The TIGD5 gene located in 8q24 and frequently amplified in ovarian cancers is a tumor suppressor.

Ovarian cancer (OC) is the fifth most common cancer of female cancer death and leading cause of lethal gynecological cancers. High-grade serous ovarian carcinoma (HGSOC) is an aggressive malignancy that is rapidly fatal. Many cases of OC show amplification of the 8q24 chromosomal region, which contains the well-known oncogene MYC. Although MYC amplification is more frequently observed in OCs than in other tumor types, due to the large size of the 8q24 amplicon, the functions of the vast majority of the genes it contains are still unknown. The TIGD5 gene is located at 8q24.3 and encodes a nuclear protein with a DNA-binding motif, but its precise role is obscure. We show here that TIGD5 often co-amplifies with MYC in OCs, and that OC patients with high TIGD5 mRNA expression have a poor prognosis. However, we also found that TIGD5 overexpression in ovarian cancer cell lines unexpectedly suppressed their growth, adhesion, and invasion in vitro, and also reduced tumor growth in xenografted nude mice in vivo. Thus, our work suggests that TIGD5 may in fact operate as a tumor suppressor in OCs rather than as an oncogene.

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.

A critical review of "uterine leiomyoma" with subsequent recurrence or metastasis: A multicenter study of 62 cases.

AIM: Histopathologic diagnosis of a subset of uterine smooth muscle tumors is challenging. We report a critical review regarding the clinicopathological point of view of 62 cases of subsequently recurred or metastasized leiomyoma. METHODS: Medical records and glass slides of 62 cases of uterine smooth muscle tumor diagnosed as leiomyoma, which subsequently recurred or metastasized, were critically reviewed by pathologists specializing in gynecologic pathology and oncology. RESULTS: In 47 (75.8%) of 62 cases, the diagnosis of leiomyoma was confirmed, including 11 intravascular leiomyomatosis (IVL) and benign metastasizing leiomyoma (BML). In 29 cases (46.8%) laparoscopic surgery was performed, of which morcellator without a bag was employed in 23 cases. Fifteen cases (24.2%) appeared to be underestimated and were re-classified as smooth muscle tumor of uncertain malignant potential (STUMP), leiomyosarcoma, or other malignant mesenchymal tumors. Recurrences in seven cases (11.3%) were interpreted to be a malignant transformation, and one STUMP recurred as STUMP. CONCLUSION: The recurrence or metastasis in cases of "leiomyoma" is attributed to iatrogenic or under-evaluation of primary tumors, although a subset of cases is a rare example of biological progression.

Surveillance of radical hysterectomy for early-stage cervical cancer in the early experienced period of minimally invasive surgery in Japan.

OBJECTIVE: The purpose of our study was to conduct a detailed survey of radical hysterectomy in Japanese patients with early-stage cervical cancer, and to compare oncologic outcomes between open and minimally invasive radical hysterectomy. METHODS: In Japan during 2015, the medical records of 929 patients with FIGO stage IB1 and IIA disease treated with radical hysterectomy were retrospectively reviewed. We assessed patients' characteristics, disease-free survival (DFS), overall survival (OS) and prognostic factors for survival. RESULTS: The median patient age was 44 (20-80) years. Most patients (94.4%) had stage IB1 disease. Of the patients who underwent radical hysterectomy, 91.2% underwent open surgery and 8.8% underwent minimally invasive surgery (MIS). The median follow-up period was 40.8 months (range, 0.49-51.1 months). The rate of DFS and OS at 4 years in all patients was 88.3% and 96.4%, respectively. Multivariate analysis identified age (≥ 47), adenocarcinoma histology, tumor size (≥ 2 cm), parametrial invasion, positive lymph node metastasis and institutional accreditation as independent predictors of recurrence, and adenocarcinoma, other cell types, and positive lymph node metastasis as independent predictors of death. Oncologic outcomes in all patients were similar between open and MIS, including DFS and OS. CONCLUSION: The survival rate of the Japanese patients underwent radical hysterectomy for early-stage cervical cancer was favorable. No significant differences were observed for DFS and OS between open and MIS performed by a limited number of surgeons at a limited number of facilities in Japan. Further investigations are required to identify the appropriate patients might benefit from MIS.

