A longitudinal study to explore unmet care needs, social support, and hope of women with gynecological cancer.

The experience of a life-threatening illness, such as cancer, can have an array of health impacts and social and psychological well-being can be compromised. This study compared differences in unmet care needs, social support, and hope of Taiwanese women with either newly diagnosed (n = 72) or recurring (n = 39) gynecological cancer at baseline (T0) and three follow-up surveys every 2 months (T1; T2; T3). Sociodemographic questions and three standardized self-administered questionnaires were used. The generalized estimating equations (GEE) method was used to analyze data. Women with recurrent cancer reported higher levels of care needs and lower levels of hope than those with a primary diagnosis. Significant positive correlations between social support and hope scores were observed for women with recurring cancer at T1 and T2. However, these women reported less hope at T3 compared to those with a primary diagnosis. Routine assessment of women's care needs related to their medical condition and provision of different kinds of support can aim to improve well-being and their hope for the future.

Longitudinal perceptions of the side effects of chemotherapy in patients with gynecological cancer.

PURPOSE: This study aimed to assess the incidence and difference of side effects among six courses of chemotherapy (C/T) in gynecological cancer patients. METHODS: The study period was from Sep. 2010 to Dec. 2011 at the Kaohsiung Veterans General Hospital in Taiwan. The treating protocols, courses, and drugs of C/T in patient were considered according to the different malignant cancers and clinical conditions. The patient data of age, marriage status, education, religion, and experiences of C/T were collected. The patients' or their families' reported side effects of C/T were recorded daily from the beginning of C/T to the 10th day after C/T in each cycle and every course of C/T. RESULTS: Total 89 patients enrolled into the study received total 450 courses of C/T. The mean age was 54.52 ± 11.02. Ovarian cancer was the most common malignant disease (64.0%). The most often combination of drugs used was Taxol and carboplatin (40.9%). Patients complained peripheral numbness of limbs, with the highest incidence of 58.6%. The side effects with incidence about 50% were decreased fatigue (55.0%) and hair loss (49.9%). Other side effects with different levels of incidence were also noticed, such as lack of appetite, changes in taste, and muscle ache. The incidences of peripheral limb numbness and hair loss were increased with following courses of C/T. The high incidence of fatigue did not show variation between different courses of C/T. CONCLUSION: This study revealed the incidence of side effects and occurrence timing during C/T in patients with gynecological cancer. These data provide substantial information to patients and their families to understand the potential side effects of C/T courses, which might increase their compliance in receiving adjuvant C/T. Relieving the side effects in C/T would be important to improve their quality of daily life and treatment willingness.

Assessing the risk of clinical and pathologic factors for relapse of borderline ovarian tumours.

The objective of this study was to identify clinical and pathologic factors that are significant to relapse in borderline ovarian tumours (BOT). All patients with BOTs from 1997 to 2012 in our institute were identified. 115 patients were included in the study. The Cox proportional hazards model was used to identify significant factors. The median age was 42 years (range 14-85 years). The majority of the patients were at FIGO stage I (88.7%), and most of the patients had mucinous histology (66.1%), reflecting the predominant distribution of mucinous BOTs in East Asia. The median follow-up was 3.3 years (range 0-4.1 years). Twelve patients (10.4%) relapsed and two died consequently. Advanced stage, invasive implants and restaging surgery were significant factors of recurrence. Serous tumours had slightly higher risk than mucinous tumours, but the difference was not significant. As the study was performed in an area where mucinous BOTs are predominant, the results may complement current literature on BOT management.

A randomized trial comparing concurrent chemoradiotherapy with single-agent cisplatin versus cisplatin plus gemcitabine in patients with advanced cervical cancer: An Asian Gynecologic Oncology Group study.

