Clinicopathologic Features and Treatment Outcomes in Patients with Stage I, High-Risk Histology or High-Grade Endometrial Cancer after Primary Staging Surgery: A Taiwanese Gynecologic Oncology Group Study.

To investigate the clinicopathological features and treatment outcomes in patients with stage I, high-risk endometrial cancer. Patients with International Federation of Gynecology and Obstetrics stage I, papillary serous, clear cell, or grade 3 endometrioid carcinoma treated between 2000 and 2012 were analyzed for the clinical and pathological factors in relation to prognosis. A total of 267 patients (stage IA; n = 175, stage IB; n = 92) were included. Among the clinicopathological features, stage and age were significant prognostic factors. The recurrence rate and overall survival for stage IB versus IA were 22.8% versus 9.1% (p = 0.003) and 149.7 months versus 201.8 months (p < 0.001), respectively. The patients >60 years of age also had a higher recurrence rate (21.7% versus 9.7%, p = 0.008) and poorer survival (102.0 months versus 196.8 months, p = 0.001) than those ≤60 years of age. Distant recurrence (64.9%) occurred more frequently than local recurrence (24.3%) and local combined with distant recurrence (10.8%) (p < 0.001). The postoperative treatment modality had no impact on tumor recurrence rate, recurrence site, or overall survival. Distant recurrence is a major cause of treatment failure in patients with stage I, high-risk endometrial cancer. However, current adjuvant treatment appeared to have little effect in preventing its occurrence.

Treatment outcomes of patients with stage II pure endometrioid-type endometrial cancer: a Taiwanese Gynecologic Oncology Group (TGOG-2006) retrospective cohort study.

OBJECTIVE: Choice of hysterectomy and adjuvant treatment for International Federation of Gynecology and Obstetrics (FIGO) 2009 stage II endometrioid endometrial cancer (EEC) is still controversial. Aims of this study were to evaluate survival benefits and adverse effects of different hysterectomies with or without adjuvant radiotherapy (RT), and to identify prognostic factors. METHODS: The patients at 14 member hospitals of the Taiwanese Gynecologic Oncology Group from 1992 to 2013 were retrospectively investigated. Patients were divided into simple hysterectomy (SH) alone, SH with RT, radical hysterectomy (RH) alone, and RH with RT groups. Endpoints were recurrence-free survival (RFS), overall survival (OS), disease-specific survival (DSS), adverse effects and prognostic factors for survival. RESULTS: Total of 246 patients were enrolled. The 5-year RFS, OS, DSS and recurrence rates for the entire cohort were 89.5%, 94.3%, 96.2% and 10.2%, respectively. Patients receiving RH had more adverse effects including blood loss (p<0.001), recurrent urinary tract infections (p=0.013), and leg lymphedema (p=0.038). Age over 50-year (HR=9.2; 95% confidence interval [CI]=1.2-70.9) and grade 3 histology (HR=7.28; 95% CI=1.45-36.6) were independent predictors of OS. Grade 3 histology was an independent predictor of RFS (HR=5.13; 95% CI=1.38-19.1) and DSS (HR=5.97; 95% CI=1.06-58.7). Patients receiving adjuvant RT had lower locoregional recurrence (p=0.046), but no impact on survival. CONCLUSION: Different treatment modalities yield similar survival outcomes. Patients receiving SH with RT had lower locoregional recurrent with acceptable morbidity. Age and tumor grading remained significant predictors for survival among patients with FIGO 2009 stage II EEC.

Outcomes of Patients With Surgically and Pathologically Staged IIIA-IVB Pure Endometrioid-type Endometrial Cancer: A Taiwanese Gynecology Oncology Group (TGOG-2005) Retrospective Cohort Study (A STROBE-Compliant Article).

