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Aims Sexual dimorphism is a common trait in plants with sex separation, which could influence female and male functions differently. In a subdioecious population of Dasiphora glabra on the Qinghai-Tibet Plateau, we investigated sexual dimorphism of floral traits and their effects on pollinator visitation, pollen flow and seed production. We also examined differences in genome size of hermaphroditic and dioecious plants. Methods We examined sexual dimorphism in flower number, flower size, and pollen and ovule production in a subdioecious population of D. glabra. We compared pollinator visitation, pollen dispersal and seed production between sexes. We also examined the genome size of three sex morphs using flow cytometry. Important Findings The number of hermaphroditic plants was significantly more than that of male and female plants, and dioecious plants accounted for ca. 40% in the study population. Hermaphroditic plants produced significantly more flowers than male and female plants. Flower size of male flowers was significantly larger than that of female and hermaphroditic flowers. Male flowers did not produce more pollen grains than hermaphroditic flowers, but female flowers produced more ovules than hermaphroditic flowers. Flies were the most frequent flower visitors and preferred large flowers, but their movements between flowers did not show any preference to large flowers. Simulated pollen flows suggested that effective pollen transfer was generally low for both hermaphroditic and male flowers, corresponding to the low seed set of naturally pollinated flowers. DNA contents of male and female plants were ca. four times than those of hermaphroditic plants. These results suggest male and female individuals have undergone polyploidy events and thus are not compatible with hermaphroditic individuals. Sexual dimorphism in floral traits in relation to pollination of dioecious plants might show an advantage in female and male functions, but this advantage is masked largely by low effectiveness of pollen transfer.

Human papillomavirus (HPV) is the well‐established etiologic factor for cervical neoplasia. Cervical conization constitutes an effective treatment for high‐grade cervical intraepithelial neoplasia (HG‐CIN). We conducted an observational study for long‐term outcomes and HPV genotype changes after conization for HG‐CIN. Between 2008 and 2014, patients with newly diagnosed HG‐CIN before conization (surveillance new [SN] group) and those who had undergone conization without hysterectomy (surveillance previous [SP] group) were enrolled. HPV testing and Pap smear were performed periodically for the SN and SP (collectively S) groups. All other patients receiving conization for HG‐CIN during the study period were identified from our hospital database. Those eligible but not enrolled into our study were assigned to the non‐surveillance (non‐S) group. For the S group (n = 493), the median follow‐up period was 74.3 months. Eighty‐four cases had recurrent CIN Grade 2 or worse (CIN2+) (5‐year cumulative rate: 14.8%), of which six had invasive cancer. Among the 84 patients, 65 (77.4%) exhibited type‐specific persistence in the paired HPV results, whereas only 7 (8.3%) harbored new HPV types that belonged to the 9‐valent vaccine types. Among the 7397 non‐S patients, 789 demonstrated recurrent CIN2+, of which 57 had invasive cancer. The stages distribution of those progressed to invasive cancer in the non‐S group were more advanced than the S group (P = .033). Active surveillance might reduce the severity of those progressed to cancer. Because a majority of the patients with recurrent CIN2+ had persistent type‐specific HPV infections, effective therapeutic vaccines are an unmet medical need., What's new? High‐grade cervical intraepithelial neoplasia (HG‐CIN), a cervical carcinoma precursor, frequently is caused by high‐risk human papillomavirus (hr‐HPV) infection. HG‐CIN can be treated by cervical conization, though the procedure does not eradicate hr‐HPV, potentially enabling CIN recurrence. Here, in Taiwanese patients, investigation of HPV genotype changes in relation to HG‐CIN status after conization shows that 77.4 percent of patients with recurrent CIN 2 grade or worse (CIN2+) after conization had persistent type‐specific HPV infections. Vaccination against the remaining high‐risk HPVs prevented recurrent CIN2+ in only 8.3 percent of patients, revealing an unmet need for effective therapeutic vaccines.

Background/purpose: Ovarian clear cell carcinoma (OCCC) with recurrence/progression after treatment has dismal prognosis. We aimed to investigate the management and outcomes of such patients. Methods: OCCC patients who were treated between 2000 and 2013 with cancer recurrence or progression after primary treatment were analyzed. Univariate and multivariate analyses were used to identify the independent predictors of survival after recurrence (SAR) and cancer-specific survival (CSS). Results: A total of 64 patients experienced treatment failure (49 recurred after remission and 15 progressed without remission). The 5-year CSS rates of recurrent/progressive OCCC patients were 22.9% (progression group: median CSS 5.9 months [range, 0.8–25.2] vs recurrence group: 43.6 months [range, 7.1–217.8]; p 12 months (HR: 0.22–0.40, p = 0.001 and p = 0.023), CA125

