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Objective To evaluate efficacy of stereotactic body radiotherapy (SBRT) for pelvic boost irradiation in gynecological cancer patients with pelvic recurrence or with intact uterus unsuitable for brachytherapy. Materials and methods We retrospectively reviewed the medical records of 25 gynecological cancer patients who received SBRT boost for pelvic recurrence (salvage group, n = 14), or for local dose escalation instead of intracavitary brachytherapy due to unfavorable medical condition (definitive group, n = 11). The pelvis was irradiated with a median dose of 54 Gy in six weeks, and then SBRT was prescribed with a range of 10–25Gy in two to five fractions. The cumulative radiobiological equivalent dose in 2-Gy fractions (EQD2) to the tumors ranged from 62.5 to 89.5 Gy10 (median, 80.7). Overall survival (OS) and in-field relapse-free survival (IFRFS) were calculated using the Kaplan–Meier method. Results At the initial assessment, eighteen (72%) patients achieved complete or partial remission, and seven (28%) had stable or progressive disease. With a median follow duration of 12 months, the 1-year IFRFS for salvage and definitive group were 64.5% and 90.0%, whereas the 1-year OS for the two groups were 80.8% and 49.1%, respectively. One patient developed entero-vaginal fistula and one had sigmoid perforation. No patient experienced ≧ grade 3 genitourinary complications. Conclusion In gynecological cancer patients with recurrent pelvic tumors or intact uterus unsuitable for brachytherapy, local dose escalation with SBRT resulted in an initial response rate of 72% with acceptable early toxicities. A long-term follow-up is required to assess the impact on local control or survival.

Platinum-based therapy remains the cornerstone for cancer therapy; however, its efficacy varies. The role of lipoprotein receptor-mediated lipid entry for cancer development has been reported. Yet, the roles and mechanism of the low-density lipoprotein receptor (LDLR) in chemo-sensitivities are unknown. In the current report, we used epithelial ovarian cancer (EOC), composed of various cellularities, to study this issue. Using public cDNA microarray database and single cohort study, LDLR expressions were positively associated with epithelial ovarian carcinomas (EOCs) platinum-based chemotherapy patients’ disease prognosis. In vitro and in vivo add-in/silencing LDLR was introduced to determine cisplatin sensitivity and cancer growth. Results revealed that knocked-down LDLR could sensitize while overexpressed LDLR could insensitize EOC cells to the cytotoxic effects of cisplatin. Moreover, the trans-omics approaches depicted an LDLR→LPC (Lyso-phosphatidylcholine)→FAM83B (phospholipase-related)→FGFRs (cisplatin sensitivity and phospholipase-related) regulatory axis. Finally, the manipulation of LDLR expression in EOC cells was found to determine the efficacy of cisplatin therapy in terms of tumor suppression. In conclusion, the LDLR→LPC→FAM83B→FGFRs axis is an example of tumor macroenvironmental regulation of therapy outcomes. Relatedly, LDLR expression could serve as a biomarker of chemotherapy sensitivity in EOCs. Significance: this study describes the role of LDLR in the development of insensitivity to platinum-based chemotherapy in epithelial ovarian cancer. The lipidome (e.g., LPC) and transcriptome (e.g., FAM38B) interactions revealed using trans-omics approaches an LDLR→LPC→FAM83B→FGFRs regulatory axis in cancer cells, in an animal model, and in patients.

Platinum-based therapy remains the cornerstone for cancer therapy; however, its efficacy varies. The role of lipoprotein receptor-mediated lipid entry for cancer development has been reported. Yet, the roles and mechanism of the low-density lipoprotein receptor (LDLR) in chemo-sensitivities are unknown. In the current report, we used epithelial ovarian cancer (EOC), composed of various cellularities, to study this issue. Using public cDNA microarray database and single cohort study, LDLR expressions were positively associated with epithelial ovarian carcinomas (EOCs) platinum-based chemotherapy patients' disease prognosis. In vitro and in vivo add-in/silencing LDLR was introduced to determine cisplatin sensitivity and cancer growth. Results revealed that knocked-down LDLR could sensitize while overexpressed LDLR could insensitize EOC cells to the cytotoxic effects of cisplatin. Moreover, the trans-omics approaches depicted an LDLR→LPC (Lyso-phosphatidylcholine)→FAM83B (phospholipase-related)→FGFRs (cisplatin sensitivity and phospholipase-related) regulatory axis. Finally, the manipulation of LDLR expression in EOC cells was found to determine the efficacy of cisplatin therapy in terms of tumor suppression. In conclusion, the LDLR→LPC→FAM83B→FGFRs axis is an example of tumor macroenvironmental regulation of therapy outcomes. Relatedly, LDLR expression could serve as a biomarker of chemotherapy sensitivity in EOCs. Significance: this study describes the role of LDLR in the development of insensitivity to platinum-based chemotherapy in epithelial ovarian cancer. The lipidome (e.g., LPC) and transcriptome (e.g., FAM38B) interactions revealed using trans-omics approaches an LDLR→LPC→FAM83B→FGFRs regulatory axis in cancer cells, in an animal model, and in patients.

Ovarian cancer (OVCA) arises from three cellular origins, namely surface epithelial cells, germ cells, and stromal cells. More than 85% of OVCAs are EOCs (epithelial ovarian carcinomas), which are the most lethal gynecological malignancies. Cancer stem/progenitor cells (CSPCs) are considered to be cancer promoters due to their capacity for unlimited self-renewal and drug resistance. Androgen receptor (AR) belongs to the nuclear receptor superfamily and can be activated through binding to its ligand androgens. Studies have reported an association between AR expression and EOC carcinogenesis, and AR is suggested to be involved in proliferation, migration/invasion, and stemness. In addition, alternative AR activating signals, including both ligand-dependent and ligand-independent, are involved in OVCA progression. Although some clinical trials have previously been conducted to evaluate the effects of anti-androgens in EOC, no significant results have been reported. In contrast, experimental studies evaluating the effects of anti-androgen or anti-AR reagents in AR-expressing EOC models have demonstrated positive results for suppressing disease progression. Since AR is involved in complex signaling pathways and may be expressed at various levels in OVCA, the aim of this article was to provide an overview of current studies and perspectives regarding the relevance of androgen/AR roles in OVCA.

AIM To compare the advantage of image-guided brachytherapy (IGBT) over conventional two-dimensional brachytherapy (2DBT) in patients with advanced cervical squamous cell carcinoma. PATIENTS AND METHODS This study included 253 patients with stage IB2-IVA diseases treated with two schemes of brachytherapy. One hundred and thirty-six patients received 2DBT, whereas 117 patients received IGBT. Tumor stage, age, and tumor diameter were matched between the two groups. Local relapse-free survival, overall survival, and cumulative incidences of gastrointestinal and genitourinary complications were compared between the two groups. RESULTS The overall and local relapse-free survival rates were similar between the two groups. The cumulative rate of grade 2 and higher gastrointestinal complication was 21.3% for the 2DBT group, and 8.5% for the IGBT group (p=0.007), whereas that of grade 2 and higher genitourinary injury was 11.8% for the 2DBT group, and 1.7% for the IGBT group (p=0.002). CONCLUSION In patients with advanced cervical squamous cell carcinoma, IGBT achieves a higher therapeutic ratio compared to 2DBT technique by minimizing the late toxicities.