OBJECTIVE: A recent randomized trial demonstrated that concurrent chemoradiotherapy (CCRT) with weekly cisplatin and gemcitabine, followed by two adjuvant cycles of cisplatin and gemcitabine improved survival for advanced cervical cancer patients. An Asian Gynecologic Oncology Group (AGOG) study was designed to determine whether only adding gemcitabine in the chemoradiation phase without adjuvant chemotherapy could improve survival. METHODS: Between March 2009 and March 2013, 74 eligible patients with International Federation of Obstetrics and Gynecology stage III/IVA cervical cancer or stage I/II with positive pelvic/para-aortic nodal metastasis were enrolled. Thirty-seven patients were randomized to arm C (weekly cisplatin 40mg/m(2)) and 37 patients were randomized to arm CG (weekly cisplatin 40mg/m(2) and gemcitabine 125mg/m(2)), for six cycles. Six eligible patients were excluded before the beginning of treatment. RESULTS: An interim analysis showed superimposable progression-free (PFS) and overall survival (OS), a decision of closing accrual was made. A 3-year PFS was similar in both arms (arm C 65.1% vs. arm CG 71.0%, p=0.71), and a 3-year OS was 74.1% in arm C vs. 85.9% in arm CG (p=0.89), but crossed over at 5years. Grade 2-4 hematological toxicities, including neutropenia (p=0.028) and thrombocytopenia (p=0.001), were more frequent in arm CG than arm C. CONCLUSIONS: Despite limitation in power, it suggests that only adding gemcitabine at the CCRT phase does not provide substantially superior results, but treatment toxicities could increase. Further studies are required to determine the role of post-CCRT adjuvant chemotherapy in advanced cervical cancer.

Primary treatment and prognostic factors of carcinosarcoma of the ovary, fallopian tube, and peritoneum: a Taiwanese Gynecologic Oncology Group Study.

OBJECTIVE: This study aimed to determine the clinical prognostic factors involved in carcinosarcoma of the ovary, fallopian tube, and peritoneum. MATERIALS AND METHODS: This retrospective study was undertaken by the Taiwanese Gynecologic Oncology Group. The retrieved clinical data included demographic characteristics, medical disease, tumor status, extent of surgery, and adjuvant chemotherapy. RESULTS: In total, 63 patients with carcinosarcoma of the ovary, fallopian tube, and peritoneum were identified. Sixty-one patients with complete data were enrolled for further data analysis. The mean follow-up period was 1.0 year, and the mean overall survival was 15.4 months. By log-rank tests, age, menopausal status, parity, hypertension, diabetes, primary tumor size, para-aortic lymph node metastasis, pretreatment CA-125, preceding diagnostic surgery, hysterectomy, lymphadenectomy, other surgeries, and paclitaxel use were not predictive of overall survival.Omentectomy, no gross residual implants after surgery, platinum treatment, and no pelvic lymph node metastasis had a trend toward better survival. Early diagnosis at stage I and cisplatin/ifosfamide regimen were significant associated with a better overall survival in log-rank and simple Cox regression tests. Bilateral ovarian tumors and metastatic tumors larger than 2 cm were significantly associated with a poorer overall survival. CONCLUSIONS: Early diagnosis at stage I, unilateral ovarian tumor, metastatic tumors less than 2 cm, and cisplatin/ifosfamide regimen were predictive of a better survival.Omentectomy and complete debulking surgery also showed a trend toward better survival. Thus, these treatment strategies should be applied in patients with carcinosarcoma of the ovary, fallopian tube, and peritoneum.

A long-term follow-up study of 176 cases with adult-type ovarian granulosa cell tumors.

OBJECTIVE: Because of rarity, indolent clinical course, and of most importance, small sample size studies of previous ovarian granulosa cell tumors (GCTs), this study was conducted to report the clinical characteristics and long-term outcomes of 176 pathologically confirmed GCTs. METHODS: Between 1984 and 2010, we retrospectively evaluated 176 patients from multiple medical centers in Taiwan. RESULTS: The mean age at the diagnosis was 46 years and nearly half of the patients (45.7%) were in their fourth or fifth decades of life. The most common symptoms included abdominal pain (28.5%), followed by irregular menstruation (16.7%). The mean tumor size was 10.4 cm. The stage distribution at diagnosis was stage I in 77.8% of patients, stage II in 5.1%, stages III-V in 6.1%, and unknown in 11% of patients. The median follow-up period was 60.7 months. The recurrence rate was 21%. The overall 5- and 10-year survival rates were 96.5% and 94.1%, respectively. In univariate analysis, initial stage, presence of residual tumor after initial surgery, need for adjuvant chemotherapy, and tumor size were associated with disease recurrence. In the multivariate analysis, only the presence of residual tumor after initial surgery and tumor size were significantly associated with recurrence. CONCLUSIONS: The outcomes of patients with GCTs were good, with nearly to 95% of patients surviving 5 and 10 years. The prognosis was related to initial stage, presence of residual tumor after initial surgery, and tumor size (>13.5 cm). Different surgical methods and/or adjuvant therapy appear not to affect the outcome.

Comparison of FDG-PET/CT for Cancer Detection in Populations With Different Risks of Underlying Malignancy.

