Shun-Ichiro Izumi

Context: Achieving durable prolactinoma remission while preserving safe pregnancy remains a central unmet goal of cabergoline therapy. Objective: To prospectively evaluate individualized-dose cabergoline therapy for safe pregnancy, remission, and dosing optimization. Methods: Women with 310 prolactinomas comprised 97 bromocriptine (Bc)-resistant, 93 Bc-intolerant, and 120 naïve patients, harboring 56 large macroprolactinomas (≥20 mm), 80 small macroprolactinomas (≥10 mm), and 174 microprolactinomas. Cabergoline dosing was individualized to maintain nadir prolactin within the lowest achievable normal range. In 129 macroprolactinomas and 19 microprolactinomas at risk of gestational enlargement, medical debulking prophylactically restored the optic–pituitary (O–P) distance to >5.0 mm before conception. Cabergoline was discontinued immediately after conception. Results: Treatment achieved 100% biochemical normalization; 84-100% prepregnancy tumor debulking; 365 uneventful pregnancies in 294 patients (95%); no symptomatic tumor enlargement during pregnancy; and 72% postpartum remission overall (naïve 82%, Bc-resistant 70%, Bc-intolerant 61%; microprolactinomas 73%, macroprolactinomas 72%). Responder frequency was subtype-specific across 0.25-9.0 mg/week doses with distinct ED50 values ranging from 0.66 in Bc-intolerant to 3.71 in Bc-resistant patients. AIC-based multivariate analysis identified nadir prolactin—markedly lower in nonvisible than residual prolactinomas—as the dominant determinant of tumor disappearance. No cardiac valvulopathy or impulse control disorders were observed on longitudinal follow-up. Conclusion: Despite marked ED50 heterogeneity, nadir prolactin-guided individualized-dose cabergoline therapy safely achieved durable remission with excellent pregnancy outcomes. These findings establish a clinically actionable, outcome-directed framework that prospectively integrates endocrine normalization, anatomical risk reduction, and tumor eradication, rendering durable remission and safe pregnancy realistically achievable therapeutic objectives in prolactinomas.

After a FDA recommendation in April 2014, power morcellation (PM) in laparoscopic myomectomy (LM) has become less common. We now collect a myoma using manual morcellation (MM) from a wound in the umbilical region. In this study, we compared the PM and MM methods. The subjects were 69 patients who underwent LM from April 2013 to March 2016 using PM (n = 37) or MM (n = 32). With PM, the myoma was collected using a 4-hole 12-mm parallel trocar in the left lower abdomen. Using MM, an EZ ACCESSTM (2-cm skin incision) was placed on the umbilical region, and the myoma was put in a collection purse and guided into the access hole for MM using scissors under direct vision. None required allogeneic transfusion or a transition to open surgery, and had surgical or post surgical complications. At multiple linear regression analysis, which was adjusted by age, body mass index, and intraoperative blood loss, significant difference was not observed in operation time between the PM and MM groups. Manual morcellation was found to be a safe method for collection of myoma that prevents scattering of tissues and does not prolong the operation time.

Objective: To evaluate the reasons for nonreportable cell‐free DNA (cfDNA) results in noninvasive prenatal testing (NIPT), we retrospectively studied maternal characteristics and other details associated with the results.Methods: A multicenter retrospective cohort study in pregnant women undergoing NIPT by massively parallel sequencing (MPS) with failed cfDNA tests was performed between April 2013 and March 2017. The women's data and MPS results were analyzed in terms of maternal characteristics, test performance, fetal fraction (FF), z scores, anticoagulation therapy, and other details of the nonreportable cases.Results: Overall, 110 (0.32%) of 34 626 pregnant women had nonreportable cfDNA test results after an initial blood sampling; 22 (20.0%) cases had a low FF (z score. Among the women with nonreportable results because of altered genomic profile, the success rate of retesting using a second blood sampling was relatively low (25.0%‐33.3%). Thirteen (11.8%) of the women with nonreportable results had required hypodermic heparin injection.Conclusions: The classification of nonreportable results using cfDNA analysis is important to provide women with precise information and to reduce anxiety during pregnancy.

Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome is characterized by congenital absence of the vagina and uterus. We conducted genome-wide SNP analyses and exome sequencing to detect the causes of MRKH syndrome. We identified de novo variants of MYCBP2, NAV3, and PTPN3 in three families and a variant of MYCBP2 in a sporadic case. Here, we demonstrated the partial genetic makeup of Japanese MRKH syndrome.

