Search

Supplementary Tables 1-2 - PDF file 85K, MicroRNAs significantly associated with overall survival and response to therapy in ovarian cancer patients using TCGA 2009 database (Table S1) and Clinical and bio-pathological features of the 91 MDACC ovarian cancer samples used in the study (Table S2)

Supplementary Figures 1-12 - PDF file 897K, Relative expression of miR-520d-3p (miR-520d) and miR-520d-5p (miR-520d*) in ovarian cancer cell lines (Figure S1), Kaplan-Meier curves representing the percent progression-free survival in patients with ovarian cancer based on miR-520d-3p median expression levels (Figure S2), miR-520d-5p does not target EphA2 (Figure S3), miR-520d-3p and EphA2 expression levels in miR-520d-3p overexpressing stable clones (Figure S4), Effect of miR-520d-3p expression on cell proliferation (Figure S5), miR-520d-3p and EphA2 levels in xenograft models of miR-520d-3p overexpressing HeyA8 and SKOV3ip1 models (Figure S6), Efficiency of EphA2 targeting siRNAs in HeyA8 cells (Figure S7), Combination of miR-520d-3p and siRNA-EphA2 treatment shows enhanced EphA2 inhibition in vitro (Figure S8), Dose-response curve of miR-520d-3p, si-EphA2-1 and combined miR-520d-3p + si-EphA2-1 in SKOV3ip1 and HeyA8 cells (Figure S9), Treatment with anti-miR-520d-3p can restore EphA2 protein levels in a dose-dependent manner in SKOV3ip1 cells (Figure S10), Effect of combined miR-520d-3p+siEphA2-1 treatment on angiogenesis, proliferation and apoptosis in HeyA8 cells (Figure S11), and Differentially expressed coding genes in miR-520d-3p overexpressing stable clones (Figure S12)

Purpose:Src is an attractive target because it is overexpressed in a number of malignancies, including ovarian cancer. However, the effect of Src silencing on other Src family kinases (SFKs) is not known. We hypothesized that other SFK members could compensate for the lack of Src activity.Experimental Design: Cell viability after either Src or Fgr silencing was examined in ovarian cancer cell lines by MTT assay. Expression of SFKs after Src silencing in ovarian cancer cells was examined by real-time reverse transcriptase (RT)-PCR. Therapeutic effect of in vivo Src and/or Fgr silencing was examined using siRNA incorporated into chitosan nanoparticles (siRNA/CH-NP). Microvessel density, cell proliferation, and apoptosis markers were determined by immunohistochemical staining in ovarian tumor tissues.Results:Src silencing enhanced cytotoxicity of docetaxel in both SKOV3ip1 and HeyA8 cells. In addition, Src silencing using siRNA/CH-NP in combination with docetaxel resulted in significant inhibition of tumor growth compared with control siRNA/CH-NP (81.8% reduction in SKOV3ip1, P = 0.017; 84.3% reduction in HeyA8, P < 0.005). These effects were mediated by decreased tumor cell proliferation and angiogenesis, and increased tumor cell apoptosis. Next, we assessed the effects of Src silencing on other SFK members in ovarian cancer cell lines. Src silencing resulted in significantly increased Fgr levels. Dual Src and Fgr silencing in vitro resulted in increased apoptosis that was mediated by increased caspase and AKT activity. In addition, dual silencing of Src and Fgr in vivo using siRNA/CH-NP resulted in the greatest reduction in tumor growth compared with silencing of either Src or Fgr alone in the HeyA8 model (68.8%, P < 0.05).Conclusions: This study demonstrates that, in addition to Src, Fgr plays a biologically significant role in ovarian cancer growth and might represent an important target. Clin Cancer Res; 17(7); 1713–21. ©2011 AACR.

