Oncologic outcomes in elderly patients who underwent hysterectomy for endometrial cancer: a multi-institutional survey in Kinki District, Japan.

BACKGROUND: The goal of this study is to assess the oncologic outcomes of elderly patients who underwent hysterectomy for endometrial cancer across three variables: hysterectomy approach, lymph node resection, and adjuvant therapy. METHODS: Hospital records of patients aged ≥ 70 years who underwent hysterectomy for endometrial cancer were obtained from 19 institutions. Patients were categorized into three risk groups: low, intermediate, and high. In each group, disease-free survival and overall survival were compared according to hysterectomy approach, lymph node resection, and adjuvant therapy using Kaplan-Meier method. Cox regression analysis with a 95% confidence interval was performed to estimate relative risk (RR) of death. RESULTS: A total of 1246 patients were included. In the low-risk group, the adjusted RR for death for minimally invasive surgery (MIS) versus laparotomy and lymph node resection versus no lymph node resection were 0.64 (0.24-1.72) and 0.52 (0.24-1.12), respectively. In the intermediate-risk group, the adjusted RR for death for MIS versus laparotomy, lymph node resection versus no lymph node resection, and adjuvant therapy versus no adjuvant therapy were 0.80 (0.36-1.77), 0.60 (0.37-0.98), and 0.89 (0.55-1.46), respectively. In the high-risk group, the adjusted RRs for death for lymph node resection versus no lymph node resection and adjuvant therapy versus no adjuvant therapy were 0.56 (0.37-0.86) and 0.60 (0.38-0.96), respectively. CONCLUSIONS: MIS is not inferior to laparotomy in uterine-confined diseases. Lymph node resection improved the outcome for all disease stages and histological types. In contrast, adjuvant therapy improved the outcomes only in high-risk patients.

Risk factors of retained products of conception after miscarriage or termination with gemeprost in the second trimester of pregnancy: a retrospective case-controlled study in Japanese population.

Retained products of conception (RPOC) is a complication that occurs in the second trimester of pregnancy. We enrolled 98 women who had a miscarriage or termination with gemeprost in the second trimester of pregnancy. Eighteen cases (18.4%) were RPOC-positive. The gestational week at miscarriage or termination was earlier in the RPOC-positive group than those in the RPOC-negative group (p = .003). The period of the third stage of labour was longer in the RPOC-positive group than in RPOC-negative group (p = .040). The proportion of placental forceps use was higher in the RPOC-positive group than in RPOC-negative group (p = .003). Multivariate logistic regression analysis showed that gestational week (OR: 3.53; p = .04) and use of placental forceps at delivery (OR: 2.21; p = .012) were independent risk factors for RPOC. Earlier gestational weeks at miscarriage or termination and use of placental forceps at delivery were predictive factors for RPOC after second trimester miscarriage or termination with gemeprost.Impact StatementWhat is already known on this subject? There have been some reports on risk factors of RPOC. A previous report showed that the termination of pregnancy with misoprostol at earlier periods was associated with an increased risk of RPOC.What the results of this study add? There have been few studies on the risk factors of RPOC after miscarriage or termination with gemeprost. In this study, we evaluated the risk factors of RPOC after miscarriage or termination of pregnancy with gemeprost in the second trimester. We found that an earlier gestational age (between 12 and 17 weeks) at delivery and using placental forceps to remove placenta were significant risk factors of RPOC after miscarriage or termination of pregnancy with gemeprost in the second trimester.What the implications are of these findings for clinical practice and/or further research? An earlier gestational age and using forceps to remove placenta may be significant risk factors for RPOC. The accurate evaluation and treatment for RPOC is important for maternal life-saving efforts and subsequent pregnancies. Further research is needed to draft a standardised protocol for RPOC.

Bevacizumab-associated events in Japanese women with cervical cancer: a multi-institutional survey of Obstetrical Gynecological Society of Kinki district, Japan.