We designed a deep learning model for assessing 18F-FDG PET/CT for early prediction of local and distant failures for patients with locally advanced cervical cancer. All 142 patients with cervical cancer underwent 18F-FDG PET/CT for pretreatment staging and received allocated treatment. To augment the amount of image data, each tumor was represented as 11 slice sets each of which contains 3 2D orthogonal slices to acquire a total of 1562 slice sets. In each round of k-fold cross-validation, a well-trained proposed model and a slice-based optimal threshold were derived from a training set and used to classify each slice set in the test set into the categories of with or without local or distant failure. The classification results of each tumor were aggregated to summarize a tumor-based prediction result. In total, 21 and 26 patients experienced local and distant failures, respectively. Regarding local recurrence, the tumor-based prediction result summarized from all test sets demonstrated that the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 71%, 93%, 63%, 95%, and 89%, respectively. The corresponding values for distant metastasis were 77%, 90%, 63%, 95%, and 87%, respectively. This is the first study to use deep learning model for assessing 18F-FDG PET/CT images which is capable of predicting treatment outcomes in cervical cancer patients. • This is the first study to use deep learning model for assessing 18 F-FDG PET/CT images which is capable of predicting treatment outcomes in cervical cancer patients. • All 142 patients with cervical cancer underwent 18 F-FDG PET/CT for pretreatment staging and received allocated treatment. To augment the amount of image data, each tumor was represented as 11 slice sets each of which contains 3 2D orthogonal slices to acquire a total of 1562 slice sets. • For local recurrence, all test sets demonstrated that the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 71%, 93%, 63%, 95%, and 89%, respectively. The corresponding values for distant metastasis were 77%, 90%, 63%, 95%, and 87%, respectively.

We retrospectively reviewed the records of 142 patients with stage IB–IIIB cervical cancer who underwent 18F-FDG-PET/CT before external beam radiotherapy plus intracavitary brachytherapy and concurrent chemotherapy. The patients were divided into training and validation cohorts to confirm the reliability of predictors for recurrence. Kaplan–Meier analysis was performed and a Cox regression model was used to examine the effects of variables on overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and pelvic relapse-free survival (PRFS). High gray-level run emphasis (HGRE) derived from gray-level run-length matrix most accurately and consistently predicted the presence of pelvic residual or recurrent tumors for both cohorts. In multivariate analysis, stages IIIA–IIIB (P = 0.001, hazard ratio [HR] = 4.07) and a low HGRE (P P = 0.001, HR = 2.86) and nonsquamous cell histology (P = 0.003, HR = 2.76) were prognostic factors for inferior PFS. The nonsquamous cell histology (P P = 0.001, HR = 4.69) were predictors for low PRFS. In cervical cancer patients receiving definitive chemoradiotherapy, pretreatment textural features on 18F-FDG-PET/CT can supplement the prognostic information.

The androgen receptor (AR) poly‐glutamine polymorphism (AR‐Q) was reported to play role in endometrial cancer (EMCA) development, yet controversial. Environmental factors interact with genetic variation have been reported in EMCA. Aerosol toxins, polycyclic aromatic hydrocarbon benzo[a]pyrene (BaP), are EMCA facilitators. This report examined the interplay between AR‐Qs and BaP in EMCA. During analysing patient AR‐Q polymorphism and Aryl hydrocarbon Receptor (AhR) expressions, we found overall survival (OS) benefit is ascending with AR‐Q lengths (5‐year OS of 61.3% in Q length 23). And AhR is higher expressed in short AR‐Q tumour compared to that in long AR‐Q patient. In vitro study found androgen‐response element (ARE) activity descends with AR‐Qs length (Q13 > Q25 > Q35), whereas BaP suppresses ARE activities in EMCA cells. Furthermore, AR‐Q13 (but not AR‐Q25, or ‐35) enhances BaP‐induced dioxin‐responsive element (DRE) activity. Lastly, AR‐Q13 exerts higher colony‐forming capacity than other AR‐Qs, and knock‐down AhR abolished AR‐Q13‐mediated colony numbers. This study demonstrated a possible interaction of gene (AR‐Q polymorphism) and environmental toxins (e.g. BaP) to affect cancer progression. A large‐scale epidemiology and public health survey on the interaction of environmental toxin and AR poly‐Q in EMCA is suggested.

Background/aim To determine the prognostic effects of immunohistochemical biomarkers for predicting chemoradiotherapy (CRT)-based treatment outcomes in patients with adenocarcinoma of the uterine cervix. Materials and methods This study included 42 patients receiving definitive CRT. According to the International Federation of Gynecology and Obstetrics staging system, 13, 21, and 8 patients were classified as having stage IB2, II, and III disease, respectively. Baseline immunohistochemical biomarkers, including those for hypoxia, cell proliferation, cell adhesion, immunogenicity, and evasion of apoptosis, were analyzed using tissue microarrays from biopsy specimens. Results Myeloid cell leukemia-1 (MCL1) overexpression and the presence of pelvic lymph node metastasis were two prognostic factors for inferior cancer-specific survival. A higher H-score for c-MYC proto-oncogene, bHLH transcription factor (c-MYC) was associated with lower pelvic relapse-free survival. Conclusion For patients with adenocarcinoma of the uterine cervix requiring definitive CRT, treatment outcomes can be stratified by the immunohistochemical biomarkers MCL1 and c-MYC for cancer death and local failure, respectively.

OBJECTIVES An Asian Gynecologic Oncology Group phase III randomized trial was conducted to determine whether maintenance chemotherapy could improve progression-free survival (PFS) in stages III/IV ovarian cancer. METHODS Between 2007 and 2014, 45 newly-diagnosed ovarian cancer patients were enrolled after complete remission and randomized (1:1) to arm A (4-weekly carboplatin area under the curve 4 and pegylated liposomal doxorubicin [PLD] 30 mg/m², n=24) for 6 cycles or arm B (observation, n=21). The primary end-point was PFS. A post hoc translational study was conducted to deep sequence BRCA/homologous recombination deficiency (HRD) genes, because BRCA/HRD mutations (BRCA/HRDm) are known to be associated with better prognosis. RESULTS Enrollment was slow, accrual was closed when 7+ years had passed. With a median follow-up of 88.9 months, the median PFS was significantly better in arm A (55.5 months) than arm B (9.2 months) (hazard ratio [HR]=0.40; 95% confidence interval [CI]=0.19-0.87; p=0.020), yet the median overall survival was not significantly different in arm A (not reached) than arm B (95.1 months) (p=0.148). Overall grade 3/4 adverse events were more frequent in arm A than arm B (60.9% vs 0.0%) (p

Background: Platinum-based therapy remains the cornerstone for cancer therapy; however, efficacy varies. The role of tumor macroenvironmental lipid entry via lipoprotein receptors has been reported. Yet, the roles and mechanism of low-density lipoprotein receptor (LDLR) in chemo-sensitivities are in large. Method: Patient study: Single cohort or public database cDNA microarray to associate LDLR expressions of epithelial ovarian carcinomas (EOCs) with disease prognosis. Laboratory study: In vitro and in vivo add-in/silencing LDLR were introduced to determines cisplatin sensitivity. Transcriptome-Lipidome Trans-omics and bioinformatic analyses to model molecular mechanism. Translation study: LDLR-lipidome was implemented to formulate efficacy boosting liposome. Findings: The LDLR expression is associate with platin-based chemotherapy patients prognosis. The LDLR abundance in EOC subtypes is associated with cisplatin sensitivity. Knocked-down or overexpressed LDLR in EOC could reversed the chemosensitivity pattern in vitro and in vivo. Trans-omics analyses elucidated the LDLR→LPC (Lyso-PhosphotidylCholine)→FAM83B (phospholipase-related)→FGFRs (cisplatin sensitivity and phospholipase-related) regulatory axis in cisplatin insensitivity. Implementing LPC-liposome encapsulated cisplatin facilitated DNA-adduct formation via lipid droplets (LDs) delivery. Bioinformatics analyses found that the LDL/R-route alters LD homeostasis, which is critical for therapeutic prognosis. Lastly, using LPCliposome could improve multiple cancer types of cisplatin insensitive cells. Interpretation: The LDL/R-route as tumor macroenvironmental lipid entry which impulses platinum insensitivity and disease outcome. The drug specific lipidome for liposome manufacture might be an efficienct pharmaceutics strategy for chemoagents. Funding Statement: This study was supported by Taiwan Ministry of Science and Technology (MOST104-2628-B-039-001-MY4; MOST106-2221-E-039-011-MY3); National Health Research Institute (NHRI-EX107-10705BI); and China Medical University/Hospital (CMU107-S-05; CMU107-TC-02; DMR-108-080; DMR-CELL-17014; DMR-CELL-1806; DMR-108-079). Declaration of Interests: All the authors in this work claimed no interests conflict. Ethics Approval Statement: Access to the tissue samples was approved by the Internal Review Board of China Medical University Hospital (DMR101-IRB2-276; and CMU105-REC3-122(CR1)). All the animal studies were performed under the supervision and guidelines of the China Medical University Animal Care and Use Committee (#CMOIACUC-2018-089).

