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Radical surgery after cervical conization is a common approach for the treatment of cervical cancer. In some cases, disease progression is observed after positive margins at conization, but the effect of conization on disease progression remains unclear. Thus, the aim of this study was to investigate the clinical outcomes of positive margins at conization in cervical cancer. A total of 101 patients who underwent cervical conization before radical hysterectomy and pelvic lymph node dissection were considered eligible by reviewing medical records. The association between the positive margins and patient outcomes, including subsequent lymph node metastasis, was evaluated. The rate of lymphovascular space invasion (LVSI) positivity at radical surgery was significantly higher in patients with positive margins (p = 0.017) than in those with negative margins, although there was no significant difference in the rate of pelvic lymph node metastasis (p = 0.155). Moreover, there was no significant difference in the overall survival or progression-free survival between the two groups (p = 0.332 and 0.200, respectively). A positive margin at conization presented no significant prognostic disadvantage; thus, diagnostic conization is one of the most suitable treatment options for early-stage cervical cancer that is difficult to accurately assess.

Aim Management of hydatidiform mole is important to reduce the mortality and morbidity of choriocarcinoma. This study aims to understand the existing health services for hydatidiform mole and to estimate the incidence of gestational trophoblastic disease (GTD) in Cambodia. Methods A questionnaire was used to collect information on the existing health services for pregnancy and hydatidiform mole at health facilities from attendants of the 16th Annual Conference of the Cambodian Society of Gynecology and Obstetrics in 2017. The incidence of GTD in 2014-2017 was estimated using Health Information System data. Results A total of 126 attendants, who were from all provinces except three provinces, answered the questionnaire. The work places were national hospitals (n = 29), provincial hospitals (n = 42), district hospitals (n = 20), health centers (n = 6), and others (n = 29). The answers of participants from the public sector suggested the following: Ultrasonography is available at all hospitals but not health centers; Human chorionic gonadotropin (hCG) measurement is only available at national hospitals; Treatment of hydatidiform mole is performed at national hospitals and provincial hospitals; and Treatment of gestational trophoblastic neoplasia (GTN) is provided at national hospitals. The incidence of hydatidiform mole and GTN at health facilities in the public sector in 2014-2017 was 0.95 per 1000 deliveries and 6.58 per 100 000 deliveries, respectively. Conclusions The results suggest that provincial hospitals are important to detect suspected invasive mole and refer to national hospitals for diagnosis and treatment. Further studies on the management of GTD and development of the guidelines of GTD are needed.

(1) This study investigated the prognostic impact of tumor size in patients with metastatic cervical cancer. (2) Methods: Seventy-three cervical cancer patients in our institute were stratified into two groups based on distant metastasis: para-aortic lymph node metastasis alone (IIIC2) or spread to distant visceral organs with or without para-aortic lymph node metastasis (IVB) to identify primary tumor size and concurrent chemoradiotherapy. (3) Results: The overall survival (OS) for patients with a tumor &gt, 6.9 cm in size was significantly poorer than that for patients with a tumor ≤6.9 cm in the IVB group (p = 0.0028), the corresponding five-year OS rates in patients with a tumor ≤6.9 and &gt, 6.9 cm were 53.3% and 13.4%, respectively. In the multivariate analysis, tumor size and primary treatment were significantly associated with survival in metastatic cervical cancer. (4) Conclusions: Tumor size ≤6.9 cm and concurrent chemoradiotherapy as the primary treatment were favorable prognostic factors for patients with metastatic cervical cancer.

Background Pure ovarian choriocarcinoma can be gestational or nongestational in origin. Nongestational pure ovarian choriocarcinoma is extremely rare and the prognosis is thought to be worse than that of the gestational type in patients with metastatic disease. We present a case of metastatic pure ovarian choriocarcinoma with poor prognosis in which the origin was identified as nongestational by DNA short tandem repeat (STR) analysis. Case presentation A nulliparous woman in her thirties with metastatic choriocarcinoma was referred to our hospital after initial treatment proved unsuccessful. Two months earlier, she had undergone brain tumor resection and histological examination confirmed choriocarcinoma. Serum human chorionic gonadotropin (hCG) concentration at initial diagnosis was 5030 IU/L. Two cycles of a combination chemotherapy regimen of methotrexate, etoposide, and actinomycin-D (MEA therapy), which is commonly used for gestational choriocarcinoma, was administered. However, the disease could not be controlled. Imaging modalities at presentation revealed tumor present in the left ovary and left lung, but not in the uterus, which led us think that the choriocarcinoma was nongestational. Bleomycin, etoposide, and cisplatin (BEP therapy) which is commonly used for nongestational choriocarcinoma (malignant germ cell tumor) and surgical resection of the uterus, bilateral ovaries, and an affected part of the left lung led to the nadir level of hCG, but the tumor relapsed and levels of hCG again increased. To investigate the origin of choriocarcinoma, we performed DNA STR analysis of tumor cells and oral mucosal cells. Analysis revealed the origin of the choriocarcinoma as nongestational, as the genotype of tumor cells entirely corresponded with that of oral mucosal cells. BEP therapy and chemotherapy regimens administered for nongestational choriocarcinoma and gestational choriocarcinoma proved ineffective, and the patient died 21 months after diagnosis of metastatic choriocarcinoma. Conclusion Metastaic nongestational pure choriocarcinoma of ovary is an extremely rare and an aggressive disease, frequently resulting in poor outcome.

Background. Lower-limb lymphedema (LLL) is a chronic and progressive complication of gynecologic cancer treatment, including pelvic lymphadenectomy. This study aims to investigate the therapeutic effect of goreisan, a traditional Japanese medicine, which has been used for hydrostatic modulation on patients with LLL. Methods. Patients diagnosed with LLL in our hospital in 2018 were included and principally treated with complex decongestive therapy (CDT), including elastic clothing and lymph drainage. The patients who received a combination therapy of CDT and goreisan (CDT-G group) were prescribed goreisan extract granules, with a dose of 7.5 g per os daily in three doses. Patients who were not prescribed goreisan received CDT alone (CDT group). The severity of lymphedema was evaluated by the estimated limb volume calculated by limb circumferences and the ratio of extracellular water (ECW) to total body water (TBW). Results. Nineteen women with LLL after pelvic lymphadenectomy were included in the study. The number of patients in the CDT and CDT-G groups was 8 and 11, respectively. There were no statistically significant differences between the CDT and CDT-G groups in terms of patient characteristics and severity of LLL before treatment. Reduction in ECW/TBW in the CDT-G group (in the whole body and the affected lower limb) after the intervention was significantly more remarkable than that in the CDT group. Conclusions. Goreisan-based Japanese herbal therapy may be effective in patients with LLL after retroperitoneal lymphadenectomy.

The prognostic nutritional index (PNI), which reflects preoperative malnutrition, is useful for predicting the incidence of postoperative complications and has been reported in recent years to predict the long-term prognosis of various malignancies. The purpose of this study was to clarify the significance of PNI as a prognostic factor for early-stage clear cell ovarian carcinoma. A total of 82 patients with stage I–II (FIGO 2014) ovarian clear cell carcinoma undergoing primary surgery at our hospital from January 2005 to December 2017 were enrolled. PNI was calculated using the formula: 10 × serum albumin (g/ dL) + 0.005 × peripheral blood lymphocyte count (/mm3). Preoperative PNI exhibited relatively high area under the curve value (0.709) for 5 year survival, and the optimal cutoff value was 46.5. The overall survival was significantly shorter in the PNI-low group than in the PNI-high group. Multivariate analysis showed that high PNI was a significant independent prognostic factor for favorable prognosis (hazard ratio = 0.102, p = 0.010). There was no significant difference in recurrence-free survival between the two groups (p = 0.220), but the postrecurrence survival was significantly longer in the PNI-high group than in the PNI-low group (p = 0.0383). The preoperative PNI was a useful predictor of prognosis, even in early-stage ovarian clear cell carcinoma.

