A case of ovarian serous cystadenofibroma with scattered lesions in pelvic cavity, like malignant disseminations.

Ovarian serous cystadenofibroma is a relatively rare subtype of serous cystadenoma classified as ovarian benign epithelial tumor. We report a rare case of ovarian serous cystadenofibroma with scattered lesions in pelvic cavity, like malignant disseminations. The patient was 22 years old, gravida 0, para 0. In the laparoscopic surgery, numerous hard yellowish-white solid masses of various sizes were present in the bilateral ovaries. Grossly similar masses were scattered in the fimbria of the fallopian tubes, peritoneum, and great omentum. Because the intraoperative rapid histological diagnosis was benign tumor, surgery was completed for only tumor excision. Postoperative histopathological diagnosis is serous cystadenofibroma. Similar pathological findings were noted in the scattered lesions in the peritoneum and great omentum. No malignant or borderline malignant finding was observed. Because of a benign disease, careful treatment taking fertility preservation into consideration is necessary, especially for young patients.

[Cooperative Surgery with Gastroenterological Surgeons in Gynecologic Malignant Tumors].

Secondary debulking surgery(SDF)for gynecologic malignancies may improve prognosis. However, recurrent lesions may be invasions of the intestinal tract and observed peritoneal dissemination. SDF can be safely carried out by performing cooperative surgery with a gastroenterological surgeon and gynecologists. Precise cooperation is indispensable for the operation, especially when it comes to aspects such as the contact method and perioperative management at that time. In our hospital, if the gynecologist suspects other organs invasion during a preoperative examination, they contact the gastroenterological surgeon in an elective manner. If other organs invasion is not clear during a preoperative examination or bowel injury occurs during surgery, the gastroenterological surgeon would be contacted urgently. To ensure smooth cooperation, it is necessary to run regular joint conferences. By sharing in planned and combining the expertise of all the department of interest, it is possible to perform highly curative and safe surgery.

Ovarian cancer-associated mesothelial cells induce acquired platinum-resistance in peritoneal metastasis via the FN1/Akt signaling pathway.

Peritoneal dissemination of ovarian cancer (OvCa) arises from the surface of the peritoneum, covered by monolayer of mesothelial cells (MCs). Given that both OvCa cells and MCs are present in the same peritoneal metastatic microenvironment, they may establish cell-to-cell crosstalk or phenotypic alterations including the acquisition of platinum-resistance in OvCa cells. Herein, we report how OvCa-associated mesothelial cells (OCAMs) induce platinum-resistance in OvCa cells through direct cell-to-cell crosstalk. We evaluated mutual associations between OvCa cells and human primary MCs with in vitro coculturing experimental models and in silico omics data analysis. The role of OCAMs was also investigated using clinical samples and in vivo mice models. Results of in vitro experiments show that mesenchymal transition is induced in OCAMs primarily by TGF-ß1 stimulation. Furthermore, OCAMs influence the behavior of OvCa cells as a component of the tumor microenvironment of peritoneal metastasis. Mechanistically, OCAMs can induce decreased platinum-sensitivity in OvCa cells via induction of the FN1/Akt signaling pathway via cell-to-cell interactions. Histological analysis of OvCa peritoneal metastasis also illustrated FN1 expression in stromal cells that are supposed to originate from MCs. Further, we also confirmed the activation of Akt signaling in OvCa cells in contact with TGF-ß1 stimulated peritoneum, using an in vivo mice model. Our results suggest that the tumor microenvironment, enhanced by direct cell-to-cell crosstalk between OvCa cells and OCAMs, induces acquisition of platinum-resistance in OvCa cells, which may serve as a novel therapeutic target for prevention of OvCa peritoneal dissemination.

Is standard radical surgery necessary for elderly patients with early-stage epithelial ovarian carcinoma? ~Propensity score matched analysis~.

