiltrating lymphocytes (TILs) was shown to have a better prognosis, opposite to the trend seen with ER-negative BC. We hypothesized that ER-positive BC with high expression of AR will have fewer TILs and an inferior response to NAC, but with a better prognosis. In both TCGA and METABRIC cohorts, AR expression was significantly higher in ER-positive BCs compared to ER-negatives (p < 0.001, p < 0.001, respectively) and it correlated with ER expression (R = 0.630, R = 0.509, respectively). In ER-positive tumors, AR high tumors enriched UV response down (NES = 2.01, p < 0.001), and AR low tumors enriched DNA repair (NES = −2.02, p < 0.001). AR high tumors were significantly associated with procancer regulatory T-cells, and AR low tumors were associated with anticancer immune cells, such as CD4, CD8, and Gamma-Delta T-cells and memory B-cells in ER-positive BC (p < 0.01). Further, cytolytic activity was significantly lower in AR high BC in both cohorts. Finally, AR high tumors had a significantly lower rate of attaining pathological complete response to NAC (GSE22358), but better survival. In conclusion, our results demonstrated that high AR has fewer tumor infiltrating lymphocytes as well as cytolytic activity and an inferior response to NAC, but better survival in ER-positive BC