Comparison of Postoperative Acute Kidney Injury Between Laparoscopic and Laparotomy Procedures in Elderly Patients Undergoing Colorectal Surgery.

OBJECTIVES: Postoperative acute kidney injury (AKI) has an unfavorable impact on both short-term and long-term outcomes. The aim of this retrospective study was to compare the incidence of postoperative AKI between laparoscopic and laparotomy procedures in elderly patients undergoing colorectal surgery. METHODS: Medical records of elderly (65 y and older) patients who underwent colorectal cancer surgery between May 2016 and July 2018 at our tertiary hospital were reviewed. Patients with Union Internationale Contre le Cancer (UICC) stage II and III colorectal cancer, without neoadjuvant treatment, were divided into laparoscopic procedure group and laparotomy group. AKI, determined by the Acute Kidney Injury Network criteria, was compared between the 2 groups, before and after propensity matching. Multivariable analysis was made to identify independent risk factors of AKI. RESULTS: In all, 285 patients met the study inclusion criteria. Postoperative AKI occurred only in 16 patients from the laparotomy group (n=212). The incidence of AKI was significantly lower in the laparoscopic procedure group (n=73) compared with the laparotomy group (0% vs. 7.5%; P=0.015). Seventy-three patients who underwent laparoscopic surgery were matched with 73 of 212 patients who underwent open surgery, by using propensity score analysis, and the incidence of AKI in the 2 groups was similar (0% vs. 8.3%; P=0.028). Multivariable analysis showed that intraoperative metaraminol dose >1 mg (odds ratio=2.742, P=0.042) is an independent risk factor for postoperative AKI. CONCLUSION: In elderly patients, the incidence of AKI after colorectal cancer surgery is lower in the laparoscopic procedure group, maybe related to hemodynamic stability and less vasoconstriction.

GOLPH3 inhibition reverses oxaliplatin resistance of colon cancer cells via suppression of PI3K/AKT/mTOR pathway.

OBJECTIVE: To explore whether GOLPH3 regulated oxaliplatin (L-OHP) resistance of colon cancer cells via PI3K/AKT/mTOR pathway. METHODS: HCT116/L-OHP cells were divided into Blank, Control/GOLPH3 shRNA, BEZ235 (a PI3K/AKT/mTOR inhibitor), and GOLPH3 + BEZ235 groups followed by the detection with MTT, soft agar colony formation, flow cytometry and TUNEL assays. Mice bearing HCT116/L-OHP xenografts were randomized into Control, L-OHP, NC/GOLPH3 shRNA, L-OHP + NC/GOLPH3 shRNA groups. The expressions of Ki67, Caspase-3, and PI3K/AKT/mTOR pathway proteins were examined by immunohistochemistry. RESULTS: HCT116/L-OHP cells had increased GOLPH3 expression compared to HCT116 cells, which positively regulated PI3K/AKT/mTOR pathway in HCT116/L-OHP cells. BEZ235 declined IC50 of HCT116/L-OHP cells to L-OHP, decreased the expressions of ABCB1, ABCC1, ABCG2, ATP7A, ATP7B, MATE1, p-gp, MRP1 and BCRP, induced cell apoptosis, reduced cell proliferation, and arrested cells at G0/G1, which was reversed by GOLPH3 overexpression. L-OHP and GOLPH3 shRNA decreased tumor volume and reduced expression of Ki67 in tumor tissues with the increased Caspase-3. Meanwhile, the combined treatment had the better treatment effect. CONCLUSION: GOLPH3 inhibition reduced proliferation and promoted apoptosis of HCT116/L-OHP cells, and also reversed the L-OHP resistance of HCT116/L-OHP, which may be associated with the suppression of P13K/AKT/mTOR pathway.