Mean platelet volume as a potential biomarker for survival outcomes in ovarian clear cell carcinoma.

OBJECTIVE: This study aimed to explore the prognostic value of mean platelet volume (MPV) in patients with ovarian clear cell carcinoma (OCCC) and evaluate the predictive performance of a random forest model incorporating MPV and other key clinicopathological factors. METHODS: A total of 204 patients with OCCC treated between January 2004 and December 2019 were retrospectively analyzed. Clinicopathological characteristics and preoperative laboratory data were collected, and survival outcomes were evaluated using the Kaplan-Meier method and Cox proportional hazards models. An optimal MPV cutoff was determined by receiver operating characteristic (ROC) curve analysis. A random forest model was then constructed using the identified independent prognostic factors, and its predictive performance was evaluated. RESULTS: The ROC analysis identified 9.3 fL as the MPV cutoff value for predicting 2-year survival. The MPV-low group had lower 5-year overall survival and progression-free survival rates than the MPV-high group (p = 0.003 and p = 0.034, respectively). High MPV emerged as an independent prognostic factor (p = 0.006). The random forest model, incorporating the FIGO stage, residual tumors, peritoneal cytology, and MPV, demonstrated robust predictive performance (area under the curve: 0.905). CONCLUSION: MPV is a promising prognostic indicator in OCCC. Lower MPV correlated with worse survival rates, advocating its potential utility in refining patient management strategies. The commendable predictive performance of the random forest model, integrating MPV and other significant prognostic factors, suggests a pathway toward enhanced survival prediction, thereby warranting further research.

Does uterine preservation affect survival outcomes of patients with stage I ovarian sex cord-stromal cell tumours? A multi-institutional study.

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.

Impact of uterus-preserving surgery on Stage I primary mucinous epithelial ovarian carcinoma: A multi-institutional study with propensity score-weighted analysis.

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.

Impact of age on clinicopathological features and survival of epithelial ovarian neoplasms in reproductive age.

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 < 0.001); stage I disease (85.9% vs. 70.4%, p < 0.001); mucinous type (69.2% vs. 35.6%, p < 0.001); conservative surgery (83.8% vs. 41.6%, p < 0.001); no adjuvant chemotherapy (67.2% vs. 44.7%, p < 0.001); and CA125 ≤ 35 U/mL (39.4% vs. 28.8%, p < 0.05). There was a significant difference in the overall survival (p = 0.0051) and the disease-free survival (p = 0.0039) between the two groups. Multivariate analysis revealed that the independent prognostic factors for the overall survival were age, stage, histology, and ascitic fluid cytology. CONCLUSION: In epithelial ovarian neoplasms, younger patients had a survival advantage over older patients.

Prognostic impact of pelvic and para-aortic lymphadenectomy on clinically-apparent stage I primary mucinous epithelial ovarian carcinoma: a multi-institutional study with propensity score-weighted analysis.

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.

Fertility-sparing surgery and oncologic outcome among patients with early-stage ovarian cancer ~propensity score- matched analysis~.

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.

Epidemiological overview of metastatic ovarian carcinoma: long-term experience of TOTSG database.

Malignant ovarian neoplasm is one of the most lethal malignancies among cancers of the female reproductive system. Occasionally, these tumors originate from non-ovarian organs as metastatic lesions since the ovary is a frequent metastatic target of many cancers. However, there limited clinical information on metastatic ovarian carcinoma (MOC) and its hallmarks are unknown. During the period of 1986-2015, 4,284 patients with malignant ovarian neoplasm were identified using the Tokai Ovarian Tumor Study Group (TOTSG) database. Of these, excluding borderline malignant tumor, 3,478 patients with malignant ovarian cancer were extracted. The pathological slides were evaluated under central pathological review. Among them, a total of 143 (4.1%) patients with MOC were identified. The median age of patients with MOC was 54 (29-82) years. The most and second most frequent original tumors were colorectal (43%, N=62) and gastric (29%, N=42) carcinoma, respectively. The rates of carcinoma of the appendix, breast, and pancreas were 8, 6, and 4%, respectively. This is the one of the largest studies clarifying the rates of MOC among malignant ovarian neoplasms. Although the rate is low, we should keep in mind that MOC, particularly from colorectal and gastric cancer should be considered when encountering clinical practice of ovarian cancer.

Long-term oncologic outcome and its prognostic indicators in reproductive-age women with ovarian clear-cell carcinoma.

BACKGROUND: 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. PATIENTS AND METHODS: 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). RESULTS: 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 < 0.0001). Confining analysis to stage I patients, there was no difference in OS between those who underwent fertility-sparing surgery and those who received radical surgery (P = 0.1593). In relapsed patients, the median survival after recurrence was 11.6 months. In multivariable analysis of stage I patients, the capsule status was an independent prognostic indicator of OS {IC2/IC3 vs. IA/IC1: HR 4.293 (95% CI 1.140-16.422), P = 0.0318}. CONCLUSION: CCC patients staged greater than IC2/IC3 show a markedly increased risk of mortality. Thus, it is important to diagnose patients staged under IC2/IC3.