Inverted organic light-emitting diodes (IOLEDs) have a bottom cathode, making them convenient to integrate with the preferred n-type active matrix OLED driving technologies. Furthermore, inverted OLEDs show much better air-stability compared with conventional OLEDs, due to the very reactive and sensitive of alkali doped electron injection layer (EIL) towards ambient oxygen and moisture. For inverted OLEDs, the bottleneck to limit their efficiency and stability is the interface at cathode/EIL and light emitting layer (EML)/charge transporting layer. In this paper, we have investigated the effect of different electron/hole transporting layers on the turn-on voltage, efficiency roll-off and power consumption of inverted orange OLEDs. We found that the device exhibits extremely-low efficiency roll-off and a significant lifetime improvement.

Shu-Han Chang,1 Ting-Chang Chang,1,2 Min-Yu Chen,1 Wei-Chun Chen,1,3 Hung-Hsueh Chou1,2 1Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital Linkou Medical Center, Taoyuan, Taiwan; 2Chang Gung University, College of Medicine, Taoyuan, Taiwan; 3Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital Keelung Branch, Keelung, TaiwanCorrespondence: Hung-Hsueh ChouDepartment of Obstetrics and Gynecology, Chang Gung Memorial Hospital Linkou Medical Center, #5 Fushing Street, Kwei-Shan, Taoyuan, 333, TaiwanTel +886-33281200Email ma2012@cgmh.org.twObjective: We aimed to investigate the effects of dinalbuphine sebacate (DNS), fentanyl-based patient-controlled analgesia (PCA), and conventional analgesia (CA) for pain management after laparotomy for gynecologic cancers.Methods: A total of 137 eligible patients who underwent laparotomy through a midline incision wound for gynecologic cancer between July 2019 and June 2020 were retrospectively evaluated. The patients were divided into three groups as follows: the intramuscular DNS, intravenous PCA, and CA groups. Postoperative pain (POP) intensity as measured with a numerical rating scale (NRS), total consumption of analgesics, and incidence of treatment-emergent adverse events were compared between the three groups.Results: The DNS group showed significant reduction in NRS pain intensity than the PCA and CA groups on day 1 (4.8 vs 6.2, p < 0.01 and 6.2, p < 0.05, respectively), day 2 (3.0 vs 4.7, p < 0.01 and 4.8, p < 0.001, respectively), day 3 (2.0 vs 3.9, p < 0.001 and 3.5, p < 0.001, respectively), day 4 (1.1 vs 3.1, p < 0.001 and 2.9, p < 0.001, respectively), and day 5 (0.7 vs 2.3, p < 0.001 and 2.4, p < 0.001, respectively). The total consumption of morphine equivalents per day was similar between the DNS and PCA groups (142.8 ± 7.3 mg vs 137.7 ± 70.0 mg, p = 0.8032) and lowest in the CA group (11.7 ± 30.7 mg, p < 0.0001). The overall safety profile was comparable between the DNS, PCA, and CA groups. The patients in the DNS group complained less of dizziness postoperatively than those in the PCA group (27% vs 47%) and had less nausea than those in the CA group (13% vs 33%).Conclusion: A single DNS injection was more effective for relieving POP than PCA and CA in the patients who had a longitudinal incision for gynecologic cancer surgery. DNS was well tolerated and had less adverse effects than PCA and CA.Keywords: dinalbuphine sebacate, postoperative pain, nalbuphine, PCA, laparotomy

To investigate outcomes and morbidity of patients undergoing secondary cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in recurrent ovarian cancer.Between April 2014 and January 2019, a total of 51 recurrent ovarian cancer patients receiving secondary CRS and HIPEC were retrospectively reviewed.Among the 51 patients, median peritoneal cancer index score was 13 (range 3-34), and completeness of cytoreduction (CC) score of 0/1 was achieved in 41 patients (78.8%). Regimen of HIPEC included cisplatin and paclitaxel in 39 (75%) cases. The median follow-up duration of survivors was 20.2 months. Sixteen (30.8%) patients remained free of recurrence after HIPEC. The median progression-free survival (PFS) and overall survival (OS) were 11.8 months and 34.5 months respectively. Multivariate analysis showed previous chemotherapylt;2 lines (HR 0.24, 0.11-0.52; p = 0.001), chemotherapy-free interval ≥6 months (HR 0.19, 0.09-0.37; p lt; 0.001) and CA125 lt; 35 U/mL before HIPEC (HR 0.133, 0.021-0.0832; p = 0.031) were good prognostic factors for PFS. CC0/1 was not significant in multivariate analysis. The most common grade 3/4 toxicity was anemia (17.3%), pleural effusion (11.5%) and renal insufficiency (5.7%). Patients with age ≥50, peritoneal carcinomatosis index (PCI) ≥ 11, operation time ≥10 h and diaphragm surgery had significantly higher incidence of pleural effusion.The current study showed adding HIPEC to secondary CRS might prolong PFS especially in patients with previous chemotherapylt;2 lines, chemotherapy-free interval ≥6 months and CA125 lt; 35 U/mL before HIPEC.