Uterine sarcoma is a very aggressive and highly lethal disease. Even after a comprehensive staging surgery or en block cytoreduction surgery followed by multimodality therapy (often chemotherapy and/or radiation therapy), many patients relapse or present with distant metastases, and finally die of diseases. The worst outcome of uterine sarcomas is partly because of their rarity, unknown etiology, and highly divergent genetic aberration. Uterine sarcomas are often classified into four distinct subtypes, including uterine leiomyosarcoma, low-grade uterine endometrial stromal sarcoma, high-grade uterine endometrial stromal sarcoma, and undifferentiated uterine sarcoma. Currently, evidence from tumor biology found that these tumors showed alternation and/or mutation of genomes and the intracellular signal pathway. In addition, some preclinical studies showed promising results for targeting receptor tyrosine kinase signaling, phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin pathway, various kinds of growth factor pathways, Wnt/beta-catenin signaling pathway, transforming growth factor β/bone morphogenetic protein signal pathway, aurora kinase A, MDM2 proto-oncogene, histone deacetylases, sex hormone receptors, certain types of oncoproteins, and/or loss of tumor suppressor genes. The current review is attempted to summarize the recurrent advance of targeted therapy for uterine sarcomas.

Endometrial stromal tumors are rare uterine tumors (

This study investigated the prognostic effects of genomic biomarkers for predicting chemoradiotherapy (CRT)-based treatment outcomes in patients with adenocarcinoma (AC) of the uterine cervix. In all, 21 patients receiving definitive CRT were included. In accordance with the International Federation of Gynecology and Obstetrics (FIGO) staging system, 5, 8, and 8 patients were classified as having stage IB3, II, and III disease, respectively. Pretreatment biomarkers were analyzed using tissue microarrays from biopsy specimens. Genomic alterations were examined by next-generation sequencing (NGS). The outcome endpoints were disease-free survival (DFS), distant metastasis-free survival (DMFS), and local relapse-free survival (LRFS). A Cox regression model was used to examine the prognostic effects of the biomarkers and clinical parameters. The presence of myeloid cell leukemia-1 (MCL1) gene amplification and a lower immunohistochemical (IHC) marker of tumor necrotic factor alpha (TNF-&alpha, ) H-score were two prognostic factors for inferior DFS. The four-year DFS was 28% and 68% for patients with or without MCL1 copy number gain, respectively (p = 0.028). In addition, MCL1 amplification predicted poor DMFS. A lower tumor mutation number (TMN) calculated from nonsynonymous mutations was associated with lower LRFS. For patients with adenocarcinoma of the uterine cervix receiving definitive CRT, prognostic information can be supplemented by MCL1 amplification, the TMN, and the TNF-&alpha, H score.

Analysis of circulating tumor DNA (ctDNA) offers an unbiased and noninvasive way to assess the genetic profiles of tumors. This study aimed to analyze mutations in ctDNA and their correlation with tissue mutations in patients with a variety of cancers. We included 21 cancer patients treated with surgical resection for whom we collected paired tissue and plasma samples. Next-generation sequencing (NGS) of all exons was performed in a targeted human comprehensive cancer panel consisting of 275 genes. Six patients had at least one mutation that was concordant between tissue and ctDNA sequencing. Among all mutations (n = 35) detected by tissue and blood sequencing, 20% (n = 7) were concordant at the gene level. Tissue and ctDNA sequencing identified driver mutations in 66.67% and 47.62% of the tested samples, respectively. Tissue and ctDNA NGS detected actionable alterations in 57.14% and 33.33% of patients, respectively. When somatic alterations identified by each test were combined, the total proportion of patients with actionable mutations increased to 71.43%. Moreover, variants of unknown significance that were judged likely pathogenic had a higher percentage in ctDNA exclusively. Across six representative genes (PIK3CA, CTNNB1, AKT1, KRAS, TP53, and MET), the sensitivity and specificity of detection using mutations in tissue sample as a reference were 25 and 96.74%, respectively. This study indicates that tissue NGS and ctDNA NGS are complementary rather than exclusive approaches; these data support the idea that ctDNA is a promising tool to interrogate cancer genetics.

Background: We designed a deep learning model for assessing 18F-FDG PET-CT for early prediction of local and distant failures for patients with locally advanced cervical cancer. Methods: All 142 patients with cervical cancer underwent 18F-FDG PET-CT for pretreatment staging and received allocated treatment. To augment the amount of image data, each tumor was represented as 11 slice sets each of which contains 3 2D orthogonal slices to acquire a total of 1562 slice sets. In each round of k-fold cross-validation, a well-trained proposed model and a slice-based optimal threshold were derived from training set and used to classify each slice set in the test set into the categories of with or without the local or distant failure. The classification results of each tumor were aggregated to summarize a tumor-based prediction result. Results: In total, 21 and 26 patients experienced local and distant failures, respectively. Regarding local recurrence, the tumor-based prediction result summarized from all test sets demonstrated that the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 71%, 93%, 63%, 95%, and 89%, respectively. The corresponding values for distant metastasis were 77%, 90%, 63%, 95%, and 87%, respectively. Conclusion: This is the first study to use deep learning model for assessing 18F-FDG PET-CT images which is capable of predicting treatment outcomes in cervical cancer patients. Funding Statement: This work was supported by grants from the Ministry of Health and Welfare, Taiwan (MOHW107-TDU-B-212-123004), China Medical University Hospital (DMR-107-192, CRS-106-036, CRS106-039, CRS106-040, CRS106-041); Asia University (DMR-106-150); Academia Sinica Stroke Biosignature Project (BM10701010021); MOST Clinical Trial Consortium for Stroke (MOST 107-2321-B-039 -004-); Tseng-Lien Lin Foundation, Taichung, Taiwan; and Katsuzo and Kiyo Aoshima Memorial Funds, Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding received for this study Declaration of Interests: All authors declare that they have no conflict of interest. Ethics Approval Statement: This study was approved by the local institutional review board (certificate numbers CMUH102-REC2-74 and DMR99-IRB-010-1). Informed consent: This is a retrospective study for images’ analyses. The IRB also specifically waived the consent requirement.

