Reuse of carboplatin and paclitaxel in patients with relapsed endometrial cancer--the British Columbia Cancer Agency experience

ObjectiveTo evaluate the efficacy of reusing carboplatin and taxol in women with relapsed endometrial cancer.MethodsRetrospective analysis of our database of newly diagnosed high-risk patients with endometrial cancer treated with carboplatin–paclitaxel at diagnosis, with subsequent relapse for the period of 1995–2007.Results111 patients of 200 relapsed. They had either endometroid or papillary serous histologies. Strategies utilized upon first relapse were: no treatment (n = 33), surgery (n = 4), hormones (n = 8), irradiation (n = 14) and chemotherapy (n = 52). Carboplatin and paclitaxel was reused in 31 (60% of 52 retreated with chemotherapy or 29% of the total cohort of 111). There was no statistically significant difference in stage at diagnosis or grade at diagnosis between those retreated with chemotherapy or not or with carboplatin–paclitaxel versus another regimen. The patients retreated were a selected subgroup as only those with initial response or treated adjuvantly were offered carboplatin–paclitaxel. CR or PR were achieved in 8 (42%) patients with endometroid type cancer. In the papillary serous group 6 (50%) had CR or PR. Median PFS from first relapse was 8 months for endometroid and 9 months for papillary serous histology. OS was 15 months and 26 months respectively from first relapse.ConclusionCarboplatin–taxol regimen is an efficacious treatment. Due to the patient selection these outcomes reported are likely to be an overstatement of what could be achieved in practice.     

A retrospective assessment of outcomes of chemotherapy-based versus radiation-only adjuvant treatment for completely resected stage I-IV uterine carcinosarcoma

PurposeTo determine the progression-free survival (PFS) and overall survival (OS) in a cohort of patients who received either platinum-based chemotherapy with or without radiation therapy (pelvic or WAI), or RT alone.MethodsMemorial Sloan-Kettering Cancer Center (MSKCC) electronic medical records from 8/1/1995 to 10/3/2007 were reviewed for patient age, diagnosis date, type of primary surgery, residual disease at the completion of primary surgery, FIGO stage, treatment details, dates of progression and death, and site(s) of first recurrence. PFS and OS by stage (I/II v III/IV) and by treatment type (chemotherapy with or without RT v RT alone) were determined using landmark analyses 8 weeks after surgery. Patients who received chemotherapy with or without RT (pelvic or abdominal) or RT alone (pelvic or abdominal) were included in the analysis. Both groups were allowed to have received intravaginal radiation therapy (IVRT).ResultsForty-nine patients met study criteria. Thirty-eight/49 patients received chemotherapy: 23/38 (60.5%) received paclitaxel-carboplatin; 7/38 (18.4%) received ifosfamide-platinum; 8/38 (21.0%) received other chemotherapy. FIGO stage was: I = 15 (31%); II = 5 (10%); III = 21 (43%); IV = 8 (16%). Three-year PFS for the entire cohort was 24%. Three-year OS for the entire cohort was 60%. Three-year median PFS time for the entire cohort was 15 months (95% CI: 11–25 months). Three-year median OS time for the entire cohort was 67 months (95% CI: 23–89 months). Three-year PFS for stages I–II was 43% v 14% for stages III–IV (HR = 1.98 [0.9–4.33]); P = 0.082. Three-year OS for stages I–II was 68% v 55% for stages III–IV (HR = 1.26 [0.47–3.41]); P = 0.648. Three-year PFS for chemotherapy with or without RT was 35% v 9% for RT alone (HR = 1.74 [0.79–3.85]); P = 0.164. Three-year OS for chemotherapy with or without RT was 66% v 34% for RT alone (HR = 2.02 [0.77–5.33]); P = 0.146.ConclusionsOur study corroborates GOG 150 results, and shows that paclitaxel-carboplatin appears to be an efficacious adjuvant chemotherapy regimen for completely resected uterine carcinosarcoma. The role of adjuvant RT in addition to chemotherapy warrants further investigation.     

