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Background The phase 3 VELIA trial evaluated veliparib with carboplatin/paclitaxel and as maintenance in patients with high-grade serous ovarian carcinoma. Methods Patients with previously untreated stage III–IV high-grade serous ovarian carcinoma were randomized 1:1:1 to control (placebo with carboplatin/paclitaxel and placebo maintenance), veliparib-combination-only (veliparib with carboplatin/paclitaxel and placebo maintenance), or veliparib-throughout (veliparib with carboplatin/paclitaxel and veliparib maintenance). Randomization stratification factors included geographic region (Japan versus North America or rest of the world). Primary end point was investigator-assessed median progression-free survival. Efficacy, safety, and pharmacokinetics were evaluated in a subgroup of Japanese patients. Results Seventy-eight Japanese patients were randomized to control (n = 23), veliparib-combination-only (n = 30), and veliparib-throughout (n = 25) arms. In the Japanese subgroup, median progression-free survival for veliparib-throughout versus control was 27.4 and 19.1 months (hazard ratio, 0.46; 95% confidence interval, 0.18–1.16; p = 0.1 [not significant]). In the veliparib-throughout arm, grade 3/4 leukopenia, neutropenia, and thrombocytopenia rates were higher for Japanese (32%/88%/32%) versus non-Japanese (17%/56%/28%) patients. Grade 3/4 anemia rates were higher in non-Japanese (65%) versus Japanese (48%) patients. Early introduction of olanzapine during veliparib monotherapy maintenance phase may help prevent premature discontinuation of veliparib, via its potent antiemetic efficacy. Conclusions Median progression-free survival was numerically longer in Japanese patients in the veliparib-throughout versus control arm, consistent with results in the overall study population. Pharmacokinetics were comparable between Japanese and non-Japanese patients. Data for the subgroup of Japanese patients were not powered to show statistical significance but to guide further investigation.

Background: Comorbidities can affect survival of ovarian cancer patients by influencing treatment efficacy. However, little evidence exists on the association between individual concurrent comorbidities and prognosis in ovarian cancer patients.Methods: Among patients diagnosed with invasive ovarian carcinoma who participated in 23 studies included in the Ovarian Cancer Association Consortium, we explored associations between histories of endometriosis; asthma; depression; osteoporosis; and autoimmune, gallbladder, kidney, liver, and neurological diseases and overall and progression-free survival. Using Cox proportional hazards regression models adjusted for age at diagnosis, stage of disease, histology, and study site, we estimated pooled HRs and 95% confidence intervals to assess associations between each comorbidity and ovarian cancer outcomes.Results: None of the comorbidities were associated with ovarian cancer outcome in the overall sample nor in strata defined by histologic subtype, weight status, age at diagnosis, or stage of disease (local/regional vs. advanced).Conclusions: Histories of endometriosis; asthma; depression; osteoporosis; and autoimmune, gallbladder, kidney, liver, or neurologic diseases were not associated with ovarian cancer overall or progression-free survival.Impact: These previously diagnosed chronic diseases do not appear to affect ovarian cancer prognosis. Cancer Epidemiol Biomarkers Prev; 26(9); 1470–3. ©2017 AACR.

Description of the studies included in the pooled analysis and methods of data collection

PURPOSE This phase III, multicenter, randomized, open-label study investigated the efficacy and safety of nivolumab versus chemotherapy (gemcitabine [GEM] or pegylated liposomal doxorubicin [PLD]) in patients with platinum-resistant ovarian cancer. MATERIALS AND METHODS Eligible patients had platinum-resistant epithelial ovarian cancer, received ≤ 1 regimen after diagnosis of resistance, and had an Eastern Cooperative Oncology Group performance score of ≤ 1. Patients were randomly assigned 1:1 to nivolumab (240 mg once every 2 weeks [as one cycle]) or chemotherapy (GEM 1000 mg/m2 for 30 minutes [once on days 1, 8, and 15] followed by a week's rest [as one cycle], or PLD 50 mg/m2 once every 4 weeks [as one cycle]). The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), overall response rate, duration of response, and safety. RESULTS Patients (n = 316) were randomly assigned to nivolumab (n = 157) or GEM or PLD (n = 159) between October 2015 and December 2017. Median OS was 10.1 (95% CI, 8.3 to 14.1) and 12.1 (95% CI, 9.3 to 15.3) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.0; 95% CI, 0.8 to 1.3; P = .808). Median PFS was 2.0 (95% CI, 1.9 to 2.2) and 3.8 (95% CI, 3.6 to 4.2) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.5; 95% CI, 1.2 to 1.9; P = .002). There was no statistical difference in overall response rate between groups (7.6% v 13.2%; odds ratio, 0.6; 95% CI, 0.2 to 1.3; P = .191). Median duration of response was numerically longer with nivolumab than GEM or PLD (18.7 v 7.4 months). Fewer treatment-related adverse events were observed with nivolumab versus GEM or PLD (61.5% v 98.1%), with no additional or new safety risks. CONCLUSION Although well-tolerated, nivolumab did not improve OS and showed worse PFS compared with GEM or PLD in patients with platinum-resistant ovarian cancer.

Background Standard treatments for small cell carcinoma of the cervix (SCCC) have not been established. In this study, we aimed to estimate the optimal treatment strategy for SCCC. Methods This was a multicenter retrospective study. Medical records of patients with pathologically proven SCCC treated between 2003 and 2016 were retrospectively analyzed. Overall survival (OS) was plotted using the Kaplan-Meier method. Log-rank tests and Cox regression analysis were used to assess the differences in survival according to stage, treatment strategy, and chemotherapy regimen. Results Data of 78 patients were collected, and after excluding patients without immunohistopathological staining, 65 patients were evaluated. The median age of the included patients was 47 (range: 24–83) years. The numbers of patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stages I-IIA, IIB-IVA, IVB were 23 (35%), 34 (52%), and 8 (12%), respectively. Of 53 patients who had undergone chemotherapy, 35 and 18 received SCCC and non-SCCC regimens as their first-line chemotherapy regimen, respectively. The 5-year OS for all patients was 49%, while for patients with FIGO stages I-IIA, IIB-IVA, IVB, it was 60, 50, and 0%, respectively. The 5-year OS rates for patients who underwent treatment with SCCC versus non-SCCC regimens were 59 and 13% (p Conclusion Our results suggest that the application of an SCCC regimen such as EP or IP as first-line chemotherapy for patients with locally advanced SCCC may play a key role in OS. These findings need to be validated in future nationwide, prospective clinical studies.

