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Laparoscopic power morcellator (LPM) can be used for tissue retrieval through laparoscopic port site, but the dissemination of uterine and/or myoma tissues is a serious complication. To study the use of LPM for uterine fibroid treatment in Japan, we aimed to perform two national cross-sectional surveys comprising multiple questionnaires.The first survey (2011-2013) was conducted in November 2014, and 203 medical institutions responded. The second survey (2017-2019) was conducted in December 2020, and 302 medical institutions were investigated.Overall, 72 104 and 120 425 surgeries and 0.04% and 0.05% cases of postoperative malignancy diagnosis were reported in the first and second surveys, respectively. Magnetic resonance imaging was performed in90% of the cases in the first and second surveys as preoperative examinations. The frequency of LPM at hysterectomy was 8.9% and 4.6% and the frequency of LPM at laparoscopic myomectomy was 80.4% and 54.8% in the first and second surveys, respectively; both the parameters decreased in the second survey.It is impossible to completely exclude malignant diseases even if extensive preoperative diagnosis has been done before surgery. Therefore, the use of LPM in patients requires careful attention and informed consent in Japan.

Introduction: We previously reported that preoperative human papillomavirus (HPV) type 16/18 positivity and postoperative high-risk (HR)-HPV test positivity are associated with abnormal postoperative cytology. In this study, we further examined whether preoperative and postoperative HR-HPV genotyping could predict cytological abnormalities and the risk of additional surgery. Methods: Patients who underwent cervical conization at our hospital between July 2009 and June 2018 were enrolled. HPV genotyping was performed preoperatively for all patients with HPV-positive. The association among preoperative and postoperative HR-HPV genotyping results, the cumulative risk of cytological abnormalities, and additional surgery were evaluated. The endpoint approach was used to investigate the cumulative incidence of additional surgery owing to cytological abnormalities, such as low-grade squamous intraepithelial lesion positivity and recurrence 2 years after cervical conization. Results: Positive and negative histological margins were observed in 21 and 287 of 308 cases, respectively. The cumulative incidence of abnormal cytology and additional surgery was significantly higher in margin-positive cases than that in margin-negative cases. Examination established according to the margin status demonstrated that the postoperative HR-HPV-positive group had a significantly worse prognosis than the HR-HPV-negative group. Additionally, 32 cases, wherein the same genotype detected before and after surgery, demonstrated significantly unfavorable outcomes. Fifteen patients with persistent HPV 16/18 had the worst prognosis than the other types. Conclusion: Preoperative and postoperative HR-HPV genotype tests were used to predict the cumulative incidence of abnormal cytology and additional surgery. Particularly, patients with suspected persistent HPV type 16/18 infection are at a high recurrence risk.

The pathogenesis of endometriosis has not been fully elucidated. We focused on the behavior of the ectopic endometrium, that is, the origin of the endometriotic lesion, before adhering to the peritoneal cavity. To observe lesion formation in the very early phase, we developed a novel endometriosis animal model using bioluminescence technology. We established a new transgenic mouse that expressed Emerald luciferase (ELuc) under the control of the CAG promoter. This transgenic mouse, called the CAG-ELuc mouse, showed strong bioluminescence emission; we succeeded in tracing the lesion location by the emission of ELuc. The accuracy of tracing by ELuc was high (57.7-100% of correspondence) and depended on the dosage of E2 administration. In the very early phase after transplantation, the process of lesion formation can be observed non-invasively and chronologically. We have verified that the preferred location of the uterus (transplanted grafts) was fixed immediately after the transplantation of the grafts.

