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Objective To investigate the clinical characteristics of women with Stage I primary mucinous epithelial ovarian carcinoma (mEOC) and evaluate the impact of uterus-preserving surgery (UPS) in terms of survival prognosis. Methods A regional multi-institutional retrospective study conducted between January 1986 and March 2017 by reviewing records of the Tokai Ovarian Tumor Study Group. Clinical and pathologic data and survival outcomes were assessed for women with Stage I primary mEOC. The baseline imbalance between women with and those without UPS was adjusted by an inverse probability of treatment weighting method using the propensity score (PS) of independent clinical variables. Results Among 4730 women with malignant ovarian tumors, 185 had Stage I primary mEOC and were included in the study. The mean age was 47.6 years (range 12-87 years), and 56 (30.3%) women underwent UPS. After PS-based adjustment, women in the UPS group did not have a poorer prognosis regarding overall survival (P=0.776) or recurrence-free survival (P=0.683). Even after age stratification, there was no statistical difference in survival outcomes between the UPS and non-UPS groups. Conclusion UPS was not associated with decreased survival and may be a treatment option for women with Stage I primary mEOC irrespective of age.

Background Long-term follow-up reports of low-grade endometrial stromal sarcoma (LGESS) including its clinical course and pathological data are rare. We previously reported the case of a Japanese woman diagnosed with LGESS, who was treated with multidisciplinary therapy. She had been suffering from uterine cervical tumor diagnosed as cervical polyps, or fibroid in statu nascendi, since 24 years old. The patient had survived for 25 years with the disease. This report presents her progress and pathological change since the previous report. Case presentation At age 45, the patient experienced a relapse of the remnant LGESS tumor between the right diaphragm and liver. Although chemotherapy was not effective, the tumor was eliminated by proton therapy. At age 46 years, the remnant tumors outside the irradiated field were resected. The disease was originally diagnosed as “neuroendocrine carcinoma (NEC)” using the surgical specimen. Therefore, cisplatin and irinotecan combination chemotherapy were administered to treat the remnant dissemination. After 4 cycles of chemotherapy, the liver metastases had enlarged and were resected surgically. Consequently, no remnant tumor was visible in the abdominal cavity at the end of the surgery. To determine the origin of NEC, we examined the previously resected specimens obtained from her ileum at age 40 years. A boundary between the LGESS and neuroendocrine tumor grade 2 (NET G2)-like lesion was found in the tumor, indicating that the origin of these tumors was LGESS. After less than 2 years of chemotherapy and undergoing surgery, a relapse of the tumor in the liver induced biliary duct obstruction with jaundice, which was treated with endoscopic retrograde biliary drainage. Although pazopanib prolonged her life for 10 months, she died from sepsis at age 49 years, which was caused by the infection that spread to the liver metastatic tumor via the stented biliary ducts. Autopsy revealed adenocarcinoma-like differentiation of the tumor. Conclusion This LGESS patient has survived for a long time owing to multidisciplinary treatment including proton therapy. The LGESS tumor differentiated to NET G2-like tissue and then further to adenocarcinoma-like tissue during the long-term follow-up.

Background The aim of this study was to investigate how much the risks of recurrence and death are increased as a consequence of selecting fertility-sparing surgery (FSS) in young women with epithelial ovarian cancer (EOC). Methods After a central pathological review and search of the medical records from 14 collaborating hospitals, a non-randomized, observational cohort study was conducted between 1987 and 2015, including 1183 women with stage I EOC. Finally, a total of 285 patients with stage I EOC at reproductive age were recruited. Oncologic outcomes were compared between the FSS (N = 101) and radical surgery (RS) group (N = 184) using a propensity score (PS)-matching technique to adjust for relevant risk factors: the age, substage, histological type, grade, CA125 values, ascites cytology, ascites volume, and chemotherapy. Results During 66.0 months (median) of follow-up, 42 patients (14.7%) developed recurrence, and 31 patients (10.9%) died. In the original cohort, there was no significant difference in overall survival (OS) or recurrence-free survival (RFS) between the FSS and RS groups {Log-rank: OS (P = 0.838), RFS (P = 0.377)}. In the PS-matched cohort after adjustment for multiple clinicopathologic factors, there was no significant difference in RFS or OS between the FSS and RS groups {RFS (FSS vs. RS), HR: 1.262 (95% CI: 0.559–2.852), P = 0. 575; OS (FSS vs. RS), HR: 1.206 (95% CI: 0.460–3.163), P = 0.704}. Conclusions After adjustment for clinicopathologic factors, FSS in itself may not worsen the oncologic outcome in young women with early-stage EOC. A large-scale clinical study is necessary to validate the findings.