BACKGROUND: The development of perforations or fistulas in the Gastrointestinal (GI) tract or genitourinary (GU) system is a serious adverse effect of bevacizumab. The aim of this study was to investigate the incidences of these GI/GU events as well as their association with previous radiotherapy (RT) in Japanese women with cervical cancer. METHODS: We conducted a written questionnaire survey among 14 gynecological institutions belonging to the Oncology Research Committee of the Obstetrical and Gynecological Society of Kinki District, Japan. The severity of GI/GU events was classified according to the National Cancer Institute's Common Terminology Criteria for Adverse Events version 5.0. All data were extracted from survey responses and maintained in an Excel spreadsheet and summarized using descriptive statistics. RESULTS: The information of 224 Japanese women with cervical cancer (152 recurrent and 72 advanced) who were treated with bevacizumab-containing chemotherapy was collected from 14 institutions. Of these, 65% had been previously treated with RT. GI/GU events of any grade developed in 25 (11.2%) patients, leading directly to death in 3 (1.3%) patients. When compared, the incidence of GI/GU events was higher in recurrent disease patients than in advanced disease patients (13.8% vs 5.6%, p = 0.0728). When examined according to the history of RT, the incidence of GI/GU events was greater in patients with a history of RT than in those without (14.5% vs 5.1%, p = 0.044). CONCLUSION: More than 10% of patients experience GI/GU events during or after receiving bevacizumab-containing chemotherapies. Prior RT is a risk factor for bevacizumab-associated GI/GU events.

Clinicopathologic Factors of Cervical Adenocarcinoma Stages IB to IIB.

OBJECTIVE: The aim of this study was to clarify the clinicopathologic factors of stages IB to IIB cervical adenocarcinoma. METHODS: Several clinicopathologic factors were compared between 35 patients who underwent radical hysterectomy and pelvic lymphadenectomy due to cervical adenocarcinoma stages IB to IIB and 77 patients with squamous cell carcinoma (SCC). RESULTS: In patients with adenocarcinoma, univariate analysis demonstrated that International Federation of Gynecology and Obstetrics stage, tumor size, and lymphovascular space invasion were significantly associated with progression-free survival (PFS), whereas FIGO stage, lymphovascular space invasion, and lymph node metastasis were significantly associated with overall survival (OS). However, multivariate analysis revealed that FIGO stage was the only significant factor for PFS in patients with adenocarcinoma. In patients with SCC, univariate analysis demonstrated that FIGO stage and lymph node metastasis were significantly associated with PFS, whereas FIGO stage, lymphovascular space invasion, and lymph node metastasis were significantly associated with OS. Multivariate analysis revealed that lymph node metastasis was the only significant factor for PFS and OS in patients with SCC. In 26 patients who were positive for high-risk human papillomavirus (HPV), including both adenocarcinoma and SCC patients, univariate and multivariate analyses revealed that HPV18 was significantly associated with poorer PFS compared with non-HPV18. There was a significant difference in distribution of HPV genotype between adenocarcinoma and SCC. CONCLUSIONS: Careful treatment may be necessary for the patients with lymphovascular space invasion in early-stage cervical adenocarcinoma. The presence of HPV18 may have an influence on the prognosis of early-stage cervical carcinoma.

Vaginal carcinoma in a young woman who underwent fertility-sparing treatment involving chemotherapy and conservative surgery.

Vaginal carcinoma is a rare gynecological malignancy that is usually treated by radiation therapy and/or surgery combined with chemotherapy. Here, we report a case of invasive vaginal carcinoma in a young woman who underwent fertility-sparing treatment involving neoadjuvant chemotherapy and conservative surgery. A 36-year-old non-parous woman had a solid tumor in the vagina. Positron emission tomography/computed tomography showed a tumor in the vagina with high FDG uptake (SUV = 17.33) but no metastatic lesions. The patient was diagnosed with vaginal squamous cell carcinoma, FIGO stage I, T1N0M0. Because she wished to retain her fertility, neoadjuvant chemotherapy consisting of irinotecan hydrochloride and nedaplatin was initiated. After four courses of chemotherapy, partial vaginectomy was carried out and the pathological diagnosis of the residual lesion was VAIN 3. Following two further courses of the same chemotherapy, she obtained complete response, and has shown no evidence of disease for 14 months.

Indoleamine 2,3-dioxygenase promotes peritoneal metastasis of ovarian cancer by inducing an immunosuppressive environment.

Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-catabolizing enzyme that has immunoregulatory functions. Our prior study showed that tumoral IDO overexpression is involved in disease progression and impaired patient survival in human ovarian cancer, although its mechanism remains unclear. The purpose of the present study is to clarify the role of IDO during the process of peritoneal dissemination of ovarian cancer. Indoleamine 2,3-dioxygenase cDNA was transfected into the murine ovarian carcinoma cell line OV2944-HM-1, establishing stable clones of IDO-overexpressing cells (HM-1-IDO). Then HM-1-IDO or control vector-transfected cells (HM-1-mock) were i.p. transplanted into syngeneic immunocompetent mice. The HM-1-IDO-transplanted mice showed significantly shortened survival compared with HM-1-mock-transplanted (control) mice. On days 11 and 14 following transplantation, the tumor weight of peritoneal dissemination and ascites volume were significantly increased in HM-1-IDO-transplanted mice compared with those of control mice. This tumor-progressive effect was coincident with significantly reduced numbers of CD8(+) T cells and natural killer cells within tumors as well as increased levels of transforming growth factor-ß and interleukin-10 in ascites. Finally, treatment with the IDO inhibitor 1-methyl-tryptophan significantly suppressed tumor dissemination and ascites with reduced transforming growth factor-ß secretion. These findings showed that tumor-derived IDO promotes the peritoneal dissemination of ovarian cancer through suppression of tumor-infiltrating effector T cell and natural killer cell recruitment and reciprocal enhancement of immunosuppressive cytokines in ascites, creating an immunotolerogenic environment within the peritoneal cavity. Therefore, IDO may be a promising molecular target for the therapeutic strategy of ovarian cancer.

Diagnostic value of preoperative SUVmax on FDG-PET/CT for the detection of ovarian cancer.

OBJECTIVE: The objective of this study was to investigate the preoperative diagnostic value of F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography and computed tomography (PET/CT) in patients with ovarian cancer. METHODS: One hundred sixty patients suspected of having malignant ovarian tumors were included in this study. All patients underwent FDG-PET/CT scans before operation, and the maximum standardized uptake value (SUVmax) of the primary tumor was measured. We evaluated the diagnostic accuracy of SUVmax for detecting malignancy and its relationship with histological findings. RESULTS: Postoperative pathological diagnoses showed that 67 were malignant, 14 were borderline malignant, and 79 were benign tumors. With the use of a cutoff SUVmax of 2.9 obtained from the receiver operating characteristic curve analysis, the sensitivity, specificity, positive predictive value, and negative predictive value for detecting malignancy were 80.6%, 94.6%, 91.5%, and 87.1%, respectively. Positive FDG accumulation (SUVmax ≥ 2.9) was shown in 89.5% of serous adenocarcinoma and in 92.3% of endometrioid adenocarcinoma. In contrast, lower frequencies of positive FDG accumulation were shown in clear cell adenocarcinoma (54.5%), mucinous adenocarcinoma (66.7%), and metastatic carcinoma (66.7%), and the median SUVmax of these 3 histological types were significantly lower than those of serous and endometrioid types. In addition, a positive FDG accumulation was shown in all patients with malignant transformation of mature cystic teratoma. Finally, of the 14 borderline malignant tumors, only 2 (14.3%) showed positive FDG accumulation. CONCLUSIONS: The SUVmax on FDG-PET/CT is useful for differentiating ovarian cancer from borderline or benign tumor with a high specificity and positive predictive value. However, our data also demonstrated a lower FDG uptake value in clear cell or mucinous histological finding, suggesting that SUVmax may vary depending on the tumor histological subtype.

Monoclonality of composite large-cell neuroendocrine carcinoma and invasive intestinal-type mucinous adenocarcinoma of the cervix: a case study.

A rare case of mixed carcinoma of the cervix is reported, composed of a large-cell neuroendocrine carcinoma and an invasive intestinal-type mucinous adenocarcinoma. The large-cell neuroendocrine carcinoma was composed of solid nests, sheets, and trabeculae of medium-sized to large-sized cells, and was positive for chromogranin-A and CD56. The invasive intestinal-type mucinous adenocarcinoma showed sparsely scattered immunoreactivity for chromogranin-A. Using an X-chromosome clonality assay, these 2 components showed patterns of monoclonality. These results suggest that the large-cell neuroendocrine carcinoma may have arisen from the invasive mucinous adenocarcinoma.

HBOC syndrome with an uncharacterized variant in the BRCA1 gene in a patient diagnosed with endometrial cancer after surgery for bilateral breast cancer: A case report.