Background Ubiquitin-associated protein 2-like (UBAP2L) has been demonstrated to be associated with the progression of multiple types of cancer. However, the function of UBAP2L in uterine cervical cancer remains unclear. Materials and methods Between 2005 and 2015, 84 patients who underwent surgery were included in this study. The patients were stratified into two groups on the basis of immunohistochemical staining for UBAP2L, and survival analysis was performed. Moreover, loss-of-function analysis was performed using the cervical cancer cell lines CaSki and SiHa. Results Based on immunohistochemistry, the overall survival in patients with low UBAP2L expression was significantly longer than that of those with high UBAP2L expression (p=0.045). The in vitro experiment revealed that knockdown of UBAP2L remarkably inhibited cell proliferation in both live cell imaging and the MTS assay. Conclusion Patients with high UBAP2L expression had unfavorable prognosis and UBAP2L appears to play an important role in proliferation.

Background Previous studies showed that although the risk of thyroid dysfunction [thyroid immune-related adverse events (irAEs)] induced by anti-programmed cell death-1 antibodies (PD-1-Ab) was as low as 2% to 7% in patients negative for anti-thyroid antibodies (ATAs) at baseline, it was much higher (30%-50%) in patients positive for ATAs. However, whether a similar increase occurs with combination therapy using PD-1-Ab plus anti-cytotoxic T-lymphocyte antigen-4 antibody (CTLA-4-Ab) is unknown. Methods A total of 451 patients with malignancies treated with PD-1-Ab, CTLA-4-Ab, or a combination of PD-1-Ab and CTLA-4-Ab (PD-1/CTLA-4-Abs) were evaluated for ATAs at baseline and for thyroid function every 6 weeks for 24 weeks after treatment initiation and then observed until the last clinical visit. Results Of the 451 patients, 51 developed thyroid irAEs after immunotherapy [41 of 416 (9.9%) treated with PD-1-Ab, 0 of 8 (0%) treated with CTLA-4-Ab, and 10 of 27 (37.0%) treated with PD-1/CTLA-4-Abs]. The cumulative incidence of thyroid irAEs was significantly higher in patients who were positive vs negative for ATAs at baseline after both PD-1-Ab [28/87 (32.2%) vs 13/329 (4.0%), P < 0.001] and PD-1/CTLA-4-Abs [6/10 (60.0%) vs 4/17 (23.5%), P < 0.05] treatments. The risk of thyroid irAEs induced by PD-1/CTLA-4Abs, which was significantly higher than that induced by PD-1-Ab, in patients negative for ATAs at baseline was not statistically different from that induced by PD-1-Ab in patients positive for ATAs at baseline. Conclusions This study showed that the incidence of thyroid irAEs was high and not negligible after PD-1/CTLA-4-Abs treatment even in patients negative for ATAs at baseline.

Objective To investigate the impact of cystectomy for borderline ovarian tumor (BOT) on tumor recurrence compared with salpingo-oophorectomy using inverse probability of treatment weighting (IPTW). Methods A central pathologic review and a search of the medical records from 14 collaborating institutions from 1986 to 2017 identified 4708 women with a malignant ovarian neoplasm. Data for young women with Stage I BOT were extracted. To compare recurrence-free survival between the surgery groups, Cox regression analyses and the IPTW-adjusted Kaplan-Meier method were employed. Results During a median follow-up of 62.0 (1.2-270.4) months, 10 of the 285 patients identified (3.5%) developed recurrence. In multivariate analysis, the practice of cystectomy was not a significant prognostic indicator of recurrence-free survival (hazard ratio [95% confidence interval] 1.276 [0.150-10.864]; P = 0.823). In the IPTW-adjusted cohort, the 5-year recurrence-free survival rates were 95.8% and 96.0% in patients receiving cystectomy and salpingo-oophorectomy, respectively (P = 0.378). Conclusion If patients are selected appropriately, cystectomy in itself may not increase tumor recurrence in young women with early-stage BOT. A large-scale prospective clinical study is necessary to validate this finding.

Radical surgery after cervical conization is a common approach for the treatment of cervical cancer. Clinically, rapid disease progression is sometimes observed in patients with positive margins at conization, but the details are unclear. This study aimed to investigate the clinical impact of positive margins at conization in cervical cancer. The medical records of patients with cervical cancer between 2010 and 2020 were reviewed retrospectively and we identified 101 eligible patients who underwent radical hysterectomy, including pelvic lymph node dissection. The association between the positive margins of the conization samples and outcomes, including subsequent lymph node metastasis, was evaluated. The rate of lymphovascular space invasion positivity at radical surgery was significantly higher in patients with positive margins (p = 0.017) than in those with negative margins, although there was no significant difference in the rate of pelvic lymph node metastasis (p = 0.155). Moreover, Kaplan–Meier curves showed that there were no significant difference in overall survival or progression-free survival between the two groups (p = 0.332 and p = 0.200, respectively). A positive margin at conization presented no significant prognostic disadvantage, and therefore, diagnostic conization is one of the reasonable options for locally advanced cervical cancer.

Background Epithelial ovarian cancer remains one of the leading causes of cancer deaths among women worldwide, and advanced epithelial ovarian cancer frequently metastasizes to the omentum. The characteristics of metastatic cancer may differ from those of primary ovarian cancer and reflect the unique omental microenvironment. This study investigated metabolomic differences in epithelial ovarian cancers. Methods Patients with advanced epithelial ovarian cancer were eligible for this study. Five patients underwent surgery and resection of paired primary ovarian and omental metastatic cancer at Nagoya University. Metabolome analysis was performed in these paired cancer and metastatic cancer tissues through a facility service (C-SCOPE) at Human Metabolome Technologies, Inc. The concentrations of 116 compounds were measured by CE-TOFMS and CE-QqQMS, and 30 metabolic parameters were calculated. For statistical analyses, Welch’s t-test was used for comparisons between two independent groups. Results Metabolite profiles were all different, which reflects diversity among these cancer tissues. Of the measured compounds, urea was the only metabolite that was significantly decreased in omental metastatic cancers compared with the primary cancers (p = 0.031). Moreover, in omental metastatic cancers, the pentose phosphate pathway was more dominant than glycolysis. Furthermore, in some cases, lactic acids in omental metastatic cancers were markedly decreased compared with primary cancers. With regard to histological subtype, the total levels of amino acids, especially the percentage of glutamine, were significantly enriched in serous carcinomas compared with nonserous carcinomas (p = 0.004 and p = 0.001). Moreover, the reduced forms of glutathione and polyamines were also more abundant in serous carcinomas than in nonserous carcinomas (p = 0.025 and 0.048). Conclusions The metabolite profiles differed depending on tumor location and histological subtype. Metabolome analysis may be a useful tool for identifying cancer diagnostic and prognostic markers.

