生水 真紀夫

OBJECTIVE: Therapy-related myeloid neoplasms (t-MNs) are often fatal and arise as late complications of previous anticancer drug treatment. No single-center case series has examined t-MNs in epithelial ovarian cancer (EOC). METHODS: All patients with EOC treated at Chiba University Hospital between 2000 and 2021 were included. We retrospectively analyzed the characteristics, clinical course, and outcomes of patients who developed t-MNs. RESULTS: Among 895 cases with EOC, 814 cases were treated with anticancer drugs. The median follow-up period was 45 months (interquartile range, 27-81) months. Ten patients (1.2%) developed t-MNs (FIGO IIIA in one case, IIIC in three, IVA in one, and IVB in five). Nine patients were diagnosed with myelodysplastic syndrome and one with acute leukemia. One patient with myelodysplastic syndrome developed acute leukemia. The median time from the first chemotherapy administration to t-MN onset was 42 months (range, 21-94 months), with t-MN diagnoses resulting from pancytopenia in four cases, thrombocytopenia in three, and blast or abnormal cell morphology in four. The median number of previous treatment regimens was four (range, 1-7). Paclitaxel + carboplatin therapy was administered to all patients, gemcitabine and irinotecan combination therapy to nine, bevacizumab to eight, and olaparib to four. Six patients received chemotherapy for t-MN. All patients died (eight cancer-related deaths and two t-MN-related deaths). None of the patients was able to restart cancer treatment. The median survival time from t-MN onset was 4 months. CONCLUSIONS: Patients with EOC who developed t-MN were unable to restart cancer treatment and had a significantly worse prognosis.

Twelve years after the first edition of The Guideline for Gynecological Practice, which was jointly edited by The Japan Society of Obstetrics and Gynecology and The Japan Association of Obstetricians and Gynecologists, the 5th Revised Edition was published in 2023. The 2023 Guidelines includes 5 additional clinical questions (CQs), which brings the total to 103 CQ (12 on infectious disease, 30 on oncology and benign tumors, 29 on endocrinology and infertility and 32 on healthcare for women). Currently, a consensus has been reached on the Guidelines, and therefore, the objective of this report is to present the general policies regarding diagnostic and treatment methods used in standard gynecological outpatient care that are considered appropriate. At the end of each answer, the corresponding Recommendation Level (A, B, C) is indicated.

Immunostaining with p57KIP2 is a widely used diagnostic technique to differentiate complete hydatidiform moles (CHMs) from partial hydatidiform moles (PHM) and non-molar hydropic abortion. However, distinguishing between PHMs and non-molar hydropic abortions using histopathology alone is often challenging. This study aimed to evaluate the technical validity and additional benefits of using fluorescence in situ hybridization (FISH) in combination with p57KIP2 immunostaining to diagnose molar and non-molar conceptuses. The study involved 80 specimens, which underwent genetic diagnosis using short tandem repeat analysis, including 44 androgenetic CHMs, 20 diandric monogynic PHMs, 14 biparental non-molar hydropic abortions, 1 monoandric digynic triploid abortion, and 1 vaginal specimen of gestational trophoblastic neoplasia. Two pathologists independently diagnosed the cases based on morphology and p57KIP2 immunostaining while the clinical information was masked. FISH analysis was performed using 3 probes (CEP17, CEPX, and CEPY), which revealed that all androgenetic CHM and biparental diploid non-molar hydropic abortion specimens were diploid. Among the 20 diandric monogynic PHM cases examined by analyzing short tandem repeat polymorphisms, 18 were triploid, and the remaining 2 were diploid. These two specimens were possibly androgenetic/biparental mosaics based on FISH analysis, where the three-signal ratios counting 50 cells were clearly within the diploid ranges. Eight of the 20 genetic PHMs and 2 of the 14 genetically confirmed non-molar hydropic abortions that were falsely diagnosed based on morphology and immunohistochemistry by at least 1 pathologist were correctly diagnosed as PHM and non-molar hydropic abortion, respectively, by FISH analysis. However, 1 monoandric digynic villus was classified as triploid by FISH analysis, leading to a false PHM diagnosis. In conclusion, the combination of FISH analysis with p57KIP2 immunostaining helps in diagnosing molar and non-molar conceptuses in numerous cases; nevertheless, exceptional cases should be considered.

BACKGROUND/AIM: Single-agent chemotherapy typically has curative outcomes in patients with low-risk gestational trophoblastic neoplasia (GTN). Although surgical intervention is a potential alternative, its efficacy in these patients remains unclear. This report describes a case in which surgical excision of a uterine polypoid lesion resolved chemotherapy-resistant low-risk GTN. CASE REPORT: A 43-year-old patient received pulse actinomycin D treatment for post-molar low-risk GTN without extrauterine metastasis. However, the patient showed resistance to the chemotherapy regimen. There was no initial evidence of protrusion of GTN into the uterine cavity; however, a polypoid lesion grew into the uterine cavity during therapy. This growth was successfully excised via a transvaginal approach using forceps with minimal blood loss. There was a postoperative decrease in human chorionic gonadotropin levels, which ultimately reached the predetermined threshold without the need for changing the therapeutic protocol. CONCLUSION: Surgical resection should be considered a viable therapeutic strategy for uterine polypoid growth in chemotherapy-resistant low-risk GTN.