The association between endometrial cancer and the BRCA1 and BRCA2 genes is not fully understood, and the risk elevation of endometrial cancer in patients with hereditary breast and ovarian cancer (HBOC) is not understood. The present report examines a rare case of HBOC syndrome and an uncharacterized variant of the BRCA1 gene in a patient diagnosed with endometrial cancer. A 46-year-old woman, gravida 1 para 1, was referred to Wakayama Medical University Hospital (Wakayama, Japan) because positron emission tomography/computed tomography (PET/CT) showed a high FDG uptake in the corpus uteri and the left ovary. PET/CT was performed just after mastectomy for left-sided breast cancer (triple negative). The patient had previously undergone partial mastectomy for right-sided breast cancer (triple negative) and was treated with radiation therapy to the right residual breast when she was 39 years old. Laparoscopic hysterectomy and bilateral adnexectomy were performed, and the histological diagnosis was endometrioid carcinoma, grade 1. Her germline BRCA status was tested by blood examination and the result was 'NM_007294.4(BRCA1):c.49G>C (p.Ala17Pro)'. The variant was evaluated as 'likely pathogenic'. The patient was diagnosed with HBOC syndrome and endometrial cancer, pT1ANxM0. The patient had no recurrence of breast or endometrial cancer 16 months after gynecologic surgery.

OHVIRA syndrome pre-operatively diagnosed using vaginoscopy and hysteroscopy: A case report.

Obstructed hemivagina and ipsilateral renal anomaly (OHVIRA) syndrome is a rare Mullerian duct anomaly. Cases with pelvic inflammatory disease or endometriosis have been reported, which may influence fertility or the quality of life of patients; therefore, an accurate and early diagnosis is essential. The present study reports the case of patient (25-year-old female, gravida 0 para 0) with OHVIRA syndrome. Magnetic resonance imaging and a computed tomography scan revealed uterus didelphys and right renal agenesis. An opening was found on the vaginal septum during the menstrual period. Upon diagnostic vaginoscopy and hysteroscopy through the opening, the right vaginal cavity was enclosed, and the right uterine cervix and cavity were normal. The patient was diagnosed with OHVIRA syndrome. Her vaginal septum was surgically removed under direct visualization and the pathological findings of the resected septum revealed a benign squamous epithelium. The post-operative course was uneventful and restenosis of the vagina was not observed. On the whole, the present study demonstrates that the technique, diagnostic vaginoscopy and hysteroscopy, is minimally invasive and is sufficient for the diagnosis of incomplete vaginal obstruction-type OHVIRA syndrome.

Low-grade endometrial stromal sarcoma in a young woman diagnosed after resection of endometrial polyp-like lesions: A case report.

Low-grade endometrial stromal sarcoma (LG-ESS) is a rare tumor that mostly occurs in perimenopausal women. Treatment with total hysterectomy and bilateral salpingo-oophorectomy is recommended, although fertility preservation or ovarian preservation may be considered in younger patients. The present study reports a case of LG-ESS in a young woman diagnosed after resection of endometrial polyp-like lesions. A 26-year-old nulligravid woman was referred to our hospital after being diagnosed with endometrial polyps. Hysteroscopic endometrial polypectomy was performed twice, and LG-ESS was suspected on postoperative pathological examination. Magnetic resonance imaging revealed a tumor 5-cm in diameter on the right side of the uterus. In light of the young age of the patient, tumorectomy was first performed, and postoperative pathological diagnosis was LG-ESS with the positive resection margin. After thorough discussion with the patient about fertility preservation and recurrence risk, a total abdominal hysterectomy and ovarian preservation was performed. Medroxyprogesterone therapy was performed postoperatively and no recurrence was observed for 2 years.

Malignant melanoma treated with pembrolizumab during pregnancy: A case report and review of the literature.

There have been very few reports on the use of immune checkpoint inhibitors for malignant tumors during pregnancy. Herein, the current study reports a case of a patient diagnosed with advanced malignant melanoma who was treated with pembrolizumab during pregnancy. A 40-year-old primigravida underwent noninvasive prenatal testing at 10 weeks of gestation, and the result was inconclusive, suggesting the possibility of maternal malignancy. A biopsy of the gluteal mass led to a diagnosis of malignant melanoma, and computed tomography revealed extensive metastases in her lungs and lymph nodes. She had a strong desire to proceed with pregnancy. In consideration of fetal growth and maturation, monotherapy was administered with pembrolizumab from 21 weeks of gestation, aiming for 28 weeks of gestation. The fetus grew well without maternal complications. At 28 weeks of pregnancy, the patient gave birth to a healthy boy by cesarean section. There was no evidence of metastasis in the placenta. The patient received nivolumab-ipilimumab combination therapy from postpartum day 13, followed by nivolumab monotherapy, and has been alive with controlled disease for 20 months.

