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1.  Is there any clinical significance of compression of left common iliac vein? 
PMCID: PMC3893668  PMID: 24459573
2.  Definitive extended field intensity-modulated radiotherapy and concurrent cisplatin chemosensitization in the treatment of IB2-IIIB cervical cancer 
To assess the toxicity of delivering extended field intensity-modulated radiotherapy (EF-IMRT) and concurrent cisplatin chemotherapy for locally advanced cervical carcinoma.
Forty-five patients who underwent EF-IMRT and concurrent cisplatin chemotherapy for the treatment of stage IB2 to IIIB cervical cancer were retrospectively reviewed. The clinical target volume included all areas of gross and potentially microscopic disease and regional lymph node regions. All patients underwent high-dose-rate brachytherapy. The acute and late toxicity were scored using the Common Terminology Criteria for Adverse Events and the Radiation Therapy Oncology Group late radiation morbidity scoring criteria, respectively.
The median follow-up was 28 months (range, 5 to 62 months). Forty-two patients had a complete response, and three had a persistent disease. Of those 42 patients, 15 patients (35.7%) had recurrence. The regions of recurrence were in-field in 2 patients and out-field in 13 patients. Acute grade ≥3 gastrointestinal, genitourinary and hematologic toxicity occurred in 3, 1, and 9 patients, respectively. Three patients (6.7%) suffered from late grade 3 toxicities. Seven patients experienced ovarian transposition, 5 of those patients (71%) maintained ovarian function. Thirty-eight patients (84.4%) were alive at the last follow-up.
Concurrent cisplatin chemotherapy with EF-IMRT was safe. The acute and late toxicities are acceptable. EF-IMRT provides an opportunity to preserve endocrine function for patients with ovarian transposition.
PMCID: PMC3893669  PMID: 24459576
Cervical cancer; Chemotherapy; Extended field; Intensity-modulated radiotherapy; Toxicity
3.  Role of paclitaxel and cisplatin as the neoadjuvant treatment for locally advanced squamous cell carcinoma of the vulva 
The therapeutic outcomes of patients with advanced vulvar cancer are poor. Multi-modality treatments including concurrent chemoradiation or different regimens of neoadjuvant chemotherapy (NACT), and surgery have been explored to reduce the extent of surgery and morbidity. The present single-institution trial aimed to evaluate the efficacy and toxicity of paclitaxel and cisplatin in locally advanced vulvar cancer.
From 2002 to 2009, 10 patients with stage III-IV locally advanced squamous cell carcinoma of the vulva were prospectively treated with 3 courses of paclitaxel-ifosfamide-cisplatin or paclitaxel-cisplatin. Nine of them subsequently underwent radical local excision or radical partial vulvectomy and bilateral inguino-femoral lymphadenectomy.
The clinical response rate of all enrolled patients was 80%, whereas the pathological responses included 1 case with complete remission, 2 with persistent carcinoma in situ, and 6 invasive cancer cases with tumor shrinkage of more than 50%. Four patients had positive nodes. Forty percent of patients experienced grade 3-4 bone marrow toxicity, which was successfully managed with granulocyte-colony stimulating factor, even in cases of elderly patients. Median progression-free survival after surgery was 14 months (range, 5 to 44 months). Six of the 7 recurrent cases were local, and 3 of them were treated with salvage surgery while the other 3 received radiation with or without chemotherapy. After a median follow-up period of 40 months (range, 5 to 112 months), 55.5% of patients remained alive with no evidence of disease, including 2 long-term survivors after recurrence at 5 and 9 years.
Based on the high response rate and manageable toxicity, NACT with paclitaxel and cisplatin with or without ifosfamide followed by surgery could be considered as a therapeutic option for locally advanced vulvar cancer.
PMCID: PMC3893670  PMID: 24459577
Locally advanced vulvar cancer; Morbidity; Neoadjuvant chemotherapy; Paclitaxel and cisplatin; Surgical treatment
4.  Cervical preneoplasia biomarkers: a conundrum for the community based gynecologic surgical pathologist 
The integration of high-risk (HR) human papillomavirus (HPV) in the cell genome is an essential step in the oncogenic pathway of lower ano-genital HPV-related squamous preinvasive and invasive lesions. The expression of HR-HPV surrogate biomarkers of HR-HPV integration by immunohistocytochemistry (IHC) serves as a diagnostic and/or a prognostic tool of cervical preinvasive lesions. IHC is claimed to decrease the interobserver variability in the diagnosis of histomorphologically equivocal lesions, and to be helpful in evaluating the potentiality of regression, persistence or progression. The most common biomarkers used in cervical pathology are p16INK4a, Ki-67, the HPV capsid L1 antigen, and ProEXc. Critical review of the literature shows a great variability in the diagnostic accuracy, risk evaluation, and relative distribution of these biomarkers in low and high grade preinvasive lesions. Review of the literature suggests that currently dual IHC with p16 and L1 provide the best diagnostic and prognostic evaluation of lesions diagnosed histomorphologically as low and high-grade.