Purpose To evaluate the efficacy of two progestins, levonorgestrel intrauterine system (LNG‐IUS) and dienogest (DNG), for adenomyosis. Methods This study enrolled 157 women with adenomyosis, randomized to either LNG‐IUS (n = 76) or DNG (n = 81) groups as a controlled clinical trial for 72 months. Participants were classified by three different localizations of adenomyosis: diffuse, focal, and extrinsic. VAS (Visual analog scale) score, days, and amount of uterine bleeding were assessed. Uterine volume or bone mineral density (BMD) were measured by three‐dimensional ultrasonography or dual‐energy X‐ray absorptiometry. Results LNG‐IUS and DNG comparably reduced pain scores in patients with adenomyosis. With regard to pain control, DNG offered greater efficacy than LNG‐IUS in 3 months of treatment. In all types of adenomyosis, the days of bleeding after 12 months with DNG were significantly decreased compared to those with LNG‐IUS. The decrease of whole uterine body was transient in any subtypes. A comparable decrease in BMD due to age‐related changes in both groups was observed. Conclusions LNG‐IUS and DNG could be useful for long‐term management of adenomyosis. In terms of durations of uterine bleeding, DNG was superior to LNG‐IUS for 6 years., We described the efficacy of two progestins, levonorgestrel intrauterine system (LNG‐IUS) and dienogest (DNG) in the treatment of adenomyosis as a first controlled clinical trial. Patients were classified by three different localizations of adenomyosis: diffuse, focal, and extrinsic. DNG proved superior to LNG‐IUS in terms of the duration of uterine bleeding.

Background Endometriosis has been accepted as an estrogen-dependent disease for more than two decades. So far, estrogen modulators that targeting estrogen depletion in endometriotic lesions have been expected as the first option of treatments to improve the symptoms associated with endometriosis. However, the limits of treatment are becoming apparent. Objective As the background of limits, we hypothesized the heterogeneity of genetic and/or epigenetic environments in endometriotic lesions (1). To test our hypothesis, we examined the expression profile of estrogen-responsive genes using endometriotic stromal cells as a model. Patients: Institutional Review Boards approved this project. We obtained informed consent from all patients. The chocolate cyst lining in the ovaries of patients with endometriosis was the source of endometriotic tissue. As a control, the eutopic endometrial tissues were obtained from uteri of premenopausal women who had uterine leiomyoma. Methods Stromal cells were prepared from endometriotic and endometrial tissues. ESR1 and ESR2 expression were evaluated using RT-PCR (2). For RNA-seq analysis of estrogen-responsive genes, total cellular RNAs from endometriotic cells treated with or without 10nM estradiol for 8hr were prepared. Following the quality control (concentration>50ng/ul, RIN>9), RNA samples were used for polyA+ selected library preparation and the strand-specific RNA-seq (NovaSeq, DNBSEQ-G400, 20M paired- end (PE) reads and 2×150bp PE/sample). Estrogen-responsive genes were extracted using RNA-seq bioinformatics analysis. Genes with adjusted p-values < 0. 05 and absolute log2 fold changes > 1 were extracted as estrogen-responsive genes (DESeq2 BP). Principal component analysis (PCA) was used to visualize sample-to-sample distances. Differential gene GO enrichment analysis was performed (GOseq. v1.34.1). Results 1) wild type ERα mRNA expression in endometriotic cells was one-tenth of that in endometrial cells. wild type ERβ1 and the splice variant ERβ2 mRNAs were expressed in endometriotic cells at a comparable level of the ERα. 2) PCA suggested the presence of at least two cell types in endometriotic cells. 3) Cluster analysis of gene expression suggested the presence of 2 cell types: endometriotic cells with or without GATA6 expression (3). 4) Estrogen-responsive genes were significantly different among the cells examined. 4) Differential gene GO enrichment analysis suggested the diversity of gene expression profiles depending on the cells. Conclusion In the hope of overcoming the limits of endocrine-targeted therapy in endometriosis, we examined the estrogen-responsive genes in endometriotic cells. The finding suggests the diversity of estrogen-responsive genes in endometriotic lesions. References(1) Fertil Steril (2019) 111: 327–39. (2) Reprod Sci (2016) 23: 871-6. (3) Am J Reprod Immunol (2019) 81: e13078. Presentation: No date and time listed

