生水 真紀夫

BACKGROUNDS: In 2013, the total number of obstetrician-gynecologists decreased. The Japanese Society of Obstetrics and Gynecology established the Obstetrics and Gynecology MIRAI Committee in 2015. Within the MIRAI Committee, Japanese Trainees in Obstetrics and Gynecology (JTOG) was established; it was comprised of 20 promising young obstetrician-gynecologists recommended from regions across Japan. The office term is 2 years. OBJECTIVE: The purpose of this report is to learn and inform about the results of MIRAI's activities. METHODS: We surveyed the trends in new obstetrician-gynecologists and also matched each seminar participant with them. RESULT: The number of new memberships has been increasing since the nadir in 2016. In particular, there are over 100 more new physicians specializing in the field in 2020 than there were at the nadir in 2016. It was revealed that approximately 50% of the participants in the summer school specialized in obstetrics and gynecology. Furthermore, approximately 70% of POP2 participants specialized in obstetrics and gynecology, which shows that these two recruitment seminars are extraordinarily effective events that result in an increase in the number of new obstetricians and gynecologists. CONCLUSION: We conclude that the activities of this MIRAI Committee and JTOG have been effective. With the spread of COVID-19 and the inability of obstetrician-gynecologists and students/clinical trainees to perform social distancing, it is currently difficult to hold hands-on seminars. However, we hope that new JTOG members will be able to create a new seminar format.

The clinical significance of carbon-ion radiotherapy (CIRT) for adenocarcinoma (AC) of the uterine cervix has been assessed in several single-institutional studies. To validate the significance, we conducted a multi-institutional survey of CIRT for locally advanced AC (LAAC) of the uterine cervix. We retrospectively analyzed the clinical outcomes of patients with stage IIB-IVA LAAC of the uterine cervix who underwent chemo-CIRT or CIRT alone between April 2010 and April 2016. Patients received 74.4 Gy (relative biological effectiveness [RBE]) in 20 fractions of CIRT or 55.2 Gy (RBE) in 16 fractions of CIRT plus three sessions of brachytherapy. Patients aged ≤ 70 years with adequate bone marrow and organ function were administered cisplatin weekly (40 mg/m2 per week for up to 5 weeks). Fifty-five patients were enrolled in this study. The median follow-up period was 67.5 months. The 5-year overall survival (OS) and local control (LC) rates were 68.6% and 65.2%, respectively. Multivariate analysis showed that the initial tumor response within 6 months was significantly associated with LC and OS. The present study represents promising outcomes of CIRT or chemo-CIRT for LAAC of the uterine cervix, especially in the cases showing initial rapid regression of the tumor.

Aim: To provide information including the trend of gynecological malignancies in Japan, we hereby present the Annual Patient Report for 2017 and the Annual Treatment Report for 2012, on the outcomes of patients who started treatment in 2012. Methods: The Japan Society of Obstetrics and Gynecology maintains an annual tumor registry, where information on gynecological malignancies from various participating institutions is gathered. The data of patients whose treatment with gynecologic malignancies was initiated in 2017 were analyzed retrospectively. Survival of the patients who started treatment with cervical, endometrial and ovarian cancer in 2012 was analyzed by using the Kaplan-Meier, log-rank and Wilcoxon tests. Results: Treatment was initiated in 2017 for 7710 patients with cervical cancer; 11 120 with endometrial cancer; 7029 with ovarian, tubal and peritoneal cancer; 2164 with ovarian borderline tumors; and with the others (213 vulvar cancer, 139 vaginal cancer, 366 uterine sarcoma, 41 uterine adenosarcoma and 131 trophoblastic diseases). This clinicopathological information was summarized as the patient annual report. The 5-year survival rates of the patients with cervical cancer were 92.9, 75.5, 58.2 and 26.7% for stages I, II, III and IV, respectively. The 5-year survival rates for the patients with endometrial cancer were 93.6, 85.6, 72.6 and 27.3% for stages I, II, III and IV, respectively. The 5-year survival rates for the patients with ovarian cancer (surface epithelial-stromal tumors) were 92.5, 83.5, 49.5 and 30.8% for stages I, II, III and IV, respectively. Conclusion: The annual tumor report is an important survey that provides knowledge on gynecological malignancy trends in Japan.

