Comparison of the O-RADS and ADNEX models regarding malignancy rate and validity in evaluating adnexal lesions.

OBJECTIVE: This study aimed to compare the ability of the O-RADS and ADNEX models to classify benign or malignant adnexal lesions. METHODS: This retrospective single-center study included women who underwent surgery for adnexal lesions. Two gynecologists independently categorized the adnexal lesions according to the O-RADS and ADNEX models. Four additional readers were included to validate the new quick-access O-RADS flowchart. RESULTS: Among the 322 patients included in this study, 264 (82.0%) had a benign diagnosis, and 58 (18.0%) had a malignant diagnosis. The malignant rates of O-RADS 2, O-RADS 3, O-RADS 4, and O-RADS 5 were 0%, 3.0%, 37.7%, and 78.9%, respectively. The AUC of the O-RADS in the 322 patients was 0.93. On comparing the O-RADS and ADNEX models in the remaining 281 patients, the AUCs of the O-RADS, ADNEX model with CA125, and ADNEX model without CA125 were 0.92, 0.95, and 0.94, respectively. When setting a uniform cutoff of ≥ 10% (≥ O-RADS 4) to predict malignancy, the O-RADS had higher sensitivity than the ADNEX model (96.6% vs. 91.4%), and relatively similar specificity. In addition, the readers with the quick-access flowchart spent less time categorizing O-RADS than the readers with only the original O-RADS table (mean analysis time: 99 min 15 s vs. 111 min 55 s). CONCLUSIONS: The O-RADS classification of the adnexal lesions as benign or malignant was comparable to that of the ADNEX model and had higher sensitivity at the 10% cutoff value. A quick-access O-RADS flowchart was helpful in O-RADS categorization and might shorten the analysis time. KEY POINTS: • Both O-RADS and ADNEX models had good diagnostic performance in distinguishing adnexal malignancy, and O-RADS had higher sensitivity than ADNEX model in uniform 10% cutoff to predict malignancy. • Quick-access O-RADS flowchart was developed to help review O-RADS classification and might help reduce the analysis time.

Maintenance Therapy for Preventing Endometrioma Recurrence after Endometriosis Resection Surgery - A Systematic Review and Network Meta-analysis.

OBJECTIVE: To evaluate the efficacy of different hormone therapies in preventing postoperative endometrioma recurrence. DATA SOURCES: The MEDLINE, COCHRANE, and Embase electronic databases were searched from inception to 30 April 2021. METHODS OF STUDY SELECTION: Randomized controlled trials (RCTs) or cohort studies including reproductive age women with endometriosis undergoing ovarian cystectomy or excision of endometriotic lesions compared the effects of postoperative adjuvant therapy (gonadotropin-releasing hormone agonist [GnRHa]) and postoperative maintenance hormone interventions for more than 1 year (i.e., oral contraceptive pills [OCPs], dienogest [DNG], levonorgestrel-releasing intrauterine system [LNGIUS]) on endometrioma recurrence. TABULATION, INTEGRATION, AND RESULTS: Data collection and analysis of the data were independently performed 2 two reviewers. A total of 11 studies were included, of which 2 were RCTs, and 9 were cohort studies. There were 2394 patients with 6 interventions (cases: 1665, 69.6%) and expectant management (cases: 729, 30.4%). Relative treatment effects were estimated using network meta-analysis and ranked in descending order. The clinical effectiveness of these drugs (vs expectant management) was as follows: GnRHa plus DNG (odds ratio [OR], 0.04; 95% confidence interval [CI], 0.01-0.27), surface under the cumulative ranking (SUCRA) = 94.0; DNG (OR, 0.11; 95% CI, 0.04-0.32), SUCRA = 69.7; GnRHa plus OCP (OR, 0.12; 95% CI, 0.02-0.64), SUCRA = 63.4; GnRHa plus LNGIUS (OR, 0.13; 95% CI, 0.03-0.66), SUCRA = 59.4; and OCP (OR, 0.21; 95% CI, 0.13-0.36), SUCRA = 43.6. The effectiveness of GnRHa (OR, 0.47; 95% CI, 0.12-1.89), SUCRA = 17.3 was not significantly different from that of controls. CONCLUSION: In network meta-analysis, combined postoperative adjuvant therapy and longer maintenance hormone treatment are better than a single agent in preventing postoperative endometrioma recurrence. GnRHa plus DNG maintenance treatment might be the most effective intervention. Large-scale RCTs of these agents are still required.