PMCID: PMC3893671  PMID: 24459574
Biomarkers; Cervix uteri; Preinvasive lesions
5.  FIGO 1988 versus 2009 staging for endometrial carcinoma: a comparative study on prediction of survival and stage distribution according to histologic subtype 
The surgical staging system for endometrial carcinoma developed by International Federation of Gynecology and Obstetrics (FIGO) in 1988 was revised in 2009. Given the importance of continuous validation of the prognostic performance of staging systems, we analyzed the disease specific survival for patients with endometrial carcinoma using FIGO 1988 and 2009 systems. Further, the stage distribution of endometrioid and nonendometrioid carcinomas was studied.
Eight hundred twenty-one women with endometrial carcinoma were retrospectively staged using FIGO 1988 and 2009 systems.
FIGO 1988 IC was associated with an inferior survival compared with IA-IB. Survival overlapped for 1988 IA and IB, for 1988 IC and IIA, and for 2009 IB and II. FIGO 2009 IA-II patients with negative peritoneal cytology had a superior survival compared with 1988 IIIA patients with positive cytology only. The survival was similar for 1988 IIIA with positive cytology only and for 2009 IIIA. Cox proportional hazards model recognized grade 3 endometrioid and nonendometrioid histology, tumor spread beyond the uterine corpus and cervix, and positive peritoneal cytology as significant predictors of death. Among 2009 IIIC substages, the proportion of IIIC2 tumors was higher for nonendometrioid than for endometrioid carcinomas (p=0.003).
Stage I with deep myometrial invasion and stage II endometrial carcinoma seem to have similar survival outcomes. Although positive peritoneal cytology does not alter the stage according to the FIGO 2009 system, it should be considered a poor prognostic sign. The high proportion of nonendometrioid carcinomas in the stage IIIC2 category may reflect different patterns of retroperitoneal spread among tumors with different histologic subtypes.
PMCID: PMC3893672  PMID: 24459578
Disease specific survival; Endometrial carcinoma; International Federation of Gynecology and Obstetrics; Tumor staging
6.  Correlation between the overexpression of epidermal growth factor receptor and mesenchymal makers in endometrial carcinoma 
The objective of this study was to evaluate the effect of overexpression of epidermal growth factor receptor (EGFR) on the expression of epithelial cell markers (E-cadherin and α-catenin) and mesenchymal cell markers (N-cadherin and vimentin) in endometrial carcinoma.
The expression of all 4 markers was evaluated in EGFR overexpressing Ishikawa cells, control Ishikawa cells, and KLE cells using reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. The expression of these 4 markers was also determined in cancerous tissues of patients with endometrial carcinoma using immunohistochemical staining.
Ishikawa cells transfected with EGFR showed decreased expression of E-cadherin and α-catenin and increased expression of N-cadherin and vimentin compared with control Ishikawa cells (p<0.01 for all). The expression of N-cadherin and vimentin was higher and the expression of E-cadherin and α-catenin was lower in stage II-III than stage I and in grade II-III than grade I endometrial carcinoma tissue (p<0.01 for all).
Decreased expression of epithelial markers (E-cadherin and α-catenin) and increased expression of mesenchymal markers (N-cadherin and vimentin) were observed in human endometrial carcinoma tissue. These findings correlate with high EGFR expression in cultured endometrial carcinoma cells.
PMCID: PMC3893673  PMID: 24459579
Endometrial carcinoma cells; Epidermal growth factor receptor; Epithelial-mesenchymal transition
7.  Survival benefit of taxane plus platinum in recurrent ovarian cancer with non-clear cell, non-mucinous histology 
This study was conducted to examine the effects of front-line chemotherapy on overall survival (OS) and postrecurrence survival (PRS) of patients with recurrent ovarian cancer, when stratifying the histologic type.