EphB4 is a transmembrane receptor tyrosine kinase that plays an important role in neural plasticity and angiogenesis. EphB4 is overexpressed in ovarian cancer and is predictive of poor clinical outcome. However, the biological significance of EphB4 in ovarian cancer is not known and is the focus of the current study. Here, we examined the biological effects of two different methods of EphB4 targeting (a novel monoclonal antibody, EphB4-131 or siRNA) using several ovarian cancer models. EphB4 gene silencing significantly increased tumor cell apoptosis and decreased migration (P < 0.001) and invasion (P < 0.001). Compared with controls, EphB4 siRNA–1,2-dioleoyl-sn-glycero-3-phosphatidylcholine alone significantly reduced tumor growth in the A2780-cp20 (48%, P < 0.05) and IGROV-af1 (61%, P < 0.05) models. Combination therapy with EphB4 siRNA–1,2-dioleoyl-sn-glycero-3-phosphatidylcholine and docetaxel resulted in the greatest reduction in tumor weight in both A2780-cp20 and IGROV-af1 models (89–95% reduction versus controls; P < 0.05 for both groups). The EphB4-131 antibody, which reduced EphB4 protein levels, decreased tumor growth by 80% to 83% (P < 0.01 for both models) in A2780-cp20 and IGROV-af1 models. The combination of EphB4-131 and docetaxel resulted in the greatest tumor reduction in both A2780-cp20 and IGROV-af1 models (94–98% reduction versus controls; P < 0.05 for both groups). Compared with controls, EphB4 targeting resulted in reduced tumor angiogenesis (P < 0.001), proliferation (P < 0.001), and increased tumor cell apoptosis (P < 0.001), which likely occur through modulation of phosphoinositide 3-kinase signaling. Collectively, these data identify EphB4 as a valuable therapeutic target in ovarian cancer and offer two new strategies for further development. Mol Cancer Ther; 9(8); 2377–88. ©2010 AACR.

PDF file, 366KB, Effects of MET and MTD HA-TXL treatment in the HeyA8-MDR model on biological endpoints.

Supplementary Figure 1 from Converging Evidence for Efficacy from Parallel EphB4-Targeted Approaches in Ovarian Carcinoma

PDF file, 104KB, Effects of MET and MTD HA-TXL therapy on tumor nodules in ovarian cancer models.

Supplementary Figures S1-S5.

Purpose: Most primary human ovarian tumors and peritoneal implants, as well as tumor vascular endothelial cells, express the CD44 family of cell surface proteoglycans, the natural ligand for which is hyaluronic acid. Metronomic dosing, the frequent administration of chemotherapeutics at substantially lower than maximum tolerated doses (MTD), has been shown to result in reduced normal tissue toxicity and to minimize “off-treatment” exposure resulting in an improved therapeutic ratio.Experimental Design: We tested the hypothesis that hyaluronic acid (HA) conjugates of paclitaxel (TXL; HA-TXL) would exert strong antitumor effects with metronomic (MET) dosing and induce antiangiogenic effects superior to those achieved with MTD administration or with free TXL. Female nude mice bearing SKOV3ip1 or HeyA8 ovarian cancer cells were treated intraperitoneally (i.p.) with MET HA-TXL regimens (or MTD administration) to determine therapeutic and biologic effects.Results: All MET HA-TXL–treated mice and the MTD group revealed significantly reduced tumor weights and nodules compared with controls (all P values < 0.05) in the chemotherapy-sensitive models. However, the MTD HA-TXL–treated mice showed significant weight loss compared with control mice, whereas body weights were not affected in the metronomic groups in HeyA8-MDR model, reflecting reduced toxicity. In the taxane-resistant HeyA8-MDR model, significant reduction in tumor weight and nodule counts was noted in the metronomic groups whereas the response of the MTD group did not achieve significance. While both MTD and metronomic regimens reduced proliferation (Ki-67) and increased apoptosis (TUNEL, terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling), only metronomic treatment resulted in significant reductions in angiogenesis (CD31, microvessel density). Moreover, metronomic treatment resulted in substantial increases in thrombospondin-1 (Tsp-1), an inhibitor of angiogenesis.Conclusions: This study showed that MET HA-TXL regimens have substantial antitumor activity in ovarian carcinoma, likely via a predominant antiangiogenic mechanism. Clin Cancer Res; 18(15); 4114–21. ©2012 AACR.

PDF file, 67KB, Effects of HA-TXL MTD and HA-TXL MET on white blood count (WBC)and hemoglobin levels.

