Undiagnosed myotonic dystrophy: A case report and literature review.

Myotonic dystrophy (MD) is an autosomal dominant disorder primarily characterized by myotonia. The present study describes the case of a 42-year-old woman who was transferred to the authors' department with acute abdomen and restrictive respiratory failure. Computed tomography revealed a 15-cm right ovarian tumor and atelectasis. An abdominal right salpingo-oophorectomy was performed under general anesthesia. She was then extubated after surgery; however, shortly thereafter she was re-incubated due to poor oxygenation and was then moved to the intensive care unit (ICU) for a further analysis of weaning failure. During her stay in the ICU, weaning was attempted twice, but failed both times. The patient underwent a tracheotomy 7 days after surgery. Consultation with a neurologist suggested possible MD. Following genetic testing, type I MD with ~700-1,100 cytosine-thymine-guanine repeats in the dystrophia myotonia protein kinase gene was confirmed. The patient was then transferred to a specialty hospital at 2 months after surgery. On the whole, the case described herein suggests that clinicians need to become familiar with this disease as a differential diagnosis for post-operative weaning failure.

MicroRNA-210-3p Regulates Endometriotic Lesion Development by Targeting IGFBP3 in Baboons and Women with Endometriosis.

MicroRNAs (miRs) play an important role in the pathophysiology of endometriosis; however, the role of miR-210 in endometriosis remains unclear. This study explores the role of miR-210 and its targets, IGFBP3 and COL8A1, in ectopic lesion growth and development. Matched eutopic (EuE) and ectopic (EcE) endometrial samples were obtained for analysis from baboons and women with endometriosis. Immortalized human ectopic endometriotic epithelial cells (12Z cells) were utilized for functional assays. Endometriosis was experimentally induced in female baboons (n = 5). Human matched endometrial and endometriotic tissues were obtained from women (n = 9, 18-45 years old) with regular menstrual cycles. Quantitative reverse transcript polymerase chain reaction (RT-qPCR) analysis was performed for in vivo characterization of miR-210, IGFBP3, and COL8A1. In situ hybridization and immunohistochemical analysis were performed for cell-specific localization. Immortalized endometriotic epithelial cell lines (12Z) were utilized for in vitro functional assays. MiR-210 expression was decreased in EcE, while IGFBP3 and COL8A1 expression was increased in EcE. MiR-210 was expressed in the glandular epithelium of EuE but attenuated in those of EcE. IGFBP3 and COL8A1 were expressed in the glandular epithelium of EuE and were increased compared to EcE. MiR-210 overexpression in 12Z cells suppressed IGFBP3 expression and attenuated cell proliferation and migration. MiR-210 repression and subsequent unopposed IGFBP3 expression may contribute to endometriotic lesion development by increasing cell proliferation and migration.

Coexistence of Ovarian Endometrioma and Ovarian Pregnancy: A Case Report.

Both ovarian pregnancy and endometrioma can rupture and cause life-threatening hemoperitoneum. However, little is known about their coexistence. We report the case of a 34-year-old Japanese woman with a life-threatening hemoperitoneum in the first trimester coexisting with ovarian endometrioma and ovarian pregnancy. The patient was hospitalized in our department for acute hypogastric pain and massive hemoperitoneum during pregnancy. She had a history of miscarriage at eight weeks of gestation one year prior. Her serum beta-human chorionic gonadotropin (hCG) level was >2,000 mIU/mL. Also, a transvaginal ultrasound showed an empty uterus, an intact right ovary, an inhomogeneous left ovary, and a massive hemoperitoneum. An exploratory laparoscopy revealed a rupture of the left ovarian endometrioma, a left corpus luteal cyst, and intraperitoneal bleeding of approximately 1,200 mL. However, no ectopic lesions were observed. Microscopic examination revealed an endometriotic cyst with decidual changes in the stroma, a corpus luteal cyst, and chorionic villi with hemorrhage. Serum beta-hCG levels became negative on the 27th postoperative day. The postoperative course was uneventful. This case shows that, in addition to the differential diagnosis of ovarian pregnancy from ovarian endometrioma, clinicians should consider the coexistence of both conditions.