Objective : To evaluate the role of surgery, radiation therapy and chemotherapy in the management of small cell carcinoma of the uterine cervix (SCCC) through a retrospective study of Taiwanese Gynecologic Oncology Group. Methods : We reviewed the medical records and histological files of 144 patients with FIGO stages IA–IIB SCCC treated in 11 main hospitals in Taiwan from 1987 to 2009. Results : There were 110 patients receiving primary surgery and 34 primary radiation therapy. Most patients in each group also received chemotherapy as part of primary treatment. A lower loco-regional failure rate was observed in patients who received primary radiation therapy than in those who had primary surgery (6% vs. 27%; P =0.009). The 5-year overall survival (OS) was 89% for 13 surgically treated patients with cervical tumor ≤2cm and no lymphovascular space involvement (LVSI) in whom recurrence was noted in 2 of 4 patients without receiving adjuvant chemotherapy and none in the 9 patients who had chemotherapy. Excluding these 13 patients, primary radiation therapy with at least 5cycles of platinum-based chemotherapy ( n =14, including 12 stages IB2–IIB) resulted in a 5-year OS of 78%, better than that of 46% by primary surgery ( n =97, including 40 stages IB2–IIB) ( P =0.046). Conclusions : None of the 9 patients with cervical tumor ≤2cm and no LVSI showed disease recurrence after primary surgery and adjuvant chemotherapy. For most patients with stages I–II, primary radiation therapy with aggressive chemotherapy was associated with better survival than surgery.

Background Breast and cervical cancer are the most common cancers affecting women. The symptom distresses experienced by cancer survivors are critical factors influencing their quality of life (QOL). This study investigated the QOL of breast and cervical cancer survivors, their physical, psychological and social conditions. Methods The participants were older than 20 years, had been diagnosed with breast or cervical cancer for more than 2 years, and had completed their cancer treatment. The survey incorporated the QOL questionnaires developed by the European Organization of Research and Treatment for Cancer and a self-designed questionnaire. Results The mean age at diagnosis was 48.89 ± 8.53 years for the breast cancer survivors and 49.00 ± 10.30 years for the cervical cancer survivors. The corresponding QOL scores were 75.33 ± 20.25 and 75.56 ± 17.93. The factors influencing QOL of breast cancer survivors were household income, number of comorbidities, stage of cancer, type of cancer treatment and duration of illness, whereas the factor related to QOL of cervical cancer survivors was only household income. Conclusions The QOL of the two groups was similar. Healthcare providers should demonstrate greater concern toward breast and cervical cancer survivors.

Endometrial cancer (EMC) is a sex steroid hormone-related female malignancy. Androgen and androgen receptor (androgen/AR) signals have been implicated in EMC progression. Cancer stem/progenitor cells (CSPCs) are suspected to link to chemoresistance in patients with EMC. In this study, we examined the androgen/AR roles in cisplatin resistance and CSPC population. We found AR expression increased naive EMC side population, CSPC population, cell migration, and epithelial–mesenchymal transition. Meanwhile, it decreased cisplatin cytotoxic effect on EMC cells. Collaterally, endogenous AR expressions in EMC cells were upregulated in the cisplatin-resisting state. Moreover, AR expression could further enhance CD133 expression, CSPC-related markers, and drug-resistance gene messenger RNA expression in EMC cells. Finally, the AR-associated gene expression might go through indirect regulation. This is the first report revealing AR function on EMC cells’ CSPC and cisplatin resistance.

Uterine sarcomas account for 3–7% of all uterine cancers. Because of their rarity, unknown etiology, and highly divergent genetic aberration, there is a lack of consensus on risk factors for occurrence and predictive poor outcomes as well as optimal therapeutic choices. Tumor types according to the World Health Organization classification include leiomyosarcoma, endometrial stroma sarcoma, and undifferentiated sarcoma. Staging is done using the 2014 Federation International Gynecology and Obstetrics and 2010 American Joint Committee on Cancer tumor, lymph node, and metastases systems. Tumor grade can be classified based on the French Federation of Cancer Centers Sarcoma Group system or the Broder’s system that incorporates tumor differentiation, mitotic count, and tumor necrosis. This review is a series of articles discussing uterine sarcoma, and this is Part I, which focuses on one of the subtypes of uterine sarcomas—uterine leiomyosarcoma. The clinical characteristics, diagnosis, outcome, and recent advances are summarized in this article.

The authors report a case of congenital hepatoblastoma that was diagnosed in the antenatal period at 39 weeks' gestation. The infant was delivered vaginally without rupture of the tumor. The neonate then received chemotherapy and underwent surgical excision of the tumor. After 1 year, no tumor recurrence has been noted.

Purpose This study aimed to assess the predictive values of geometrical sparing factors for the rectum and bladder in high-dose-rate intracavitary brachytherapy (HDRICB) for Grade 2 and higher late sequelae in patients with cervical cancer. Methods A total of 392 patients were enrolled in this study. They were treated with external beam radiotherapy to the pelvis, after which HDRICB was performed using Ir-192 remote after-loading at 1-week intervals for three or four sessions. The geometrical sparing factor (GSF) was defined as the average of the ratios between the reference doses and the Point A dose. Results A total of 46 patients (11.7%) had Grade 2 or higher late rectal complications (36 Grade 2, 9 Grade 3, and 1 Grade 4). In all, 32 patients (8.2%) had Grade 2 or higher late bladder complications (14 Grade 2, 16 Grade 3, and 2 Grade 4). Multivariate analysis demonstrated a high risk of rectal sequelae in patients who developed bladder complications ( p = 0.0004, hazard ratio 3.54) and had a rectal GSF greater than 0.7 ( p = 0.01, hazard ratio 1.99). The high risk factors for bladder complications were development of rectal complications ( p = 0.0004, hazard ratio 3.74), concurrent chemotherapy ( p = 0.0001, relative risk 3.94), and a bladder GSF greater than 0.9 ( p = 0.01, hazard ratio, 2.53). Conclusion This study demonstrates the predictive value of GSFs in HDRICB for cervical cancer. Patients with rectal GSFs greater than 0.7 or bladder GSFs greater than 0.9 are at risk for Grade 2 and higher late sequelae.

SUMMARY Background: Human ovarian carcinoma is a silent killer. Most patients with human ovarian carcinoma are diagnosed in the advanced stages. Currently, no effective means of early detection are available. Identifying genes that distinguish early cancers from normal tissue may provide insight to the initiation and progression of ovarian cancer. Methods: A large-scale gene expression profiling using 9,600 genes-complementary DNA array to study ovarian tumors was conducted. We analyzed 13 benign tumors, 22 invasive cancers (seven stage I and 15 stage III), and 16 normal ovaries. Cluster analysis revealed two major groups: the early-stage cluster that included 13 benign tumors and seven stage I cancers; and the late-stage cluster that included all stage III cancers. Results: There were 433 upregulated and 60 downregulated genes from the early-stage cluster, and 395 upregulated and 101 downregulated genes from the late-stage cluster. These genes showed altered functions for tumor/cancers, functions such as cell growth, cell cycle control, differentiation, signaling, apoptosis, ion transport, and morphogenesis. Of most interest is the downregulation of nuclear receptor proteins. Differentially expressed genes between early-stage cluster and late-stage clusters were identified. We found 90 genes preferentially overly expressed and 165 genes relatively downregulated at late-stage cancers. The advanced cancer appears differently from early-stage cancer in cell growth, cell adhesion, hormone activity, morphology, and cell–cell signaling compared with benign or early-stage cancer. Of particular interest are enzymes corresponding to pteridine biosynthesis, reported for the first time in this study. Real-time reverse transcription polymerase chain reaction showed that GCH1, KRT18, H3F3A, and MYBL2 were overly expressed in all cancer tissues, while MDFI, ARP3BETA, COL16A1, and MLN discriminated late-stage from early-stage cancers. Conclusion: The microarray provides valuable resources for comparing expression profiles of cancers at various stages and helps research the diagnosis and mechanism of ovarian cancer. [International Journal of Gerontology 2009; 3(3): 163–169]

Background An evidence-based initiation of quality improvement activity for reducing the usage of prophylactic antibiotic in laparoscopic-assisted vaginal hysterectomy (LAVH) in a tertiary hospital. Aims The authors investigated whether single or multiple doses of cefazoline were more cost-effective in preventing postoperative infection associated with LAVH. Methods The study groups comprised of 310 patients who had undergone LAVH continuously in a medical centre. Patients were divided into two groups on the basis of whether they received a single dose or multiple doses (range: two to four doses) of cefazoline during the perioperative period. Postoperative infections such as pelvic cellulitis or abscess, vaginal cuff abscess, wound infection and urinary tract infection that occurred either during hospitalisation or within one month after discharge were observed and recorded. Incremental cost-effectiveness ratio (ICER) was calculated using the mean direct drug cost and the prophylactic effect of infection in both groups. Results The prophylactic effect of infection was similar in the single-dose group and the multiple-dose group (94.6% vs 93.9%, P = 0.986). The ICER was significantly lower in the single-dose group (153.3 vs 460.4, P Conclusions The result revealed that a single dose of cefazoline is more cost-effective than multiple doses in the prevention of infection associated with LAVH. It fulfils the goal of cost minimisation and quality of care in today's environment of medical cost containment.