Five hundred and seventy-four patients with recurrent ovarian cancer with sufficient clinical information, including front-line chemotherapy, were analyzed. The pathologic slides were evaluated by central pathologic review. The patients were divided into two groups: group A (n=261), who underwent taxane plus platinum, and group B (n=313), who underwent conventional platinum-based chemotherapy without taxanes.
The median age was 54 years (range, 14 to 89 years). Group A had significantly better median OS (45.0 months vs. 30.3 months, p<0.001) and PRS (23.0 months vs. 13.0 months, p<0.001) compared to group B. The OS and PRS were similar between the groups in patients with clear cell or mucinous histology. In contrast, among patients with non-clear cell, non-mucinous histologies, the OS and PRS of group A were significantly better than those of group B (OS, p<0.001; PRS, p<0.001). Multivariable analyses revealed that, among patients with non-clear cell, non-mucinous histologies, chemotherapy including taxane and platinum was an independent predictor of favorable survival outcomes. Conversely, in patients with clear cell or mucinous histology, taxane-including platinum-based combination chemotherapy did not improve the OS and PRS compared to a conventional platinum-based regimen which did not include taxanes.
Since the emergence of taxane plus platinum, the prognosis of patients with recurrent ovarian cancer has improved. However, we here demonstrate that this improvement is limited to patients with non-clear cell, non-mucinous histologies.
PMCID: PMC3893674  PMID: 24459580
Chemotherapy; Histologic type; Overall survival; Postrecurrence survival; Recurrent ovarian cancer
8.  A longitudinal analysis with CA-125 to predict overall survival in patients with ovarian cancer 
The objective of this study was to explore the association of longitudinal CA-125 measurements with overall survival (OS) time by developing a flexible model for patient-specific CA-125 profiles, and to provide a simple and reliable prediction of OS.
A retrospective study was performed on 275 patients with ovarian cancer who underwent at least one cycle of primary chemotherapy in our institute. Serial measurements of patients' CA-125 levels were performed at different frequencies according to their clinical plans. A statistical model coupling the Cox proportional hazards and the mixed-effects models was applied to determine the association of OS with patient-specific longitudinal CA-125 values. Stage and residual tumor size were additional variables included in the analysis.
A total of 1,601 values of CA-125 were included. Longitudinal CA-125 levels, stage, and the residual tumor size were all significantly associated with OS. A patient-specific survival probability could be calculated. Validation showed that, in average, 85.4% patients were correctly predicted to have a high or low risk of death at a given time point. Comparison with a traditional model using CA-125 half-life and time to reach CA-125 nadir showed that the longitudinal CA-125 model had an improved predicative value.
Longitudinal CA-125 values, measured from the diagnosis of ovarian cancer to the completion of primary chemotherapy, could be used to reliably predict OS after adjusting for the stage and residual tumor disease. This model could be potentially useful in clinical counseling of patients with ovarian cancer.
PMCID: PMC3893675  PMID: 24459581
CA-125; Longitudinal analysis; Ovarian cancer; Overall survival; Prediction
9.  Decreased ARID1A expression is correlated with chemoresistance in epithelial ovarian cancer 
Loss of ARID1A is related to oncogenic transformation of ovarian clear cell adenocarcinoma. The present study was conducted in epithelial ovarian cancer of all tissue types to investigate whether an increased or decreased expression level of ARID1A can be a prognostic factor for ovarian cancer or can influence the sensitivity to anticancer drugs.
The expression level of ARID1A was investigated in 111 patients with epithelial ovarian cancer who received initial treatment at the Hirosaki University Hospital between 2006 and 2011. The expression level of ARID1A was immunohistochemically graded using staining scores, which were calculated by multiplying the staining intensity of the nuclei by the stain-positive area.
The level of ARID1A was significantly lower in clear cell adenocarcinoma than in other histologic types. Among the patients with stage III, IV cancer (n=46), the level of ARID1A was significantly lower (p=0.026) in patients who did not achieve complete response (CR; n=12) than in patients who achieved CR (n=34). The level of ARID1A was relatively lower (p=0.07) in patients who relapsed after achieving CR (n=21) than in patients who did not relapse (n=13). When the staining score of 0 was defined as ARID1A-negative and other staining scores were defined as ARID1A-positive, there was significant difference in progression-free survival between ARID1A-negative (n=11) and ARID1A-positive (n=35) patients in stage III, IV disease.