Prophylactic oophorectomy and aromatase inhibitors for premenopausal deep angiomyxoma: A case report and literature review.

Deep angiomyxoma is a rare, infiltrative, hormone-dependent, benign-mesenchymal neoplasm that occurs in the deep soft tissues of the perineal regions. In total, 33% females with newly diagnosed deep angiomyxoma will typically relapse within 5 years after the standard treatment of radical resection. Postoperative hormone therapy is frequently administered to prevent recurrence, but the role of prophylactic oophorectomy in premenopausal women remain to be fully elucidated. In the present report, a 42-year-old Japanese woman was referred for a refractory Bartholin's cyst that is 14 cm in diameter. Based on the results of imaging (unenhanced CT and MRI) and histopathology, deep angiomyxoma was suspected, but no definitive diagnosis was possible. Tumor resection and bilateral salpingo-oophorectomy were performed before the postoperative diagnosis was confirmed to be deep angiomyxoma. The patient received an aromatase inhibitor (2.5 mg letrozole daily) as adjuvant hormonal therapy. There was no evidence of recurrence at the 1-year postoperative follow-up. In conclusion, prophylactic oophorectomy and postoperative adjuvant therapy with aromatase inhibitors may be a promising treatment option for deep angiomyxoma to optimize the outcome of surgical treatment. Long-term follow-up is required to monitor for the late and/or local recurrence of deep angiomyxoma and possible adverse effects of adjuvant hormonal therapy.

Factors affecting the recruitment of new obstetrician-gynecologists in Japan: A report of the MIRAI Committee of the Japanese Society of Obstetrics and Gynecology.

AIM: There is a chronic shortage of obstetrician-gynecologists in Japan. To increase the number of obstetrician-gynecologists, it is crucial to increase the number of residents being recruited. The purpose of this study was to identify the factors that led students and interns to specialize in obstetrics and gynecology through a questionnaire survey. METHODS: We sent a questionnaire to the obstetrics and gynecology departments of all the medical schools in Japan (N = 81) and collected data about the institutional background, including the location, total number of obstetrician-gynecologists employed, and number of newly joined obstetrics-gynecology residents and resigned obstetrician-gynecologists and the educational and recruitment activities for medical students and interns. The net balance (increased or decreased) over the fiscal years 2013-2015 was considered a surrogate marker for the number of newly joined obstetrics-gynecology residents. We used binomial logistic regression analysis to determine the factors related to a positive net balance of obstetrician-gynecologists. RESULTS: We obtained responses from 59 (72.8%) medical schools. Medical students who observed deliveries were more likely to become obstetrician-gynecologists than those who did not (95% confidence interval: 1.000-1.045, p = 0.052). Medical school location (rural or urban), providing medical students with preparatory lectures for national board examinations, and providing interns with experience as the first assistant during surgery were not associated with an increase in the number of newly joined obstetrician-gynecologists. CONCLUSIONS: The experience of observing deliveries may encourage medical students to become obstetrician-gynecologists.

Demons syndrome with pericardial effusion followed by intensive care unit-acquired weakness: A case report and literature review.

Demons syndrome is defined by hydrothorax and ascites associated with a benign genital tumor that resolves after resection of the tumor. However, Demons syndrome with pericardial effusion has never been reported. Intensive care unit-acquired weakness is a neurological sequela to sepsis/systemic inflammatory response syndrome, or multi-organ failure. A 47-year-old, nulligravid, Japanese woman, was transferred to our hospital for refractory heart failure and a ruptured ovarian tumor. She had an 11-cm left ovarian tumor with ascites, hydrothorax, and pericardial effusion; she was intubated for pulmonary hypertension and admitted to the intensive care unit for septic shock. Four days later, a left salpingo-oophorectomy was performed for Demons syndrome with pericardial effusion. The histological diagnosis indicated a serous cystadenoma with fibrotic changes. Following surgery, ventilator weaning was delayed due to intensive care unit-acquired weakness. The association between Demons syndrome and pericardial effusion should be recognized to ensure early treatment and for preventing sequalae from the disease.