OBJECTIVE: The impact of 'standard full-staged radical surgery (SRS)' on overall survival (OS) in elderly patients with early-stage epithelial ovarian cancer (EOC) remains unclear. In the current study, we investigated the impact of SRS on OS in elderly patients with early-stage EOC in a multicentric analysis using a propensity score (PS)-matching technique. METHODS: Between 1986 and 2017, 3227 patients with EOC were registered and accumulated by the Tokai Ovarian Tumor Study Group, consisting of 14 collaborating institutions, after a central pathological review. Among them, 204 elderly patients aged older than or equal to 65 years who had a stage I EOC were analyzed, including 72 patients who had received SRS (Group I) and 132 who had undergone non-SRS limited surgery (Group II). Oncologic outcomes were compared between the two groups using a PS-matching technique to adjust for various clinicopathologic risk factors. RESULTS: The median follow-up duration of all surviving patients was 55.9 months. Consequently, 54 patients (26.5%) developed recurrence. In addition, 33 patients (16.2%) died of the disease. In the original cohort, the 5-year OS rates of Groups I and II were 95.8 and 82.3%, respectively. We identified a marginally significant difference between the two groups (Log-rank: P = 0.086). In the PS-matched cohort after adjustment for multiple clinicopathologic factors, there was no significant difference in OS between the two groups [OS (Group I vs. II), HR: 0.766 (95% CI: 0.271-2.165), P = 0.615]. CONCLUSIONS: After adjustment for clinicopathologic factors, non-SRS limited surgery may not worsen the oncologic outcome in elderly women with early-stage EOC. A large-scale clinical study is necessary to validate the findings.

Unique miRNA profiling of squamous cell carcinoma arising from ovarian mature teratoma: comprehensive miRNA sequence analysis of its molecular background.

Owing to its rarity, the carcinogenesis and molecular biological characteristics of squamous cell carcinoma arising from mature teratoma remain unclear. This study aims to elucidate the molecular background of malignant transformation from the aspects of microRNA (miRNA) profiling. We examined 7 patients with squamous cell carcinoma and 20 patients with mature teratoma and extracted their total RNA from formalin-fixed paraffin-embedded tissues. Then we prepared small RNA libraries and performed comprehensive miRNA sequencing. Heatmap and principal component analysis revealed markedly different miRNA profiling in cancer, normal ovarian and mature teratoma tissues. Then we narrowed down cancer-related miRNAs, comparing paired-cancer and normal ovaries. Comparisons of cancer and mature teratoma identified two markedly upregulated miRNAs (miR-151a-3p and miR-378a-3p) and two markedly downregulated miRNAs (miR-26a-5p and miR-99a-5p). In addition, these findings were validated in fresh cancer tissues of patient-derived xenograft (PDX) models. Moreover, several miRNAs, including miR-151a-3p and miR-378a-3p, were elevated in the murine plasma when tumor tissues were enlarged although miR-26a-5p and miR-99a-5p were not elucidated in the murine plasma. Finally, we performed target prediction and functional annotation analysis in silico and indicated that targets genes of these miRNAs markedly correlated with cancer-related pathways, including 'pathway in cancer' and 'cell cycle'. In conclusion, this is the first study on miRNA sequencing for squamous cell carcinoma arising from mature teratoma. The study identified four cancer-related miRNAs that were considered to be related to the feature of malignant transformation. Moreover, miRNAs circulating in the murine plasma of the PDX model could be novel diagnostic biomarkers.

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

BACKGROUND: The aim of this study was to investigate how much the risks of recurrence and death are increased as a consequence of selecting fertility-sparing surgery (FSS) in young women with epithelial ovarian cancer (EOC). METHODS: After a central pathological review and search of the medical records from 14 collaborating hospitals, a non-randomized, observational cohort study was conducted between 1987 and 2015, including 1183 women with stage I EOC. Finally, a total of 285 patients with stage I EOC at reproductive age were recruited. Oncologic outcomes were compared between the FSS (N = 101) and radical surgery (RS) group (N = 184) using a propensity score (PS)-matching technique to adjust for relevant risk factors: the age, substage, histological type, grade, CA125 values, ascites cytology, ascites volume, and chemotherapy. RESULTS: During 66.0 months (median) of follow-up, 42 patients (14.7%) developed recurrence, and 31 patients (10.9%) died. In the original cohort, there was no significant difference in overall survival (OS) or recurrence-free survival (RFS) between the FSS and RS groups {Log-rank: OS (P = 0.838), RFS (P = 0.377)}. In the PS-matched cohort after adjustment for multiple clinicopathologic factors, there was no significant difference in RFS or OS between the FSS and RS groups {RFS (FSS vs. RS), HR: 1.262 (95% CI: 0.559-2.852), P = 0. 575; OS (FSS vs. RS), HR: 1.206 (95% CI: 0.460-3.163), P = 0.704}. CONCLUSIONS: After adjustment for clinicopathologic factors, FSS in itself may not worsen the oncologic outcome in young women with early-stage EOC. A large-scale clinical study is necessary to validate the findings.