The result suggests that decreased ARID1A expression is correlated with chemoresistance and may be a predictive factor for the risk of relapse of advanced cancer after achieving CR.
PMCID: PMC3893676  PMID: 24459582
ARID1A; Chemoresistance; Epithelial ovarian cancer; Relapse
10.  ASGO's Third Biennial Meeting, December 12-14, 2013 
PMCID: PMC3893677
11.  Surgical anatomy of the common iliac veins during para-aortic and pelvic lymphadenectomy for gynecologic cancer 
Compression of the left common iliac vein between the right common iliac artery and the vertebrae is known to be associated with the occurrence of left iliofemoral deep vein thrombosis (DVT). In this study, we described the variability in vascular anatomy of the common iliac veins and evaluated the relationship between the degree of iliac vein compression and the presence of DVT using the data from surgeries for gynecologic cancer.
The anatomical variations and the degrees of iliac vein compression were determined in 119 patients who underwent systematic para-aortic and pelvic lymphadenectomy during surgery for primary gynecologic cancer. Their medical records were reviewed with respect to patient-, disease-, and surgery-related data.
The degrees of common iliac vein compression were classified into three grades: grade A (n=28, 23.5%), with a calculated percentage of 0%-25% compression; grade B (n=47, 39.5%), with a calculated percentage of 26%-50% compression; and grade C (n=44, 37%), with a calculated percentage of more than 50% compression. Seven patients (5.9%) had common iliac veins with anomalous anatomies; three were divided into small caliber vessels, two with a flattened structure, and two had double inferior vena cavae. The presence of DVT was associated with the elevated D-dimer levels but not with the degree of iliac vein compression in this series.
Although severe compression of the common iliac veins was frequently observed, the degree of compression might not be associated with DVT in surgical patients with gynecologic cancer. Anomalous anatomies of common iliac veins should be considered during systematic para-aortic and pelvic lymphadenectomy in the gynecologic cancer patients.
PMCID: PMC3893678  PMID: 24459583
Anatomy; Deep vein thrombosis; Gynecologic cancer; Iliac veins; Lymphadenectomy
12.  Epidemiologic characteristics of cervical cancer in Korean women 
Cervical cancer is the most common female genital tract malignancy in Korean women. Although age-standardized cancer incidence rate of cervical cancer has decreased from 18.6 per 100,000 women in 1999 to 12.3 per 100,000 women in 2010 in Korea with widespread routine screening, several epidemiologic characteristics are still present. Incidence of cervical cancer still varies according to geographic area, and a significant portion of cases are detected at a locoregionally advanced stage, without significant improvement of five-year survival rate.2014-01-15 Cervical screening techniques such as the Pap smear should be the gold standard strategy to decrease incidence and to improve the survival outcomes of patients with cervical cancer. In addition, screening programs for cervical cancer should be designed, organized and directed within the context of a nationwide program for cancer control.
PMCID: PMC3893679  PMID: 24459584
Cervical cancer; Incidence; Korea; Screening programs; Survival outcomes
13.  Reproductive outcomes after laparoscopic radical trachelectomy for early-stage cervical cancer 
The objective of this study was to estimate the reproductive outcome of young women with early-stage cervical cancer who underwent fertility-sparing laparoscopic radical trachelectomy (LRT).
We performed a retrospective review of the medical records of patients with early-stage cervical cancer who underwent LRT. Clinicopathological data were obtained from patient medical records, and reproductive outcome data were obtained from patient medical records and telephone interviews.
Fifty-five patients who underwent successful LRT were included in this study. The median age of patients was 32 years (range, 22 to 40 years), and the median follow-up time after LRT was 37 months (range, 3 to 105 months). Menstruation resumed in all patients after LRT, with fifty patients (90.9%) and five patients (9.1%) reporting regular and irregular menstruation, respectively. Six patients (10.9%) presented with cervical stenosis, which was manifested by regular but decreased menstrual flow and newly-developed dysmenorrhea. These patients underwent cervical cannulation and dilatation. Eighteen patients (32.7%) attempted to conceive, with six out of 18 patients receiving fertility treatments. Fourteen pregnancies (i.e., four missed abortions, six preterm births and four full-term births) occurred in 10 patients after LRT. Nine out of 10 patients gave birth to 10 healthy babies. The pregnancy rate after LRT was 55.6% (10/18). The spontaneous abortion rate and live birth rate were 28.6% (4/14) and 71.4% (10/14), respectively. The preterm birth rate was 60% (6/10).