PDF file - 122K

PDF file - 66K

PDF file - 38K

PDF file - 37K

PDF file - 67K

PDF file - 38K

The prevalence of germline

Although endometrial cancer is extremely rare during pregnancy, the placental metastasis of endometrial cancer is even rarer. The current study presents a case of endometrial carcinoma that was diagnosed through the pathological examination of the placenta. A 35-year-old primipara woman who underwent frozen-thawed embryo transfer at the Keiai Ladies Clinic in Tokushima prefecture (Japan) received regular prenatal check-ups. She was transferred to Tokushima University Hospital for perinatal management due to the preterm premature rupture of membranes at 21 weeks and 6 days gestation. The administration of antibiotics and tocolytic agents was continued; however, labor pain occurred at 23 weeks and 3 days gestation, and a female fetus weighing 524 g was delivered vaginally. The placenta weighed 262 g and had no macroscopic abnormalities. It was submitted for pathological examination, which revealed metastatic adenocarcinoma (clear cell carcinoma suspected). The patient was subsequently diagnosed with endometrial cancer (stage I suspected), and underwent abdominal total hysterectomy, bilateral salpingo-oophorectomy, partial omentectomy and pelvic lymph node dissection. The final diagnosis was stage IA endometrial cancer (endometrioid carcinoma, G2). At 1 year after surgery, there was no evidence of disease. The present case highlights the importance of considering the emergence of endometrial cancer during pregnancy.

Background The association between salt intake and clinical outcomes in hemodialysis patients has been controversial. This study aimed to clarify the association between salt intake and mortality in hemodialysis patients. Method The present study included patients who underwent hemodialysis from June 1st 2016 to May 31st 2020. Corrected salt intake by ideal body weight was the main predictor of outcomes. Ideal body weight was calculated assuming that the ideal body mass index is 22 kg/m2 for the Japanese population. The multivariate Cox proportional hazards model was used to determine the association between corrected salt intake and mortality, adjusting for potential confounders. The outcomes considered were all-cause mortality and cumulative incidence of cardiovascular events at year 4. Result A total of 492 adult patients were enrolled in the study. The mean daily salt intake and corrected salt intake at baseline were 9.5 g/day and 0.17 g/kg/day, respectively. The low corrected salt intake group (< 0.13 g/kg/day) demonstrated the highest 4-year all-cause mortality. No association was observed between corrected salt intake and the cumulative incidence of cardiovascular events. In multivariate Cox proportional hazards analysis, only the group with corrected salt intake of 0.16–0.20 g/kg/day was associated with a decreased hazard risk for all-cause death compared with the low corrected salt intake group. Conclusion The present study found that a low salt intake was associated with high all-cause mortality in hemodialysis patients. Reduced long-term survival may be attributed to malnutrition resulting from excessive salt restriction.

Human papillomavirus vaccination is not widespread in Japan, and the low screening rates result in many cases of locally advanced cervical cancer. We investigated the prognostic significance of sarcopenia in patients with cervical cancer to guide healthcare policies to improve treatment outcomes.This retrospective study included 83 patients with cervical cancer without distant metastasis who underwent primary concurrent chemoradiotherapy between 2013 and 2018. We analyzed the indicators of physical condition and muscle quantity using the SYNAPSE VINCENT software. Muscle mass and the relationship between treatment toxicity and prognosis were evaluated.The patients' median age was 60 (range 33‒80) years. Cancer stage distribution was as follows: cT2b or higher, 84.3%; N1, 65.1%; and MA, 27.7%. The overall sarcopenia (skeletal muscle index [SMI] 38.5) rate was 30.1%, and the rate was 33.9 and 22.2% in patients aged 64 and ≥ 65 years, respectively. No correlation was observed between clinical stage and musculoskeletal indices. Treatment resulted in decreased body weight and SMI; after treatment, the sarcopenia rate increased to 37.3%. A higher intramuscular adipose tissue content (IMAC) reduced the number of chemotherapy cycles needed. Treatment-associated SMI decreases of ≥ 7% indicated poor prognosis, with significant differences in progression-free survival and overall survival (p = 0.013 and p = 0.012, respectively). Patients who were very lean (body mass index 18.5 kg/mOur findings emphasize the importance of assessing original nutritional status and maintaining muscle mass and quality during the treatment of patients with cervical cancer.

The objective of this study was to examine the clinical significance of EZH2 expression and the therapeutic efficacy of its silencing in endometrial cancer. EZH2 expression in clinical samp...