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

OBJECTIVE: Complete tumor resection is considered essential in the management of patients with ovarian clear-cell carcinoma. There is a debate regarding whether patients with recurrent ovarian clear-cell carcinoma benefit from secondary cytoreductive surgery. METHODS: Details of patients with clear-cell carcinoma were collected by the Tokai Ovarian Tumor Study Group (Nagoya University Hospital and 13 affiliated institutions) and evaluated between January 1990 and December 2015. Histology was confirmed after central pathological review. The primary endpoint of the study was disease-free survival after secondary cytoreductive surgery. Distributions of events were evaluated using the χ2 test. Survival analysis was based on the Kaplan-Meier method. Survival curves were compared using the log-rank test. A value of p<0.05 was considered significant. RESULTS: A total of 169 patients who underwent secondary cytoreductive surgery (N=25) or medical management (N=144) for recurrent clear-cell carcinoma were collected. The median age for patients undergoing secondary cytoreductive surgery was 50 years (range 35-66). Overall, 18 patients had complete resection. In patients who underwent secondary cytoreductive surgery, the median disease-free and post-recurrence survival periods were 10.9 months and 21.2 months, respectively. Moreover, among 18 patients who underwent complete resection, seven showed no evidence of disease during the observation periods. The median post-recurrence survival periods of patients with complete or incomplete resection were 30.1 months and 10.4 months, respectively (p=0.002). On stratification by the recurrence site, patients with intraperitoneal recurrence showed poorer post-recurrence survival than those with recurrence at other sites (p=0.016). However, comparison between the secondary cytoreductive surgery group versus the medical management group showed there was no difference in post-recurrence survival, even when considering complete tumor resection (p=0.114). CONCLUSION: Patients with intraperitoneal recurrence or incomplete tumor resection had the worst survival after secondary cytoreductive surgery.

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

BACKGROUND: Fertility-sparing surgery (FSS) has mainly been chosen for young women with ovarian-confined/well-differentiated epithelial ovarian cancer (EOC). In general, FSS consists of at least conservation of contralateral ovary and the uterus with a staging surgery. However, information on the clinical outcome in women who underwent cystectomy as a fertility-preserving option is lacking. METHODS: After a central pathological review and search of the medical records from multiple institutions between 1987 and 2015, a total of eight early-stage EOC patients treated with cystectomy as FSS were retrospectively evaluated. Diagnosis and staging were based on International Federation of Gynecology and Obstetrics criteria (2014). Surgery consisted of uni- or bilateral cystectomy. The oncologic and reproductive outcomes were assessed. RESULTS: The median age was 29 years (range 26-38 years). The median follow-up time was 103.6 months (range 42.2-218.3 months). The stage was IA in 3, IC1 in 4, and IC3 in one patient. Five patients received adjuvant chemotherapy. After cystectomy, two patients experienced recurrence in the pelvic cavity and bilateral ovaries, respectively. The former patient died of the disease 42 months after cystectomy, and conversely, the latter one was rescued by subsequent radical surgery. Four full-term childbirths were observed in three patients. CONCLUSIONS: Although oophorectomy is considered as an appropriate fertility-preserving operation, cystectomy may be an unavoidable option when it is the only surgical procedure available. It is desirable to verify the utility by accumulating larger numbers of patients through a future registry system.

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

BACKGROUND: Occasionally, ovarian tumors are found to have originated from non-ovarian organs as metastatic lesions since the ovary is a common site of metastasis from many cancers. The aim of the current study was to estimate the long-term oncologic outcome of patients with metastatic mucinous ovarian carcinoma (MmOC) in comparison with those with primary mucinous ovarian carcinoma (PmOC) at an advanced stage. MATERIALS AND METHODS: The data of one hundred and sixty-seven patients with mucinous ovarian cancer, including 91 patients with MmOC from the digestive organs and 76 patients with stage III-IV PmOC, were retrospectively analyzed. The prognostic significances of clinicopathologic factors were evaluated employing both uni- and multivariable analyses. Pathological slides were evaluated based on centralized pathological review. RESULTS: The median age of patients with PmOC and MmOC was 55 (18-81) and 51 years (30-82), respectively. With follow-up of a total of 167 patients, 145 patients (86.8%) developed recurrence. In addition, 122 patients (73.0%) died of the disease. Regardless of the residual tumor status, patients with PmOC did not a show a significantly poorer OS than those with MmOC. Furthermore, in a Cox multivariable hazard model, after adjustment for various clinicopathologic confounders, a gastric cancer (GC)-originated tumor and larger residual tumor were significant predictors of poorer OS [GC (vs. PmOC): HR (95% CI) 2.205 (1.303-3.654), P = 0.0036]. CONCLUSION: The oncologic outcome of patients with MmOC was extremely poor; however, it was almost the same as that of those with PmOC. We should recognize MmOC derived from gastric carcinoma as a highly aggressive malignancy.