Objectives To analyze prevalence of HPV DNA, HPV genotype distribution, prognostic factors and long-term outcomes of vulvar carcinoma. Methods We retrospectively reviewed medical records of patients with vulvar carcinoma who received primary surgeries between 1985 and 2014 in a single institution. General polymerase chain reaction (PCR) SPF1/GP6+ followed by revert-blot detection was performed for human papillomavirus (HPV) genotyping. E6 type-specific PCR of the top-5 prevalent types was performed to reconfirm HPV-negative status. P16INK4a immunohistochemistry staining was performed. Univariate and multivariate analyses were performed to identify predictors of clinical outcomes of squamous cell carcinomas (SCCs). Results A total of 150 vulvar carcinoma patients eligible for analysis were retrieved. Medial follow up time was 71.4 months (0.2–341.8 months). One hundred and twenty-nine patients (86.0%) were diagnosed as SCC. In SCC specimens, HPV DNA sequences were detected in 56.6%, and 14.3% of non-SCC vulvar cancer (n = 21) were HPV positive. The leading 4 types were HPV16 (54.0%), HPV58 (15.8%), HPV52 (6.6%), and HPV18 (5.3%). HPV-positivity was associated with better 5-year cancer-specific survival (CSS) (P = 0.037). In multivariable analysis, older age (continuous, hazard ratio [HR] 1.06, 95% confidence interval [CI] 1.03–1.08, P Conclusion Advanced FIGO stage and older age were significant adverse predictors, while p16-positivity was a significant factor of better prognosis.

Purpose To define the optimal dose of paclitaxel combining cisplatin, as weekly neoadjuvant chemotherapy (NAC) for early-stage bulky squamous cell carcinoma of the uterine cervix. Methods A prospective trial was conducted for International Federation of Gynecology and Obstetrics stages IB2 and IIA2 cervical squamous cell carcinoma patients with magnetic resonance imaging or positron emission tomography-defined lymph node negative. Weekly fixed-dose cisplatin (40 mg/m) and 4-level dose escalation of paclitaxel (50, 60, 70, 80 mg/m) for 3 courses was given and followed by radical hysterectomy and pelvic lymph node dissection (RH-PLND) 14 to 28 days later. Postoperative adjuvant therapy was tailored according to pathologic response. Results No dose-limiting toxicity occurred. Twelve subjects were enrolled without reaching maximum tolerated dose, nor was any RH-PLND procedure delayed for >2 weeks. Pathologic response rate was 50% (complete in 2 and partial in 4). Paclitaxel dose level seemed unrelated to pathologic response. No subjects had grade ≥3 acute adverse events. Seven patients (58.3%) received postoperative radiotherapy or chemoradiation. Patients with human papillomavirus 16-negative tumor and aged 55 years and older had marginally higher risk (100%) of adjuvant radiotherapy or chemoradiation after NAC than those with human papillomavirus 16-positive or age less than 55 (P=0.081). With a median follow-up of 45.5 months, all 12 patients remained alive without disease. Conclusions Weekly paclitaxel and cisplatin NAC for 3 courses can be tolerated with excellent short-term outcome. With the caveat of small number of patients, this study supports future phase II trials of weekly paclitaxel and cisplatin NAC for 4 to 5 cycles.

本研究以期望價值理論為架構，進行國際數學與科學成就趨勢調查（TIMSS）2011 年臺灣八年級學生數學和科學成就之多層次結構方程式模型分析，瞭解學生層次（學生知覺教師期望、能力信念、實用價值、內在價值）及班級層次（班級知覺教師期望、班級能力信念、班級實用價值、班級內在價值）重要變項之影響力，並探究能力信念在學生知覺教師期望與數理成就之間的中介效果。本研究發現，學生層次和班級層次的模型結構並不相同，在學生層次的分析中，數學和科學的能力信念對學生學業成就的直接效果最大，而在數學與科學的班級層次分析中，班級能力信念皆對班級學業成就產生相當大的直接影響。此外，學生能力信念在學生知覺教師期望與數理成就之間扮演中介角色。最後依據研究結果提供建議，以供 實務應用及未來研究之參考。 On the basis of expectancy-value theory, multilevel structural equation models and trends in mathematics and science study 2011 data were applied to investigate the effects of the student-level variables (perception of teachers’ expectations, ability beliefs, utility values, and intrinsic values) and their respective class-level variables on math and science achievement, and to test the mediation effect of ability belief between students’ perception of teachers’ expectations and the math and science achievements of eighth-grade students in Taiwan. The study revealed the following results: (1) The student-level and class-level structures exhibited differences. (2) At the student level, students’ ability belief had the strongest effect on their math and science achievement; the class level of ability belief had a positive effect on math and science achievement. (3) Ability belief had a significant mediating effect between the perception of teachers’ expectations and math and science achievement. Finally, according to the results, some suggestions for practical applications and future research were introduced.

