Efficacy of estrogen-progestogen therapy for women with vascular retained products of conception following miscarriage or abortion.

OBJECTIVE: To assess the clinical characteristics and endocrinological background of women with vascular retained products of conception (RPOC) after miscarriage or abortion and evaluate the effect of estrogen-progestogen therapy (EPT) as an initial treatment on this population based on their endocrinological background. MATERIALS AND METHODS: Women with vascular RPOC after miscarriage or abortion at less than 20 weeks of pregnancy who were given EPT (conjugated estrogen and norethisterone) were retrospectively reviewed. Their clinical characteristics, hormonal parameters, ultrasonographic findings, and outcomes were evaluated. RESULTS: Of 35 women with vascular RPOC, 30 (86%) presented with vaginal bleeding at a visit, and 6 (17%) required inpatient management due to heavy bleeding. Among women who presented with vaginal bleeding, serum progesterone levels were significantly lower (0.25 vs. 6.5 ng/mL, p = 0.004) than those in women who did not present with vaginal bleeding. There were no differences in serum hCG levels (10.5 vs. 3.1 mIU/mL) or serum estradiol levels (65.4 vs. 162.3 pg/mL). After withdrawal bleeding following the first course of EPT, vaginal bleeding was stopped in 27 of the 30 women (90%), and 23 (66%) of all women had a thin and linear endometrium. All women could be treated by up to two courses of EPT and did not require additional interventions. The median duration to hCG normalization after the initial EPT was 24.5 (9-88) days. CONCLUSION: Women with vascular RPOC who have no bleeding had significantly higher levels of serum progesterone, indicating that administration of progestogen may have an effect on hemostasis. Endometrial bleeding can be prevented or stopped, and retained tissues can be conservatively expelled by oral administration of EPT, including norethisterone, in women with vascular RPOC.

Human papillomavirus vaccine impact on invasive cervical cancer in Japan: Preliminary results from cancer statistics and the MINT study.

The first prophylactic vaccine against human papillomavirus (HPV) 16 and HPV18 was licensed in Japan in 2009. HPV vaccine effectiveness against high-grade cervical lesions has been demonstrated among young Japanese women, but evidence of its effects on invasive cervical cancer (ICC) is lacking. Using data from two different cancer registries, we compared recent trends of new ICC cases by age group using Poisson regression analysis. We also analyzed time trends in HPV16/18 prevalence among 1414 Japanese women aged <40 years newly diagnosed with ICC in the past decade. Based on the population-based cancer registry, the incidence of ICC among young women aged 20-29 years showed a significant decline from 3.6 to 2.8 per 100 000 women-years during 2016-2019, but no similar decline was observed for older age groups (p < 0.01). Similarly, using data from the gynecological cancer registry of the Japan Society of Obstetrics and Gynecology, the annual number of ICCs among women aged 20-29 years also decreased from 256 cases to 135 cases during 2011-2020 (p < 0.0001). Furthermore, a declining trend in HPV16/18 prevalence in ICC was observed only among women aged 20-29 years during 2017-2022 (90.5%-64.7%, p = 0.05; Cochran-Armitage trend test). This is the first report to suggest population-level effects of HPV vaccination on ICC in Japan. Although the declining trend in HPV16/18 prevalence among young women with ICC supports a causal linkage between vaccination and results from cancer registries, further studies are warranted to confirm that our findings are attributable to vaccination.

Advantages and limitations of estrogen replacement therapy on hypogonadal survivors of childhood cancer.

BACKGROUND: Hypogonadism is a significant late complication in childhood cancer survivors (CCS). The aim of this study was to elucidate the advantages and limitations of estrogen replacement therapy (ERT) for CCS with hypogonadism. METHODS: Seventeen CCS were divided into two groups: gonadal hypogonadism (GH) group (n = 8) and central hypogonadism (CH) group (n = 9). Pearson correlation coefficients were used to investigate the impact of cancer management on final height, bone density, and uterine development. RESULTS: Seven of GH group had hematologic malignancies, and all of them underwent total body irradiation before bone marrow transplantation. The GH group showed significant positive correlations between the onset age of disease treatment and final height (p < 0.05, R = 0.712) and uterine size following ERT (p < 0.05, R = 0.775). All CCS in the CH group had brain tumors, and seven of them received chemotherapy. There were trends towards positive and negative correlations between the onset age of disease treatment and final height (p = 0.09, R = 0.598) or uterine size (p = 0.07, R = - 0.669), respectively. A negative correlation trend was observed between the age at ERT initiation and final height (p = 0.07, R = - 0.769) or bone density (p = 0.18, R = - 0.626) in six CH patients who received growth hormone therapy. Five CCS in both groups experienced osteoporosis, despite receiving ERT. CONCLUSION: Individualized management strategies beyond ERT are essential to reduce long-term complications in CCS with hypogonadism, considering the type and timing of cancer treatment.

