Atsumu Terada

RECQL1 DNA Repair Helicase: A Potential Therapeutic Target and a Proliferative Marker against Ovarian Cancer

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.

Validity of intraoperative diagnosis at laparoscopic surgery for ovarian tumors.

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.

Polypoid endocervical adenomyoma: A case report with clinicopathologic analyses

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.

A phase II trial of irinotecan in patients with advanced or recurrent endometrial cancer and correlation with biomarker analysis

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.

Controversies surrounding type III radical abdominal hysterectomy and its procedure using new instruments

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.