Two cases of vasa previa diagnosed prenatally using three-dimensional ultrasonography.

We report two cases in which we describe the impact of sonography (US) in the management of vasa previa. In the first case, with two-dimensional US, the diagnosis of vasa previa was made at 21 weeks gestation. In the second case, using three-dimensional US, the diagnosis of vasa previa was made at 19 weeks gestation. An elective Cesarean section was carried out at 34 weeks in both cases. Diagnosis of vasa previa is critical when low-lying placenta or velamentous insertion of the umbilical cord is detected during the pregnancy.

Laparoscopically resected Castleman's disease in the pelvic retroperitoneum: A case report.

Castleman's disease is a rare benign disorder of unknown etiology characterized by proliferation of lymphoid tissues. Castleman's disease arising from pelvic retroperitoneum is clinically rare. The present case report describes a rare case of laparoscopically resected Castleman's disease in the pelvic retroperitoneum associated with benign ovarian cyst. A 47-year-old woman, gravida 5, para 3, was referred to to the Department of Obstetrics and Gynecology of Wakayama Medical University with a suspected pelvic tumor. Magnetic resonance imaging revealed that the solid tumor was localized in the retroperitoneal space at the right side of the pelvis. The patient underwent laparoscopic surgery for the resection of the pelvic retroperitoneal tumor, with complete tumor resection. Postoperative pathological examination established the diagnosis of Castleman's disease. The postoperative course was uneventful, with no evidence of local recurrence or systemic disease 6 months after diagnosis.

Short term outcomes of helical tomotherapy during concurrent chemoradiotherapy for advanced cervical cancer.

The aim of the present study was to clarify the feasibility and efficacy of helical tomotherapy during concurrent chemoradiotherapy for treating cervical cancer. The medical records of 13 patients who underwent oncurrent chemoradiotherapy using helical tomotherapy for cervical cancer at Wakayama Medical University Hospital between 2013 and 2015 were retrospectively reviewed. A total of 15 patients who underwent oncurrent chemoradiotherapy using conventional radiotherapy (CRT) between 2008 and 2013 at our institution were also examined for comparison. The median age of patients treated with helical tomotherapy was 60 (range, 35-71), and the median age of patients treated with CRT was 57 (range, 43-77). The median follow-up period was 27 months (range, 3-46) in the tomotherapy group and 35 months (range, 7-88) in the CRT group. The frequency of G3/4 thrombocytopenia in the tomotherapy group was significantly higher than that in the CRT group (P=0.049). However, the platelet count spontaneously recovered without transfusion. There were no significant differences between the groups in terms of frequency of G3/4 neutropenia, diarrhea or late intestine injury. The rate of complete response in the tomotherapy group and the CRT group was 84.6 and 73.3%, respectively, and there was no significant difference in the response rate between the groups. There were no significant differences in the progression-free survival or progression-free rate in the irradiation field between the groups. Adverse events from concurrent chemoradiotherapy using helical tomotherapy were acceptable and clinically controllable. The present results suggest that helical tomotherapy is efficient during concurrent chemoradiotherapy for treatment of advanced cervical cancer.

Identical twins with mature cystic teratomas treated with laparoscopic surgery: Two case reports.

Mature cystic teratomas are the most common among all ovarian neoplasms, representing 30-40% of the cases. However, to the best of our knowledge, there have been only two reports of mature cystic teratomas occurring in identical twins to date. We herein report a case of identical twins with mature cystic teratomas who were treated with laparoscopic surgery. A 32-year-old woman was referred to our hospital due to a tumor in the right ovary. The patient underwent laparoscopic resection of the ovarian tumor and the pathological diagnosis was benign mature cystic teratoma. Two years later, the identical twin of the abovementioned patient was referred to our hospital also due to a right ovarian tumor. The patient underwent laparoscopic resection of the ovarian tumor and the pathological diagnosis was benign mature cystic teratoma. Therefore, for early diagnosis, it may be important to consider the possibility of mature cystic teratoma in the identical twin of a patient, even in the absence of symptoms.

