Optimal timing of portal vein embolization (PVE) after preoperative biliary drainage for hilar cholangiocarcinoma.

BACKGROUND: Preoperative biliary drainage (PBD) followed by portal vein embolization (PVE) has increased the chance of resection for hilar cholangiocarcinoma (CCC). We aim to identify the optimal timing of PVE after PBD in patients undergoing hepatectomy for hilar CCC. METHODS: We retrospectively reviewed 64 patients who underwent hepatectomy after PBD and PVE for hilar CCC. The patients were classified into 3 groups: Group 1 (PBD-PVE interval ≤7 days), Group2 (8-14 days) and Group 3 (>14 days). The primary end points were 90 days mortality and grade B/C posthepatectomy liver failure (PHLF). RESULTS: There was no significant difference in primary end points between three groups. A marginally significant difference was found in the incidence of Clavien-Dindo grade ≥3 complications and wound infection (57.1% vs 38.1% vs 72.4%, p = 0.053 and 21.4% vs 38.1% vs 55.2%, p = 0.099). In multivariable analysis, Bismuth type IIIb or IV was independent risk factors for grade B/C PHLF (HR: 4.782, 95% CI 1.365-16.759, p = 0.014). CONCLUSIONS: Considering that the PBD-PVE interval did not affect PHLF, and the surgical complications increased as the interval increases, PVE as early as possible after PBD would be beneficial.

Effect of Preoperative Low Maximal Flow Rate on Postoperative Voiding Trials after the Midurethral Sling Procedure in Women with Stress Urinary Incontinence.

OBJECTIVES: To evaluate the effects of preoperative low maximal flow rate (Qmax) on voiding trials after the midurethral sling (MUS) procedure in women with stress urinary incontinence (SUI). METHODS: One hundred and sixty-eight women who underwent MUS procedure were enrolled. Preoperative free uroflowmetry was performed and patients were divided by Qmax. Low Qmax was defined as a Qmax under 15 mL/sec with voided volume at least 150 mL. Surgical results, failure of voiding trial, and postoperative uroflowmetry parameters were compared between the groups. Failure of voiding trial was defined by a PVR more than 100 mL on postoperative uroflowmetry. RESULTS: At the discharge day, there were 42 cases showing failure of voiding trial and 33 cases requiring CIC, but only one patient showed failure of voiding trial at 12 months postoperatively. Overall, 48 patients had preoperative low Qmax. Low Qmax group showed lower Qmax in all of postoperative uroflowmetry, but there were no significant differences in the rate of postoperative voiding trial failure or CIC. The low Qmax group was then divided into two groups according to the preoperative detrusor pressure at Qmax over and under 20 cmH2 O in pressure flow study. Comparing the two groups, no significant differences were observed in the cure rate, voiding trial failure or CIC. CONCLUSIONS: Our results suggest that women with preoperative low Qmax experienced no definite unfavorable voiding problem from the MUS procedure compared to those with normal voiding function. MUS procedure may be regarded as a safe and successful procedure in SUI women with low Qmax.

NVP-BEZ235, a dual PI3K/mTOR inhibitor synergistically potentiates the antitumor effects of cisplatin in bladder cancer cells.

The PI3K/Akt/mTOR pathway is a prototypic survival pathway and constitutively activated in many malignant conditions. Moreover, activation of the PI3K/Akt/mTOR pathway confers resistance to various cancer therapies and is often associated with a poor prognosis. In this study, we explored the antitumor effect of NVP-BEZ235, a dual PI3K/mTOR inhibitor in cisplatin-resistant human bladder cancer cells and its synergistic interaction with cisplatin. A human bladder cancer cell line with cisplatin resistance was exposed to escalating doses of NVP-BEZ235 alone or in combination with cisplatin and antitumor effects was determined by the CCK-8 assay. Based on a dose-response study, synergistic interaction between NVP-BEZ235 and cisplatin was evaluated by combination index (CI), three-dimensional model and clonogenic assay. The combination of NVP-BEZ235 and cisplatin caused significant synergistic antitumor effect in cisplatin-resistant bladder cancer cells over a wide dose range and reduced the IC50 of NVP-BEZ235 and cisplatin by 5.6- and 3.6-fold, respectively. Three-dimensional synergy analysis resulted in a synergy volume of 388.25 µM/ml2% indicating a strong synergistic effect of combination therapy. The combination therapy caused cell cycle arrest and caspase-dependent apoptosis. Although NVP-BEZ235 suppressed PI3K/mTOR signaling without any paradoxical induction of Akt activity, it caused MEK/ERK pathway activation. The present study demonstrated that the PI3K/mTOR dual inhibitor NVP-BEZ235 can synergistically potentiate the antitumor effects of cisplatin in cisplatin-resistant bladder cancer cells though the suppression of cell cycle progression and the survival pathway as well as induction of caspase-dependent apoptosis.