The tensile-fatigue behavior of sintered-copper die-attach materials was investigated by focusing on sintering-pressure dependence. Specimens for fatigue tests were prepared by sintering copper oxide paste made from copper oxide particles with a mean diameter of 200 nm in hydrogen atmosphere under low (4 MPa) and high (13 MPa) pressures at 623 K for 15 min. The tensile-fatigue test was conducted using micro-load testing equipment in air at room temperature. The fatigue tests were conducted under pulsating load conditions. The fatigue strength of the high-pressure specimens was higher than that of the low-pressure specimens when comparing them within the nominal stress range $\Delta \sigma $ . The fracture at the narrow neck part and the dimpled fracture at the peripheral part of the voids were observed in both types of specimens from fractographic studies. The $\Delta \sigma $ was converted to the total strain range $\Delta \varepsilon _{t}$ by using finite element analysis (FEA). It was confirmed that the fatigue strength of the high-pressure specimens was higher than that of the low-pressure specimens even when comparing them within $\Delta \varepsilon _{t}$ . The strain distributions at the neck part and peripheral voids were calculated through FEA using a microporous structure model to clarify the cause of the fatigue lifetime difference between the low-pressure and high-pressure specimens. The calculated strain in the low-pressure specimens was locally concentrated at some of the narrow necks and could be linked to perpendicular cracks with a high strain level, whereas that in the high-pressure specimens was broadly distributed between the voids with a low strain level. This difference in strain distribution seemed to be the cause of the difference in the fatigue lifetime between the low-pressure and high-pressure specimens.

Aim: Type III collagen abundantly exists in the cardiovascular system, including the aorta and heart. We prospectively investigated whether serum levels of aminoterminal propeptide of type III procollagen (PIIINP), a circulating biomarker of cardiovascular fibrosis, could predict cardiovascular events in patients undergoing hemodialysis. Methods: Serum PIIINP concentrations were measured in 244 patients undergoing maintenance hemodialysis (men, 126; women, 118; mean age, 64 ± 11 years; dialysis duration, 11.5 ± 7.8 years) by immunoradiometric assay in February 2005. The endpoint was cardiovascular events, and the patients were followed up until the endpoint was reached, or until January 31, 2011. Results: During the follow-up for 4.7 ± 1.8 years, cardiovascular events occurred in 78 (30.3%) of 244 patients. Stepwise Cox hazard analysis revealed that cardiovascular events were associated with increased serum PIIINP concentration (1 U/mL; hazard ratio, 1.616; P = 0.0001). The median serum PIIINP concentrations were higher in patients with cardiovascular events than in those without (2.30 ± 0.19 U/mL vs 1.30 ± 0.03 U/mL; P < 0.0001). When the patients were assigned to subgroups based on serum PIIINP cut-off value for cardiovascular events of 1.75 U/mL, defined by receiver operating characteristic analysis, cardiovascular event-free survival rates at 5 years were lower (P = 0.0001) in the subgroup of serum PIIINP ≥ 1.75 U/mL than in that of serum PIIINP < 1.75 U/mL (31.9% vs 88.2%). Conclusions: Serum PIIINP could be a new biomarker for predicting the cardiovascular events in patients undergoing hemodialysis.

The effect of loading type on the fatigue lifetime of sintered-silver die attach was investigated. The fatigue lifetime was measured by fatigue testing with micro-load testing equipment. The fatigue tests were conducted under displacement control with (reversed loading (stress ratio ${R}= -1$ ), pulsating-tensile loading ( ${R} =0$ ), and pulsating-compression loading ( ${R} = -\infty $ )) at room temperature. The strain of the fatigue test was estimated by strain-displacement relation obtained from previous tensile test using the strain gauge. Sintered-silver specimens were made from prebaked microscale silver paste and pressurized at 10 MPa for 10 minutes in air atmosphere at 573 K. The fatigue lifetime of reversed-loading case was 1000 cycles, that of pulsating-tensile-loading case was 4000 cycles, and the pulsating-compression-loading case remained unbroken. This suggests that compression load does not contribute to the destruction of the sintered silver. These measured fatigue lifetimes were aligned in a row when these are organized by maximum stress (tensile stress range). For fatigue lifetime evaluation of sintered silver, evaluation focusing on tensile stress seems to be important.

