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.

Long-term multidisciplinary treatment including proton therapy for a recurrent low-grade endometrial stromal sarcoma and pathologically prominent epithelial differentiation: an autopsy case report.

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.

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.

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.

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.

MET amplification in endometrial cancers with clear-cell carcinoma components.

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.

Napsin A is a specific marker for ovarian clear cell adenocarcinoma.

Ovarian clear cell adenocarcinoma has a relatively poor prognosis among the ovarian cancer subtypes because of its high chemoresistance. Differential diagnosis of clear cell adenocarcinoma from other ovarian surface epithelial tumors is important for its treatment. Napsin A is a known diagnostic marker for lung adenocarcinoma, and expression of napsin A is reported in a certain portion of thyroid and renal carcinomas. However, napsin A expression in ovarian surface epithelial tumors has not previously been examined. In this study, immunohistochemical analysis revealed that in 71 of 86 ovarian clear cell adenocarcinoma patients (83%) and all of the 13 patients with ovarian clear cell adenofibroma, positive napsin A staining was evident. No expression was observed in 30 serous adenocarcinomas, 11 serous adenomas or borderline tumors, 19 endometrioid adenocarcinomas, 22 mucinous adenomas or borderline tumors, 10 mucinous adenocarcinomas, or 3 yolk sac tumors of the ovary. Furthermore, expression of napsin A was not observed in the normal surface epithelium of the ovary, epithelia of the fallopian tubes, squamous epithelium, endocervical epithelium, or the endometrium of the uterus. Therefore, we propose that napsin A is another sensitive and specific marker for distinguishing ovarian clear cell tumors (especially adenocarcinomas) from other ovarian tumors.

Expression of chromobox homolog 7 (CBX7) is associated with poor prognosis in ovarian clear cell adenocarcinoma via TRAIL-induced apoptotic pathway regulation.

Ovarian cancer is the most lethal gynecologic malignancy, and clear cell adenocarcinoma of the ovary (OCCA), in particular, has a relatively poor prognosis among the ovarian cancer subtypes because of its high chemoresistance. Chromobox (CBX) 7 is a polycomb repressive complex 1 component that prolongs the lifespan of normal human cells by downregulating the INK4a/ARF expression which promotes cell-cycle progression. However, recent reports studying the relationship between CBX7 expression and patient survival have differed regarding the tumor cell origins, and the precise role of CBX7 in human carcinomas remains obscure. In this study, we analyzed CBX7 expression by immunohistochemistry in 81 OCCA patients and evaluated its association with their clinical outcomes. Both the overall and progression-free survival rates of the CBX7-positive patients were significantly shorter than those of the CBX7-negative patients (p < 0.05). CBX7 knockdown experiments using two OCCA cell lines, TOV21G and KOC-7C, revealed that cell viability was significantly reduced compared to the control cells (p < 0.001). Expression microarray analysis revealed that apoptosis-related genes, particularly tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), were significantly upregulated in CBX7 knockdown cells (p < 0.01). We further confirmed that CBX7 knockdown resulted in TRAIL-induced apoptosis in the OCCA cells. Thus, in this study, we showed for the first time that CBX7 was associated with a decreased OCCA prognosis. We also successfully demonstrated that the TRAIL pathway is a novel target for CBX7 expression modulation in these cells, and therapeutic agents utilizing the TRAIL pathway may be particularly effective for targeted OCCA therapy.

Injectable bone tissue engineering using expanded mesenchymal stem cells.

Patients suffering from bone defects are often treated with autologous bone transplants, but this therapy can cause many complications. New approaches are therefore needed to improve treatment for bone defects, and stem cell therapy presents an exciting alternative approach. Although extensive evidence from basic studies using stem cells has been reported, few clinical applications using stem cells for bone tissue engineering have been developed. We investigated whether injectable tissue-engineered bone (TEB) composed of mesenchymal stem cells (MSCs) and platelet-rich plasma was able to regenerate functional bone in alveolar deficiencies. We performed these studies in animals and subsequently carried out large-scale clinical studies in patients with long-term follow-up; these showed good bone formation using minimally invasive MSC transplantation. All patients exhibited significantly improved bone volume with no side effects. Newly formed bone areas at 3 months were significantly increased over the preoperation baseline (p < .001) and reached levels equivalent to that of native bone. No significant bone resorption occurred during long-term follow-up. Injectable TEB restored masticatory function in patients. This novel clinical approach represents an effective therapeutic utilization of bone tissue engineering.