Aim: The aim of this study was to provide medical terms to describe the condition of a girl who should be evaluated for primary amenorrhea in order to facilitate intervention at an appropriate time.Methods: We performed a literature and clinical guidelines search for recent practices with regard to menarche and discussed relevant cases that had been experienced by committee members. Additionally, we theoretically reviewed medical terms defined in the Glossary Book of Obstetrics and Gynecology in Japan (Japan Society of Obstetrics and Gynecology, 3rd edition).Results: The committee for the redefinition of primary amenorrhea proposed the introduction of two terms and the deletion of one term that had been defined by the Japan Society of Obstetrics and Gynecology, instead of changing the age definition of primary amenorrhea. ‘Delayed menarche’ was introduced to describe a condition in which a girl has never experienced cyclic menstruation (menarche) by 15–17 years of age. ‘Late menarche’ was also introduced to describe a condition in which a girl has experienced menarche at 15 years of age or older. ‘Delayed menstruation,’ which was defined as a condition in which a girl experiences menarche at 15–18 years of age, was deleted.Conclusion: The new terms ‘delayed menarche’ and ‘late menarche’ were introduced, and the term ‘delayed menstruation’ was deleted. The new system might help in the early detection and appropriate treatment of primary amenorrhea.

Aim: The purpose of this study was to report the 3‐year experience of a nationwide demonstration project to introduce non‐invasive prenatal testing (NIPT) of maternal plasma for aneuploidy, and review the current status of NIPT in Japan.Methods: Tests were conducted to detect aneuploidy in high‐risk pregnant women, and adequate genetic counseling was provided. The clinical data, test results, and pregnancy outcomes were recorded. We discuss the problems of NIPT on the basis of published reports and meta‐analyses.Results: From April 2013 to March 2016, 30 613 tests were conducted at 55 medical sites participating in a multicenter clinical study. Among the 30 613 women tested, 554 were positive (1.81%) and 30 021 were negative (98.1%) for aneuploidy. Of the 289, 128, and 44 women who tested positive for trisomies 21, 18, and 13, respectively, and underwent definitive testing, 279 (96.5%), 106 (82.8%), and 28 (63.6%) were determined to have a true‐positive result. For the 13 481 women with negative result and whose progress could be traced, two had a false‐negative result (0.02%). The tests were performed on the condition that a standard level of genetic counseling be provided at hospitals.Conclusion: Here, we report on the 3‐year nationwide experience with NIPT in Japan. It is important to establish a genetic counseling system to enable women to make informed decisions regarding prenatal testing. Moreover, a welfare system is warranted to support women who decide to give birth to and raise children with chromosomal diseases.

Japanese physicians prescribe Kampo medicine, but Kampo education is not standardized. We surveyed training hospitals and residents to identify problems and suggest solutions to promote Kampo education during and after residency. This was a double questionnaire survey of 1011 training hospitals in Japan and 93 Tokai University School of Medicine graduates of 2011. There were 816 effective responses (81%) from the training hospitals. Most instructors (84%) thought physicians should have Kampo clinical skills; 67% thought positively about introducing Kampo education into clinical training; 23% of the hospitals provided Kampo education; 70% of instructors at hospitals without Kampo education indicated the lack of Kampo instructors, 16% lack of time, and 7% no necessity for Kampo education; hospitals permitted Kampo education through voluntary study (42%), lectures sponsored by Kampo manufacturers (35%), and study sessions with other hospitals (32%); independent study sessions (10%); smaller hospitals were less active in Kampo education than larger ones. The survey of residents had 72 effective responses (77%): 91% were interested in Kampo medicine; 96% thought it worth learning; 31% could learn it during residency; 52% were not satisfied with the training, 83% wanted to learn it; 73% thought it should be introduced into the curricula; 93% prescribed Kampo medicine, and residents who learned it prescribed it more; 48% were reluctant to prescribe it after residency; 89% thought Western and Kampo medicine should be integrated. Instructors knew Kampo education was needed, but little of it was taught, especially in small hospitals, because of the lack of Kampo instructors. Residents recognized the need for Kampo medicine and were motivated to learn it. Kampo medicine was mostly prescribed because instructors suggested it. Because of the limited opportunities to learn Kampo medicine, it should be taught during residency. In small hospitals, cooperation with other hospitals could be a solution to teach Kampo medicine.

The objective of the present study is to conduct a retrospective analysis comparing graduate-entry program (GEP) and school-leaver-entry program (SEP) students from the perspective of scholastic achievements from admission through the national examination for medical practitioners. The number of students who repeated one or more years, because of their poor results on examinations, the scores of graduation examinations, and the pass rates for the national examination for medical practitioners were compared, retrospectively, over the last 8 academic years between GEP and SEP students at Tokai University School of Medicine. The ratio of students who graduated in the prescribed course length was significantly higher (p = 0.002) in GEP students than that in SEP students. There were no differences between the average scores on the graduation examinations for GEP and SEP students, except in two academic years. The pass rate of GEP students (97%) of the national examination for medical practitioners was significantly higher (p < 0.001) than that of SEP students (89%). These results suggest that GEP students are more favorable candidates in terms of becoming physicians in the usualprescribed number of years than SEP students.