Postoperative maintenance levonorgestrel-releasing intrauterine system and endometrioma recurrence: a randomized controlled study.

BACKGROUND: According to 3 randomized trials, the levonorgestrel-releasing intrauterine system significantly reduced recurrent endometriosis-related pelvic pain at postoperative year 1. Only a few studies have evaluated the long-term effectiveness of the device for preventing endometrioma recurrence, and the effects of a levonorgestrel-releasing intrauterine system as a maintenance therapy remain unclear. OBJECTIVE: The objective of the study was to evaluate whether a maintenance levonorgestrel-releasing intrauterine system is effective for preventing postoperative endometrioma recurrence. STUDY DESIGN: From May 2011 through March 2012, a randomized controlled trial including 80 patients with endometriomas undergoing laparoscopic cystectomy followed by six cycles of gonadotropin-releasing hormone agonist treatment was conducted. After surgery, the patients were randomized to groups that did or did not receive a levonorgestrel-releasing intrauterine system (intervention group, n = 40, vs control group, n = 40). The primary outcome was endometrioma recurrence 30 months after surgery. The secondary outcomes included dysmenorrhea, CA125 levels, noncyclic pelvic pain, and side effects. RESULTS: Endometrioma recurrence at 30 months did not significantly differ between the 2 groups (the intervention group, 10 of 40, 25% vs the control group 15 of 40, 37.5%; hazard ratio, 0.60, 95% confidence interval, 0.27-1.33, P = .209). The intervention group exhibited a lower dysmenorrhea recurrence rate, with an estimated hazard ratio of 0.32 (95% confidence interval, 0.12-0.83, P = .019). Over a 30 month follow-up, the intervention group exhibited a greater reduction in dysmenorrhea as assessed with a visual analog scale score (mean ± SD, 60.8 ± 25.5 vs 38.7 ± 25.9, P < .001, 95% confidence interval, 10.7-33.5), noncyclic pelvic pain visual analog scale score (39.1 ± 10.9 vs 30.1 ± 14.7, P = .014, 95% confidence interval, 1.9-16.1), and CA125 (median [interquartile range], -32.1 [-59.1 to 14.9], vs -15.6 [-33.0 to 5.0], P = .001) compared with the control group. The number-needed-to-treat benefit for dysmenorrhea recurrence at 30 months was 5. The number of recurrent cases requiring further surgical or hormone treatment in the intervention group (1 of 40, 2.5%, 95% confidence interval, -2.3% to 7.3%) was significantly lower than that in the control group (8 of 40, 20%, 95% confidence interval, 7.6-32.4%; P = .031). CONCLUSION: Long-term maintenance therapy using a levonorgestrel-releasing intrauterine system is not effective for preventing endometrioma recurrence.

Front-line intraperitoneal versus intravenous chemotherapy in stage III-IV epithelial ovarian, tubal, and peritoneal cancer with minimal residual disease: a competing risk analysis.

BACKGROUND: In the analysis of survival data for cancer patients, the problem of competing risks is often ignored. Competing risks have been recognized as a special case of time-to-event analysis. The conventional techniques for time-to-event analysis applied in the presence of competing risks often give biased or uninterpretable results. METHODS: Using a prospectively collected administrative health care database in a single institution, we identified patients diagnosed with stage III or IV primary epithelial ovarian, tubal, and peritoneal cancers with minimal residual disease after primary cytoreductive surgery between 1995 and 2012. Here, we sought to evaluate whether intraperitoneal chemotherapy outperforms intravenous chemotherapy in the presence of competing risks. Unadjusted and multivariable subdistribution hazards models were applied to this database with two types of competing risks (cancer-specific mortality and other-cause mortality) coded to measure the relative effects of intraperitoneal chemotherapy. RESULTS: A total of 1263 patients were recruited as the initial cohort. After propensity score matching, 381 patients in each arm entered into final competing risk analysis. Cumulative incidence estimates for cancer-specific mortality were statistically significantly lower (p = 0.017, Gray test) in patients receiving intraperitoneal chemotherapy (5-year estimates, 34.5%; 95% confidence interval [CI], 29.5-39.6%, and 10-year estimates, 60.7%; 95% CI, 52.2-68.0%) versus intravenous chemotherapy (5-year estimates, 41.3%; 95% CI, 36.2-46.3%, and 10-year estimates, 67.5%, 95% CI, 61.6-72.7%). In subdistribution hazards analysis, for cancer-specific mortality, intraperitoneal chemotherapy outperforms intravenous chemotherapy (Subdistribution hazard ratio, 0.82; 95% CI, 0.70-0.96) after correcting other covariates. CONCLUSIONS: In conclusion, results from this comparative effectiveness study provide supportive evidence for previous published randomized trials that intraperitoneal chemotherapy outperforms intravenous chemotherapy even eliminating the confounding of competing risks. We suggest that implementation of competing risk analysis should be highly considered for the investigation of cancer patients who have medium to long-term follow-up period.