5540 Background: The objective of this study is to evaluate the safety and efficacy of adding bevacizumab to dose-dense adjuvant chemotherapy with bevacizumab maintenance after neoadjuvant chemotherapy (NAC) and interval debulking surgery (IDS) for stage III/IV ovarian, tubal, and primary peritoneal cancer. Methods: This phase II clinical trial using Simon's minimax two-stage design was conducted. At the first stage, 13 subjects were enrolled, and the trial would proceed to second stage if ≤3 subjects discontinued treatment for study-defined significant adverse events (AEs). Patients with stage III/IV ovarian, tubal, and primary peritoneal cancer deemed not feasible for primary cytoreductive surgery were enrolled after 3 to 4 cycles of NAC and IDS without disease progression. NAC could be either weekly paclitaxel (80mg/m2) (dose-dense) plus 3-weekly carboplatin (AUC5-6) or 3-weekly conventional schedule. After IDS, postoperative dose-dense adjuvant chemotherapy for 3 cycles at least (best to 6 cycles), and 3-weekly bevacizumab 15mg/kg was given since postoperative cycle 2. Further 3-weekly maintenance bevacizumab 15mg/kg was given intravenously for 17 cycles. Results: Of the 22 enrolled subjects, 13 (59.1%) had no gross lesion after IDS. Of the 13 subjects enrolled on the 1st stage, one study-defined significant AE occurred, therefore the trial proceeded to the 2nd stage (n = 9). The median progression-free survival (PFS) was 22.1 months (95% confidence interval [CI], 13.7 – 30.5), and the median overall survival (OS) was 49.2 months (95% CI, 33.8 – 64.6). Peritoneal Cancer Index score at entering abdomen during IDS was significant for PFS (>12 vs ≤ 12: p = 0.003). One of the 22 subjects did not receive any study treatment. In the safety analysis (n = 21), grade 3/4 AEs included thrombocytopenia of 38.1%, neutropenia 71.4%, and anemia 28.6%. Study-defined significant AEs of bowel perforation, poor-healing wound, and hypertension were found in 1 case each, respectively. Conclusions: This phase II trial demonstrated adding bevacizumab to dose-dense adjuvant chemotherapy with bevacizumab maintenance after NAC was feasible with tolerable toxicity and comparable PFS/OS as compared to other studies using bevacizumab in the NAC phase or dose-dense scheduling throughout. Clinical trial information: NCT02022917.

本研究使用國際數學與科學成就趨勢調查（Trends in International Mathematics and Science Study, TIMSS）2007年臺灣八年級學生的資料，以期望價值理論為架構，先進行能力信念與價值相關構面及題項的信度與效度分析，接續探討這些構面對數學成就之影響，並以多群組結構方程模型分析男、女生模型之差異。研究發現，數學能力信念、實用與內在價值三構面及其對應的題項都有良好的信度與效度，三構面中以能力信念的預測力最高，能解釋數學成就約三成六的變異量。男、女生模型在因素負荷量、題項截距、路徑係數及因素變異數／共變異數上皆具跨性別不變性，不過，在構面平均數上，男生的數學能力信念、實用與內在價值的平均數都顯著較女生高，且以在能力信念的差異最大。最後依據結果提出實務應用及未來研究上的建議。 Based on expectancy-value theory, we applied trends in mathematics and science study (TIMSS) data to investigate the reliability and validity of items relating to ability beliefs and task values, examine their effects on mathematical achievements, and test gender invariance in the proposed models by using multiple-group structural equation modeling. The results supported a three-factor solution reflecting ability beliefs, utility values, and intrinsic values. These factors and corresponding items all possessed strong reliability and validity. Among the three factors, ability beliefs exerted the strongest effect on mathematical achievements, explaining 36% of the variance of mathematical achievements. Gender invariance evidence was exhibited in the factor loadings, item intercepts, path coefficients, and factor variance/covariance. However, comparisons of latent factor means suggested that boys had significantly high mean scores regarding ability beliefs, utility values, and intrinsic values. Finally, suggestions for practical applications and future research are provided.