Extremely poor postrecurrence oncological outcome for patients with recurrent mucinous ovarian cancer.

BACKGROUND: This study was conducted to assess the long-term clinical outcome for patients with recurrent mucinous epithelial ovarian cancer (RmOC) in comparison with recurrent serous epithelial ovarian cancer (RsOC). METHODS: Three hundred and eighty-four patients with recurrent ovarian cancer, including 340 RsOC and 44 RmOC patients, were analyzed in this study. The pathological slides were evaluated under central pathological review. The prognostic significance of clinicopathological factors was evaluated employing both uni- and multivariable analysis. RESULTS: The 3- and 5-year postrecurrence survival (PRS) rates of patients with RmOC were 17.3, and 6.9 %, respectively. In contrast, those of patients with RsOC were 29.8 and 18.8 %, respectively. The PRS of patients with RmOC was significantly poorer than that of patients with RsOC (PRS: P = 0.0006). Moreover, either in the presence or absence of a residual tumor (RT) at initial surgery, the PRS of patients with RmOC was markedly poorer than that of patients with RsOC [RT (-): P < 0.0001: RT (+): P = 0.0912]. In multivariable analysis, a mucinous histology predicted a significantly poorer PRS (RmOC vs. RsOC: hazard ratio (HR) 2.080, 95 % confidence interval (CI) 1.434-3.016, P = 0.0001). Confining analysis to deceased patients (N = 302), the proportion of RmOC patients who died within 12 months following recurrence was markedly higher than that of RsOC [RmOC 69.2 %, RsOC: 41.1 % (P < 0.0001)]. CONCLUSIONS: The clinical outcome after recurrence in patients with RmOC was extremely poor. This confirms that RmOC should be considered a different entity from other epithelial ovarian cancers.

A recurrence-predicting prognostic factor for patients with ovarian clear-cell adenocarcinoma at reproductive age.

OBJECTIVES: 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. PATIENTS AND METHODS: 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). RESULTS: 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 < 0.0001). In multivariable analysis confined to stage I patients, the substage group was only an independent prognostic factor for RFS [IA vs. IC(non-r)] [hazard ratio (HR) = 9.394; 95 % CI, 1.445-61.070; P = 0.0190]. CONCLUSION: We should keep in mind the greater risk of recurrence in patients with stage IC disease or higher, other than those stage IC patients with intraoperative rupture.

New diagnostic technique for rapid fluorescence immunocytochemical staining of adenocarcinoma and mesothelial cells using liquid-based cytology.

OBJECTIVE: To evaluate the expression of antibodies against calretinin, cytokeratin 5/6, desmin, D2-40, HBME-1, mesothelin, thrombomodulin, WT1, Ber-EP4, CEA, EMA and MOC-31 individually and to compare it with a new rapid procedure for fluorescence immunocytochemistry (ICC) using liquid-based cytology (LBC). STUDY DESIGN: Sixty-four peritoneal cell specimens prepared with the LBC method were stained with these markers to evaluate their usefulness and develop a rapid fluorescence immunostaining method using Ber-EP4 that is applicable to intraoperative cancer cytodiagnosis. RESULTS: The adenocarcinoma markers were positive in 92% of adenocarcinoma cases, 57% of cases with suspicion of adenocarcinoma, and 5% of negative cases (reactive mesothelial cells). On the other hand, the mesothelial cell markers were positive in 8-15% of adenocarcinoma cases, 43-57% of cases with suspicion of adenocarcinoma, and 93-95% of negative cases. The rapid new fluorescence ICC procedure clearly stained only the adenocarcinoma cells within 20 min. CONCLUSION: Immunocytochemical examination with the LBC method is a powerful ancillary technique for discriminating adenocarcinoma cells from mesothelial cells. This rapid new fluorescence ICC procedure can be used as an ancillary technique for accurate detection of adenocarcinoma cells in the intraoperative cytological examination of peritoneal or pleural washing fluid.