BACKGROUND: Although abdominal or hysteroscopic metroplasty for septate uterus is considered to reduce pregnancy loss and increase the take-home baby (THB) rate in women with a history of recurrent pregnancy loss, there exists an inherent risk of impaired fertility. This study aimed to clarify the reproductive outcomes of women with septate uterus who underwent abdominal and hysteroscopic metroplasty in a single center. METHODS: This retrospective observational study enrolled 27 women who underwent metroplasty between 2007 and 2019. The analysis included women with septate uterus [European Society of Human Reproduction and Embryology (ESHRE)/European Society for Gynaecological Endoscopy (ESGE) type U2)] or septate-bicornuate uterus (ESHRE/ESGE type U3b) who underwent either abdominal or hysteroscopic metroplasty. Women who did not have an immediate desire to conceive were excluded from the analysis. As a rule, we recommended pregnancy without surgery for women who had not experienced repeated pregnancy loss. Abdominal metroplasty (ABM) was performed using the modified Tompkins' method and hysteroscopic metroplasty was performed using hysteroscopic transcervical resection of the septum [transcervical metroplasty (TCM)]. The conception ratio was calculated as the number of women who achieved ≥ 1 conception/total number of women, the pregnancy loss ratio was calculated as the number of women who experienced ≥ 1 pregnancy loss/the number of women who conceived, and the THB ratio was calculated as the number of women who achieved ≥ 1 THB/total number of women. RESULTS: Seventeen women underwent ABM and 10 women underwent TCM. Thirty-three conceptions and 26 babies were taken home after surgery. ABM did not change the ≥ 1 conception ratio (76% vs. 83% before and after surgery, respectively; RR = 1.08, p = 0.80). Meanwhile, ABM decreased the ≥ 1 pregnancy loss ratio (100% vs. 36%, RR = 0.36, p < 0.001) and increased the ≥ 1 THB ratio (12% vs. 71%, RR = 6.00, p < 0.01). Similarly, TCM did not change the ≥ 1 conception ratio, decreased the ≥ 1 pregnancy loss ratio, and increased the ≥ 1 THB ratio. CONCLUSIONS: Both abdominal and hysteroscopic metroplasty for septate uterus increased the THB rate by preventing pregnancy loss without affecting the chance of pregnancy. TRIAL REGISTRATION: Not applicable.

AIM: To identify the symptoms and relevant factors associated with acute adrenal insufficiency of early-onset Sheehan syndrome. METHODS: We retrospectively reviewed the charts of 125 women admitted to our intensive care unit because of postpartum hemorrhage between January 2011 and December 2021. Three women developed acute adrenal insufficiency. We investigated the total blood loss, shock status, consciousness level upon arrival, and intensive care provided to the women. We also analyzed the symptoms and laboratory data that led to the diagnosis of acute adrenal insufficiency. Continuous variables were presented by median (minimum-maximum). RESULTS: The medians and ranges of age, total blood loss, and shock index [heart rate/systolic blood pressure] on admission were 33.1 (17.2-45.3) years, 3351 (595-20 260) g, and 0.94 (0.55-2.94), respectively. Seven women were older than 40 years, 28 experienced >5000 g blood loss, 17 had shock index >1.5, 27 had impaired consciousness upon arrival, and 15 underwent hysterectomy. Women who developed acute adrenal insufficiency were <40 years old and had a bleeding volume of over 5000 g, impaired consciousness upon arrival, and had undergone hysterectomy. They had experienced lactation failure, presented with hyponatremia-related symptoms on postpartum days 8-9, experienced general malaise, headache, and impaired consciousness, and showed severe hyponatremia. CONCLUSIONS: Massive postpartum hemorrhage over 5000 g, impaired consciousness upon arrival, and hysterectomy as a hemostatic measure were relevant factors associated with acute adrenal insufficiency of early-onset Sheehan syndrome. Hyponatremia-related symptoms occurring after lactation failure are indicative of the onset of acute adrenal insufficiency.