Background/Aim: Whole-body positron-emission tomography/computed tomography with the glucose analog 2-[ 18 F]fluoro-2-deoxy-D-glucose (FDG-PET/CT) has been used to screen examinees for underlying malignancy in many countries. The aim of this study was to compare the potential value of FDG-PET/CT application in asymptomatic individuals with those with suspected malignancy. Patients and Methods: A total of 9,408 examinees underwent whole-body FDG-PET/CT at our hospital from July 2006 to August 2013. Three thousand and seven hundred asymptomatic individuals and 848 individuals with laboratory and clinical/radiologicaI suspicion of malignancy who had undergone FDG-PET/CT for cancer screening were recruited. The final confirmation of cancer and outcomes were based on a pathological report and continuous follow-up. Results: Forty-five out of 3,700 asymptomatic individuals (1.2%) had proven malignancy, and 42 of them (93.3%) were found by FDG-PET/CT. Two hundred and twelve out of 848 with suspected malignancy (25%) had proven malignancy, and 196 of them (92.5%) were detected by FDG-PET/CT. Most of these cancers in asymptomatic individuals were clinically at an early stage. The discovery rate in asymptomatic individuals and those with suspected malignancy was 1.1% and 23.1%, respectively. The overall survival of patients with cancer diagnosed with PET/CT was higher than those with suspected malignancy (78.6% vs. 48.5%, p<0.001). Patients with a resectable lesion, early-stage disease, and lower maximal standardized uptake value had significantly better survival than those without. Conclusion: FDG-PET/CT is useful in the early diagnosis of cancer and thus might improve the survival rates of these patients. Considering the costs and risk of radiation exposure, it would be better used as a priority in patients with laboratory and clinical/radiologic suspicion of malignancy.

Overexpression of wild type or a Q311E mutant MB21D2 promotes a pro-oncogenic phenotype in HNSCC.

Cadherin-mediated cell-cell contacts regulated by intracellular binders play critical roles in tissue homeostasis and tumorigenesis. Here, we screened mutational profiles of 312 annotated genes involved in cadherin binding in human squamous cell carcinomas and found MB21D2 to carry a unique recurrent Q311E mutation. MB21D2 overexpression was also frequently found in head and neck cancer (HNSCC) and was associated with poor clinical outcomes. Cell-based characterizations revealed pro-oncogenic roles for MB21D2 wild-type (WT) and its Q311E mutant (Q311E) in cell proliferation, colony formation, sphere growth, and migration/invasion by promoting epithelial-mesenchymal transition. Conversely, MB21D2 knockdown in MB21D2-overexpressing cells resulted in cell growth arrest and apoptosis. Xenograft tumor models with Q311E-expressing cells formed larger and more aggressive lesions, compared to models with WT-MB21D2-expressing cells or an empty vector. Transcriptome and protein interactome analyses revealed enrichment of KRAS signaling by MB21D2 expression. Immunoblotting confirmed RAS elevation, along with upregulation/phosphorylation of PI3K, AKT, and CREB. Blocking RAS signaling in MB21D2-expressing cells by manumycin significantly reduced cell growth and survival. Our study thus defined RAS signaling-dependent pro-oncogenic roles for MB21D2 overexpression and Q311E MB21D2 expression in HNSCC development.

Long-term compliance of vaginal pessaries: Does stress urinary incontinence matter?

Vaginal pessary treatment for pelvic organ prolapse (POP) is relatively safe and cost-effective. Since long-term use is an important key to keep the benefit of pessary treatment, we would like to investigate the factors which might affect the compliance of vaginal pessaries. In this retrospective study, 65 women were included, and we found poor compliance in women with severe stress urinary incontinence (SUI) after reduction (1-hour pad test >10 gm vs ≦10 gm, 57.1% vs. 84.3%, P = .027). Besides, women younger than 60 years-old also had poor compliance (age ≦60-year-old vs >60-year-old, 58.3% vs 83.0%, P = .04). Other factors such as POP stage, history of hysterectomy, and types of pessaries, did not show significant influence on the long-term compliance in this study. Therefore, to evaluate the severity of SUI after reduction before providing pessary treatment is important to predict long-term compliance. Meanwhile, long-term pessary treatment seems to be more acceptable to elderly patients.

The short-term outcome of laser in the management of female pelvic floor disorders: Focus on stress urine incontinence and sexual dysfunction.