Introduction/Background For patients with carcinomatosa peritonitis who are diagnosed to be difficult to completely remove in the first surgery, our hospital is performing tumor reduction surgery after neoadjuvant chemotherapy (NAC). Methodology NAC has performed 4–5 courses of dose dense TC, and when it is judged that complete removal is possible, interval debulking surgery (IDS) is performed. Of the 39 cases of advanced ovarian cancer (stage III/IV) whose treatment was started in 2013–2018, 17 cases underwent surgery (PDS) and 22 cases underwent NAC for first treatment. The 22 cases consisted of 2 cases of test laparotomy, 2 cases of partial resection at the first surgery (PDS) and 18 cases of NAC. Results Seventeen of the 18 NAC cases were diagnised by needle biopsy. The response rate for NAC was 94% (17/18). The complete resection rate at IDS was 72% (13/18). Recurrence was observed in 46% (6/13) of the cases achieving complete resection and 80% (4/5) in the remaining cases. The response rate of subsequent chemotherapy was 100% (5/5) in 5 patients with large residual tumors with PDS, and no recurrence was found in 3 patients who could be completely resected with subsequent IDS. The 5-year survival rate was 92% in the PDS group and 48% in the NAC and IDS group. The survival rate of patients with completely resection was 90%, and that of the remaining tumor was 18%. In addition, even in the case of patients with carcinomatosa peritonitis, 5 year survival rate was 85% in cases where there was no residual tumor at IDS. Conclusion The prognosis was extremely good if complete resection with NAC and IDS was possible even in cases where complete resection was difficult in the first surgery. There were no surgical complications or deaths. NAC is considered a very effective treatment for carcinomatosa peritonitis cases. Disclosure Nothing to disclose.

Introduction/Background In Japan, the number of BRCA testing is increasing annually. But, till recently, genetic counselling for epithelial ovarian cancer (EOC) has not been generalized. We investigated the awareness survey and the rate of HRD mutation included gBRCA1/2 mutation with EOC, regardless of their family histories. Methodology 127 EOC who had treated at our hospital were enrolled. After genetic counselling, DNA was extracted from whole blood, and all coding exons and their flanking intron regions of 11 genes included BRCA1/2, RAD51C/D, ATM, PALB2 and CHEK2 were sequenced with next-generation sequencing in our laboratory. Results 127 EOC patients who had treated at our hospital were enrolled. After genetic counselling, DNA was extracted from whole blood, and all coding exons and their flanking intron regions of 11 genes included BRCA1/2, RAD51C/D, ATM, PALB2 and CHEK2 were sequenced with next-generation sequencing in our laboratory.In 121 of 125 patients, consent was obtained, of which 84% wanted to disclose results. Mutations were found in 19 (15.7%);7 in gBRCA1 mutation, 10 in gBRCA2 mutation, 1 in gRAD51C mutation, and one in VUS. 12 of pathogenic mutation were high grade serous carcinoma, two; adenocarcinoma, and 4;others.Median age at diagnosis was gBRCA1; 64 years (49–87 years), gBRCA2; 60 years (42–67 years). TC therapy was administered to 10 cases as the first treatment in 19 cases, and all cases PR - CR were obtained. There was no significant difference in OS and PFS with FIGO stage lll of gBRCA mutation (p=0.3, p=0.52) Conclusion Almost patients with EOC wanted to know genetic risk after genetic counselling. The rate of gBRCA1/2 mutation in tested Japanese EOC patients with an inherited risk, regardless of a family history, was 15.7%. This finding indicates that the cooperation of genetic counselling with other department would be important for patients with ovarian cancers. Disclosure Nothing to disclose.