Objective The malignant transformation (MT) of ovarian mature cystic teratoma (MCT) to squamous cell carcinoma (SCC) is very rare. This study analyzed cases from multiple medical centers in Taiwan to investigate the clinicopathologic characteristics, treatment, and prognostic factors of this disease and reviewed related literature. Methods Pathological reports of 16,001 patients with primary ovarian cancer who were treated at Taiwan medical centers from 1990 to 2011 were reviewed. In total, 52 patients with MT of MCT to SCC were identified. Results Among all ovarian MCTs, the incidence of MT to SCC is 0.2%. The median age of patients was 52 years (range, 29–89 years), and the mean tumor size was 10.5 cm (range, 1–40 cm). We analyzed the patients in our study and those in the literature and determined that early identification and complete surgical resection of the tumor are essential for long-term survival. In addition, adjuvant chemotherapy or concurrent chemoradiotherapy can be used to treat this malignancy. Old age, large tumor size (≥15.0 cm), and solid components in MCTs are suitable indicators predicting the risk of MT of MCT to SCC. Conclusion Similar to general epithelial ovarian cancers, the early detection of MT of MCT to SCC is critical to long-term survival. Therefore, older patients with a large tumor or those with a tumor containing a solid component in a clinically diagnosed MCT should be evaluated to exclude potential MT to SCC.

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

Background To prospectively evaluate the value of positron emission tomography (PET) or integrated computed tomography (CT) and PET (PET/CT) in the management of documented or suspected recurrent ovarian cancer. Methods Patients with ovarian cancer who had completed primary cytoreductive surgery and standard adjuvant chemotherapy were studied to evaluate the following indications: (1) CA125 elevation after complete remission with negative CT or magnetic resonance imaging (MRI) result; (2) post-therapy surveillance CT/MRI-detected suspicious lesions that guided biopsy was not feasible; (3) documented relapse for restaging prior to or after curative salvage therapy. The clinical impact of PET, as compared with those of CT/MRI, was determined on a per scan basis. Results From 2002 to 2009, 73 patients were recruited, and 92 PET scans were performed. Up to June 2015, 53 patients had died of disease, four were alive with disease, and the remaining 16 were alive without disease. Among the 92 scans, PET had positive impacts in 72.8%, no clinical impacts in 21.7%, and negative impacts in 5.4%. For indication 1, the sensitivity and positive predictive value of PET in detecting recurrence were 80.0% and 92.3%, respectively. For indication 2, the sensitivity, specificity, positive predictive value, and negative predictive value of PET were 91.2%, 62.5%, 91.2%, and 62.5%, respectively. For indication 3, PET provided positive impact in 85.3% and negative impact in 2.9% of the 34 scans. Conclusion PET has value in the management of suspected or documented recurrent ovarian cancer, with positive impacts on confirming recurrent status and offering a better treatment plan.

BACKGROUND: In this large-scale, retrospective study, the authors evaluated the diagnostic performances of computed tomography (CT), magnetic resonance (MR) imaging, and 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG–PET) in detecting hematogenous bone metastasis in patients with cervical cancer. The associated risk factors also were analyzed. METHODS: Patients with invasive cervical cancer who had both 18F-FDG–PET studies and CT or MR imaging studies were selected. Patients who had either International Federation of Gynecology and Obstetrics (FIGO) stage III/IV disease or positive lymph node metastasis at the time of primary staging and patients who had suspected recurrent disease were included in the analyses. The diagnostic performances of PET was compared with the performance of CT and MR imaging by using the area under the receiver-operating-characteristic curve (AUC). Both univariate and multivariate analyses were applied to assess the risk factors for hematogenous bone metastasis at primary staging. RESULTS: PET was more sensitive than CT (P = .004) and was more specific than MR imaging (P = .04). The diagnostic performance of PET was significantly superior to the performance CT (AUC, 0.964 vs 0.662; P < .001) and MR (AUC, 0.966 vs 0.833; P = .033). Both FIGO stage and the extent of lymph node metastases were associated with hematogenous bone metastasis in univariate analysis. However, the extent of lymph node metastases was the only significant risk factor in multivariate analysis (P = .025). CONCLUSIONS: The current study demonstrated the superiority of 18F-FDG–PET over CT and MR imaging for detecting hematogenous bone metastasis in patients with advanced cervical cancer. Hematogenous bone metastasis in cervical cancer was associated with the extent of lymph node metastases rather than with FIGO stage. Cancer 2009. © 2009 American Cancer Society.