OBJECTIVE: Female pelvic floor disorders, including female stress urinary incontinence (SUI) or sexual dysfunction are notorious for affecting the quality of women's life. It is reported that laser therapy might result in collagen remodeling and improvement in tissue firmness. The study was conducted to evaluate the short-term outcome of female pelvic floor disorders treated by laser therapy. MATERIALS AND METHODS: Women with self-reported symptoms of female pelvic floor disorders (limited to SUI and sexual dysfunction) were included in the study. The participants were treated with the Er:YAG laser or the fractional microablative carbon dioxide (CO2) laser system. The therapeutic effect was focused on SUI symptoms and sexual dysfunction. RESULTS: There were 31 women underwent laser treatment, including 21 patients treated with Erbium:YAG laser and 10 treated with CO2 laser. In the Erbium:YAG laser group, International Consultation on Incontinence Questionnaire - Urinary Incontinence Short Form (ICIQ- SF) scores were dropped from 8.25 ± 5.66 to 5.00 ± 3.99 (P = 0.007); and in the CO2 laser group, scores were dropped from 11.11 ± 6.85 to 6.44 ± 4.25 (P = 0.035), contributing to the drop of ICI-Q-SF scores from 9.14 ± 6.08 to 5.45 ± 4.05 for all enrolled patients (P = 0.001). However, objective measure using pad test did not show a statistically significant difference between before and after treatment (from 3.20 ± 5.84 g to 1.54 ± 3.18 g, P = 0.224). Sexual dysfunction was improved in 13 patients (44.83%), but Female Sexual Function Index (FSFI) scores were not different before and after laser treatment (44.22 ± 23.36 vs. 44.09 ± 24.51, P = 0.389). CONCLUSION: Laser therapy either by Erbium:YAG laser or CO2 laser seemed to be useful for female pelvic floor disorders, especially on improvement of SUI symptoms; however, the effectiveness needs further confirmation.

Increased Risk of Intracranial Hemorrhage in Patients With Pregnancy-Induced Hypertension: A Nationwide Population-Based Retrospective Cohort Study.

Pregnancy-induced hypertension (PIH) may be a major predictor of pregnancy-associated intracranial hemorrhage (ICH). However, the relationship between PIH and long-term ICH risk is unknown.The objective of the study was to determine the association between PIH and ICH and to identify the predictive risk factors.Patients with newly diagnosed PIH were recruited from the Taiwan National Health Insurance Research Database. PIH patients were divided into gestational hypertension (GH) and preeclampsia groups. The 2 groups were separately compared with matched cohorts of patients without PIH based on age and date of delivery. The occurrence of ICH was evaluated in both cohorts. The overall observational period was from January 1, 2000 to December 31, 2013.Among the 23.3 million individuals registered in the National Health Insurance Research Database, 28,346 PIH patients, including 7390 with GH and 20,956 with preeclampsia, were identified. The incidences of ICH were increased in both groups (incidence rate ratio [IRR] = 3.72 in the GH group, 95% confidence interval [CI] 3.63-3.81, P < 0.0001 and IRR = 8.21 in the preeclampsia group, 95% CI 8.12-8.31, P < 0.0001, respectively). In addition, according to the results of stratification of follow-up years, both groups were associated with a highest risk of ICH at 1 to 5 years of follow-up (IRR = 11.99, 95% CI 11.16-12.88, P < 0.0001 and IRR = 21.83, 95% CI 21.24-22.44, P < 0.0001, respectively). After adjusting for age, parity, severity of PIH, number of PIH occurrences, gestational age, and comorbidities in the multivariate survival analysis using Cox regression model, age ≥30 years (hazard ratio [HR] 1.99, 95% CI 1.27-3.10, P = 0.0026), patients with preeclampsia (HR 2.18, 95% CI 1.22-3.90, P = 0.0089), multiple PIH occurrences (HR 4.08, 95% CI 1.85-9.01, P = 0.0005), hypertension (HR 4.51, 95% CI 1.89-10.74, P = 0.0007), and obesity (HR 7.21, 95% CI 1.58-32.84, P = 0.0107) were independent risk factors for the development of ICH among patients with PIH.Patients with PIH, especially those with older age, preeclampsia, and multiple PIH occurrences, may have an increased risk of developing ICH later in life.

Bisdemethoxycurcumin Inhibits Adipogenesis in 3T3-L1 Preadipocytes and Suppresses Obesity in High-Fat Diet-Fed C57BL/6 Mice.