Aims To identify risk factors for disease-free survival (DFS) and para-aortic lymph node (PALN) metastasis in advanced cervical cancer patients after concurrent chemoradiotherapy (CCRT) using risk stratification. Materials and methods In total, 148 patients with stage IB2–IVA cervical cancer without PALN metastasis treated with a full course of CCRT were included for analysis. Radiotherapy consisted of external beam irradiation followed by four courses of high-dose rate intracavitary brachytherapy using 6.0 Gy to point A. Chemotherapy consisted of weekly cisplatin at a dose of 40mg/m 2 for a planned six cycles. Cox's proportional hazards model was used for risk stratification for DFS and PALN relapse-free survival. Results Patients were divided into low- and high-risk groups. The low-risk group was composed of patients with stage IB–IIB disease without enlarged pelvic nodes, whereas the high-risk group was comprised of patients with stage IB2–IIB tumours with enlarged nodes or those with stage III–IVA disease. The 4-year DFS for the low- and high-risk groups was 83 and 52%, respectively ( P =0.0001, relative risk 4.51, 95% confidence interval 1.3–10.7), whereas the 4-year PALN metastasis-free survival for the low- and high-risk groups was 92 and 61%, respectively ( P =0.0003, relative risk 4.93, 95% confidence interval 1.2–12.5). Conclusion The risk of failure in advanced cervical cancer patients treated in the CCRT era can be predicted. For patients with high risk of PALN relapse, this study can provide patient selection criteria when considering prophylactic PALN irradiation.

Endometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities.

Objective To determine the association of human papillomavirus (HPV) infection with the expression of dihydrodiol dehydrogenase (DDH) in uterine cervical cancer (UCC). Methods In situ hybridization (ISH) and immunohistochemistry were applied to examine pathological specimens of 145 patients with UCC. Results By ISH, HPV16/18 DNA was detected in 108 (74.5%) UCC cases. DDH expression determined by immunohistochemistry was detected in 81 (75%) lesions among 108 HPV-positive cases. In contrast, of 37 HPV-negative cases, DDH was only detected in 16 (43.2%) of the lesions. A significant correlation was found between DDH expression and the presence of HPV ( P P = 0.004), lymph node involvement ( P P = 0.002). In vitro, DDH expression was also found closely associated with HPV infection, and DDH content was proportional to cell sensitivity for cisplatin and doxorubicin. Conclusions HPV infection provokes local inflammation, which can then induce DDH expression and drug resistance in UCC. The detailed biological relationship among HPV infection, expression of DDH and drug resistance, however, remains to be clarified.

Summary Objective Fetal tachyarrhythmia may cause fetal hydrops and lead to fetal morbidity and mortality. Supraventricular tachycardia and atrial flutter have been the most diagnosed. We present a case of fetal atrial flutter diagnosed during the second trimester treated with digoxin and sotalol and delivered at term. Case Report A 30-year-old primigravid woman was diagnosed with fetal atrial flutter at the gestational age of 25 weeks with atrial rates of 480-520 bpm and ventricular rates of 200-250 bpm. Initially, she was treated with digoxin then with a combination of digoxin and sotalol. The fetal heart beat slowed after sotalol treatment but did not return to sinus rhythm. The fetus was delivered vaginally. Neonatal echocardiography showed a small apical ventricular septal defect and small patent ductus arteriosus. Electrocardiography also revealed atrial flutter with occasional atrial fibrillation. Conclusion The efficacy of antiarrhythmic drug therapy for fetal atrial flutter has not been well established. In our case, we used sotalol combined with digoxin and the fetal heart beat slowed after therapy. Sotalol may be considered the drug of choice for fetal atrial flutter. If the fetal atrial flutter is resistant to these therapies, a combination of other congenital cardiac diseases or organic abnormalities should be considered.

HER-2 codon 655 polymorphism together with human papillomavirus (HPV) types were examined in a total of 279 cervical smear samples. Forty-nine patients with high-grade squamous intraepithelial lesion had higher frequency of high-risk HPV than 167 patients with low-grade squamous intraepithelial lesion and 63 controls. There was no statistical difference in the frequencies of HER-2 Ile/Ile, Ile/Val, and Val/Val genotypes between squamous intraepithelial lesions (SILs) and controls. When the Ile/Ile genotype was compared to the Ile/Val + Val/Val genotypes, there was also no statistical difference in the genotype prevalence between SILs and controls either in 91 or 188 patients with or without high-risk HPV, respectively. These results suggest that the HER-2 polymorphism at codon 655 in cervical cell samples is unlikely to be associated with HPV status and the onset of cervical cancer in a Japanese population.

Background. In this study, we compared the differences in dynamic changes of the bladder neck between women with and without urodynamic stress incontinence by computer-aided vector-based perineal ultrasound. Methods. The function and morphology of the lower urinary tract were assessed in 48 women with or without urodynamic stress incontinence by urodynamic study and computer-aided vector-based perineal ultrasound. Results. Patients in the urodynamic stress incontinence group had a significantly higher parity and higher prevalence of funneling of the bladder neck than participants in the control group (p B /0.05). After adjusting for parity, women with a corrected bladder neck movement ] /10 mm were 9.0 times more at risk of having urodynamic stress incontinence than women with a corrected bladder neck movement B /10 mm (pB /0.05). If we used corrected bladder neck movement ] /10 mm as the cut-off point for diagnosis of urodynamic stress incontinence, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 77.8%, 66.7%, 87.5%, 50%, and 75%, respectively. Conclusions. The increase in corrected bladder neck movement is associated with functional impairment of urethral closure. Computer-aided vector-based perineal ultrasound is valuable in assessing anatomic change of the bladder neck, but it is not a sensitive tool for predicting urodynamic stress incontinence.

Objective To investigate the biological significance of single nucleotide polymorphism (SNP) at Fas gene promoter in cervical carcinogenesis. Methods SNP at −670 of Fas gene promoter (A/G) together with human papillomavirus (HPV) types were examined in a total of 279 cervical smear samples and 8 human cervical squamous carcinoma cell lines using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) techniques. Results 49 patients with high-grade squamous intraepithelial lesion (HSIL) had higher frequency of high-risk HPV and GA + GG genotype than 167 with low-grade SIL (LSIL) and 63 controls. G allele frequency was also higher in HSIL than in LSIL and controls. There was an increased OR (6.00; CI, 1.32–27.37; P = 0.021) for GA + GG genotype in HSIL cases compared to controls among 96 patients with high-risk HPV. 7 of 8 cervical carcinoma cell lines also showed GA or GG genotype. Conclusion Fas gene promoter −670 polymorphism (A/G) may be closely associated with cervical carcinogenesis in a Japanese population.