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

BACKGROUND: Clear-cell carcinoma (CCC) in reproductive-age women is likely to become an increasingly critical issue regarding possibilities of infertility, hormonal dysfunction, and mortality. The aim of this study was to examine the long-term oncologic outcome and its prognostic indicators based on a multicentric cohort of young patients with CCC. PATIENTS AND METHODS: During the period of 1990-2015, a total of 164 patients aged 45-year-old or younger were enrolled in the study. Clinicopathologic data of these young patients with CCC collected under a centralized pathological review system were subjected to uni- and multivariable analyses to evaluate overall survival (OS). RESULTS: The median follow-up was 73.8 months (range 5.2-244.2) in the surviving patients. Among these patients, 104 (63.4%) had FIGO I disease, and 22 (13.4%), 31 (18.9%), and 7 (4.3%) had II, III, and IV disease, respectively. The 5-year OS rate was 74.5%. On stratification by the FIGO stage, the 5-year OS rates were as follows: stage I (90.2%), stage II (57.9%), and stage III/IV (39.3%), respectively (P < 0.0001). Confining analysis to stage I patients, there was no difference in OS between those who underwent fertility-sparing surgery and those who received radical surgery (P = 0.1593). In relapsed patients, the median survival after recurrence was 11.6 months. In multivariable analysis of stage I patients, the capsule status was an independent prognostic indicator of OS {IC2/IC3 vs. IA/IC1: HR 4.293 (95% CI 1.140-16.422), P = 0.0318}. CONCLUSION: CCC patients staged greater than IC2/IC3 show a markedly increased risk of mortality. Thus, it is important to diagnose patients staged under IC2/IC3.

Dengue fever during pregnancy.

Dengue fever during pregnancy is an expanding issue in Southeast Asia; however, the knowledge of adverse effects on mothers and neonates remains limited. Therefore, we aimed to determine the impact of dengue fever. The clinical information of 20 patients of dengue fever during pregnancy in Vietnam from January 1, 2015 to December 31, 2015 was collected and their outcomes were retrospectively investigated. A total of 18 patients (90%) presented with positivity of nonstructural protein 1, and a primary infection. Additionally, 4 patients (20%) had preterm deliveries and 1 (5%) had a stillborn child. All live-born neonates were discharged from the hospital uneventfully. Also, 6 patients (30%) required platelet transfusion and 3 of them received transfusion before delivery, but there were no maternal death. In addition, 3 cases of patients (15%) developed to postpartum hemorrhage (PPH), and their platelet concentrations were significantly lower than those of patients without PPH [90.0 (19.0 - 374.0) × 103 vs. 40.0 (12.0 - 57.0) × 103 cell/µl, p = 0.001]. In addition, patients with PPH also presented with elevated liver enzymes. Pregnant patients with low platelet counts should be recognized as being at high risk for PPH.

Efficacy of medroxyprogesterone acetate treatment and retreatment for atypical endometrial hyperplasia and endometrial cancer.

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.

c-Rel Promotes Invasion of Choriocarcinoma Cells via PI3K/AKT Signaling.