Comparison of long-term oncologic outcomes between metastatic ovarian carcinoma originating from gastrointestinal organs and advanced mucinous ovarian carcinoma.

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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]. CONCLUSION: 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.

Oncologic outcomes after secondary surgery in recurrent clear-cell carcinoma of the ovary.

OBJECTIVE: Complete 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. METHODS: Details 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 p<0.05 was considered significant. RESULTS: A 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). CONCLUSION: Patients with intraperitoneal recurrence or incomplete tumor resection had the worst survival after secondary cytoreductive surgery.

Oncologic and reproductive outcomes of cystectomy as a fertility-sparing treatment for early-stage epithelial ovarian cancer.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Survival impact of capsule status in stage I ovarian mucinous carcinoma-A mulicentric retrospective study.

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.

Analysis of late adverse events and their chronological changes after radiation therapy for cervical cancer.

Several late adverse events occur after radiation therapy (RT) for cervical cancer. However, there has been little reported about their chronological changes. It is still unclear whether concurrent chemoradiotherapy (CCRT) increases late complications. We aimed to evaluate the late adverse events and their chronological changes and whether CCRT increases their incidence and severity. For this purpose, we retrospectively analyzed 157 women with histologically proven cervical cancer. We reviewed all late adverse events and compared the frequency and severity between the patients who underwent CCRT and those who underwent RT alone. We calculated the cumulative occurrence rates of late adverse events stratified by the site and severity, and determined the chronological changes. With survivors' median follow-up time of 74.3 months, late adverse events occurred in 49.0% and serious complications developed in 24.2% of all patients. There was no significant difference in the cumulative incidence rate of all late adverse events between the CCRT and RT-alone groups (p = 0.720). The incidence rate of rectal bleeding was 25.5%. Serious rectal bleeding developed in 5 patients, all within 20 months from the start of RT. Importantly, the symptoms of rectal bleeding disappeared or were relieved in most patients during follow-up. In conclusion, we evaluated the late adverse events and their chronological changes after RT for cervical cancer and showed that adding chemotherapy to RT did not affect the frequency and severity of late complications, and the symptoms of rectal bleeding were relieved over time.

Fertility-sparing surgery of malignant transformation arising from mature cystic teratoma of the ovary.

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.

The possible existence of occult metastasis in patients with ovarian clear-cell carcinoma who underwent complete resection without any residual tumours.

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<0.0001 (recurrence) / P<0.0001 (death)}. Furthermore, confining analysis to relapsed patients, 1-, 2-, and 3-year CID after recurrence were 41.5, 60.9, and 73.9, respectively. Confining analyses to patients with sufficient information about adjuvant chemotherapy, the 5-year CIR / CID of stage IA-IC1 patients with or without chemotherapy were as follows: recurrence {13.0% (yes) / 9.6% (no)}, death {9.3% (yes) / 4.2% (no)}, respectively {P=0.947 (CIR) / P=0.224 (CID)}. CCC patients staged greater than IC2/ IC3 show a marked risk of mortality, even after complete surgical resection.

Prediction of neutrophil reduction using plasma paclitaxel concentration after administration in patients with uterine, ovarian, or cervical cancers in an outpatient clinic.

PURPOSE: Plasma paclitaxel (PTX) concentration 24 h or later after PTX administration may predict myelosuppression. Here, we explored predictive markers for neutropenia induced by intravenous administration of PTX in an outpatient clinic. METHODS: Thirty women suffering from uterine, ovarian or cervical cancer were enrolled in this study. PTX (mean dose: 167 mg/m2) was intravenously infused and followed by carboplatin. Plasma samples were obtained 4 h after PTX administration. Genotyping was carried out for CYP3A5*3, ABCB1 1236 C>T, 2677 G>T/A, and 3435 C>T. RESULTS: There was no significant relationship between genotype and reduced neutrophil count. Neutrophil reduction rate correlated with the patient's height, neutrophil count on the day of administration, and plasma PTX concentration. Multiple regression analysis with those three indices explained 47.7% of the interindividual variability of the neutrophil reduction rate. The model with plasma PTX concentration, patient's height, and plasma 6-α-hydroxy-paclitaxel /PTX concentration ratio also explained 30.0% of the interindividual variability for the neutrophil nadir count after PTX administration. CONCLUSIONS: These results indicate that neutrophil reduction after PTX administration can be partially predicted by multiple regression analysis involving plasma concentration data collected at outpatient clinics.

Oncologic outcome after recurrence in patients with stage I epithelial ovarian cancer: are clear-cell and mucinous histological types a different entities?

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.

Mutational analysis of FOXL2 p.C134W and expression of bone morphogenetic protein 2 in Japanese patients with granulosa cell tumor of ovary.