Associations between p53 overexpression and multiple measures of clinical outcome in high-risk, early stage or suboptimally-resected, advanced stage epithelial ovarian cancers A Gynecologic Oncology Group study

ObjectiveThe Gynecologic Oncology Group (GOG) performed a detailed analysis of p53 overexpression in previously-untreated women with invasive early or advanced stage epithelial ovarian cancer (EOC).MethodsWomen were eligible for the study if they provided a tumor block for translational research and participated in either GOG-157, a randomized phase III trial of three versus (vs.) six cycles of paclitaxel + carboplatin in high-risk, early stage EOC, or GOG-111, a randomized phase III trial of cyclophosphamide + cisplatin vs. paclitaxel + cisplatin in suboptimally-resected, advanced stage EOC. The N-terminal DO-7 p53 antibody was used to examine the expression of the major normal and mutant p53-isoforms. p53 overexpression was defined as ≥ 10% tumor cells exhibiting nuclear staining.Resultsp53 was overexpressed in 51% (73/143) and 66% (90/136) of cases in the GOG-157 and GOG-111 cohorts, respectively. In the GOG-157 cohort, p53 overexpression was not associated with any clinical characteristics or overall survival (OS) but was associated with worse progression-free survival (PFS) (logrank test: p = 0.013; unadjusted Cox modeling: p = 0.015). In the GOG-111 cohort, p53 overexpression was associated with GOG performance status (p = 0.018) and grade (p = 0.003), but not with age, stage, cell type or with tumor response and disease status after primary chemotherapy, PFS or OS. Adjusted Cox regression modeling demonstrated that p53 overexpression was not an independent prognostic factor for PFS or OS in either cohort.Conclusionsp53 overexpression assessed by DO-7 immunostaining is common in early and advanced stage EOC, but has limited prognostic value in women treated with surgical staging and platinum-based combination chemotherapy.     

Comparison of laparoscopy and laparotomy for endometrial cancer

ObjectiveTo compare the safety and efficacy of laparoscopy and laparotomy on clinical outcomes among patients with endometrial cancer.MethodsEligible randomized controlled trials (RCTs) conducted between 1966 and June 2010 were analyzed by meta-analysis.ResultsEight RCTs were included, with 3599 patients in total. No significant difference was observed between laparoscopy and laparotomy in overall (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.50–1.82; P = 0.892), disease-free (OR, 0.96; 95% CI, 0.50–1.82; P = 0.892), or cancer-related (OR, 0.90; 95% CI, 0.27–3.08; P = 0.871) survival. More intraoperative complications (OR, 1.33; 95% CI, 1.03–1.73; P = 0.030), fewer postoperative complications (OR, 0.59; 95% CI, 0.46–0.75; P < 0.001), longer operative time (standardized mean difference [SMD], 0.80; 95% CI, 0.46–1.15; P < 0.001), lower blood loss (SMD, –2.29; 95% CI, –3.67 to ? 0.91; P = 0.001), and shorter hospital stay (SMD, –2.60; 95% CI, –3.47 to ? 1.72; P < 0.001) were associated with laparoscopy. There was no significant difference between the groups in pelvic (SMD, 0.22; 95% CI, –0.03 to 0.48; P = 0.086) or para-aortic (SMD, 0.54; 95% CI, –0.04 to 1.11; P = 0.067) lymph node yield.ConclusionLaparoscopy has short-term advantages and seemingly equivalent long-term outcomes and, in experienced hands, might be a feasible alternative to laparotomy for endometrial cancer.     

Uterine adenosarcoma: An analysis on management,outcomes, and risk factors for recurrence

ObjectivesUterine adenosarcoma is a rare malignancy with little data on optimal management. We aimed to clarify the impact of adjuvant therapy in patients with uterine adenosarcoma and identify risk factors for recurrence and death.MethodsWe performed a retrospective review of patients undergoing primary evaluation and treatment for uterine adenosarcoma at a single institution from July 1982 through December 2011. Univariate and multivariate analyses were used to identify prognostic factors for progression-free survival (PFS) and overall survival (OS).ResultsWe identified 100 patients with uterine adenosarcoma, and 74 patients met the inclusion criteria. On multivariate analysis, sarcomatous overgrowth (SO) and lymphovascular space invasion (LVSI) were predictors of worse PFS and OS. Median PFS and OS were 29.4 and 55.4 months for patients with SO, compared to 105.9 and 112.4 months for patients without SO (PFS HR 2.58, 95% CI 1.37–4.84, p = 0.003; OS HR 2.45, 95% CI 1.26–4.76, p = 0.008). Among patients with stage I disease, 17 of 22 patients (77%) with SO and 8 of 37 patients (22%) without SO had a recurrence (p < 0.001). Among patients with stage I disease with SO, adjuvant therapy appeared to be associated with longer PFS and OS, but these differences were not statistically significant (PFS, 46.7 vs. 29.4 months, p = 0.28; OS, 97.3 vs. 55.4 months, p = 0.18).ConclusionIn patients with uterine adenosarcoma, the presence of SO or LVSI confers a higher risk of recurrence. We did not identify an optimal treatment strategy for patients with SO, but adjuvant therapy may be associated with prolonged PFS.     

