AMIGO2 is involved in the spread of peritoneal metastasis in serous ovarian cancer via promoting adhesion to the peritoneal mesothelial cells.

BACKGROUND: Amphoterin-induced gene and open reading frame 2 (AMIGO2) have been reported to be related to the prognosis of colorectal, gastric, and cervical cancer. However, their association with ovarian cancer remains unclear. This study aimed to elucidate the role of AMIGO2 in ovarian cancer. METHODS: AMIGO2 expression was evaluated using immunohistochemistry in patients with ovarian serous carcinoma. We validated in vitro studies using four serous ovarian cancer cell lines and in vivo studies using a murine model. RESULTS: The AMIGO2-high group had significantly shorter progression-free survival (PFS) than the AMIGO2-low group. The predictive index of the AMIGO2-high group was considerably higher than that of the AMIGO2-low group. The rate of complete cytoreductive surgery was lower in the AMIGO2-high group than in the AMIGO2-low group. Moreover, in vitro studies revealed that four serous ovarian cancer cell lines exhibited AMIGO2 expression and adhesion to mesothelial cells. Adhesion to mesothelial cells was attenuated by AMIGO2 knockdown in SKOV3 and SHIN3 cells. Furthermore, AMIGO2 downregulation in SKOV3 cells significantly suppressed peritoneal dissemination in the murine model. CONCLUSION: These results suggest that high AMIGO2 expression in serous ovarian carcinoma cells contributes to a poor prognosis by promoting peritoneal metastasis through enhanced cell adhesion to mesothelial cells.

Efficacy and safety of a novel pain management device, AT-04, for endometriosis-related pain: study protocol for a phase III randomized controlled trial.

BACKGROUND: Endometriosis-related pain encompassing dysmenorrhea, dyspareunia, and chronic pelvic pain, reduces the quality of life in premenopausal women. Although treatment options for endometriosis alleviate this pain, approximately one-third of women still experience pain even after receiving treatment, indicating the need for novel approaches to pain relief in those women. The Angel Touch device (AT-04) is a portable magnetic fields irradiation device that incorporates a combination of mixed alternative magnetic fields at 2 kHz and 83.3 MHz. A phase III trial confirmed the efficacy and safety of AT-02, a prototype of AT-04, for pain relief in patients with fibromyalgia. METHODS: This is a phase III, multicenter, prospective, randomized, sham device-controlled, double-blind, parallel study. The participants will be premenopausal women aged > 18 years who have endometriosis-related pain with at least moderate severity. Considering dropouts, 50 participants have been deemed appropriate. Eligible women will be centrally registered, and the data center will randomly allocate them in a 1:1 ratio to the intervention and control groups. Women in the intervention group will receive electromagnetic wave irradiation generated by AT-04 and those who in the control group will wear a sham device for 16 weeks, and both groups will wear AT-04 for another 4 weeks. The primary outcome measure is the change in the Numeric Rating Scale score at 16 weeks compared with the baseline. Secondary outcome measures are efficacy for pelvic pain including dysmenorrhea and non-menstrual pain, and chronic pelvic pain not related to menstruation, dysmenorrhea, and dyspareunia, and improvement of quality of life during the study period. Safety will be evaluated by device defects and the frequency of adverse events. The study protocol has been approved by the Clinical Study Review Board of Chiba University Hospital, Chiba, Japan, and will be conducted in accordance with the principles of the Declaration of Helsinki and the Japanese Clinical Trials Act and relevant notifications. DISCUSSION: This study aims to develop a novel method of managing endometriosis-related pain. The AT-04 is an ultralow-invasive device that can be used without inhibiting ovulation, suggesting potential benefits to women of reproductive-age. Trial registration number Japan Registry of Clinical Trials (jRCTs032230278).

Endometriosis is a chronic inflammatory disorder that negatively impacts reproductive health via endometriosis-related pain, infertility, and endometriosis-associated ovarian cancer. Although current therapeutic options for endometriosis are effective for the endometriosis-related pain, approximately one-third of women still experience pain even after receiving treatment, indicating the need for novel approaches to pain relief in those women. This is the first randomized controlled trial to investigate the efficacy and safety of a novel portable pain management device, AT-04, that incorporates a combination of mixed alternating magnetic fields, for endometriosis-related pain. This is a multicenter, prospective, sham device-controlled, double-blind, parallel study. Enrolled women will have undergone standard hormonal treatment for endometriosis at baseline, and this allows for assessing whether the device remains effective when used in conjunction with existing treatment methods. The study also will explore the impact of AT-04 on reducing the size of ovarian endometriotic cysts that reflect the activity of endometriosis. The study reflects the strong desire by physicians to liberate women from the unbearable pain associated with endometriosis. The sole efficacy of AT-04 in treating endometriosis-related pain is difficult to evaluate as there is a possibility that menstrual cycles may influence the assessment of pain and quality of life. However, the study findings regarding the effectiveness of AT-04 for the treatment of endometriosis-related pain may benefit women with endometriosis who have pain that is not effectively relieved by other treatments. Consequently, it may contribute to the improvement of reproductive health within society.