BACKGROUND: Data are limited regarding the use of poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors, such as veliparib, in combination with chemotherapy followed by maintenance as initial treatment in patients with high-grade serous ovarian carcinoma. METHODS: In an international, phase 3, placebo-controlled trial, we assessed the efficacy of veliparib added to first-line induction chemotherapy with carboplatin and paclitaxel and continued as maintenance monotherapy in patients with previously untreated stage III or IV high-grade serous ovarian carcinoma. Patients were randomly assigned in a 1:1:1 ratio to receive chemotherapy plus placebo followed by placebo maintenance (control), chemotherapy plus veliparib followed by placebo maintenance (veliparib combination only), or chemotherapy plus veliparib followed by veliparib maintenance (veliparib throughout). Cytoreductive surgery could be performed before initiation or after 3 cycles of trial treatment. Combination chemotherapy was 6 cycles, and maintenance therapy was 30 additional cycles. The primary end point was investigator-assessed progression-free survival in the veliparib-throughout group as compared with the control group, analyzed sequentially in the BRCA-mutation cohort, the cohort with homologous-recombination deficiency (HRD) (which included the BRCA-mutation cohort), and the intention-to-treat population. RESULTS: A total of 1140 patients underwent randomization. In the BRCA-mutation cohort, the median progression-free survival was 34.7 months in the veliparib-throughout group and 22.0 months in the control group (hazard ratio for progression or death, 0.44; 95% confidence interval [CI], 0.28 to 0.68; P

Background We aimed to compare the detection rate of pelvic sentinel lymph node between the radio-isotope with 99m technetium (99mTc)-labeled phytate and near-infrared fluorescent imaging with indocyanine green in patients with endometrial cancer. Methods This study included 122 patients who had undergone sentinel lymph node mapping using 99mTc and indocyanine green. In the radio-isotope method, sentinel lymph nodes were detected using uterine cervix 99mTc injections the day before surgery. Following injection, the number and locations of the sentinel lymph nodes were evaluated by lymphoscintigraphy. In addition, indocyanine green was injected into the cervix immediately before surgery. Results The overall pelvic sentinel lymph node detection rate (at least one pelvic sentinel lymph node detected) was not significantly different between 99mTc (95.9% [117/122]) and indocyanine green (94.3% [115/122]). Similarly, the bilateral sentinel lymph node detection rate was not significantly different between 99mTc (87.7% [107/122]) and indocyanine green (79.5% [97/122]). More than two sentinel lymph nodes per unilateral pelvic lymph node were found in 12.3% (15/122) and 27% (33/122) of cases with 99mTc and indocyanine green, respectively, in the right pelvic side, and 11.5% (14/122) and 32.8% (40/122) of cases with 99mTc and indocyanine green, respectively, in the left pelvic side. indocyanine green showed that there were significantly more than two sentinel lymph nodes in either the left or right pelvic sentinel lymph nodes (P Conclusion Although indocyanine green is useful for sentinel lymph node identification, we believe it is better to use it in combination with 99mTc until the surgeon is accustomed to it.

OBJECTIVE. Genome-wide association studies (GWASs) for epithelial ovarian cancer (EOC) have focused largely on populations of European ancestry. We aimed to identify common germline variants associated with EOC risk in Asian women. METHODS. Genotyping was performed as part of the OncoArray project. Samples with >60% Asian ancestry were included in the analysis. Genotyping was performed on 533,631 SNPs in 3238 Asian subjects diagnosed with invasive or borderline EOC and 4083 unaffected controls. After imputation, genotypes were available for 11,595,112 SNPs to identify associations. RESULTS. At chromosome 6p25.2, SNP rs7748275 was associated with risk of serous EOC (odds ratio [OR] = 1.34, P = 8.7 × 10(−9)) and high-grade serous EOC (HGSOC) (OR = 1.34, P = 4.3 × 10(−9)). SNP rs6902488 at 6p25.2 (r(2) = 0.97 with rs7748275) lies in an active enhancer and is predicted to impact binding of STAT3, P300 and ELF1. We identified additional risk loci with low Bayesian false discovery probability (BFDP) scores, indicating they are likely to be true risk associations (BFDP

PURPOSE: Previous epidemiologic studies have shown that smoking, obesity, and physical inactivity are associated with poor survival following a diagnosis of ovarian cancer. Yet, the combined relationship of these unfavorable lifestyle factors on ovarian cancer survival has not been sufficiently investigated. METHODS: Using data pooled from 13 studies, we examined the associations between combined exposures to smoking, overweight/obesity weight, and physical inactivity and overall survival (OS) as well as progression-free survival (PFS) among women diagnosed with invasive epithelial ovarian carcinoma (N=7,022). Using age-, stage, and site-adjusted Cox proportional hazards regression models, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) associated with joint exposure to these factors. RESULTS: Combined exposure to current smoking, overweight/obesity, and physical inactivity prior to diagnosis was associated with a significantly increased risk of mortality compared to women who never smoked, had normal body mass index (BMI), and were physically active (HR=1.37; 95% CI=1.10–1.70). The association for a joint exposure to these factors exceeded that of each exposure individually. In fact, exposure to both current smoking and overweight/obesity, and current smoking and physical inactivity was also associated with increased risk of death (HR=1.28; 95 % CI=1.08–1.52, and HR=1.26; 95% CI=1.04–1.54, respectively). The associations were of a similar magnitude when former smoking was assessed in combination with the other exposures and when excessive weight was limited to obesity only. No significant associations were observed between joint exposure to any of these factors and PFS. CONCLUSIONS: Joint exposure to smoking, excessive weight, and physical inactivity may negatively impact survival of ovarian cancer patients. These results suggest the importance of examining the combined effect of lifestyle factors on ovarian cancer patients’ survival.

