Liquid-based endometrial cytology using SurePath™ is not inferior to suction endometrial tissue biopsy for detecting endometrial malignancies: Midterm report of a multicentre study advocated by Japan Association of Obstetricians and Gynecologists.

OBJECTIVE: We conducted a prospective, multicentre study to compare the clinical performance of liquid-based endometrial cytology (LBEC) using SurePath™ with that of suction endometrial tissue biopsy (SETB). This study is officially advocated and reported by the Japan Association of Obstetricians and Gynecologists. By publishing our midterm data, we intend to disseminate the benefits of LBEC system, using the descriptive reporting format and algorithmic interpretational approach. METHODS: From April 2014 to December 2015, we consecutively assessed 1116 LBEC specimens and 1044 SETB specimens in our five outpatient clinics. RESULTS: The sensitivity of suction tissue biopsies was 85.2%, whereas the sensitivity of LBEC was 92.2%. The specificity of suction tissue biopsies was 98.9% and that of LBEC was 98.5%. The negative predictive value of LBEC (99.1%) was higher than that of SETB (98.1%), although the difference between these values was not significant. CONCLUSIONS: The clinical performance of LBEC for detecting endometrial malignancies was almost identical to the performance of SETB. This indicates that LBEC was not inferior to SETB for the detection of endometrial cancer. The LBEC is appropriate for various clinical situations as the first-step detecting tool. In addition, it could be used for cancer surveillance for women with signs highly suggestive of endometrial malignancies and in Lynch syndrome patients, on a larger scale.

Durable response by olaparib for a Japanese patient with primary peritoneal cancer with multiple brain metastases: A case report.

Brain metastases (BM) from epithelial ovarian cancer (EOC) or primary peritoneal cancer (PPC) are extremely rare, accounting for 1-2.5% of all cases. Although therapeutic options, such as surgery, irradiation and chemotherapy are proven to yield survival benefit, the overall prognosis of these patients remains unsatisfactory. Poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor, olaparib is useful for patients with recurrent EOC or PPC. However, reports suggesting the efficacy of PARP inhibitors for patients with EOC or PPC with BM are limited. We report the case of a 58-year-old Japanese woman with recurrent PPC with multiple BM. After obtaining informed consent from the patient, we performed BRCA testing that detected a deleterious BRCA 1 mutation. At that time, olaparib was not yet approved in Japan, we learned about the compassionate use program of olaparib called Managed Access Program (MAP). Of note, we have established a system to enroll patients in MAP. After olaparib treatment, the patient exhibited a considerable decrease of BMs. Eighteen months since the initiation of olaparib treatment, the patient has reported no evidence of disease progression. Olaparib maintenance treatment could be effective for Japanese patients with PPC and multiple BMs.

BRCA1 and BRCA2 mutations in Japanese patients with ovarian, fallopian tube, and primary peritoneal cancer.

BACKGROUND: The contribution of BRCA1 and BRCA2 to ovarian cancer in Japanese patients is still unclear. This study investigated the frequency of germline mutations in BRCA1/2 in Japanese patients with ovarian, peritoneal, or fallopian tube cancer, regardless of their family histories, which were suggestive of hereditary breast and ovarian cancer. METHODS: Ninety-five unselected women with ovarian cancer who were seen from 2013 to 2015 at Yamanashi Prefectural Central Hospital were enrolled. Analyses of BRCA1/2 gene mutations were performed with next-generation sequencing. RESULTS: Twelve of the 95 patients (12.6%), including 5 in the BRCA1 (5.3%) and 7 in the BRCA2 (7.4%), had deleterious mutations. Among the 36 cases with a family history, 6 (16.7%) were found to carry mutations in BRCA1 and BRCA2. Notably, 6 of the 59 cases (10.2%) without a family history also had BRCA1/2 germline mutations. There was no statistical difference between the 2 groups (P = .36). The presence of mutations and their clinical relevance were studied. Mutation carriers were diagnosed at advanced stages (100% of positive cases among stage III or IV cases) and had poor prognostic histological subtypes (100% of positive cases had high-grade serous adenocarcinomas). CONCLUSIONS: In this unselected Japanese population, approximately 13% of the cases with ovarian cancer appeared to be associated with an inherited risk, regardless of a family history. This finding indicates that BRCA1/2 genetic testing should be performed for all patients with ovarian cancers.

Effectiveness of human papillomavirus vaccination in young Japanese women: a retrospective multi-municipality study.

In Japan, government support for human papillomavirus (HPV) vaccination began in November 2010. However, the mass media repeatedly reported on severe adverse events. The Japanese Ministry of Health, Labor and Welfare suspended proactive recommendations for HPV vaccines in June 2013. Japan's HPV vaccination rate dropped from 70% to less than 1% in 2017.We examined cervical cancer screening results in terms of abnormal cytology, histology, and HPV vaccination status among 11,903 women aged 20 to 25 y in the fiscal year 2015. The overall rate of HPV vaccination was 26.1% (3,112/11,903). Regarding cytology, the rate of atypical squamous cells of undetermined significance (ASC-US) or worse was 3.3% (103/3,112) in women who received HPV vaccination (vaccine (+) women) and 5.6% (496/8,791) in women who did not (vaccine (-) women). The rate of high-grade squamous intraepithelial lesion (HSIL) or worse was 0.26% (8/3,112) in vaccine (+) women and 0.81% (72/8,791) in vaccine (-) women. Regarding histology, the rate of cervical intraepithelial neoplasia 1 or worse (CIN1+) was 1.4% (42/3,112) in vaccine (+) women and 2.1% (178/8,791) in vaccine (-) women. The rates of CIN2+ and CIN3+ were similar regardless of vaccination. We found a significantly lower incidence of CIN in vaccine (+) women. These results suggest that the resumption of recommending HPV vaccination as primary prevention for cervical cancer is needed in Japan.