AIM: The Ministry of Health, Labour, and Welfare of Japan proposed a regulation of overtime work as a reform in work style. However, the regulation may deteriorate the quality of medical services due to the reduction in training time. Thus, the study aimed to reveal perceptions in terms of generation gaps in views on self-training and overtime work, among members of the Japan Society of Obstetrics and Gynecology (JSOG). METHODS: A web-based, self-administered questionnaire survey was conducted among members of the JSOG. In total, 1256 respondents were included in the analysis. Data were collected on age, sex, experience as a medical doctor, location of workplace, work style, the type of main workplace, and number of full-time doctors in the main workplace. The study examined the attitudes of the respondents toward overtime work and self-training. The respondents were categorized based on experience as a medical doctor. RESULTS: According to years of experience, 112 (8.9%), 226 (18.0%), 383 (30.5%), 535 (42.6%) doctors have been working for ≤5, 6-10, 11-19, and ≥ 20 years, respectively. Although 54.5% of doctors with ≤5 years of experience expected the regulation on working hours to improve the quality of medical services, those with ≥20 years of experience expressed potential deterioration. After adjusting for covariates, more years of experience were significantly related with the expectation of deterioration in the quality of medical services. CONCLUSIONS: The study revealed a generation gap in the views about self-training and overtime work among obstetricians and gynecologists in Japan.

When transplacental therapy is conducted, the maternal serum concentrations of digoxin and flecainide may fluctuate throughout third trimester. Therefore, TDM may be effective in improving the efficacy and safety of treatment.

BACKGROUND: To investigate whether rectosigmoid colectomy can improve the prognosis of patients with early-stage ovarian cancer when the ovarian tumor adheres to the rectum. METHODS: We retrospectively studied 210 consecutive patients with stage I/II ovarian cancer treated between 2000 and 2016. The surgical strategy differed between the periods 2000-2007 and 2008-2016 with respect to adhesion between the ovarian tumor and rectum. In the former period, ovarian tumor was exfoliated from the rectum. Only when the residual tumor was apparently observed on the rectal surface after salpingo-oophorectomy with hysterectomy, it was subsequently removed by colorectal surgeons performing rectosigmoid colectomy. In the latter period, the ovarian tumor was resected en bloc with the rectum by performing rectosigmoid colectomy. We compared the progression-free survival (PFS) between the two treatment periods. RESULTS: Rectosigmoid colectomy was performed more frequently in the latter period than in the former period (43 patients, 31% vs. 6 patients, 8%, p < 0.001). There was no significant difference in complete resection rate between the two periods (97% in the former period, 99% in the latter period, p = 0.278). However, the 5-year PFS rate was significantly higher in the latter period than in the former period (86.0% vs. 74.4%, log-rank test, p = 0.034). Multivariate Cox proportional-hazards regression analysis indicated that disease stage (hazard ratio [HR], 2.87, 95% confidence interval [CI] 1.14-7.34) and treatment period (HR 0.32, 95% CI 0.14-0.73) were independent risk factors for recurrence. CONCLUSIONS: Rectosigmoid colectomy could improve the prognosis of patients with early-stage ovarian cancer when the ovarian tumor adheres to the rectum.

A complete hydatidiform mole (CHM) is a conceptus with only sperm-derived chromosomes. Here, we report on a CHM with genomic DNA identical to that of the paternal somatic cells. The CHM developed in a woman who had undergone intrauterine implantation of a blastocyst obtained through in vitro injection of a presumed round spermatid into one of her oocytes. The CHM was genetically identical to peripheral white cells of her husband and contained no maternally derived nuclear DNA. We hypothesize that a spermatogonium, rather than a round spermatid, was inadvertently selected for the procedure. The CHM developed into a gestational trophoblastic neoplasia, which resolved after chemotherapy. (Funded by the Japan Society for the Promotion of Science.).