Second-Line Intraperitoneal Chemotherapy for Recurrent Epithelial Ovarian, Tubal and Peritoneal Cancer: A Propensity Score-Matching Study.

BACKGROUND: The superiority of frontline intraperitoneal (IP) over intravenous (IV) chemotherapy is well established in the treatment of epithelial ovarian cancer. However, the role of IP chemotherapy in the second-line setting has rarely been investigated. METHODS: Consecutive patients diagnosed with recurrent epithelial, tubal and peritoneal cancers between January 2000 and December 2012 were recruited using a propensity score-matching technique to adjust relevant risk factors. RESULTS: In total, 310 patients were included in the final analysis (94 for platinum-refractory/resistant disease and 216 for platinum-sensitive disease). IP chemotherapy demonstrated significantly longer median progression-free survival than IV chemotherapy (4.9 vs. 2.4 months, p < 0.001, for platinum-refractory/resistant disease, and 9.8 vs. 6.9 months, p < 0.001, for platinum-sensitive disease). CONCLUSIONS: Second-line IP chemotherapy confers longer progression-free survival than IV chemotherapy. Large-scale clinical trials should be conducted to validate the true efficacy.

The risk of irritable bowel syndrome in patients with endometriosis during a 5-year follow-up: a nationwide population-based cohort study.

PURPOSE: Studies have suggested that endometriosis may coexist with irritable bowel syndrome (IBS). Using a population-based cohort study, we followed subjects for a 5-year period to identify the risk of IBS after a diagnosis of endometriosis. METHODS: This cohort study used the Taiwan National Health Insurance Database as a source of subjects. A total of 6076 patients with endometriosis from 2000 to 2005 were identified. Their data were compared with those of 30,380 age-matched controls without endometriosis who were randomly selected from the same database. All subjects were tracked for 5 years from the date of cohort entry to identify the risk of IBS. The Cox model was used to evaluate the 5-year event occurrence of IBS. RESULTS: Nine hundred twenty-six patients were diagnosed with IBS, including 256 in the case cohort (4.2%) and 670 in the control cohort (2.2%). The Kaplan-Meier survival curves demonstrated significantly lower event-free rates in the case cohort than in the control cohort (P = 0.001). After adjusting for urbanization level, monthly income, residential region and comorbidities, the hazard ratio (HR) within 5 years revealed a 1.79-fold (95% confidence interval [CI] 1.55-2.07) greater risk among the cases than the controls. The HR was higher within the first year of follow-up (HR 1.90, 95% CI 1.42-2.55) and in those women aged 25-34 years (HR 2.17, 95% CI 1.61-2.92). CONCLUSIONS: The risk of IBS among endometriosis patients persisted over 5 years of follow-up. The association detected in this study might have proceeded through shared risk and pathogenic factors.

Global distribution pattern of histological subtypes of epithelial ovarian cancer: a database analysis and systematic review.