The outcome and efficacy of adjuvant chemotherapy alone in patients with stage IIIA endometrial carcinoma with solitary adnexal involvement: A retrospective single-institution study

ObjectivesThe appropriate adjuvant therapy for patients with endometrial carcinoma with solitary adnexal involvement is unclear. We conducted a retrospective single-institution study to evaluate the outcome and efficacy of adjuvant chemotherapy alone in this population.MethodsAll patients with endometrial carcinoma who received primary surgical treatment between January 1999 and May 2010 were reviewed. The patients who were diagnosed with stage IIIA disease based only on isolated adnexal involvement and treated with surgical procedures followed by adjuvant chemotherapy alone were included. Demographic, clinicopathologic, treatment and outcome data were collected. Recurrence and survival were analyzed.ResultsAmong 1453 reviewed patients, 67 patients were identified. The median age was 48 years. All patients were treated with platinum-based adjuvant chemotherapy, with the majority (36/67, 53.7%) receiving paclitaxel plus carboplatin. The total number of cycles of chemotherapy administered was 305 (median four cycles/person). Most of the chemotherapy related toxicities were mild or moderate. The median follow-up time was 76 months. Eight patients experienced recurrence. The majority of initial relapses were distant (7/8, 87.5%), characterized by liver metastases (3/8, 37.5%). The 5-year disease-free survival (DFS) and overall survival (OS) rates were 89.6% and 91.9%, respectively. Multivariate analysis confirmed that grade 3 tumor was an independent predictor of worse DFS and OS (HR = 5.19, P = 0.048; HR = 6.55, P = 0.037, respectively).ConclusionPatients with stage IIIA endometrial carcinoma with solitary adnexal involvement have favorable outcomes. Adjuvant chemotherapy alone may be effective and feasible for these patients.     

Twenty-year review of radiotherapy for vaginal cancer: an institutional experience

ObjectiveTo evaluate clinical outcome, prognostic factors and chronic morbidity with radiotherapy for vaginal cancer treatment.Materials and methods68 patients with vaginal cancer treated by radical or adjuvant radiotherapy (RT) were selected. Five with rare subtypes of histopathology and 8 with adenocarcinoma were excluded from this study. 76.4% of the remainder had early-stage diseases (stage I: 14, II: 28, III: 9, and IV: 4). The patients in the years from which they were treated were almost evenly distributed (1st 5 years: 13, 2nd: 14, 3rd: 16, and 4th: 12). There were four treatment groups: external beam radiotherapy (EBRT) alone (n = 18), brachytherapy (BT) alone (n = 4), EBRT and BT (n = 30), and surgery plus RT (n = 3).ResultsMedian follow-up was 50.3 months ranging from 3 to 213 months. 5-year overall survival (OS) was 55.6%, disease-specific survival (DSS) was 77.3%, disease-free survival was 74.2%, and local control was 87.7%. Independent prognostic factors for DSS and OS were tumor stage, site and size (p < 0.05). Late radiation toxicity was minimal in the bladder (4.6%) and bowel (4.6%). Vaginal morbidity was observed in 35 patients (63.6%). It was lowest in the BT alone (0%), and highest in the EBRT and BT group (82.1%), especially for those received more than 70 Gy (p = 0.05, Odds ratio = 4.64, 95% confidence interval: 1.01–21.65).ConclusionThis retrospective review suggested that tumor stage, site, and size were important prognostic factors in patients with vaginal cancer. Higher radiation dose was associated with more frequent vaginal toxicity.     