Aim Tokishakuyakusan (TSS) is representative of popular Kampo medicines for Japanese women to treat dysmenorrhea, irregular menstruation and menopause. Current hormonal treatments and low-dose oral contraceptives (OCs) used as a first-choice drug for primary symptoms, however, have a high incidence of adverse events without improving patients' satisfaction. We evaluated the efficacy of TSS as additional treatment on the quality of life (QOL) of patients taking OCs with reduced therapeutic satisfaction. Methods Twelve patients treated with OCs for endometriosis were enrolled. TSS (7.5 g/day) in combination with OCs were given for three menstrual cycles. The main outcome was the degree of QOL assessed using the Endometriosis Health Profile-30 (EHP-30). Secondary outcomes were the Menstrual Distress Questionnaire (MDQ), patient's satisfaction using a Likert scale and cold feeling-visual analogue scale (VAS). Results In EHP-30, significant changes by TSS with OCs in each menstrual cycle were not found, although the scores for pain and emotional well-being tended to decrease. In MDQ, water retention in the premenstrual phase was improved. With regard to cold feeling-VAS, 61.6 mm at pretreatment decreased to 31.3 mm at the endpoint. Average Likert scale values after TSS treatment declined from 4.3 to 2.6. Cold feeling and patient's satisfaction have improved. Conclusion Although the influence of TSS add-on therapy on QOL was moderate, possible improvement of cold feeling and menstruation-related symptoms was suggested.

Objective To evaluate the effects of gonadotropin-releasing hormone agonists (GnRH-a) on fertility in women with mild endometriosis who are undergoing in vitro fertilization and embryo transfer (IVF-ET) procedures. Design Prospective, randomized, controlled trial. Setting Three tertiary university hospitals. Patient(s) Four hundred infertile women with mild endometriosis, documented with laparoscopy, undergoing IVF and 200 women with tubal factor infertility. Intervention(s) Administration of GnRH-a for 3 months before an IVF attempt (group A, n = 200) or IVF without GnRH-a (group B, n = 200). Main Outcome Measure(s) Follicular fluid (FF) levels of tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), IL-6, IL-8, and IL-1 receptor antagonist; fertilization rate (FR), implantation rate (IR), quality of embryos, and clinical pregnancy rate (PR). Result(s) Women who received GnRH-a had a statistically significantly reduced concentration of FF cytokines compared with women who did not receive this regimen. Women in group B had a reduced FR (61.7; 95% CI, 59.20–64.20) compared with the women in group A (72.7; 95% CI, 70.50–74.90) and compared with the women with tubal factor infertility (74.7; 95% CI, 72.00–77.24). The embryo quality, IR, and clinical PR showed no statistically significant improvement in the women of group A compared with group B. Conclusion(s) Women who received GnRH-a for 3 months had a lower concentration of FF cytokines. These women had also a higher FR than the women who did not receive GnRH-a. However, the IR, embryo quality, and clinical PR showed no statistically significant difference when comparing the two groups. ClinicalTrials.gov ID NCT01269125.

Pregnancy increases the risk of venous thromboembolism (VTE). During pregnancy and a post-cesarean section, an increase in D-dimer levels can be observed. However, to date, the usefulness of the D-dimer level measurement for thrombosis in pregnant women has not been determined.We aimed to evaluate the changes in D-dimer levels after a cesarean section, the risk factors of high D-dimer levels, and enoxaparin sodium's preventive effects on VTE.This retrospective study enrolled 160 pregnant women who underwent a cesarean section. D-dimer levels were measured on postoperative day (POD)1 and POD6. If on POD1, the D-dimer levels were ≥10 µg/mL, enoxaparin sodium was administered until POD7. Regardless of enoxaparin administration, when the D-dimer levels on POD6 were ≥10 µg/mL, lower-limb venous ultrasonography was performed. After a cesarean section, patients were screened for the following: factors causing high D-dimer levels, incidence of deep vein thrombosis (DVT), and need for enoxaparin.The median D-dimer levels on POD1 and POD6 were 7.5 µg/mL (1.1-34.1) and 4.2 µg/mL (0.02-31.4), respectively. Enoxaparin sodium was administered to 56 patients (35%). The D-dimer levels on POD6 decreased more significantly than on POD1. The median D-dimer levels in the enoxaparin administration group significantly dropped from 14.3 (POD1) to 3.9 (POD6) (When the D-dimer levels on POD1 after a cesarean section are ≥10 µg/mL, enoxaparin reduces D-dimer levels six days after cesarean section. Moreover, patients aged ≥35 years represent an independent factor for high D-levels. These findings should be validated by further studies.