Uterine fibroids (UFs) are benign tumors arising from the uterus, characterized by accumulation of abundant extracellular matrix (ECM) and sex steroids dependent growth. Women with symptomatic UFs have reduced quality of life and decreased labor productivity. Among the driver gene mutations identified in UFs, mutations in MED12, a component of the cyclin-dependent kinase (CDK) Mediator module, are the most common and observed in 50-80% of UFs. They are gain-of-function mutations and are more frequently observed in Black women and commonly observed even in small UFs. MED12 mutation-positive UFs (MED12-UFs) often develop multiple rather than solitary UFs and have distinct gene expression profiles, DNA methylomes, transcriptomes, and proteomes. Gene expressions related to ECM organization and collagen-rich ECM components are upregulated, and impaired Mediator kinase activity and dysregulation of Wnt/β-catenin signaling are identified in MED12-UFs. Clinically, the UF shrinking effect of gonadotropin-releasing hormone agonists and ulipristal acetate is dependent on the MED12 mutation status. Understanding of characteristics of MED12-UFs and functions of MED12 mutations for UF tumorigenesis may elucidate the pathophysiology of UFs, leading to the development of new therapeutic options in women with symptomatic UFs.

OBJECTIVE: To clarify the reproductive outcomes of women who underwent abdominal repair surgery for cesarean scar defect (CSD). STUDY DESIGN: This is a retrospective observational study performed in a tertiary center. We retrospectively reviewed 20 women who underwent abdominal repair between 2007 and 2021. The indication for the repair was a minimal residual myometrial thickness (RMT) of ≦3.0 mm. We investigated surgical complications, changes in minimal RMT before and three-months after the repair, and reproductive outcomes. RESULTS: The median age at the time of repair was 36 years (27-40), with a median body mass index of 21.0 (17.7-28.7) and a median of 1 prior cesarean section (1-5). Twelve women reported secondary infertility, while eight women were concerned about the potential risk of uterine rupture in future pregnancies due to thin RMT. Additionally, one woman had a co-existing vesicouterine fistula, two had abscess and hematoma formation at the precedent cesarean section, and three showed remarkable dehiscence of the defect. The median minimal RMT significantly increased to 5.05 mm (range; 2.5-14.2 mm) after the repair. Seven women had a total of eight live births, with a median duration from the repair to a live-birth pregnancy of 11.5 months (range; 4-20 months). No surgical complications occurred during the repair, and there were no instances of uterine rupture in subsequent pregnancies. However, one woman who became pregnant with twins following double blastocyst transfer required a cesarean section at 25 weeks of pregnancy due to bulging towards the bladder side of the repaired CSD. CONCLUSION: Abdominal repair for CSD is feasible in women with thin RMT who experience secondary infertility. Twin pregnancies can promote thinning of the CSD repair site, potentially increasing the risk of uterine rupture.

Several cancers harbor "enhancer-type" mutations of the telomerase reverse transcriptase (TERT) promoter for immortalization. Here, we report that 8.6% (8/93) of ovarian clear cell carcinomas (OCCCs) possess the "suppressor-type" TERT promoter mutation. The recurrence rate of OCCCs with "suppressor-type" TERT promoter mutations was 62.5% (5 of 8) and was significantly higher than that of the "unaffected-type" with no mutation (20.8%, 15 of 72) or "enhancer-type" TERT promoter mutations (7.7%, 1 of 13). Our findings show that the acquired suppression of TERT is closely associated with OCCC development and recurrence, indicating the need for further research on telomerase suppression in cancers.

【緒言】拡張型心筋症(dilated cardiomyopathy,DCM)は左室のびまん性収縮障害と拡大を特徴とする疾患で,妊娠により心停止や心機能低下のリスクが上昇する.妊娠を契機に心室頻拍の増加と心機能低下をきたしたDCM症例を経験したので報告する.【症例】36歳,G1P0.5歳時にDCMと診断され,両心室ペースメーカーで管理されていた.NYHAII度,左心室駆出率34%であったが,強く妊娠を希望した.妊娠に向けて内服薬を調整している間に妊娠し,妊娠16週で当院に紹介された.妊娠21週から非持続性心室頻拍(Non-sustained ventricular tachycardia,NSVT)が出現し,経過中に頻度が増加したため致死性不整脈による心停止のリスクがあると考えられた.妊娠22週から入院管理とし抗不整脈薬投与を開始,関連部署と急変対応の準備を行った.妊娠27週時,左心室駆出率29.8%と心機能低下を認め,妊娠28週0日に帝王切開を施行した.分娩後もNSVTが持続したため,両室ペーシング機能付き植込み型除細動器に交換した.産褥42日に心機能の増悪なく退院した.【結語】NYHAII度のDCM合併妊娠で妊娠28週まで妊娠を継続して生児を得ることができた症例を経験した.DCM合併妊娠では,妊娠中の致死的不整脈に伴う母体急変を想定した準備が必要である.(著者抄録)