Mismatch repair protein deficiency in endometriosis: Precursor of endometriosis-associated ovarian cancer in women with lynch syndrome.

OBJECTIVE: We aimed to elucidate the pathogenesis of ovarian cancer through the loss of mismatch repair (MMR) proteins in women with Lynch syndrome (LS) in this report. CASE REPORT: Two women with LS underwent surgery for synchronous endometrial cancer and ovarian cancer. In both cases, immunohistochemical examination showed concomitant MMR protein deficiency in endometrial cancer, ovarian cancer, and contiguous ovarian endometriosis. In Case 1, the macroscopically normal ovary included multiple endometrioses with MSH2 and MSH6 expression, and FIGO grade 1 endometrioid carcinoma and contiguous endometriosis without MSH2 and MSH6 expression. In Case 2, all endometriotic cells contiguous with carcinoma in the lumen of the ovarian cyst showed loss of the expression of MSH2 and MSH6. CONCLUSION: Ovarian endometriosis with MMR protein deficiency may progress to endometriosis-associated ovarian cancer in women with LS. Diagnosing endometriosis in women with LS during surveillance is important.

Surgical efficacy and quality of wide resection of the pelvic peritoneum in patients with epithelial ovarian cancer.

PURPOSE: The aim of the study was to evaluate the impact of adding an extensive pelvic peritoneal stripping procedure, termed "wide resection of the pelvic peritoneum," (WRPP) to standard surgery for epithelial ovarian cancer on survival effectiveness and to investigate the role of ovarian cancer stem cells (CSCs) in the pelvic peritoneum. METHODS: A total of 166 patients with ovarian cancer undergoing surgical treatment at Kumamoto University Hospital between 2002 and 2018 were retrospectively analyzed. Eligible patients were divided into three groups based on the surgical approach: standard surgery (SS) group (n = 36), WRPP group (standard surgery plus WRPP, n = 100), and rectosigmoidectomy (RS) group (standard surgery plus RS, n = 30). Survival outcomes were compared between the three groups. CD44 variant 6 (CD44v6) and EpCAM expression, as markers of ovarian CSCs, in peritoneal disseminated tumors were evaluated using immunofluorescence staining. RESULTS: With respect to patients with stage IIIA-IVB ovarian cancer, there were significant differences in overall and progression-free survival between the WRPP and SS groups, as revealed by univariate (hazard ratio [HR], 0.35; 95% confidence interval [CI], 0.17-0.69; P = 0.003 and HR, 0.54; 95% CI, 0.31-0.95; P = 0.032, respectively) and multivariate Cox proportional hazards models (HR, 0.35; 95% CI, 0.17-0.70; P = 0.003 and HR, 0.54; 95% CI, 0.31-0.95; P = 0.032, respectively). Further, no significant differences were observed in survival outcomes between the RS group and the SS or WRPP group. Regarding the safety of WRPP, no significant differences in major intraoperative and postoperative complications were found between the three groups. Immunofluorescence analysis revealed a high percentage of CD44v6/EpCAM double-positive ovarian cancer cells in peritoneal disseminated tumors. CONCLUSION: The present study demonstrates that WRPP significantly contributes to improved survival in patients with stage IIIA-IVB ovarian cancer. WRPP could result in eradicating ovarian CSCs and disrupting the CSC niche microenvironment in the pelvic peritoneum.

Regional differences in human papillomavirus type 52 prevalence among Japanese women with cervical intraepithelial neoplasia†.