Pregnancy and live birth rates after LRT were promising; however, the preterm birth rate was relatively high. Cervical stenosis also occurred in a small percentage of patients.
PMCID: PMC3893680  PMID: 24459575
Cervical cancer; Fertility; Laparoscopic radical trachelectomy; Pregnancy outcome; Reproductive outcome
14.  Squamous cell carcinoma antigen in cervical cancer and beyond 
Journal of Gynecologic Oncology  2013;24(4):291-292.
PMCID: PMC3805906  PMID: 24167661
15.  Staging of ovarian cancer: time to subdivide more? 
Journal of Gynecologic Oncology  2013;24(4):293-294.
PMCID: PMC3805907  PMID: 24167662
16.  Potential opportunities to reduce cervical cancer by addressing risk factors other than HPV 
Journal of Gynecologic Oncology  2013;24(4):295-297.
Cervical cancer is the most common cancer in developing world and 80% of global burden is reported from these nations. Human papillomavirus along with poverty, illiteracy/lower education level and standards, multi-parity, tobacco, malnutrition and poor genital hygiene may act synergistically to cause cervical cancer. Risk factor of cervical cancer may in itself be the reason for non-viability of cervical cancer vaccine program in this part of the world. Interventions to address these risk factors in addition to vaccination of girls before their sexual debut may hold promises of reducing the morbidity and mortality of female genital cancers.
PMCID: PMC3805908  PMID: 24167663
Cervical cytologic screening; Developing countries; Gynecologic cancers; HPV typing; HPV vaccine
17.  Incidence of cervical, endometrial, and ovarian cancer in Korea, 1999-2010 
Journal of Gynecologic Oncology  2013;24(4):298-302.
To investigate the recent incidence of and trends in cervical, endometrial, and ovarian cancer in Korean females.
Data from the Korea Central Cancer Registry between 1999 and 2010 were analyzed. Age-standardized rates (ASRs) and annual percent changes (APCs) were calculated.
The absolute incidence rates of the three major gynecologic cancers increased: 6,394 in 1999 to 7,454 in 2010. The ASR for gynecologic cancer was 23.7 per 100,000 in 1999 and decreased to 21.0 in 2010 (APC, -1.1%; 95% confidence interval [CI], -1.53 to -0.70) due to a definitive decrease in the incidence of cervical cancer (APC, -4.3%). Endometrial cancer has been definitively increasing (APC, 6.9% during 1999-2010), especially in females <30 years old (APC, 11.2%) and in females ≥80 years old (APC, 9.5%). The incidence of ovarian cancer is increasing gradually (APC, 1.5%).
ASRs and APC for gynecologic cancers overall are decreasing due to the decrease in the incidence of cervical cancer. However, the incidence of endometrial and ovarian cancer has been increasing.
PMCID: PMC3805909  PMID: 24167664
Cancer; Cervix uteri; Endometrium; Ovary; Korea
18.  Learning curve analysis of robot-assisted radical hysterectomy for cervical cancer: initial experience at a single institution 
Journal of Gynecologic Oncology  2013;24(4):303-312.
The aim of this study was to evaluate the learning curve and perioperative outcomes of robot-assisted laparoscopic procedure for cervical cancer.
A series of 65 cases of robot-assisted laparoscopic radical hysterectomies with bilateral pelvic lymph node dissection for early stage cervical cancer were included. Demographic data and various perioperative parameters including docking time, console time, and total operative time were reviewed from the prospectively collected database. Console time was set as a surrogate marker for surgical competency, in addition to surgical outcomes. The learning curve was evaluated using cumulative summation method.
The mean operative time was 190 minutes (range, 117 to 350 minutes). Two unique phases of the learning curve were derived using cumulative summation analysis; phase 1 (the initial learning curve of 28 cases), and phase 2 (the improvement phase of subsequent cases in which more challenging cases were managed). Docking and console times were significantly decreased after the first 28 cases compared with the latter cases (5 minutes vs. 4 minutes for docking time, 160 minutes vs. 134 minutes for console time; p<0.001 and p<0.001, respectively). There was a significant reduction in blood loss during operation (225 mL vs. 100 mL, p<0.001) and early postoperative complication rates (28% vs. 8.1%, p=0.003) in phase 2. No conversion to laparotomy occurred.