Background 5-Aminolaevulinic acid (5ALA) is a precursor of the strong sensitizer protoporphyrin IX (PpIX) in the heme synthesis pathway. We conducted aclinical trial designed to evaluate the efficacy and safety of 5ALA photodynamic therapy (PDT) using a light-emitting diode (LED) in patients with cervical intraepithelial neoplasia (CIN). Methods Data for 51 CIN patients who underwent 5ALA-PDT between 2012 and 2017 were prospectively analysed. After a 20 % 5ALA jelly formulation was topically applied to the cervix, the region was irradiated with red light at approximately 633 nm to excite PpIX for treatment. We estimated outcomes by cytology, pathology, and human papilloma virus (HPV) testing after PDT. Results Patients underwent two PDT sessions at one-week intervals during outpatient treatment and achieved favourable results without photosensitivity and severe adverse events. Over a long follow-up period, 96.1 % of all patients showed some positive effects, including approximately 70 % with a complete response (CR), 10 % with a partial response, and 15 % with downgrades. The HPV clearance rate in patients with CR was 79.4 %. Recurrence occurred in five patients who mostly remained HPV-positive after PDT. Conclusions Based on our study, topical 5ALA-PDT using an LED light source potentially represents a safe treatment for CIN on an outpatient basis.

The development of cervical cancer is initiated by human papillomavirus (HPV) infection and involves both viral and host genetic factors. Genome-wide association studies (GWAS) of cervical cancer have identified associations in the HLA locus and two loci outside HLA, but the principal genes that control infection and pathogenesis have not been identified. In the present study, we performed GWAS of cervical cancer in East Asian populations, involving 2609 cases and 4712 controls in the discovery stage and 1461 cases and 3295 controls in the follow-up stage. We identified novel-significant associations at 5q14 with the lead single nucleotide polymorphism (SNP) rs59661306 (P = 2.4 × 10-11) and at 7p11 with the lead SNP rs7457728 (P = 1.2 × 10-8). In 5q14, the chromatin region of the GWAS-significant SNPs was found to be in contact with the promoter of the ARRDC3 (arrestin domain-containing 3) gene. In our functional studies, ARRDC3 knockdown in HeLa cells caused significant reductions in both cell growth and susceptibility to HPV16 pseudovirion infection, suggesting that ARRDC3 is involved in the infectious entry of HPV into the cell. Our study advances the understanding of host genes that are responsible for cervical cancer susceptibility and guides future research on HPV infection and cancer development.

ObjectiveThe aim of this study was to compare the outcomes and toxicities of radical hysterectomy (RH) and definitive chemoradiation (CRT) for International Federation of Gynecology and Obstetrics (FIGO) stage IIB cervical cancer.Materials and MethodsA retrospective analysis was performed on FIGO stage IIB patients who underwent RH with adjuvant radiotherapy (surgery group) or intended to receive CRT (CRT group). The distributions of disease-free survival (DFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Propensity score matching (PSM) was performed for the 2 groups based on age, tumor diameter, histological type, and pelvic node metastasis in pretreatment imaging tests.ResultsMedian follow-up times were 58 months in the surgery group (n = 75) and 55 months in the CRT group (n = 65). Propensity score matching identified 37 patients with similar characteristics from each group. Significant differences were observed in the ratio of the chemotherapy combination between the surgery and CRT groups before (47% vs 98%) and after PSM (51% vs 100%). Five-year DFS rates were slightly higher in the surgery group than in the CRT group before PSM (69% vs 58%, P = 0.30) but were similar after PSM (76% vs 82%, P = 0.36). Five-year OS rates were similar between the surgery and CRT groups before (70% vs 75%, P = 0.59) and after PSM (78% vs 77%, P = 0.97). The results of multivariate analyses also showed that neither DFS nor OS was associated with the treatment modalities regardless of PSM. The incidence of late toxicities grade 2 or greater was similar between the surgery and CRT groups before (17% vs 23%, P = 0.31) and after PSM (19% vs 24%, P = 0.78).ConclusionsThe results of this study suggest that RH with adjuvant radiotherapy and definitive CRT are equivalent treatment options for patients with FIGO stage IIB cancer. However, prospective larger studies are needed to confirm this.

Objective This multicenter phase II Japanese Gynecologic Oncology Group study (JGOG1067) was designed to evaluate the efficacy and safety of postoperative chemotherapy in patients with node-positive cervical cancer. Methods Patients with stage IB–IIA squamous cervical cancer who underwent radical hysterectomy and were confirmed to have pelvic lymph node metastasis were eligible for this study. The patients postoperatively received irinotecan (CPT-11; 60mg/m 2 intravenously on days 1 and 8) and nedaplatin (NDP; 80mg/m 2 intravenously on day 1). Chemotherapy administration commenced within 6weeks after surgery and was repeated every 28days for up to 5cycles. The primary endpoint of this study was the 2-year recurrence-free survival (RFS) rate. The secondary endpoints were the 5-year overall survival (OS) rate, 5-year RFS rate, and adverse events such as complications of chemotherapy and lower-limb edema. Results Sixty-two patients were analyzed according to our protocol, among whom 55 (88.7%) completed 5cycles of scheduled treatment. The median follow-up period was 66.1months (range, 16.8–96.6months). The 2-year and 5-year RFS rates were 87.1% (95% confidence interval [CI]: 75.9–99.3) and 77.2% (95% CI: 64.5–85.8), respectively. Fourteen patients (22.5%) experienced recurrence during the follow-up period, 8 of whom died of the disease. The 5-year OS rate in this study was 86.5% (95% CI: 74.8–93.0). Only 9.7% of the patients experienced lymphedema in their legs. Conclusion Postoperative chemotherapy without radiotherapy was found to be very effective in high-risk patients with node-positive cervical cancer.

その他, Miscellaneous, 看護学教育の基礎教育課程では、学生が看護を学問として初めて学修し、看護専門職者を目指すものとして知識、態度を育成することが求められる。看護過程を展開する技術は看護実践能力の基盤となる技術として位置づけられ、根拠のある看護実践の基本として修得すべき技術である。2017年度基礎看護学領域において、ディプロマポリシーを踏まえ科目概要を見直すこととなった。そこで、基礎看護学実習Ⅱでは、学生が対象を受け持ち、対象の療養生活を理解し、対象に必要な日常生活援助のための計画を立案することに目標を変更した。学生の学修目標達成のため、教育方略を検討し、実習施設との調整を経て教育方略を変更した経緯を報告する。