Risk of spilling cancer cells during total laparoscopic hysterectomy in low-risk endometrial cancer.

OBJECTIVE: To evaluate the risk of spilling cancer cells during total laparoscopic hysterectomy (TLH) using a uterine manipulator in early-stage endometrial cancer patients. MATERIALS AND METHODS: We conducted a prospective study among women undergoing TLH for Clinical Stage IA endometrial cancer between March 2015 and November 2015. Peritoneal washings before the insertion of the uterine manipulator and after TLH were obtained. The two sets of washings were reviewed by a cytopathologist to determine the presence or absence of malignant cells in a blinded manner. RESULTS: Thirteen endometrial cancer patients (age 39-79 years, median: 62.2 years) were enrolled. The postoperative tumor grades were: G1: 11 (84.6%) and G2: 2 (15.4%). All patients underwent TLH and bilateral salpingo-oophorectomy. Pelvic/para-aortic lymph node dissection was not performed in all cases. Only one patient showed positive peritoneal cytology in the pre-TLH sample. There was high agreement (92.3%) between the two sets of washings in all patients. No patients received postoperative treatment. CONCLUSION: We conclude that fallopian tubal cauterization is sufficient to provide protection from the dissemination of cancer cells into the peritoneal cavity at the time of TLH for endometrial cancers in early stages.

CITRUS, cervical cancer screening trial by randomization of HPV testing intervention for upcoming screening: Design, methods and baseline data of 18,471 women.

BACKGROUND: To assess the efficacy of screening with concurrent liquid-based cytology and human papillomavirus (HPV) testing for primary cervical cancer screening, we initiated a randomized trial entitled CervIcal cancer screening Trial by Randomization of HPV testing intervention for Upcoming Screening (CITRUS). METHODS: Between June 2013 and March 2015, women aged 30-64 years of age who participated in a regular cervical cancer screening program (every 2 years) were invited to enrollment of our study. After giving their informed consent, 18,402 women were randomly assigned to liquid-based cytology as the control group (n=9145) or to HPV DNA testing with liquid-based cytology as the intervention group (n=9257). We subsequently compared the incidence rate of cervical intraepithelial neoplasia (CIN), the rate of false positive tests and the rate of overdiagnosis, as well as assessing the risks and benefits of receiving screening for women in both groups. The primary outcome of our study was the incidence of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) during the study period of around 6 years. RESULTS: In the control group, 97.9% of women were NILM, and 2.06% ASC-US or worse (ASC-US+). In the intervention group, 87.13% of women were NILM/HPV negative, 0.72% ASC-US/HPV negative, 10.34% NILM/HPV positive, 0.69% ASC-US/HPV positive, 0.90% worse than ASC-US/either HPV. Positive HPV testing was not linearly related to age in our study. CONCLUSIONS: Insights from CITRUS will provide future prospects for cervical cancer screening focused on the use of HPV testing in Japan. CLINICAL TRIAL REGISTRATION NUMBER: NCT01895517, UMIN000010843, TRIUC1312.

Cardiac arrest during spinal anesthesia for cervical conization: a case report.

Spinal anesthesia is regularly performed worldwide and is an integral part of the modern day anesthesia practice. Although unexpected cardiac arrests during this procedure are very rare, medical professionals should be aware of the potential for this complication. In making the decision to use spinal anesthesia, judicious patient selection, adequate preventive measures, and strict monitoring are important.

Cytological features of atypical carcinoid combined with adenocarcinoma of the uterine cervix.

Neuroendocrine tumors of the uterine cervix (UC) are rare, and atypical carcinoid (AC) combined with adenocarcinoma of the uterine cervix (ACAUC) is particularly rare. Only the histopathology has been investigated in the English literature. A 49-year-old female with a polypoid lesion of the UC visited Yamanashi Prefectural Central Hospital. Scraping cytology, biopsy, and hysterectomy was performed. EC smears showed solid, rosette, honeycomb,true tubular, and trabecular clusters. Solid clusters were oval, thin-edge, delicate, small-large nuclei, pale, granular, scant, nothing,and well-preserved (though ill-defined border) cytoplasm. Rosette clusters were eccentric, oval nuclei, mixture of coarsely granular chromatin and euchromatin, and cyanophilic luminal content. Solid and rosette clusters impress AC. Honeycomb clusters involved a clearly defined border and translucent mucin. True tubular clusters were oval nuclei of fine chromatin or euchromatin, thick cytoplasm,and orange luminal content. Honeycomb and true tubular clusters suspected adenocarcinoma. Trabecular clusters were fusiform, columnar, cuboidal, and polygonal cell shapes of small,monotonous nuclei, and contained coarsely granular chromatin with occasionally intracytoplasmic translucent mucin and were difficult to differentiate typical carcinoid and adenocarcinoma.Histology was AC combined with adenocarcinoma. The aim of this study was to investigate the cytological characteristics of ACAUC.