【緒言】広範な腹腔内播種や腹水貯留があり,原発巣が不明な場合にはまず卵管癌や腹膜癌が疑われる.今回,腹腔内播種や腹水貯留があり進行卵管癌・腹膜癌を疑ったが,腹膜サルコイドーシスであった症例を経験したため報告する.【症例】患者は50歳女性.右下腹部および排尿時痛,発熱が出現し,腹水と腹膜播種を指摘され当科に紹介受診となった.CA125 387U/mlで,胸腹骨盤部CT検査では,腹水貯留と腹膜の肥厚,縦隔リンパ節腫大を認めたが,腹水細胞診は陰性であった.原発不明癌と術前診断し,試験開腹術を施行したところ,腹膜全体に1～3mm程度の結節が多数集簇していた.両側付属器は正常大で,表面に1～2mmの結節を認めた.病理組織検査では,右付属器,左卵管および大網に多数の非乾酪性類上皮肉芽腫を認め,肉芽腫性炎症性疾患が疑われた.病理,血液検査より,腹膜サルコイドーシスと診断した.試験開腹術後,自覚症状は軽快し,無治療で現在は経過観察している.【結語】本症例では,病理学的に腹膜サルコイドーシスの診断に至り,試験開腹術が診断に有効であった.腹水細胞診が陰性かつ腹膜の均一な肥厚を認めた症例は,腹膜サルコイドーシスや結核性腹膜炎を鑑別に挙げながら検査を進めていく必要があると考えられる.(著者抄録)

AIM: To evaluate whether an acute vulvar ulcer that developed after the COVID-19 vaccine administration is an adverse effect of the vaccine. METHODS: This is a descriptive study of two cases that we observed in addition to cases that have been reported in the literature. We searched for case reports in the PubMed. The consistency of clinical manifestations among cases and the association between ulceration and vaccination were assessed. RESULTS: Fourteen female patients were identified, including 12 patients from 8 literatures published in 2021 and 2022 and 2 patients from our cases. Of the 14 patients, 11 had received the BNT162b2 vaccine, 2 had received the ChAdOx1 nCoV-19 vaccine, and one had received the mRNA-1273 vaccine. The patient's ages were 16.9 ± 5.0 (mean ± SD) years. Postvaccination, the disease progressed in the following sequence (time interval from vaccination): fever and other systemic inflammatory reactions (0.9 ± 0.4 days), development of vulvar ulcers (2.4 ± 1.2 days), and resolution of the ulcer (16.9 ± 7.4 days). The ulcers eventually healed in all cases, except one where the prognosis was not noted. For two-dose vaccine recipients, more patients developed the ulcer after the full vaccination (the second or third doses) compared with after the first dose: n = 10 and n = 2, respectively. CONCLUSION: The acute vulvar ulcer was closely associated with COVID-19 vaccination in terms of temporality and vaccine doses, supporting the notion that a vulvar ulcer is an adverse event of the COVID-19 vaccines.

We conducted a phase Ib study to examine the safety of a combination of carbon-ion RT (CIRT) with durvalumab (MEDI4736; AstraZeneca) in patients with locally advanced cervical cancer. This was an open-label, single-arm study with a modified 3 + 3 design. Patients with newly diagnosed histologically proven locally advanced cervical cancer were enrolled. All patients received 74.4 Gy of CIRT in 20 fractions and concurrent weekly cisplatin (chemo-CIRT) at a dose of 40 mg/m2. Durvalumab was administered (1500 mg/body) at weeks two and six. The primary endpoint was the incidence of adverse events (AEs) and serious AEs (SAEs), including dose-limiting toxicity (DLT). All three enrolled patients completed the treatment without interruption. One patient developed hypothyroidism after treatment and was determined to be an SAE. No other SAEs were observed. The patient recovered after levothyroxine sodium hydrate treatment. None of the AEs, including hypothyroidism, were associated with DLT in the present study. All three patients achieved complete responses within the CIRT region concerning treatment efficacy. This phase 1b trial demonstrates the safety of combining chemo-CIRT and durvalumab for locally advanced cervical cancer in the early phase. Further research is required as only three patients were included in this study.

OBJECTIVE(S): To assess the prevalence of chronic endometritis (CE) in patients with infertility and hydrosalpinx or peritubal adhesions and to examine the effects of laparoscopic surgical correction (LSC) on CE and pregnancy rates post in vitro fertilization and embryo transfer (IVF-ET). STUDY DESIGN: This is a retrospective cohort study at private IVF-ET centers. A total of 438 patients, known to have hydrosalpinx (n = 194) or peritubal adhesions (n = 244), and undergoing IVF treatment between April 1, 2018 and September 30, 2020 were included in the study. Hysterosalpingography, magnetic resonance imaging, and transvaginal ultrasonography were used to diagnose the hydrosalpinx or peritubal adhesions. Laparoscopic examination and surgical correction were performed on patients with CE. IVF-ET was performed after recovery from LSC. RESULTS: CE was present in 45.9% of patients (89/194) with hydrosalpinx and 14.3% with peritubal adhesions (35/244). All the 89 patients with CE and hydrosalpinx underwent laparoscopic salpingostomy and/or fimbrioplasty, and 64 (71.9%) further underwent proximal tubal occlusion. All the 35 patients with CE and peritubal adhesions underwent laparoscopic adhesiolysis and/or fimbrioplasty, and 19 (54.3%) further underwent proximal tubal occlusion. CD138 PC levels after LSC decreased to < 5 in 70 of 124 patients (56.5%) in one menstrual cycle and decreased to < 5 in all cases within 6 months. Of the 66 patients who underwent a single blastocyst transfer, 57 delivered (cumulative live birth rate (LBR): 86.3%). The cumulative LBR of patients treated for CE with LSC (86.3%) was significantly different from those given antibiotic therapy (320 patients; 38.4%; p <.0001) and the CD138-negative groups (811; 31.8%; p <.0001). CONCLUSION: CE is prevalent in patients with hydrosalpinx and/or peritubal adhesions who present with infertility. LSC improved CE without antibiotic therapy, improving the CP and LBR after IVF-ET.