BACKGROUND: This study aimed to evaluate the safety and efficacy of weekly paclitaxel and cisplatin chemotherapy (wTP) in patients with ovarian cancer who developed carboplatin hypersensitivity reaction (HSR). METHODS: We retrospectively investigated 86 patients with ovarian, fallopian tube, and peritoneal carcinoma who developed carboplatin HSR during previous chemotherapy (carboplatin and paclitaxel) at our institution between 2011 and 2019. After premedication was administered, paclitaxel was administered over 1 h, followed by cisplatin over 1 h (paclitaxel 80 mg/m2; cisplatin 25 mg/m2; 1, 8, 15 day/4 weeks). We investigated the incidence of patients who successfully received wTP for at least one cycle, treatments compliance, progression-free survival (PFS), and overall survival (OS). RESULTS: The median number of wTP administration cycles was 4 (Interquartile Range IQR, 3-7), 71 patients (83%) successfully received wTP, and 15 patients (17%) developed cisplatin HSR. The efficacy of treatment was as follows: 55 (64%) patients completed the scheduled wTP, 9 (10%) patients discontinued due to HSR to cisplatin within 6 cycles, 1 (1%) patient discontinued due to renal toxicity (grade 2) at the 6th cycle, and 21 (24%) patients discontinued due to progressive disease within 6 cycles. The median PFS and OS after administration of wTP were 10.9 months (95% CI: 7.7-17.7) and 25.9 months (95% CI: 19.0-50.2), respectively. CONCLUSIONS: wTP was safe and well-tolerated in patients who developed carboplatin HSR.

AIM: In Japan, most of the patients with primary amenorrhea or related conditions, such as delayed menarche, are diagnosed by pediatricians or gynecologists; accordingly, the number of the patients and the ratio of the causes were unclear. To clarify them, we conducted a nationwide survey in both the departments for the first time. METHODS: We sent a questionnaire about the patients with chief complaint of no menarche whose first visit was from January 2015 to December 2017, to 596 training institutions for specialist physicians of the Japan Society of Obstetrics and Gynecology and 152 facilities to which councilors of the Japanese Society for Pediatric Endocrinology belong. RESULTS: We received replies from 283 (37.8%) institutions. During the 3 years, 1043 patients first visited pediatrics or gynecology for no menarche. In 303 patients under 16 years old at the first visit, 177 (58.4%) patients had menarche by the age of 16. Of them, 41 (13.5%) patients had menarche spontaneously. Among 308 patients aged 16 to 17 at the first visit, 216 patients were 18 years or older at the survey. Of them, 124 (57.4%) patients had menarche by the age of 18, and 21 (9.7%) of them had menarche spontaneously. The causes of amenorrhea were detected in 462 patients. Abnormal karyotype including Turner syndrome was the most common at 122 (26.4%), followed by Mullerian agenesis at 73 (15.8%). CONCLUSIONS: The first national survey revealed the number and causes of primary amenorrhea and related conditions. This report will provide better information for clinicians.