Background Photodynamic therapy (PDT) is known as a minimally invasive treatment for cancer. 5-Aminolevulinic acid (ALA) is a precursor of the photosensitizing agent protoporphyrin IX (PpIX). Patients with ovarian clear-cell carcinoma (CCC) have poorer prognoses than those of patients with other histological CCC types. We evaluated the efficacy of ALA-PDT on CCC cells in vitro. Methods We used seven human CCC cell lines to measure the cytotoxicity of ALA-PDT. PpIX production in cancer cells was measured using a micro-plate reader. Quantitative real-time PCR was performed to assess the mRNA levels of genes involved in the accumulation of PpIX in cancer cells. Additionally, we measured the enhancement in cytotoxicity with the use of an ABCG2 inhibitor. Results We found that three cell lines were highly sensitive to ALA-PDT. In contrast, one cell line was resistant to ALA-PDT. The cytotoxicity of ALA-PDT varied among CCC cell lines. The IC50 values of ALA-PDT for the CCC cell lines had a wide range (30–882 μM). The cytotoxicity of ALA-PDT was correlated with the intracellular PpIX accumulation. The cell lines sensitive to ALA-PDT expressed PEPT1 (an ALA uptake transporter). The cell line resistant to ALA-PDT expressed ABCG2 (a PpIX export transporter). In the resistant cell line, a combination treatment with both ALA and an ABCG2 inhibitor resulted in the promotion of cytotoxic sensitivity. Conclusion The present study revealed the efficacy of ALA-PDT against CCC with chemoresistance in vitro.

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

The aldehyde dehydrogenase 2 (ALDH2) polymorphism rs671 (Glu504Lys) causes ALDH2 inactivation and adverse acetaldehyde exposure among Asians, but little is known of the association between alcohol consumption and rs671 and ovarian cancer (OvCa) in Asians. We conducted a pooled analysis of Asian ancestry participants in the Ovarian Cancer Association Consortium. We included seven case-control studies and one cohort study comprising 460 invasive OvCa cases, 37 borderline mucinous OvCa and 1274 controls of Asian descent with information on recent alcohol consumption. Pooled odds ratios (OR) with 95% confidence intervals (CI) for OvCa risk associated with alcohol consumption, rs671 and their interaction were estimated using logistic regression models adjusted for potential confounders. No significant association was observed for daily alcohol intake with invasive OvCa (OR comparing any consumption to none = 0.83; 95% CI = 0.58-1.18) or with individual histotypes. A significant decreased risk was seen for carriers of one or both Lys alleles of rs671 for invasive mucinous OvCa (OR = 0.44; 95% CI = 0.20-0.97) and for invasive and borderline mucinous tumors combined (OR = 0.48; 95% CI = 0.26-0.89). No significant interaction was observed between alcohol consumption and rs671 genotypes. In conclusion, self-reported alcohol consumption at the quantities estimated was not associated with OvCa risk among Asians. Because the rs671 Lys allele causes ALDH2 inactivation leading to increased acetaldehyde exposure, the observed inverse genetic association with mucinous ovarian cancer is inferred to mean that alcohol intake may be a risk factor for this histotype. This association will require replication in a larger sample.

Purpose We aimed to determine appropriate treatment guidelines for patients with stages I–II high-grade neuroendocrine carcinomas (HGNEC) of the uterine cervix in a multicenter retrospective study. Patients and methods We reviewed the clinicopathological features and prognoses of 93 patients with HGNEC of International Federation of Gynecology and Obstetrics (FIGO) stages I and II. All patients were diagnosed with HGNEC by central pathological review. Results The median overall survival (OS) and disease-free survival (DFS) were 111.3months and 47.4months, respectively. Eighty-eight patients underwent radical surgery, and five had definitive radiotherapy. The hazard ratio (HR) for death after definitive radiotherapy to death after radical surgery was 4.74 (95% confidence interval [CI], 1.01–15.90). Of the surgery group, 18 received neoadjuvant chemotherapy. Pathological prognostic factors and optimal adjuvant therapies were evaluated for the 70 patients. Forty-one patients received adjuvant chemotherapy with etoposide–platinum (EP) or irinotecan–platinum (CPT–P). Multivariate analyses identified the invasion of lymphovascular spaces as a significant prognostic factor for both OS and DFS. Pelvic lymph node metastasis was also a prognostic factor for DFS. Adjuvant chemotherapy with an EP or CPT–P regimen appeared to improve DFS (HR=0.27, 95% CI, 0.10–0.69). A trend toward improved OS was also observed, but was not statistically significant (HR=0.39, 95% CI, 0.15–1.01). Conclusion Radical surgery followed by adjuvant chemotherapy with an EP or CPT–P regimen was optimal treatment for stages I and II HGNEC of the uterine cervix.

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

A structured approach to self-monitoring of blood glucose and blood glucose pattern management (BGPM) is crucial in diabetes management. However, nursing processes for supporting BGPM among people ...

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

According to the specified primary objective, a regimen of cisplatin, paclitaxel and bevacizumab was tolerable in Japanese patients and demonstrated encouraging activity in this small single-arm study., Background Adding bevacizumab to chemotherapy for recurrent, persistent or metastatic cervical cancer significantly improved overall survival (primary endpoint), progression-free survival and overall response rate in the randomized Phase III GOG-0240 trial. However, data for bevacizumab-containing therapy are scarce in Japanese patients with advanced cervical cancer. Methods The primary objective of the single-arm multicenter Phase II JO29569 study was to evaluate the tolerability of paclitaxel (135 mg/m2 over 24 h or 175 mg/m2 over 3 h), cisplatin (50 mg/m2) and bevacizumab (15 mg/kg), administered every 3 weeks until disease progression or unacceptable toxicity in Japanese patients with stage IVB, persistent or recurrent cervical cancer. Results The seven treated patients received a median of nine (range 7–12) bevacizumab cycles and six (range 4–12) chemotherapy cycles. None of the predefined adverse events occurred during the tolerability evaluation period. The most common all-grade adverse events were alopecia, hypertension, decreased appetite, nausea and peripheral sensory neuropathy. There were no cases of fistula. The most common grade ≥3 adverse events were hypertension, neutrophil count decreased and neutropenia. Only one patient experienced febrile neutropenia. The overall response rate was 86% (95% confidence interval, 42–100%), including a complete response in one patient. At data cutoff, disease had progressed in one patient; bevacizumab therapy was ongoing in the remaining six. Conclusions According to the specified primary objective, a regimen of cisplatin, paclitaxel and bevacizumab was tolerable in Japanese patients and demonstrated encouraging activity in this small single-arm study. Further study is warranted to confirm the safety and effectiveness of bevacizumab in Japanese patients with cervical cancer.