Although geographical differences in the distribution of human papillomavirus genotypes have been observed worldwide, no studies have reported on national differences in the prevalence of human papillomavirus types in Japan. Here, we report a cross-sectional study to explore regional differences in the prevalence of human papillomavirus types among Japanese women with cervical intraepithelial neoplasia or invasive cervical cancer. Using human papillomavirus genotyping data from the nationwide prospective study on human papillomavirus vaccine effectiveness, we compared the frequency of detection of 15 high-risk and two low-risk human papillomavirus types in each disease category between the women who visited hospitals located in eastern Japan and those who visited hospitals located in western Japan. The risk of cervical intraepithelial neoplasia progression was assessed by calculating a prevalence ratio of each human papillomavirus type for cervical intraepithelial neoplasia grade 2/3 versus grade 1. Among the human papillomavirus types studied, human papillomavirus 52 was detected significantly more frequently in western hospitals than in eastern hospitals in cervical intraepithelial neoplasia grade 1 patients, but was less frequent in cervical intraepithelial neoplasia grade 2/3. The prevalence of particular human papillomavirus types was not significantly different between patients in hospitals in eastern Japan and those in hospitals in western Japan for invasive cervical cancer. In both eastern and western hospitals, a higher risk of cervical intraepithelial neoplasia progression was observed in patients infected with human papillomavirus 16, 31 or 58. In contrast, there was a significantly higher prevalence of human papillomavirus 52 infection in women with cervical intraepithelial neoplasia grade 2/3 than in those with cervical intraepithelial neoplasia grade 1 in eastern hospitals (prevalence ratio, 1.93; 95% confidence interval, 1.48-2.58), but not in western hospitals (prevalence ratio, 1.03; 95% confidence interval, 0.83-1.30). Regional differences of human papillomavirus 52 prevalence in cervical intraepithelial neoplasia lesions may exist and emphasize the importance of continuous monitoring of human papillomavirus type prevalence throughout the country in order to accurately assess the efficacy of human papillomavirus vaccines.

Fertility-sparing surgery for early-stage cervical cancer: A case series study on the efficacy and feasibility of cervical conization followed by pelvic lymphadenectomy.

OBJECTIVES: To evaluate the oncologic and obstetric outcomes of cervical conization followed by pelvic lymphadenectomy, which is used as a fertility-sparing procedure, in reproductive-aged patients with early-stage cervical cancer. METHODS: We performed a retrospective study of patients with stage IA1-IB1 cervical cancer who underwent cervical conization followed by pelvic lymphadenectomy from 2011 to 2020 at Kumamoto University Hospital. RESULTS: In total, eight patients underwent conization followed by pelvic lymphadenectomy. The median age of the patients was 33 (range: 28-36) years. Four (50.0%) patients were nulliparous. Seven (87.5%) patients were diagnosed with squamous cell carcinoma (87.5%) and one (12.5%) with adenocarcinoma. Five (62.5%), two (25.0%), and one (12.5%) presented with stage IA1, IA2, and IB1 disease, respectively. Five (62.5%) patients had lymphovascular space invasion (LVSI) based on the assessment of specimens obtained via conization. However, none had lymph node metastasis based on pelvic lymphadenectomy. Regarding long-term oncologic outcomes, recurrence was not observed at a median follow-up of 60 (range: 8-107) months. In addition, obstetric outcomes were consistently favorable in terms of achieving pregnancy, preterm delivery, and live birth. During the study period, two patients who actively attempted to conceive had four pregnancies, resulting in full-term deliveries, and one was on her first trimester of pregnancy. CONCLUSION: Cervical conization combined with pelvic lymphadenectomy represents a feasible conservative management for histologically well-selected patients with early-stage cervical cancer. Furthermore, an optimal histopathological evaluation of conization specimens will contribute to decision-making regarding the use of this fertility-sparing procedure.

Changes in HPV16/18 Prevalence among Unvaccinated Women with Cervical Intraepithelial Neoplasia in Japan: Assessment of Herd Effects following the HPV Vaccination Program.