Endometrial cancer with a POLE mutation progresses frequently through the type I pathway despite its high-grade endometrioid morphology: a cohort study at a single institution in Japan.

POLE-mutated endometrial cancer (EC) frequently shows high-grade endometrioid histology, which represents heterogeneity in the dualistic classification of EC. This study aimed to assess the clinicopathology and pathogenesis of POLE-mutated EC due to the scarcity of related information for Asian women. POLE variants were sequenced in tissues of Japanese women with EC. The tumor mutation burden (TMB) was assessed in tissues with a POLE variant of unknown significance. In the POLE-mutated EC tissues, the immunostaining expression of CD8, hormonal receptors, and p53 was evaluated, and the POLE variants in cancer and atypical endometrial hyperplasia (AEH) lesions were assessed by laser-capture microdissection. POLE variants were identified in five patients (3.9%) with high-grade endometrioid carcinoma among 127 patients with EC (S459F in two tissues and P441P in three tissues with a high TMB). The five cancer tissues coexisted with normal endometrium and/or AEH. Both AEH and cancer cells showed hormonal receptor positivity and harbored the same POLE mutation. Two patients showed a subclonal overexpression pattern of p53 in cancer and AEH lesions. In conclusion, POLE-mutated EC progresses through the type I pathway, even though it frequently shows high-grade endometrioid morphology. The common POLE mutation sites in EC might vary among races.

Endogenous YAP1 activation drives immediate onset of cervical carcinoma in situ in mice.

Cervical cancer (CC) is usually initiated by infection with high-risk types of human papillomavirus (HPV). The HPV E6 and E7 proteins target p53 and RB, respectively, but other cellular targets likely exist. We generated uterus-specific MOB1A/B double KO (uMob1DKO) mice, which immediately developed cervical squamous cell carcinoma in situ. Mutant cervical epithelial cells showed YAP1-dependent hyperproliferation, altered self-renewal, impaired contact inhibition, and chromosomal instability. p53 activation was increased in uMob1DKO cells, and additional p53 loss in uMob1DKO mice accelerated tumor invasion. In human CC, strong YAP1 activation was observed from the precancerous stage. Human cells overexpressing HPV16 E6/E7 showed inactivation of not only p53 and RB but also PTPN14, boosting YAP1 activation. Estrogen, cigarette smoke condensate, and PI3K hyperactivation all increased YAP1 activity in human cervical epithelial cells, and PTPN14 depletion along with PI3K activation or estrogen treatment further enhanced YAP1. Thus, immediate CC onset may initiate when YAP1 activity exceeds an oncogenic threshold, making Hippo-YAP1 signaling a major CC driver.

Serum Prolactin Contributes to Enhancing Prolactin Receptor and pJAK2 in Type I Endometrial Cancer Cells in Young Women Without Insulin Resistance.

Elevated levels of serum prolactin and a high expression of prolactin receptor (PRLR) in cancer cells was recently identified in patients with endometrial cancer (EC). However, the impact of prolactin on EC remains unknown. The aim of this study was to elucidate the clinical and immunohistochemical characteristics of hyperprolactinemic patients with EC according to the pathogenetic types, type I and type II. EC patients were retrospectively divided into a high prolactin (HP) group and a low prolactin (LP) group by a serum prolactin level of 20 ng/mL and were compared between 2 groups. The expression of PRLR, phosphorylated Janus-kinase 2 (pJAK2), estrogen receptor-α, progesterone receptor, and PTEN in cancer tissue were evaluated by immunohistochemistry. Ninety-nine patients were identified. In the type I group, HP group was significantly younger (45.2 vs. 52.2, P=0.028) and their insulin resistance was significantly lower (1.6 vs. 2.5, P=0.033) than those in LP group, and the expression of PRLR and pJAK2 in the HP group was significantly higher than that in the LP group (immunoreactive score: 6.8 vs. 3.9, P=0.003; 5.7 vs. 2.6, P<0.001, respectively). In the type 2 group, there were no differences between all the term. In the type I group, the rate of loss of PTEN in the HP group was significantly lower than the LP group (25.0% vs. 60.7%, P=0.024). Prolactin-PRLR signaling may play a crucial role for the progression of type I EC without involving the PTEN mutation in young hyperprolactinemic women without insulin resistance.