Gestational choriocarcinoma is a gestational trophoblastic neoplasia (GTN) originating from trophoblastic cells with abnormal proliferation. Although chemotherapy is effective for treating this cancer, when patients develop chemoresistance, personalized treatment, such as the use of drugs matching their genomes, is required. The present report describes a case of intractable gestational choriocarcinoma identified using a next-generation sequencing (NGS)-based tumor panel. A 51-year-old woman was diagnosed with gestational choriocarcinoma via pathological and short tandem repeat analyses. The patient did not achieve remission despite many regimens of chemotherapy, including high-dose therapy with autologous peripheral blood stem cell transplantation. To identify drugs tailored to this particular choriocarcinoma, NGS was performed on the tumor of the patient, and the tumor genome was compared with that of the patient's blood sample using the NCC Oncopanel System. Consequently, 245 single nucleotide variants (SNVs) with a mean SNV allele frequency of 63.1% were identified. This high frequency was because the genome of the gestational choriocarcinoma contained part of the genome of the partner. Therefore, our experience of the present intractable case of choriocarcinoma suggested that matched normal-tumor pair analysis is not appropriate for treatment decisions in GTN cases. When using an NGS-based tumor panel to assess choriocarcinoma, researchers must consider whether the genomic DNA of the patient and their partner are involved in the GTN.

The standard treatment for cervical cancer is chemoradiation although some patients showed treatment resistance. The purpose of this study was to investigate the clinical efficacy of surgery after chemoradiation for cervical cancer. Patients with FIGO stage IB2 to IIB cervical cancer were included in the study between 2005 and 2015. A total of 50 patients who underwent surgery after neoadjuvant chemoradiation and 76 patients who received only chemoradiation were compared. Baseline differences between the two groups were adjusted with inverse probability of treatment weighting method using propensity scores composed of the following independent variables: age, stage, tumor size, lymph node metastasis, and histological subtypes. Median follow-up was 64.8 (range 4.8–143.9) months. After adjustment with inverse probability of treatment weighting, Kaplan–Meier curves showing adjusted progression-free survival and overall survival were significantly longer in the neoadjuvant chemoradiation compared with the chemoradiation-only group (p = 0.027 and p = 0.017, respectively). Moreover, in patients with squamous cell carcinoma, recurrence in previously irradiated field and recurrence both in and out of previously irradiated field were significantly decreased in the neoadjuvant chemoradiation compared with the chemoradiation-only group (3.1% and 18.4%, respectively; OR 0.142, p = 0.001]. Adverse events of surgery after chemoradiation were acceptable, although temporary hydronephrosis was frequently observed (23.1%). Surgery after chemoradiation reduced pelvic recurrence, and as a result, patients who underwent neoadjuvant chemoradiation showed more favorable survival outcomes compared with those who only underwent chemoradiation.

Background: Little is known about the effect of age on the prognosis of epithelial ovarian neoplasms. In the reproductive age, fertility-sparing surgery had been widely implemented. This study aimed to elucidate impact of age on the clinicopathologic characteristics and survival of epithelial ovarian neoplasms in the reproductive age. Methods: The clinical records of patients diagnosed as epithelial ovarian cancer or epithelial borderline ovarian tumor at the age of 40 years or younger at multiple institutions in the Tokai Ovarian Tumor Study Group were reviewed retrospectively. All patients were stratified into two age groups: group A (≤ 30 years) and group B (31–40 years). Univariate and multivariate analyses were performed to evaluate overall survival and disease-free survival. Results: A total of 583 patients (325 patients: cancer, 258 patients: borderline) were included. The median follow-up time was 62.0 months (range 1–270 months). Compared with group B, group A had a significantly higher rate of borderline tumor (66.7% vs. 32.7%, p, ファイル公開：2021/01/01

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2018 there were nine themed workshops, five of which are summarised in this report. These workshops discussed new perspectives and knowledge in the following areas of research: 1) preeclampsia; 2) abnormally invasive placenta; 3) placental infection; 4) gestational trophoblastic disease; 4) drug delivery to treat placental dysfunction.

Aim Cancer treatment involves long-term therapy and follow-up, with mental disorders (MD) often affecting the treatment process. Hence, in this study, we retrospectively analyze cases involving gynecologic cancer with MD and clarify the relationship between psychosis and cancer prognosis. Methods Patients with both gynecologic cancer and MD from January 2003 to August 2016 were recruited in this study. Cases were limited to those whose MD had been diagnosed before their cancer. Control patients without MD were also analyzed. Both cases and controls were adjusted for age, cancer type, and cancer stage. Results A total of 54 patients with gynecologic cancer and MD, as well as 108 controls without MD, were included. The median age of the patients was 52 years. Details regarding cancer type were as follows: 11 ovarian cancers, 26 uterine corpus cancers and 17 cervical cancers. Among these, 25 schizophrenia cases, 15 depressive disorders, 4 bipolar disorders and 10 other MD were recorded. No significant differences in the 5-year survival rate were found between patients and controls. In advanced-stage cervical cancer, however, the prognosis was significantly poor given the low rate of initial treatment completion. Moreover, patients with advanced-stage cervical cancer had significantly lower chemotherapy completion rates compared to those with other gynecologic malignancies. Conclusion Mental disorders do not affect the prognosis of gynecologic cancers, except for advanced cervical cancer. Accordingly, improving the low rate of initial treatment completion seems to be a focal point for better prognosis in advanced cervical cancer.

Clear-cell carcinoma (CCC) in reproductive-age women is likely to become an increasingly critical issue regarding possibilities of infertility, hormonal dysfunction, and mortality. The aim of this study was to examine the long-term oncologic outcome and its prognostic indicators based on a multicentric cohort of young patients with CCC. During the period of 1990–2015, a total of 164 patients aged 45-year-old or younger were enrolled in the study. Clinicopathologic data of these young patients with CCC collected under a centralized pathological review system were subjected to uni- and multivariable analyses to evaluate overall survival (OS). The median follow-up was 73.8 months (range 5.2–244.2) in the surviving patients. Among these patients, 104 (63.4%) had FIGO I disease, and 22 (13.4%), 31 (18.9%), and 7 (4.3%) had II, III, and IV disease, respectively. The 5-year OS rate was 74.5%. On stratification by the FIGO stage, the 5-year OS rates were as follows: stage I (90.2%), stage II (57.9%), and stage III/IV (39.3%), respectively (P

Fertility-sparing surgery (FSS) has mainly been chosen for young women with ovarian-confined/well-differentiated epithelial ovarian cancer (EOC). In general, FSS consists of at least conservation of contralateral ovary and the uterus with a staging surgery. However, information on the clinical outcome in women who underwent cystectomy as a fertility-preserving option is lacking. After a central pathological review and search of the medical records from multiple institutions between 1987 and 2015, a total of eight early-stage EOC patients treated with cystectomy as FSS were retrospectively evaluated. Diagnosis and staging were based on International Federation of Gynecology and Obstetrics criteria (2014). Surgery consisted of uni- or bilateral cystectomy. The oncologic and reproductive outcomes were assessed. The median age was 29 years (range 26–38 years). The median follow-up time was 103.6 months (range 42.2–218.3 months). The stage was IA in 3, IC1 in 4, and IC3 in one patient. Five patients received adjuvant chemotherapy. After cystectomy, two patients experienced recurrence in the pelvic cavity and bilateral ovaries, respectively. The former patient died of the disease 42 months after cystectomy, and conversely, the latter one was rescued by subsequent radical surgery. Four full-term childbirths were observed in three patients. Although oophorectomy is considered as an appropriate fertility-preserving operation, cystectomy may be an unavoidable option when it is the only surgical procedure available. It is desirable to verify the utility by accumulating larger numbers of patients through a future registry system.