Since the human papillomavirus (HPV) vaccination program for Japanese girls aged 12-16 years began in 2010, vaccination uptake has been low in women born before 1993 but high (approximately 70%) in those born during 1994-1999. We previously compared the prevalence of vaccine types HPV16 and HPV18 in cervical intraepithelial neoplasia grade 1-3 (CIN1-3) or adenocarcinoma in situ (AIS) between vaccinated and unvaccinated cohorts and found direct protection effects among vaccinated women in Japan. In this study, we focused on changes in HPV16/18 prevalence among "unvaccinated" cohorts with CIN/AIS. We analyzed HPV16/18 prevalence among 5051 unvaccinated women aged <40 years, newly diagnosed with CIN/AIS during 2012-2021 for time trends. Declining trends in HPV16/18 prevalence over 9 years were observed in CIN1 (36.0-10.0%, Ptrend = 0.03) and CIN2-3/AIS (62.5-36.4%, Ptrend = 0.07) among women aged <25 years. HPV16/18 prevalence in CIN1 and CIN2-3/AIS diagnosed at age 20-24 years was lower in 1994-1999 birth cohorts compared with 1988-1993 birth cohorts (4.5% vs. 25.7% for CIN1 and 40.0% vs. 58.1% for CIN2-3/AIS, both p = 0.04). Significant reduction in HPV16/18 prevalence among young unvaccinated women with CIN1 and CIN2-3/AIS suggests herd effects of HPV vaccination in Japan.

Human papillomavirus vaccine effectiveness by age at first vaccination among Japanese women.

In Japan, the National Immunization Program against human papillomavirus (HPV) targets girls aged 12-16 years, and catch-up vaccination is recommended for young women up to age 26 years. Because HPV infection rates increase soon after sexual debut, we evaluated HPV vaccine effectiveness by age at first vaccination. Along with vaccination history, HPV genotyping results from 5795 women younger than 40 years diagnosed with cervical intraepithelial neoplasia grade 2-3 (CIN2-3), adenocarcinoma in situ (AIS), or invasive cervical cancer were analyzed. The attribution of vaccine-targeted types HPV16 or HPV18 to CIN2-3/AIS was 47.0% for unvaccinated women (n = 4297), but 0.0%, 13.0%, 35.7%, and 39.6% for women vaccinated at ages 12-15 years (n = 36), 16-18 years (n = 23), 19-22 years (n = 14), and older than 22 years (n = 91), respectively, indicating the greater effectiveness of HPV vaccination among those initiating vaccination at age 18 years or younger (P < .001). This finding was supported by age at first sexual intercourse; among women with CIN2-3/AIS, only 9.2% were sexually active by age 14 years, but the percentage quickly increased to 47.2% by age 16 and 77.1% by age 18. Additionally, the HPV16/18 prevalence in CIN2-3/AIS was 0.0%, 12.5%, and 40.0% for women vaccinated before (n = 16), within 3 years (n = 8), and more than 3 years after (n = 15) first intercourse, respectively (P = .004). In conclusion, our data appear to support routine HPV vaccination for girls aged 12-14 years and catch-up vaccination for adolescents aged 18 years and younger in Japan.

Angiopoietin-like protein 2 decreases peritoneal metastasis of ovarian cancer cells by suppressing anoikis resistance.

Peritoneal metastasis is a common mode of spread of ovarian cancer. Despite therapeutic advances, some patients have intractable peritoneal metastasis. Therefore, in-depth characterization of the molecular mechanism of peritoneal metastasis is a key imperative. Angiopoietin-like protein 2 (ANGPTL2) is an inflammatory factor which activates NF-κB signaling and plays an important role in the pathogenesis of various inflammatory diseases including cancers, such as lung and breast cancer. In this study, we examined the role of ANGPTL2 in ovarian cancer peritoneal metastasis. We observed no difference of cell proliferation between ANGPTL2-expressing and control cells. In the mouse intraperitoneal xenograft model, formation of peritoneal metastasis by ANGPTL2-expressing cells was significantly decreased compared to control. In the in vitro analysis, the expressions of integrin α5ß1, α6, and ß4, but not those of αvß3, α3, α4, and ß1, were significantly decreased in ANGPTL2-expressing cells compared to control cells. ANGPTL2-expressing cells showed significantly inhibited adherence to laminin compared to control. In addition, we observed upregulation of anoikis (a form of programmed cell death occurring under an anchorage-independent condition) and significant decrease in the expression of Bcl-2 in ANGPTL2-expressing cells as compared to control cells. These results suggest that ANGPTL2 expression in ovarian cancer cells represses peritoneal metastasis by suppressing anoikis resistance.

