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Platinum-resistant ovarian cancer (PROC) is usually treated with single-agent chemotherapy. A synergistic effect of gemcitabine and platinum has been reported in PROC. We evaluated the efficacy and safety of gemcitabine and carboplatin with or without bevacizumab (GC ± B) in patients with PROC.From April 2014 to April 2018, patients with PROC received gemcitabine on days 1 and 8, and carboplatin on day 1, with or without bevacizumab (Bev) on day 1 every 3 weeks. The primary endpoint was objective response rate (ORR). The secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and rate of adverse events.In total, 215 cycles were administered to 31 patients, of whom 21 received Bev and the median number of cycle for each patient was 6 (range, 2-19). The median platinum-free interval (PFI) was 4 months. The ORR and DCR were 51.9% and 92.6%, respectively. Median PFS and OS were 7.9 months and 16.1 months, respectively. PFS and OS of patients with 3-6 months PFI were significantly longer than those with PFI 3 months (median PFS, 9.7 vs. 5.8 months; p 0.01; median OS, 20.0 vs. 12.1 months; p = 0.03). Grade 3 or 4 hematological toxicities observed included neutropenia (71.0%), leukopenia (54.8%), anemia (51.6%), and thrombocytopenia (25.8%). No other grade 2-4 nonhematological toxicity was observed except for hypertension in one and CBDCA hypersensitivity reaction in two.GC ± B may be effective and safe treatment alternative for PROC, especially with PFI of 3-6 months, despite hematological toxicity.

AIM Type-specific persistent infection (TSPI) of human papillomavirus (HPV) is reportedly associated with a high risk of residual/recurrent disease after local treatment for cervical intraepithelial neoplasia (CIN). This study aimed to evaluate whether HPV genotyping is more accurate in detecting residual/recurrent disease than HPV DNA testing and identify which HPV genotype can predict a high risk of residual/recurrent disease. METHODS We retrospectively reviewed patient outcomes and results of HPV DNA testing and genotyping at 6-12 months after local treatment for CIN2/3 for 439 women. We investigated residual/recurrent disease occurrence according to the TSPI and new infections. Sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively) of the two testing methods for predicting residual/recurrent diseases were also evaluated. RESULTS Eighty-five (19.4%) patients were positive for HPV DNA testing after treatment, of which 74 (87.1%) had TSPI. Residual/recurrent disease was identified in 34 (7.7%) patients, of which 30 were positive for HPV DNA testing and had TSPI of HPV16, 18, 31, 33, 52, and 58 (six HPV genotypes). The sensitivity and NPV of HPV DNA testing and TSPI were equal at 88.2% and 98.9%, respectively. The specificity and PPV of TSPI were higher than those of HPV DNA testing (89.1% vs. 86.4%, 40.5% vs. 35.2%, respectively). Furthermore, the TSPI of the six HPV genotypes further improved specificity (90.6%) and PPV (44.1%) with the same sensitivity and NPV. CONCLUSION HPV genotyping is more useful than HPV DNA testing for determining TSPI, especially of the six HPV genotypes.

Carcinomatous meningitis presents with a variety of neurological symptoms and has a poor prognosis. We encountered a case of carcinomatous meningitis from cervical cancer. A 30-year-old patient was diagnosed with cervical cancer (glassy cell carcinoma), stage IIB. She underwent radical hysterectomy and chemoradiotherapy. Nine months later, the disease recurred with iliac lymph node and right lung metastases. The patient received chemotherapy; however, after seven cycles, the lung lesions increased. The patient responded to supportive care; nevertheless, symptoms including headaches developed and were followed by diplopia. A contrast-enhanced magnetic resonance image of the head confirmed the diagnosis of carcinomatous meningitis. She was transferred to the palliative care unit and died approximately 1 week later. Carcinomatous meningitis has a poor prognosis and is difficult to treat; however, early diagnosis may provide meaningful time to patients. Therefore, attention must be paid to meningeal irritation and neurological symptoms.