[On the correlation between histological and cytological diagnosis, and the intrinsic 5 subtypes].

Japanese General Rules presented by the Japanese Breast Cancer Society have been long time applied in Japan. This classification uniquely adds subtypes into the group of invasive ductal carcinomas (IDC) and reported to be correlated to patients' clinical course. The latest St. Gallen consensus meeting reported the use of 5 molecules, and introduced alternative definition in the breast cancer classification. The purpose of this study is to relate the Japanese subgrouping of IDC with the 5 subtypes and to investigate whether these classifications could predict early and late recurrence and whether cytological diagnosis is influenced by the tumor phenotypes. Analyzing 127 cases, we observed that the Ki-67 labeling index (LI) of the 5 subtypes, luminal A, luminal B-Her2--/- Her2+, Her2-subtype and basal-like, is increased in this order. Though the Japanese histological groups, papillotubular, solid-tubular and scirrhous, included more or less those subtypes, the luminal types were more represented in papillotubular and scirrhous subtypes, and the solid-tubular type in non luminal subtypes. The Ki-67 LI 14% served as a cutoff for differentiating invasive from non-invasive ductal carcinomas. Breast cancers recur within 5 years after the clinical onset when the Ki-67 LI exceeded 14%. These data suggest that, (1) the intrinsic subtyping is an accurate modality in diagnosing breast cancers, (2) it can predict the recurrence duration, (3) the solid-tubular type of the Japanese classification is likely an aggressive form among breast cancers, and (4) the cytological diagnosis is presently a powerful tool in determining malignancy.

Long-term clinical outcome of patients with recurrent epithelial ovarian carcinoma: is it the same for each histological type?

OBJECTIVE: This study was conducted to estimate the long-term clinical outcome of patients with recurrent ovarian carcinoma (ROC). METHODS: Six hundred three patients with ROC were analyzed in this study. The pathological slides were evaluated under central pathological review. The prognostic significances of clinicopathologic factors were evaluated using both univariate and multivariate analysis. RESULTS: The 5-year overall survival (OS) and postrecurrence survival (PRS) rates were 31.1 and 16.9%, respectively. On stratifying to treatment periods, the PRS has been prolonged over the last decade (year ≥2000) compared with before this period (year ≤1999) (P = 0.0002). In contrast, on stratifying to histological types and treatment periods, in both OS and PRS, the prognosis of patients with the nonmucinous/clear-cell histology, including serous, endometrioid, and other histological types, was significantly improved after 2000 compared with before (year ≤1999) (OS, P = 0.0009; PRS, P < 0.0001). In contrast, that of patients with the mucinous/clear-cell histology did not significantly differ regardless of the treatment period (≥2000 vs ≤1999: OS, P = 0.3887; PRS, P = 0.7617). In multivariate analysis, the stage, period of starting initial treatment, histological type, and the treatment-free interval were independent prognostic factors of a poor OS and PRS (OS/PRS: histological type: mucinous/clear-cell vs nonmucinous/clear-cell: hazard ratio, 1.300/1.498; 95% confidence interval [CI], 1.039-1.626/1.197-1.874). CONCLUSIONS: Despite the continuous administration of treatment for ROC, survival is poor, and the extent of therapeutic progress differs according to the histological type.

Postrecurrent oncologic outcome of patients with ovarian clear cell carcinoma.