Adipocyte-like signature in ovarian cancer minimal residual disease identifies metabolic vulnerabilities of tumor-initiating cells.

Similar to tumor-initiating cells (TICs), minimal residual disease (MRD) is capable of reinitiating tumors and causing recurrence. However, the molecular characteristics of solid tumor MRD cells and drivers of their survival have remained elusive. Here we performed dense multiregion transcriptomics analysis of paired biopsies from 17 ovarian cancer patients before and after chemotherapy. We reveal that while MRD cells share important molecular signatures with TICs, they are also characterized by an adipocyte-like gene expression signature and a portion of them had undergone epithelial-mesenchymal transition (EMT). In a cell culture MRD model, MRD-mimic cells showed the same phenotype and were dependent on fatty acid oxidation (FAO) for survival and resistance to cytotoxic agents. These findings identify EMT and FAO as attractive targets to eradicate MRD in ovarian cancer and make a compelling case for the further testing of FAO inhibitors in treating MRD.

The hallmarks of ovarian cancer stem cells and niches: Exploring their harmonious interplay in therapy resistance.

The concept of a "cancer stem cell" has evolved over the past decades, and research on cancer stem cell biology has entered into a stage of remarkable progress. Cancer stem cells are a major determining factor contributing to the establishment of phenotypic and functional intratumoral heterogeneity in synchronization with their surrounding "cancer stem cell niches." They serve as the driving force for cancer initiation, metastasis, and therapeutic resistance in various types of malignancies. In verity, reciprocal interplay between ovarian cancer stem cells and their niches involves a complex but ingeniously orchestrated tumor microenvironment within the intraperitoneal milieu and especially contribute to chemotherapy resistance in patients with advanced ovarian cancer. Herein, we review the principles of our current understanding of the biological features of ovarian cancer stem cells, focusing mainly on the precise mechanisms underlying acquired chemotherapy resistance. Furthermore, we highlight the specific roles of various cancer-associated stromal and immune cells in creating possible cancer stem cell niches that regulate ovarian cancer stemness.

Omental metastasis as a predictive risk factor for unfavorable prognosis in patients with stage III-IV epithelial ovarian cancer.

BACKGROUND: Epithelial ovarian cancer has a clear predilection for the omentum as the site of metastasis; however, its contribution to clinical outcomes remains unresolved. This study aimed to evaluate the prognostic significance and efficacy of chemotherapy in the presence of omental metastasis. METHODS: A retrospective cohort study was performed in 56 patients with stage III-IV ovarian cancer who underwent primary debulking surgery between 2004 and 2018 at Kumamoto University Hospital. RESULTS: Thirty-six (64.3%) patients were categorized into the omental metastasis-positive group, whereas 20 (35.7%) patients were in the omental metastasis-negative group. The 5-year overall survival rates were 43.4% in the omental metastasis-positive group and 93.8% in the omental metastasis-negative group. Statistically significant differences were observed in overall survival (p = 0.002) and progression-free survival (p = 0.036) between the omental metastasis-positive and metastasis-negative groups. Notably, multivariate analysis demonstrated that the existence of omental metastasis is an independent risk factor for overall survival in patients with stage III-IV ovarian cancer (hazard ratio 8.90, 95% confidence interval 1.16-69.77; p = 0.038). Furthermore, the omental metastasis-positive group had significantly lower overall response rates to chemotherapy for recurrent disease, compared to the omental metastasis-negative group (31.6% vs. 85.7%, p = 0.026). CONCLUSION: Our present data demonstrated that omental metastasis is closely associated with an unfavorable prognosis due to increased chemoresistance in patients with stage III-IV ovarian cancer. Elucidating the biological mechanism of omental metastasis will shed light on novel therapeutic approaches for the management of advanced ovarian cancer patients.

Human papillomavirus genotype contribution to cervical cancer and precancer: Implications for screening and vaccination in Japan.