This study was to analyze patterns and risk factors of relapse after postoperative adjuvant chemotherapy for endometrial cancer.Among patients enrolled in a randomized phase III trial (JGOG2043) investigating the efficacy of adjuvant chemotherapy for endometrial cancer at a high risk of progression, the recurrent patients were studied. Clinical information were collected, and correlation between relapse-related factors and clinicopathological factors were analyzed.Among 193 patients analyzed, 50% had local relapse and 63% had distant relapse. Local relapse involved regional lymph nodes in 30%, while distant relapse involved the abdominal cavity in 42%. Imaging was used to confirm relapse in 83%, and the median disease-free interval (DFI) was 11.5 months. Factors showing a significant correlation with DFI ≤12 months were residual tumor at surgery (p 0.01), Grade 3 histology (p 0.01), and lymph node metastasis (p = 0.03). In contrast, treatment with paclitaxel and carboplatin showed a significant correlation with DFI12 months (p = 0.04). The median post-relapse overall survival (RS) was 23.9 months. In multivariate analysis, CA125 ≥ 100 U/mL prior to relapse (p 0.01), distant metastasis (p 0.01), DFI ≤ 12 months (p = 0.02), and not performing para-aortic lymphadenectomy (p = 0.01) were independently related to poor RS.Relapse of endometrial cancer following adjuvant chemotherapy often occurs by 1 year after treatment, with common relapse sites of the abdominal cavity and regional lymph nodes. Among treatment-related factors, RS was correlated with DFI and para-aortic lymphadenectomy.

BACKGROUND: Angiopoietin 1 and 2 regulate angiogenesis and vascular remodelling by interacting with the tyrosine kinase receptor Tie2, and inhibition of angiogenesis has shown promise in the treatment of ovarian cancer. We aimed to assess whether trebananib, a peptibody that inhibits binding of angiopoietin 1 and 2 to Tie2, improved progression-free survival when added to carboplatin and paclitaxel as first-line therapy in advanced epithelial ovarian, primary fallopian tube, or peritoneal cancer in a phase 3 clinical trial. METHODS: TRINOVA-3, a multicentre, multinational, phase 3, double-blind study, was done at 206 investigational sites (hospitals and cancer centres) in 14 countries. Eligible patients were aged 18 years or older with biopsy-confirmed International Federation of Gynecology and Obstetrics (FIGO) stage III to IV epithelial ovarian, primary peritoneal, or fallopian tube cancers, and an ECOG performance status of 0 or 1. Eligible patients were randomly assigned (2:1) using a permuted block method (block size of six patients) to receive six cycles of paclitaxel (175 mg/m2) and carboplatin (area under the serum concentration-time curve 5 or 6) every 3 weeks, plus weekly intravenous trebananib 15 mg/kg or placebo. Maintenance therapy with trebananib or placebo continued for up to 18 additional months. The primary endpoint was progression-free survival, as assessed by the investigators, in the intention-to-treat population. Safety analyses included patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01493505, and is complete. FINDINGS: Between Jan 30, 2012, and Feb 25, 2014, 1164 patients were screened and 1015 eligible patients were randomly allocated to treatment (678 to trebananib and 337 to placebo). After a median follow-up of 27·4 months (IQR 17·7-34·2), 626 patients had progression-free survival events (405 [60%] of 678 in the trebananib group and 221 [66%] of 337 in the placebo group). Median progression-free survival did not differ between the trebananib group (15·9 months [15·0-17·6]) and the placebo group (15·0 months [12·6-16·1]) groups (hazard ratio 0·93 [95% CI 0·79-1·09]; p=0·36). 512 (76%) of 675 patients in the trebananib group and 237 (71%) of 336 in the placebo group had grade 3 or worse treatment-emergent adverse events; of which the most common events were neutropenia (trebananib 238 [35%] vs placebo 126 [38%]) anaemia (76 [11%] vs 40 [12%]), and leucopenia (81 [12%] vs 35 [10%]). 269 (40%) patients in the trebananib group and 104 (31%) in the placebo group had serious adverse events. Two fatal adverse events in the trebananib group were considered related to trebananib, paclitaxel, and carboplatin (lung infection and neutropenic colitis); two were considered to be related to paclitaxel and carboplatin (general physical health deterioration and platelet count decreased). No treatment-related fatal adverse events occurred in the placebo group. INTERPRETATION: Trebananib plus carboplatin and paclitaxel did not improve progression-free survival as first-line treatment for advanced ovarian cancer. The combination of trebananib plus carboplatin and paclitaxel did not produce new safety signals. These results show that trebananib in combination with carboplatin and paclitaxel is minimally effective in this patient population. FUNDING: Amgen. ispartof: LANCET ONCOLOGY vol:20 issue:6 pages:862-876 ispartof: location:England status: published

Importance The efficacy of taxane plus platinum regimens has been demonstrated for advanced or recurrent endometrial cancer; however, it has not been assessed in postoperative adjuvant chemotherapy for endometrial cancer. Objective To evaluate the clinical benefit of taxane plus platinum compared with standard doxorubicin plus cisplatin as postoperative adjuvant chemotherapy in endometrial cancer. Design, Setting, and Participants In this multicenter, open-label, phase 3 randomized clinical trial, patients with endometrial cancer at high-risk stage I or II or stage III or IV that did not extend beyond the abdominal cavity and had 2 cm or greater residual tumor were included from 118 institutions in Japan from November 24, 2006, to January 7, 2011. Data was analyzed from March 15, 2017, to June 30, 2017. Interventions Eligible patients were randomly assigned (1:1:1) to receive 6 cycles of doxorubicin, 60 mg/m2, plus cisplatin, 50 mg/m2, on day 1; docetaxel, 70 mg/m2, plus cisplatin, 60 mg/m2, on day 1; or paclitaxel, 180 mg/m2, plus carboplatin (area under the curve, 6.0 mg/mL × min) on day 1 every 3 weeks. Main Outcomes and Measures The primary end point was progression-free survival. Secondary end points were overall survival, occurrence of adverse events, tolerability, and status of lymph node dissection. Results Among 788 eligible patients, the median (SD) age was 59 (22-74) years; 263 patients were assigned to doxorubicin plus cisplatin treatment, 263 patients to docetaxel plus cisplatin treatment, and 262 patients to paclitaxel plus carboplatin treatment. The number of patients who did not complete 6 cycles was 53 (20.1%) for the doxorubicin plus cisplatin group, 45 (17.1%) for the docetaxel plus cisplatin group, and 63 (24.0%) for the paclitaxel plus carboplatin group. Tolerability of these regimens were not statistically different. After a median follow-up period of 7 years, there was no statistical difference of progression-free survival (doxorubicin plus cisplatin, 191; docetaxel plus cisplatin, 208; paclitaxel plus carboplatin, 187;P = .12) or overall survival (doxorubicin plus cisplatin, 217; docetaxel plus cisplatin, 223; paclitaxel plus carboplatin, 215;P = .67) among the 3 groups. The 5-year progression-free survival rate was 73.3% for the doxorubicin plus cisplatin group, 79.0% for the docetaxel plus cisplatin group, and 73.9% for the paclitaxel plus carboplatin group, while the 5-year overall survival rates were 82.7%, 88.1%, and 86.1%, respectively. Conclusions and Relevance There was no significant difference of survival among patients receiving doxorubicin plus cisplatin, docetaxel plus cisplatin, or paclitaxel plus carboplatin as postoperative adjuvant chemotherapy for endometrial cancer. Because each regimen showed adequate tolerability but different toxic effects, taxane plus platinum regimens may be a reasonable alternative to treatment with doxorubicin plus cisplatin. Trial Registration UMIN-CTR identifier:UMIN000000522