In the management of patients with advanced-stage pure endometrioid-type endometrial cancer (E-EC), such as positive lymph nodes (stage III) or stage IV, treatment options are severely limited. This article aims to investigate the outcome of women with FIGO III-IV E-EC (based on FIGO 2009 system). The retrospective cohort study, based on the Taiwanese Gynecologic Oncology Group (TGOG-2005), enrolled patients undergoing staging surgery to have a pathologically confirmed FIGO III-IV E-EC from 22-member hospitals between 1991 and 2010. This cohort included 541 patients (stage III, n = 464; stage IV, n = 77). Five-year overall survival (OS) was 70.4%. Median progression-free survival (PFS) was 43 months (range 0-258 months) and median OS was 52 months (range 1-258 months). Multivariate analysis showed that FIGO stage, >1/2 myometrial invasion (hazard ratio [HR] 1.53, 95% confidence interval [CI] 1.12-2.09; P = 0.007), histological grade 3 (HR 2.0, 95% CI 1.47-2.75; P < 0.001), and metastases of pelvic and para-aortic lymph nodes (PLN and PALN) (HR 2.75, 95% CI 1.13-6.72; P < 0.001) were independent risk factors for PFS. FIGO stage, >1/2 myometrial invasion (HR 1.89, 95% CI 1.34-2.64; P < 0.001), and histological grade 3 (HR 2.42, 95% CI 1.75-3.35; P < 0.001) influenced OS. Complete dissection of PLN and PALN (HR 0.27, 95% CI 0.16-0.45; P < 0.001, and HR 0.14, 95% CI 0.08-0.26; P < 0.001) and the following paclitaxel-based therapy (HR 0.61, 95% CI 0.79-0.92; P = 0.017, and HR 0.48; 95% CI 0.31-0.75; P = 0.001) provided the better PFS and OS, respectively. In management of women with FIGO III-V E-EC, combination of complete staging surgery (complete dissection of PLN and PALN is included) and the following paclitaxel-based therapy could provide the better chance to survive. Patients with tumor >1/2 myometrial invasion and histological grade 3 are risky for disease-related mortality.

Clinical parameters associated with absence of endocervical/transformation zone component in conventional cervical Papanicolaou smears.

OBJECTIVE: To study clinical factors predicting the absence of endocervical/transformation zone (EC/TZ) components of conventional cervical Papanicolaou (Pap) smears. MATERIALS AND METHODS: The medical charts of patients who received Pap smears between March 2006 and August 2006 in the hospital were reviewed. The results of their Pap smears were retrieved while their demographic and clinical information were obtained from the medical charts. After excluding 378 cases with incomplete demographic data and 1397 cases with a history of pelvic irradiation, pelvic malignancy, and hysterectomy, 5662 cases were enrolled for data analysis. The relationship between clinical parameters and the absence of EC/TZ component was analyzed by Pearson Chi-square tests with Yates continuity correction and binary logistic regression tests. RESULTS: The incidence of satisfactory but absence of EC/TZ component was 8.7% (491/5662). Pregnancy increased the absence of EC/TZ component [odds ratio (OR}: 2.84, 95% confidence interval (CI): 2.14-3.77, p<0.0001]. Postpartum status and endocervical polyps decreased incidence (OR: 0.61, 95% CI: 0.38-0.98, p = 0.043 and OR: 0.33, 95% CI: 0.25-0.44, p<0.0001, respectively). CONCLUSIONS: Pregnancy is the only clinical factor associated with increased incidence of absence of EC/TZ cells. For these pregnant women undergoing a Pap smear, a more effective strategy may be needed to get a satisfactory smear with adequate EC/TZ components.

Outcome of ovarian preservation during surgical treatment for endometrial cancer: A Taiwanese Gynecologic Oncology Group study.