Japan Society of Gynecologic Oncology guidelines 2017 for the treatment of uterine cervical cancer.

The Japan Society of Gynecologic Oncology (JSGO) Guidelines 2017 for the Treatment of Uterine Cervical Cancer are for the purpose of providing standard treatment strategies for cervical cancer, indicating treatment methods currently considered appropriate for cervical cancer, minimizing variances in treatment methods among institutions, improving the safety of treatment and prognosis of diseases, reducing the economic and psychosomatic burden of patients by promoting performance of appropriate treatment, and enhancing mutual understanding between patients and healthcare professionals. The guidelines were prepared through consensus of the JSGO Guideline Committee, based on careful review of evidence gathered through the literature searches and in view of the medical health insurance system and actual clinical practice situations in Japan. The guidelines comprise eight chapters and five algorithms. The main features of the 2017 revision are as follows: (1) evidence was collected using a search formula and with cooperation of the Japan Library Association. The bibliographical search formula was placed at the end of the book; (2) regarding clinical questions (CQs) where evidence or clinical inspection in Japan was lacking, opinions of the Guidelines Committee were described as "proposals for future directions"; (3) cervical intraepithelial neoplasia (CIN) 3 and adenocarcinoma in situ (AIS) were treated as a cervical precancerous lesion; (4) the CQs of endoscopic surgery, radical trachelectomy, and sentinel node biopsy were newly added in Chapter 3, "primary treatment for stage IB-II cervical cancer"; and (5) the CQ about hormone replacement therapy after cancer treatment was newly established. Each recommendation is accompanied by a classification of recommendation categories based on the consensus reached by the Guideline Committee members. Here, we present the English version of the JSGO Guidelines 2017 for the Treatment of Uterine Cervical Cancer.

Novel therapeutic strategies for advanced ovarian cancer by using induced pluripotent stem cell-derived myelomonocytic cells producing interferon beta.

Although first-line chemotherapy has a high rate of complete responses in ovarian cancer patients, the vast majority of patients present with recurrent disease that has become refractory to conventional chemotherapy. Peritoneal dissemination and malignant ascites are the hallmarks of recurrent or advanced ovarian cancer and severely reduce quality of life. Development of therapeutic measures to treat such patients is eagerly anticipated. Macrophage infiltration is observed in various types of cancer including epithelial ovarian cancer. In addition, macrophages are involved in the formation of spheroids in the malignant ascites of ovarian cancer and promote cancer growth. iPS-ML, macrophage-like myelomonocytic cells generated from human induced pluripotent stem (iPS) cells, made close contacts with ovarian cancer cells in vitro. We hypothesized that, if we inoculate iPS-ML-producing IFN-ß (iPS-ML/IFN-ß) into the peritoneal cavity of patients with ovarian cancer, IFN-ß produced by the iPS-ML/IFN-ß would efficiently act on the cancer cells to suppress cancer growth. To evaluate this hypothesis, we injected iPS-ML/IFN-ß into SCID mice bearing peritoneally disseminated human ovarian cancer cells, SKOV3. Immunohistochemical analysis of the intraperitoneal tumors detected iPS-ML/IFN-ß infiltrating into the cancer tissues. Therapy with iPS-ML/IFN-ß significantly suppressed tumor progression. In addition, dramatic reduction of cancer-related ascites was observed. Collectively, it is suggested that iPS-ML/IFN-ß therapy offers a new approach for the treatment of patients with advanced ovarian cancer.

Administration of Cabergoline Contributes to Preserving Fertility in Young Hyperprolactinemic Patients With Endometrial Cancer Treated With Medroxyprogesterone Acetate.