Study Objective To identify the clinical presentation, diagnostic evaluation, operative or medical management, and postoperative recurrence of umbilical endometriosis. Design A retrospective national survey. Setting Obstetrics and Gynecology and Plastic Surgery Departments at a teaching hospital in Japan. Patients Patients with umbilical endometriosis or malignant transformation. Interventions A national survey was conducted to identify and evaluate cases of umbilical endometriosis or malignant transformation documented between 2006 and 2016. Measurements and Main Results The following were evaluated for each patient: age at diagnosis, body mass index, medical history, presence of extragenital endometriosis, surgical history, symptoms, imaging modalities, surgical therapy, hormonal therapy, follow-up period, postoperative recurrence, and time to recurrence. Ninety-six patients were identified with pathologically diagnosed benign umbilical endometriosis. The patients frequently had swelling (86.5%), pain (81.3%), or bleeding (44.8%) in the umbilicus. Sensitivity was 87.1% for physical examination, 76.5% for transabdominal ultrasonography, 75.6% for computed tomography, and 81.8% for magnetic resonance imaging. The cumulative recurrence rate was 1.34% at 6 months, 6.35% at 12 months, and 6.35% at 60 months after surgery. Importantly, there was no recurrence after wide resection including of the peritoneum (0 of 37 cases). The efficacy of dienogest (an oral progestin), gonadotropin-releasing hormone agonists, and oral contraceptives was 91.7%, 81.8%, and 57.1%, respectively. Finally, 2 cases of malignant transformation were identified. Conclusion There was a low recurrence rate following surgery, and hormonal treatment is an option, although the current findings suggest surgical therapy as the first choice of treatment for umbilical endometriosis.

In Japan, the first endoscopic surgery, a laparoscopic cholecystectomy, was performed in 1990. Since then, operative procedures have been standardized, and the safety and efficacy of endoscopic surgery have been evaluated. In accordance with the social acceptance of endoscopic surgery as a less invasive type of surgery, the number of endoscopic procedures performed has increased in all surgical domains. The Japan Society for Endoscopic Surgery (JSES) has played an important role in the development of endoscopic surgery in Japan. Notably, a technical skills certification system for surgeons was established by the JSES to train instructors on how to teach safe endoscopic surgery. Furthermore, the JSES has conducted a national survey every 2 years. In 2019, 291,792 patients underwent endoscopic surgery in all surgical domains, such as abdominal, thoracic, mammary and thyroid gland, cardiovascular, obstetrics and gynecology, urologic, orthopedic, and plastic surgery. The 15th National Survey of Endoscopic Surgery conducted by the JSES demonstrated the status of laparoscopic surgery in Japan in 2018-2019.

Endometriosis, which exhibits enigmatic pathological features such as stromal fibrosis and proliferation of ectopic epithelial cells, is known as a refractory disease. Mesenchymal stem cells modulate the fibrosis in stromal tissues through their trophic and immunomodulatory properties. To investigate the potential of stem cells in treating endometriosis, we examined the secondary morphology and molecular alterations in endometriosis-like lesions after the administration of adipose tissue-derived stem cells (ASCs) to an experimental murine model of endometriosis. The infused ASCs were found integrated in the endometriosis-like lesions. Accompanied by the suppression of stromal fibrosis and proliferation of endometriotic epithelial cells, the infusion of ASCs with stemness potential suppressed the growth of endometriosis-like lesions and inhibited the expression of pro-inflammatory and pro-fibrotic cytokines, whereas no significant attenuation of endometriosis-like lesions occurred after the infusion of ASCs without stemness potential. Accordingly, it is plausible that the trophic and immunomodulatory properties of ASCs may regulate fibrosis in endometriosis-like lesions, suggesting that regenerative medicine has strong potential as an innovative treatment for patients with endometriosis.