膀胱腟瘻は、長期の経過で瘻孔内に石灰化を伴う結石を形成し、帯下異常や腹痛、慢性膀胱炎を呈することがある。今回、17歳時に子宮奇形による月経モリミナに対し子宮全摘が行われ、術後35年を経過して、膀胱腟瘻と瘻孔内結石が発見された症例を経験したので報告する。患者は53歳で、思春期に子宮頸部低形成による月経モリミナ症状があり、15歳で子宮頸部形成術、17歳時に子宮全摘術の既往があった。52歳頃から腟奥の仙痛、帯下増加、就寝中の尿失禁、慢性的な膀胱炎症状が出現し、近医で抗菌薬が繰り返し投与されていた。53歳で骨盤内腫瘍を指摘され当科に紹介された。腟断端の頭側に長径4cm大の骨様硬の石灰化腫瘤を認め、同部位に圧痛を認めた。また、この腫瘤の最下端で腟断端に位置する2mmの瘻孔から膿の流出を認め、異常帯下の原因と考えられた。骨盤部CTで膀胱内に遊離ガスを認めたが、膀胱造影や膀胱鏡検査では膀胱腟瘻を確認することはできなかった。症状の改善を目的として開腹による腫瘤摘出術を施行したところ、腫瘤は後腹膜腔の腟断端頭側で膀胱壁や直腸壁と強固に癒着していた。細断しながら摘出した腫瘤はリン酸マグネシウムアンモニウム結石であり、膀胱腟瘻に伴う瘻孔内結石と診断した。手術直後は尿失禁と腟断端からの尿流出を認めたが、膀胱充満を避けることで尿失禁は改善され、患者の腟奥の仙痛や帯下の訴えもなくなった。膀胱腟瘻は子宮全摘術後の合併症の一つであるが、子宮や腟の先天奇形を有する女性ではとくにリスクが高いと考えられる。また、長期間の経過で腟内異物や腟腫瘍と鑑別を要する瘻孔内結石を形成する可能性を念頭に置く必要がある。(著者抄録)

OBJECTIVE: We investigated the efficacy and toxicity of tailored-dose chemotherapy with gemcitabine and irinotecan for platinum-refractory/resistant ovarian or primary peritoneal cancer. METHODS: We enrolled patients with ovarian or primary peritoneal cancer who received ≥2 previous chemotherapeutic regimens but developed progressive disease during platinum-based chemotherapy or within 6 months post-treatment. All patients received gemcitabine (500 mg/m²) and irinotecan (50 mg/m²) on days 1 and 8 every 21 days at the starting dose. The dose was increased or decreased by 4 levels in subsequent cycles based on hematological or non-hematological toxicities observed. The primary endpoint was progression-free survival (PFS), and secondary endpoints were disease control rate (DCR), overall survival (OS), and adverse events. RESULTS: We investigated 25 patients who received 267 cycles (median 8 cycles/patient) between October 2008 and May 2011. Tailored-dose gemcitabine was administered up to the 5th cycle as follows: 1,000 mg/m² in 1 (4%), 750 mg/m² in 16 (64%), 500 mg/m² in 6 (24%), and 250 mg/m² in 2 patients (8%). The median PFS and OS were 6.2 months (95% confidence interval [CI]=2.7-10.7) and 16.8 months (95% CI=9.4-30.7), respectively. The DCR was 76%, and PFS was >6 months in 12 of 25 patients (48%). Grade 3 hematological toxicities included leukopenia (9.4%), neutropenia (11.2%), anemia (9.8%), and thrombocytopenia (1.1%). Grade 3/4 non-hematological toxicities did not occur except for fatigue in one patient. CONCLUSIONS: Tailored-dose chemotherapy with gemcitabine and irinotecan was effective and well tolerated in patients with platinum-refractory/resistant ovarian or primary peritoneal cancer. TRIAL REGISTRATION: UMIN Clinical Trials Registry Identifier: UMIN000004449.