OBJECTIVE: The goal of this study was to investigate the impact of ovarian preservation on the survival of women with early-stage endometrial cancer, particularly young women. MATERIALS AND METHODS: A study cohort of 64 patients with histologically confirmed early-stage endometrial cancer was retrospectively collected from 10 member hospitals of the Taiwanese Gynecologic Oncology Group between 1998 and 2009. Survivorship and overall survival were compared between these two groups using a log-rank test. RESULTS: All patients who underwent surgery were adult women with a mean age of 40.4 ± 9.2 years (range 24-63 years). Ovary-preserving surgery was performed in 38 (59.4%) patients who desired to preserve their ovaries, incidentally in 19 (29.7%) patients with a preoperative diagnosis other than endometrial carcinoma, and in seven patients (10.9%) with unknown reasons. The 5-year recurrence-free survival rate was 98.3% with a median follow up of 44.6 months (range 1.0-126.9 months). Eight patients required adjuvant treatment (12.5%); one patient had documented local recurrence (1.6%); and no metachronous ovarian malignancy occurred during follow up. CONCLUSION: Preservation of bilateral ovaries does not increase cancer-related mortality. A more conservative approach to surgical staging may be considered in premenopausal women with early-stage endometrial cancer without risk factors.

Tanshinone IIA enhances the effects of TRAIL by downregulating survivin in human ovarian carcinoma cells.

BACKGROUND: Tanshinone IIA (TIIA), a diterpene quinone from the medicinal plant Salvia miltiorrhiza Bunge (Lamiaceae) was shown to possess apoptotic and TRAIL-sensitizing effects. Still, the molecular mechanisms whereby TIIA induces apoptosis remain largely unknown. PURPOSE: The role of survivin, an inhibitor of apoptosis protein, in TIIA-induced apoptosis has never been addressed before and hence was the primary goal of this study. METHODS: In this study, we explored the anticancer effect of TIIA in TOV-21G, SKOV3, and OVCAR3 ovarian carcinoma cells. Cytotoxicity was determined by MTS assay. Real-time RT-PCR and Western blotting were used to assess the mRNA and protein expression of related signaling proteins. RESULTS: Our results illustrated that TIIA's cytotoxic effect was caused by apoptosis with the involvement of caspases activity. Moreover, TIIA downregulated survivin in a concentration-dependent manner without affecting the expression of Bcl-2, Bcl-xL, and Bax. TIIA-induced survivin downregulation is regulated by both transcriptional processes and proteasomal degradation. Using TOV-21G cells as our cellular model, we demonstrated that TIIA-induced survivin downregulation requires p38 MAPK activation. Importantly, genetic overexpression of survivin rendered cells more resistant to TIIA, indicating an essential role of survivin downregulation in TIIA-induced apoptosis. This TRAIL sensitization effect of TIIA is ascribed to survivin downregulation because the effect was abrogated in cells that overexpressed survivin. CONCLUSION: Our findings provide new insights into the action modes of TIIA-mediated anticancer effects and further implicate a rational design for cancer therapeutic regimens by combining TIIA-sensitized TRAIL via downregulating survivin to elicit ovarian cancer cell death.

Prognostic factors and treatment outcomes for patients with surgically staged uterine clear cell carcinoma focusing on the early stage: A Taiwanese Gynecologic Oncology Group study.

OBJECTIVE: The aim of this study was to investigate the clinical and pathological characteristics of uterine clear cell carcinoma (UCCC) and the treatment of this disease in relation to patient outcomes. METHODS: The clinicopathological data for and the management of all patients with UCCC who presented between 1991 and 2010 at 11 member hospitals of the Taiwanese Gynecologic Oncology Group (TGOG) were retrospectively reviewed. RESULTS: There were no significant differences in 5-year overall survival (OS) rates between patients with pure UCCC (n=100) and non-pure UCCC (n=53) at the same surgical stage, with OS rates of 92.6%, and 87.7% for stage I; 83.3% and 83.3% for stage II; 64.0% and 67.8% for stage III; and 16.7% and 0% for stage IV (n=1), respectively. Tumor stage and age independently influenced the OS rate of UCCC. For the patients with early stage UCCC, the adjuvant therapy modality was the only significant prognostic factor for recurrence-free survival. The patients with early stage UCCC who received adjuvant therapy had excellent 5-year recurrence-free survival and OS rates compared to those who received radiotherapy (100% vs. 74%, p=0.01; 100% vs. 72%, p=0.03). CONCLUSIONS: The 5-year survival rates of patients with pure UCCC and non-pure UCCC were similar. The prognosis for surgical staging of patients with stage I/II UCCC was encouraging. Postoperative adjuvant platinum-based chemotherapy is recommended for patients with early stage UCCC who are at a high risk of recurrence.