Assisted reproductive technology in Japan: A summary report for 2021 by the Ethics Committee of the Japan Society of Obstetrics and Gynecology.

Purpose: The Japan Society of Obstetrics and Gynecology (JSOG) registry gathers comprehensive data from registered assisted reproductive technology (ART) facilities in Japan. Herein, we report 2021 ART cycle characteristics and outcomes. Methods: Descriptive statistics were used to summarize and analyze 2021 data. Results: In 2021, 625 ART facilities participated in the registry; 27 facilities did not conduct ART cycles and 598 registered treatment cycles. In total, 498 140 cycles were registered, and there were 69 797 neonates (increases of 10.7% and 15.5%, respectively, from the previous year). The number of freeze-all in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles decreased in 2021; the number of neonates born was 2268 for IVF-embryo transfer (ET) cycles and 2850 for ICSI cycles. Frozen-thawed ET (FET) cycles increased markedly from 2020 (11.2% increase). In 2021, 239 428 FET cycles were conducted, resulting in 87 174 pregnancies and 64 679 neonates. For fresh transfers, the total single ET, singleton pregnancy rate, and singleton live birth rates were 82.7%, 97.0%, and 97.3%; for FET, these rates were 84.9%, 96.9%, and 97.1%. Conclusions: The 2021 Japanese ART registry analysis showed marked increases in both total treatment cycles and live births from the previous year.

Impact of adenomyosis on perinatal outcomes: a large cohort study (JSOG database).

BACKGROUND: A previous study investigated the effect of adenomyosis on perinatal outcomes. Some studies have reported varying effect of adenomyosis on pregnancy outcomes in some patients and dependence on the degree and subtype of uterine lesions. To elucidate the impact of adenomyosis on perinatal outcomes. METHODS: This large-scale cohort study used the perinatal registry database of the Japan Society of Obstetrics and Gynecology. A dataset of 203,745 mothers who gave birth between January 2020 and December 2020 in Japan was included in the study. The participants were divided into two groups based on the presence or absence of adenomyosis. Information regarding the use of fertility treatment, delivery, obstetric complications, maternal treatments, infant, fetal appendages, obstetric history, underlying diseases, infectious diseases, use of drugs, and maternal and infant death were compared between the groups. RESULTS: In total, 1,204 participants had a history of adenomyosis and 151,105 did not. The adenomyosis group had higher rates of uterine rupture (0.2% vs. 0.01%, P = 0.02) and placenta accreta (2.0% vs. 0.5%, P < 0.001) than the non-adenomyosis group. A history of adenomyosis (odds ratio: 2.26; 95% confidence interval: 1.43-3.27; P < 0.001), uterine rupture (odds ratio: 3.45; 95% confidence interval: 0.89-19.65; P = 0.02), placental abruption (odds ratio: 2.11; 95% confidence interval: 1.27-3.31; P < 0.01), and fetal growth restriction (odds ratio: 2.66; 95% confidence interval: 2.00-3.48; P < 0.01) were independent risk factors for placenta accreta. CONCLUSION: Adenomyosis in pregnancies is associated with an increased risk of placenta accreta, uterine rupture, placental abruption, and fetal growth restriction. TRIAL REGISTRATION: Institutional Review Board of Tottori University Hospital (IRB no. 21A244).

Evaluation of the Characteristics of Ovarian Endometriomas in Patients with Endometriosis: Efficacy of a Low-Dose Estrogen/Progestogen Combination.

OBJECTIVES: Approximately 17-44% of women diagnosed with endometriosis have ovarian endometriomas (cysts). Although ovarian endometriomas may adversely affect quality of life and work performance, the associations among patient characteristics, cyst size, and pain in women with endometriosis have not yet been reported. Thus, the objective of this study was to assess the association among age, cyst size, and pain in women with ovarian endometriomas. DESIGN: This was a retrospective secondary analysis of pooled data from six randomized clinical trials on the use of low-dose estrogen/progestogen drugs for endometriosis. PARTICIPANTS/MATERIALS, SETTING, AND METHODS: Data on 491 patients enrolled in four randomized and two nonrandomized trials between 2003 and 2017 were pooled. None of the participants had undergone surgical treatment before trial participation. We examined differences in dysmenorrhea score, menstrual pain score, analgesic score, and pelvic pain, as measured using a visual analog scale (VAS), by age and endometrioma size. RESULTS: The mean dysmenorrhea, menstrual pain, and analgesic scores were 4.2, 2.2, and 2.0, respectively. The mean VAS for pelvic pain was 55, which decreased significantly with an increase in age. Age was not associated with endometrioma size, including volume and maximum diameter, or dysmenorrhea score. Additionally, endometrioma volume and maximum diameter were not associated with menstrual pain, analgesic score, or pelvic pain. LIMITATIONS: The details of past treatment history were not available; therefore, these could not be considered in the analysis. Additionally, the assessment of pain is heavily influenced by psychological factors, making it difficult to assess the true extent of pain. CONCLUSIONS: Endometrioma size was not associated with dysmenorrhea or pelvic pain measured using the VAS.