＜文献概要＞●プロラクチンは,視床下部ドパミンにより抑制的に制御されている.●プロラクチンは,プロラクチン受容体を介して自分自身の分泌を抑制している.●高プロラクチン血症により,乳漏と月経異常が生じる.●プロラクチン受容体欠損症は,泌乳欠如と高プロラクチン血症を示す.

PURPOSE: In terms of medical policy for cervical cancer prevention, Japan lags far behind other industrialized countries. We initiated a randomized controlled trial to evaluate the self-sampling human papillomavirus (HPV) test as a tool to raise screening uptake and detection of pre-cancer. This study was conducted to explore the acceptability and preference of self-sampling using a subset of the data from this trial. METHODS: A pre-invitation letter was sent to eligible women, aged 30-59 years who had not undergone cervical cancer screening for three or more years. After excluding those who declined to participate in this trial, the remaining women were assigned to the self-sampling and control groups. A second invitation letter was sent to the former group, and those wanting to undergo the self-sampling test ordered the kit. A self-sampling HPV kit, consent form, and a self-administered questionnaire were sent to participants who ordered the test. RESULTS: Of the 7,340 participants in the self-sampling group, 1,196 (16.3%) administered the test, and 1,192 (99.7%) answered the questionnaire. Acceptability of the test was favorable; 75.3-81.3% of participants agreed with positive impressions (easy, convenient, and clarity of instruction), and 65.1-77.8% disagreed with negative impressions (painful, uncomfortable, and embarrassing). However, only 21.2% were confident in their sampling procedure. Willingness to undergo screening with a self-collected sample was significantly higher than that with a doctor-collected sample (89.3% vs. 49.1%; p<0.001). Willingness to undergo screening with a doctor-collected sample was inversely associated with age and duration without screening (both p<0.001), but that with a self-collected sample was not associated. CONCLUSIONS: Among women who used the self-sampling HPV test, high acceptability was confirmed, while concerns about self-sampling procedures remained. Screening with a self-collected sample was preferred over a doctor-collected sample and the former might alleviate disparities in screening rates.

膵癌が原発巣の転移性卵巣癌は稀であり,その特徴はあまり知られていない.今回,膵癌の卵巣転移を3症例経験した.症例1は68歳,膵体尾部癌IIB期のため標準治療を施行し寛解していた.膵癌発症から1年4ヵ月後,右卵巣多房性嚢胞性腫瘤を認めた.化学療法を開始したが,腹部膨満感と腹痛の緩和目的に両側付属器切除術(bilateral salpingo-oophorectomy:BSO)を施行した.症例2は69歳,膵体部癌IV期で切除不能のため化学療法を施行した.膵癌発症1年3ヵ月目,骨盤内に多房性嚢胞性腫瘤を認め,腹痛の緩和目的でBSOを施行した.症例3は81歳,子宮筋腫で単純子宮全摘術と右付属器切除術後である.膵体部癌IV期のため膵体部切除術と右肺部分切除術後,化学療法を施行し寛解していた.膵癌発症から3年10ヵ月後,左卵巣多房性嚢胞性腫瘤を認めた.左卵巣腫瘍は増大傾向のため,左付属器切除術を施行した.膵癌の卵巣転移は多房性嚢胞性であることが比較的多いが,原発性粘液性卵巣癌も多房性嚢胞性であり,それだけで両者の鑑別は困難である.今回の3症例に共通して,超音波検査で認めた多房性腫瘤を呈し血流を伴う薄い隔壁は,膵癌卵巣転移の特徴的な所見の1つと考えられた.膵癌の治療歴を有する卵巣腫瘍は,この超音波所見と合わせることで,膵癌の卵巣転移と術前に診断できる可能性が示唆された.(著者抄録)