Introduction Gestational trophoblastic neoplasia (GTN) include a group of malignant neoplasms that originate from the trophoblasts of placental tissue in molar or nonmolar pregnancy. Currently, it is unclear whether the prognosis of high-risk GTN or gestational choriocarcinoma succeeding molar pregnancy or that following a nonmolar one is better. Comparison of the genetic short tandem repeat (STR) patterns of the DNA extracted from the tumor, patient, and her partner allows the genetic origins of the choriocarcinoma to be distinguished - whether it is gestational or non-gestational and whether it is derived from a molar or nonmolar pregnancy in the event it is gestational. This study aimed to investigate the causative pregnancy of patients with high-risk GTN, especially those with poor outcomes, and assess the impact of the causative pregnancy on patient outcome. Methods We evaluated 24 patients who were diagnosed with high-risk GTN between January 2000 and October 2019, including 15 cases of pathologically proven gestational choriocarcinomas and the causative pregnancy was investigated by STR analysis in which tumor DNA could be extracted. Results In high-risk GTN without history of anteceding molar pregnancies, nonmolar pregnancy was the causative pregnancy, which was confirmed in three cases. Molar pregnancy appeared be the causative pregnancy of high-risk GTN in patients with a history of antecedent molar pregnancies either with or without interruption by subsequent nonmolar pregnancies prior to developing high-risk GTN. High-risk GTN in most of the evaluated deceased cases (three of four) was due to nonmolar pregnancy, while all but one case with molar pregnancy as the causative pregnancy survived. Discussion STR analysis can distinguish the causative pregnancy of high-risk GTN, and nonmolar pregnancy as the causative pregnancy might have negative effects on the outcome of the disease.

The objective of this study was to estimate the frequency of possible occult metastasis through long-term survival analyses in patients with clear cell carcinoma (CCC) who had undergone complete resection. During the period of 1990-2015, 799 patients with stage I-IV CCC were identified in the TOTSG database. Of these, a total of 528 patients without a residual tumor were enrolled in the study and classified into four groups: Group 1: FIGO stage IA-IB (N=104), Group 2: FIGO stage IC1 (N=170), Group 3: FIGO stage IC2/IC3 (N=98), and Group 4: FIGO stage II-III (no residual tumor: N=156). Cumulative incidences of recurrence (CIR) and death (CID) were examined. The median age was 54, ranging from 29-87. The 5-year CIR / CID of each group were as follows: Group 1 (7.3% / 3.8%), Group 2 (14.3% / 10.2%), Group 3 (37.7% / 18.4%), and Group 4 (46.5% / 33.8%), respectively {P

Aim Medroxyprogesterone acetate (MPA) is used to preserve fertility in patients with Grade 1 endometrial cancer without myometrial invasion (G1EA) and those with atypical endometrial hyperplasia (AEH). However, the efficacy of retreatment with MPA has not been sufficiently established for patients who experience recurrence but wish to retain their fertility. This study aimed to show the effectiveness of MPA treatment and retreatment for AEH and G1EA. Methods A total of 39 patients received MPA treatment between 2005 and 2015, including nine with G1EA and 30 with AEH. The patients received high-dose (600 mg/day) MPA for 26 weeks. If a complete response was not achieved, MPA treatment was continued. After complete remission, if there was a recurrence, the patient was offered a choice of a hysterectomy or retreatment with MPA. The gynecologic and obstetric outcomes were retrospectively analyzed. Results The median age was 34 years, and the median body mass index was 23.3 kg/m2. The median follow-up period was 52 months. Complete response rates for the initial treatment were 89% for G1EA and 93% for AEH. Recurrence occurred in 88% of patients with G1EA (7/8) and 50% of those with AEH (14/28). Seven patients with G1EA and 11 with AEH received MPA retreatment, and 100% and 92% of these achieved a complete response. During the study period, a total of 14 pregnancies were recorded with 10 live births. Conclusion MPA can be effective for G1EA and AEH treatment even when they recur.

// Akira Yokoi 1, 2 , Yusuke Yoshioka 1 , Akihiro Hirakawa 3 , Yusuke Yamamoto 1 , Mitsuya Ishikawa 3 , Shun-ichi Ikeda 3 , Tomoyasu Kato 4 , Kaoru Niimi 2 , Hiroaki Kajiyama 2 , Fumitaka Kikkawa 2 and Takahiro Ochiya 1 1 Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan 2 Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan 3 Statistical Analysis Section, Center for Advanced Medicine and Clinical Research, Nagoya University Graduate School of Medicine, Nagoya, Japan 4 Department of Gynecology, National Cancer Center Hospital, Tokyo, Japan Correspondence to: Takahiro Ochiya, email: tochiya@ncc.go.jp Keywords: circulating microRNAs, ovarian cancer, exosomes, biomarkers, liquid biopsy Received: May 10, 2017 Accepted: July 25, 2017 Published: September 06, 2017 ABSTRACT Ovarian cancer is the leading cause of gynecologic cancer mortality, due to the difficulty of early detection. Current screening methods lack sufficient accuracy, and it is still challenging to propose a new early detection method that improves patient outcomes with less-invasiveness. Although many studies have suggested the utility of circulating microRNAs in cancer detection, their potential for early detection remains elusive. Here, we develop novel predictive models using a combination of 8 circulating serum miRNAs. This method was able to successfully distinguish ovarian cancer patients from healthy controls (area under the curve, 0.97; sensitivity, 0.92; and specificity, 0.91) and early-stage ovarian cancer from patients with benign tumors (0.91, 0.86 and 0.83, respectively). This method also enables subtype classification in 4 types of epithelial ovarian cancer. Furthermore, it is found that most of the 8 miRNAs were packaged in extracellular vesicles, including exosomes, derived from ovarian cancer cells, and they were circulating in murine blood stream. The circulating miRNAs described in this study may serve as biomarkers for ovarian cancer patients. Early detection and subtype determination prior to surgery are crucial for clinicians to design an effective treatment strategy for each patient, as is the goal of precision medicine.

// Jun Sakata 1 , Fumi Utsumi 1 , Shiro Suzuki 1 , Kaoru Niimi 1 , Eiko Yamamoto 2 , Kiyosumi Shibata 3 , Takeshi Senga 4 , Fumitaka Kikkawa 1 and Hiroaki Kajiyama 1 1 Department of Obstetrics and Gynecology, Graduate School of Medicine, Nagoya University, Nagoya, Japan 2 Department of Healthcare Administration, Graduate School of Medicine, Nagoya University, Nagoya, Japan 3 Department of Obstetrics and Gynecology, Banbuntane Hotokukai, Fujita Health University, Fujita, Japan 4 Division of Tumor Biology, Graduate School of Medicine, Nagoya University, Nagoya, Japan Correspondence to: Hiroaki Kajiyama, email: kajiyama@med.nagoya-u.ac.jp Keywords: epithelial ovarian carcinoma, epithelial-mesenchymal transition, ZEB1, chemoresistance, metastasis Received: June 07, 2017 Accepted: July 25, 2017 Published: August 10, 2017 ABSTRACT ZEB1, a member of the zinc-finger E-box binding homeobox family, is considered to play a crucial role in cancer progression and metastasis. In the current study, we investigated the role of ZEB1 in metastasis and chronic chemoresistance of epithelial ovarian carcinoma (EOC) cells. Using several EOC and acquired paclitaxel (PTX)-resistant EOC cell lines, we investigated whether silencing ZEB1 led to a reversal of the chemoresistance and metastatic potential in vitro and in vivo . Subsequently, the expression of ZEB1 in EOC tissues and its association with the oncologic outcome were investigated. According to the immunohistochemical staining of EOC tissues, as the positivity of ZEB1 expression was increased, the overall survival of EOC patients became poorer ( P = 0.0022 for trend). Additionally, cell migration and invasion were significantly decreased by ZEB1 silencing in both PTX-sensitive and PTX- resistant cells. Although PTX-sensitivity was not changed by silencing ZEB1 in parental EOC cells, the depletion of ZEB1 made the PTX-resistant EOC cells more sensitive to PTX treatment. In an animal model, mice injected with ZEB1-silencing PTX-resistant cells survived for longer than the control cell-injected mice. Although the intravenous injection of PTX did not affect the tumor weight of shCtrl cells, the tumor weight of shZEB1 cells was significantly reduced by PTX treatment. The current data indicate the possible involvement of ZEB1 in the metastasis and paclitaxel resistance of EOC, and suggest that targeting this molecule may reverse the malignant potential and improve the oncologic outcome for EOC patients.