Improvement of surgical performance in robot-assisted surgery for cervical cancer can be achieved after 28 cases. The two phases identified by cumulative summation analysis showed significant reduction in operative time, blood loss, and complication rates in the latter phase of learning curve.
PMCID: PMC3805910  PMID: 24167665
Cervical neoplasms; Laparoscopic surgery; Learning curve; Robotics
19.  Posttreatment cut-off levels of squamous cell carcinoma antigen as a prognostic factor in patients with locally advanced cervical cancer treated with radiotherapy 
Journal of Gynecologic Oncology  2013;24(4):313-320.
The aim of the present study was to assess prognostic factors for patients with locally advanced cervical cancer treated with radiotherapy as the primary treatment and to assess the posttreatment cut-off levels of squamous cell carcinoma antigen (SCC-Ag) to predict three-year overall survival (OS) rates.
One hundred and twenty-eight patients with cervical squamous cell carcinoma (International Federation of Gynecology and Obstetrics [FIGO] stage IIB-IVA) treated using radiotherapy or concurrent chemoradiotherapy were identified. Of these patients, 116 who had SCC-Ag levels >1.5 ng/mL prior to treatment were analyzed retrospectively.
Median age was 68 years (range, 27 to 79 years). The complete response rate was 70.7% and the three-year OS rate was 61.1%. The median levels of pretreatment and posttreatment SCC-Ag were 11.5 ng/mL (range, 1.6 to 310.0 ng/mL) and 0.9 ng/mL (range, 0.4 to 41.0 ng/mL), respectively. Multivariate analysis showed that pretreatment anemia (p=0.041), pelvic lymph node metastasis (p=0.016) and posttreatment SCC-Ag levels (p=0.001) were independent prognostic factors for three-year OS. The SCC-Ag level cut-off point for three-year OS rates, calculated using a receiver operating characteristic curve, was 1.15 ng/mL (sensitivity, 80.0%; specificity, 74.0%).
Pretreatment anemia and pelvic lymph node metastasis are poor prognostic factors in locally advanced cervical cancer. Furthermore, posttreatment SCC-Ag levels <1.15 ng/mL predicted better three-year OS rates.
PMCID: PMC3805911  PMID: 24167666
Cervical cancer; Radiotherapy; Squamous cell carcinoma antigen
20.  Utility of serum squamous cell carcinoma antigen levels at the time of recurrent cervical cancer diagnosis in determining the optimal treatment choice 
Journal of Gynecologic Oncology  2013;24(4):321-329.
To investigate the utility of serum squamous cell carcinoma antigen (SCC-Ag) levels upon the diagnosis of recurrent cervical cancer for decision making in patient management.
Clinical records from 167 cervical cancer patients who developed recurrence between April 1996 and September 2010 were reviewed. A Cox proportional hazards regression model was used to investigate the prognostic significance of serum SCC-Ag levels at the time of recurrence. The effects of various salvage treatments on survival outcomes of recurrent cervical cancer were examined with respect to serum SCC-Ag levels.
Serum SCC-Ag levels were elevated (>2.0 ng/mL) in 125 patients (75%) when recurrence was diagnosed. These patients exhibited significantly shorter postrecurrence survival than those with normal SCC-Ag levels (log-rank; p=0.033). Multivariate analyses revealed that an elevated serum SCC-Ag level was an independent prognostic factor for poor postrecurrence survival. In patients with SCC-Ag levels <14.0 ng/mL, radiotherapy or surgery resulted in improved survival compared with chemotherapy or supportive care. In contrast, in patients with SCC-Ag levels of ≥14.0 ng/mL, salvage treatment with radiotherapy had only a minimal impact on postrecurrence survival.
The serum SCC-Ag level measured when cervical cancer recurrence is diagnosed can be useful for deciding upon the appropriate salvage treatment.
PMCID: PMC3805912  PMID: 24167667
Decision-making; Recurrent cervical cancer; Squamous cell carcinoma antigen; Survival
21.  Clinical outcome of 31 patients with primary malignant melanoma of the vagina 
Journal of Gynecologic Oncology  2013;24(4):330-335.
To investigate the clinical characteristics of and prognostic factors for primary malignant melanoma of the vagina.
Clinical data from 31 patients treated for primary malignant melanoma of the vagina at the Sun Yat-sen University Cancer Center between March 1970 and June 2005 were retrospectively analyzed.