A multi-institutional cohort study of adjuvant therapy in stage I-II uterine carcinosarcoma

ObjectiveTo evaluate the impact of adjuvant post-operative therapy in women with early stage uterine carcinosarcoma.MethodsAfter IRB approval was obtained at all sites, a multi-center retrospective study of women with FIGO stage I–II uterine carcinosarcoma diagnosed from 1997 to 2007 was conducted. Post-operative treatment included observation (OBS), radiation (RT), chemotherapy (CT) alone or with RT (CT + RT). Data analyzed included demographic and pathologic factors, adjuvant therapy outcomes, and time-to-event information. The Kaplan–Meier method was used to estimate time-to-event functions. Cox regression modeling was used to examine the impact of selected covariates on progression free survival (PFS), and overall survival (OS).Results111 women were identified: 94 (85%) had stage I and 17 (15%) had stage II uterine carcinosarcoma. Forty-four women (40%) did not receive adjuvant therapy (OBS), 29 (26%) women had adjuvant CT, 23 (20%) women underwent RT and 15 (14%) women underwent RT + CT. Seventy-three patients were alive without disease and 38 had progressed or died at the close of data collection. In multivariate analysis, CT (p = 0.003), LVSI (p < 0.0001) and a pre-existing cancer (p = 0.004) were most predictive of PFS. LVSI was predictive of shortened OS (p = 0.01).ConclusionsIn women with FIGO stage I–II uterine carcinosarcoma, adjuvant chemotherapy is associated with improved PFS compared to radiation or observation alone. Ongoing clinical trials will clarify the role of chemotherapy in women with this disease.     

A phase I study of lapatinib in combination with carboplatin in women with platinum sensitive recurrent ovarian carcinoma

ObjectivesTo determine the maximum tolerated dose (MTD), spectrum of toxicities, clinical activity, and pharmacokinetics of carboplatin given in combination with lapatinib in women with a first recurrence of platinum sensitive epithelial ovarian carcinoma.MethodsPatients with measurable, platinum sensitive recurrent epithelial ovarian carcinoma were eligible. Cohorts of 3–6 patients were to receive up to 6 cycles of intravenous carboplatin AUC of 6 every 21 days in combination with escalating dosages of oral lapatinib (starting at a dose of 750 mg daily). Toxicity was assessed using NCI CTC for Adverse Events. Clinical response was monitored using RECIST criteria. Pharmacokinetic (PK) analysis was performed for the second cohort of patients.ResultsTwelve patients were enrolled. No dose limiting toxicity was noted. Two of 6 patients in the first cohort had unanticipated excessive delays in treatment due to non-dose limiting G3 neutropenia. Therefore, the study was modified to reduce the carboplatin dose in the second cohort. The median number of courses administered to the 11 evaluable patients in these two cohorts was 2.8 (range 1–6). Drug-related grade 3 or 4 toxicities included non-dose limiting G4 thrombocytopenia (n = 1), and non-dose limiting G3 neutropenia (n = 3). Of the 11 patients who received ≥ 1 course of therapy, 3 (27%) had a partial response, and 3 (27%) had stable disease. The pharmacokinetics of carboplatin were not significantly altered by concomitant administration of lapatinib.ConclusionsThis regimen of lapatinib and carboplatin was associated with unacceptable non-dose limiting toxicities, excessive treatment delays and limited clinical responses.     

Genetic polymorphisms in the Fas and FasL genes are associated with epithelial ovarian cancer risk and clinical outcomes

AimIn this study, we evaluated whether functional polymorphisms within the Fas and FasL genes were associated with the risk of developing epithelial ovarian cancer (EOC) and survival of patients with EOC.MethodsA case–control study was performed in 342 EOC patients and 344 control women. The genotypes of three promoter region polymorphisms (Fas ? 1377G/A, ? 670A/G and FasL ? 844T/C) were determined using ligase detection reaction-polymerase chain reaction (LDR-PCR). The clinical outcomes in 202 EOC patients were compared across genotypes.ResultsThe genotype frequencies of the FasL ? 844 T/C polymorphism were significantly different between the case and control groups (P = 0.034). Compared to the T/T and T/C genotypes, the C/C genotype significantly increased the risk of developing EOC (OR = 1.46, 95% CI = 1.08–1.99). The survival analysis showed that the Fas ? 1377G/A and ? 670A/G polymorphisms were related to prognosis in EOC patients. Compared with patients with the G/G genotype of the ? 1377G/A polymorphism, patients carrying the A allele had a shorter PFS and OS, as determined by univariate and multivariate analysis (HR = 1.81, 95% CI = 1.26–2.62 and HR = 1.86, 95% CI = 1.15–3.00, respectively). Similarly, Kaplan–Meier and Cox proportional hazard model analyses indicated that patients carrying the G allele of Fas ? 670A/G polymorphisms had shorter PFS and OS than those carrying the AA genotype (HR = 1.67, 95% CI = 1.15–2.42 and HR = 1.80, 95% CI = 1.10–2.94, respectively).ConclusionsFunctional polymorphisms in the Fas and FasL genes may be involved in epithelial ovarian cancer development and progression in northern Chinese women.     