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.

Objective Sex cord-stromal tumours of the ovary are relatively uncommon neoplasms that account for 3 % of all ovarian cancers. Uterine preservation with careful staging is achievable; however, conservative surgery remains controversial. This study examined the prognostic effects of uterine preservation in patients with stage I sex cord-stromal tumours. Study design This retrospective cohort study was undertaken between January 1986 and February 2019, and the clinicopathological data of 4897 women with malignant ovarian tumours were collected. Seventy-seven patients with stage I sex cord-stromal tumours were eligible for inclusion. The characteristics and survival outcomes of these patients were examined. To investigate the prognostic effects of uterine-preserving surgery, baseline imbalances between patients with and without uterine-preserving surgery were adjusted using an inverse probability of treatment weighting with propensity scores composed of independent clinical variables. Results The mean ages of patients in the uterine-preserving surgery and non-uterine-preserving surgery groups were 39.8 and 57.8 years, respectively. After inverse probability of treatment weighting adjustments, no significant differences in overall survival (p = 0.205) or recurrence-free survival (p=0.071) were observed between the uterine-preserving surgery and non-uterine-preserving surgery groups. Estimated 10-year overall survival rates were 98.7 % in the uterine-preserving surgery group and 95.9 % in the non-uterine-preserving surgery group, and 10-year recurrence-free survival rates were 87.2 % in the uterine-preserving surgery group and 78.2 % in the non-uterine-preserving surgery group. Uterine-preserving surgery did not significantly affect the site of tumour recurrence. Conclusion Uterine-preserving surgery may be a feasible surgical option for patients with stage I sex cord-stromal tumours. Further research is needed to guarantee prognostic accuracy and develop effective therapeutic approaches for sex cord-stromal tumours.

Background The exact impact of full-staging lymphadenectomy on patients with primary mucinous epithelial ovarian carcinoma confined to the ovary is still unclear. In this study, we investigated the prognostic impact of lymphadenectomy covering both pelvic and para-aortic lymph nodes in patients with clinically-apparent stage I mucinous epithelial ovarian carcinoma, using data from multi-institutions under a central pathological review system and analyses with a propensity score-based method. Methods We conducted a regional multi-institutional retrospective study between 1986 and 2017. Among 4730 patients with malignant ovarian tumors, a total of 186 women with mucinous epithelial ovarian carcinoma were eligible. We evaluated differences in survival outcomes between patients with both pelvic and para-aortic lymphadenectomy and those with only pelvic lymphadenectomy and/or clinical lymph node evaluation. To analyze the therapeutic effects, the baseline imbalance between patients with both pelvic and para-aortic lymphadenectomy and others was adjusted with an inverse probability of treatment weighting using propensity score involving independent clinical variables. Results Fifty-five patients received both pelvic and para-aortic lymphadenectomy. With PS-based adjustment, both pelvic and para-aortic lymphadenectomy did not have additive effects regarding overall survival (P = 0.696) and recurrence-free survival (P = 0.978). Multivariate analysis similarly showed no significant impact of both pelvic and para-aortic lymphadenectomy on their prognosis. Conclusions The effect of pelvic and para-aortic lymphadenectomy is limited for clinically-apparent stage I primary mucinous epithelial ovarian carcinoma as long as full peritoneal and clinical lymph node evaluations are conducted. The results of this study should be used as the basis for additional studies, including prospective trials.