Aim Women with ovarian cancer (OC) often experience relapse and receive further repetitive chemotherapy. The objective of this study was to overview the remaining survival time after the final chemotherapy and to examine influential clinicopathologic indicators in those patients. Methods The medical charts of deceased OC patients who had died of the disease between 2003 and 2012 were retrospectively reviewed. We investigated post-cancer-treatment survival (PCS) defined as the interval between the date of the final chemotherapy and death. Results In all, 77 patients were enrolled. Three patients (3.9%) had received chemotherapy in the last 2 weeks. Eight (10.4%), 28 (36.4%), and 44 (57.2%) patients had received chemotherapy in the last 30, 60, and 90 days, respectively. There were no differences in either survival after recurrence or overall survival between the shorter (

Hydatidiform moles are known to pose an extremely high risk of severe early-onset preeclampsia if left untreated. TNF superfamily cytokine, LIGHT has recently been reported to contribute to pathophysiology of preeclampsia. The present study aimed to investigate the involvement of LIGHT in hydatidiform moles. We measured the serum levels of LIGHT and sFlt-1 by ELISA in 17 women with complete hydatidiform mole (HM) and 20 gestational-age-matched normal pregnant women (control). As a result, the serum LIGHT levels were significantly higher in HM as compared with those in control (69.9 ± 9.6 pg/ml vs 25.4 ± 5.3 pg/ml, p = 0.0001) and the serum levels of LIGHT were significantly positively correlated with those of sFlt-1 in HM (r = 0.68, p = 0.0029). Immunohistochemical analysis revealed that the expression levels of LIGHT were increased in HM placentas as compared with controls, and LIGHT and sFlt-1 were co-localized in the trophoblast cells of HM. In vitro studies using primary syncytiotrophoblast cells demonstrated that LIGHT directly induced sFlt-1 expression in trophoblast cells. Our results indicated that elevated LIGHT in the trophoblast cells of hydatidiform mole induces sFlt-1, which might underlie the pathogenic mechanism of early-onset preeclampsia developing secondary to molar pregnancies.

This study aimed to evaluate the efficacy and toxicity of 4-day chemotherapy with methotrexate, etoposide, and actinomycin D (MEA) for patients who were diagnosed with choriocarcinoma and high-risk gestational trophoblastic neoplasia (GTN). Between January 1999 and December 2015, 29 patients were treated with 4-day MEA after being diagnosed with choriocarcinoma or high-risk GTN. Complete remission to 4-day MEA and adverse effects were retrospectively evaluated. The complete remission rates were 79.3% (23/29) and 87.5% (21/24) in all patients and in those who received 4-day MEA as first-line therapy, respectively. Of six patients who developed drug resistance to 4-day MEA, three patients showed complete remission by other treatments, while the other three patients died of the disease. The major adverse effects were leukocytopenia, anemia, and nausea. Of 23 patients who were cured with 4-day MEA, treatment was changed to the etoposide and actinomycin D (EA) regimen in 14 patients, because of leukocytopenia, hepatotoxicity, and stomatitis. Among 20 patients who required hormonal therapy, 15 patients showed normal menstrual cycles after therapy. Five patients had nine conceptions (seven term live births and two spontaneous abortions). No babies were premature or had low birth weight nor did they have congenital anomalies. The results suggest that the efficacy and the adverse effects of 4-day MEA for choriocarcinoma and high-risk GTN may be the same level as EMA/CO. However, further study will be needed for determining the criteria of changing the treatment regimen from 4-day MEA to the EA regimen.

Occasionally, ovarian tumors are found to have originated from non-ovarian organs as metastatic lesions since the ovary is a common site of metastasis from many cancers. The aim of the current study was to estimate the long-term oncologic outcome of patients with metastatic mucinous ovarian carcinoma (MmOC) in comparison with those with primary mucinous ovarian carcinoma (PmOC) at an advanced stage. The data of one hundred and sixty-seven patients with mucinous ovarian cancer, including 91 patients with MmOC from the digestive organs and 76 patients with stage III–IV PmOC, were retrospectively analyzed. The prognostic significances of clinicopathologic factors were evaluated employing both uni- and multivariable analyses. Pathological slides were evaluated based on centralized pathological review. The median age of patients with PmOC and MmOC was 55 (18–81) and 51 years (30–82), respectively. With follow-up of a total of 167 patients, 145 patients (86.8%) developed recurrence. In addition, 122 patients (73.0%) died of the disease. Regardless of the residual tumor status, patients with PmOC did not a show a significantly poorer OS than those with MmOC. Furthermore, in a Cox multivariable hazard model, after adjustment for various clinicopathologic confounders, a gastric cancer (GC)-originated tumor and larger residual tumor were significant predictors of poorer OS [GC (vs. PmOC): HR (95% CI) 2.205 (1.303–3.654), P = 0.0036]. The oncologic outcome of patients with MmOC was extremely poor; however, it was almost the same as that of those with PmOC. We should recognize MmOC derived from gastric carcinoma as a highly aggressive malignancy.

Recently, connective tissue growth factor (CTGF) was demonstrated to be associated with aggressive characteristics, including proliferation, invasion and metastasis, in a number of malignancies. Here, we investigated the expression and function of CTGF in epithelial ovarian carcinoma (EOC) to clarify its molecular mechanism and clinical significance. Paraffin sections from clinical samples of EOC (N=104) were immunostained with the CTGF antibody, and then the staining positivity was semiquantitatively examined. Moreover, we explored the role of CTGF expression in the migration-promoting effect on and chemoresistance of EOC cells. The results revealed that of the 104 EOC patients, the low and high CTGF staining expression rates were 65 (62.5%) and 39 (37.5%), respectively. Patients belonging to the higher-level CTGF group showed poorer progression-free (PFS) and overall survival (OS) rates than those in the lower-level group [PFS (log-rank: P=0.0076) and OS (log-rank: P=0.0078), respectively]. Multivariable analysis showed that CTGF expression was a significant predictor of poorer PFS and OS [PFS: HR (high vs. low): 1.837, 95% CI: 1.023–3.289 (P=0.0418); OS: HR: 2.141, 95% CI: 1.077–4.296 (P=0.0300)]. In in vitro studies, in acquired paclitaxel (PTX)-resistant EOC cells, the silencing of CTGF expression led to the restoration of PTX sensitivity. Furthermore, we confirmed that the TGF-β-dependent migration-promoting effect on these CTGF-depleted cells was completely inhibited. In conclusion, the results of the present study suggest the possible involvement of CTGF in the migration-promoting effect and chemoresistance of EOC, suggesting that it may be a target for overcoming the malignant properties of EOC.