Promising therapeutic targets of endometriosis obtained from microRNA studies.

Endometriosis is a benign tumor that affect 6-10% women of reproductive age. To date, it is suggested that the aberrant microRNA (miRNA) expressions play important roles in the pathogenesis of endometriosis. Reviewing the literature, we found nine overexpressed miRNAs, which were thoroughly investigated in the context of endometriotic tissues and cells. Most of the overexpressed miRNAs induced endometriosis-specific characteristics including inhibition of apoptosis and decidualization, upregulation of fibrogenesis, invasion, migration, cell proliferation, attachment to extracellular matrix, inflammation, and angiogenesis in the endometriotic cells. Then, we found that the downstream target molecules of these miRNAs, such as early growth response protein-1, extracellular signal-regulated kinase, matrix metallopeptidase 1, signal transducer and activator of transcription 3, cyclooxygenase-2, phosphoinositide 3-kinase, AKT, mammalian target of rapamycin, and vascular endothelial growth factor-A are promising for the therapeutic targets of endometriosis. Recent findings suggest that complex molecular mechanisms leading to development and progression of endometriosis by miRNAs may exist in endometriosis. The meticulous balance between tumorigenic miRNAs and tumoristatic miRNAs may destine the natural course and response to the surgical, medical, and hormonal treatments of this disease. Further investigations into endometriosis-associated miRNAs may elucidate the pathogenesis of endometriosis and help to develop novel therapeutics.

Role of repressed microRNAs in endometriosis.

Endometriosis is a common, estrogen-dependent benign tumor that affect 3-10% women of reproductive age, and is characterized by the ectopic growth of endometrial tissue, which is found primarily in the rectovaginal septum, ovaries, and pelvic peritoneum. To date, accumulating evidence suggests that various epigenetic aberrations, including the expression of aberrant microRNAs (miRNAs), play definite roles in the pathogenesis of endometriosis. This review summarizes the recent findings on the aberrantly repressed miRNAs, as well as their potential roles regarding the pathogenesis of endometriosis.

Pathological processes and pretreatment cytologic diagnosis of neuroendocrine carcinoma of the endometrium: addendum report of the Kansai Clinical Oncology Group/Intergroup study in Japan.

A previous retrospective study of a neuroendocrine carcinoma of the endometrium including 42 cases employed a central pathologic review to ensure the reliability of the findings. However, the pathological processes were not described in detail. In this study, we further analyzed these processes and the results of pretreatment endometrial cytology of neuroendocrine carcinoma. Of the 65 patients from 18 institutions registered in the study, 42 (64.6%) were diagnosed with neuroendocrine carcinoma of the endometrium based on the central pathological review. Thirteen of the 23 excluded cases conflicted from their original diagnoses: 5 (38.5%) were diagnosed with endometrioid adenocarcinoma, 5 (38.5%) with undifferentiated carcinoma, and 3 (23.1%) with carcinosarcoma. Immunohistochemical staining led to a change in diagnosis for 8 (61.5%) of the 13 cases. Pretreatment endometrial cytology was examined in 38 (90.5%) cases; 34 (89.5%) of these 38 cases were found, or suspected, to be positive. To ensure the selection of appropriate therapy and keeping patients correctly informed, it is important to distinguish neuroendocrine carcinoma from other similar histologic types. Endometrial cytology may help in the early detection of this disease.

Mixed large and small cell neuroendocrine carcinoma and endometrioid carcinoma of the endometrium with high microsatellite instability: A case report and literature review.

