Predictors of 30-day morbidity after hysterectomy for benign disease.

OBJECTIVE: To determine the 30-day morbidity rate after hysterectomy for benign disease and identify predictors of 30-day morbidity. METHODS: A retrospective study was conducted among women undergoing hysterectomy for benign indications between January 1, 2010, and December 31, 2015, at Konkuk University Hospital, South Korea. Multivariable regression analysis identified independent factors for morbidity. RESULTS: 1609 women were included. 30-day morbidity rates were 4.5% (n=72) for the whole cohort: 7.5% (28/371), 3.2% (22/686), and 4.0% (22/552) for abdominal hysterectomy, laparoscopic-assisted vaginal hysterectomy (LAVH), and vaginal hysterectomy, respectively. The most common 30-day postoperative morbidities were urinary complications (1.2%, 20/1609), wound infection (0.9%, 14/1609), and blood transfusion more than 4 units (0.7%, 11/1609). In multivariate regression analysis, Charlson comorbidity index of 2 or more, operative time, and estimated blood loss were independently associated with morbidity. Propensity score-matching indicated no difference in morbidity rates for the abdominal hysterectomy and LAVH or vaginal hysterectomy groups (P=0.351), whereas the LAVH or vaginal hysterectomy groups were more strongly associated with operation time, estimated blood loss, and length of postoperative hospital stay. CONCLUSION: Comorbidity index, operative time, and blood loss were independently associated with morbidity following hysterectomy. These findings supported the preoperative optimization of comorbidities and the appropriate selection of surgical approaches.

Prediction model for 30-day morbidity after gynecological malignancy surgery.

OBJECTIVE: The potential risk of postoperative morbidity is important for gynecologic cancer patients because it leads to delays in adjunctive therapy and additional costs. We aimed to develop a preoperative nomogram to predict 30-day morbidity after gynecological cancer surgery. METHODS: Between 2005 and 2015, 533 consecutive patients with elective gynecological cancer surgery in our center were reviewed. Of those patients, 373 and 160 patients were assigned to the model development or validation cohort, respectively. To investigate independent predictors of 30-day morbidity, a multivariate Cox regression model with backward stepwise elimination was utilized. A nomogram based on this Cox model was developed and externally validated. Its performance was assessed using the concordance index and a calibration curve. RESULTS: Ninety-seven (18.2%) patients had at least one postoperative complication within 30 days after surgery. After bootstrap resampling, the final model indicated age, operating time, and serum albumin level as statistically significant predictors of postoperative morbidity. The bootstrap-corrected concordance index of the nomogram incorporating these three predictors was 0.656 (95% CI, 0.608-0.723). In the validation cohort, the nomogram showed fair discrimination [concordance index: 0.674 (95% CI = 0.619-0.732] and good calibration (P = 0.614; Hosmer-Lemeshow test). CONCLUSION: The 30-day morbidity after gynecologic cancer surgery could be predicted according to age, operation time, and serum albumin level. After further validation using an independent dataset, the constructed nomogram could be valuable for predicting operative risk in individual patients.

Pharmacokinetic drug interactions between ondansetron and tamoxifen in female Sprague-Dawley rats with DMBA-induced mammary tumor.

Tamoxifen, which is used to treat breast cancer, and ondansetron, used for the treatment of chemotherapy-induced nausea, are commonly metabolized via cytochrome P450 (CYP) 2D subfamily and 3A1/2 in rats, as in humans. This study was conducted to investigate the pharmacokinetic interactions between ondansetron and tamoxifen after intravenous and oral administration of ondansetron (both 8 mg/kg) and/or tamoxifen (2 and 10 mg/kg for intravenous and oral administration, respectively), in rats bearing 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammarian tumors (DMBA rats), used as an animal model of human breast cancer. The total area under the plasma concentration-time curve, from time zero to infinity (AUC) of tamoxifen was significantly greater after both intravenous and oral administration with ondansetron, compared to that after administration of tamoxifen-alone. The hepatic and intestinal metabolism of tamoxifen in DMBA rats was inhibited by ondansetron. Taken together, the significant increase in tamoxifen AUC in DMBA rats after intravenous or oral administration with ondansetron may be attributed to non-competitive hepatic (intravenous) and competitive intestinal (oral) inhibition of CYP2D subfamily- and 3A1/2-mediated tamoxifen metabolism by ondansetron.

Pharmacokinetic interaction between tamoxifen and ondansetron in rats: non-competitive (hepatic) and competitive (intestinal) inhibition of tamoxifen metabolism by ondansetron via CYP2D subfamily and 3A1/2.

PURPOSE: Tamoxifen and ondansetron were commonly metabolized via rat hepatic CYP2D subfamily and 3A1/2, and ondansetron is used to treat chemotherapy-induced nausea. The purpose of this study was to report the pharmacokinetic interaction between tamoxifen and ondansetron in rats. METHODS: The pharmacokinetics of tamoxifen and ondansetron were evaluated after the intravenous and oral administration of tamoxifen, ondansetron, and both drugs together to rats. The Vmax (maximum velocity), Km (apparent Michaelis-Menten constant), CLint (intrinsic clearance), Ki (inhibition constant), and [I] (concentration of inhibitor in the liver and intestine)/Ki ratio of ondansetron were also measured. RESULTS: The AUC0-infinitys of tamoxifen were significantly greater after both intravenous and oral administration with ondansetron compared to those of tamoxifen alone. The significantly slower hepatic and intestinal CLints for the disappearance of tamoxifen with both drugs together were due to inhibition of metabolism of tamoxifen by ondansetron via CYP2D subfamily and 3A1/2. CONCLUSIONS: The significantly greater AUC0-infinity of tamoxifen after the intravenous administration of both drugs together could have possibly been attributable to a non-competitive (hepatic) inhibition of CYP2D subfamily- and 3A1/2-mediated tamoxifen metabolism by ondansetron. The significantly greater AUC0-infinity of tamoxifen after the oral administration of both drugs together could have been attributable to a competitive (intestinal) inhibition of CYP2D subfamily- and 3A1/2-mediated tamoxifen metabolism by ondansetron in addition to non-competitive inhibition in the liver.