BACKGROUND: Epithelial ovarian cancer is basically a heterogeneous disease with different chemosensitivity and distinct molecular alternations for each histological subtype. In order to assess whether the results of clinical trials can be extrapolated to a new country, it is critical to first examine whether the relative frequencies is homogenous across countries. METHODS: Cancer registry database from a single institution in Taiwan combined with systematic review of the global literature on the relative frequencies of histological subtypes between 2003 and 2012 was provided. RESULTS: Of 175 titles identified, 41 studies met inclusion/exclusion criteria. Globally, for each subtype, the median value of relative frequencies for serous subtype was 45.0%, with the Philippines (16.0%), Indonesia (22.7%), and Brazil (30.1%) as the three lowest countries and South Africa (68.0%), Greece (71.5%), and India (86.7%) as the three highest countries; for mucinous subtype, 11.4%, Italy (3.0%), Australia (3.4%), and Japan (5.4%) were the three lowest countries, while Indonesia (29.1%), Singapore (30.3%), and South Korea (38.6%) were the three highest countries; for endometrioid subtype, 12.6%, India (1.6%), Greece (5.7%), and Portugal (7.6%) were the three lowest countries, while Taiwan (24.8%), Egypt (25.0%), and Austria (25.5%) were the three highest countries; and for clear cell subtype, 5.3%, Pakistan (1.0%), Iran (2.0%), and Brazil (2.1%) were the three lowest countries while Thailand (16.0%), Taiwan (16.8%), and Spain (18.8%) were the three highest countries. CONCLUSIONS: Relative frequencies of subtypes were not homogenous across countries. This diversity may reflect the geographical and ethnic variations. Globally, epithelial ovarian cancer is a heterogeneous disease with a heterogeneous distribution pattern.

Robot-assisted sacrohysteropexy vs robot-assisted sacrocolpopexy in women with primary advanced apical prolapse: A retrospective cohort study.

BACKGROUND: This study aimed to evaluate the anatomic and clinical outcomes of robot-assisted sacrohysteropexy (RASH) against robot-assisted sacrocolpopexy (RASC) for the treatment of primary advanced apical prolapse. METHODS: We conducted a retrospective cohort study of all robot-assisted pelvic organ prolapse surgeries for primary advanced apical prolapse (stage ≥II) between January 2011 and May 2021 at an academic tertiary hospital. Surgical outcomes and pelvic organ function were evaluated using the Pelvic Organ Prolapse Quantitative (POP-Q) stage and validated questionnaires (POPDI-6) during preoperative and postoperative 12-month follow-up evaluations. All data were obtained from electronic medical records. RESULTS: A total of 2368 women underwent surgery for apical prolapse repair, and 18 women underwent either RASH (n = 11) or RASC (n = 7). Compared to the RASC group, the RASH group was significantly younger, premenopausal, and less parous. Preoperative prolapse stage, operative time, estimated blood loss, and hospitalization length was comparable between the groups. No intraoperative complications were observed. All women had a median follow-up duration of 24 months (range: 12-108 months). During the 12-month follow-up period, women in the RASH group reported higher satisfaction with the surgery than those in the RASC group (100% vs. 71.4%, p = 0.137). The mesh exposure rate was significantly higher in the RASC group (3/7, 42.9%) than in the RASH group (0/11, 0%) ( p = 0.043), which was found at 12 to 36 months postoperatively and was successfully managed with vaginal estrogen cream. In the RASH group, one woman required reoperation with anterior colporrhaphy for recurrent anterior prolapse at 60 months postoperatively. The apical success rate was 100% at one year postoperatively, without apical recurrence in either group during the follow-up period. CONCLUSION: RASH represents an effective and feasible option for the surgical treatment of advanced primary apical prolapse in women who desire uterine preservation and have a significantly lower risk of mesh erosion than RASC.

Maintenance dienogest therapy following adjuvant gonadotropin-releasing hormone agonist treatment after uterus-sparing surgery in adenomyosis: A retrospective cohort study.

OBJECTIVE: To investigate the safety and efficacy of adjuvant gonadotropin-releasing hormone agonist (GnRH-a) treatment followed by maintenance dienogest (DNG) therapy after uterus-sparing surgery. METHODS: Retrospective cohort study. A total of 190 patients with severe adenomyosis underwent uterus-sparing surgery between January 2010 and June 2020. Of these patients, 90 were analyzed. Forty-six patients (control group) received adjuvant 6-month GnRH-a therapy alone after uterus-sparing surgery, and 44 patients (maintenance group) received postoperative 6-month GnRH-a treatment followed by maintenance DNG therapy (2 mg/day orally). The median follow-up period was 18 months. The study was analyzed using generalized estimating equations. RESULTS: At baseline, the characteristics of patients in each group were comparable. Compared with the control group, the maintenance group had a significant improvement in the visual analog scale score of dysmenorrhea (P < 0.001), hemoglobin level (P = 0.004), and uterine volume (P = 0.004) from baseline to 18 months after uterus-sparing surgery. The symptom recurrence rate was significantly lower in the maintenance group than in the control group (4.6% vs. 37.0%, P < 0.001). CONCLUSIONS: The findings of this study suggest that combinatorial treatment with GnRH-a (adjuvant treatment) and DNG (maintenance therapy) represents a safe and effective short-term therapy after uterus-sparing surgery for adenomyosis.