Background: The number of elderly patients with gynecological cancer in Japan is increasing in line with the aging of society. However, little has been reported on the survival of elderly patients aged 75 or older with gynecological cancer in Japan. Methods: To clarify survival in women aged 75 years or older with gynecological cancer, we analyzed data of 4,089 gynecological cancer cases (cervical cancer, 1,309 cases; endometrial cancer, 1,319 cases; and ovarian cancer, 1,461 cases) in patients aged 75 or older from 21 population-based cancer registries in Japan, diagnosed in 2006-2008. We calculated the net survival (NS) of younger (75-79 years old), older (80-84 years old) and the oldest age group (85-99 years old). We also calculated NS stratified by extent of disease and histological type. Results: Five-year NS of cervical cancer patients was 54.5% in the younger age group, 40.8% in the older age group and 28.2% in the oldest age group. Five-year NS of endometrial cancer patients was 64.5%, 51.6% and 39.0% in the younger, older and oldest age groups, respectively. Five-year NS of ovarian cancer was 34.7%, 18.8% and 8.3%, respectively. Conclusion: We estimated NS in elderly patients aged 75 years or older with gynecological cancers in Japan using data from population-based cancer registries.

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

報告, Reports, 本研究は、看護師の筋・骨格系のフィジカルアセスメントに関する知識と実践について質問紙による実態調査を行った。対象は、総合病院勤務の看護師322 名とし、回収数は120 名（37.3％）であった。その結果、112 名（93.3％）の看護師は、フィジカルアセスメントを学んだ経験があった。必要な形態・機能の知識では、「四肢の動脈」を除くすべての項目で「まったくわからない」または「なんとなくわかる」と回答した者が４割以上を占めていた。フィジカルアセスメントの実践では、「臨床での活用の頻度」と「検査：MMT」などに関連を認めた。フィジカルアセスメントを活用している者の方が知識を持ち、実践できる傾向にあった。「実践できない」が最も多かった項目は、「検査：筋トーヌス」27.5％であった。このことから、フィジカルアセスメントに必要な形態・機能の知識を教授する研修が必要である。「臨床での活用の頻度」と関連を認めた「MMT の実践」などは、臨床場面で正確に修得できる可能性がある。

Anticancer drug sensitivity affects prognosis in ovarian carcinoma. Previously, we purified spectrin αII and βII tetramers from cisplatin‐resistant ovarian serous adenocarcinoma cells and demonstrated that they contribute to platinum anticancer drug resistance. In this clinical study, we focused on the role of spectrin αII expression. It is our objective to demonstrate the potential of spectrin αII expression as a useful predictor of anticancer drug resistance and postoperative prognosis in epithelial ovarian carcinoma. Spectrin αII expression in the ovarian adenocarcinoma surgical specimens of 193 patients was examined by immunohistochemical staining. Staining strength was scored 3+, regarded as positive expression, and 2+, 1+, and 0, regarded as non‐positive expression. Prognoses obtained from clinical records were evaluated by statistical analysis. In the 193 cases studied, positive spectrin αII expression was associated with worse overall survival when compared with non‐positive expression (P

Background/aim The incidence of delayed chemotherapy-induced nausea and vomiting (CINV), especially nausea, in gynecologic cancer patients who receive paclitaxel and carboplatin (TC) chemotherapy is unclear. We assessed risk factors for delayed CINV in these patients, and examined whether it was controlled with combination antiemetic therapy. Materials and methods Data were pooled from two prospective studies, and compared between the two antiemetic prophylaxis groups using inverse probability of treatment weighted (IPTW) analysis. Results Among the 182 evaluable patients (mean age: 56.2 years), three antiemetics gave better overall control than two for delayed nausea (42.9% vs. 57.4%,) and vomiting (13.8% vs. 34.5%). Risk factor for delayed nausea was age [odds ratio (OR)=0.953; p=0.0898[and use of two antiemetics (vs. three antiemetics) for delayed vomiting (OR=0.304; p=0.0732). Conclusion A combination of three antiemetics controls delayed CINV among patients who undergo TC chemotherapy. Identification of risk factors can facilitate personalized treatments.

Aim The purpose of this study was to develop a scale to assess daily time management capabilities among working patients with diabetes and to test this scale's reliability and validity. Methods A self-administered questionnaire survey was conducted among 277 diabetes outpatients, and data from 220 participants (mean age = 54.3 ± 10.2 years, 76.8% male) were analyzed. Questionnaire items were selected through exploratory factor analysis. During the process of developing the questionnaire, opinions were solicited from experts on education for patients with diabetes, and Cronbach's α was calculated as a coefficient of reliability. Correlations with the Instrument of Diabetes Self-Care Agency (IDSCA) were examined and confirmatory factor analysis was performed to check for validity. Results Adequacy of a 4-factor, 16-item scale was confirmed. Cronbach's α coefficient was ≥.7 for the entire scale and for the subscale items. There was a significant correlation between total IDSCA scores and various factors (r = .280-.469). However, there was no correlation between the "adjustment of life rhythms" and parts of the IDSCA subscale. Conclusion Although some aspects warrant further investigation, the developed scale provides a reliable and valid means of assessing daily time management capabilities among working patients with diabetes, and can thus be applied to help diabetes patients to manage their daily lives.