A 65-year-old, gravida 3, para 2 Japanese woman was referred to our hospital for symptomatic thickening of the endometrial lining. Endocervical and endometrial cytology revealed an adenocarcinoma. The endometrial biopsy specimen was mixed, with a glandular part diagnosed as endometrioid carcinoma and a solid part diagnosed as high-grade mixed large and small cell neuroendocrine carcinoma (L/SCNEC). She underwent extra-fascial hysterectomy with bilateral salpingo-oophorectomy, complete pelvic and para-aortic lymphadenectomy, and omentectomy (FIGO IIIB, pT3b pN0 M0). She currently has no deleterious germline mutation, but high tumor mutation burden and high microsatellite instability (MSI) were identified. She underwent six cycles of platinum-based frontline chemotherapy and achieved complete remission. Immune checkpoint blockade therapy is a promising second-line therapy for MSI-high solid tumors. However, the MSI or mismatch repair (MMR) status of endometrial L/SCNEC remains unclear in the literature. Universal screening for MSI/MMR status is needed, particularly for a rare and aggressive disease.

Correlation of World Health Organization 2010 Classification for Gastroenteropancreatic Neuroendocrine Neoplasms with the Prognosis of Ovarian Neuroendocrine Neoplasms: Kansai Clinical Oncology Group-Protocol Review Committee/Intergroup Study.

BACKGROUND: In 2014, the World Health Organization (WHO) released a classification system introducing neuroendocrine neoplasms (NENs) of the female reproductive tract, excluding the ovaries. This study aimed to evaluate whether retrospective adaption of the gastroenteropancreatic (GEP)-NEN classification is feasible for ovarian NENs (O-NENs) and correlates with prognosis. METHODS: Sixty-eight patients diagnosed with carcinoid, small cell carcinoma (pulmonary type), paraganglioma, non-small/large cell neuroendocrine carcinoma (NEC), mixed NEC, or undifferentiated carcinomas at 20 institutions in Japan were included in this retrospective cross-sectional study. We identified O-NENs through central pathological review using a common slide set, followed by reclassification according to WHO 2010 guidelines for GEP-NENs. A proportional hazards model was used to assess the association of prognostic factors (age, stage, performance status, histology, and residual disease) with overall survival (OS) and progression-free survival (PFS). RESULTS: Of the 68 enrolled patients, 48 were eligible for analysis. All carcinoids (n = 32) were reclassified as NET G1/G2, whereas 14 of 16 carcinomas were reclassified as NEC/mixed adeno-NEC (MANEC) (Fisher's exact test; p < 0.01). The OS/PFS was 49.0/42.5 months and 6.5/3.9 months for NET G1/G2 and NEC/MANEC, respectively. Histology revealed that NEC/MANEC was associated with increased risk of death (HR = 48.0; 95% CI, 3.93-586; p < 0.01) and disease progression (HR = 51.6; 95% CI, 5.54-480; p < 0.01). CONCLUSION: Retrospective adaption of GEP-NEN classification to O-NENs is feasible and correlates well with the prognosis of O-NENs. This classification could be introduced for ovarian tumors.

Clinical practice guidelines for the treatment of extragenital endometriosis in Japan, 2018.

The aim of this publication is to disseminate the clinical practice guidelines for the treatment of intestinal, bladder/ureteral, thoracic and umbilical endometriosis, already published in Japanese, to non-Japanese speakers. For developing the original Japanese guidelines, the clinical practice guideline committee was formed by the research team for extragenital endometriosis, which is part of the research program of intractable disease of the Japanese Ministry of Health, Labor and Welfare. The clinical practice guideline committee formulated eight clinical questions for the treatment of extragenital endometriosis, which were intestinal, bladder/ureteral, thoracic and umbilical endometriosis. The committee performed a systematic review of the literature to provide responses to clinical questions and developed clinical guidelines for extragenital endometriosis, according to the process proposed by the Medical Information Network Distribution Service. The recommendation level was determined using modified Delphi methods. The clinical practice guidelines were officially approved by the Japan Society of Obstetrics and Gynecology and the Japan Society of Endometriosis. This English version was translated from the Japanese version.