Background Venous thromboembolism often develops after surgery and childbirth, resulting in death in some cases. Although early deep vein thrombosis (DVT) detection can predict pulmonary thromboembolism, there is no early screening method for DVT in pregnant women. Lack of consensus regarding significance or setting and cut-off value interpretation of D-dimer levels further impedes venous thromboembolism screening in pregnant women. This study aimed to examine the utility of third-trimester serum D-dimer levels as a screening test for DVT during pregnancy and to determine the frequency of asymptomatic DVT using lower-limb compression ultrasonography. Methods This single-center retrospective study included 497 pregnant women who underwent elective cesarean section at term in our hospital between January 2013 and December 2019. Serum D-dimer levels were preoperatively measured at 32–37 weeks’ gestation. The presence or absence of DVT in patients with serum D-dimer levels ≥ 3.0 µg/ml, the cut-off value, was examined using compression ultrasonography. In all patients, the presence or absence of clinical venous thrombosis (symptoms such as lower-limb pain, swelling, and heat sensation) was examined within 4 postoperative weeks. The Royal College of Obstetricians and Gynecologists Guideline 2015 was referred to determine risk factors for the onset of venous thrombosis during pregnancy. Among those, we examined the risk factors for DVT that result in high D-dimer levels during pregnancy. Results The median age and body mass index were 35 (20–47) years and 21.2 (16.4–41.1) kg/m2, respectively. Further, the median gestational age and D-dimer levels were 37 weeks and 2.1 (0.2–16.0) µg/ml, respectively. Compression ultrasonography was performed on 135 (26.5%) patients with a D-dimer level ≥ 3.0 µg/ml, with none of the patients showing DVT. All patients were followed up for 4 postoperative weeks, with none presenting with venous thromboembolism. Multivariate analysis showed that hypertensive disorders of pregnancy are an independent risk factor for venous thromboembolism that causes high D-dimer levels (odds ratio: 2.48, 95% confidence interval: 1.05–6.50, P = 0.04). Conclusion There may be low utility in screening for DVT using D-dimer levels in the third trimester. Further, prepartum asymptomatic DVT has a low frequency, indicating the low utility of compression ultrasonography. Trial registration Institutional Review Board of Tottori University Hospital (IRB no. 20A149).

Background We evaluated the necessity of urinary trypsin inhibitor for patients with threatened premature labor. Methods We enrolled 146 women with singleton pregnancies who were treated for threatened premature labor as inpatients. The uterine cervical length of each patient was ≤ 25 mm at 22-35 weeks of gestation on transvaginal ultrasonography. The patients were divided into two groups: the urinary trypsin inhibitor group (91 patients treated with urinary trypsin inhibitor daily) or non-urinary trypsin inhibitor group (55 patients not treated with urinary trypsin inhibitor). The childbirth outcomes were retrospectively assessed. Results The median cervical length measured on the day of admission was almost similar between the urinary trypsin inhibitor and non-urinary trypsin inhibitor groups. Depending on the symptoms of uterine contractions, we determined whether ritodrine hydrochloride and/or magnesium sulfate would be appropriate for treatment. The median gestational week at birth was 38 weeks in the urinary trypsin inhibitor group, and no obvious differences were observed when compared with the non-urinary trypsin inhibitor group. With regard to birth weight, no significant difference was found between the two groups (urinary trypsin inhibitor group, 2776 g; non-urinary trypsin inhibitor group, 2800 g). Conclusion Our data showed no significant beneficial effects of urinary trypsin inhibitor in the maternal course and delivery outcomes.