Objectives The objective of this study was to assess the effect of extensive lymphadenectomy on survival of early-stage cervical cancer patients with radical hysterectomy followed by adjuvant radiotherapy (RT). Materials and Methods A retrospective analysis was performed on early-stage patients with high-risk factors who received radical hysterectomy with lymphadenectomy followed by adjuvant RT. All patients were divided into the less than or equal to 40 dissected pelvic lymph nodes (DPLN ⩽40) and greater than 40 dissected pelvic lymph nodes (DPLN >40) groups to assess the effect of extensive lymphadenectomy. Distributions of disease-free survival (DFS) and overall survival (OS) were calculated by the Kaplan-Meier method. Significance of survival was assessed by the log-rank test. Cox proportional hazards models were applied to assess the effects of the factors on survival by univariate and multivariate analyses. Results After a median follow-up of 76 months for a total of 178 patients, 5-year DFS of the DPLN >40 group was significantly higher than that of the DPLN ⩽40 group (86% vs 74%, P = 0.045). Five-year OS was comparable between the 2 groups (85% vs 78%, P = 0.49). The multivariate analysis showed that the DPLN ⩽40 group was at a significantly higher risk of recurrence (hazard ratio, 2.3; 95% confidence interval (CI), 1.1–4.8; P = 0.020), whereas OS was not affected by the DPLN group (P = 0.26). Positive pelvic lymph node, parametrial invasion, histological type, and the absence of RT-combined chemotherapy remained significant prognostic factors for lower DFS and OS by the multivariate analysis. Adjusted hazard ratio of DPLN ⩽40 for DFS was 1.2 (95% CI, 0.11–12; P = 0.91) in patients with negative pelvic lymph node (PLN) whereas it was 2.6 (95% CI, 1.1–5.8; P = 0.024) in patients with positive PLN. Conclusions These results suggest that more extensive lymphadenectomy significantly improve the outcomes of patients with positive PLN even followed by adjuvant RT.

Introduction: To reveal the actual conditions of blood glucose pattern management (BGPM) performed by nurses certified in diabetes nursing (DCNs) in Japan and clarification of the related factors. DCNs are the specialists for people with diabetes and are certified by the Japanese Nursing Association (JNA). BGPM refers to a method aimed at improving blood glucose control by ascertaining changes (patterns) in blood glucose levels and conducting a systematic and multi-dimensional analysis of the factors contributing to these patterns.Method: Subjects were DCNs (n = 303) whose names and affiliations were publicly available on the JNA website in November 2011. The study was conducted through a postal questionnaire, involving items about how they were conducting guidance, the details of the BGPM (i.e. method and target) and the state of their overview of facilities, from January 2012 to February 2012.Result: The questionnaire was returned by 148 respondents. Regarding the statement ‘Looking with the people with...

We aimed to evaluate the radioprotective effect of hydrolyzed rice bran (HRB) on acute gastroenteritis due to chemoradiotherapy for treatment of cervical cancer. This placebo-controlled, double-blind study was conducted as an exploratory investigation of the colitis-inhibiting effects of HRB in alleviating acute-phase gastrointestinal side effects of chemoradiotherapy. The study involved 20 patients (10 in the HRB group, 10 in the control group). The patients in the control group underwent the same chemoradiotherapy regimen as those in the HRB group, but they received a placebo instead of HRB. The diarrheal side effect assessment score was lower in the HRB than control group, and a trend toward a reduction in diarrhea symptoms was observed with the oral intake of HRB. Additionally, no significant difference was observed in the administration of intestinal regulators and antidiarrheal agents, but again the assessment score was lower in the HRB than control group, and diarrhea symptoms were alleviated with the oral intake of HRB. A trend toward no need for strong antidiarrheal agents was seen. Although this study was an exploratory clinical trial, the results suggest that HRB may relieve diarrhea, an acute-phase gastrointestinal side effect of chemoradiotherapy.

Objective Perifosine exhibits anti-tumor activity by inhibiting AKT phosphorylation. The purpose of this phase II basket trial was to evaluate the efficacy and safety of perifosine monotherapy for ovarian, endometrial, and cervical cancers. Methods Recurrent or persistent ovarian, endometrial, or cervical cancer patients were assigned to PIK3CA wild-type or mutant groups. Each patient received 600 mg oral perifosine on day 1 followed by a maintenance dose of 100 mg daily. The primary endpoint was disease control rate; secondary endpoints included response rate, progression-free survival, overall survival, and safety. Immunohistochemical staining and targeted sequencing were used to explore new biomarkers in such patients. Results Sixteen and 5 ovarian, 17 and 7 endometrial, and 18 and 8 cervical cancer patients with PIK3CA wild-type and mutant, respectively, were enrolled. Disease control rates (wild-type/mutant) were 12.5/40.0%, 47.1/14.3%, and 11.1/25.0% in ovarian, endometrial, and cervical cancer, respectively. The most common grade 3/4 toxicities were anemia (22.5%) and anorexia (11.3%). Immunohistochemical staining revealed that the disease control rate in patients with negative phosphatase and tensin homolog (PTEN) expression was 50.0%, and the odds ratio of positive to negative patients was 0.24 in all patients. Conclusions Perifosine monotherapy showed good tolerability but expected efficacy was not achieved. Modest efficacy was demonstrated in ovarian cancer patients with PIK3CA mutations and endometrial cancer patients with PIK3CA wild-type; no difference was observed between PIK3CA wild-type and mutant in cervical cancer. Absence of PTEN expression may be predictive of clinical efficacy with perifosine monotherapy.

Findings from in vitro studies suggest that increased exposure to thyroid hormones can influence progression of ovarian tumours. However, epidemiologic evidence on this topic is limited. We pooled data from 11 studies from the Ovarian Cancer Association Consortium. Using multivariate Cox proportional hazards models, we estimated associations between hyper- and hypothyroidism and medications prescribed for these conditions with 5-year all-cause survival among women diagnosed with invasive ovarian cancer. Overall, there was a nonsignificant association with history of hyperthyroidism (n=160 cases) and mortality (HR=1.22; 95% CI=0.97–1.53). Furthermore, diagnosis of hyperthyroidism within the 5 years before ovarian cancer diagnosis was associated with an increased risk of death (HR=1.94; 95% CI=1.19–3.18). A more modest association was observed with history of hypothyroidism (n=624 cases) and mortality (HR=1.16; 95% CI=1.03–1.31). Neither duration of hypothyroidism nor use of thyroid medications was associated with survival. In this large study of women with ovarian cancer, we found that recent history of hyperthyroidism and overall history of hypothyroidism were associated with worse 5-year survival.