Loss of Major Histocompatibility Complex Class I, CD8 + Tumor-infiltrating Lymphocytes, and PD-L1 Expression in Ovarian Clear Cell Carcinoma.

Ovarian clear cell carcinoma (OCCC), a chemoresistant ovarian cancer, shows a modest response to anti-programmed death-1/programmed death ligand-1 (PD-1/PD-L1) therapies. The effects of anti-PD-1/PD-L1 therapies rely on cytotoxic T-cell response, which is triggered by antigen presentation mediated by major histocompatibility complex (MHC) class I. The loss of MHC class I with simultaneous PD-L1 expression has been noted in several cancer types; however, these findings and their prognostic value have rarely been evaluated in OCCC. We collected data from 76 patients with OCCC for clinicopathologic analysis. Loss of MHC class I expression was seen in 44.7% of the cases including 39.3% to 47.4% of the PD-L1 + cases and was associated with fewer CD8 + tumor-infiltrating lymphocytes (TILs). PD-L1 positivity was associated with a higher number of CD8 + TILs. Cox proportional hazard models showed that high (≥50/mm 2 ) CD8 + TILs was associated with shorter disease-specific survival (hazard ratio [HR]=3.447, 95% confidence interval [CI]: 1.222-9.720, P =0.019) and overall survival (HR=3.053, 95% CI: 1.105-8.43, P =0.031). PD-L1 positivity using Combined Positive Score was associated with shorter progression-free survival (HR=3.246, 95% CI: 1.435-7.339, P =0.005), disease-specific survival (HR=4.124, 95% CI: 1.403-12.116, P =0.010), and overall survival (HR=4.489, 95% CI: 1.553-12.972, P =0.006). Loss of MHC class I may contribute to immune evasion and resistance to anti-PD-1/PD-L1 therapies in OCCC, and CD8 + TILs and PD-L1 positivity using Combined Positive Score may have a negative prognostic value.

MEX3A Mediates p53 Degradation to Suppress Ferroptosis and Facilitate Ovarian Cancer Tumorigenesis.

Epithelial ovarian cancer is a highly heterogeneous and malignant female cancer with an overall low survival rate. Mutations in p53 are prevalent in the major ovarian cancer histotype, high-grade serous ovarian carcinoma (HGSOC), while p53 mutations are much less frequent in other ovarian cancer subtypes, particularly in ovarian clear cell carcinoma (OCCC). Advanced stage OCCC with wild-type (WT) p53 has a worse prognosis and increased drug resistance, metastasis, and recurrence than HGSOC. The mechanisms responsible for driving the aggressiveness of WT p53-expressing ovarian cancer remain poorly understood. Here, we found that upregulation of MEX3A, a dual-function protein containing a RING finger domain and an RNA-binding domain, was critical for tumorigenesis in WT p53-expressing ovarian cancer. MEX3A overexpression enhanced the growth and clonogenicity of OCCC cell lines. In contrast, depletion of MEX3A in OCCC cells, as well as ovarian teratocarcinoma cells, reduced cell survival and proliferative ability. MEX3A depletion also inhibited tumor growth and prolonged survival in orthotopic xenograft models. MEX3A depletion did not alter p53 mRNA level but did increase p53 protein stability. MEX3A-mediated p53 protein degradation was crucial to suppress ferroptosis and enhance tumorigenesis. Consistently, p53 knockdown reversed the effects of MEX3A depletion. Together, our observations identified MEX3A as an important oncogenic factor promoting tumorigenesis in ovarian cancer cells expressing WT p53. SIGNIFICANCE: Degradation of p53 mediated by MEX3A drives ovarian cancer growth by circumventing p53 tumor suppressive functions, suggesting targeting MEX3A as a potential strategy for treating of ovarian cancer expressing WT p53.