BACKGROUND: An association between high levels of serum prolactin and endometrial cancer (EC) has been reported. However, the effect of antiprolactin drugs on hyperprolactinemic patients with EC has not been determined. The aim of this study was to confirm the effect of cabergoline on young hyperprolactinemic patients treated with medroxyprogesterone acetate (MPA) for the preservation of fertility. METHODS: A retrospective observational study was conducted to identify patients with atypical endometrial hyperplasia or early-stage EC aged 40 years or younger who were treated with oral MPA in Kumamoto University Hospital between 1998 and 2016. RESULTS: Thirty-four patients were identified and divided into two groups of 17 patients each, including a nonadministration of cabergoline group (noncabergoline group) and an administration of cabergoline group (cabergoline group). The ratio of pathological diagnoses of EC in the noncabergoline group was significantly lower than that in the cabergoline group (29.4% vs 70.6%, P = 0.016). The mean serum prolactin levels showed a significant decrease after the administration of cabergoline in the cabergoline group (25.2 [24.0] vs 5.2 [4.2] ng/mL, P = 0.003), and this decreased level was also significantly lower than that in the noncabergoline group (5.2 [4.2] vs 12.0 [5.0] ng/mL, P < 0.001). Kaplan-Meier analysis conducted for 150 months revealed that the estimated mean period until hysterectomy in the noncabergoline group was significantly shorter than that in the cabergoline group (83.5 vs 140.8 months, P = 0.007). Significant differences were observed in EC but not atypical endometrial hyperplasia based on histological classification (25.6 vs 138.0 months, P = 0.001). CONCLUSIONS: The administration of cabergoline may contribute to preserving fertility in young hyperprolactinemic patients with EC who were treated with MPA.

Japan Society of Gynecologic Oncology guidelines 2015 for the treatment of vulvar cancer and vaginal cancer.

BACKGROUND: Vulvar cancer and vaginal cancer are relatively rare tumors, and there had been no established treatment principles or guidelines to treat these rare tumors in Japan. The first version of the Japan Society of Gynecologic Oncology (JSGO) guidelines for the treatment of vulvar cancer and vaginal cancer was published in 2015 in Japanese. OBJECTIVE: The JSGO committee decided to publish the English version of the JSGO guidelines worldwide, and hope it will be a useful guide to physicians in a similar situation as in Japan. METHODS: The guideline was created according to the basic principles in creating the guidelines of JSGO. RESULTS: The guidelines consist of five chapters and five algorithms. Prior to the first chapter, basic items are described including staging classification and history, classification of histology, and definition of the methods of surgery, radiation, and chemotherapy to give the reader a better understanding of the contents of the guidelines for these rare tumors. The first chapter gives an overview of the guidelines, including the basic policy of the guidelines. The second chapter discusses vulvar cancer, the third chapter discusses vaginal cancer, and the fourth chapter discusses vulvar Paget's disease and malignant melanoma. Each chapter includes clinical questions, recommendations, backgrounds, objectives, explanations, and references. The fifth chapter provides supplemental data for the drugs that are mentioned in the explanation of clinical questions. CONCLUSION: Overall, the objective of these guidelines is to clearly delineate the standard of care for vulvar and vaginal cancer with the goal of ensuring a high standard of care for all women diagnosed with these rare diseases.

[Diagnosis and Treatment of MSI-H Cancer in Gynecological Cancer].

Among gynecological cancers, microsatellite instability(MSI)is most commonly found in endometrial carcinoma. When an allelic variation is observed in multiple microsatellite regions, it is called MSI-high(MSI-H). Hereditary MSI-H endometrial cancer develops through a germline mutation ofthe mismatch repair(MMR)gene, resulting in Lynch syndrome, and increased risk ofsporadic MSI-H endometrial cancer is caused by somatic lineage mutations or methylation abnormalities. Clinical characteristics ofendometrial cancer involved in Lynch syndrome include symptoms such as onset at a younger age, a lower corpus segment at the site, earlier stage cancer, and varied histology, when compared with those ofthe sporadic cancer. Alternatively, somatic mutations ofthe MMR gene are highly heterogeneous; however, a meta-analysis showed no difference in prognosis between with and without MSI-H. MSI-H is considered to be a biomarker, showing the therapeutic effects of an immune checkpoint inhibitor. A recent randomized controlled trial(RCT)demonstrated that an immune checkpoint inhibitor was effective against colorectal cancer with MSI-H. An additional RCT proved its effectiveness for MSI-H solid cancers, regardless oforgan type, including endometrial cancer. As the number ofcases ofendometrial cancer is increasing in Japan, MSI-H may hold utility as a biomarker for new molecular-target drugs, including immune checkpoint inhibitors. Ongoing surveillance ofcarcinomas in patients and family members is important because endometrial carcinoma associated with Lynch syndrome is a hereditary tumor. However, there is currently no established surveillance method for endometrial cancer. To improve the overall prognosis ofpatients with Lynch syndrome, genetic counseling and cross-division management are necessary, and also establishing the system is urgently required.