OBJECTIVE. The aim of this study was to examine the significance of lymphovascular space invasion (LVSI) with a sarcomatous component on the tumor characteristics and clinical outcomes of women with uterine carcinosarcoma (UCS). METHODS. This was a secondary analysis of a prior multicenter retrospective study that examined women with stage I–IV UCS who underwent primary hysterectomy. Archived histopathology slides were reviewed and LVSI was scored as follows: LVSI with a carcinomatous component alone (LVSI-carcinoma; n = 375, 76.8%) or LVSI containing a sarcomatous component with or without a carcinomatous component (LVSI-sarcoma; n = 113, 23.2%). Qualitative metrics of LVSI were correlated to clinicopathological factors and survival outcome. RESULTS. Tumors in the LVSI-sarcoma group were more likely to have sarcoma dominance (82.1 vs. 26.4%) heterologous sarcomatous component (51.3 vs. 37.9%), low-grade carcinoma (42.5 vs. 22.4%), and large tumor size (81.0 vs. 70.2%) in the primary tumor site compared with tumors in the LVSI-carcinoma group (all p < 0.05). On multivariate analysis, LVSI-sarcoma was independently associated with decreased progression-free survival (5-year rates: 34.9 vs. 40.8%, adjusted hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.36–2.50, p < 0.001), and cause-specific survival (5-year rates: 41.8 vs. 55.9%, adjusted HR 1.95, 95% CI 1.39–2.75, p < 0.001) compared with LVSI-carcinoma. Postoperative radiotherapy for women with LVSI-sarcoma had a higher reduction rate of recurrence/progression of disease (54% reduction, p = 0.04) compared with postoperative radiotherapy for women with LVSI-carcinoma (26% reduction, p = 0.08). CONCLUSION. In UCS, the presence of a sarcomatous component in LVSI is particularly prevalent when a tumor has sarcoma dominance. Our study suggests that LVSI containing a sarcomatous component may be a predictor of decreased survival for women with UCS.

Case Approximately 3%‐25% of cases of endometrial carcinoma (EC) or atypical endometrial hyperplasia (AH) occur in women aged

Macro- and micro-deformation properties of sintered copper die-attach material were evaluated. The macro-deformation properties are the properties, including the contribution of voids, and the micro-deformation properties are the properties, excluding the contribution of voids. Macro-deformation properties were evaluated by tensile tests at room temperature along with finite-element analysis (FEA). The specimens for these tests were made by sintering copper-oxide nano particles in the form of paste in a hydrogen atmosphere under low and high pressures. The micro-deformation properties were estimated by tensile test and FEA using a model that reproduces the micro-porous structure obtained from processing focused-ion beam scanning electron microscope data. The micro-stress/strain curve estimated for sintered copper was found to lie above the sintered silver and below the bulk copper. The porosity dependency of the macro-deformation properties of sintered copper was calculated using FEA models and the estimated micro-deformation property. The results obtained show that the macro-deformation properties of sintered copper are higher than those of sintered silver with similar porosity. This suggests that sintered copper die-attach material requires a lower sintering pressure than for sintered silver to achieve the same strength.

OBJECTIVE: To identify risk factors for venous thromboembolism (VTE) and to examine the association of VTE and survival in women with uterine carcinosarcoma. METHODS: This multicenter retrospective study examined 906 women who underwent primary surgical treatment for stage I-IV uterine carcinosarcoma. Time-dependent analyses were performed for cumulative incidence of VTE after surgery on multivariate models. RESULTS: There were 72 (7.9%) women who developed VTE after surgery with 1-, 2-, and 5-year cumulative incidences being 5.1%, 7.3%, and 10.2%, respectively. On multivariate analysis, older age (hazard ratio [HR] per year 1.03, P = 0.012), non-Asian race (HR 6.28, P< 0.001), large body habitus (HR per kg/m(2) 1.04, P = 0.014), residual disease at surgery (HR 3.04, P = 0.003), tumor size ≥5 cm (HR2.73, P = 0.003), and stage IV disease (HR2.12, P = 0.025) were independently associated with increased risk of developing VTE. A risk pattern analysis identified that obese Non-Asian women with large tumors (13.7% of population) had the highest incidence of VTE (2-year cumulative rate, 26.1%) whereas Asian women with no residual disease (47.1% of population) had the lowest (2-year cumulative rate, 1.6%) (P< 0.001). Presence of carcinoma/sarcoma in metastatic sites was significantly associated with increased risk of VTE compared to carcinoma alone (2-year rates, 31.2% versus 8.4%, P = 0.049). VTE was independently associated with decreased progression-free survival on multivariate models (5-year rates, 24.9% versus 47.2%, HR 1.46,95%CI 1.05–2.04, P = 0.026). CONCLUSION: Our study suggests that VTE represents a surrogate marker of aggressive tumor behavior and diminished patient condition in uterine carcinosarcoma; obese Non-Asian women with large tumors carry a disproportionally high risk of VTE, suggesting that long-term prophylaxis may benefit this population.