Postoperative maintenance levonorgestrel-releasing intrauterine system for symptomatic uterine adenomyoma.

OBJECTIVE: To evaluate whether a maintenance levonorgestrel-releasing intrauterine system is effective for preventing the recurrence of postoperative adenomyosis-related symptoms. MATERIALS AND METHODS: From January 2005 through December 2014, a retrospective study including 133 patients with symptomatic adenomyosis undergoing conservative uterine-sparing surgery followed by gonadotropin-releasing hormone agonist treatment was conducted. We excluded the 18 patients who did not meet the inclusion criteria. The patients of intervention group (n = 54) received a levonorgestrel-releasing intrauterine system (LNG-IUS), which was inserted after surgery. The patients without LNG-IUS insertion were enrolled in the control group (n = 61). The primary outcome was improvement of adenomyosis-related dysmenorrhea, which was evaluated by the visual analog scale (VAS) and by hemoglobin (Hgb) and CA-125 levels. RESULTS: Over a 12-month follow-up, the intervention group exhibited a greater reduction in dysmenorrhea as assessed with a VAS score (mean ± SD: 6.5 ± 2.5 vs 4.1 ± 3.6, p = 0.001) and a greater elevation in the Hgb level (2.1 ± 1.9 vs 1.0 ± 1.7, p = 0.008) than the control group. At the end of the 24-month follow-up period, the intervention group also exhibited a greater reduction in dysmenorrhea as assessed with a VAS score (mean ± SD 6.1 ± 2.7 vs 3.7 ± 3.7, p = 0.002) and a greater elevation in the Hgb level (1.9 ± 2.1 vs 0.7 ± 1.8, p = 0.022) than the control group. The CA-125 level was significantly lower in the intervention group during the postoperative follow up (12th month follow-up, intervention vs control, 24.5 ± 28.8 vs 50.1 ± 44.0, p = 0.005; 24th month follow-up, 28.6 ± 26.2 vs 75.4 ± 68.5, p = 0.002). CONCLUSION: The maintenance therapy of LNG-IUS is effective and well accepted for long-term therapy after conservative surgery for patients with adenomyosis.

Salvage intraperitoneal chemotherapy for relapsed type II endometrial cancer: A pilot case-control study.

OBJECTIVE: Epithelial ovarian cancer and relapsed type II endometrial cancer share common characteristics. Although the role of intraperitoneal (IP) chemotherapy in the treatment of epithelial ovarian cancer has been well-established, its role in the treatment of relapsed type II endometrial cancer remains to be elucidated. MATERIAL AND METHODS: From January 2000 to December 2012, patients who were diagnosed with relapsed type II endometrial cancer and underwent secondary cytoreductive surgery, patients with residual tumors less than 1 cm in diameter were initially screened for this study. Of the screened patients, consecutive patients who received salvage IP chemotherapy (IP platinum plus intravenous paclitaxel) were considered the case group. The case study group was matched to a control group that was composed of patients who received salvage systemic chemotherapy (intravenous platinum plus intravenous paclitaxel) in a 1:2 ratio. The overall survival was compared between the case group and the control group, and the IP treatment-related toxicities were reported. RESULTS: In total, 11 patients were assigned into the case group and 22 patients were assigned into the control group. The median overall survival (95% confidence interval) was 40.5 (25.5-56.2) months for the case group versus 28.0 (18.0-37.0) for the control group (hazard ratio=0.37 (95% confidence interval, 0.15-0.95); p=0.032, by the log-rank test). The most commonly observed toxicity was of gastrointestinal origin (81.8%). Toxicities that stemmed from hematological, cardiovascular, neurological, and catheter-related complications were similar to results published in other studies on IP chemotherapy for ovarian cancer. CONCLUSION: Salvage IP chemotherapy may potentially confer a longer overall survival than conventional systemic chemotherapy in the treatment of relapsed type II endometrial cancer.

Does adding intraperitoneal paclitaxel to standard intraperitoneal regimen yield incremental survival? A propensity score-matched cohort study.