Prognostic significance of CD169-positive lymph node sinus macrophages in patients with endometrial carcinoma.

Lymph node (LN) macrophages play critical roles in anti-tumor immunity, which develops via the activation of cytotoxic T cells (CTL) and NK cells. The present study aims to determine the prognostic significance of CD169(+) LN macrophages in patients with endometrial carcinoma (EC). The number of CD169(+) cells or the CD169(+) -to-CD68(+) macrophage ratio in regional LN (RLN), and the number of CD8(+) CTL or CD57(+) NK cells in tumor tissues were investigated by immunohistochemistry in paraffin-embedded tissue samples from 79 patients with EC. A high density of CD169(+) cells in the RLN of patients with EC was correlated with an early clinical stage or no LN metastasis. A high number of CD169(+) cells and a high CD169(+) -to-CD68(+) macrophage ratio were significantly associated with longer overall survival in EC. We also found that the density of CD169(+) macrophages was positively correlated with the number of CD8(+) CTL and CD57(+) NK cells that infiltrated into tumor tissues. A high density of CD57(+) cells in EC tissues was associated with a better prognosis, while a high density of CD8(+) cells was not linked to an altered prognosis. The present study showed that the density of CD169(+) macrophages in RLN was associated with an improved prognosis in EC patients. CD169(+) macrophages in RLN might represent a useful marker for assessing clinical prognoses and monitoring anti-tumor immunity in patients with EC.

An Ovarian Carcinoid Tumor With Peptide YY-Positive Insular Component: A Case Report and Review of the Literature.

Ovarian carcinoid tumors are uncommon and account for 1% of all carcinoid tumors. The insular type of ovarian carcinoid tumor is common in western countries; in contrast, the strumal and trabecular types seem to be common in Asian countries. Strumal and trabecular types are associated with peptide YY (PYY) production, which may cause constipation. Here, we report the case of a 70-yr-old Japanese woman with chronic constipation who was referred to Kumamoto University Hospital because of a right adnexal mass. Imaging tests suggested that the solid mass might be malignant; therefore, abdominal total hysterectomy, bilateral salpingo-oophorectomy, and omentectomy were performed. A subsequent histopathologic examination confirmed an insular carcinoid tumor with a trabecular component in the right ovary. Both components were positive for PYY but not for serotonin. The patient complained of diarrhea instead of constipation soon after the surgery. Because PYY-positive insular carcinoid tumor in the ovary has not been previously reported, we reviewed 19 reported cases of patients with PYY-positive ovarian carcinoid tumors. The origins, common histologic types and symptoms caused by specific peptides secreted in ovarian carcinoid tumors differ between western and Asian countries.

Development of a mouse model for testing therapeutic agents: the anticancer effect of dienogest on endometrial neoplasms.