AIM We aimed to describe the clinical presentation, operative or medical management, and postoperative recurrence of bladder endometriosis (BE). METHODS We conducted a national survey to investigate BE cases from 2006 to 2016 in Japan. Histologically diagnosed cases were extracted and then investigated for the following factors: age at diagnosis, body mass index, symptoms, imaging modalities, surgical therapy, hormonal therapy, follow-up period, and postoperative recurrence. RESULTS Eighty-nine patients with pathologically benign BE were identified. Eighty patients underwent surgery, whereas nine did not. Moreover, 34 and 44 patients underwent transurethral resection (TUR) and partial cystectomy (PC), respectively. Cumulative recurrence rates were significantly higher with TUR than with PC (p

BACKGROUND: Endometriosis is an estrogen-dependent, inflammatory disease, and the role of estrogen is obvious because the symptoms associated with endometriosis often disappear after menopause, and GnRH agonists or progestin relieve the pelvic lesions and endometriosis-associated pain. However, there are limitations to these treatments that target the estrogen reduction in endometriotic lesions. We sought to define an aberrant gene expression derived from an epigenetic background in endometriosis.Objective: In the hope of overcoming the limitations of endocrine treatments in endometriosis, we examined estrogen receptor (ER)-dependent and -independent gene expressions promoted by active enhancers specifically hypomethylated in endometriotic cells. Patients: Institutional Review Boards approved this project. We obtained the informed consent from all patients. The chocolate cyst lining in ovaries of patients with endometriosis was the source of endometriotic tissue. As the control, the eutopic endometrial tissues were obtained from uteri of premenopausal women who had uterine leiomyoma.Methods: Stromal cells were prepared from endometriotic and endometrial tissues. Gene expression was examined using RT-PCR. The potential function of hypomethylated gene sequence as an active enhancer was evaluated by ChIP analysis using anti-H3K4me1 and anti-H3K27ac antibodies and eRNA expression analysis. Using ChIP-seq and ChIA-PET analysis in silico, ER-specific loci within gene bodies and the up- and downstream regions were extracted. ER-dependent gene expression was examined using estradiol or SERM.Results: ER expression in endometriotic cells.1) Relative expression of ERα mRNA was estimated to be one tenth of that in endometrial cells. 2) Relative expression of ERβ1 mRNA was 40-fold higher than that in endometrial cells, which is at a comparable level of the ERα. 3) ERβ2 mRNA expression was at a comparable level of the ERβ1. From our DNA methylation and gene expression analysis, 6 genes were selected and classified into 3 categories: estrogen-responsive genes with specific methylation (ESR1 and ESR2) or without any methylation (TGFα and GREB1), and estrogen-unresponsive but upregulated genes depending on specific hypomethylation (GATA6 and CYP19). 4) ChIP-seq and ChIA-PET analysis in silico suggested the presence of ER-specific loci within gene bodies and the up- and downstream in estrogen-responsive genes. 5) ChIP and eRNA expression analysis predicted active enhancer regions both in estrogen-responsive and -unresponsive genes. 6) In response to estrogen, TGFα and GREB1 expressions were upregulated, but ESR1 and ESR2 showed marginal responses.Conclusion: We focused on estrogen-responsive and -unresponsive genes linked to the epigenetic environment of endometriotic lesions, and revealed a facet of gene expression in endometriotic cells.

The Japan Society of Reproductive Medicine (JSRM) issued the guideline for cryopreservation of unfertilized eggs and ovarian tissue in 2013. The Japan Society of Obstetrics and Gynecology also announced the society opinions concerning cryopreservation of unfertilized/fertilized eggs and ovarian tissue in 2016, independently. To integrate these statements and to reflect the development of current therapeutic modalities in Japan, ethics committee of JSRM revised the guideline for cryopreservation of unfertilized eggs and ovarian tissues. First, considering that medical interventions for the treatment of malignancies might cause iatrogenic ovarian dysfunction, medical indication for cryopreservation of unfertilized eggs and ovarian tissues was specified. Second, the guideline of cryopreservation of unfertilized eggs and ovarian tissues for women that do not apparently possess malignancies and hope to preserve probable future fecundity was also described. Furthermore, requirements to be obeyed by facilities of reproductive medicine were raised to avoid the easy execution of these treatments. We hope that this new guideline could help the specialists of reproductive medicine in their daily practice and also would be helpful for women that definitely desire to preserve future fecundity.