OBJECTIVES: We investigated prospectively whether, in cervical cancer (CC) treated with concurrent chemoradiotherapy (CCRT), the Apparent diffusion coefficient (ADC) histogram and texture parameters and their change rates during treatment could predict prognosis. METHODS: Fifty-seven CC patients treated with CCRT at our institution were included. They underwent MRI scans up to four times during the treatment course (1st, before treatment [n = 41], 2nd, at the start of image-guided brachytherapy (IGBT) [n = 41], 3rd, in the middle of IGBT [n = 27], 4th, after treatment [n = 53]). The entire tumor was manually set as the volume of interest (VOI) manually in the axial images of the ADC map by two radiologists. A total of 107 image features (morphology features 14, histogram features 18, texture features 75) were extracted from the VOI. The recurrence prediction values of the features and their change rates were evaluated by Receiver operating characteristics (ROC) analysis. The presence or absence of local and distant recurrence within two years was set as an outcome. The intraclass correlation coefficient (ICC) was also calculated. RESULTS: The change rates in kurtosis between the 1st and 3rd, and 1st and 2nd MRIs, and the change rate in grey level co-occurrence matrix_cluster shade between the 2nd and 3rd MRIs showed particularly high predictive powers (area under the ROC curve = 0.785, 0.759, and 0.750, respectively), which exceeded the predictive abilities of the parameters obtained from pre- or post-treatment MRI only. The change rate in kurtosis between the 1st and 2nd MRIs had good reliability (ICC = 0.765). CONCLUSIONS: The change rate in ADC kurtosis between the 1st and 2nd MRIs was the most reliable parameter, enabling us to predict prognosis early in the treatment course.

膵癌が原発巣の転移性卵巣癌は稀であり,その特徴はあまり知られていない.今回,膵癌の卵巣転移を3症例経験した.症例1は68歳,膵体尾部癌IIB期のため標準治療を施行し寛解していた.膵癌発症から1年4ヵ月後,右卵巣多房性嚢胞性腫瘤を認めた.化学療法を開始したが,腹部膨満感と腹痛の緩和目的に両側付属器切除術(bilateral salpingo-oophorectomy:BSO)を施行した.症例2は69歳,膵体部癌IV期で切除不能のため化学療法を施行した.膵癌発症1年3ヵ月目,骨盤内に多房性嚢胞性腫瘤を認め,腹痛の緩和目的でBSOを施行した.症例3は81歳,子宮筋腫で単純子宮全摘術と右付属器切除術後である.膵体部癌IV期のため膵体部切除術と右肺部分切除術後,化学療法を施行し寛解していた.膵癌発症から3年10ヵ月後,左卵巣多房性嚢胞性腫瘤を認めた.左卵巣腫瘍は増大傾向のため,左付属器切除術を施行した.膵癌の卵巣転移は多房性嚢胞性であることが比較的多いが,原発性粘液性卵巣癌も多房性嚢胞性であり,それだけで両者の鑑別は困難である.今回の3症例に共通して,超音波検査で認めた多房性腫瘤を呈し血流を伴う薄い隔壁は,膵癌卵巣転移の特徴的な所見の1つと考えられた.膵癌の治療歴を有する卵巣腫瘍は,この超音波所見と合わせることで,膵癌の卵巣転移と術前に診断できる可能性が示唆された.(著者抄録)

The 2017 clinical guidelines for obstetrical practice by the Japan Society of Obstetrics and Gynecology and the Japan Association of Obstetricians and Gynecologists were revised and published as the 2020 edition (in Japanese). The aim of these guidelines is to present appropriate standard obstetric diagnosis and management procedures that have reached consensus among Japanese obstetricians. The 2020 guidelines include 113 clinical questions and an appendix, followed by answers (CQ&A; originally 112 in the 2017 edition), a discussion, list of references, and some tables and figures presenting common problems and questions encountered in obstetrical practice. Each answer comes with a recommendation level of A, B, or C and has been prepared based principally on evidence or a consensus among Japanese obstetricians in situations where "evidence" is weak or lacking. Answers with a recommendation level of A or B represent current standard care practices in Japan. All 113 CQ&As and the appendix are presented here to promote a better understanding of the current standard care practices for pregnant and lactating women in Japan.

症例は腟トリコモナス(本症)の20代女性で、メトロニダゾール(MNZ)、チニダゾール(TNZ)は効果がなかった。新たな治療薬の探索として、中国古来の漢方医学書(神農本草経、一本堂薬選)で本症への有効性の記載がある生薬7種(草果、青蒿、蛇床子、黄連、黄柏、白頭翁、苦参)を用いて、この症例から得たMNZ、TNZ耐性の本症の臨床分離株に対する運動抑制効果をin vitro培養系で測定し効果の検証を行った。その結果、原虫数2×10^5細胞/mLでは青蒿、黄柏、白頭翁、苦参で運動性が低下し、原虫数4×0^5細胞/mLでは白頭翁、苦参のみが運動を阻害した。以上より、白頭翁、苦参は治療抵抗性の本症に対する新たな治療薬となる可能性を示した。なお、今までに、日本においてMNZ、TNZに耐性を示した本症の報告はない。