OBJECTIVE: As the number of younger women with endometrial carcinoma has increased, fertility-sparing treatments have received more attention. Although there have been several reports on conservative treatments with progestins for endometrial carcinoma, only medroxyprogesterone acetate (MPA) is available in Japan. Dienogest has been developed as a fourth-generation progestin for treating endometriosis. Because of its high progesterone activity, its antitumor activity has attracted attention. In this study, we investigated the anticancer effect of dienogest on endometrial neoplasms using mouse model of endometrial carcinoma. METHODS/MATERIALS: Pten(loxP/loxP) mice were injected with MPA or dienogest subcutaneously to evaluate the anticancer effect against endometrial neoplasms that developed in the mice. One week after injections, histopathological analyzes were performed. RESULTS: Endometrial neoplasms were found in one of the eight (12.5%) mice from each group treated with either dienogest or MPA. In contrast, they were found in seven of eight (87.5%) mice not treated with progestins. Each progestin treatment showed anticancer activity against endometrial neoplasms that developed in the mice compared to those without treatment. CONCLUSIONS: Dienogest and MPA showed potent anticancer activity against endometrial neoplasms in our mouse model. The present study demonstrated that dienogest might be a useful therapeutic agent for human endometrial neoplasms.

CD44 variant 6 is correlated with peritoneal dissemination and poor prognosis in patients with advanced epithelial ovarian cancer.

Cancer stem cells (CSCs) drive tumor initiation and metastasis in several types of human cancer. However, the contribution of ovarian CSCs to peritoneal metastasis remains unresolved. The cell adhesion molecule CD44 has been identified as a major marker for CSCs in solid tumors, including epithelial ovarian cancer. CD44 exists as a standard form (CD44s) and also as numerous variant isoforms (CD44v) generated by alternative mRNA splicing. Here we show that disseminated ovarian tumors in the pelvic peritoneum contain highly enriched CD44v6-positive cancer cells, which drive tumor metastasis and are responsible for tumor resistance to chemotherapy. Clinically, an increased number of CD44v6-positive cancer cells in primary tumors was associated with a shortened overall survival in stage III-IV ovarian cancer patients. Furthermore, a subpopulation of CD44v6-positive cancer cells manifested the ability to initiate tumor metastasis in the pelvic peritoneum in an in vivo mouse model, suggesting that CD44v6-positive cells show the potential to serve as metastasis-initiating cells. Thus, the peritoneal disseminated metastasis of epithelial ovarian cancer is initiated by the CD44v6-positive subpopulation, and CD44v6 expression is a biomarker for the clinical outcome of advanced ovarian cancer patients. Given that a distinct subpopulation of CD44v6-positive cancer cells plays a critical role in peritoneal metastasis, definitive treatment should target this subpopulation of CD44v6-positive cells in epithelial ovarian cancer.

Long-Term Outcome of Aromatase Inhibitor Therapy With Letrozole in Patients With Advanced Low-Grade Endometrial Stromal Sarcoma.

BACKGROUND: There has been no consensus on the indications for the treatment of advanced low-grade endometrial stromal sarcoma (LGESS), and the possible effects of hormonal treatment including progestins and aromatase inhibitors have been reported. The aim of this study was to investigate the efficacy of aromatase inhibitor therapy with letrozole for patients with residual or recurrent LGESS. METHODS: We retrospectively reviewed the clinical response of patients with advanced LGESS who had been treated with letrozole. We also analyzed the adverse effects after the administration of letrozole. The expression levels of estrogen receptor and aromatase in the tumors were immunohistochemically examined. RESULTS: In 5 patients who had been treated for unresectable LGESS lesions after initial or repeat surgical procedures, residual lesions in 3 patients and recurrence lesions in 2 patients were the indications for hormonal therapy with letrozole. The median duration of letrozole exposure at retrospective analysis was 53 (10-96) months. The clinical outcomes were classified as complete response in 2 patients, partial response in 1 patient, and stable disease in 2 patients. Myalgias, hot flashes, and arthralgias were not observed during the follow-up period in any patients. The median serum levels of estradiol were <5.0 (cutoff value, <0.5-11.8) pg/mL. The median age-matched bone mineral densities were 92% (79%-123%). The LGESS tissues in all 5 patients were positive for estrogen receptor and aromatase expression. CONCLUSIONS: Letrozole as well as progestins could be the first choice of treatment for patients with recurrent or residual LGESS, which is difficult to resect surgically because of its efficacy and minimal adverse effects.

A Giant Ovarian Tumor Causing Anasarca and Dyspnea Successfully Managed after Preoperative Drainage.

