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Uterine carcinosarcomas (UCSs) are rare and aggressive tumors. The prognostic factors are not sufficiently known. We performed a multi-institutional, retrospective study of women with stage I–IV UCS, diagnosed between 2007 and 2012. Data obtained from medical records included demographic, clinicopathological, treatment, and outcome information. A total of 486 patients (median age 65 years) were identified—224 (46 %) were stage I, 32 (7 %) were stage II, 139 (28 %) were stage III, and 91 (19 %) were stage IV. Among them, 277 (57 %) had disease recurrence. Median disease-free survival (DFS) was 16.4 months [95 % confidence interval (CI) 15.7–27.2], and median overall survival (OS) was 72.0 months (95 % CI 43.0–not reached). In total, 454 (94 %) patients received adjuvant treatment, and 440 (91 %) received adjuvant chemotherapy. In multivariate analysis, stage III–IV disease, CA-125 level, and lymphovascular space invasion (LVSI) were significantly associated with shorter median DFS. Stage III–IV disease, performance status 2–4, ≥50 % myometrial invasion depth, and postsurgical residual tumor size >1 cm were significantly associated with shorter median OS. Conversely, pelvic lymph node lymphadenectomy was associated with improved DFS and OS. Stage, performance status, CA-125 level, LVSI, and myometrial invasion were associated with poor prognoses. Pelvic lymphadenectomy was associated with improved survival, and may be necessary for the surgical management of UCS.

This survey sought to determine Japanese gynecologists' attitudes concerning administering hormone replacement therapy (HRT) for patients after surgery for endometrial cancer (EC).Eight hundred and eighty-eight members of the Japanese Gynecologic Oncology Group (JGOG) were asked to respond to an anonymous questionnaire on the JGOG website. The survey asked whether or not HRT was to be administered when surgery was performed (including a hysterectomy and bilateral oophorectomy) to treat EC before or after menopause. If HRT was not to be administered, respondents were asked the reason why. Respondents were presented with the same hypothetical patients that were featured in a previous survey in Germany, and differences in the mindsets of Japanese and German physicians were compared.Responses from 363 individuals (response rate 40.9 %) were analyzed. Seventy-eight percent of physicians considered HRT for patients undergoing surgery before menopause. The most prevalent reason of refusal to prescribe HRT was the risk of EC recurrence. Forty-eight percent of physicians considered HRT for patients undergoing surgery after menopause. The most prevalent reasons of refusal of HRT were its limited benefit and the availability of alternative therapies. Sixty-five percent of Japanese physicians responded that they would administer HRT to patients with low risk of recurrence vs. 46 % of physicians in Germany (P0.0002). Forty-nine percent of Japanese physicians approved of prescribing HRT for patients with high risk of recurrence vs. 25 % of physicians in Germany (P0.0001).Many Japanese gynecologists have a favorable attitude toward prescribing HRT after treatment of EC.

Pelvic exenteration has attained an important role in the treatment of advanced or recurrent cervical cancer for obtaining a complete cure or longer disease-free survival. The purpose of this study was to evaluate patients undergoing pelvic exenteration and to determine the clinical features associated with outcome and survival.We retrospectively analyzed the records of 12 patients who underwent pelvic exenteration for uterine cervical cancer between July 2002 and August 2011.Two patients had primary stage IVA cervical adenocarcinoma and 10 patients had recurrent cervical cancer. Eight patients underwent anterior pelvic exenteration, 3 patients underwent total pelvic exenteration, and 1 patient underwent posterior pelvic exenteration. With a median duration of follow-up of 22 months (range 3-116 months), 5 patients were alive without recurrence. Of 5 patients with no evidence of disease, 4 were recurrent or residual tumor, all of whom had common factors, such as a tumor size ≤ 30 mm, negative surgical margins, complete resection, and no lymph node involvement. The 5-year overall survival rate for 12 patients was 42.2 %. Ileus was the most common complication (42 %) and post-operative intestinal anastomosis leaks developed in 3 patients, but no ureteral anastomosis leaks occurred.Pelvic exenteration is a feasible surgical procedure in advanced and/or recurrent cervical cancer patients with no associated post-operative mortality, and the only therapeutic option for complete cure or long-term survival; however, post-operative complications frequently occur.

The fourth edition of the Japan Society of Gynecologic Oncology guidelines for the treatment of ovarian cancer including primary peritoneal cancer and fallopian tube cancer was published in 2015. The guidelines contain seven chapters and six flow charts. The major changes in this new edition are as follows—(1) the format has been changed from reviews to clinical questions (CQ), and the guidelines for optimal clinical practice in Japan are now shown as 41 CQs and answers; (2) the ‘flow charts’ have been improved and placed near the beginning of the guidelines; (3) the ‘basic points’, including tumor staging, histological classification, surgical procedures, chemotherapy, and palliative care, are described before the chapter; (4) the FIGO surgical staging of ovarian cancer, fallopian tube cancer, and primary peritoneal cancer was revised in 2014 and the guideline has been revised accordingly to take the updated version of this classification into account; (5) the procedures for examination and management of hereditary breast and ovarian cancer are described; (6) information on molecular targeting therapy has been added; (7) guidelines for the treatment of recurrent cancer based on tumor markers alone are described, as well as guidelines for providing hormone replacement therapy after treatment.