Prognostic value of responsiveness of neoadjuvant chemotherapy before surgery for patients with stage IB2/IIA2 cervical cancer

ObjectiveTo evaluate the factors that might affect the putative survival benefit from pre-operative neoadjuvant chemotherapy (NAC) in patients with early stage bulky cervical cancer.MethodsA retrospective review for 304 patients with stage IB₂/IIA₂ cervical cancer was performed. Two groups were made according to pre-operative NAC or not: NAC group (n = 154) and primary surgery group (PST, n = 150). Recurrence risks and survival were analyzed.ResultsThe total response rate was 72.1%. For those NAC-responders, NAC decreased the ratio of lymphovascular space invasion (0 vs. 4.7%, p = 0.022; 0 vs. 3.3%, p = 0.052), deep stromal invasion (19.8% vs. 53.5%, p = 0.000; 19.8% vs. 29.3%, p = 0.08), lymph node metastasis (8.1% vs. 25.6%, p = 0.004; 8.1% vs. 17.3%, p = 0.031), and the need of adjuvant radiotherapy (5.5% vs. 30.2%, p = 0.000; 5.4% vs. 15.3%, p = 0.012), whereas improve 5-year PFS rate (94% vs. 86%, p = 0.041; 94% vs. 80%, p = 0.089) and 5-year OS rate (96% vs. 86%, p = 0.015; 96% vs. 82%, p = 0.05), as compared with non-responders and PST. Multivariate analysis suggested that the response to NAC is an independent prognostic factor of PFS (HR 0.221, 95% CI 0.048–1.022, p = 0.053) and OS (HR 0.126, 95% CI 0.016–1.000, p = 0.05); as compared, stage IIA disease demonstrates negative impact upon PFS (HR 4.778, 95% CI 1.490–15.317, p = 0.009) and OS (HR 4.142, 95% CI 1.258–13.639, p = 0.019).ConclusionResponsiveness of NAC before surgery might be an independent prognostic factor for the patients with early stage bulky cervical cancer.     

Preeclampsia,gestational hypertension and subsequent hypothyroidism

ObjectivesTo evaluate the effect of preeclampsia (PE) and gestational hypertension (GH) on subsequent hypothyroidism. Recent studies suggest that women with PE have increased risk for reduced thyroid function, but the association between PE and GH with overt hypothyroidism has not been examined.Study designTwo prospective population-based cohort studies, the Northern Finland Birth Cohorts 1966 and 1986, followed women who had PE (N = 955), GH (N = 1449) or were normotensive (N = 13531) during pregnancy. Finnish national registers were used to confirm subsequent hypothyroidism. Adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) estimated hypothyroidism risk when comparing women with PE or GH with normotensive women.Main outcome measuresPrimary hypothyroidism during follow-up of 20–40 years.ResultsThe subsequent prevalence of hypothyroidism was higher among women with PE (4.0%) and GH (4.5%) compared with normotensive women (3.5%), but the risk increase was not significant (aHR for PE 1.13, 95% CI 0.80–1.59 and aHR for GH 1.11, 95% CI 0.85–1.45).Subgroup analysis among nulliparous women revealed a significant association between late PE and subsequent hypothyroidism (aHR 1.82, 95% CI 1.04–3.19).Early or recurrent PE was not associated with hypothyroidism (aHR 0.93, 95% CI 0.46–1.81 and aHR 1.35, 95% CI 0.63–2.88, respectively).ConclusionsOverall, PE or GH during pregnancy was not significantly associated with subsequent hypothyroidism in Finnish women after 20–40 years of follow-up. However, late PE in nulliparous women was associated with a 1.8-fold increased risk of subsequent hypothyroidism, a finding that merits further study in other populations.     