Purpose: To investigate the biological correlation between vascular endothelial growth factor (VEGF)-C expression and invasive phenotype in ovarian carcinomas. Experimental Design: Gene and protein expression levels of VEGF-C in 10 ovarian carcinoma cell lines were correlated with invasive activity of the cells. The correlation between immunohistochemical expression of VEGF-C and tumor aggressiveness in 73 ovarian carcinomas was also examined with respect to clinicopathologic features and patient outcome. Results: VEGF-C gene and protein expression differed remarkably among the cell lines, and there was a statistical correlation among VEGF-C expression, in vitro invasive activity, and matrix metalloproteinase-2 (MMP-2) gene expression and its activity. Anti-VEGF-C and anti-MMP-2 antibodies inhibited the invasive activity of tumor cells. VEGF-C expression in clinical tissue samples was well correlated with clinical stages, retroperitoneal lymph node metastasis, MMP-2 expression, angiogenesis, lymphangiogenesis, and low apoptotic index (AI). The patients whose tumors had strong VEGF-C expression and low AI underwent a poorer prognosis than did those with weak VEGF-C expression and high AI. Conclusion: VEGF-C expression is closely related to invasive phenotype and affects the patient's survival in ovarian carcinomas.

Objective. To investigate the clinical significance of glutathione-S-transferase GSTM1, GSTT1 and p53 codon 72 polymorphisms in cervical carcinogenesis. Methods. GSTM1, GSTT1 and p53 codon 72 polymorphisms together with human papillomavirus (HPV) types were examined in a total of 198 cervical smear samples using multiplex polymerase chain reaction (PCR) and PCR restriction fragment length polymorphism (RFLP) techniques. Results. Forty-two patients with high-grade squamous intraepithelial lesion (HSIL) had higher frequency of high-risk HPV and null GSTT1 genotype than 102 with low-grade SIL (LSIL) and 54 controls. Thirty-one patients with HSIL had also statistically higher frequency of null GSTT1 genotype than 28 with LSIL among 69 patients with high-risk HPV. There was no statistical difference in p53 Arg, Arg/Pro and Pro genotypes between SILs and controls with or without high-risk HPV. Conclusion. GSTT1 null genotype in cervical cell samples may be associated with more severe precancerous lesions of the cervix in a Japanese population. The p53 codon 72 polymorphism is unlikely to be related to HPV status and the onset of cervical cancer.

Angiogenesis is essential for the pathogenesis of endometriosis. Gene expression levels of vascular endothelial growth factor (VEGF) A and C in 10 eutopic endometrial, 23 normal peritoneal, and 62 endometriotic tissues surgically obtained from 47 women with endometriosis (group 2) were compared with those in 12 control eutopic endometrial and 9 normal peritoneal tissues from 15 women without endometriosis (group 1). VEGF-A mRNA expression levels in eutopic endometrium of group 2 were higher than those of group 1 throughout the menstrual cycle (P0.01) and increased in the secretory phase. VEGF-A gene expression in peritoneal endometriotic lesion was statistically higher than that in normal peritoneum (P0.01) and similar to that in eutopic endometrium of group 2. In contrast, gene expression levels of VEGF-C were relatively lower than those of VEGF-A in each lesion, and no cyclic variation was found. VEGF-A and C mRNA expression levels were significantly higher in ovarian endometriomas6 cm in size than in those6 cm in size. Immunohistochemical expression of VEGF-A and C was detected in the cytoplasm of glandular epithelial and stromal cells of ovarian endometrioma. These results suggest that endometriosis may arise from eutopic endometrium with higher levels of angiogenic activity possibly induced by VEGF-A in women with endometriosis. Moreover, VEGF-C as well as VEGF-A may be involved in the pathogenesis of ovarian endometrioma.

Objective: To evaluate how endometriosis affects expression of vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) in granulosa cells. Design: Prospective study. Setting: IVF-ET program at Osaka Medical College. Patient(s): Seventeen patients with revised American Fertility Society stage IV endometriosis and 17 patients with tubal infertility and no endometriosis. Intervention(s): Granulosa cells obtained at oocyte retrieval were examined for VEGF and IL-6 gene expression. Main Outcome Measure(s): Serum E 2 and P levels at hCG administration, number of oocytes, fertilization rate, high-quality embryo rate, and pregnancy rate, and expression of VEGF and IL-6 genes. Result(s): Total hMG and FSH levels were statistically significantly higher in patients with endometriosis; however, the number of retrieved oocytes and the fertilization rate were lower compared with patients with tubal infertility. Serum E 2 levels and expression of VEGF in patients with tubal infertility were statistically significantly higher than those in patients with endometriosis. Interleukin-6 gene expression did not differ between the groups. Conclusion(s): In severe endometriosis, lower VEGF gene expression in granulosa cells may adversely affect oocyte development and maturation.

Survivin is a novel inhibitor of apoptosis and is expressed during fetal development and in cancer tissues, but its expression has not been reported in normal adult tissues or benign diseases. We investigated survivin gene and protein expression in a tumor-like benign disease, endometriosis, and correlated them with apoptosis and invasive phenotype of endometriotic tissues. Gene expression levels of survivin, matrix metalloproteinase (MMP)-2, MMP-9, and membrane type 1 (MT1)-MMP in 63 pigmented or nonpigmented endometriotic tissues surgically obtained from 35 women with endometriosis were compared with those in normal eutopic endometrium obtained from 12 women without endometriosis. Survivin, MMP-2, MMP-9, and MT1-MMP mRNA expression levels in clinically aggressive pigmented lesions were significantly higher than those in normal eutopic endometrium, and survivin gene expression in pigmented lesions was also higher than that in nonpigmented lesions (P < 0.05). There was a close correlation between survivin and MMP-2, MMP-9, or MT1-MMP gene expression levels in 63 endometriotic tissues examined (P < 0.01). Apoptotic cells detected by the dUTP nick-end labeling were rare in 11 ovarian endometriotic tissues, which showed positive immunohistochemical expression for survivin and MMPs. Our findings suggest that up-regulation of survivin and MMPs may cooperatively contribute to survival and invasion of endometriosis.

Objective Vulvar cancer is rare in Eastern females, especially in pre- and peripubertal girls. The prognosis of vulvar cancer is poor and treatment is variable. Case Report A 14-year-old girl suffered from a left vulvar tenderness mass and underwent excision of the mass. The diagnosis of the pathology was vulvar yolk tumor with an embryonal carcinoma. After the vulvectomy, inguinal area lymph node dissection, chemotherapy (bleomycin, etoposide and cisplatin) treatment and radiotherapy, metastasis to lung was also noted after eight months. Resection of lung tumor was performed. She received chemotherapy with a combination of paclitaxel, ifosphamide and cisplatin (TIP) and received peripheral blood stem cell transplantation (PBSCT) twice and chemotherapy treatment of gemitabine and oxaliplatin (GEMOX). Up until now, the patient has been free of disease. Conclusion High-dose TIP and GEMOX chemotherapy plus PBSCT for bone marrow rescues could be considered to treat patients with metastatic malignant vulvar germ cell tumor after failed first-line chemotherapy and radiation.