OBJECTIVES: To estimate the long-term clinical outcome of patients with recurrent clear cell carcinoma (RCCC) of the ovary in comparison with those with recurrent serous adenocarcinoma (RSAC). PATIENTS AND METHODS: In this study, 113 patients with RCCC and 365 patients with RSAC were analyzed. The pathological slides were evaluated under central pathological review. End points were the overall survival (OS), postrecurrence survival (PRS), and timing of death of mortality cases. RESULTS: The 5-year OS and PRS rates of patients with RCCC were 22.5 and 13.2%, respectively. In both OS and PRS, the prognosis of patients with RCCC was significantly poorer than that of the patients with RSAC (OS: P = 0.0007; PRS: P < 0.0001). Moreover, regardless of the status of the residual tumor (RT) at the initial surgery, the OS and PRS of the patients with RCCC were markedly shorter than those with RSAC (RT [-]: OS, P = 0.0005: PRS, P = 0.0002: RT [+]: OS, P < 0.0001: PRS, P < 0.0001). In multivariable analysis, the histological type was a significantly poorer prognostic indicator for OS and PRS (OS [RCCC vs RSAC]: hazard ratio, 2.302: 95% confidence interval, 1.723-3.076; P < 0.0001: PRS [RCCC vs RSAC]; hazard ratio, 2.353: 95% confidence interval, 1.756-3.155; P < 0.0001). Even in the deceased patients (n = 350), the rate of patients with RCCC dying within 12 months of recurrence was higher than that of RSAC (RCCC, 67.8%; RSAC, 40.7%; [P < 0.0001]). CONCLUSIONS: The long-term clinical outcome of patients with RCCC was extremely poor. We confirmed that RCCC should be investigated as a different malignancy compared with RSAC.

Adjuvant chemotherapy for stage i ovarian clear cell carcinoma: is it necessary for stage IA?

BACKGROUND: It is controversial whether patients with stage I ovarian clear cell carcinoma (CCC) benefit from postoperative chemotherapy. This study was designed to evaluate the postoperative outcomes associated with the inclusion or exclusion of adjuvant therapy in these patients. METHODS: A total of 185 patients who were treated for stage I CCC between 1991 and 2007 were retrospectively evaluated. All of the patients had received comprehensive surgical staging, and their condition had been diagnosed by a central pathological review system. Only one patient with stage IB was excluded from this study. RESULTS: Median follow-up time was 62 months (range 7-191 months). Median age was 52 years (30-75 years). There were 41, 93, and 50 patients in stage IA, intraoperative capsule ruptured IC (rupture-IC), and all other-IC groups, respectively. The 5-year recurrence-free survival rates for the substage were 97.6%, 87.8%, and 70.4% (P < 0.001), respectively. Among 134 patients consisting of those in the stage IA and rupture-IC groups, 91 patients received adjuvant chemotherapy (AC) and 43 patients did not (non-AC). There was no significant survival difference in each substage group between the non-AC and AC groups in 5-year recurrence-free survival rate (stage IA, 100% vs 93.8%; rupture-IC, 94.1% vs 86.6%). Multivariate analysis demonstrated that there was no significant prognostic factor for both recurrence and survival among the IA and rupture-IC groups. Postoperative therapy, regimen, and chemotherapy cycles were not significantly affected. CONCLUSIONS: This study indicates that adjuvant chemotherapy does not contribute to the improving prognosis of stage IA ovarian CCC. Whereas the histological type is CCC, the routine adjuvant chemotherapy after comprehensive surgical staging may be unnecessary for patients with at least stage IA.

Is there any association between retroperitoneal lymphadenectomy and survival benefit in advanced stage epithelial ovarian carcinoma patients?