The median age was 58 years (range, 18 to 73 years), and the main symptoms reported were vaginal bleeding and vaginal discharge. Most tumors were of the nodular type and classified as stage I according to International Federation of Gynecology and Obstetrics staging criteria. Surgery was performed on 22 patients, chemotherapy was administered to 7 patients, and immunotherapy was administered to 19 patients. Recurrent tumors developed in 11 patients (35.5%) during a median follow-up period of 20.2 months (range, 1 month to 18 years). The 5-year overall survival rate was 32.3%. Univariate analysis revealed that macroscopic tumor growth and the treatment method significantly affected survival outcome (p=0.039 and p<0.001, respectively), whereas the radicality of surgery did not (p=0.296). Multivariate analysis revealed that macroscopic tumor growth (hazard ratio [HR], 4.1; 95% confidence interval [CI], 1.4 to 12.1; p=0.010) and treatment method (HR, 0.3; 95% CI, 0.1 to 0.9; p=0.025) were independent prognostic factors for overall survival.
Patients with primary vaginal melanoma have a poor prognosis. Macroscopic tumor growth and treatment method are prognostic factors for primary malignant melanoma of the vagina.
PMCID: PMC3805913  PMID: 24167668
Immunotherapy; Malignant melanoma; Surgical treatment; Vaginal malignancies
22.  Serum leptin, adiponectin and endometrial cancer risk in Chinese women 
Journal of Gynecologic Oncology  2013;24(4):336-341.
To investigate the relationship between serum concentrations of leptin or adiponectin, and endometrial carcinoma in Chinese women.
We conducted a case-control study of a total of 516 Chinese women to detect the relationships between serum concentrations of leptin or adiponectin, and endometrial carcinoma in Chinese women. The study subject constituted 206 cases of endometrial cancer and 310 normal controls.
Patients with endometrial carcinoma had higher serum leptin concentrations than controls (28.8±2.2 ug/L vs. 19.8±1.4 ug/L; p<0.001). The adiponectin levels in patients were lower than in controls with borderline statistical significance (2,330.7±180.5 ug/L vs. 2,583.9±147.2 ug/L; p=0.078). Logistic regression analysis confirmed the associations between leptin or adiponectin, and endometrial carcinoma after adjustment for age, body mass index, fasting insulin, serum glucose, cholesterol, triglycerides, and high-density lipoprotein cholesterol (odds ratio for the top tertile vs. the bottom tertile: leptin 2.05; 95% confidence interval [CI], 1.28 to 3.29; p<0.001; adiponectin 0.52; 95% CI, 0.32 to 0.83; p<0.001).
Increased leptin or decreased adiponectin levels are associated with endometrial carcinoma.
PMCID: PMC3805914  PMID: 24167669
Adiponectin; Endometrial carcinoma; Insulin resistance; Leptin
23.  Trends in incidence and survival outcome of epithelial ovarian cancer: 30-year national population-based registry in Taiwan 
Journal of Gynecologic Oncology  2013;24(4):342-351.
To investigate the changes of incidence and prognosis of epithelial ovarian cancer in thirty years in Taiwan.
The databases of women with epithelial ovarian cancer during the period from 1979 to 2008 were retrieved from the National Cancer Registration System of Taiwan. The incidence and prognosis of these patients were analyzed.
Totally 9,491 patients were included in the study. The age-adjusted incidences of epithelial ovarian cancer were 1.01, 1.37, 2.37, 3.24, 4.18, and 6.33 per 100,000 person-years, respectively, in every 5-year period from 1979 to 2008. The age-specific incidence rates increased especially in serous, endometrioid and clear cell carcinoma, and the age of diagnosis decreased from sixty to fifty years old in the three decades. Patients with mucinous, endometrioid, or clear cell carcinoma had better long-term survival than patients with serous carcinoma (log rank test, p<0.001). Patients with undifferentiated carcinoma or carcinosarcoma had poorer survival than those with serous carcinoma (log rank test, p<0.001). The mortality risk of age at diagnosis of 30-39 was significantly higher than that of age of 70 years or more (test for trend, p<0.001). The mortality risk decreased from the period of 1996-1999 (hazard ratio [HR], 0.90; p=0.054) to the period after 2000 (HR, 0.74; p<0.001) as compared with that from the period of 1991-1995.
An increasing incidence and decreasing age of diagnosis in epithelial ovarian cancer patients were noted. Histological type, age of diagnosis, and treatment period were important prognostic factors for epithelial ovarian carcinoma.