Motivation: Ovarian cancer is the fifth leading cause of cancer deaths in women in the western world for 2013. In ovarian cancer, benign tumors turn malignant, but the point of transition is difficult to predict and diagnose. The 5-year survival rate of all types of ovarian cancer is 44%, but this can be improved to 92% if the cancer is found and treated before it spreads beyond the ovary. However, only 15% of all ovarian cancers are found at this early stage. Therefore, the ability to automatically identify and diagnose ovarian cancer precisely and efficiently as the tissue changes from benign to invasive is important for clinical treatment and for increasing the cure rate. This study proposes a new ovarian carcinoma classification model using two algorithms: a novel discretization of food sources for an artificial bee colony (DfABC), and a support vector machine (SVM). For the first time in the literature, oncogene detection using this method is also investigated. Results: A novel bio-inspired computing model and hybrid algorithms combining DfABC and SVM was applied to ovarian carcinoma and oncogene classification. This study used the human ovarian cDNA expression database to collect 41 patient samples and 9600 genes in each pathological stage. Feature selection methods were used to detect and extract 15 notable oncogenes. We then used the DfABC-SVM model to examine these 15 oncogenes, dividing them into eight different classifications according to their gene expressions of various pathological stages. The average accuracyof the eight classification experiments was 94.76%. This research also found some oncogenes that had not been discovered or indicated in previous scientific studies. The main contribution of this research is the proof that these newly discovered oncogenes are highly related to ovarian or other cancers. Availability and implementation: http://mht.mis.nchu.edu.tw/moodle/course/view.php?id=7 Contact: mychen@nutc.edu.tw

ObjectiveThis study aimed to determine the clinical prognostic factors involved in carcinosarcoma of the ovary, fallopian tube, and peritoneum.Materials and MethodsThis 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.ResultsIn 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.ConclusionsEarly 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.

Mullerian anomalies occur in 0.1–0.5% of women [1]. Failure of the paired mullerian ducts to fuse laterally can result in uterus didelphys with obstructed unilateral vagina. This congenital disorder is often associated with renal anomalies, such as ipsilateral renal agenesis, renal dysplasia, a double collecting system, and an ectopic ureter [2–4]. Affected girls may present with low abdominal pain, severe dysmenorrhea, a pelvic or vaginal mass, abnormal vaginal discharge, and intermenstrual bleeding. These symptoms usually appear in adolescent girls after menarche. Because of the small vaginal orifice and relatively high location of the vaginal septum in affected girls with an intact hymen, it is difficult to correct the vaginal anomaly without a hymenectomy. However, young female virgins with this congenital anomaly may have a strong desire to preserve the integrity of their hymenal ring for ethnic or personal reasons. Hysteroscopic resection of the vaginal septum with obstructed hemivagina has been reported to maintain the patient’s virginity [5]. Ultrasound guidance can be used to improve the safety of resectoscopic surgical procedures. [6]. We present the case of a female virgin with this rare syndrome, pyocolpos, and a vertical vaginal septum. She was treated with a minimally invasive resectoscopic operation under transabdominal ultrasound guidance. The integrity of her hymen was preserved after the surgery. A 15-year-old girl visited our department with a 6month history of intermittent low abdominal pain and fever. She denied having any sexual experience. Menarche had occurred at 12 years, with subsequent regular menstrual intervals. A pelvic examination revealed low

To determine the factors associated with hysteroscopic surgery long-term outcome in patients with intrauterine adhesions or submucosal myomas.Factors thought to be associated with outcome were retrospectively evaluated from the records of 591 patients who were followed up for at least 5years after undergoing hysteroscopic adhesiolysis (n=203) or myomectomy (n=388).The major factors affecting outcome were degree of adhesion (OR, 1.91; P=0.03) in the former group and parity (OR, 0.55; P=0.005) and depth of intramural penetration of the myoma (OR, 30.74; P0.001) in the latter. Severe intrauterine adhesion, low parity, and deep intramural penetration of submucosal myoma had an associated increase risk of poor outcome. The overall complication rate was 1.35% and, respectively, 12.8% and 9.3% of the patients who underwent hysteroscopic adhesiolysis or myomectomy needed a second intervention.Hysteroscopic surgery is a safe and effective procedure. Degree of adhesion or parity and depth of intramural penetration of myomas are the major factors affecting outcome in patients with these lesions.

ObjectiveThe objective of this study was to assess prospectively the clinical outcomes of low-dose prophylactic extended-field, intensity-modulated radiotherapy (IMRT) plus concurrent weekly cisplatin for patients with stage IB2-IIIB cervical cancer, positive pelvic lymph nodes (PLNs), and negative para-aortic lymph nodes (PALNs).MethodsThirty-two patients with stage IB2-IIIB cervical cancer with positive PLN and negative PALN were included prospectively. All lymph nodes were assessed with positron emission tomography. The PALN field, including lymphatics from the superior border of L1 to the L4-L5 interphase, was irradiated concurrently with pelvic IMRT with a prescribed dose of 40 Gy in 25 fractions. Chemotherapy consisted of cisplatin delivered weekly at a dose of 40 mg/m2. Using historical controls treated with pelvic radiotherapy, the survival curves were compared to assess the difference between the 2 treatment periods.ResultsThirty-one patients completed the allocated extended-field IMRT, and all finished the planned pelvic IMRT and brachytherapy. Acute ≥ grade 3 gastrointestinal, genitourinary, and hematologic toxicities were seen in 2, 1, and 18 patients, respectively. During a median follow-up of 33 months, 5 patients developed out-field distant recurrences. One patient had a late grade 3 gastrointestinal complication, and 1 patient had genitourinary toxicity. The 3-year actuarial overall survival, disease-free survival, and distant metastasis–free survival for the study cohort and historic controls were 87% versus 62% (P = 0.02), 82% versus 54% (P = 0.02), and 79% versus 57% (P = 0.01), respectively.ConclusionsExtended-field IMRT of 40 Gy to the PALN plus concurrent cisplatin can effectively eradicate subclinical disease at the PALN and improve the outcome for patients with PLN-positive stage IB2-IIIB cervical cancer.

Cervical cancer ranks as the fourth leading cause of cancer death in women worldwide. In Taiwan, although the universal health insurance system has achieved 99.9% coverage and ensured easy access to medical care, some cervical cancer patients continue to delay initiation of definitive treatment after diagnosis. This study focused on cervical cancer patients who delayed treatment for at least 4 months, and examined the characteristics, related factors, and survival in these patients.Data on patients with a new confirmed diagnosis of cervical cancer by the International Federation of Gynecology and Obstetrics (FIGO) staging system between 2005 and 2010 were obtained from the National Health Insurance Research Database and the Taiwan Cancer Registry. Logistic regression analysis was performed to analyze the association of various factors with treatment delay. The Cox proportional hazards model was used to analyze the effects of various factors on mortality risk.The rate of treatment delay for cervical cancer decreased steadily from 6.46% in 2005 to 2.48% in 2010. Higher rates of treatment delay were observed among patients who were aged ≥75 years (9.91%), had severe comorbidity, had stage IV (9.50%), diagnosing hospital level at nonmedical center, or at public hospital ownership. Factors that correlated with treatment delay were age ≥75 years (odds ratio [OR] = 2.42), higher comorbidity Charlson comorbidity index (CCI) 4-6, or ≥7 (OR = 1.60, 2.00), cancer stage IV (OR = 2.60), the diagnosing hospital being a regional, district hospital, or other (OR = 3.00, 4.01, 4.60), and at public hospital ownership. Those who delayed treatment had 2.31 times the mortality risk of those who underwent timely treatment (P

Background. Comparing initial 45 Gy of pelvic intensity-modulated radiation therapy (IMRT) and non-IMRT in terms of the late toxicities associated with advanced cervical cancer that has also been treated with definitive concurrent chemoradiotherapy and high-dose rate intracavitary brachytherapy (HDRICB). Patients and methods. This retrospective study included 320 stage IB2-IIIB cervical cancer patients treated with CCRT (83 IMRT and 237 non-IMRT). The two groups had similar stage and HDRICB ratings. Following 45 Gy to the pelvis, HDRICB of 24 Gy in four courses was prescribed. Late toxicities, including rectal complications (RC), bladder complications (BC) and non-rectal intestinal injury (NRRII), were scored by the Common Terminology Criteria for Adverse Events. A logistic regression was used to estimate the odds ratio (OR) of the complications. Results. With a median follow-up duration of 33 and 77 months for IMRT and non-IMRT, 33 patients had Grade 2 or higher late RC (7.2% IMRT, 11.4% non-IMRT), whereas that for BC was 40 (9.6% IMRT, 13.5% non-IMRT) and for NRRII was 48 (12.0% IMRT, 16.0% non-IMRT). The cumulative rate for total grade 3 or higher gastrointestinal or genitourinary toxicities was 8.4% and 11.8% (p = 0.33). IMRT did not reduce the OR for all endpoints; however, the ORs for rectum and bladder reference doses to Point A were associated with RC and BC. Conclusions. Locally advanced cervical cancer patients treated with initial 45Gy of pelvic IMRT and HDRICB have similar treatment-related late toxicities as those treated with non-IMRT. Optimization of the brachytherapy scheme is essential to minimize late toxicities.