Port-site implantation of parasitic leiomyoma after laparoscopic myomectomy and its histopathology.

Although parasitic leiomyoma could be spontaneous or iatrogenic in origin, port-site implantation of parasitic leiomyoma is an iatrogenic benign sequela of laparoscopic surgery. A 30-year-old, primigravida Japanese woman was referred after unresponsiveness to preoperative gonadotropin-releasing hormone for intramural fibroids. Magnetic resonance imaging showed multiple intramural fibroids and left ovarian endometrioma with no malignant features. Laparoscopic myomectomy with power morcellation and ovarian cystectomy were performed, followed by treatment with a combined oral contraceptive. Seven years after the primary surgery, she underwent abdominal myomectomy for a port-site, and peritoneal recurrence of the leiomyoma and intramural leiomyomas was detected. Microscopic examination revealed that resected specimens from the port-site demonstrated leiomyoma with lesser cell density and more prominent hyalinization than those from the uterus. Therefore, clinicians should counsel patients regarding the risks and benefits of laparoscopy with morcellation versus laparotomy. Further development of techniques for uterine tissues extraction is warranted.

Clinicopathologic features, treatment, prognosis and prognostic factors of neuroendocrine carcinoma of the endometrium: a retrospective analysis of 42 cases from the Kansai Clinical Oncology Group/Intergroup study in Japan.

OBJECTIVE: We conducted a retrospective, multi-institutional, collaborative study to accumulate cases of neuroendocrine carcinoma of the endometrium, to clarify its clinicopathologic features, treatment, prognosis and prognostic factors to collate findings to establish future individualized treatment regimens. To our knowledge, this is the largest case study and the first study to statistically analyze the prognosis of this disease. METHODS: At medical institutions participating in the Kansai Clinical Oncology Group/Intergroup, cases diagnosed at a central pathologic review as neuroendocrine carcinoma of the endometrium between 1995 and 2014 were enrolled. We retrospectively analyzed the clinicopathologic features, treatment, prognosis and prognostic factors of this disease. RESULTS: A total of 65 cases were registered from 18 medical institutions in Japan. Of these, 42 (64.6%) cases were diagnosed as neuroendocrine carcinoma of the endometrium based on the central pathological review and thus included in the study. Advanced International Federation of Gynecology and Obstetrics stages (stage III and IV) and pure type small cell neuroendocrine carcinoma cases had a significantly worse prognosis. Upon multivariate analysis, only histologic subtypes and surgery were significant prognostic factors. Pure type cases had a significantly worse prognosis compared to mixed type cases and complete surgery cases had a significantly better prognosis compared to cases with no or incomplete surgery. CONCLUSION: Our findings suggest that complete surgery improves the prognosis of neuroendocrine carcinoma of the endometrium. Even among cases with advanced disease stages, if complete surgery is expected to be achieved, clinicians should consider curative surgery to improve the prognosis of neuroendocrine carcinoma of the endometrium.

Small cell carcinoma of the uterine cervix during pregnancy.

Small cell carcinoma of the uterine cervix is a rare histological entity that has a poor prognosis. We report the case of a patient with small cell carcinoma of the uterine cervix who underwent a radical hysterectomy during pregnancy. A 33-year-old Japanese woman with genital bleeding was referred at 15 weeks' gestation. A speculum exam revealed a 5.4-cm-dia. mass in the cervix, and a cervical biopsy revealed small cell carcinoma of the uterine cervix. Imaging studies demonstrated a tumor confined to the cervix, swelling of intra-pelvic lymph nodes, and no distant spread of the tumor. She was diagnosed as having small cell carcinoma of the uterine cervix, stage IB2, and underwent a radical hysterectomy with pelvic lymphadenectomy. She refused any adjuvant therapies, had a systemic relapse 4 months after surgery, and died of the disease 5 months after surgery. Early-stage small cell carcinoma of the uterine cervix should be treated with a definitive therapy soon after diagnosis whether the patient is pregnant or not. Saving the mother's life should be the top priority.