Impact of management on the prognosis of pure uterine papillary serous cancer - a Taiwanese Gynecologic Oncology Group (TGOG) study.

OBJECTIVE: To investigate the clinical and pathological characteristics and the management of uterine papillary serous carcinoma (UPSC) in relation to patients' outcomes. METHODS: Clinicopathological data and the management of patients treated between 1991 and 2010 at 11 member hospitals of the Taiwanese Gynecologic Oncology Group (TGOG) were retrospectively reviewed. The Kaplan-Meier method was used to generate survival curves, and factors predictive of outcome were compared using the log-rank test and Cox regression analysis. RESULTS: A total of 119 pure UPSC patients were recruited. Stages I, II, III, and IV were identified in 34.5%, 2.5%, 36.1%, and 26.9% of the patients, respectively. The recurrence rate was 20.5% in FIGO stage I/II disease and 55.2% in FIGO stage III/IV disease. The 5-year overall survival rates for the patients with stage I, II, III, and IV disease were 92.0%, 66.7%, 34.2%, and 17.3%, respectively. Multivariate analysis showed that tumor stage (stage III/IV hazard ratio [HR] 8.65, 95% confidence interval [CI] 3.00-24.9) and optimal cytoreduction (HR 0.40, 95% CI 0.22-0.73) independently influenced the overall survival rate of UPSC patients. In addition, optimal cytoreduction (HR 0.36, 95% CI 0.17-0.78) and the combination of chemotherapy and radiation (HR 0.11, 95% CI 0.04-0.37) improved the overall survival of the advanced stage (FIGO stage III/IV) UPSC patients. CONCLUSIONS: UPSC represents an aggressive subtype of endometrial cancer commonly accompanied by extra-uterine disease. Comprehensive surgical staging with cytoreductive surgery is mandatory and beneficial for UPSC patients. Systemic chemotherapy combined with radiation should be considered as an adjuvant therapy for advanced stage UPSC patients.

Report of two cases of adenoid cystic carcinoma of Bartholin's gland and review of literature.

OBJECTIVE: Primary adenoid cystic carcinoma (ACC) of Bartholin's gland is a rare gynecologic malignancy. We report two cases from primary treatment to recurrence and the adjuvant treatment. CASE REPORT: A woman aged 37 years presented with a mass on the right posterior labia minor and underwent right radical hemi-vulvectomy and right-side inguino-femoral node dissection. Final pathology showed ACC arising from Bartholin's gland with positive margins. She received adjuvant external beam radiation to the pelvis, right vulva, and groin area. However, distal metastasis occurred 42 months after initial treatment and she eventually died of multiple metastases. Another woman aged 48 years presented with a mass on the right posterior labia with intermittent pain. She underwent right hemi-vulvectomy and right inguino-femoral lymph node dissection only because pathology showed ACC of Bartholin's gland with negative surgical margins. Lung metastasis occurred 59 months after initial treatment. She took tamoxifen only and achieved stable disease status for 4 years. CONCLUSION: To date, about 70 cases have been reported. We treated our second patient with antiestrogen therapy for 4 years and achieved good quality of life and stable disease status. However, further study on hormone therapy for ACC of Bartholin's gland is needed.

Risk factor analysis of coexisting endometrial carcinoma in patients with endometrial hyperplasia: a retrospective observational study of Taiwanese Gynecologic Oncology Group.