Obesity is caused by excessive accumulation of body fat and is closely related to complex metabolic diseases. Adipogenesis is a key process that is required in adipocyte hypertrophy in the development of obesity. Curcumin (Cur) has been reported to inhibit adipocyte differentiation, but the inhibitory effects of other curcuminoids present in turmeric, such as demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC), on adipogenesis have not been investigated. Here, we investigated the effects of curcuminoids on adipogenesis and the molecular mechanisms of adipocyte differentiation. Among three curcuminoids, BDMC was the most effective suppressor of lipid accumulation in adipocytes. BDMC suppressed adipogenesis in the early stage primarily through attenuation of mitotic clonal expansion (MCE). In BDMC-treated preadipocytes, cell cycle arrest at the G0/G1 phase was found after initiation of adipogenesis and was accompanied by downregulation of cyclin A, cyclin B, p21, and mitogen-activated protein kinase (MAPK) signaling. The protein levels of the adipogenic transcription factors peroxisome proliferator-activated receptor (PPAR)γ and CCAAT/enhancer-binding proteins (C/EBP)α were also reduced by BDMC treatment. Furthermore, 0.5% dietary BDMC (w/w) significantly lowered body weight gain and adipose tissue mass in high-fat diet (HFD)-fed mice. The results of H&E staining showed that dietary BDMC reduced hypertrophy in adipocytes. These results demonstrate for the first time that BDMC suppressed adipogenesis in 3T3-L1 adipocytes and prevented HFD-induced obesity. Our results suggest that BDMC has the potential to prevent obesity.

Impact of adjuvant therapy on survival of patients with early-stage uterine papillary serous carcinoma.

PURPOSE: To determine the efficacy of adjuvant therapy in patients with early-stage uterine papillary serous carcinoma. METHODS AND MATERIALS: Data were collected on all surgically staged Stage I-II uterine papillary serous carcinoma patients. Statistical analyses were performed using the Kaplan-Meier and Cox proportional hazards regression methods. RESULTS: Of 68 patients, 50 had Stage I and 18 had Stage II disease; 35 underwent adjuvant treatment, including radiotherapy in 26, chemotherapy in 7, and combined RT and chemotherapy in 2. The remaining 33 were treated expectantly. The median follow-up was 56 months (range 1-173). The 5-year overall survival rate was 69%. Of 19 patients with disease limited to the endometrium, 10 received no additional therapy, 3 of whom developed recurrence. However, all 9 women who underwent adjuvant treatment remained free of disease. Patients receiving adjuvant therapy with chemotherapy or radiotherapy had a prolonged 5-year overall and disease-free survival compared with those who were treated expectantly (85% vs. 54%, p = 0.002 for overall survival and 85% vs. 49%, p = 0.01 for disease-free survival). In multivariate analysis, adjuvant therapy (p = 0.035) and the absence of lymphovascular space invasion (p = 0.001) remained as independent prognostic factors for improved survival. CONCLUSION: Adjuvant therapy with chemotherapy or radiotherapy improves the survival of women with early-stage uterine papillary serous carcinoma.

Differentiating between borderline and invasive malignancies in ovarian tumors using a multivariate logistic regression model.

OBJECTIVE: The objective of this study was to build a model to differentiate between borderline and invasive ovarian tumors. MATERIALS AND METHODS: We performed a retrospective study involving 148 patients with borderline or invasive ovarian tumors in our institute between 1997 and 2012. Clinical and pathologic data were collected. Logistic regression was used to build the model. RESULTS: The model was created based on the following variables (p < 0.05): menopausal status; preoperative serum level of cancer antigen 125; the greatest diameter of the tumor; and the presence of solid parts on ultrasound imaging. The sensitivity and specificity of the model were 94.6% [95% confidence interval (CI), 0.887-1] and 78.3% (95% CI, 0.614-0.952) for patients aged ≥ 50 years, and 76.0% (95% CI, 0.622-0.903) and 60.0% (95% CI, 0.438-0.762) for those aged < 50 years, respectively. The performance of the model was tested using cross-validation. CONCLUSION: Differentiation between borderline and invasive ovarian tumors can be achieved using a model based on the following criteria: menopausal status; cancer antigen 125 level; and ultrasound parameters. The model is helpful to oncologists and patients in the initial evaluation phase of ovarian tumors.

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.

Outcome of patients with recurrent adult-type granulosa cell tumors--a Taiwanese Gynecologic Oncology Group study.