Endometrial clear-cell carcinoma (ECC) is relatively rare. The expression of diagnostic markers in this disease is similar to that of clear-cell carcinoma, but the molecular carcinogenic events and therapeutic targets are mostly unknown. MET gene amplification has been reported in various cancers, including ovarian clear-cell carcinomas; however, the MET gene status has not previously been examined in ECC. We performed real-time quantitative PCR (QPCR) and fluorescence in situ hybridization (FISH) to analyze the MET gene statuses of 12 ECC cases. We found MET amplifications in two cases (2/12; 16.7%) by both methods. Of the 12 cases, 9 were pure clear-cell carcinomas, and 3 were mixed types that included mixes with endometrioid carcinomas in 2 cases, and the remaining case was a heterologous-type carcinosarcoma that primarily consisted of a clear-cell carcinoma component and a scarce chondrosarcoma component. Both of the MET amplification cases were mixed; one contained endometrioid features, and the other chondrosarcoma features. This is the first report to analyze the statuses of the MET gene in ECCs, and the two mixed cases exhibited amplifications that are shared with ovarian clear-cell carcinomas. Further studies with larger numbers of cases are necessary to reveal the relationship between ECC and MET amplification.

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

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.

ObjectiveComplete tumor resection is considered essential in the management of patients with ovarian clear-cell carcinoma. There is a debate regarding whether patients with recurrent ovarian clear-cell carcinoma benefit from secondary cytoreductive surgery.MethodsDetails of patients with clear-cell carcinoma were collected by the Tokai Ovarian Tumor Study Group (Nagoya University Hospital and 13 affiliated institutions) and evaluated between January 1990 and December 2015. Histology was confirmed after central pathological review. The primary endpoint of the study was disease-free survival after secondary cytoreductive surgery. Distributions of events were evaluated using the χ2 test. Survival analysis was based on the Kaplan-Meier method. Survival curves were compared using the log-rank test. A value of pResultsA total of 169 patients who underwent secondary cytoreductive surgery (N=25) or medical management (N=144) for recurrent clear-cell carcinoma were collected. The median age for patients undergoing secondary cytoreductive surgery was 50 years (range 35–66). Overall, 18 patients had complete resection. In patients who underwent secondary cytoreductive surgery, the median disease-free and post-recurrence survival periods were 10.9 months and 21.2 months, respectively. Moreover, among 18 patients who underwent complete resection, seven showed no evidence of disease during the observation periods. The median post-recurrence survival periods of patients with complete or incomplete resection were 30.1 months and 10.4 months, respectively (p=0.002). On stratification by the recurrence site, patients with intraperitoneal recurrence showed poorer post-recurrence survival than those with recurrence at other sites (p=0.016). However, comparison between the secondary cytoreductive surgery group versus the medical management group showed there was no difference in post-recurrence survival, even when considering complete tumor resection (p=0.114).ConclusionPatients with intraperitoneal recurrence or incomplete tumor resection had the worst survival after secondary cytoreductive surgery.

Background The influence of capsule rupture on patients’ oncologic outcome has been controversial in early-stage ovarian carcinoma. The aim of this study was to investigate the significance of the capsule status in early-stage patients with mucinous epithelial ovarian carcinoma (mEOC). Patients and methods During the period of 1990–2015, 351 patients with stage I-IV mEOC were identified in the multicentric database. Of these, a total of 194 mEOC patients with a stage I tumor were in the study. Results The median follow-up of the surviving patients was 67.6 (2.0–248.1) months. The FIGO stage distribution was IA in 85 (43.8%), IB in 2 (1.0%), IC1 in 58 (29.9%), IC2 in 18 (9.3%), and IC3 in 31 (16.0%). The 5-year overall survival (OS) rates in patients with stage IA-B, IC1, and IC2-3 tumors were 95.8, 82.5, and 82.9%, respectively {IA-B vs. IC1: P = 0.0031, IA vs. IC2-3: P = 0.0042}. Similarly, the 5-year recurrence-free survival rates in patients with stage IA-B, IC1, and IC2-3 tumors were 93.5, 73.0, and 79.2%, respectively (Log-rank: P = 0.0034). Among all patients, 104 received adjuvant chemotherapy and 90 did not. There was no significant difference in each substage group between the non-chemotherapy and chemotherapy groups in the 5-year overall survival rate {chemotherapy (yes vs. no): 87.0 vs. 90.3%: P = 0.5389}. Multivariate analysis demonstrated that the capsule status was a significant prognostic factor for OS {IA-B (referent) vs. IC1: HR (95% CI): 3.527 (1.125–12.568), P = 0.0300)}. Conclusion mEOC patients staged greater than IC1 show a marked risk of mortality even after postoperative chemotherapy.