Background/Purpose Under-utilization of Papanicolaou (Pap) smear causes a gap in the prevention of cervical neoplasms. A prospective population-based study was conducted investigating whether a self-sampling human papillomavirus (HPV) test was feasible for under-users of Pap smear and factors associated with under-screening in Taiwan. Methods Women not having Pap smear screening for > 5 years were invited to participate in this study. Invitation letters and educational brochures were mailed to 4% of randomly selected eligible women from Taoyuan City, Taiwan, and responders received an HPV self-sampling kit. Those with HPV-positive results were recalled for a Pap smear and colposcopy. Results Between March 2010 and June 2012, 10,693 women were invited, 354 responded (3.3%), and 282 (2.6%) gave valid informed consent, answered the questionnaire, and submitted HPV samples. The median age of enrolled women was 48.1 years. Forty-seven women (16.7%) had a positive HPV test, and 14 women accepted further survey to find two CIN2+. Another two cases of CIN2+ were identified from a national registry database. The cost of direct mailing self-samplers was less than that done on request (from NT$434,866 to NT$164,229, response rate of 5% to 15%, respectively, versus NT$683,957 for detecting 1 CIN2+). Reasons for not attending screening included lack of time, embarrassment, assumed low risk, fear of positive results, and perceived potential pain. Among the responders, 90.8% found the method acceptable. Conclusion Our study indicated that different approaches (e.g., direct mailing self-samplers to under-users and/or various educational interventions) must be explored to improve coverage in populations with culture characteristics similar to Taiwan.

Small-cell cervical cancer (SCCC) is rare and prone to metastasize. We conducted a prospective study to evaluate the role of (18)F-FDG PET in the management of this aggressive malignancy.Patients with untreated primary, histologically confirmed SCCC were enrolled. (18)F-FDG PET (or PET/CT) was performed immediately after MRI or CT, for primary staging, monitoring response to treatment or restaging when there was suspicion of recurrence. The clinical impact of PET was determined on a scan basis.A total of 25 patients were recruited and 43 PET scans were performed. The PET images were obtained for primary staging (25 patients), monitoring response (10 patients) and restaging when there was suspicion of recurrence (8 patients). The median follow-up time in event-free patients was 109.3 months (range 97.5 - 157.7 months). A positive impact of PET was found in 8 (18.6 %) of the 43 scans, which included detection of additional regions of distal lymph node (LN) metastasis (one primary staging scan, two restaging scans), bone metastasis (two primary staging scans, one monitoring response scan), and exclusion of false-positive lesions on MRI (one primary staging scan, one restaging scan). On the other hand, one negative impact was recorded as one false-positive lesion on a restaging PET scan. One positive impact was noted for monitoring response (bone metastasis). The impact of three scans was indeterminate. The positive impact of down-staging in avoiding overtreatment but finding additional distal LN (except one on restaging) or bone metastases had no beneficial effect on long-term survival.The results of this preliminary study suggest that PET is useful in the management of SCCC. PET could have more value in detecting occult metastases if future novel therapies are able to offer better control of extensive SCCC.

BACKGROUND During follow-up for patients with cervical carcinoma, elevation of serum squamous cell carcinoma antigen (SCC-Ag) levels in the absence of detectable recurrent lesions presents a diagnostic and therapeutic challenge. In the current prospective study, the authors evaluated the use of fluorine-18-labeled fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) to detect disease recurrence in this setting. METHODS Women with cervical carcinoma who experienced complete responses to primary treatment or salvage therapy and who had no evidence of recurrent disease as detected by conventional methods but had serum SCC-Ag levels ≥ 2.0 ng/mL on 2 consecutive occasions were eligible for the study. PET was performed within 2 weeks after the completion of conventional studies for the assessment of recurrence. RESULTS Twenty-seven consecutive patients were registered for the current study. PET findings were positive for 19 patients: 14 who had a distant lesion or lesions, 2 who had a local lesion or lesions, and 3 who had both local and distant lesions. Of these 19 patients, 17 were confirmed to have recurrent disease; the remaining two were found to be free of disease but had severe anthracosis in the PET-positive mediastinal lymph nodes. Seven of the eight patients with negative PET findings were not found to have recurrent disease on follow-up. Overall, PET detected FDG-avid lesions in 17 (94%; P < 0.001) of the 18 patients with recurrent disease. Seven of these 18 patients received therapy with curative intent; complete control was achieved in 6, four of whom currently are alive and free of disease. The addition of PET in the current setting curbed the use of futile curative therapy and significantly increased overall survival for patients in the current cohort compared with a historical group of 30 consecutive patients who had elevated SCC-Ag levels as a first sign of recurrence. CONCLUSIONS PET expedited the detection of recurrent cervical carcinoma in patients with unexplained elevation of SCC-Ag levels. Such expedited detection may have positive effects on patient survival. Cancer 2004. © 2004 American Cancer Society.

