Anti-cancer effect of fenbendazole-incorporated PLGA nanoparticles in ovarian cancer.

OBJECTIVE: Fenbendazole (FZ) has potential anti-cancer effects, but its poor water solubility limits its use for cancer therapy. In this study, we investigated the anti-cancer effect of FZ with different drug delivery methods on epithelial ovarian cancer (EOC) in both in vitro and in vivo models. METHODS: EOC cell lines were treated with FZ and cell proliferation was assessed. The effect of FZ on tumor growth in cell line xenograft mouse model of EOC was examined according to the delivery route, including oral and intraperitoneal administration. To improve the systemic delivery of FZ by converting fat-soluble drugs to hydrophilic, we prepared FZ-encapsulated poly(D,L-lactide-co-glycolide) acid (PLGA) nanoparticles (FZ-PLGA-NPs). We investigated the preclinical efficacy of FZ-PLGA-NPs by analyzing cell proliferation, apoptosis, and in vivo models including cell lines and patient-derived xenograft (PDX) of EOC. RESULTS: FZ significantly decreased cell proliferation of both chemosensitive and chemoresistant EOC cells. However, in cell line xenograft mouse models, there was no effect of oral FZ treatment on tumor reduction. When administered intraperitoneally, FZ was not absorbed but aggregated in the intraperitoneal space. We synthesized FZ-PLGA-NPs to obtain water solubility and enhance drug absorption. FZ-PLGA-NPs significantly decreased cell proliferation in EOC cell lines. Intravenous injection of FZ-PLGA-NP in xenograft mouse models with HeyA8 and HeyA8-MDR significantly reduced tumor weight compared to the control group. FZ-PLGA-NPs showed anti-cancer effects in PDX model as well. CONCLUSION: FZ-incorporated PLGA nanoparticles exerted significant anti-cancer effects in EOC cells and xenograft models including PDX. These results warrant further investigation in clinical trials.

Robotic versus laparoscopic radical hysterectomy in cervical cancer patients: a matched-case comparative study.

OBJECTIVE: This study aimed to compare initial surgical outcomes and complication rates of patients with early-stage cervical cancer who underwent robotic radical hysterectomy (RRH) and conventional laparoscopic radical hysterectomy (LRH). METHODS: Patients diagnosed with invasive cervical cancer (International Federation of Gynecology and Obstetrics stage I-IIA) who underwent RRH (n = 23) at Samsung Medical Center from January 2008 to May 2013 were compared with matched patients who underwent LRH (n = 69) during the same period. The 2 surgical groups were matched 3:1 for variables of age, body mass index, International Federation of Gynecology and Obstetrics stage, histological subtype, tumor size, and node positivity. All patient information and surgical and postoperative follow-up data were retrospectively collected. RESULTS: Operating time was significantly longer (317 vs 236 minutes; P < 0.001) in the RRH group compared with the LRH group but mean estimated blood loss was significantly reduced in the RRH group (200 vs 350 mL; P = 0.036). Intraoperative and postoperative complications were not significantly different between the 2 groups (4.3% for RRH vs 1.45% for LRH; P = 0.439). Recurrences were 2 (8.7%) in the RRH and 7 (10.1%) in the LRH group. The overall 3-year recurrence-free survival was 91.3% in RRH group and 89.9% in the LRH group (P = 0.778). CONCLUSIONS: Although operating time was longer in the RRH cases because of lesser experience on robotic platform, we showed that surgical outcomes and complication rate of RRH were comparable to those of LRH. In addition, surgical skills for LRH easily and safely translated to RRH in case of experienced laparoscopic surgeon.

Surgical outcomes of a new approach to laparoscopic myomectomy: single-port and modified suture technique.

STUDY OBJECTIVE: To introduce a new technique of laparoscopic myomectomy (LM) using single-port access and a modified suture technique. DESIGN: Retrospective review of medical records. SETTING: University medical center. PATIENTS: From October 2011 through December 2012, 55 consecutive patients underwent single-port LM using a modified suture technique with Hem-o-lock ligation clips and myoma morcellation through the umbilical incision site (Choi's LM). As a historic control, patients who underwent conventional multi-port LM from January 2008 through November 2010 were included in the study. INTERVENTIONS: Medical records for 157 patients (55 Choi's LM and 102 LM) were reviewed retrospectively. Inclusion criteria were <3 symptomatic myomas ≤10 cm. Outcomes measured were operative time, estimated blood loss, complications, length of postoperative hospital stay, and postoperative pain. MEASUREMENTS AND MAIN RESULTS: Age, symptoms resulting from myomas, location and type of dominant myomas, and number of myomas were similar in the 2 groups. There were no significant differences in mean diameter of the myomas between the groups (6.8 cm vs 7.0 cm; p = .40). The mean duration of the operation was shorter in the Choi's LM group compared with the conventional LM group (104 min vs 152 min; p < .001). Choi's LM also resulted in a statistically significant decrease in blood loss (139 mL vs 222 mL; p < .001). Postoperative pain scores were significantly lower in the Choi's LM group than in the conventional LM group at 1, 6, 12, and 24 hours after surgery. CONCLUSION: Choi's LM with modified suture technique is associated with shorter operative time and less postoperative pain. A prospective trial is needed to confirm the results.

Bone metastasis in primary endometrial carcinoma: features, outcomes, and predictors.

OBJECTIVES: This study aimed to describe the clinicopathologic characteristics and outcomes and to assess the predictors associated with prognosis in endometrial carcinoma that developed bone metastasis. METHODS: A retrospective review of medical records was performed to identify the patients with endometrial carcinoma who developed bone metastasis between October 1994 and May 2012. RESULTS: Of the 1185 patients with endometrial carcinoma, 22 (1.8%) were identified with bone metastasis, and 21 patients were analyzed in the study. Seventeen (80.9%) patients had advanced-stage disease (2009 International Federation of Gynecologists and Obstetricians stages III-IV). Four (19.0%) patients had a bone lesion at the diagnosis of endometrial cancer. The median time of recurrence to the bone in 17 patients was 9 months (range, 2-43 months). The median overall survival (OS) and survival after bone metastasis of the entire cohort were 33 months (range, 9-57 months) and 15 months (range, 12-17 months), respectively. The patients with bone metastasis at recurrence had significantly longer OS than those patients with bone metastasis at diagnosis of endometrial cancer (36 vs 13 months; P = 0.042). Metastasis to extrapelvic bone was significantly associated with longer OS (46 vs 19 months; P = 0.001) and longer survival after bone metastasis (25 vs 12 months; P = 0.002). Isolated bone recurrence without extraosseous metastases and extrapelvic bone metastasis revealed independent predictors for survival after bone metastasis (hazard ratio, 0.09; 95% confidence interval, 0.01-0.67; P = 0.019 and hazard ratio, 0.07; 95% confidence interval, 0.01-0.53; P = 0.01). CONCLUSIONS: In endometrial carcinoma that develops bone metastasis, isolated bone recurrence and extrapelvic bone metastasis are significant predictors of prolonged survival after the diagnosis of bone metastasis. Further researches on the optimal treatment modality and factors that have the clinical implications are warranted.