Clinical practice guidelines for gynecologic cancers have been published by the National Comprehensive Cancer Network and the National Cancer Institute. Whereas these guidelines form the basis for the standard of care for gynecologic malignancies in the United States, it has proven difficult to institute them in Japan due to differences in patient characteristics, health-care delivery systems, and insurance programs. Therefore, evidence-based guidelines for treating cervical cancer specifically in Japan have been under development. The Guidelines Formulation Committee and Evaluation Committee were independently established within the Committee for Treatment Guidelines for Cervical Cancer. Opinions from within and outside the Japan Society of Gynecologic Oncology (JSGO) were incorporated into the final draft, and the guidelines were published after approval by the JSGO. These guidelines are composed of ten chapters and comprise three algorithms. Each chapter consists of a clinical question, recommendations, background, objectives, explanations, and references. The objective of these guidelines is to clearly delineate the standard of care for cervical cancer treatment in Japan in order to ensure equitable care for all Japanese women diagnosed with cervical cancer.

Total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO) have been performed as a standard surgical treatment for endometrial cancer. Many studies have reported on issues such as whether retroperitoneal lymphadenectomy should also be performed with TAH+BSO, to what extent lymphadenectomy should be performed when TAH+BSO is performed, and in what type of patients should lymphadenectomy be performed. These issues have been actively discussed, but there has not been any consensus. In this review article, the benefits of retroperitoneal lymphadenectomy in the initial surgical treatment for endometrial cancer will be discussed in terms of patients with pelvic lymphadenectomy and those with paraaortic (PA) lymphadenectomy. From the previous data, the establishment of TAH+BSO plus pelvic lymphadenectomy as the standard surgical treatment for endometrial cancer is thought to be reasonable. In this situation, is there benefit in performing PA lymphadenectomy? A discussion will be provided by separating the diagnostic significance from the therapeutic significance of this treatment. At present, there are no established treatments for PA-lymph node-positive patients that can be recommended more than the adjuvant therapies that are already performed at various institutions. A scientific basis that clearly indicates the therapeutic effect of PA lymphadenectomy does not exist at the present time. Despite performing thorough PA lymphadenectomy, the route of progression to extrauterine sites cannot be completely controlled. The standard surgical procedure for endometrial cancer is TAH+BSO+pelvic lymphadenectomy, which is considered necessary and sufficient. At present, the addition of PA lymphadenectomy for endometrial cancer can be regarded as only an investigated protocol.

Interleukin-18 (IL-18), a cytokine produced by macrophages, is capable of inducing T-lymphocyte synthesis of interferon-gamma (IFN-gamma). In this study, for the first time, the serum concentration of IL-18 and its significance as a prognostic indicator was evaluated in patients with epithelial ovarian cancer.The serum IL-18 level was measured by an enzyme-linked immunosorbent assay (ELISA) in 69 patients with epithelial ovarian cancer and 8 healthy controls. Relationships between the IL-18 level and clinicopathological features were examined by univariate and multivariate analyses.The median serum IL-18 level in the ovarian cancer patients was 229.6 pg/ml, and the level was significantly elevated compared with that in the normal controls (151.3 pg/ml; P0.01). No significant correlations were detected between the IL-18 level and stage or histology (P = 0.08 and P = 0.12, respectively). On univariate analysis, overall survival was shown to be affected by IL-18 serum levels. However, multivariate analysis failed to demonstrate an independent prognostic significance for IL-18 serum levels, while confirming the role of previously established prognostic variables, such as performance status, stage, and residual tumor.This study showed that IL-18 serum levels were elevated in ovarian cancer patients and were correlated with overall survival, although they were shown not to be an independent prognostic factor.

Background: In the present study, we conducted a multicenter retrospective analysis to elucidate the prognostic significance of second-look laparotomy (SLL) in early-stage epithelial ovarian cancer that was confirmed by complete surgical exploration. Methods: In July 2001, 12 Japanese institutions received questionnaires regarding patients with early-stage epithelial ovarian cancer and SLL. Eligibility criteria included patients with stage I or II epithelial ovarian cancer who were surgically diagnosed between January 1988 and December 1997. Data were collected regarding age, performance status, tumor histologic subtype, stage, preoperative carbohydrate antigen (CA) 125 level, results of SLL if performed, recurrence, disease-free survival, and overall survival. Survival analyses and comparisons were performed by univariate methods. Results: There were 87 patients who met the eligibility criteria. There were no significant differences in the backgrounds of patients who had had SLL (n = 30) and the non-SLL group (n = 57). Of the 30 SLL-group patients, 28 had negative SLL findings and 2 had positive findings. Six and 5 patients in the SLL group and the non-SLL group, respectively, had recurrence (P = 0.177), and 4 patients in the SLL group had a recurrence after “negative” SLL findings. There was no significant difference between the two groups for either overall (P = 0.73) or disease-free survival (P = 0.273). On univariate analysis, only clear-cell histology was associated with a poor prognosis in early-stage epithelial ovarian cancer (P = 0.031). Conclusion: SLL is not beneficial for early-stage epithelial ovarian cancer. More favorable outcomes will be achieved for early-stage patients with the improvement of treatment for clear-cell adenocarcinoma.