© 2020 American Society for Reproductive Medicine Objective: To evaluate timing and a prediction model for pregnancy in early-stage cervical cancer patients who underwent fertility-sparing trachelectomy. Design: Retrospective cohort. Setting: Academic multicenter. Patient(s): Women ages <45 years with clinical stage I–II cervical cancer were enrolled between 2009 and 2013 (n = 393). Intervention(s): Planned fertility-sparing trachelectomy. Main Outcome Measure(s): Cumulative incidences and clinicopathological characteristics of those who developed subsequent pregnancy were examined. Result(s): There were 77 (21.6%) women who had subsequent pregnancies after fertility-sparing trachelectomy with 1-, 2-, and 5-year cumulative pregnancy rates of 2.8%, 6.2%, and 17.4%, respectively. The median time to develop subsequent pregnancy was 3.2 years. In a competing risk analysis, women had a higher risk of recurrent cancer than conception during the first 11 months postsurgery. On multivariable analysis, younger age, being married, and postoperative reproductive treatment were independently associated with an increased chance of developing a subsequent pregnancy. The subsequent pregnancy index (SPI) score to predict the likelihood of having pregnancy was proposed, and it was calculated based on age, marital status, and reproductive treatment (2, 2, and 4 points, respectively). Women with a higher SPI score had significantly higher subsequent pregnancy rates (5-year pregnancy rate; the score was 3 in 4.7% of cases; 4 to 5 in 11.3%; 6 to 7 in 27.4%; and 8 in 50.8%), but they had similar recurrence rates (5.0%). Conclusion(s): The SPI score proposed in our study is useful in predicting subsequent pregnancy in women with early-stage cervical cancer undergoing fertility-sparing trachelectomy.

We examined whether the extent of initial peritoneal dissemination affected the prognosis of patients with advanced ovarian, fallopian tube, and peritoneal carcinoma when initially disseminated lesions > 1 cm in diameter were removed, regardless of the timing of aggressive cytoreductive surgery. The extent of peritoneal dissemination was assessed by the peritoneal cancer index (PCI) at initial laparotomy in 186 consecutive patients with stage IIIC/IV. Sixty patients underwent primary debulking surgery and 109 patients underwent neoadjuvant chemotherapy followed by interval debulking surgery. Seventeen patients could not undergo debulking surgery because of disease progression during neoadjuvant chemotherapy. The median initial PCI were 17. Upper abdominal surgery and bowel resection were performed in 149 (80%) and 171 patients (92%), respectively. Residual disease ≤ 1 cm after surgery was achieved in 164 patients (89%). The initial PCI was not significantly associated with progression-free survival (PFS; p = 0.13) and overall survival (OS; p = 0.09). No residual disease and a high-complexity surgery significantly prolonged PFS (p < 0.01 and p = 0.02, respectively) and OS (p < 0.01 and p ≤ 0.01, respectively). The extent of initial peritoneal dissemination did not affect the prognosis when initially disseminated lesions > 1 cm were resected.

OBJECTIVES: Complete hydatidiform moles (CHMs) are androgenetic and have a high rate of progression to gestational trophoblastic neoplasia (GTN). CHMs are negative when immunostained for p57KIP2 protein, the product of the maternally expressed gene on chromosome 11p15.5, whereas biparental partial hydatidiform moles and hydropic abortion are positive for p57KIP2. This study presents two cases of p57KIP2-positive androgenetic CHMs and explores the cause of this inconsistency. METHODS: Androgenetic CHMs were diagnosed using multiplex short tandem repeat polymorphism analysis. Single-nucleotide polymorphism arrays were performed for molecular karyotyping. RESULTS: Among the consecutive 188 androgenetic CHMs, two cases were positive for p57KIP2. The first case remitted spontaneously, whereas the second case developed into low-risk GTN. The first case was positive for p57KIP2 in all villi. The karyotype was 48,XX,+7,+11, with the additional chromosome 11 confirmed to be of maternal origin. The second case presented a mosaic of both positively and negatively stained villi. The karyotype was 46,XX. CONCLUSIONS: The cause of one of the CHMs was trisomy with an additional maternal chromosome 11. Although rare, the confirmation of p57KIP2-positive androgenetic CHM status is necessary to manage GTN risk.