To obtain baseline data for cervical cancer prevention in Japan, we analyzed human papillomavirus (HPV) data from 5045 Japanese women aged less than 40 years and diagnosed with cervical abnormalities at 21 hospitals during 2012-2017. These included cervical intraepithelial neoplasia grade 1 (CIN1, n = 573), CIN2-3 (n = 3219), adenocarcinoma in situ (AIS, n = 123), and invasive cervical cancer (ICC, n = 1130). The Roche Linear Array was used for HPV genotyping. The HPV type-specific relative contributions (RCs) were estimated by adding multiple infections to single types in accordance with proportional weighting attributions. Based on the comparison of type-specific RCs between CIN1 and CIN2-3/AIS/ICC (CIN2+), RC ratios were calculated to estimate type-specific risks for progression to CIN2+. Human papillomavirus DNA was detected in 85.5% of CIN1, 95.7% of CIN2-3/AIS, and 91.2% of ICC. Multiple infections decreased with disease severity: 42.9% in CIN1, 40.4% in CIN2-3/AIS, and 23.7% in ICC (P < .0001). The relative risk for progression to CIN2+ was highest for HPV16 (RC ratio 3.78, 95% confidence interval [CI] 3.01-4.98), followed by HPV31 (2.51, 1.54-5.24), HPV18 (2.43, 1.59-4.32), HPV35 (1.56, 0.43-8.36), HPV33 (1.01, 0.49-3.31), HPV52 (0.99, 0.76-1.33), and HPV58 (0.97, 0.75-1.32). The relative risk of disease progression was 1.87 (95% CI, 1.71-2.05) for HPV16/18/31/33/35/45/52/58, but only 0.17 (95% CI, 0.14-0.22) for HPV39/51/56/59/66/68. Human papillomavirus 16/18/31/33/45/52/58/6/11 included in a 9-valent vaccine contributed to 89.7% (95% CI, 88.7-90.7) of CIN2-3/AIS and 93.8% (95% CI, 92.4-95.3) of ICC. In conclusion, our data support the Japanese guidelines that recommend discriminating HPV16/18/31/33/35/45/52/58 genotypes for CIN management. The 9-valent vaccine is estimated to provide over 90% protection against ICC in young Japanese women.

Ovarian Cancer Stemness: Biological and Clinical Implications for Metastasis and Chemotherapy Resistance.

Epithelial ovarian cancer is a highly lethal gynecological malignancy that is characterized by the early development of disseminated metastasis. Though ovarian cancer has been generally considered to preferentially metastasize via direct transcoelomic dissemination instead of the hematogenous route, emerging evidence has indicated that the hematogenous spread of cancer cells plays a larger role in ovarian cancer metastasis than previously thought. Considering the distinctive biology of ovarian cancer, an in-depth understanding of the biological and molecular mechanisms that drive metastasis is critical for developing effective therapeutic strategies against this fatal disease. The recent "cancer stem cell theory" postulates that cancer stem cells are principally responsible for tumor initiation, metastasis, and chemotherapy resistance. Even though the hallmarks of ovarian cancer stem cells have not yet been completely elucidated, metastasized ovarian cancer cells, which have a high degree of chemoresistance, seem to manifest cancer stem cell properties and play a key role during relapse at metastatic sites. Herein, we review our current understanding of the cell-biological mechanisms that regulate ovarian cancer metastasis and chemotherapy resistance, with a pivotal focus on ovarian cancer stem cells, and discuss the potential clinical implications of evolving cancer stem cell research and resultant novel therapeutic approaches.

An evolving story of the metastatic voyage of ovarian cancer cells: cellular and molecular orchestration of the adipose-rich metastatic microenvironment.

Metastasis is a complex multistep process that involves critical interactions between cancer cells and a variety of stromal components in the tumor microenvironment, which profoundly influence the different aspects of the metastatic cascade and organ tropism of disseminating cancer cells. Ovarian cancer is the most lethal gynecological malignancy and is characterized by peritoneal disseminated metastasis. Evidence has demonstrated that ovarian cancer possesses specific metastatic tropism for the adipose-rich omentum, which has a pivotal role in the creation of the metastatic tumor microenvironment in the intraperitoneal cavity. Considering the distinct biology of ovarian cancer metastasis, the elucidation of the cellular and molecular mechanisms underlying the reciprocal interplay between ovarian cancer cells and surrounding stromal cell types in the adipose-rich metastatic microenvironment will provide further insights into the development of novel therapeutic approaches for patients with advanced ovarian cancer. Herein, we review the biological mechanisms that regulate the highly orchestrated crosstalk between ovarian cancer cells and various cancer-associated stromal cells in the metastatic tumor microenvironment with regard to the omentum by illustrating how different stromal cells concertedly contribute to the development of ovarian cancer metastasis and metastatic tropism for the omentum.