Serious complications are likely to accompany the treatment of giant ovarian tumors, and resection with or without preoperative drainage has been previously reported. Here, we report the case of a 27-year-old Japanese woman with a significant weight gain of 50 kg, who was referred to the Kumamoto University Hospital because of gait impairment and dyspnea. Imaging tests revealed an ovarian tumor, 37 cm in diameter, with two solid components. The patient's condition improved after the removal of 31.5 l tumor fluid by using a suprapubic urinary catheter for 3 days. The tumor was subsequently resected without complications, and was diagnosed as a left mucinous ovarian tumor with malignant components, weighing 37 kg (81.5 lb). The patient was discharged after her anasarca improved, and her body weight decreased from 100 to 50 kg with accompanying considerable urination within two weeks. She was in good condition with no evidence of recurrence at 15 months after surgery. Tumor resection after preoperative drainage was effective in the management of a patient with dyspnea induced by a giant ovarian tumor. We suggest the use of a suprapubic urinary catheter for preoperative drainage because of its ease of use in preventing fluid leakage from the possibly malignant tumor.

Clinicopathological heterogeneity in ovarian clear cell adenocarcinoma: a study on individual therapy practice.

Ovarian clear cell adenocarcinoma (CCA) has been believed to be a lethal histological subtype of an epithelial ovarian adenocarcinoma (EOA); its precursor has been assumed to be endometriosis. However, it has been reported that CCAs occasionally exhibit different clinical behaviors, suggesting that CCAs might not belong to a single category. We focused on CCAs combined with other histological types of EOAs; we re-evaluated the pathology of 46 CCAs and divided them into two subgroups: 35 CCAs alone (pure-type CCAs); and 11 CCAs with other histological types, endometrioid adenocarcinomas (EAs) or/and serous adenocarcinomas (SAs) (mixed-type CCAs). Immunohistochemical analysis for expression of ARID1A, p53, PTEN, Annexin 4, hepatocyte nuclear factor-1ß (HNF-1ß), and WT-1 was employed. We identified that patients with endometriosis were younger than those without endometriosis in pure-type CCAs (P < 0.005). In mixed-type CCAs, the immunohistochemical-staining patterns revealed internal transition of each histological component. In pure-type CCAs, expressions of ARID1A and p53 were mutually altered, and altered expression of p53 was associated with worse prognosis than that of ARID1A (P < 0.001). Our results provide evidence that CCAs would have clinicopathological heterogeneity, determining the patient's prognosis. Furthermore, immunohistochemical analysis may shed light on the selection of appropriate treatment, including chemotherapy.

Transvaginal methotrexate injection for the treatment of cesarean scar pregnancy: efficacy and subsequent fecundity.

STUDY OBJECTIVE: To investigate the efficacy of local methotrexate (MTX) injections under transvaginal ultrasound guidance for treatment of cesarean scar pregnancy (CSP) and to assess fecundity after treatment. DESIGN: Retrospective review (Canadian Task Force classification II-3). SETTING: University hospital. PATIENTS: Eight women with CSP. INTERVENTION: Transvaginal MTX injection. MEASUREMENTS AND MAIN RESULTS: We retrospectively reviewed 8 CSP cases treated with local MTX injection under transvaginal ultrasonographic guidance. In all cases, the serum human chorionic gonadotropin concentration was monitored and the gestational sac was evaluated using ultrasonography after treatment. Magnetic resonance imaging was performed as necessary. Patient clinical characteristics, clinical course after treatment, treatment efficacy, and fecundity after treatment in patients desiring subsequent pregnancies were evaluated. All 8 women were successfully treated without the need for blood transfusions or surgical procedures, although 2 required additional MTX therapy via local injection or systemic administration. The mean (SD) time to human chorionic gonadotropin normalization was 78.5 (37.7) days (range, 42-166 days). Four of 5 patients desiring subsequent pregnancies after the treatment had uneventful parturition, and recurrent CSP was diagnosed in 1 patient. CONCLUSIONS: Transvaginal MTX injection was effective and safe as sole treatment of CSP. Although the treatment course tended to be long, this method can be considered the first choice of treatment in patients desiring future pregnancies. However, careful attention should be paid to the possibility of CSP recurrence.