AIMS Dydrogesterone is a retro-progesterone preparation widely used for over a half century. We sought to evaluate the efficacy and safety of dydrogesterone in Japanese women with dysmenorrhea. METHODS This study was conducted as an open-label, single-arm, multicenter study. One dydrogesterone 5-mg tablet (Duphaston) was administered orally twice daily for 21 days from the 5th to 25th day of each menstrual cycle. A total of 44 (safety analysis) and 31 patients (efficacy analysis) were enrolled. Total dysmenorrhea score, dysmenorrhea subscale scores, dysmenorrhea visual analog scale, severity of menstruation-related lower abdominal pain, low back pain, headache, and nausea/vomiting, basal body temperature, and serum estradiol and progesterone levels were evaluated. RESULTS Baseline of the total dysmenorrhea score was 4.61, which went down over time following the administration of dydrogesterone, and the decrease was statistically significant at and after 2nd cycle of menstruation. Mean change from baseline at the final evaluation point was -1.84 (P < 0.001). Severity of menstruation-related lower abdominal pain, low back pain, headache, and nausea/vomiting, in the evaluated menstruation cycles tended to decrease over time. Basal body temperature showed a biphasic pattern in 70% at baseline, 50% in 2nd menstruation cycle, and 61% in 5th menstruation cycle, and at least half of the patients may have had ovulation during the treatment. Incidence of adverse drug reactions was 31.8%, and the most common adverse event was metrorrhagia. CONCLUSION Dydrogesterone is efficacious, safe, and clinically beneficial in patients with dysmenorrhea, thereby indicating that dydrogesterone can be considered as a treatment option for patients with dysmenorrhea.

Aim Since 2014, Japan Society of Gynecologic and Obstetric Endoscopy and minimally invasive therapy (JSGOE) conducted a nationwide survey on gynecologic endoscopic surgery. We aimed to evaluate the current status and complications associated with endoscopic surgery by Japan gynecologic and obstetric endoscopy-database registry system (JOE-D). Methods Electrical medical records concerning the endoscopic surgery were generated from the daily use of reporting system. The subjects were all patients who underwent gynecologic endoscopic surgery. In addition to assessment of actual numbers, diagnosis, and operative methods, adverse events were registered. Results Total 203 970 patients performed laparoscopic, hysteroscopic and falloposcopic surgery for 3 years, 2014-2016. The numbers of endoscopic surgeries conducted in 2016 were increased more than 67 000, 13 000 or 450 cases, respectively. Incidence rates of complications involving these three types of surgeries in each year were approximately 3.1%. Incidences of intraoperative complications were relatively high in malignant diseases, laparoscopic-assisted vaginal hysterectomy (LAVH) and myomectomy (LAM). In total laparoscopic hysterectomy/laparoscopic hysterectomy (TLH/LH) performed from 2014 to 2016, ureteral injury as intra and postoperative complication occurred in 0.35%. In the past 3 years, the rates of vascular injury, urinary tract, and bowel injury as intraoperative complications caused by laparoscopic surgery were approximately 0.1%. In the hysteroscopic surgery, the rates of total intra- and postoperative complications were 0.78%. Conclusion We exhibited the current status by the nationwide survey of gynecologic endoscopic surgery all over Japan. Severe intra or postoperative complications were identified over the 3 years at a rate of 0.04%.

Endometriosis may be a definitive risk factor for ovarian cancer, the most fatal gynecological cancer. The ability of endometriosis to transform into malignancy, first described by Dr. Sampson in 1925, is considered a rare occurrence, affecting approximately 1% of ovarian endometriomas. Recently we conducted a retrospective study regarding the malignant transformation of endometriosis in Japanese women. Many studies have reported a consistent correlation between endometriosis and ovarian cancer according to histological subtypes. However, the existing epidemiological evidence linking this association is insufficient to define the role of endometriosis as a cause of ovarian cancer and to influence changes to current clinical practice. Prospective cohort studies are therefore needed to clarify this issue. Additionally, the results of many molecular studies are conflicting, and earlier studies showing the molecular aberrations involved in genomic instability and mutation that enable malignant transformation have not been replicated in later studies. Careful long-term observation of a patient with endometrioma is required to detect possible subsequent incidence of malignant transformation. More importantly, a precise strategy should be set up for better prevention, early detection, specific diagnosis and treatment targeting molecular pathogenesis to understand the mechanisms of endometriosis-associated ovarian cancer. Clinicians need to be aware of the increased ovarian cancer risk in women with endometriosis.