We recruited consecutive patients with stage III epithelial ovarian, tubal, and peritoneal cancers who had optimal residual tumor after primary cytoreductive surgery and who received intraperitoneal chemotherapy between 2002 and 2012. Two propensity score-matched sample cohorts were created. We found that the addition of paclitaxel as a second intraperitoneal agent on a 3-week dosing schedule did not yield significant incremental survival benefits over the intraperitoneal delivery of a single cisplatin-based regimen. If our findings could be confirmed by a prospective randomized study, then it would be interesting to explore the efficacy of shifting back to a dose-dense intraperitoneal delivery of paclitaxel or a dose-dense delivery of a new formulation of paclitaxel for the patients with stage III epithelial ovarian, tubal, and peritoneal cancers.

Intraperitoneal delivery of a novel liposome-encapsulated paclitaxel redirects metabolic reprogramming and effectively inhibits cancer stem cells in Taxol(®)-resistant ovarian cancer.

Taxol(®) remained as the mainstay therapeutic agent in the treatment of ovarian cancer, however recurrence rate is still high. Cancer stem cells (CSCs) represent a subset of cells in the bulk of tumors and play a central role in inducing drug resistance and recurrence. Furthermore, cancer metabolism has been an area under intensive investigation, since accumulating evidence has shown that CSCs and cancer metabolism are closely linked, an effect named as metabolic reprogramming. In this work, we aimed to investigate the impacts of a novel liposome-encapsulated paclitaxel (Nano-Taxol) on the stemness phenotype and metabolic reprogramming. A paclitaxel-resistant cell line (TR) was established at first. Tumor growth was induced in the mice peritoneal cavity by inoculation of TR cells. A 2x2 factorial experiment was designed to test the therapeutic efficacy in which factor 1 represented the comparison of drugs (Taxol(®) versus Nano-Taxol), while factor 2 represented the delivery route (intravenous versus intraperitoneal delivery). In this work, we found that intraperitoneal delivery of Nano-Taxol redirects metabolic reprogramming, from glycolysis to oxidative phosphorylation, and effectively suppresses cancer stem cells. Also, intraperitoneal delivery of Nano-Taxol led to a significantly better control of tumor growth compared with intravenous delivery of Taxol(®) (current standard treatment). This translational research may serve as a novel pathway for the drug development of nanomedicine. In the future, this treatment modality may be extended to treat several relevant cancers that have been proved to be suitable for the loco-regional delivery of therapeutic agents, including colon cancer, gastric cancer, and pancreatic cancer.

Subtype-specific binding peptides enhance the therapeutic efficacy of nanomedicine in the treatment of ovarian cancer.

Currently, epithelial ovarian cancer is viewed as a heterogeneous disease with five major histological subtypes. Clear cell carcinoma represents a specific histological subtype of epithelial ovarian cancer that demonstrates more aggressive clinical behavior and drug resistance compared with other subtypes. Nevertheless, clear cell carcinoma is treated in the same manner as the other subtypes without any particular consideration to its unique clinical characteristics. To improve the therapeutic efficacy of the current liposomal doxorubicin approach for the treatment of clear cell carcinoma, we aimed to develop a novel peptide-conjugated liposomal doxorubicin to actively target this subtype. Two phage clones (OC-6 and OC-26) that specifically bound to clear cell carcinoma were isolated from a phage peptide display library after biopanning procedures. The peptide sequences were translated and aligned (OCSP-6 for OC-6, and OCSP-26 for OC-26, respectively). Peptide-conjugated nanoparticles demonstrated better tumor endocytosis and time-dependent gradual increase of intracellular drug uptake than non-targeting liposomal nanoparticles. Furthermore, peptide-conjugated liposomal doxorubicin better controlled tumors than did non-targeting liposomal doxorubicin. The current work may pave a new way for the development of drugs that target each subtype of epithelial ovarian cancer in the future.

Robotic-assisted laparoscopic complex myomectomy: a single medical center's experience.