OBJECTIVES: We aimed to understand how SARS-CoV-2 antibody titer decrease following SARS-CoV-2 mRNA vaccination and to estimate the timing of booster vaccination. STUDY DESIGN: Six hundred sixty-two healthcare workers were administered with total of three doses of SARS-CoV-2 mRNA vaccine during the same short period. Of them, three volunteers were enrolled to measure anti-receptor binding domain (RBD) antibody titers (IgG) monthly following the second and the third doses. METHODS: Serum anti-RBD antibody titers were measured monthly and the decay curve of the antibody was analyzed. We estimate the timing of the third and fourth vaccine based on the observed antibody titer decrease and the period of breakthrough infections in the vaccine recipients. RESULTS: Anti-RBD antibody decreased exponentially following the 2nd dose. Between 108 and 117 days following the second dose, breakthrough infection of SARS-CoV-2 occurred in 11 out of the 662 vaccine recipients. Based on the decrease in anti-RBD antibody and the timing of the breakthrough infections, we estimate that the optimal timing of a third dose would be at earliest 108 days after the second dose, when anti-RBD antibody titers are less than 338 BAU/mL. The anti-RBD antibody titers were sustained relatively higher for 161 days following the third dose (416 days following the second dose). CONCLUSIONS: We estimate that the optimal timing of a third dose would be at earliest 108 days after the second dose, or anti-RBD antibody titers are less than 338 BAU/mL. We suggest that a fourth dose should be administered later than 161 days following the third dose.

Objectives: To investigate the association between online activities and the number of new obstetrics and gynecology senior residents. Methods: A nationwide web-based, self-administered anonymous survey was conducted to investigate recruitment and clerkship activities during the coronavirus disease 2019 pandemic. An online questionnaire was sent to 576 obstetrics and gynecology training institutions in Japan between December 21, 2020, and January 31, 2021. Overall, 334 institutions that gave valid responses were included (response rate: 58.0%). Multivariate logistic regression analysis examined the association between online activities, including recruitment and clerkship activities, and the number of new obstetrics and gynecology senior residents in 2021. The stratified analysis by implementing face-to-face activities was conducted to clarify the association. Results: The number of new senior residents increased in 187 facilities (56.0%) and decreased in 147 facilities (44.0%). The facilities that implemented face-to-face and online activities were 185 (55.4%) and 120 (35.9%), respectively. In multivariate logistic regression analysis, an increased number of new obstetrics and gynecology senior residents was significantly associated with face-to-face activities (adjusted odds ratio (AOR)=2.58, 95% confidence interval (CI): 1.11-5.97, p<.001) but not with online activities. In the stratified analysis, online activities were significantly associated with an increased number of new obstetrics and gynecology senior residents among the facilities without face-to-face activities (AOR=3.81, 95% CI: 1.40-10.32, p=.009) but not among those with face-to-face activities (AOR=0.87, 95% CI: 0.42-1.78). Conclusions: Online activities were associated with an increased number of new obstetrics and gynecology senior residents among the facilities that did not conduct face-to-face activities.

Background: We evaluated whether the serum hormone levels are useful in the differential diagnosis of granulosa cell tumors (GCTs), regardless of menopausal status. Methods: Serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, estradiol, and progesterone were measured preoperatively in all patients (n = 471) who underwent surgery for ovarian tumors at Chiba University Hospital between 2009 and 2021. These were compared in two groups, a GCT group (n = 13) and a group with other histological types (non-GCT) (n = 458). Results: The GCT group had significantly lower serum LH and FSH (p = 0.03 and p &lt; 0.001, respectively) and significantly higher testosterone, estradiol, and progesterone (p &lt; 0.001, p &lt; 0.001, and p = 0.045, respectively) than the non-GCT group. Multivariate analysis revealed that serum FSH and estradiol were significantly associated with GCT (FSH, odds ratio (OR) = 0.0046, 95% confidence interval (CI) = 0.0026–0.22, p = 0.004; estradiol, OR = 0.98, 95% CI = 0.96–0.998, p = 0.046). Receiver-operating characteristic curve analysis for GCTs showed that the area under the curve of serum FSH was 0.99, with a sensitivity of 100% and a specificity of 98%, when the cutoff level was set at 2.0 IU/L. Conclusions: Preoperative serum FSH level is an extremely useful marker for differentiating GCTs from all ovarian tumors.