AIM: To assess whether FOXL2 p.C134W mutation may play a role in the development of human ovarian tumors in the Japanese, we investigated the FOXL2 codon 134 mutation and protein expression of inhibin-α, bone morphogenetic protein 2 (BMP2) and follistatin (FST) in Japanese patients with granulosa cell tumor (GCT) of the ovary and other ovarian tumors. METHODS: We analyzed 114 tumor tissues from ovarian tumors, including 44 adult-type and two juvenile-type GCT of the ovary and 68 ovarian tumors by DNA sequencing. Immunohistochemistry was also performed in the adult and juvenile GCT tissues by immunostaining inhibin-α, BMP2 and FST. RESULTS: We found the FOXL2 p.C134W mutation in 27 out of 44 (61.4%) adult-type GCT of the ovary, but none in other ovarian tumors. Histologically, all of the adult-type GCT sections were positive for inhibin-α, and the expression of BMP2 and FST was detected in 14 of 44 (31.8%) and zero of 47 (0%), respectively. No significant differences regarding the diagnosed age, preoperative serum carbohydrate antigen 125 levels, or BMP2 immunopositivity between the FOXL2 p.C134W mutation-positive and mutation-negative were found in the adult-type GCT patients. CONCLUSION: Our findings suggest that FOXL2 p.C134W mutation-positive adult-type GCT of the ovary may not be common in the Japanese as compared to the previous data.

Clinicopathologic features of epithelial ovarian carcinoma in younger vs. older patients: analysis in Japanese women.

OBJECTIVE: The purpose of this study was to clarify the clinical features of epithelial ovarian carcinoma (EOC) in younger vs. older patients in Japan. METHODS: We collected data on 1,562 patients with EOC treated at multiple institutions in the Tokai Ovarian Tumor Study Group, and analyzed them retrospectively. All patients were divided into 2 groups: group A (≤40 years old) and group B (>40 years old). The data were analyzed to evaluate prognostic factors and the distribution of features in each group. Patients were subjected to univariate and multivariate analyses to evaluate overall survival (OS). RESULTS: The median follow-up time was 45.1 months (range, 1 to 257 months). Patients in group A had a significantly higher rate of stage I disease (67.3% vs. 42.6%, respectively; p<0.001) and the mucinous type (36.7% vs. 13.5%, respectively; p<0.001) than those in group B. There was a significant difference of OS between the 2 groups (p=0.013). However, upon stratification according to the stage, there were no significant differences in the OS between the 2 groups (group A vs. B: stage I, p=0.533; stage II-IV, p=0.407). Multivariate analysis revealed that younger age was not an independent prognostic factor for OS. CONCLUSION: On the basis of our data, younger patients had a different clinical profile than older patients, particularly regarding the stage of the disease and pathological distribution; however, they showed a similar long-term prognosis, even upon stratification according to the stage.

Recurrence-predicting prognostic factors for patients with early-stage epithelial ovarian cancer undergoing fertility-sparing surgery: a multi-institutional study.

OBJECTIVES: We reviewed the clinical outcomes of patients with early-stage epithelial ovarian cancer (EOC) who had undergone fertility-sparing surgery (FSS) to assess recurrence-free survival (RFS). STUDY DESIGN: After central pathological review and scanning of the medical records of multiple institutions, a total of 94 patients with stage I EOC (IA: 43 and IC: 51) treated with FSS were analyzed. IC substages were defined as follows: intraoperative spillage (IC1), preoperative capsule rupture or surface invasion (IC2), and positive cytology results (IC3). RESULTS: The median age was 30.5 (13-40) years. The median follow-up time was 66.6 months. Fourteen patients (14.9%) showed carcinoma recurrence. Eleven (11.7%) patients died of the disease. The total 5-year RFS rate including all women who received FSS was 84.3%. There was no significant difference in RFS between patients with IC1 and those with stage IA (P=0.9411). In contrast, the RFS rate of patients with IC2/3 was significantly poorer than in patients with stage IA (IA vs. IC2/3: P=0.0487, IC1 vs. IC2/3: P=0.0471). In further analyses according to each histological type and grade, the RFS rate of subjects with the mucinous type was the same as that of those with a clear-cell histology (P=0.3350). There was a significant difference in RFS of patients with grade 1 (G1) and G2-3 (P=0.0004). To eliminate selection bias from a number of clinicopathologic factors as thoroughly as possible, the age, FIGO stage, histological type, grade, and postoperative adjuvant chemotherapy were entered into multivariate RFS analyses. Cox multivariable analysis showed that the substage group and grade were independent prognostic factors for RFS. CONCLUSIONS: Confined to young women with intraoperative rupture, FSS may be proposed, if without tumor-associated dense adhesion. However, those with preoperative rupture, surface invasion, and positive cytology showed a greater risk of recurrence, suggesting that they are not recommended candidates. Although patients with G2-3 tumors showed a poorer prognosis than those with G1, the number of these subjects was so small that the current results should be reconfirmed in the next study.