Objective Although studies have evaluated learning curves for laparoscopic surgery (LS), this issue has not yet been addressed in gynecologic oncologists. The present study aimed to evaluate LS proficiency for early-stage endometrial cancer among gynecologic oncologists. Methods We examined 25 cases in which LS with pelvic lymphadenectomy (PLA) for endometrial cancer was performed by two gynecologic oncologists undergoing training in LS. The LS duration, estimated blood loss (EBL), number of dissected pelvic lymph nodes (PLNs), and perioperative complications were assessed as measures of surgical proficiency. Results Operators A and B performed 10 and 15 cases, respectively, with median LS durations of 348.5 and 378 minutes, respectively. Although the LS duration and number of procedures did not exhibit a significant correlation, the regression lines for both operators showed decreasing trends. Both operators had a consistently low median EBL (A, 57 ml; B, 60 ml). Operators A and B dissected a median of 21.5 and 22 PLNs, respectively. Although both operators dissected a relatively large number of PLNs, with a median of over 20 per patient after the introduction of LS, this number decreased as the number of LS increased for Operator B (p=0.009). However, no correlation was observed between the LS duration and number of PLNs dissected by Operator B (ρ=0.353, p=0.197). A severe perioperative complication, specifically perforation of the sigmoid colon requiring emergent laparotomy, occurred in one case; however, the association with surgical manipulation was not definitive. Conclusion The observed gynecologic oncologists were able to acquire early proficiency in LS for early-stage endometrial cancer.

Objective Chemotherapy for advanced or recurrent endometrial cancer requires further development. Irinotecan hydrochloride (CPT-11) suppresses tumor growth in several endometrial cancer strains. The present study evaluated the anti-tumor activity and toxicity of CPT-11 in patients with advanced or recurrent endometrial cancer. Methods Enrolled patients had advanced endometrial cancer with measurable lesions and received 2 pretreatment regimens. A 90-minute intravenous infusion of CPT-11 (100 mg/m2) was given on days 1, 8, and 15 of a 4-week cycle, aiming for an effect with ≤2 cycles. Treatment was continued until the primary disease worsened or severe toxicity occurred. The primary endpoint was response rate, and the secondary endpoints were progression-free survival, overall survival, and adverse events. Antitumor effect and adverse events were evaluated according to RECIST version 1.1 and NCI-CTC AE version 3.0, respectively. Results Twenty-two patients were registered (11 endometrioid carcinomas and 11 serous carcinomas). The median duration of the treatment-free interval (TFI) was 7.5 months, and the median number of administered cycles per patient was 4. Response rate was 36.4% (complete response: 1 patient, partial response: 7 patients). Clinical benefit rate, including stable disease, was 77.3%. Median progression-free and overall survival was 4.4 and 18.4 months, respectively. Observed adverse events included grade 4 hematotoxicity (neutropenia and thrombocytopenia), and grade 2 or 3 non-hematotoxicity (diarrhea). All adverse events were manageable. Biomarker predictors of therapeutic effectiveness were not observed. Conclusion As a single agent, CPT-11 has anti-tumor activity for advanced or recurrent endometrial cancer and has manageable adverse events.

Study Objective To evaluate the accuracy and usefulness of intraoperative diagnosis of ovarian tumor during laparoscopic surgery. Design Retrospective cohort study (Canadian Task Force classification II-3). Setting Tertiary care university hospital. Patients We reviewed the cases of 262 patients who underwent laparoscopic surgery at our institution between January 2005 and December 2011 in whom a benign ovarian tumor was diagnosed intraoperatively. Interventions Intraoperative pathologic assessment of frozen sections. Measurements and Main Results Intraoperative diagnosis of ovarian tumors demonstrated sensitivity of 80%, specificity of 99.6%, positive predictive value of 80%, and diagnostic accuracy of 99.2%. Mucinous tumors diagnosed intraoperatively showed differing intraoperative and final pathologic diagnoses significantly more frequently than did other types of tumors. Conclusion Intraoperative pathologic assessment of benign ovarian tumors during laparoscopic surgery is reliable. However, clinicians should recognize that it is possible to make an incorrect diagnosis in some situations and should exercise caution accordingly.