The endoplasmic reticulum stress marker,glucose-regulated protein-78 (GRP78) in visceral adipocytes predicts endometrial cancer progression and patient survival

ObjectiveCurrently, accurately identifying endometrial cancer patients at high risk for recurrence remains poor. To ascertain if changes in the endoplasmic reticulum (ER) stress marker, glucose-regulated-protein-78 (GRP78) can serve as a prognosticator in endometrial cancer, we examined GRP78 expression in patient samples to determine its association with clinical outcome.MethodsA retrospective cohort study was conducted in endometrial cancer patients. Archived specimens of visceral adipocytes and paired endometrial tumors were analyzed by immunohistochemistry for GRP78 and another ER stress marker, C/EBP homologous protein (CHOP). Expression of these markers was correlated with clinico-pathological information and outcomes.ResultsGRP78 expression in visceral adipocytes was detected in 95% of the 179 endometrial cancer patients with analyzable visceral adipocytes. Within individual samples, 24% of adipocytes (range, 0–90%, interquartile range 18%–38%) exhibited GRP78 expression. High visceral adipocyte GRP78 expression positively correlated with advanced-stage disease (p = 0.007) and deep myometrial invasion (p = 0.004). High visceral adipocyte GRP78 expression was significantly associated with decreased disease-free survival (DFS) in multivariate analyses (hazard ratio 2.88, 95% CI 1.37–6.04, p = 0.005). CHOP expression paralleled the GRP78 expression in adipocytes (r = 0.55, p < 0.001) and in the tumor (p = 0.018).ConclusionsOur study demonstrates that the ER stress markers, GRP78 and CHOP, are elevated in endometrial cancer patients. Furthermore, GRP78 expression levels in visceral adipocytes from these patients were significantly correlated to disease stage and patient survival. Our results demonstrate, for the first time, that the GRP78 levels in endometrial cancer patients may be a prognosticator and aid with clinical risk stratification and focused surveillance.     

The “Leuven” paclitaxel/carboplatin weekly regimen in patients with recurrent ovarian cancer,a retrospective study

ObjectiveTo evaluate the “Leuven” weekly paclitaxel/carboplatinum (TC) regimen in recurrent ovarian cancer in a retrospective study.MethodsEighteen courses of paclitaxel (60 mg/m²) and carboplatinum (AUC 2.7) were administered weekly. Platinum-resistance was defined as progression during or within 6 months after platinum-based chemotherapy.ResultsSixty-three patients were included with a median number of prior treatment regimens of 4 (range 0–10). Forty-three patients were platinum resistant and 20 were platinum sensitive (14 intermediate sensitive and 5 sensitive). One patient in the platinum resistant group and 2 patients in the platinum sensitive group achieved complete remission, 15 patients in the platinum resistant and 5 patients in the platinum sensitive group achieved partial remission according to RECIST. In the entire patient population evaluable for response (n = 62), the median progression free survival (PFS) was 6.7 months; the median overall survival (OS) was 9.7 months. Median PFS was 6 months for the platinum resistant and 8 months for the platinum sensitive group. The median OS was 9 months in the platinum resistant and 11 months in the platinum sensitive group.Toxicity was mostly bone marrow related with neutropenia grade 3/4 in 67% and neutropenic fever in 6% of patients. Dose reduction was necessary in 24% of patients. Nausea, vomiting and fatigue were the most frequent non-hematological side effects.ConclusionWeekly paclitaxel and carboplatin is an effective regimen for patients with recurrence of ovarian cancer with a response rate of 37% in platinum resistant disease and a manageable toxicity profile.     

Value of endocervical margin and high-risk human papillomavirus status after conization for high-grade cervical intraepithelial neoplasia,adenocarcinoma in situ,and microinvasive carcinoma of the uterine cervix

ObjectiveThe aim of this study was to analyze clinico-pathologic factors and the optimal cut-off value of high-risk human papillomavirus (HR-HPV) viral load for predicting high-grade residual/recurrent disease after the conization in cervical intraepithelial neoplasia (CIN 2–3), adenocarcinoma in situ (AIS), and microinvasive carcinoma of the uterine cervix (MICA).MethodsWe retrospectively reviewed data from 701 patients with CIN 2–3, AIS, and MICA who underwent conization between September 2003 and June 2012. Receiver-operating characteristic curve analysis was used to find out the cut-off value of HR-HPV viral load for predicting residual/recurrent disease. Clinico-pathologic variables, including resection margin and HR-HPV status, were evaluated as possible predictors of residual/recurrent disease.ResultsAt a cut-off value of 1.16 RLU/CO for post-cone HR-HPV viral load, the sensitivity was 88.2% and the specificity was 98.3%. Multivariate analysis demonstrated that post-cone cytology (p = 0.001, OR = 83.808, 95% CI = 6.688–1050.232), endocervical margin status (p < 0.001, OR = 80.478, 95% CI = 7.421–872.732), and post-cone HR-HPV status (p < 0.001, OR = 79.660, 95% CI = 8.539–743.129) were significantly associated with residual/recurrent disease. The post-cone HR-HPV positivity was observed more in the patients who showed positive endocervical margin than in the patients with positive ectocervical margin (32.6% vs. 5.3%, p = 0.002).ConclusionsFollow-up using liquid based cytology in combination with HR-HPV test at 12 months after the conization, and not the early HR-HPV test, might be acceptable. Post-cone endocervical margin status combined with post-cone HR-HPV test is critical for predicting residual/recurrent disease and clinical management.     