OBJECTIVE: Conventional laparoscopic myomectomy (LM) has inherent limitations due to its rigid structure. The robotic system is a newly developed technology equipped with a flexible EndoWrist that offers good performance in delicate motions. Our objective was to share our clinical experience in the management of complex myomectomy using this robotic system. MATERIALS AND METHODS: From October 2010 to March 2012, 21 patients with symptomatic complex uterine myomas were evaluated. Complex myomectomy was defined as surgery involving more than two fibroids, large fibroids, or preexisting pelvic adhesions. We recorded and analyzed the preoperative characteristics of the patients and the fibroids, the detailed surgical time, and several postoperative outcomes to evaluate the feasibility and efficacy of robotic-assisted LM (RALM) for complex fibroids. RESULTS: A total of 21 patients were enrolled in this study. The mean age of the patients was 40.1 ± 4.5 years and the mean size of the largest fibroid was 7.3 ± 3.5 cm. RALM achieved satisfactory results, including a short postoperative hospital stay (3.1 ± 0.9 days), a low conversion rate (none of our patients required conversion to either a minilaparotomy or conventional open surgery), and a low complication rate (1 case in 21 patients, 4.8%). The average estimated blood loss was 235.7 ± 283.3 mL. CONCLUSION: Our study results demonstrated that RALM is a safe and effective method for handling complex fibroids.

Prognostic factors of primary fallopian tube cancer in a single institute in Taiwan.

OBJECTIVE: To improve the understanding of primary fallopian tube carcinoma (PFTC) through an analysis of possible clinical and pathologic determinants of prognosis. METHODS: A retrospective review of the database of a tertiary hospital in Taiwan for 1978-2007 was conducted to identify patients with a diagnosis of PFTC and to evaluate the clinicopathologic features associated with PFTC outcome. RESULTS: Fifty-eight patients (mean age 62.5 years) had a diagnosis of PFTC. Stage III/IV disease (55%) and poorly differentiated tumors (52%) were most common. The median follow-up was 93 months (range, 11-333 months). The 5-year disease-free survival rate was 59%, and the overall survival rate was 64%. Factors important in disease-free and overall survival in univariate analysis included the presence of pelvic and/or para-aortic lymph node metastases, International Federation of Gynecology and Obstetrics stage, high preoperative carbohydrate antigen 125 serum level, completion of optimal debulking surgery, and the use of paclitaxel-based chemotherapy; however, only patients with optimal cytoreduction had a decreased hazard of recurrence (hazard ratio [HR] 0.06; 95% confidence interval [CI] 0.01-0.23) and mortality (HR 0.08; 95% CI, 0.02-0.31) in multivariate analysis. CONCLUSION: Advanced tumor stage, in particular the presence of lymph node metastases, worsened the prognosis of patients with PFTC. However, optimal debulking surgery significantly improved the prognosis, emphasizing the importance of the treatment strategy.

Outcome of patients with bulky IB (≥ 6 cm) cervical squamous cell carcinoma with and without cisplatin-based neoadjuvant chemotherapy.

OBJECTIVE: To study the surgical morbidity and outcomes of patients with markedly bulky cervical squamous cell carcinoma (≥ 6 cm Cx-SCC) who underwent radical hysterectomy (RH) with and without neoadjuvant chemotherapy (NACT). MATERIALS AND METHODS: This retrospective study enrolled patients with International Federation of Gynecology and Obstetrics (FIGO) IB markedly bulky Cx-SCC who were treated with either three courses of weekly single agent cisplatin NACT (50 mg/m2) and subsequent radical hysterectomy (NACT-RH) or direct radical hysterectomy (RH) between 1996 and 2001. A total of 60 patients fulfilled the criteria, including 35 and 25 patients with NsACT-RH and RH, respectively. RESULTS: There was no statistically significant difference in basic characteristics between the two groups, except the smaller pathological tumor size, less blood loss, and lower immediate complication rate in the NACT-RH group. Median survival was 143.8 months in the NACT-RH group and 129.8 months in the RH group, respectively, without a statistically significant difference. Multivariate analysis showed that large pathological tumor size [hazard ratio (HR) 10.66, 95% confidence interval (CI) 2.93-38.80], the presence of para-aortic lymph node metastases and an immediate complication (HR 8.33 and 4.55, 95% CI 1.66-41.75 and 1.35-15.27, respectively) contributed to a worse outcome. CONCLUSION: Weekly single agent cisplatin NACT indeed reduced the pathological tumor size and immediate complication rate during the RH, supporting the feasibility of subsequent RH in the management of patients with bulky Cx-SCC.