PMCID: PMC3805915  PMID: 24167670
Epithelial ovarian carcinoma; Histological type; Population-based study; Prognosis
24.  Improvements to the FIGO staging for ovarian cancer: reconsideration of lymphatic spread and intraoperative tumor rupture 
Journal of Gynecologic Oncology  2013;24(4):352-358.
To evaluate the improvement in prognosis prediction with reassignment of International Federation of Gynecology and Obstetrics (FIGO) stages for ovarian carcinoma.
This was a retrospective study of patients with epithelial ovarian, fallopian tube, and primary peritoneal cancers. Sub-staging criteria used in stage reassignment were defined as follows: surgical spillage (IC1), capsule rupture before surgery or tumor on the surface (IC2), and positive cytology results (IC3); microscopic (IIB1) and macroscopic (IIB2) pelvic spread; microscopic extrapelvic spread (IIIA1) and retroperitoneal lymph node (LN) metastasis without extrapelvic spread (IIIA2); and supraclavicular LN metastasis (IVA) and other distant metastasis (IVB). Survival outcomes associated with the current and reassigned stages were compared.
Overall, 870 patients were eligible for analysis. The median follow-up period was 45 months (range, 0 to 263 months). The 5-year overall survival rates (5YSRs) according to the current staging were 93.5% (IA), 82.5% (IC), 75.0% (IIB), 74.5% (IIC), 57.5% (IIIA), 54.0% (IIIB), 38.5% (IIIC), and 33.0% (IV). The 5YSRs of patients with IC1, IC2, and IC3 after sub-staging were 92.0%, 85.0%, and 71.0%, respectively (p=0.004). Patients who were reassigned to stage IIIA2 had a better 5YSR than those with extrapelvic tumors >2 cm (66.3% vs. 35.8%; p=0.005). Additionally, patients with newly assigned stage IVA disease had a significantly better 5YSR than those with stage IVB disease (52.0% vs. 28.0%; p=0.015).
The modified FIGO staging for ovarian carcinoma appears superior to the current staging for discriminating survival outcomes of patients with surgical spillage, retroperitoneal LN metastasis without extrapelvic peritoneal involvement, or distant metastasis to supraclavicular LNs.
PMCID: PMC3805916  PMID: 24167671
Lymph node metastasis; Ovarian cancer; Stage reassignment; Supraclavicular lymph node metastasis; Surgical spillage
25.  Feasibility, acceptability and preferences for intraperitoneal chemotherapy with paclitaxel and cisplatin after optimal debulking surgery for ovarian and related cancers: an ANZGOG study 
Journal of Gynecologic Oncology  2013;24(4):359-366.
Intraperitoneal (IP) chemotherapy in women with optimally debulked stage III ovarian cancer has been reported to prolong overall survival, but has not been widely adopted due to concerns about its toxicity, inconvenience and acceptability to patients. The purposes of this study were to determine the regimen's feasibility, adverse events, catheter-related complications, progression-free survival, health-related quality of life (HRQL), and patients' preferences for IP versus intravenous (IV) chemotherapy.
We conducted a single arm, multi-center study of IP chemotherapy with IV paclitaxel 135 mg/m2 (D1) over 3 hours, IP cisplatin 75 mg/m2 (D2), and IP paclitaxel 60 mg/m2 (D8) for 6 cycles in women with optimally debulked stage III ovarian or related cancers.
Thirty-eight eligible patients were recruited from 12 sites between July 2007 and December 2009. Seventy-one percent (n=27) completed at least 4 cycles and 63% (n=24) completed all 6 cycles. Grade 3 or 4 adverse events included nausea (n=2), vomiting (n=2), abdominal pain (n=2), and diarrhea (n=1), but not febrile neutropenia, neurotoxicity, or nephropathy. There were no treatment-related deaths. Catheter-related complications were the most frequent cause of early discontinuation of treatment (16 patients, 21%). Apart from neurotoxicity HRQL which worsened over time, HRQL was stable or improved with time. Most patients (≥50%) judged moderate benefits (e.g., an extra 6 months survival time or a 5% improvement in survival rates) necessary to make IP chemotherapy worthwhile.
IP chemotherapy was feasible, tolerable, and most participants considered moderate survival benefits sufficient to warrant the adverse effects and inconvenience.
PMCID: PMC3805917  PMID: 24167672
Chemotherapy; Decision-making; Ovarian neoplasms; Peritoneal infusions; Quality of life

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