A Case of Malignant Melanoma of the Uterine Cervix with Disseminated Metastases throughout the Vaginal Wall.

Malignant melanoma (MM) in the female genital tract accounts for less than 2% of all melanomas, and the vast majority associated occur in the vulva and vagina. Primary MM of the uterine cervix is extremely rare and its prognosis is very poor. We report a case of primary MM of the cervix with dissemination throughout the vaginal wall. A 66-year-old woman presented with postmenopausal bleeding. Gynecologic examination demonstrated a 2 cm polypoid blackish-pigmented tumor on the cervix with multiple small blackish-pigmented lesions throughout the vaginal wall. Cervical Pap smear cytology showed malignant melanoma. MRI and PET/CT did not detect any distant or lymph node metastases. She underwent radical hysterectomy, pelvic lymphadenectomy, and total vaginectomy. The pathological diagnosis was FIGO stage IIIA primary cervical MM. She received adjuvant chemotherapy with 6 courses of dacarbazine, but 6 months later, multiple lung metastases were detected. Despite 4 courses of anti-PD-1 antibody (nivolumab) treatment, she died of the disease 13 months after surgery.

Rapidly progressing large-cell neuroendocrine carcinoma arising from the uterine corpus: A case report and review of the literature.

Large-cell neuroendocrine carcinoma (LCNEC) is a high-grade neuroendocrine tumor. LCNECs arising from the genital organs are highly malignant and rare, with <20 cases of LCNEC developing from the uterine endometrium reported to date. We herein present the case of a patient with LCNEC of the endometrium. The patient was a 52-year-old woman, who exhibited lower abdominal pain and rapid uterine enlargement during outpatient treatment for uterine myoma. The endometrial biopsy suggested a diagnosis of poorly differentiated carcinoma or carcinosarcoma. Based on magnetic resonance imaging and positron emission tomography/computed tomography, endometrial stromal sarcoma was suspected. The serum lactate dehydrogenase level was abnormally high. Due to the suspicion of stage IIIC malignant tumor of the uterine corpus, surgery was performed. The pathological diagnosis was stage IIIC2 LCNEC of the endometrium. Recurrence occurred in the vaginal stump, and concurrent chemoradiotherapy (CCRT) was initiated 1 month after the surgery. The residual lesions markedly shrank, but metastasis to the upper abdominal region and cervix subsequently developed. CCRT was attempted, but the associated adverse effects were severe and was switched to palliative treatment. The patient eventually succumbed to the disease 309 days after surgery.

The autocrine effect of activin A on human ovarian clear cell adenocarcinoma cells.

The functions of activin, a member of TGF-beta superfamily, in ovarian clear cell adenocarcinoma remain unsolved, although we recently found that inhibin betaA-subunit, activin A, activin receptor type IA, type IB, type IIA, type IIB, Smad2, Smad3 and Smad4 were localized in tumor cells of the ovarian clear cell adenocarcinoma tissue by immunohistochemistry. In the present study, in order to investigate the role of activin concerning cell growth in ovarian clear cell adenocarcinoma cells, we determined the production of activin A and inhibin A, and the expression of activin receptors and Smads using the human ovarian clear cell adenocarcinoma cell line JHOC-5. Moreover, we examined the effects of activin A on the activation of activin signaling pathway and on the proliferation in JHOC-5 cells. We detected a measurable amount of activin A in the culture medium of JHOC-5 cells, although inhibin A was not detected. The expression of activin receptor type IA, IB, IIA, IIB, Smad2, Smad3 and Smad4 was observed in JHOC-5 cells. Activin A induced a significant increase in proliferation of JHOC-5 cells compared with the untreated control. On the other hand, activin A did not affect the growth of JHOC-5 cells and no statistically significant difference was observed in the presence of follistatin which is a specific binding protein of activin. Phosphorylated Smad2, an activated form of Smad2, was detected both in treated JHOC-5 cells and in untreated cells by activin A. Activin A significantly increased the expression of phosphorylated Smad2 in JHOC-5 cells. Therefore, it is possible that activin has autocrine roles in tumor growth of ovarian clear cell adenocarcinoma cells.