Risk-reducing salpingo-oophorectomy for Japanese women with hereditary breast and ovarian cancer: a single-institution 10-year experience.

BACKGROUND: For women diagnosed with hereditary breast and ovarian cancer, the clinical guidelines recommend risk-reducing salpingo-oophorectomy at age 35-40 years or after completion of childbearing. However, there is limited information regarding the current status of risk-reducing salpingo-oophorectomy in Japan. METHODS: To clarify factors influencing decision-making for risk-reducing salpingo-oophorectomy among Japanese women diagnosed with hereditary breast and ovarian cancer and their clinical outcomes, we analyzed the medical records of 157 Japanese women with germline BRCA pathogenic variants (BRCA1 n = 85, BRCA2 n = 71 and both n = 1) at our institution during 2011-21. Specimens obtained from risk-reducing salpingo-oophorectomy were histologically examined according to the sectioning and extensively examining the fimbriated end protocol. RESULTS: The risk-reducing salpingo-oophorectomy uptake rate was 42.7% (67/157). The median age at risk-reducing salpingo-oophorectomy was 47 years. Older age, married state and parity were significantly associated with risk-reducing salpingo-oophorectomy (P < 0.001, P = 0.002 and P = 0.04, respectively). History of breast cancer or family history of ovarian cancer did not reach statistical significance (P = 0.18 and P = 0.14, respectively). Multivariate analyses revealed that older age (≥45 years) and married state may be independent factors associated with risk-reducing salpingo-oophorectomy. Interestingly, the annual number of risk-reducing salpingo-oophorectomy peaked in 2016-17 and has increased again since 2020. The rate of occult cancers at risk-reducing salpingo-oophorectomy was 4.5% (3/67): ovarian cancer (n = 2) and serous tubal intraepithelial carcinoma (n = 1). CONCLUSION: Age and marital status significantly affected decision-making for risk-reducing salpingo-oophorectomy. This is the first study to suggest possible effects of Angelina Jolie's risk-reducing salpingo-oophorectomy in 2015 and the National Health Insurance introduced for risk-reducing salpingo-oophorectomy in 2020. The presence of occult cancers at risk-reducing salpingo-oophorectomy supports clinical guidelines recommending risk-reducing salpingo-oophorectomy at younger ages.

Three-Dimensional Peripheral Bloodstream Model of the Uterus for Laparoscopic Radical Hysterectomy.

Trainees require extensive experience to perform radical hysterectomy. Before starting training during an actual operation, trainees should be familiar with the pelvic anatomy and should simulate surgical procedures. Many simulators are available for virtual reality training of laparoscopic operations, but they are very expensive. The materials required to construct our model included sponges and colored wires sold in home improvement stores that allowed for superior cost effectiveness. The model represented almost all peripheral vessels and nerves around the uterus, including the minor vessels. Attaching and detaching the vessels was easy, facilitating reconstruction of the dissected vessels. The wires were easy to bend, ensuring high operability. This model allows for the simulation of laparoscopic radical hysterectomy in a dry box. Our model was superior to a 2-dimensional picture for the memorization of branching and positional relationships of the blood vessels. Comparison of our model with actual operative videos showed that the dry box provided an identical surgical view of an actual laparoscopic radical hysterectomy. We developed a peripheral bloodstream model of the uterus for repeated simulation of laparoscopic radical hysterectomy with an actual surgical view using a dry box.

Magnetic resonance imaging-based radiomics analysis of the differential diagnosis of ovarian clear cell carcinoma and endometrioid carcinoma: a retrospective study.

PURPOSE: To retrospectively evaluate the diagnostic potential of magnetic resonance imaging (MRI)-based features and radiomics analysis (RA)-based features for discriminating ovarian clear cell carcinoma (CCC) from endometrioid carcinoma (EC). MATERIALS AND METHODS: Thirty-five patients with 40 ECs and 42 patients with 43 CCCs who underwent pretherapeutic MRI examinations between 2011 and 2022 were enrolled. MRI-based features of the two groups were compared. RA-based features were extracted from the whole tumor volume on T2-weighted images (T2WI), contrast-enhanced T1-weighted images (cT1WI), and apparent diffusion coefficient (ADC) maps. The least absolute shrinkage and selection operator (LASSO) regression with tenfold cross-validation method was performed to select features. Logistic regression analysis was conducted to construct the discriminating models. Receiver operating characteristic curve (ROC) analyses were performed to predict CCC. RESULTS: Four features with the highest absolute value of the LASSO algorithm were selected for the MRI-based, RA-based, and combined models: the ADC value, absence of thickening of the uterine endometrium, absence of peritoneal dissemination, and growth pattern of the solid component for the MRI-based model; Gray-Level Run Length Matrix (GLRLM) Long Run Low Gray-Level Emphasis (LRLGLE) on T2WI, spherical disproportion and Gray-Level Size Zone Matrix (GLSZM), Large Zone High Gray-Level Emphasis (LZHGE) on cT1WI, and GLSZM Normalized Gray-Level Nonuniformity (NGLN) on ADC map for the RA-based model; and the ADC value, spherical disproportion and GLSZM_LZHGE on cT1WI, and GLSZM_NGLN on ADC map for the combined model. Area under the ROC curves of those models were 0.895, 0.910, and 0.956. The diagnostic performance of the combined model was significantly superior (p = 0.02) to that of the MRI-based model. No significant differences were observed between the combined and RA-based models. CONCLUSION: Conventional MRI-based analysis can effectively distinguish CCC from EC. The combination of RA-based features with MRI-based features may assist in differentiating between the two diseases.