OBJECTIVE: To evaluate the clinical outcome and parameters related to coexisting endometrial carcinoma in women with tissue-diagnosed endometrial hyperplasia. METHODS: Between January 1991 and December 2009, three hundred and eighty-six patients with the presumptive diagnosis of endometrial hyperplasia were retrieved. Among these, one hundred and twenty-five patients were identified as having coexisting endometrial carcinoma in hysterectomy specimens. The three hundred and eighty-six patients were divided into two groups: the hyperplasia-benign group (261 cases) and the hyperplasia-malignant group (125 cases). Several clinical parameters including age, menopausal status, history of abnormal uterine bleeding, obstetrical history, medical history of diabetes and hypertension, BMI, and preoperative pathologic results were investigated. RESULTS: Age ≥53 (odds ratio [OR], 2.40; 95% confidence interval [CI], 1.26 to 4.57), menopausal status (OR, 2.07; 95% CI, 1.14 to 3.76), diabetes history (OR, 7.33; 95% CI, 2.79 to 19.26), abnormal uterine bleeding (OR, 3.99; 95% CI, 1.22 to 13.02), atypical endometrial hyperplasia (OR, 7.38; 95% CI, 4.03 to 13.49), and body mass index ≥27 (OR, 3.24; 95% CI, 1.76 to 5.97) were independent risk factors for prediction of endometrial hyperplasia coexisting with endometrial carcinoma. The diagnostic efficacy of atypical endometrial hyperplasia to predict the endometrial hyperplasia coexisting with endometrial carcinoma was better than or similar to those of other independent factors and combinations of these factors. CONCLUSION: Coexisting malignancy should be considered when examining endometrial hyperplasia patients with the related risk factors, especially atypical endometrial hyperplasia.

Effects of somatothermal far-infrared ray on primary dysmenorrhea: a pilot study.

The purpose of this study was to assess the beneficial effects of using a far-infrared (FIR) belt on the management of patients with primary dysmenorrhea. This is the first study to determine the efficacy of somatothermal FIR using a parallel-arm randomized sham-controlled and double-blinded design with objective physical evidence and psychometric self-reports. Fifty-one Taiwanese women with primary dysmenorrhea were enrolled in the study. Results indicate that there was an increased abdominal temperature of 0.6°C and a 3.27% increase in abdominal blood flow in the FIR group (wearing FIR belt) compared to those in the control group (wearing sham belt). Verbal rating scale and numeric rating scale scores in the FIR group were both lower than those in the control group. Compared to the blank group (wearing no belt), the average dysmenorrhea pain duration of the FIR group was significantly reduced from 2.5 to 1.8 days, but there was no significant difference in the control group. These results demonstrate that the use of a belt made of far-infrared ceramic materials can reduce primary dysmenorrhea.

Temporary cross-clamping of the infrarenal abdominal aorta during cesarean hysterectomy to control operative blood loss in placenta previa increta/percreta.

OBJECTIVE: To evaluate the efficacy and safety of temporary cross-clamping of the infrarenal abdominal aorta for controlling operative blood loss during cesarean hysterectomy in severe invasive placentation. CASE REPORT: A 35-year-old woman with a significant risk factor of four previous cesarean sections and placenta previa was referred to Taichung Veterans General Hospital with suspected abnormal placentation at 37 weeks of gestation. Obstetric ultrasonography and magnetic resonance imaging showed a bulky inhomogeneous placenta with extensive uterine serosa-bladder interface hypervascularity and suspicious focal bladder invasion. Cesarean hysterectomy was performed with the use of temporary cross-clamping of the infrarenal abdominal aorta. The duration of aortic cross-clamping was 1 hour, and the estimated blood loss was 2,000 mL. The patient was discharged home on postoperative day 11 with no postoperative sequelae. CONCLUSION: With this limited experience, we are encouraged by the apparent reduction in operative blood loss after the use of temporary cross-clamping of the infrarenal abdominal aorta during cesarean hysterectomy. Further investigation is needed to determine the efficacy and safety of this procedure.

Management of pelvic lymphocysts by ultrasound-guided aspiration and minocycline sclerotherapy.