OBJECTIVE: The aim of this study is to evaluate the long-term outcome of ovarian recurrent granulosa cell tumors (GCTs) in a large series of patients treated in Taiwanese Gynecologic Oncology Group (TGOG) centers and to define the prognostic parameters for survival. MATERIALS AND METHODS: A retrospective multi-institutional review of patients with recurrent ovarian GCTs treated in TGOG centers was conducted. The clinical and pathological characteristics, treatment, and outcomes of patients with ovarian recurrent GCTs were analyzed using Kaplan-Meier and Cox proportional hazards analyses to determine the predictors for survival. RESULTS: A total of 44 patients from 16 medical centers were identified between January 1994 and December 2010. The median disease-free survival (DFS), postrecurrence survival, and overall survival (OS) were 61.5 months (range, 3.7-219.3 months), 55.8 months (range, 4.6-193.7 months), and 115.3 months (range, 17.2-390.6 months), respectively. In multivariate analysis, DFS (> 61.5 months versus ≤ 61.5 months, hazard ratio (HR) 0.15, 95% confidence interval (CI) 0.03-0.78, p = 0.024) at the initial operation after diagnosis of relapse was the only predictor that correlated with OS. CONCLUSION: DFS after the initial operation was the only important predictor for overall survival in patients with recurrent GCTs, regardless of treatment, suggesting that the natural behavior of the tumor is a critical factor for patients with recurrent GCTs.

Triage of Atypical Glandular Cell by SOX1 and POU4F3 Methylation: A Taiwanese Gynecologic Oncology Group (TGOG) Study.

INTRODUCTION: Invasive procedures including loop electrosurgical excision, cervical conization, and endometrial sampling are often recommended when atypical glandular cells (AGC) are detected on Pap smear with unsatisfactory colposcopy. These invasive procedures may result in patient anxiety, increased medical expense, and increasing the risk of preterm delivery in subsequent pregnancies. This study was performed to assess methylation biomarkers in the triage of AGC on Pap smear for invasive procedures. METHODS: We conducted a multicenter study in 13 medical centers in Taiwan from May 2012 to May 2014. A total of 55 samples diagnosed "AGC not otherwise specified" (AGC-NOS) were included. All patients with AGC underwent colposcopy, cervical biopsy, endometrial sampling, and conization if indicated. Multiplex quantitative methylation-specific polymerase chain reaction (QMSPCR) was performed. Sensitivity, specificity, and accuracy were calculated for detecting CIN3+ and endometrial complex hyperplasia. RESULTS: In 55 patients with AGC, the sensitivity for methylated (m) SOX1m, PAX1 m, ZNF582m,PTPRRm, AJAP1m, HS3ST2m, and POU4F3m for detecting CIN3+ and endometrial complex hyperplasia lesions was 100, 86, 71, 86, 86, 57, and 100%; specificity was 67, 79, 85, 50, 52, 96, and 52%, respectively. Testing for high risk-HPV had a sensitivity of 57% and specificity of 75% for CIN3+ and endometrial complex hyperplasia lesions. CONCLUSION: Methylated (m) SOX1m and POU4F3m could be new methylation biomarkers for detection of CIN3+ and endometrial complex hyperplasia in AGC. Women with AGC and positive SOX1m / POU4F3m, colposcopy, cervical conization or endometrial sampling should be considered.

A longitudinal analysis with CA-125 to predict overall survival in patients with ovarian cancer.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Pterostilbene inhibits dimethylnitrosamine-induced liver fibrosis in rats.

Pterostilbene, found in grapes and berries, exhibits pleiotropic effects, including anti-inflammatory, antioxidant, and anti-proliferative activities. This study was conducted to investigate the effect of pterostilbene on liver fibrosis and the potential underlying mechanism for such effect. Sprague-Dawley rats were intraperitoneally given dimethyl n-nitrosamine (DMN) (10mg/kg) 3 days per week for 4 weeks. Pterostilbene (10 or 20mg/kg) was administered by oral gavage daily. Liver function, morphology, histochemistry, and fibrotic parameters were examined. Pterostilbene supplementation alleviated the DMN-induced changes in the serum levels of alanine transaminase and aspartate transaminase (p<0.05). Fibrotic status and the activation of hepatic stellate cells were improved upon pterostilbene supplementation as evidenced by histopathological examination as well as the expression of α-smooth muscle actin (α-SMA), transforming growth factor-ß1 (TGF-ß1), and matrix metalloproteinase 2 (MMP2). These data demonstrated that pterostilbene exhibited hepatoprotective effects on experimental fibrosis, potentially by inhibiting the TGF-ß1/Smad signaling.