Objectives There is increasing evidence that systemic inflammatory response (SIR) markers are prognostic factors for various types of cancers. This is the first study to evaluate the usefulness of SIR markers for the prognosis of early-stage ovarian clear-cell carcinoma (OCCC). Methods We retrospectively investigated 83 patients diagnosed with stage I-II OCCC who underwent surgery between 2005 and 2017. Initially, receiver operating characteristic curve analysis for overall survival (OS) was used to determine optimal cut-off values for neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). Patients were stratified into 2 groups by the cut-off values (NLR=3.26, PLR=160). Univariate and multivariate analyses were performed to elucidate the significance of SIR markers as prognostic factors. Results In the median follow-up period of 64.1 months, 16 patients experienced recurrence, and nine patients died. The Kaplan-Meier curve showed that OS of the NLR-low group was significantly longer than the NLR-high group (p=0.021). There was no significant difference in progression-free survival between the 2 groups (p=0.668), but the post-recurrence survival of the NLR-low group was significantly longer than the NLR-high group (p=0.019). Furthermore, multivariate analysis showed that increase in NLR is a significant independent prognostic factor for poor prognosis (hazard ratio=7.437, p=0.017). There was no significant difference between PLR-low and PLR-high group. Conclusion Results suggest that NLR can be a significant independent prognostic factor for early-stage OCCC.

Endometriosis, characterized by the presence of extra-uterine endometrium, is a common gynecologic disorder in reproductive-age women. Although the detailed molecular mechanism of etiology remains unelucidated, recent studies have gradually revealed both genetic and epigenetic backgrounds of the development of endometriosis. In clinical practice, endometriosis has been recognized as a precursor lesion of several types of malignancies and endometriosis-associated carcinoma. An imbalance between reactive oxygen species and local antioxidants has been reported to contribute to the development of endometriosis-associated carcinoma as well as the pathophysiology of this disease through a systemic inflammatory response in the peritoneal cavity. This review mainly presents an epidemiology, possible etiology of endometriosis, precursor lesions, molecular features, and the association between the microenvironmental accumulations of oxidative stress in endometriosis-associated ovarian cancer progression.

Aim Radical trachelectomy (RT) is a widely used fertility-sparing treatment for patients with early cervical cancer (CCA). RT, however, is an investigational treatment, and its gynecological and obstetric efficacy are being investigated. We retrospectively assessed the efficacy of abdominal RT (ART) as a fertility-sparing surgery. Methods From 2010 to 2014, patients with stage IA2–IB1 CCA (tumor ≤2 cm) who wished to preserve their fertility underwent ART. The major outcomes were mortality, recurrence, pregnancy complications, and obstetric outcome. Results Twenty-eight patients received ART. Adjuvant chemotherapy was performed in seven patients because of lymphovascular space invasion. During the median follow-up of 43 months, no recurrences occurred. Twelve women attempted to conceive, and eight of them became pregnant. A total of five children were born, and one baby was full term. Three cases of second trimester, and one case of third trimester preterm births were recorded. Conclusions Fertility was preserved after ART in a moderate number of patients. The pregnancy and birth rates after ART have been improving, and increasing the full-term birth rate is the next goal. In addition, development of further types of minimally invasive surgery for CCA can be expected.

Background Elderly patients with uterine cervical cancer reportedly have a poorer prognosis than younger patients. Until now, the benefit of concurrent chemoradiotherapy (CCRT) for elderly patients has been considered limited. Methods We retrospectively analyzed 49 women with cervical cancer aged >70 years primarily treated with radiotherapy (RT) or CCRT in our institute between 2003 and 2014. Treatment compliance, toxicity, and survival benefit were analyzed. Results A total of 49 patients were identified in this retrospective analysis. Twenty patients with a median age of 75.4 years (range 70–77) were treated with CCRT and 29 patients with a median age of 77.9 years (range 70–89) underwent RT. In the CCRT group, 14 patients (70%) completed CCRT consisting of radiotherapy and 5 courses of cisplatin plus 5-fluorouracil including patients requiring a dose reduction of chemotherapy. The median overall survival (OS) in the CCRT and RT groups was 66.9 and 60.1 months, respectively (p = 0.156). The most common grade 3/4 acute toxicity was hyponatremia (35.0%), followed by neutropenia (15.0%) and diarrhea (10.0%) in the CCRT group, while this was anemia (17.2%) followed by radiation enteritis (10.3%) in the RT group. Conclusions CCRT was well tolerated in elderly patients with cervical cancer. Careful attention should be paid to the different characteristics of treatment-related toxicities in this group compared with younger patients.

Highlights • We present two cases of postmolar gestational trophoblastic neoplasia (GTN). • Both cases presented with lung metastases after hydatidiform mole. • Both cases showed spontaneous regression without treatment. • The mechanism behind this phenomenon remains unclear. • Patients with postmolar GTN and declining hCG values may not need chemotherapy.

In cervical cancer, para-aortic lymph nodes are common sites of metastasis. The purpose of the study was to evaluate the clinical benefits of prophylactic irradiation as postoperative therapy. A retrospective cohort study was conducted during 2001–2015 at a single institution. Patients with a high risk of para-aortic lymph nodes recurrence were eligible for this study, and we identified patients who had pelvic lymph node metastasis and underwent radical surgery and concurrent chemo-radiotherapy. As a result, 33 and 46 patients were included in the treatment (prophylactic irradiation) and non-treatment groups, respectively. Baseline differences between the two groups were adjusted with the inverse probability of treatment weighting using propensity scores composed of the independent variables including age, stage, tumor size, pathological findings, lymph node status, and pathological subtypes. In the 68-month median follow-up period (range 6–178 months), 25 patients experienced recurrence, and 17 patients were dead. After adjustment with the inverse probability of treatment weighting, the recurrence rates tended to decrease in the treatment group, but there was no significant difference between the two groups [treatment vs. non-treatment, 29.4% and 44.3%, respectively; hazard ratio, 0.593 (95% CI 0.320–1.099); P = 0.097]. However, adjusted para-aortic lymph nodes recurrence rates were not significantly different [treatment vs. non-treatment, 7.8% and 11.4%, respectively; odds ratio, 0.660 (95% CI 0.187–2.322); P = 0.558]. Moreover, Kaplan–Meier curves showing post-recurrence survival revealed no significant difference between the two groups (P = 0.141). Prophylactic para-aortic lymph nodes irradiation did not reduce the risk of recurrence.

Malignant ovarian germ cell tumors usually occur in young women. Until the 1970s, before establishment of systemic chemotherapy, malignant ovarian germ cell tumors had a very poor prognosis. Recently, prognosis has improved, and fertility-sparing treatment is being adopted in patients who desire to become pregnant. However, the number of malignant ovarian germ cell tumor survivors who actually became pregnant remains unknown.The present study aimed to clarify the reproductive outcomes in malignant ovarian germ cell tumor survivors by using data from a multicenter database and an additional survey on reproductive outcomes.The study used the Tokai Ovarian Tumor Study Group database on ovarian cancer patients. We assessed the database from 1986 through 2016 and selected malignant ovarian germ cell tumor patients40 years of age who received fertility-sparing treatment. Questionnaires on reproductive outcomes were sent to the registered facilities. The following data were collected and used in this study: age, date of onset, surgical procedure, chemotherapy regimen, tumor type, International Federation of Gynecology and Obstetrics stage, survival outcome and period, number of pregnancies and childbirths, marital status, childbearing desire, method of pregnancy, gestational weeks at delivery, birthweight of the baby, obstetric complications, and menstrual status after fertility-sparing treatment.A total of 110 malignant ovarian germ cell tumor patients who received fertility-sparing treatment were identified. The median follow-up period was 10.4 years. Five patients were excluded because of death or loss of fertility after treatment for recurrence. Thus, 105 patients were finally included. The additional survey revealed that 42 of 45 patients who desired childbirth became pregnant. The total number of pregnancies was 65, and 56 babies were born to 40 malignant ovarian germ cell tumor survivors.The reproductive outcomes of malignant ovarian germ cell tumor survivor are promising with fertility-sparing treatment. Malignant ovarian germ cell tumor survivors can become pregnant and give birth if they desire.