Effects of parity and mode of delivery on urinary incontinence among postmenopausal women in Taiwan

ObjectiveTo investigate the association between the prevalence of urinary incontinence and parity or mode of delivery among Taiwanese women aged 60 years or older.MethodsBetween July 1999 and December 2000, a nationwide epidemiologic study was conducted in Taiwan among 2410 women selected by a multistage random sampling method. Face-to-face interviews with 1517 women were conducted. The relationship between the prevalence of urinary incontinence and the number of vaginal deliveries or number of cesarean deliveries was assessed by frequency and Pearson χ² test using a significance level of less than 0.05. Logistic regression was used to investigate the significance of dichotomous dependent variables.ResultsDecades ago, most Taiwanese women (1435 of 1511 respondents, 94.97%,) gave birth via vaginal delivery and the rate of cesarean delivery was low (20 of 1513 respondents, 1.32%). Parity (odds ratio [OR], 2.42; 95% confidence interval [CI], 0.87–6.71; P = 0.091), vaginal delivery (OR, 0.76; 95% CI, 0.39–1.47; P = 0.408), and cesarean delivery (OR, 1.47; 95% CI, 0.59–3.70; P = 0.409) did not increase the risk of urinary incontinence.ConclusionThere was no association between urinary incontinence and parity or mode of delivery among Taiwanese postmenopausal women decades after their first delivery.     

Sexual dysfunction risk and associated factors in young Peruvian university women

IntroductionInformation regarding sexual dysfunction risk among young Latin American women is limited.AimAssess female sexual dysfunction (FSD) risk and associated factors in young Peruvian university women.MethodsThis was a nested case-control study, using the Female Sexual Function Index (FSFI). Cases were defined as women with total FSFI scores at or below 26.55 (increased FSD risk). Demographic characteristics, gynecologic aspects, body mass index, mood disorders, substance abuse, and issues related to the couple, were also evaluated.Main Outcome MeasuresPrimary end point was assessment of FSD risk and associated factors.ResultsA total of 625 women were surveyed of which 409 (65.4%) were sexually active. The average total FSFI score was 27.2 ± 4.3. Overall, 39.9% were at higher risk for FSD. Multivariate analysis using a binary logistic regression model found that male premature ejaculation (odds ratios [OR] = 2.47, 95% confidence interval [CI]: 1.27–4.77), oral emergency contraception use (OR = 1.87, 95% CI: 1.04–3.38), good partner relationship (OR = 0.24, 95% CI: 0.12–0.49), and length of relationship (≥3 years; OR = 0.025, 95% CI: 0.013–0.05) were factors independently associated to a higher FSD risk (goodness of fit P = 0.39).ConclusionIn this young university female population, FSD risk was high and associated to male and female factors. Escajadillo-Vargas N, Mezones-Holguín E, Castro-Castro J, Córdova-Marcelo W, Blümel JE, Pérez-López FR, and Chedraui P. Sexual dysfunction risk and associated factors in young Peruvian university women.     

Combined chemotherapy and radiation improves survival for node-positive endometrial cancer