Aims To determine versican-producing cells in normocellular bone marrow and to evaluate chronological alteration in the number of versican-producing macrophages in bone marrow of patients with acute myelogenous leukaemia (AML) after cord blood stem cell transplantation (CBSCT) to gain insight in the significance of versican in recovery of haematopoiesis. Methods We enrolled seven age-matched unrelated patients with normocellular bone marrow for determining versican-producing cells in bone marrow, CBSCT-treated patients with AML, 18 with fine and other four with poor engraftment, for determining chronological alteration of versican-expressing and CD68-expressing cells in transplanted bone marrow in reference to the total cells. Clot samples of patients with AML were collected from the +16 to +55 day after transplantation and separated into four groups. We included an AML case whose specimen was obtained on the +9 day. Cells positive in immunohistochemistry using antibodies to versican and CD68 were counted to obtain the mean±SD in a unit area of the bone marrow, plotted chronologically and compared with the numbers from the age-matched normocellular group. Results We determined by a double immunohistochemistry that the versican-expressing cells in bone marrow are macrophages. The time-course curve demonstrated an inverse relationship between the versican-positive macrophages and the total cells in the transplanted bone marrow for over 55 days. In bone marrow of poor engraftment cases, versican-positive macrophages appeared to be decreased in comparison with age-matched and sampling day-matched patients. Conclusions These results suggest that versican and/or versican-expressing macrophages positively contribute to bone marrow regeneration of patients with AML after CBSCT.

Background: Patients with FIGO stage IV epithelial ovarian carcinoma have a poor but non-uniform prognosis. This study aimed to compare the survival of patients with serous or endometrioid tumours (S/E) and clear cell or mucinous tumours (non-S/E). Methods: Data for 223 patients who underwent surgery between 1987 and 2010 and were diagnosed by centralized pathology review and were retrospectively analysed. The patients included 169 with S/E tumours and 54 with non-S/E tumours. Results: The median overall survivals (OSs) of the S/E and non-S/E groups were 3.1 and 0.9 years, respectively (P

Endometrial clear-cell carcinoma (ECC) is relatively rare. The expression of diagnostic markers in this disease is similar to that of clear-cell carcinoma, but the molecular carcinogenic events and therapeutic targets are mostly unknown. MET gene amplification has been reported in various cancers, including ovarian clear-cell carcinomas; however, the MET gene status has not previously been examined in ECC. We performed real-time quantitative PCR (QPCR) and fluorescence in situ hybridization (FISH) to analyze the MET gene statuses of 12 ECC cases. We found MET amplifications in two cases (2/12; 16.7%) by both methods. Of the 12 cases, 9 were pure clear-cell carcinomas, and 3 were mixed types that included mixes with endometrioid carcinomas in 2 cases, and the remaining case was a heterologous-type carcinosarcoma that primarily consisted of a clear-cell carcinoma component and a scarce chondrosarcoma component. Both of the MET amplification cases were mixed; one contained endometrioid features, and the other chondrosarcoma features. This is the first report to analyze the statuses of the MET gene in ECCs, and the two mixed cases exhibited amplifications that are shared with ovarian clear-cell carcinomas. Further studies with larger numbers of cases are necessary to reveal the relationship between ECC and MET amplification.

As the finalization of a hydrogen experiment towards the deuterium phase, the exploration of the best performance of hydrogen plasma was intensively performed in the large helical device. High ion and electron temperatures, Ti and Te, of more than 6 keV were simultaneously achieved by superimposing high-power electron cyclotron resonance heating onneutral beam injection (NBI) heated plasma. Although flattening of the ion temperature profile in the core region was observed during the discharges, one could avoid degradation by increasing the electron density. Another key parameter to present plasma performance is an averaged beta value $\left\langle \beta \right\rangle $ . The high $\left\langle \beta \right\rangle $ regime around 4% was extended to an order of magnitude lower than the earlier collisional regime. Impurity behaviour in hydrogen discharges with NBI heating was also classified with a wide range of edge plasma parameters. The existence of a no impurity accumulation regime, where the high performance plasma is maintained with high power heating >10 MW, was identified. Wide parameter scan experiments suggest that the toroidal rotation and the turbulence are the candidates for expelling impurities from the core region.