The learning curve of introduced robotic-assisted hysterectomy versus skilled laparoscopic hysterectomy for benign gynecologic diseases.

AIM: This study aimed to compare introduced robotic-assisted hysterectomy (RAH) and skilled total laparoscopic hysterectomy (TLH) for the treatment of benign gynecological diseases. METHODS: Patients who underwent RAH or TLH by two surgeons at the Tottori University Hospital between January 2018 and May 2022 were included in this retrospective study. Inclusion criteria were patients with 100-300 g of uterine weight. The exclusion criteria were patients with stage IV endometriosis. Mean operative time and learning curve were compared among the first-half RAH, second-half RAH, and TLH groups. RESULTS: There were 40 eligible cases (first-half RAH: 20 cases, second-half RAH: 20 cases) in the RAH group and 44 cases in the TLH group. The total operative time (TOT) of the second half of RAH was significantly shorter than that of the first half of RAH (p = 0.021) and was comparable to that of the TLH group. The operative time (OT) of the second half of RAH was shorter than that of TLH (p = 0.023). The preparation time of TLH was shorter than that of the RAH group (p < 0.01). The learning curve of the TOT in RAH crossed that of TLH on the 31st case of RAH. In contrast, both curves of the OT crossed on the 11th case of RAH. CONCLUSION: The TOT of the introduced RAH was equivalent to that of skilled TLH in approximately 30 cases since the first RAH. Furthermore, the OT of RAH was comparable to that of TLH in approximately 10 cases of surgery since the first RAH.

A nationwide survey of the use of the laparoscopic power morcellator.

AIM: 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. METHODS: 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. RESULTS: 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 in >90% 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. CONCLUSIONS: 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.

The Asian Society of Endometriosis and Adenomyosis guidelines for managing adenomyosis.

This is the first guidelines for adenomyosis from the Asian Society of Endometriosis and Adenomyosis.

D-dimer level significance for deep vein thrombosis screening in the third trimester: a retrospective study.

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 ).

Increased risk of obstetric complications in patients with adenomyosis: A narrative literature review.

Background: Reproductive-age women occasionally face the pathological condition of adenomyosis, which is often concurrent with endometriosis. It is believed that endometriosis and adenomyosis increases the risk of obstetric complications. Although new insights into the mechanism of obstetric complications due to endometriosis are emerging, there is little information on the etiology of adverse pregnancy outcomes in pregnant women with adenomyosis. Methods: We performed a literature review focusing on the pathophysiological pathways of obstetric complications in women with adenomyosis using currently available basic and clinical studies. We used the internet search engines PubMed and Google Scholar to search for studies published between January 2000 and June 2021. We carefully read pertinent sections within each document to ensure relevancy. Main findings: The prevalence of adverse pregnancy outcomes in women with adenomyosis is increased after adjusting for conceiving by assisted reproductive technology. Thus, adenomyosis emerges as a relevant factor associated with several obstetric complications such as preterm birth, preterm premature rupture of membranes, placental abruption, small for gestational age/fetal growth restriction, and preeclampsia. Conclusion: It is plausible that the impact of adenomyosis on pregnancy outcomes is not always the same; rather it is dependent on the degree of uterine involvement and subtypes.

National survey of bladder endometriosis cases in Japan.

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 < 0.05). The recurrence rate tended to be higher after laparoscopic PC (n = 24) than after open PC (n = 20), but the difference was not statistically significant (p = 0.0879). Of the nine nonsurgical patients, eight received hormonal therapy and one did not. Efficacy rates of dienogest, GnRH agonist, and OC were 85.7%, 66.7%, and 66.7%, respectively. Of five patients with BE extending to the ureter or ureteral orifices, two underwent PC and ureteroneocystostomy and one underwent total nephroureterectomy due to renal function loss. CONCLUSION: To our knowledge, this is the first study to compare the postoperative recurrence of BE after TUR and PC. We found that cumulative recurrence rate is significantly lower after PC than after TUR. BE extending to the ureter or ureteral orifices is a very challenging condition. Further studies are required for the optimal management of BE.

A controlled clinical trial comparing potent progestins, LNG-IUS and dienogest, for the treatment of women with adenomyosis.

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.

A National Survey of Umbilical Endometriosis in Japan.

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.

Cancers associated with extraovarian endometriosis at less common/rare sites: A nationwide survey in Japan.

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.

Efficacy of Tokishakuyakusan add-on therapy with low-dose oral contraceptive pills on endometriosis patients with dysmenorrhea.

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.

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.

The efficacy and safety of dydrogesterone for treatment of dysmenorrhea: An open-label multicenter clinical study.

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.

A nationwide survey on gynecologic endoscopic surgery in Japan, 2014-2016.

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%.

New knowledge and insights about the malignant transformation of endometriosis.

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.