Folium Sennae (leaves of Cassia angustifolia or senna) is a laxative and a component in diets for weight control. It contains a variety of anthranoids such as sennosides, aloe-emodin, and rhein. In order to measure the serum concentrations of senna anthranoids, Sprague-Dawley rats were orally administered with single dose and multiple doses of Folium Sennae. The concentrations of anthranoids in serum were determined by HPLC method before and after hydrolysis with sulfatase and β-glucuronidase. The results showed that in the serum, aloe-emodin glucuronides and rhein glucuronides were the major metabolites. Traces of rhein free form were present transiently during the early phase, whereas the free form of aloe-emodin was not detected. We also evaluated the modulation effect of Folium Sennae on P-glycoprotein by using the LS 180 cell model which showed that it significantly inhibited P-glycoprotein by 16–46 %. In conclusion, senna anthranoids were rapidly and extensively metabolized to rhein glucuronides and aloe-emodin glucuronides in rats. Folium Sennae ingestion inhibited the efflux function of P-glycoprotein in the intestine.

Background Our aims were to evaluate the genotype distribution of human papillomavirus (HPV) and the correlation between HPV parameters and clinicopathological/treatment variables with prognosis in cervical adeno-adenosquamous carcinoma (AD/ASC). Patients and methods Consecutive patients who received primary treatment for cervical AD/ASC International Federation of Gynecology and Obstetrics (FIGO) stages I–IV between 1993 and 2008 were retrospectively reviewed. Prognostic models were constructed and followed by internal validation with bootstrap resampling. Results A total of 456 AD/ASC patients were eligible for HPV genotyping, while 452 were eligible for survival analysis. HPV18 was detected in 51.5% and HPV16 in 36.2% of the samples. Age >50 years old, FIGO stages III–IV and HPV16-negativity were significantly related to cancer relapse, and age >50, FIGO stages III–IV, HPV16-negativity and HPV58-positivity were significant predictors for cancer-specific survival (CSS) by multivariate analyses. HPV16-positivity was also significantly associated with good prognosis in those receiving primary radiotherapy or concurrent chemoradiation (RT/CCRT) (CSS: hazard ratio 0.41, 95% confidence interval 0.21–0.78). Patients with FIGO stages I–II and HPV16-negative AD/ASC treated with primary RH-PLND had significantly better CSS (p Conclusions Age >50 years old, FIGO stages III–IV and HPV16-negativity were significant poor prognostic factors in cervical AD/ASC. Patients with HPV16-negative tumour might better be treated with primary surgery (e.g. radical hysterectomy for stages I–II and pelvic exenteration for stage IVA). Those with unresectable HPV16-negative tumour (stage IIIB) should undergo CCRT in combination with novel drugs. The inferences of a single-institutional retrospective study require prospective studies to confirm.

Objective Our aim was to investigate the clinical features and outcomes following recurrence after primary radical hysterectomy for cervical cancer. Methods Clinical data of 121 documented recurrent cervical cancer patients who received primary radical hysterectomy and bilateral pelvic lymphadenectomy between 1993 and 2000 at Chang Gung Memorial Hospital were retrospectively reviewed. Clinicopathological variables, primary treatment, failure pattern, salvage treatment and outcomes were analyzed. Outcomes of the current study were compared to those treated between 1982 and 1992 (1982–1992 cohort). Results Cancer recurrence was documented at a median time to recurrence (TTR) of 28.4months (1.2–129.9months). Assessable failure patterns (n=106) included loco-regional in 46.3%, distant in 47.2% and combined pelvic-distant in 6.6%. 5-year survival of the 121 patients was 22.3% after cancer recurrence. The median survival after recurrence (SAR) was 16.4months (range 0–144.2months). By multivariate analysis, extravaginal sites of recurrence (HR 2.56, 1.28–5.12; p =0.008) and HPV16-positive (HR 0.60, 0.38–0.96; p =0.033) were significant prognostic factors for SAR. Non-squamous histology or pelvic node metastasis at primary surgery were not significant (5-year SAR of 16.4% and 20.0%, respectively), though they were (0% and 0%) in the 1993–2000 cohort. Salvage surgery and concurrent chemoradiation were more frequently used in the 1993–2000 cohort (48.3% versus 12.4%). Conclusion HPV16-negativity and extravaginal relapse were significant poor prognostic factors. Future randomized controlled trials for recurrent cervical cancer could be stratified for these two factors if further studies using external validation confirm these results.

Two new drimane-type compounds, nigrofomins A ( 1) and B ( 2), possessing a rare dioxabicyclooctane moiety, were purified from the fruiting bodies of Nigrofomes melanoporus. Their structures were determined using 1D-, 2D-NMR and HR-ESI-MS spectroscopic analyses. In addition, 1 was established by X-ray crystallographic studies. Both nigrofomins A ( 1) and B ( 2) exhibited cytotoxicity on acute T-cell leukemia (Jurkat), human nasopharyngeal carcinoma (NPC-TW01), and lung cancer (NCI-H661) cells with IC (50) values in the range of 99.44-246.32 µM. Furthermore, the effects of 1 and 2 on cell-cycle progression of Jurkat cells displayed a concentration-dependent accumulation in the G (0)/G (1) phase.