Kinesin family member 20A (KIF20A), which is involved in cytokinesis and intracellular transportation, has been recently reported to be upregulated in several malignancies and may contribute to chemotherapeutic resistance. We examined the distribution and expression of KIF20A in clear-cell carcinoma (CCC) of the ovary to elucidate its clinical significance and molecular mechanism. Paraffin sections from ovarian CCC tissues (N=43) were immunostained with KIF20A antibody, and the staining intensities were semi-quantitatively evaluated. Furthermore, we investigated whether silencing of KIF20A contributes to the proliferation-inhibitory potential using CCC cells. During the observational period, 18 patients (41.9%) developed recurrence. The median time to recurrence was 11.5 months. Patients in the high KIF20A expression group showed poorer progression-free survival (PFS) and overall survival (OS) than those in the low expression group (P=0.0443 and P=0.0478, respectively). In multivariable analyses, KIF20A expression was also a significantly independent indicator of PFS and a marginally significant indicator of OS [PFS: HR (high vs. low), 5.488; 95% CI, 1.410–24.772 (P=0.0136); OS: HR, 2.835; 95% CI, 0.854–11.035, (P=0.0897)]. In in vitro studies, the ovarian CCC cell proliferation was significantly decreased by KIF20A silencing or in the presence of KIF20A inhibitor in CCC cells. Cell cycle G2/M arrest and a higher apoptosis-induced fraction were more frequently observed in si-KIF20A-transfected CCC cells than in the control cells. Although the present study was preliminary, these data indicate the possible involvement of KIF20A in the proliferation of CCC, suggesting that targeting this molecule may contribute to reversing the malignant potential consequently affecting the oncologic outcome of CCC patients.

// Nobuhisa Yoshikawa 1, * , Toshiya Teshigawara 1, * , Yoshiki Ikeda 1 , Kimihiro Nishino 1 , Jun Sakata 1 , Fumi Utsumi 1 , Kaoru Niimi 1 , Ryuichiro Sekiya 2 , Shiro Suzuki 1 , Michiyasu Kawai 3 , Kiyosumi Shibata 2 , Fumitaka Kikkawa 1 and Hiroaki Kajiyama 1 1 Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan 2 Department of Obstetrics and Gynecology, Fujita Health University Banbuntane Hotokukai Hospital, Nagoya, Japan 3 Department of Obstetrics and Gynecology, Toyohashi Municipal Hospital, Toyohashi, Japan * These authors have contributed equally to this work Correspondence to: Nobuhisa Yoshikawa, email: n-yoshikawa@med.nagoya-u.ac.jp Hiroaki Kajiyama, email: kajiyama@med.nagoya-u.ac.jp Keywords: malignant transformation; mature cystic teratoma; fertility-sparing surgery; oncological outcome; reproductive outcome Abbreviations: MT-MCT (malignant transformation arising from mature cystic teratoma of the ovary), FSS (fertility-sparing surgery), OS (overall survival), DFS (disease-free survival), EOC (epithelial ovarian cancer) Received: February 20, 2018 Accepted: May 19, 2018 Published: June 08, 2018 ABSTRACT Background: The purpose of this study was to evaluate the long-term clinical outcome of young women with malignant transformation arising from mature cystic teratoma of the ovary (MT-MCT) by comparing radical surgery and fertility-sparing surgery (FSS). Patients and methods: All patients treated with radical surgery or FSS for MT-MCT in multiple institutions were registered in this analysis. Univariate and multivariate analyses were performed to evaluate clinical outcome, including overall survival (OS) and disease-free survival (DFS). Results: From 1986 to 2016, 62 patients with MT-MCT were treated in our group. The median follow-up period was 38.0 (2.0-227.9) months, and the median age was 54 (17-82) years old. Multivariate analysis revealed that only advanced stage was significantly correlated with poorer prognosis of patients [hazard ratio (HR) for death: 6.58, 95% confidence interval (CI): 1.82–24.78, P = 0.0048; HR for recurrence: 5.59, 95% CI: 1.52–21.83, P = 0.01]. Of a total of 13 women with stage I-II disease at less than 45 years old, 7 were treated with FSS, and there was no recurrence except for in one woman with stage II MT-MCT. There was no significant difference in long-term oncological outcome between radical surgery and FSS. Conclusion: FSS may be indicated for patients with stage I MT-MCT, who hope to preserve fertility, as no relapse was found after FSS.

Uterine sarcomas are some of the most malignant and aggressive tumor types among the gynecologic malignancies, and they are associated with a high rate of recurrence and a poor prognosis. Due to their rarity and diversity, the optimal treatment for recurrent uterine sarcomas has not yet been elucidated. The aim of the present study was to investigate the potential of secondary cytoreductive surgery (SCS) for patients with recurrent uterine sarcomas. A total of 18 patients with recurrent uterine sarcomas were retrospectively identified at the Department of Obstetrics and Gynecology, Nagoya University (Nagoya, Japan) between January 2002 and December 2015. This included 8 patients with leiomyosarcoma, 6 with carcinosarcoma, 3 with endometrial stromal sarcoma and 1 with adenosarcoma. All patients underwent primary debulking surgery as the initial treatment. In summary, 9 patients were treated with SCS when they experienced their first recurrence, and the other 9 patients were treated with non-SCS methods, including chemotherapy or radiotherapy. In the SCS group, 5/9 patients had confined pelvic recurrences, 3 patients had extra-pelvic diseases, including pulmonary metastasis, and one patient had intra- and extra-pelvic recurrence. The 3-year overall survival (OS) rates were 77.8 and 11.1% in the SCS and non-SCS groups, respectively. The patients who underwent SCS experienced a significantly longer OS time compared with those in the non-SCS group (P=0.006). In addition, the disease-free survival after second-line therapy was significantly longer in the SCS group than in the non-SCS group (P=0.0496). These findings suggest that resection of recurrent uterine sarcomas may be beneficial for the improvement of patient survival. Prospective studies with sufficient statistical power are warranted for further evaluation of the effect of SCS.