The objective of this study was to identify pathological indicators that could be used to identify a subgroup of patients with apparent stage I endometrial cancer who do require retroperitoneal lymphadenectomy. 188 T1 endometrial cancer patients underwent primary surgery at Tokushima University Hospital. We retrospectively evaluated their clinical records and histopathological factors. Systematic lymphadenectomy was performed for 149 patients, and 39 patients (grade 1 with < 5 mm of myometrial invasion) were treated without lymphadenectomy. Lymph node metastases were found in 19 (12.8%) of the lymphadenectomy cases. Twenty-four patients with a T1a endometrium-limited lesion did not exhibit lymph node metastasis. Three (3.1%) of the 95 patients with a T1a lesion exhibited lymph node metastasis, and these 3 cases exhibited approximately 50% myometrial invasion. The 39 low-risk patients who did not undergo systematic lymphadenectomy remain alive without recurrence. Systematic lymphadenectomy could be omitted for patients with a grade 1 tumor and minor myometrial invasion of less than 5mm. J. Med. Invest. 65:221-224, August, 2018.

OBJECTIVE: To examine survival after recurrence (SAR) among women with recurrent uterine carcinosarcoma who received a taxane/platinum doublet as the first-line salvage chemotherapy. METHODS: We retrospectively examined 148 women with recurrent uterine carcinosarcoma who received salvage chemotherapy within a cohort of 906 uterine carcinosarcomas. An independent association of salvage chemotherapy type and SAR was examined with multivariate analysis. RESULTS: There were 71 (48.0%) women who received a taxane/platinum regimen. On univariate analysis, women who received a taxane/platinum doublet had a higher 2-year SAR rate compared to women who received non-taxane/platinum regimens (55.5% versus 34.8%, P < 0.001). On multivariate analysis, use of taxane/platinum regimen was independently associated with improved SAR compared to the non-taxane/platinum regimens (adjusted-hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.35 to 0.91, P = 0.02). When stratified by disease-free interval, women with a disease-free interval ≥6 months who received a taxane/platinum doublet had a higher 2-year SAR rate compared to those who received non-taxane/platinum regimens (61.9% versus 40.0%, HR 0.46, 95% CI 0.28 to 0.75, P = 0.002); conversely, in women with a disease-free interval

BACKGROUND: To examine recurrence patterns in women with stage I uterine carcinosarcoma (UCS) stratified by adjuvant therapy pattern. METHODS: We examined 443 cases of stage I UCS derived from a retrospective cohort of 1192 UCS cases from 26 institutions. Adjuvant therapy patterns after primary hysterectomy-based surgery were correlated to recurrence patterns. RESULTS: The most common adjuvant therapy was chemotherapy alone (41.5%) followed by chemotherapy/radiotherapy (15.8%) and radiotherapy alone (8.4%). Distant-recurrence was the most common recurrence pattern (5-year cumulative rate, 28.1%) followed by local-recurrence (13.3%). On multivariate analysis, chemotherapy but not radiotherapy remained an independent prognostic factor for decreased risk of local-recurrence (5-year cumulative rates 8.7% versus 19.8%, adjusted-hazard ratio [HR] 0.46, 95% confidence interval [CI] 0.25–0.83, P = 0.01) and distant-recurrence (21.2% versus 38.0%, adjusted-HR 0.41, 95%CI 0.27–0.62, P < 0.001). The chemotherapy/radiotherapy group had a lower 5-year cumulative local-recurrence rate compared to the chemotherapy alone group but it did not reach statistical significance (5.1% versus 10.1%, adjusted-HR 0.46, 95%CI 0.13–1.58, P = 0.22). Radiotherapy significantly decreased local-recurrence when tumors had high-grade carcinoma, sarcoma component dominance, and deep myometrial tumor invasion (all, P < 0.05); and combining radiotherapy with chemotherapy was significantly associated with decreased local-recurrence compared to chemotherapy alone in the presence of multiple risk factors (5-year cumulative rates, 2.5% versus 21.8%, HR 0.12, 95%CI 0.02–0.90; P = 0.013) but not in none/single factor (P = 0.36). CONCLUSION: Adjuvant chemotherapy appears to be effective to control both local- and distant-recurrences in stage I UCS; adding radiotherapy to chemotherapy may be effective to control local-recurrence when the tumor exhibits multiple risk factors.