Objective To report the natural history and prognosis of the uncommon Sertoli–Leydig cell tumor (SLCT) of the ovary. Materials and Methods A 20-year retrospective review was conducted by the Taiwanese Gynecologic Oncology Group (TGOG), including nine tertiary medical centers from different regions in Taiwan. The medical records for 40 cases of ovarian SLCT were collected. Pathology reviews were carried out by a panel of expert pathologists. Results After pathological review, 17 patients were subsequently excluded because the pathology slides were unavailable in five cases, and discrepant results from the initial diagnosis were found in 12 cases (34%). For the remaining 23 patients, the median age was 41 years. The most common symptom was irregular vaginal bleeding followed by an abdominal mass or amenorrhea. Most of the tumors were unilateral and confined to the right ovary, with an average size of 8.2 cm. Preoperative serum markers were available for 12 patients and were elevated for three patients. All patients underwent primary surgery. Six patients accepted adjuvant chemotherapy, and bleomycin, etoposide, and cisplatin were used in four of them. Clinical follow-up information was available in 21 patients with a median of 19 months. Eighty-two percent of patients were alive and free of disease up to the date of the last follow-up. Two patients died of the disease. Conclusion This study demonstrates the extreme rarity of ovarian SLCT in Taiwan. Histological discordance between the diagnosis and central review proves the need for expertise review before treatment. For an improved understanding of the biological behavior and treatment strategy for this unique tumor, international collaboration is imperative.

BACKGROUND: Epigenetic therapy has had a significant impact on the management of hematologic malignancies, but its role in the treatment of ovarian cancer remains to be defined. The authors previously demonstrated that treatment of ovarian and breast cancer cells with DNA methyltransferase and histone deacetylase (HDAC) inhibitors can up-regulate the expression of imprinted tumor suppressors. In this study, demethylating agents and HDAC inhibitors were tested for their ability to induce re-expression of tumor suppressor genes, inhibiting growth of ovarian cancer cells in culture and in xenografts. METHODS: Ovarian cancer cells (Hey and SKOv3) were treated with demethylating agents (5-aza-2′-deoxycytidine [DAC] or 5-azacitidine [AZA]) or with HDAC inhibitors (suberoylanilide hydroxamic acid [SAHA] or trichostatin A [TSA]) to determine their impact on cellular proliferation, cell cycle regulation, apoptosis, autophagy, and re-expression of 2 growth inhibitory imprinted tumor suppressor genes: guanosine triphosphate-binding Di-RAS-like 3 (ARHI) and paternally expressed 3 (PEG3). The in vivo activities of DAC and SAHA were assessed in a Hey xenograft model. RESULTS: The combination of DAC and SAHA produced synergistic inhibition of Hey and SKOv3 cell growth by apoptosis and cell cycle arrest. DAC induced autophagy in Hey cells that was enhanced by SAHA. Treatment with both agents induced re-expression of ARHI and PEG3 in cultured cells and in xenografts, correlating with growth inhibition. Knockdown of ARHI decreased DAC-induced autophagy. DAC and SAHA inhibited the growth of Hey xenografts and induced autophagy in vivo. CONCLUSIONS: A combination of DAC and SAHA inhibited ovarian cancer growth while inducing apoptosis, G2/M arrest, autophagy, and re-expression of imprinted tumor suppressor genes. Cancer 2011;. © 2011 American Cancer Society.

Summary In this article, we propose a Bayesian approach to dose–response assessment and the assessment of synergy between two combined agents. We consider the case of an in vitro ovarian cancer research study aimed at investigating the antiproliferative activities of four agents, alone and paired, in two human ovarian cancer cell lines. In this article, independent dose–response experiments were repeated three times. Each experiment included replicates at investigated dose levels including control (no drug). We have developed a Bayesian hierarchical nonlinear regression model that accounts for variability between experiments, variability within experiments (i.e., replicates), and variability in the observed responses of the controls. We use Markov chain Monte Carlo to fit the model to the data and carry out posterior inference on quantities of interest (e.g., median inhibitory concentration IC 50). In addition, we have developed a method, based on Loewe additivity, that allows one to assess the presence of synergy with honest accounting of uncertainty. Extensive simulation studies show that our proposed approach is more reliable in declaring synergy compared to current standard analyses such as the median-effect principle/combination index method (Chou and Talalay, 1984, Advances in Enzyme Regulation 22, 27–55), which ignore important sources of variability and uncertainty.