Background: Stat3 is a member of the Janus-activated kinase/STAT signalling pathway. It normally resides in the cytoplasm and can be activated through phosphorylation. Activated Stat3 (p-Stat3) translocates to the nucleus to activate the transcription of several molecules involved in cell survival and proliferation. The constitutive activation of Stat3 has been shown in various types of malignancies, and its expression has been reported to indicate a poor prognosis. However, the correlation between the constitutive activation of Stat3 and the prognosis of cervical cancer patients has not been reported. Methods: The immunohistochemical analysis of p-Stat3 expression was performed on tissues from 125 cervical squamous-cell carcinoma patients who underwent extended hysterectomy and pelvic lymphadenectomy, and the association of p-Stat3 expression with several clinicopathological factors and survival was investigated. Results: Positive p-Stat3 expression was observed in 71 of 125 (56.8%) cases and was significantly correlated with lymph node metastasis, lymph vascular space invasion, and large tumour diameter (>4 cm) by Fisher's exact test. Kaplan–Meier survival analysis showed that p-Stat3 expression was statistically indicative of a poor prognosis for overall survival (P=0.006) and disease-free survival (P=0.010) by log-rank test. Conclusion: These data showed that p-Stat3 expression in cervical cancer acts as a predictor of poor prognosis.

To reduce chemotherapy induced gonadotoxicity, co-treatment with gonadotropin releasing hormone against analogue (GnRHa) was tested using rat model. Leuprorelin acetate (Leuplin) with or without cisplatin (CDDP) was given subcutaneously at a dose of 9.4 microg/ml to Wistar strain female rats. The total number of follicles was counted and the maturation of follicles was evaluated at the largest section of the ovary on the 5th and 10th day after administration. Leuplin led the ovary to a resting phase in which primordial follicle occupied 80% of all follicles in only 5 days after administration. The serum E2 level was also down by the 5th day and maintained a low level to the 10th day. In co-treatment with GnRHa and CDDP rats, the primordial follicle occupied 90% of all follicles and the total number of follicles was higher than in CDDP alone rats. This rat model verified that GnRHa co-treatment well minimized CDDP induced gonadotoxocity by desensitization of the ovary. These results were promising for the clinical application introducing GnRHa co-treatment as ovarian protection in cancer chemotherapy in young women.

Epithelial borderline ovarian tumors (BOT) are distinctive from benign tumors and carcinoma. They occur in younger women more often than carcinoma, and there is some difficulty making correct diagnosis of BOT. Two subtypes of BOT, serous and mucinous borderline tumor have different characteristics and very different clinical behavior. Serous borderline tumor (SBT) with micropapillary pattern shows more incidence of extra ovarian disease and often coexists with invasive implant. SBT with micropapillary pattern in advanced stage has showed a worse prognosis than typical SBT. Huge mucinous borderline tumors have histologic heterogeneity, and the accuracy of frozen section diagnosis is relatively low. Extensive sampling is required to reach a correct pathological diagnosis. Mucinous adenoma (intestinal type) also runs the risk of recurrence after cystectomy, or intraoperative rupture of cyst. Laparoscopic procedure for BOT has not increased the risk of recurrence. Fertility preserving procedures are generally accepted, except in advanced stage SBT with invasive implants. Only cystectomy shows a significant risk of recurrence. Re-staging surgery and full staging surgery is not necessary for all BOT. We should not attempt to treat them uniformly, by the single diagnosis of "borderline tumor". It depends on histologic type. Close communication with the pathologist is necessary to gain more detail and ask more pathological samples in order to make the optimal treatment strategy for each individual patients.