OBJECTIVE: Choriocarcinoma is the most common epithelial cancer among gestational trophoblastic diseases (GTDs); the mechanism of trophoblastic carcinogenesis is unknown. This study aimed to examine the expression of NF-κB family proteins in GTDs and placental tissues as well as the roles of c-Rel in choriocarcinoma. METHODS: We examined the expression of NF-κB family proteins in normal placenta and hydatidiform mole tissues as well as extravillous trophoblast (EVT) and choriocarcinoma cell lines by Western blot and immunohistochemistry. Immunoprecipitation was performed to determine which proteins can bind with c-Rel in choriocarcinoma cells. To investigate the roles of c-Rel in choriocarcinoma, we examined the effects of c-Rel knockdown and overexpression on cell proliferation, migration, and invasion using small interfering RNAs and gene activation plasmid. RESULTS: The expression of c-Rel was strong in choriocarcinoma and EVTs, but very weak in villi of normal placenta and hydatidiform mole. Immunoprecipitation suggested that c-Rel heterodimerizes with p65 in choriocarcinoma. c-Rel knockdown reduced invasion, migration, and AKT phosphorylation in choriocarcinoma cells. c-Rel overexpression in choriocarcinoma increased migratory and invasive abilities, and the effect on invasion was inhibited by a PI3K inhibitor. CONCLUSION: These findings suggest that c-Rel might play a role in promoting the invasion of choriocarcinoma cells through PI3K/AKT signaling.

Postoperative chemoradiation therapy using high dose cisplatin and fluorouracil for high- and intermediate-risk uterine cervical cancer.

The purpose of this retrospective study was to analyze data in patients with stage IB-IIB uterine cervical cancer who were treated with concurrent chemoradiotherapy (CCRT) with high dose cisplatin and fluorouracil as postoperative adjuvant therapy. Between February 2003 and November 2011, 76 patients with FIGO stage IB-IIB cervical cancer were analyzed. Seventy patients were treated with postoperative CCRT and 6 patients were treated with radiation therapy alone. Data related to overall survival (OS), disease-free survival (DFS), toxicity, and failure pattern were analyzed. The median patient age was 45 years (range, 20-80 years). The median follow-up duration was 63 months (range, 10-125 months). Fifty-eight patients (76.3%) had a squamous cell histologic type, 55 patients (72.4%) had lymphovascular invasion, 31 patients (40.8%) had parametrial invasion, and 28 patients (36.8%) had lymph node metastases. Five-year OS and DFS were 96% and 92%, respectively. Five-year DFS in stage IB1 patients was significantly higher than in stage IB2-IIB patients (p = 0.022). Nineteen patients (25%) had grade 3 or 4 neutropenia, 13 patients (17.1%) had grade 3 anemia, and 2 patients (2.6%) had grade 3 thrombocytopenia, but none of these patients died from the disease. Three patients experienced chronic toxicity: one had bladder perforation, one had hydronephrosis, and one experienced ileus. CCRT as postoperative adjuvant therapy resulted in good survival and outcome without severe toxicity.

Clinical significance and predicting indicators of post-cancer-treatment survival in terminally ill patients with ovarian cancer.

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 (<75 days) and longer (≥75 days) PCS groups. On the other hand, patients in the shorter PCS group had significantly fewer chances of referral to a hospice or home-care than those in the latter group (P = 0.035). In multivariable analysis, a poorer performance status, an elevated white blood cell count, and a higher C-reactive protein value were significantly correlated with a shorter PCS (P = 0.004, 0.006 and 0.027, respectively). CONCLUSION: Half of the patients received chemotherapy within 75 days of death and we did not identify any survival benefit in patients who received chemotherapy near the end of life. We should provide information to patients about their prognosis and discuss the timing of withdrawal from chemotherapy from the early stage of their recurrence.

Radiotherapy for persistent malignant transformation from mature cystic teratoma of the ovary.

Malignant transformations of mature cystic teratomas (MCT) are extremely rare and most of them are squamous cell carcinomas (SCC). Therefore no effective postoperative treatment has been established. In this article, we report two cases in which radiotherapy was effective for SCC arising from MCT. Case 1 was a 64-year-old woman with stage IIA of this tumor. After primary surgery, chemotherapy and interval debulking surgery were performed. She received radiotherapy for relapsed tumors, and has been well for 36 months since the initial diagnosis. Case 2 was a 37-year-old woman with stage IIB of this tumor. After primary debulking surgery, she received chemoradiotherapy for a residual tumor and has been well for 27 months since the surgery. Although there is no established therapy, radiotherapy or concurrent chemoradiotherapy might have beneficial effects on this tumor, similarly to those on SCC from other tissue.

Oncologic and obstetric outcomes of early stage cervical cancer with abdominal radical trachelectomy: Single-institution experience.

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.

Paclitaxel and carboplatin in patients with completely or optimally resected carcinosarcoma of the uterus: a phase II trial by the Japanese Uterine Sarcoma Group and the Tohoku Gynecologic Cancer Unit.