AIM: The effect of systematic retroperitoneal lymphadenectomy (SRL) remains controversial in patients with advanced epithelial ovarian cancer (aEOC) who are optimally debulked. MATERIAL AND METHODS: Demographic and clinicopathologic data were obtained from the Tokai Ovarian Tumor Study Group between 1986 and 2009. All patients were divided into two groups. Group A (n = 93): (i) patients did not undergo SRL; and (ii) lymph node exploration or sampling was optional. Group B (n = 87): patients underwent SRL. Survival curves were calculated using the Kaplan-Meier method. Differences in survival rates were analyzed using the log-rank test. RESULTS: All pT3-4 aEOC patients were optimally debulked (residual tumor <1 cm). The median age was 55 years (range: 18-84). The 5-year progression-free survival (PFS) rates of groups A and B were 46.7 and 41.9%, respectively (P = 0.658). In addition, the 5-year overall survival (OS) rates were 62.9 and 59.0%, respectively (P = 0.853). Subsequently, there was no significant difference in OS and PFS in the two groups stratified to histological type (serous or non-serous type). Furthermore, there was no significant difference in recurrence rates in retroperitoneal lymph nodes regardless of completion of lymphadenectomy. CONCLUSION: Our data suggest that aEOC patients with optimal cytoreduction who underwent SRL did not show a significant improvement in survival irrespective of each histological type.

Fertility-sparing surgery in patients with clear-cell carcinoma of the ovary: is it possible?

BACKGROUND: Clear-cell carcinoma of the ovary (CCC) is often diagnosed at childbearing age, or sometimes during treatment for infertility. Therefore, most young women with early-stage CCC wish to preserve their reproductive and endocrine functions if possible. METHODS: Clinicopathologic data collected under the central pathological review system were subjected to survival analyses. We analyzed patients with stage I CCC who underwent fertility-sparing surgery (FSS, n = 16) and compared their long-term survival with those receiving radical surgery (n = 205), or patients with non-CCC undergoing FSS (n = 64). RESULTS: There was no difference in both the overall survival (OS) and disease-free survival (DFS) between patients with CCC who underwent FSS and those who received radical surgery [CCC/FSS (n = 16) versus CCC/radical (n = 205); OS: P= 0.519, DFS: P= 0.265]. Moreover, patients with CCC who underwent FSS did not show a poorer OS and DFS than non-CCC patients who underwent FSS (CCC/FSS versus non-CCC/FSS; OS: P= 0.584, DFS: P= 0.401), or those at the corresponding stage with no CCC. Furthermore, according to the series of patients with CCC in both the current study and four studies in the literature, there was no difference in the recurrence rate between patients with or without CCC who were treated conservatively (CCC/FSS: 13.2% versus non-CCC/FSS: 10.9%, P= 0.614). CONCLUSIONS: Although our study did not have sufficient power to yield a definite conclusion, our data suggests that at least patients with stage IA CCC may be treated with FSS.

Fertility-sparing surgery in young women with mucinous adenocarcinoma of the ovary.

OBJECTIVES: The purpose of this study was to clarify the clinical outcome of patients with stage IA mucinous epithelial ovarian cancer (mEOC) treated with fertility-sparing surgery (FSS). METHODS: After a central pathological review and search of the medical records from multiple institutions, a total of 148 stage I mEOC patients were retrospectively evaluated in the current study. All mEOC patients were divided into three groups: group A (FSS; age, 40≥); groups B and C {radical surgery; age, 40≥ (B); 40< (C)}. Survival analysis was performed among these three groups using Kaplan-Meier methods. RESULTS: The median follow-up time of all mEOC patients was 71.6 (4.8-448.3) months. Among the 41 patients in group A, 27 patients (65.9%) had IA disease, and 14 (34.1%) had IC disease. Five-year overall survival (OS) and disease-free survival (DFS) rates of patients in the groups were as follows: group A, 97.3% (OS)/90.5% (DFS); group B, 94.4% (OS)/94.4% (DFS); group C; 97.3% (OS)/89.3% (DFS). Collectively, there was no significant difference in OS or DFS among these groups even though they were stratified to each substage (IA/IC) (OS, P=0.180; DFS, P=0.445, respectively). Furthermore, in multivariate analyses, the surgical procedure was not an independent prognostic factor for either OS or DFS (OS, HR: 0.340, 95% CI: 0.034-3.775, P=0.352; DFS, HR: 0.660, 95% CI: 0.142-3.070, P=0.596). CONCLUSIONS: Patients with stage I mEOC treated with FSS did not necessarily show a poorer prognosis than those receiving radical surgery.