The aim of the present study was to estimate the post-recurrence survival (PRS) of patients with relapsed uterine cervical cancer (RUCC). In addition, clinicopathological indicators that influenced PRS were investigated. Between 1998 and 2014, of 740 patients with cervical cancer, 165 patients experienced recurrence (recurrence rate, 22.3%), and 83 patients succumbed to the disease within a median follow-up of 34.3 months. A total of 151 stage Ib-IV patients who experienced recurrence after initial treatment for cervical cancer at our institute were analyzed. Uni- and multivariate analyses were performed using the Kaplan Meier method, and Cox regression model. The median age was 55 years (range, 20–88 years). In all, 80 patients succumbed to the disease. The median PRS time of all the patients was 28.4 months. The 1-, 3-, and 5-year PRS rates of patients were 75.1, 41.9, and 32.1%, respectively. In addition, the median survival period in patients who had received surgery as an initial treatment was significantly longer compared with that in patients who had not previously undergone surgery (36.7 vs. 23.3 months, respectively; P=0.0338). Following the univariate analysis, the median PRS in patients with in- and out-field recurrence was 12.6, and 45.9 months, respectively (P

Vascular endothelial growth factor (VEGF) inhibitors have been utilized for the treatment against advanced or recurrent cervical carcinoma as a novel therapeutic modality. However, the expression level of VEGF in post-radiotherapy relapsed/persistent cervical cancer remains to be elucidated. The aim of the present study was to investigate the expression of VEGF and associated molecules using tumor samples from patients with post-radiotherapy relapsed/persistent cervical cancer. From a database of 826 patients who were treated at our institution between 2003 and 2015, eight patients with post-radiotherapy relapsed/persistent cervical cancer were identified, and 20 patients who underwent initial surgery alone were used as a control. Using samples from these patients, the expression levels of VEGF-A, VEGF receptor-1 (VEGFR-1) and hypoxia inducible factor-1α (HIF-1α) were immunohistochemically categorized as negative or weakly, moderately, or strongly positive according to the size of the staining area, and intensity. In carcinoma cells, the expression levels of VEGF-A, VEGFR-1 and HIF-1α were significantly higher in post-radiotherapy relapsed/persistent cervical cancer compared with control patients (P=0.0003, 0.0003, and 0.0001, respectively). In stroma cells, similar tendencies with statistical significance were observed (P=0.0014 and P

Choriocarcinoma is a malignant gestational trophoblastic neoplasia (GTN) and one of the curable types of gynecological cancer. However, 10% of choriocarcinoma patients have a poor prognosis, particularly when they have metastasis, apart from pulmonary metastasis, or do not go into remission by the second chemotherapeutic regimen. We herein present the case of a 36-year-old patient who had choriocarcinoma with metastases to the lungs, liver and kidneys. The 5th and 6th regimens with cisplatin for choriocarcinoma failed and the patient developed brain metastases. She was then treated with four cycles of high-dose ifosfamide, carboplatin and etoposide (ICE) with blood progenitor cell support after confirming the effectiveness of ICE at normal doses. The serum human chorionic gonadotropin (hCG) level was 140,009 mIU/ml at the start of high-dose ICE and the patient tolerated this regimen well. However, the beneficial effect was decreasing with each successive course of treatment, with the lowest level of hCG at 103 mIU/ml after the fourth course. The patient did not achieve complete remission and succumbed to the disease 4 months after the last chemotherapy. The findings of the present case and a review of the related literature suggest that high-dose ICE with stem cell rescue may be considered as a viable treatment option for a multi-drug resistant choriocarcinoma or GTN.

It remains unknown whether the end-of-life (EOL) environment influences survival after anticancer treatment, particularly for gynecologic malignancy.The study's objective was to clarify whether the survival time varied depending on where patients spend the EOL.This retrospective study included patients who received initial oncologic treatment but died due to cancer recurrence and/or progression. The subjects were a cohort of 181 gynecologic malignant tumor cases in a single institution from 2002 to 2008. Measurement was of postcancer treatment survival (PCS), defined as the time interval between the last date of anticancer treatment after recurrence/progression and death from the disease, analyzed on stratification by type of supportive care or where patients spent the EOL.The median survival time was 26.1 (1.0-306.4) months. The distribution of the carcinoma type was as follows: 28.7% of patients with cervical (N=52), 27.6% with endometrial (N=50), and 43.1% with ovarian (N=79) cancer. The median PCS was 13.3 weeks. Patients in the hospice/home care group showed a significantly more favorable PCS than those in the hospital group (log rank: P=0.029). On multivariate analysis, the age (60 versus ≥60) and site of supportive care (hospital versus hospice/home care) retained their significance as independent prognostic factors of poor PCS (age: HR=0.679, 95% CI, 0.496-0.928, P=0.0151; site of supportive care: HR=0.704, 95% CI, 0.511-0.970, P=0.0319).Our current data could be hypothesis generating; it is possible that the EOL environment is a crucial prognostic factor for survival after anticancer treatment.

Objectives This study was conducted to estimate the oncologic outcome of stage I epithelial ovarian carcinoma (EOC) patients after recurrence. Study design After central pathological review and searching of the medical records of multi-institutions, a total of 103 relapsed patients with stage I EOC were analyzed. The major endpoint was postrecurrence survival (PRS). Results The median follow-up for surviving patients was 57.5 (5.7–242.0) months. The median age was 52 (14–89). Among the patients, 19 (18.4%) had FIGO IA disease, and 4 (3.9%) and 80 (77.7%) had IB and IC disease, respectively. Regarding the histological type, the clear-cell type was the most frequently observed ( N = 42: 40.8%). The 3/5-year overall and PRS rates of all patients were 63.7/47.9 and 38.2/24.0%, respectively. The 5-year PRS rates of patients with serous, endometrioid, clear-cell, and mucinous tumors were 44.9, 35.0, 19.8, and 0%, respectively. On stratifying by the histological type, the overall and postrecurrence survival rates of patients with the mucinous/clear-cell types were significantly poorer than in those with the non-mucinous/clear-cell types (OS: P = 0.0253, PRS: P = 0.0016). In multivariate analyses, the FIGO stage (IA/IB vs. IC) and histological type (clear-cell/mucinous vs. non- clear-cell/mucinous) retained their significance as prognostic factors of a poorer PRS {stage IC (vs. IA/B): HR: 2.176 (95% CI: 1.059–4.470), P = 0.0343: clear-cell/mucinous (vs. non- clear-cell/mucinous): HR: 2.486(95% CI: 1.416–4.364), P = 0.0015). Conclusions Even if at stage I, once patients with a mucinous/clear-cell histology experience recurrence, subsequent survival is extremely poor.

Highlights • Gestational trophoblastic neoplasia can arise during the first trimester originating from trophoblasts of concurrent pregnancy. • Intraplacental choriocarcinoma can be developed from trophoblasts of a previous pregnancy.

We retrospectively analyzed the clinicopathological features and evaluated the prognostic indicators of recurrence in 132 patients with clear cell adenocarcinoma (CCC) of the ovary at reproductive age. Between 1986 and 2011, as a regional population-based study, clinicopathological data on 132 young patients with CCC, collected under the central pathological review system, were subjected to uni- and multivariable analyses to evaluate recurrence-free survival (RFS). The median age was 40 (27–45) years. The median follow-up period for surviving patients was 46.4 months. During the observation period, there were 16 recurrences in 87 patients with stage I tumors (18.4 %), 8 in 17 with stage II (47.1 %), and 16 in 28 with III–IV (57.1 %). Subsequently, 35 patients died of the disease. Those with stage I or II did not reach the median RFS. The median RFS of stage III–IV was 21.6 months. When analysis was confined to stage I patients, there was no significant difference in the RFS of CCC patients between IA and IC(r) (intraoperative capsule rupture) (P = 0.7957). In contrast, CCC patients with IC excluding IC(r) [IC(non-r)] showed a poorer RFS than those with IC(r) (P

Objective This study was conducted to examine the effects of front-line chemotherapy on overall survival (OS) and postrecurrence survival (PRS) of patients with recurrent ovarian cancer, when stratifying the histologic type. Methods Five hundred and seventy-four patients with recurrent ovarian cancer with sufficient clinical information, including front-line chemotherapy, were analyzed. The pathologic slides were evaluated by central pathologic review. The patients were divided into two groups: group A (n=261), who underwent taxane plus platinum, and group B (n=313), who underwent conventional platinum-based chemotherapy without taxanes. Results The median age was 54 years (range, 14 to 89 years). Group A had significantly better median OS (45.0 months vs. 30.3 months, p