ObjectiveTo evaluate the clinical outcomes for women with node-positive endometrioid adenocarcinoma of the uterusMethodsRecords were reviewed for 66 patients with Stage IIIC endometrioid adenocarcinoma diagnosed between 1/1995 and 12/2009. Study inclusion required TAH, BSO and negative chest imaging. Papillary serous and clear cell histologies were excluded. Adjuvant treatment was external beam radiation (RT) alone in 18 patients (27%), combined chemotherapy and RT in 44 (67%), chemotherapy alone in 1 (2%), and no adjuvant therapy in 3 (5%). The median follow-up was 48 months.ResultsOf 66 patients, 56 (85%) had positive pelvic nodes only, 5 (8%) had positive para-aortic nodes only, and 5 (8%) had both. Of the 62 patients who received adjuvant RT, only 4 (6%) had an in-field recurrence, including 2 with residual disease after surgery. Disease-free (DFS) and overall (OS) survival rates at 5 years were 71% and 81%, respectively. By adjuvant treatment modality, 5-year DFS and OS rates were 63% and 67% for RT alone and 79% and 90% for combined modality therapy (p = 0.15 and p < 0.01). On multivariate analysis, combined modality therapy significantly improved DFS (HR 0.12, 95% CI 0.03–0.49, p < 0.01) and OS (HR 0.20, 95% CI 0.05–0.75, p = 0.02) compared to adjuvant RT alone.ConclusionsCompared to RT alone, combined modality therapy decreased recurrence and improved survival in patients with node-positive endometrioid adenocarcinoma of the uterus. In addition, external beam RT resulted in excellent local and regional control. Future studies are needed to define the optimal chemotherapy regimen, sequencing, and radiation fields.     

Treatment results of endometrial hyperplasia after prospective D-score classification: a follow-up study comparing effect of LNG-IUD and oral progestins versus observation only

ObjectivesThree different treatment options for endometrial hyperplasia were evaluated in a prospective long-time follow-up study, comparing effects of intrauterine levonorgestrel impregnated device (LNG-IUD), low oral dose of medroxyprogesterone acetate (MPA) and no treatment (observation only). To select patients with high probability for co-existing or future carcinoma we used the objective morphometric algorithm, D-score, stratifying patients into three different risk groups. As far as we know, this is the first prospective long-time follow-up study in which treatment recommendation and outcome is based on the D-score assessment.MethodsFrom a total of 370 patients initially diagnosed with endometrial hyperplasia from eight different hospitals in North Norway, 258 were available for long-time follow-up. After D-score classification, one of three different treatment options was chosen: LNG-IUD, low oral dose of MPA or observation only. Follow-up controls were performed and biopsies taken in the local hospitals.ResultsAmong the 370 investigated cases with endometrial hyperplasia, only ten endometrial cancers were detected at the entrance of the study, all belonging to the high risk group (D-score < 0). No further cancers were detected during follow-up, irrespective of risk group. After 6 months treatment with LNG-IUD proved significantly superior to oral treatment (p = 0.001 for D-score > 1and p = 0.003 for D-score 0–1 groups) and observation only (p = 0.001 for D-score > 1 and p = 0.001 for D-score 0–1 groups). After 56 to 108 months the LNG-IUD proved significantly superior to oral treatment and to the observation group. Comparison of oral therapy to observation only showed no significant differences, neither after 6 months nor after long-time observation.ConclusionsLNG-IUD is the optimal treatment for endometrial hyperplasia. Outcome after oral low-dose MPA regimen is comparable to expectation.     

Non-steroidal anti-inflammatory drugs and endometrial cancer risk in the VITamins And Lifestyle (VITAL) cohort

ObjectiveChronic inflammation may be an important factor in the initiation and promotion of endometrial cancer. Use of non-steroidal anti-inflammatory drugs (NSAIDs), however, has been inconsistently associated with endometrial cancer risk.Methods22,268 female residents of western Washington State, ages 50–76, completed a baseline questionnaire in 2000–2002 and reported on their use of individual NSAIDs over the past 10 years. Use was categorized as none, low (< 4 days/week or < 4 years), and high (≥ 4 days/week and ≥ 4 years). Over 9 years of follow-up, 262 incident invasive endometrial cancers were identified. Multivariable proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI).ResultsRelative to non-use, high use of aspirin was inversely associated with endometrial cancer risk (HR 0.64, 95% CI: 0.41–1.01; P trend = 0.03). Findings were stronger for regular-strength than low-dose aspirin. High use of non-aspirin NSAIDs (HR 1.15, 95% CI: 0.68–1.95), including ibuprofen (HR 1.29, 95% CI: 0.73–2.28), and naproxen (HR 1.08, 95% CI: 0.39–2.95) was not associated with risk. In subgroup analyses, findings for aspirin were strongest for cancers of endometrioid histology and were restricted to non-smokers.ConclusionsThis study provides additional evidence that use of aspirin, but not non-aspirin NSAIDs, may reduce the risk of endometrial cancer, especially in estrogen-mediated cases; however additional prospective studies with high-quality measurement of NSAID use are needed. Aspirin should continue to be examined as a potential agent for cancer chemoprevention.