Early reports suggested androgen/androgen receptor (AR) signals promote hepatocarcinogenesis. However, all antiandrogen clinical trials failed in advanced hepatocellular carcinoma (HCC) without reasonable explanations. We examined AR functions in HCC cancer metastasis in this study. We examined hepatic AR roles in HCC metastasis by comparing liver hepatocyte AR knockout and wildtype in a carcinogen-induced HCC mouse model. We examined tumor histology, cancer metastatic risks, and cancer survival in vivo, as well as cell anoikis and migration using primary hepatic tumor culture in vitro. We also examined therapeutic potentials of AR expression combined with the molecular targeting agent sorafenib in an HCC metastasis mouse model. We found a novel cancer phenotype in which mice lacking hepatic AR developed more undifferentiated tumors and larger tumor size at the metastatic stage. These mice also died earlier with increased lung metastasis, suggesting that hepatic AR may play dual yet opposite roles to promote HCC initiation but suppress HCC metastasis. Mechanistic dissection found that hepatic AR could enhance anoikis and suppress migration of HCC cells by way of suppression of p38 phosphorylation/activation and the nuclear factor kappa B (NF-κB)/matrix metallopeptidase 9 (MMP9) pathway, respectively. In addition, the in vivo preclinical trials concluded that a combination therapy of increased AR expression and reduced multiple-kinase inhibitor (sorafenib) exhibited better therapeutic efficacy.Our study demonstrates that AR could orchestrate intrahepatic signaling hierarchies and cellular behaviors, consequently affect HCC progression. Results from combination therapy shed light on developing new therapeutic paradigms for battling HCC at later metastatic stages.

Objective To assess risk factors for postoperative pelvic cellulitis in women undergoing laparoscopic-assisted vaginal hysterectomy (LAVH). Materials and Methods A total of 195 patients who underwent LAVH for benign gynecological diseases during the period 2007–2008 were enrolled. Among them, 11 patients developed pelvic cellulitis (group 1, cases) and 184 did not (group 2, controls). Results The proportion of patients in American Society of Anesthesiologists physical status scale (ASA) class II was significantly higher in group 1 (p = 0.017). The grade of pelvic adhesion was significantly more severe in group 1 (p = 0.044). The mean length of hospital stay in group 1 was significantly longer than in group 2. Logistic regression analysis revealed that patients in ASA class II were six times more likely to develop postoperative pelvic cellulitis than patients in ASA class I. In addition, the analysis showed that there was a twofold increase in risk for pelvic cellulitis with each single-grade increase in the degree of pelvic adhesion. Women with postoperative pelvic cellulitis also had a significantly increased length of hospital stay. Conclusion Understanding the risk factors for postoperative pelvic infection, such as systemic disease, pelvic adhesion, and prolonged hospital stay, comprehensive care of patients, and correction of modifiable risk factors will help reduce the rate of postoperative pelvic cellulitis in women undergoing LAVH.

Our aim was to determine the association of human papillomavirus (HPV) infection with the expression of ATPase family AAA domain containing 3A (ATAD3A), an anti-autophagy factor, in uterine cervical cancer (UCC). The HPV genotype was determined by an Easychip HPV blot assay. ATAD3A expression was determined by immunohis- tochemical staining. High-risk HPV (hrHPV) was detected in 184 (88.9%) of 207 UCC cases. ATAD3A expression was detected in 164 (79.2%) UCC cases. A significant correlation was found between ATAD3A expression and the presence of hrHPV (p

Hepatitis B virus (HBV)-induced hepatitis and carcinogen-induced hepatocellular carcinoma (HCC) are associated with serum androgen concentration. However, how androgen or the androgen receptor (AR) contributes to HBV-induced hepatocarcinogenesis remains unclear. We found that hepatic AR promotes HBV-induced hepatocarcinogenesis in HBV transgenic mice that lack AR only in the liver hepatocytes (HBV-L-AR(-/y)). HBV-L-AR(-/y) mice that received a low dose of the carcinogen N'-N'-diethylnitrosamine (DEN) have a lower incidence of HCC and present with smaller tumor sizes, fewer foci formations, and less alpha-fetoprotein HCC marker than do their wild-type HBV-AR(+/y) littermates. We found that hepatic AR increases the HBV viral titer by enhancing HBV RNA transcription through direct binding to the androgen response element near the viral core promoter. This activity forms a positive feedback mechanism with cooperation with its downstream target gene HBx protein to promote hepatocarcinogenesis. Administration of a chemical compound that selectively degrades AR, ASC-J9, was able to suppress HCC tumor size in DEN-HBV-AR(+/y) mice. These results demonstrate that targeting the AR, rather than the androgen, could be developed as a new therapy to battle HBV-induced HCC.

Objective The goal of this study was to analyze the potential risk factors of surgical failure after posterior intravaginal slingplasty for uterine or vaginal vault prolapse. Study design Women with symptomatic uterine or vaginal vault prolapse that extended to or beyond the introitus were eligible for inclusion. Each woman underwent a detailed history taking and a vaginal examination for staging of pelvic organ prolapse before treatment. Follow-up evaluations were at 3, 6, 9, 12, 18, 24, and 30 months after the operation. Surgical failure is defined as the presence of symptomatic uterine or vaginal vault prolapse ≧stage 2 (higher than 0, at the hymen) after posterior intravaginal slingplasty. Results The surgical failure rate (8/61) following posterior intravaginal slingplasty was 13.1%. Using univariable logistic regression, C or D point stage IV before surgery was significantly associated with surgical failure of posterior intravaginal slingplasty for uterine or vaginal vault prolapse. Complications (11/61 = 18%) included vaginal erosion (9.8%), blood loss over 500 ml (4.9%), and perineal pain (3.3%). Conclusion Procidentia is a significant risk factor for surgical failure of posterior intravaginal slingplasty, and therefore this procedure should never be used alone in patients with complete uterine or vaginal vault prolapse.

The goal of this study was to analyze the potential risk factors determining surgical failure after sacrospinous suspension for uterine or vaginal vault prolapse. Each woman underwent a detailed history taking and a vaginal examination before treatment. Follow-up evaluations were at immediate post-operation, 1 week, 1 to 3 months, 6 months, 9 months, and annually after the operation. The surgical failure rate (27/168) following sacrospinous suspension was 16.1%. Using multivariable logistic regression, women with the presence of C or D point stage I at immediate post-operation were a significant risk factor for surgical failure after sacrospinous suspension (odds ratio, 35.34; 95% confidence interval, 8.75-162.75; p < 0.001). The success rate during the 18-month follow-up decreased significantly in women with the presence of C or D point stage I at immediate post-operation than stage 0. Although the sample size of women with symptomatic uterine or vaginal vault prolapse is small, impaired correction of anatomic defects is a significant risk factor for surgical failure of sacrospinous suspension.