Some regimens of chemotherapy cause peripheral neuropathy such as pain in muscles and joints and numbness in the limbs. It is often difficult to estimate the neuropathy accurately and analyze it in detail. The aim of this study was to investigate whether chemotherapy-induced peripheral neuropathy could be appropriately estimated by using the visual analogue scale (VAS). Ninety-three patients who received paclitaxel and carboplatin treatment (TC) or paclitaxel and docetaxel treatment (DC) participated in answering a questionnaire about peripheral neuropathy using the VAS. As a result, 134 cycles of TC and 79 cycles of DC were evaluated. The average of VAS scores at every 10 days after each cycle of chemotherapy began was calculated. The daily change in VAS scores was also analyzed, and average VAS scores compared between TC and DC. Daily changes in peripheral neuropathy for each treatment could be demonstrated in detail. Pain and numbness had separate patterns of appearance. For both pain and numbness, a greater VAS score was observed in patients receiving TC than in those receiving DC. As the number of cycles grew, peripheral neuropathy became more serious in TC. The VAS could appropriately recognize the difference in peripheral neuropathy between TC and DC. Moreover, the VAS could also catch the change in peripheral neuropathy. This result suggests that the VAS system is a useful tool for managing peripheral neuropathy.

A case of polypoid endocervical adenomyoma (PEA) in the uterine cervix was encountered in the uterine cervix of a 56-year-old woman. Grossly, a well-circumscribed polypoid tumor was observed protruding from the uterine cervix. Based on the findings of imaging studies, it was assumed to be an adenoma malignum in the uterine cervix. The tumor was composed of a mixture of proliferating glands of endocervical type and fascicles of smooth muscle. No distinct nuclear anaplasia, architectural abnormality or any evidence of destructive stromal invasion was observed. Adenoma malignum, which shows a gastric phenotype with immunoreactivity for HIK-1083, was a serious diagnostic possibility. In the present case, the tumor was a well-circumscribed polypoid lesion, with no cytologic or architectural abnormality; however, focal immunoreactivity was shown for HIK-1083, which thus suggested it to be PEA. Therefore, the results of these ancillary diagnostic modalities should be interpreted with caution and combined with the gross and light microscopy findings.

OBJECTIVE: This study analyzed the clinicopathological correlation between ovarian cancer (OC) and RECQL1 DNA helicase to assess its therapeutic potential. METHODS: Surgically resected OC from 118 retrospective cases, for which paraffin blocks and all clinical data were complete, were used in this study. RECQL1 and Ki-67 immunostaining were performed on sections to correlate RECQL1 staining with subtype and patient survival. Ten OC and two normal cell lines were then examined for RECQL1 expression and were treated with siRNA against RECQL1 to assess its effect on cell proliferation. RESULTS: Of the 118 cases of adenocarcinoma (50, serous; 26, endometrioid; 21, clear cell; 15, mucinous; 6, other histology), 104 (90%) showed varying levels of RECQL1 expression in the nuclei of OC cells. The Cox hazards model confirmed that diffuse and strong staining of RECQL1 was correlated with histological type. However, RECQL1 expression did not correlate with overall patient survival or FIGO stage. In vitro, RECQL1 expression was exceptionally high in rapidly growing OC cell lines, as compared with normal cells. Using a time-course analysis of RECQL1-siRNA transfection, we observed a significant inhibition in cell proliferation. CONCLUSIONS: RECQL1 DNA helicase is a marker of highly proliferative cells. RECQL1-siRNA may offer a new therapeutic strategy against various subtypes of OC, including platinum-resistant cancers, or in recurrent cancers that gain platinum resistance.

Type III radical abdominal hysterectomy (RAH) is standard care for early stage cervical cancer. For the past few decades, there has been a remarkable shift from surgery to radiation, in the treatment choice for stage 1b2 and 2b cervical cancer in Japan. It is still controversial, however because some of those cases recommended RAH as a suitable treatment strategy. About 8% to 10% of RAH are abandoned because of tumor status. Recent preoperative screening cannot always detect them preoperatively. Various kinds of new surgical instruments, such as bipolar scissors and the electro vessel sealing system LigaSure have contributed to reducing the operation time and blood loss, in performing RAH. Furthermore, various kinds of devices are on the market. Surgeons should choose suitable instruments depending on the state of the disease and the patient.