Therapeutic dilemma in twin reversed arterial perfusion sequence.

The dissemination of minimally invasive in utero surgery reduced the mortality of twin reversed arterial perfusion sequence, but the mortality of expectantly treated surgical candidates remains high. A 26-year-old, non-parous, Japanese woman at 13 weeks of gestation had been diagnosed with twin reversed arterial perfusion sequence and was judged as a surgical candidate for radiofrequency ablation. However, she did not undergo surgery because of the anatomical location of the acardiac twin. At 18 weeks of gestation, the blood flow to the acardiac twin disappeared spontaneously. The pump twin began to demonstrate fetal growth retardation during the third trimester. The patient delivered a 1891 g female at term. We macroscopically identified the cause of the fetal growth retardation as velamentous insertion of the umbilical cord and microscopically diagnosed the acardiac twin with acardiac acephalus. We should give the same attention to the management of post-twin reversed arterial perfusion sequence as twin reversed arterial perfusion sequence itself.

Two cesarean deliveries after hemi-hysterectomy due to gestational trophoblastic neoplasia.

OBJECTIVE: Although uterine didelphys per se is not associated with an impaired ability to conceive, the association between uterine anomalies and gestational trophoblastic neoplasia (GTN) remains unclear. The management of chemotherapy-resistant GTN in women with uterine didelphys raises a new issue regarding whether to perform a hemi-hysterectomy. CASE REPORT: A 23-year-old, gravida 1, para 0 Japanese woman was referred with a failed intermittent cervical dilatation for hematometra. Four years previously, she developed a GTN Stage III, score 5. As two cycles of chemotherapy with methotrexate (MTX) and one cycle of EMA-CO (etoposide, MTX, actinomycin D, cyclophosphamide and vincristine) did not result in remission, we performed an abdominal hemi-hysterectomy. After a canalization procedure and cervicoplasty were performed, the patient conceived naturally and prematurely delivered by cesarean section twice. CONCLUSION: A hemi-hysterectomy should be considered for fertility preservation when GTN develops on either side of a didelphic uterus and adjuvant chemotherapy does not result in remission.

Decidualization Differentially Regulates microRNA Expression in Eutopic and Ectopic Endometrial Stromal Cells.

Decidualization of the endometrium and endometriosis involves the morphological and biochemical reprogramming of the estrogen-primed proliferative stromal compartment under the continuing influence of progesterone. Here, we evaluated the involvement of microRNA in the decidualization processes of normal endometrial stromal cells (NESCs) and endometriotic cyst stromal cells (ECSCs). In vitro decidualization of NESCs and ECSCs was induced by long-term culture with a combination of 0.5 mmol/L of dibutyryl cyclic adenosine monophosphate and 100 nmol/L of dienogest. We investigated the effect of in vitro decidualization on the microRNA and messenger RNA (mRNA) expression profiles of the NESCs and ECSCs using global microarray techniques and an Ingenuity Pathways Analysis. Decidualization differentially enhanced the miR-30a-5p expression in the NESCs and the miR-210 expression in the ECSCs. The enhanced miR-30a-5p expression in the NESCs correlated with the increased mRNA expression of Krüppel-like factor 9 and period circadian clock 3 as well as the decreased mRNA expression of tolloid-like 1, tolloid-like 2, and paired-like homeodomain 1. The enhanced expression of miR-210 in the ECSCs correlated with the decreased mRNA expression of growth hormone receptor and thymidine kinase 1. Although there is no direct evidence, we speculate that the loss of miR-30a-5p-mediated mechanisms of decidualization and the acquisition of miR-210-mediated mechanisms of decidualization may be involved in the progesterone resistance in endometriosis. Further investigations are necessary to test this speculation.