OBJECTIVE: This study aimed to evaluate the efficacy of paclitaxel and carboplatin in patients with completely or optimally resected uterine carcinosarcoma. MATERIALS AND METHODS: We conducted a single-arm multicenter prospective phase II trial at 20 Japanese medical facilities. Eligible patients had histologically confirmed uterine carcinosarcoma without prior chemotherapy or radiotherapy. Patients received 6 courses of 175 mg/m (2)paclitaxel over 3 hours, followed by a 30-minute intravenous administration of carboplatin at an area under the serum concentration-time curve of 6. RESULTS: A total of 51 patients were enrolled in this study, 48 of whom underwent complete resection and 3 of whom underwent optimal resection. At 2 years, the progression-free survival and overall survival rates were 78.2% (95% confidence interval [CI], 64.1%-87.3%) and 87.9% (95% CI, 75.1%-94.4%), respectively. At 4 years, these rates were 67.9% (95% CI, 53.0%-79.0%) and 76.0% (95% CI, 60.5%-86.1%), respectively. Although 15 patients showed disease recurrence during the follow-up period (median, 47.8 months; range, 2.1-72.8 months), a total of 40 (78.4%) patients completed the 6 courses of treatment that had been planned. CONCLUSIONS: The combination of paclitaxel and carboplatin was a feasible and effective postoperative adjuvant therapy for patients with completely or optimally resected uterine carcinosarcoma.

Opioid needs of terminally ill patients with gynecologic malignancies.

BACKGROUND: Little is known about patterns and predictive factors regarding opioid use for terminally ill patients with gynecologic malignancies. The aim of this study was to elucidate predictors affecting opioid requirements of end-of-life patients with gynecologic malignancies. METHODS: A retrospective study was carried out on patients with gynecological malignancies admitted to our institute and died during the years 2002 to 2012. The association between maximum opioid dose and factors affecting opioid requirements were examined. Data extracted from medical records included age, site of primary cancer, maximum total dose of opioids prescribed over 24 h, the site of recurrence and metastasis, procedures performed during the hospital stay, total number of chemotherapy courses and overall survival. RESULTS: The study identified 189 patients. Most patients had ovarian cancer (42.3 %) followed by cervical cancer (28.0 %) and then corpus malignancy (27.0 %). Opioid requirements decreased with increasing age, especially from the 50s onward. This was particularly marked in cervical cancer patients. In addition, pelvic metastasis was associated with the maximum dose of opioids and the average opioid use was highest in patients with cervical cancer. CONCLUSION: Young age and pelvic invasion were significant predictive factors regarding opioid requirements. Additionally, cervical cancer patients may require more opioids among those with gynecologic malignancies.

The prognostic impact of pulmonary metastasectomy in recurrent gynecologic cancers: a retrospective single-institution study.

The aim was to examine the impact of pulmonary metastasectomy in patients with recurrent gynecologic cancers. Thirty-seven patients with isolated lung metastases (< 3 nodules) in recurrent epithelial gynecologic cancers were treated at Nagoya University Hospital between 1985 and 2013. The clinicopathological data for the 23 patients who underwent surgical resection were retrospectively analyzed, and their survival was compared with patients who received chemotherapy only. The median age at the time of surgery was 56 years (range 28-77). The studied population comprised 7 patients with 2 or 3 nodules and 8 patients with chemoresistant tumors, including fourteen cervical, 4 endometrial, and 5 ovarian primary tumors, with 5-year overall survivals (OSs) after surgery of 61, 100, and 100%, respectively. The survival of recurrence-free interval after initial treatment (>2 years) was significantly favorable (5-year OS 100% vs. 41.7%, p=0.006). Among the 6 patients with re-recurrence of lung metastases, 5 patients underwent a second pulmonary metastasectomy, and all of the patients are currently alive without disease. None of the 29 operations yielded severe complications. Although the survival rate showed a tendency to be higher in the surgery group than in the chemotherapy-only group, no significant difference was observed (5-year OS 81.7% vs. 49.5%, p=0.072). Our results indicate that pulmonary metastasectomy contributed to long-term survival with a low-risk of complications. Surgery to remove isolated lung metastases might provide a favorable prognosis for patients with long recurrence-free intervals and for patients with chemoresistant or re-recurrent tumors.