Radical resection of an endometrioid carcinoma arising from endometriosis in the round ligament within the right canal of Nuck: a case report and literature review.

•A patient had endometrioid adenocarcinoma arising from endometriosis in the canal of Nuck.•The tumor invaded muscles in the inguinal region.•She showed favorable prognosis by radical surgery and adjuvant chemotherapy.

Polycystic ovary syndrome: early diagnosis and intervention are necessary for fertility preservation in young women with endometrial cancer under 35 years of age.

Aim: Polycystic ovary syndrome (PCOS) is a significant risk factor for premenopausal endometrial cancer (EC) and/or atypical endometrial hyperplasia (AEH). The aim was to elucidate the clinical background and detailed menstrual history of EC and/or AEH in young women with PCOS. Methods: From January 2001 to December 2013, women under 35 years of age who had been diagnosed with EC and/or AEH and who had been treated at Kumamoto University Hospital, Japan, were recruited. The patients' clinical characteristics, clinical stages of EC and/or AEH, medication and operation methods, endocrine profiles, and menstrual history were assessed retrospectively. Results: Of all the cases of EC and/or AEH, 25 (4.6%) were under 35 years of age. The mean age was 29.0 years and all the patients were nulligravida. The clinical stages of EC and/or AEH that were identified included: AEH (five cases), stage IA (18 cases), IB (one case), and IIIA (one case). Fourteen (56%) cases met the criteria for PCOS. Both the Body Mass Index and Homeostatic Model Assessment-insulin resistance were significantly higher in the patients with PCOS than in the patients without PCOS. Medroxyprogesterone acetate therapy was not effective for the patients with PCOS and they underwent a hysterectomy more often than the patients without PCOS. All the patients with PCOS exhibited irregular menstruation or amenorrhea, the mean duration of which was 13.1 years before PCOS and EC and/or AEH were diagnosed. Conclusion: Although both the patients with and without PCOS had irregular menstruation, the patients with PCOS were less likely to have fertility-sparing surgery than the patients without PCOS because they had more advanced disease or failed to respond to medroxyprogesterone acetate therapy.

The impact of EpCAM expression on response to chemotherapy and clinical outcomes in patients with epithelial ovarian cancer.

Epithelial ovarian cancer is a highly lethal malignancy; moreover, overcoming chemoresistance is the major challenging in treating ovarian cancer patients. The cancer stem cell (CSC) hypothesis considers CSCs to be the main culprits in driving tumor initiation, metastasis, and resistance to conventional therapy. Although growing evidence suggest that CSCs are responsible for chemoresistance, the contribution of CSC marker EpCAM to resistance to chemotherapy remains unresolved.Here we have demonstrated that ovarian cancers containing high levels of EpCAM have a significantly much lower probability of achieving overall responsive rates after first-line chemotherapy. In addition, multivariate analysis revealed that EpCAM expression is an independent risk factor for chemoresistance, indicating that EpCAM expression is a predictive biomarker of chemotherapeutic response. Consistent with these clinical observations, in vitro assays, we found that the subpopulation of EpCAM-positive ovarian cancer cells shows a significantly higher viability compared with EpCAM-negative cells in response to cisplatin treatment by preventing chemotherapy-induced apoptosis, which is regulated by EpCAM-Bcl-2 axis. Furthermore, in an in vivo mouse model, platinum agents preferentially eliminated EpCAM-negative cells in comparison with EpCAM-positive cells, suggesting that the remaining subpopulation of EpCAM-positive cells contributes to tumor recurrence after chemotherapy. Finally, we also found that an increased expression of EpCAM is associated with poor prognosis in ovarian cancer patients.Our findings highlight the clinical significance of EpCAM in the resistance to chemotherapy and provide a rationale for EpCAM-targeted therapy to improve chemoresistance. Targeting EpCAM should be a promising approach to effectively extirpate the CSCs as the putative root of ovarian cancer.