Background: Comorbidities can affect survival of ovarian cancer patients by influencing treatment efficacy. However, little evidence exists on the association between individual concurrent comorbidities and prognosis in ovarian cancer patients. Methods: Among patients diagnosed with invasive ovarian carcinoma who participated in 23 studies included in the Ovarian Cancer Association Consortium, we explored associations between histories of endometriosis; asthma; depression; osteoporosis; and autoimmune, gallbladder, kidney, liver, and neurological diseases and overall and progression-free survival. Using Cox proportional hazards regression models adjusted for age at diagnosis, stage of disease, histology, and study site, we estimated pooled HRs and 95% confidence intervals to assess associations between each comorbidity and ovarian cancer outcomes. Results: None of the comorbidities were associated with ovarian cancer outcome in the overall sample nor in strata defined by histologic subtype, weight status, age at diagnosis, or stage of disease (local/regional vs. advanced). Conclusions: Histories of endometriosis; asthma; depression; osteoporosis; and autoimmune, gallbladder, kidney, liver, or neurologic diseases were not associated with ovarian cancer overall or progression-free survival. Impact: These previously diagnosed chronic diseases do not appear to affect ovarian cancer prognosis. Cancer Epidemiol Biomarkers Prev; 26(9); 1470–3. ©2017 AACR.

Aim We aimed to investigate the possibility of an association between a stem-like hallmark and radiotherapeutic sensitivity in human cervical carcinoma cells. Material and Methods Side-population (SP) cells and non-SP (NSP) cells in HeLa cells were isolated using flow cytometry and Hoechst 33342 efflux. We performed Western blot analysis to evaluate the expression of stem cell markers (CXCR4, Oct3/4, CD133, and SOX2) and apoptosis markers after irradiation. In addition, SP and NSP cells were injected into nude mice and we assessed subcutaneous tumor formation. To examine tolerance of irradiation, colony formation and apoptosis change were confirmed in the SP and NSP cells. Results SP cells showed a higher expression of CXCR4, Oct3/4, CD133, and SOX2 than NSP cells. The colony size of SP cells cultured on non-coated dishes was larger than that of NSP cells, and NSP cells were easily induced to undergo apoptosis. SP cells tended to form spheroids and showed a higher level of tumorigenicity compared with NSP cells. In addition, nude mice inoculated with SP cells showed greater tumor growth compared with NSP cells. SP cells showed a higher tumorigenicity and lower apoptotic potential, leading to enhanced radiotolerance. Conclusion Tumor SP cells showed higher-level stem-cell-like characters and radioresistance than NSP cells. SP cells may be useful for new therapeutic approaches for radiation-resistant cervical cancer.

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.

5524 Background: Patients with persistent cervical cancer after definitive radiotherapy/concurrent chemoradiotherapy (RT/CCRT) have a poor prognosis. Salvage hysterectomy (HT) is potentially curative, but eligibility criteria therefor have not been determined. Methods: Part 1) Retrospective review of patients with persistent cervical cancer treated with definitive RT/CCRT at 35 institutions of the Japanese Clinical Oncology Group (JCOG) from 2005–2014. Differences between a salvage HT group and a systemic chemotherapy (CT) group after definitive RT/CCRT for residual tumor were evaluated. Clinical variables influencing a salvage HT treatment decision were evaluated using logistic regression analysis. Part 2) Questionnaire-based survey conducted by JCOG gynecologic oncologists assessing treatment choice for patients with residual cervical disease after definitive RT/CCRT. Patients with residual cervical tumor before, during and after definitive RT/CCRT were surveyed for 86 conditions and appropriate candidates for salvage HT were evaluated using heat map analysis. Results: Part 1) We identified 298 patients who underwent salvage HT or systemic CT. Median overall survival was 3.8 and 0.9 year in the HT and CT groups, respectively (HR 0.4341, 95% CI 0.336-0.559, p < 0.01). FIGO stage and lymph node metastasis at initial treatment, performance status (PS) at diagnosis of residual cervical tumor and parametrial invasion of residual cervical tumor significantly influenced a salvage HT treatment decision. Part 2) Heat map analysis showed that surveyed variables segregated into 3 groups: i) in favor of salvage HT, ii) in favor of systemic CT, and iii) either. Conditions such as FIGO stage IB-IIB, PS of 0-1, residual tumor < 4 cm, no parametrial invasion and no residual lymph node metastasis were included in group i, in favor of salvage HT. Conclusions: Eligibility criteria could be determined based on the results of the current study, and a prospective clinical trial evaluating the survival benefit of salvage HT for residual cervical tumor after definitive RT/CCRT is being planned by JCOG.

Endoglin (CD105), an accessory receptor of transforming growth factor-β, is expressed in vascular endothelial cells. Recently, it was reported that endoglin expression was significantly associated with poorer survival in several cancers. In this study, we evaluated the role of endoglin in uterine leiomyosarcoma. We examined the expression of endoglin in 22 uterine leiomyosarcomas and the association between their expression and the outcome. Additionally, to evaluate the function of endoglin, we used SKN cells, a human uterine leiomyosarcoma cell line. We generated SKN cells stably transfected with plasmids encompassing shRNA targeting endoglin (shEng cells), and compared the ability of proliferation, migration, and invasion to control shRNA-transfected cells (shCon cells). We compared the level of VEGF and matrix metalloproteinases (MMP) in culture supernatants of shEndoglin and shControl cells. Nine patients were endoglin-positive and 13 patients were -negative. The endoglin-positive group had a significantly poorer overall survival and progression-free survival than the endoglin-negative group. In an in vitro study, there was no difference in cell proliferation between shEng and shCon cells. On the other hand, shEng cells showed a lower ability for migration and invasion than shControl cells. The activity of MMP-9 and VEGF level in the supernatant from shEng cells were lower than in shCon cells. In uterine leiomyosarcoma, endoglin expression was associated with a poor prognosis. It was suggested that endoglin up-regulated invasion and VEGF secretion. The investigation of endoglin may lead to a new strategy in uterine leiomyosarcoma therapy.

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). 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. 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