OBJECTIVE: The purpose of this study was to describe our experience with ultrasound-guided aspiration of postoperative pelvic lymphocysts followed by intracavitary minocycline injection as sclerotherapy. PATIENTS AND METHODS: From 1997 to 2003, patients who developed either symptomatic or persistent lymphocyst after pelvic lymphadenectomy for gynecological malignancy were recruited in this study. All of the lymphocysts were palpable and were further examined by ultrasonography. Percutaneous ultrasound-guided needle aspiration of the lymphocyst was performed and then immediately followed by a single-dose injection of minocycline into the collapsed cavity. Follow-up was conducted every 4 weeks with pelvic examination and ultrasonography. RESULTS: Nineteen patients with a total of 21 pelvic lymphocysts underwent this procedure. The median size of the lymphocysts was 6 cm in diameter (range, 4-9 cm). Fifteen patients received 1 treatment, 3 received 2, and 1 patient with bilateral lymphocysts received 3 treatments. Complete resolution occurred in 14 patients (74%), and the other 5 patients (26%) had partial resolution with the volume of the lymphocyst decreasing at least 50%. For the 14 patients with complete resolution, the median time from treatment to disappearance of the lymphocyst was 3 months (range, 1-10 months), and none of them developed recurrence during the average follow-up period of 40 months (range, 2-62 months). No significant complication occurred with this procedure except for transient mild to moderate pelvic pain. DISCUSSION: Minocycline sclerotherapy seems to be a simple and safe method with a satisfactory success rate in treating lymphocysts which develop after pelvic lymphadenectomy. It can be performed in an outpatient setting and can be repeated if necessary. This procedure may be considered as the initial treatment modality for patients suffering from symptomatic or persistent lymphocysts after radical gynecological surgery.

Triplet combination of gemcitabine, carboplatin, and paclitaxel in previously treated, relapsed ovarian and peritoneal carcinoma: an experience in Taiwan.

OBJECTIVE: The aim of this phase II study was to evaluate the efficacy and toxicity of gemcitabine, carboplatin, and paclitaxel (GCP) combination as salvage therapy in patients with relapsed ovarian or peritoneal cancer who had previously received platinum-based chemotherapy. PATIENTS AND METHODS: Patients with progressive ovarian or peritoneal carcinoma who had previously received platinum-based chemotherapy were enrolled. Gemcitabine was administered at 800 mg/m(2) as a 30-min intravenous infusion on days 1 and 8; carboplatin (AUC of 5) and paclitaxel (175 mg/m(2)) were administered as 60-min and 3-h intravenous infusions, respectively, on day 1. Treatment cycles were repeated every 3 weeks for a maximum of nine cycles. RESULTS: Twenty patients (ovarian carcinoma, 19; peritoneal carcinoma, 1) received this triplet regimen as salvage therapy. All the patients had previously received at least one platinum-based regimen for chemotherapy and 17 of them had received platinum plus paclitaxel. The median number of previous regimens was 2 (range, 1-4), and the median platinum-free interval was 9 months (range, 1-18). A total of 130 cycles were administered with a median of six cycles per patient (range, 3-9). The overall response rate was 75%, including 12 complete responses (60%; 95% confidence interval [CI], 36.1-80.9) and three partial responses (15%; 95% CI, 3.2-37.9). The other five patients showed stable disease (25%; 95% CI, 8.7-49.1). The median duration of the progression-free survival was 6.5 months (range, 3-20). Myelosuppression was the main toxicity, with leukopenia being the most prominent (grade 3/4 toxicity in 35% patients), followed by thrombocytopenia in 20% patients. In addition, 35% patients had grade 3 anemia. All the toxicities were manageable and the patients recovered fully. Among non-hematological toxicities, the only notable one was grades 2 and 3 hepatic toxicity seen in two and one patients, respectively, necessitating a decrease in the paclitaxel dose in two patients. CONCLUSIONS: GCP combination is an effective salvage chemotherapy in patients with heavily pretreated and relapsed ovarian and peritoneal cancer. The significant side effects of myelosuppression and hepatic toxicity were of moderate severity and manageable.