原発性卵巣腫瘍と転移性卵巣腫瘍では治療法や予後が異なるため鑑別が重要であるが,術前診断に苦慮する.今回,多房性嚢胞性腫瘍を呈した転移性卵巣腫瘍を2例経験した.症例1:81歳女性.X年6月に肝内胆管癌(高分化腺癌,Stage II)の手術を受けた.術後化学療法中のX+1年4月下腹部膨隆感があり,両側卵巣に多房性嚢胞性腫瘍を指摘され,当科紹介となった.MRI検査で粘液性腺腫が疑われ,腹腔鏡補助下両側付属器切除術を施行した.術後病理診断は肝内胆管癌の卵巣転移であった.症例2:37歳女性.Y年3月に肝内胆管癌(中〜高分化型腺癌,Stage IV)の手術を受けた.術後化学療法後,経過観察されていた.Y+1年6月に下腹部痛のため近医を受診し,卵巣嚢腫を指摘され当科紹介となった.超音波検査で両側卵巣に多房性嚢胞性腫瘤を認め粘液性腺腫を疑った.子宮頸部細胞診でAGCを検出したため,頸部と内膜組織診を施行し高分化型腺癌を検出した.肝内胆管癌の転移を疑い,子宮全摘+両側付属器切除術を施行した.術後病理診断は肝内胆管癌の卵巣・子宮転移であった.今回の2例のように,肝内胆管癌の卵巣転移は多房性嚢胞性腫瘍を呈する可能性があるため,肝内胆管癌既往の多房性卵巣腫瘍症例では,再発や転移の可能性を念頭におく必要があると考えられた.(著者抄録)

Purpose: Polycystic ovary syndrome (PCOS) is a risk factor for the development of endometrial cancer (EC). To the present authors' knowledge, no study has clarified whether pre-existing PCOS is a prognostic factor for post-surgical EC recurrences. The aim of this study was to determine whether pre-existing PCOS is a risk factor for the recurrence of EC even after the surgical treatment of EC in premenopausal women. Materials and Methods: The authors performed a retrospective cohort study on premenopausal EC patients aged 50 years or younger who underwent surgery at this hospital between 2009 and 2013. The median follow-up period was 65.5 months. Results: Of 46 patients with EC, nine (19.6%) had PCOS. Four of the nine PCOS patients developed recurrence of EC, three of whom died of the disease, whereas only one of 37 patients who did not have PCOS developed EC recurrence (44.4% and 2.7%, respectively p = 0.003). Univariate analysis showed that the progression-free and overall survival of the patients with pre-existing PCOS was worse than that of patients without pre-existing PCOS (p = 0.008 and p = 0.029, respectively). Multivariate analysis revealed that PCOS was a poor prognostic factor for progression-free survival and a marginal poor prognostic factor for overall survival (p = 0.011 and p = 0.061, respectively). Conclusions: Pre-existing PCOS was a risk factor for recurrence in premenopausal post-operative patients with EC aged 50 years or younger.

Complete hydatidiform moles (CHMs) comprise a proliferative trophoblastic disorder and are known to be androgenetic and diploid. Androgenetic CHMs are classified as having monospermic and dispermic origins. Rarely, some CHMs have other genetic constitutions, such as biparental diploid or tetraploid. Previous studies have shown the possibility that androgenetic heterozygous CHMs have an additional chromosome with high frequency. This study aimed to comprehensively analyse the molecular karyotyping of androgenetic dispermic CHMs and the parental contribution of their additional chromosomes. Single-nucleotide polymorphism arrays were performed with the genomic DNA of CHMs and patients. The B allele frequency and selected B allele frequency plotting of CHM were visualised. Among the 31 dispermic CHMs, eight showed trisomy and one showed double trisomy; of the 10 additional chromosomes, seven were of maternal original and three were of paternal origin. In addition, three disomic chromosomes comprised one maternal and one paternal chromosome, although these should theoretically have had two paternal chromosomes in the case of androgenetic CHMs. The subclassification of heterozygous CHMs, with or without maternal contribution, is a new approach and could be a candidate indicator of gestational trophoblastic neoplasia risk.