Paclitaxel and carboplatin (PC) have shown antitumor activity in carcinosarcoma of the uterus (CS). The purpose of this prospective multi-institutional study was to determine the response rate (RR), progression-free survival (PFS) and overall survival (OS) and to assess the toxicity of paclitaxel and carboplatin in patients with CS. We conducted a phase II study in which patients were administered paclitaxel 175 mg/m2 over a 3-h period followed by carboplatin (area under the serum concentration–time curve = 6) intravenously over a 30-min period on day 1 of each treatment cycle (3 weeks) until disease progression or adverse effects prohibited further therapy. Eligible patients had histologically confirmed, advanced stage (III or IV), persistent or recurrent measurable disease, and no prior chemotherapy. Six patients were enrolled between February 2006 and April 2009. The median age of the patients was 61 (range 48–77) years; one patient was stage IIIC (17 %) and five were stage IVB (83 %). Three patients (50 %) (1 at stage IIIC and 2 at stage IVB) received total abdominal hysterectomy plus bilateral salpingo-oophorectomy as part of the initial treatment; five (83 %) had homologous tumors and one (17 %) had a heterologous tumor. The median cycle number administered was 4.8 (range 2–7). The RR was 66.7 % (complete response, 2; partial response, 2); the PFS was 9.1 months and OS was not reached. The frequently observed Grade 4 toxicities were neutropenia (3 patients, 50 %). Manageable neutropenic sepsis developed in one patient. This is the first prospective multi-institutional study in Asia showing that PC may be effective and tolerable for the treatment of advanced or recurrent CS.

Uterine leiomyosarcoma (LMS) and undifferentiated endometrial sarcoma (UES) are rare, aggressive malignancies. Both are treated similarly; however, few chemotherapy agents are effective. Recently, the combination of gemcitabine (900 mg/m(2), days 1 and 8) plus docetaxel (100 mg/m(2), day 8) with granulocyte colony-stimulating factor (G-CSF, 150 μg/m(2), days 9-15) has been shown to have activity in LMS. In Japan, neither prophylactic G-CSF at a dose of 150 μg/m(2) nor docetaxel at a dose of 100 mg/m(2) are approved for use. For this reason, we evaluated the combination of 900 mg/m(2) gemcitabine plus 70 mg/m(2) docetaxel regimen without prophylactic G-CSF support in advanced or recurrent LMS and UES in Japanese patients.Eligible women with advanced or recurrent LMS and UES were treated with 900 mg/m(2) gemcitabine on days 1 and 8, plus 70 mg/m(2) docetaxel on day 8, every 3 weeks. The primary endpoint was overall response rate, defined as a complete or partial response.Of the eleven women enrolled, 10 were evaluated for a response. One complete response and 2 partial responses were observed (30 %) with an additional 4 (40 %) having stable disease. Mean progression-free survival was 5.4 months (range 1.3-24.8 months), and overall survival was 14 months (range 5.3-38.4 months). Grade 4 neutropenia was the major toxicity (50 %). The median number of cycles was 5 (range 2-18). Twenty-two cycles (44 %) employed G-CSF.The gemcitabine plus docetaxel regimen without prophylactic G-CSF support was tolerable and highly efficacious in Japanese patients with advanced or recurrent LMS and UES.

Endometrial carcinoma is one of the most common gynecologic malignancies in Japan and its incidence has increased recently. Although surgery is the cornerstone of the management of patients with endometrial cancer, there is significant variation in Japan with regard to the type of hysterectomy employed. Additionally, it remains controversial whether full nodal staging is required in all patients. Furthermore, adjuvant therapy differs between Japan and Western countries. To delineate clearly the standard of care for endometrial cancer treatment in Japan, the guidelines for the treatment of endometrial cancer were published in 2006 and revised in 2009. The 2009 edition included topics not addressed in the previous edition including the treatment of mesenchymal tumors, for example leiomyosarcoma, and sections covering the treatment of serous and clear-cell adenocarcinoma. These guidelines are composed of nine chapters and include nine algorithms. The guidelines also contain fifty-one clinical questions (CQs) and each CQ consists of recommendations, background, explanations, and references. The treatment recommendations herein are tailored to reflect current Japanese clinical practice and ensure equitable care for all Japanese women diagnosed with endometrial cancer.