Real prevalence of neural tube defects in Japan: How many of such pregnancies have been terminated?

The vital role of folic acid is to reduce the risk of having a neonate afflicted with neural tube defects. The prevalence of neural tube defects (myelomeningocele and anencephaly) has been reported in an incomplete form over the last 40 years in Japan. We aimed to evaluate the total number of neural tube defects including those delivered or terminated, to clarify the proportion of those terminated, and to internationally compare their prevalence. Through information on >311 000 deliveries obtained from 262 hospitals/clinics for 2 years of 2014 and 2015, we identified that the rate of total neural tube defects (termination of pregnancy, live births and stillbirths) was 8.29 per 10 000 deliveries for the year 2014 and was 8.72 for 2015, which were 1.5 and 1.6 times higher than the respective values (live births and stillbirths) reported. It is also observed that the ratio of the total number of myelomeningocele (termination of pregnancy, live births, and stillbirths) to that of anencephaly was approximately 1:1.2, that a half of pregnancies afflicted with neural tube defects were terminated, and that the proportion of termination of pregnancy due to myelomeningocele and due to anencephaly was 20% and 80%, respectively. Internationally, the real prevalence of neural tube defects in Japan was comparatively high, ranking fifth among the seven developed countries. In conclusion, the real prevalence of total neural tube defects was approximately 1.5 times higher than that currently reported by the Japan Association of Obstetricians and Gynecologists.

The association between p16 and Ki-67 immunohistostaining and the progression of cervical intraepithelial neoplasia grade 2.

OBJECTIVE: To compare the frequency of p16- and Ki-67-positive cells on immunohistostaining among women with progression, persistence, or regression of cervical intraepithelial neoplasia grade 2 (CIN2). METHODS: A retrospective study was conducted of women with CIN2 diagnosed by histology who were treated at a university hospital in Japan during 2004-2011. The immunostaining patterns for p16 and Ki-67 were analyzed and compared between patients with disease progression, persistence, or regression. Kaplan-Meier analysis was used to evaluate the progression rates stratified by immunostaining, and multivariate analysis of risk factors for progression was performed using the Cox proportional hazards model. RESULTS: The analysis included 59 women with progression, 35 women with persistence, and 28 women with regression. Deep p16 expression (staining in more than half of the cervical intraepithelial compartment) and positive Ki-67 staining in more than 50% of cells were significantly more common among women with progression than among those with regression. The risk factors for progression of CIN2 were deep p16 expression (P<0.001) and a Ki-67 ratio of more than 50% (P<0.001). CONCLUSION: Among women with CIN2, positive immunohistostaining for p16 and Ki-67 was strongly associated with disease progression.

Genetics of endometrial cancers.

Endometrial cancers exhibit a different mechanism of tumorigenesis and progression depending on histopathological and clinical types. The most frequently altered gene in estrogen-dependent endometrioid endometrial carcinoma tumors is PTEN. Microsatellite instability is another important genetic event in this type of tumor. In contrast, p53 mutations or Her2/neu overexpression are more frequent in non-endometrioid tumors. On the other hand, it is possible that the clear cell type may arise from a unique pathway which appears similar to the ovarian clear cell carcinoma. K-ras mutations are detected in approximately 15%-30% of endometrioid carcinomas, are unrelated to the existence of endometrial hyperplasia. A beta-catenin mutation was detected in about 20% of endometrioid carcinomas, but is rare in serous carcinoma. Telomere shortening is another important type of genomic instability observed in endometrial cancer. Only non-endometrioid endometrial carcinoma tumors were significantly associated with critical telomere shortening in the adjacent morphologically normal epithelium. Lynch syndrome, which is an autosomal dominantly inherited disorder of cancer susceptibility and is characterized by a MSH2/MSH6 protein complex deficiency, is associated with the development of non-endometrioid carcinomas.