Endometriosis is a chronic inflammatory disorder associated with pelvic pain and infertility. Because surgical and medical therapies control symptoms, but it is hard to cure completely endometriosis, long term of pharmacologic management is necessary. Norethisterone (NET), one of progestins, has safety profile and advantage that allow long-term use. In this preliminary report, we showed the efficacy of NET in 6 patients with endometriosis. The size of ovarian endometrioma was decreased after treatment with NET for 6 months, and all patients were relieved from dysmenorrhea pain within 6 months, suggesting that NET would be a suitable medication to treat endometriosis.

Aim Endometriosis mostly affects the ovary but can also be present outside of the ovary including the pelvic peritoneum, intestine, urinary tract and lung. In case of ovarian endometriotic cyst, an increased risk of ovarian cancer, especially of clear cell and endometrioid histology, has been reported. However, because of the rarity, cancer occurrence from endometriosis at less common sites/rare sites is poorly understood. Methods We conducted a nationwide survey on the less common/rare site endometriosis in 3539 authorized facilities in Japan. We requested to complete a case report form for each case, including information on the history of endometriosis, treatment for endometriosis, type of surgery, involved site(s) of cancer and endometriosis, histology of cancer, chemotherapy and outcome. Results Out of 1397 confirmed cases of less common/rare site endometriosis, 11 cases of rare site endometriosis-associated cancer (RSEAC) were reported: seven of them were associated with intestinal endometriosis, three were associated with urinary tract endometriosis and one was associated with umbilical endometriosis. Interestingly, the histology was endometrioid in seven (64%) cases, and serous, seromucinous borderline, clear cell and mucinous in one case each (10%), differing from the case of ovarian endometriosis-associated cancer, in which clear cell carcinoma are more common. Conclusion Our nationwide survey on RSEAC has revealed that: (i) the incidence of malignant transformation may be lower than ovarian endometriosis, (ii) malignant transformation from endometriosis outside the abdominal cavity may be extremely rare and (iii) the histology of RSEAC is predominantly endometrioid type, suggesting an association of a hormonal effect.

Problem How are the effects of Tokishakuyakusan (TSS), a traditional Japanese medicine (Kampo) on murine endometriosis model? Methods BALB/c mice were used for making the murine endometriosis model. Homogeneous uterus was surgically implanted with lipopolysaccharide (LPS) in peritoneal cavity. We administered 2 weeks of TSS (1.0 g/kg) orally. Upon treatment completion, we performed the hot plate test for all mice and collected blood samples before sacrifice. Then, the endometriosis-like lesions and uteri in the abdominal cavity were harvested. Concentrations of several cytokines in sera and cyst fluids were measured using Bio-Plex Suspension Array System. IL-33 localization was determined by immunohistochemistry. Gene expression of inflammatory cytokines in the endometriosis-like lesions or the eutopic endometrium was evaluated by real-time RT-PCR. Results After 14 days of TSS treatment, the numbers of endometriosis-like cysts and cyst weight were significantly decreased. In TSS-treated mice, the latency against heat stimuli was extended. Inflammatory cytokine concentrations in sera were not changed by TSS treatment. TSS intake decreased IL-33 mRNA expression in endometriosis-like lesions and led to the tendency of attenuation of the elevated IL-33 synthesis in the cyst fluids of lesions. Conclusion These results suggest the TSS ameliorated the hyperalgesia and lesion formation on the LPS-accelerated endometriosis-like model. TSS represents a possible ideal target of novel therapeutics for endometriosis patients with dysmenorrhea.