腎盂尿管移行部狭窄(ureteropelvic junction obstruction)による巨大水腎症が妊娠中に破綻し,反復穿刺により妊娠・分娩管理を行った症例を経験した.患者は1妊0産で,5年前に人間ドッグで無症候性の右巨大水腎症(19×12×12cm)を指摘され,経過観察を指示されていた.38歳で妊娠し妊娠23週までは順調に経過していた.妊娠23週に突然の右下腹部痛と血尿が出現し,腎盂腎杯内の出血が疑われた.保存的管理により症状は1週間で自然に軽快した.その後,水腎症の進行により右腎臓がさらに増大し腹部膨満感と食欲の低下が出現してきたため,腹部膨満感の軽減と拡張腎杯の再破綻の防止を目的に,妊娠31週と34週に右腎臓の穿刺排液を施行した.妊娠38週に3度目の穿刺排液後,分娩誘発を行った.健康な男児を経腟分娩した.穿刺排液は,妊娠中の巨大水腎症の管理の選択肢のひとつとなり得ると思われた.(著者抄録)

Abstract A self-sampling human papillomavirus (HPV) test could improve the morbidity and mortality of cervical cancer in Japan. However, its effectiveness and feasibility have not been demonstrated sufficiently. Hence, we launched a randomized controlled trial, which is ongoing, and report the results of a secondary analysis. To ensure autonomous participation with a minimum selection bias, opt-out consent was obtained from women who met the inclusion criteria, and written consent was obtained from those who underwent a self-sampling test. The number of women who met the inclusion criteria was 20,555; 4283 and 1138 opted out before and after the assignment, respectively. Of the 7340 women in the self-sampling arm, 1372 (18.7%) ordered and 1196 (16.3%) underwent the test. Younger women in their 30 s and 40 s tended to undertake the test more frequently than older women in their 50 s (P for trend &lt; 0.001). Invalid HPV test results were rare (1.3%), and neither adverse events nor serious complaints were reported. Despite adopting the opt-out procedure, more women than expected declined to participate, suggesting the need for a waiver of consent or assignment before consent to reduce selection bias. A self-sampling HPV test can be implemented in Japan and would be more accessible to young women, the predominant group affected by cervical cancer.

BACKGROUND: Progestin is used for fertility-sparing treatment in cases of endometrial cancer (EC). Progestin can induce hyperprolactinemia by increasing pituitary secretion and endometrial decidualization. However, progestin induces prolactin (PRL) secretion, which stimulates cell proliferation and deleteriously affects treatment. To date, the detrimental effect of PRL, the secretion of which is induced by medroxyprogesterone acetate (MPA) during fertility-sparing treatment, has not yet been fully elucidated. Therefore, we aimed to assess the effects of PRL on EC cells during combined treatment with progestin and metformin. METHODS: In total, 71 patients with EC/endometrial atypical hyperplasia who underwent fertility-sparing treatment at our institution from 2009-2019 were enrolled. Serum PRL levels were determined using enzyme immunoassays; mRNA levels in endometrial tissues were determined using quantitative reverse-transcription PCR. To evaluate MPA-induced decidualization, cancer-associated stromal cells were enzymatically released from surgically removed specimens of six patients with EC. To examine PRL-induced cell proliferation, the EC cell lines Ishikawa, HEC1B, and HEC265 were used. In vitro cell proliferation was evaluated using the WST assay; protein levels of signaling molecules were determined using western blotting. RESULTS: MPA administration significantly increased serum PRL levels at 3 and 6 months and upregulated IGFBP-1 and PRL mRNA expression in tissues at 3 months of fertility-sparing treatment. Metformin significantly reduced MPA-induced IGFBP-1 and PRL mRNA expression during fertility-sparing treatment and significantly inhibited the upregulation of IGFBP-1 and PRL mRNA and PRL levels due to decidualization induced by MPA and cAMP treatment in primary cultured EC stromal cells. In vitro, PRL increased cell proliferation and ERK1/2 phosphorylation levels, whereas metformin attenuated these increases. CONCLUSIONS: MPA upregulated PRL levels in serum and endometrial tissues during fertility-sparing treatment. Metformin co-administration reduced PRL production and attenuated PRL-induced cell-proliferation activity. This study may provide valuable insights on the application of metformin to improve the outcomes of fertility-sparing treatment.

産褥期に子宮筋腫分娩が発生した症例を経験したので文献的考察を含めて報告した。<症例1>妊娠8週で子宮体下部から頸部にかけて10cmの子宮筋腫を認めた。妊娠38週、経腟分娩困難と判断し帝王切開術を施行した。産褥27日に、発熱、腹痛・腰痛が出現した。子宮体下部から発育した筋腫核が筋腫分娩となり、感染を続発したものと診断し、開腹子宮筋腫核出術を施行した。<症例2>妊娠10週で、子宮底部に7cmの子宮筋腫を認めた。妊娠36週、急性妊娠性脂肪肝のため緊急帝王切開術を施行した。産褥19日目より発熱と悪露の増量を自覚、産褥25日目に腹部腫瘤感の消失と同時に腰痛が出現し、翌日に外来受診した。感染を併発した筋腫分娩を認め、腟式筋腫核出術を施行した。2例ともに筋腫核出術後は発熱と帯下は改善し、その後に妊娠・分娩を経験した。文献的に、7cm以上の子宮筋腫は、産褥2～4週に筋腫分娩を来すことがあること、また感染を合併する率が高いこと、筋層内筋腫と診断された症例にも発生しうることが産褥期発生の子宮筋腫分娩の特徴と考えられた。(著者抄録)