Publications by authors named "Tasuku Harada"

138 Publications

A Case Report of an Accessory and Cavitated Uterine Mass Treated with Total Laparoscopic Hysterectomy.

Yonago Acta Med 2021 May 17;64(2):207-209. Epub 2021 Mar 17.

Department of Obstetrics and Gynecology, Tottori University Faculty of Medicine, Yonago 683-8504, Japan.

Accessory and Cavitated Uterine Mass (ACUM) is a condition defined by the presence of a non-communicating uterine mass close to the insertion of the round ligament. ACUM is a rare Müllerian anomaly found in young women and is diagnosed by the presents of a central cavity in the uterus, lined by functional endometrium, and surrounded by a ring of smooth muscle. In most cases, surgical treatment is recommended due to severe dysmenorrhea. Herein, we present a case of a woman with severe dysmenorrhea since adolescence which was not relieved with any form of hormonal treatment. ACUM was suspected preoperatively based on MRI findings, and she was treated with total laparoscopic hysterectomy. A uterine mass was found at the insertion of the right round ligament during surgery. All her symptoms improved after resection.
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http://dx.doi.org/10.33160/yam.2021.05.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128662PMC
May 2021

Evaluating the efficacy and safety of ureteral stent placement as a preoperative procedure for gynecological cancer surgeries: A retrospective cohort study.

J Obstet Gynaecol Res 2021 May 11. Epub 2021 May 11.

Department of Obstetrics and Gynecology, Tottori University School of Medicine, Yonago, Tottori Prefecture, Japan.

Aim: To evaluate the efficacy and safety of ureteral stent placement (USP) as a preoperative procedure for gynecological cancer surgeries.

Methods: This was a single-institution retrospective cohort study of 259 patients with gynecological cancer who underwent laparotomy. In 126 patients (USP+ group), a ureteral stent was inserted into the bilateral ureters after the induction of general anesthesia. The remaining 133 patients (USP- group) did not undergo USP. We compared operation time, blood loss, and frequency of laparotomy-related perioperative urinary complications between the groups. The stent was removed 5-7 days postoperatively. Patients were evaluated for signs of hydronephrosis at discharge. The Fisher's exact test was used to investigate the significance of differences in patient characteristics, and multivariate analysis was performed using a Cox proportional hazards model. A p-value of <0.05 was considered statistically significant.

Results: There were no significant differences in age and body mass index between the groups. Two patients in the USP- group experienced intraoperative ureteral injury. Total operation time and blood loss were significantly increased in the USP+ group. The risk of bladder tamponade and postoperative hydronephrosis was influenced by USP. USP was unaffected by a history of abdominal surgery, stage of tumor progression, lymphadenectomy type, or hysterectomy type.

Conclusions: The incidence of bladder tamponade and hydronephrosis postoperatively was significantly higher in patients with USP than in those without USP.
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http://dx.doi.org/10.1111/jog.14829DOI Listing
May 2021

Efficacy of cyclic and extended regimens of ethinylestradiol 0.02 mg -levonorgestrel 0.09 mg for dysmenorrhea: A placebo-controlled, double-blind, randomized trial.

Reprod Med Biol 2021 Apr 27;20(2):215-223. Epub 2021 Feb 27.

Department of Integrated Women's Health St. Luke's International Hospital Tokyo Japan.

Purpose: We aimed to evaluate the efficacy and safety of 28-day Cyclic and 84-day Extended regimens of NPC-16 (ethinylestradiol 0.02 mg plus levonorgestrel 0.09 mg) in patients with dysmenorrhea.

Methods: This was a placebo-controlled, double-blind, randomized trial conducted in Japan. A total of 251 primary and secondary dysmenorrhea patients were randomly assigned to the NPC-16-Cyclic group, NPC-16-Extended group, or the Placebo group. The primary end point was a comparison of the efficacy and safety of the Cyclic and Extended NPC-16 regimen for the treatment of dysmenorrhea relative to the Placebo.

Main Findings: Significantly greater reductions in total dysmenorrhea score and visual analog scale score were observed in the Cyclic and Extended groups compared with the Placebo group. Compared with the Cyclic regimen as a secondary end point, the Extended regimen exhibited greater efficacy in the treatment of dysmenorrhea over the course of the study period, particularly in patients with severe dysmenorrhea. The incidence of adverse drug reactions (ADRs) was significantly higher in the Cyclic and Extended groups than in the Placebo group.

Conclusion: The Cyclic and Extended regimens of NPC-16 significantly reduced dysmenorrhea severity compared to placebo. The Extended regimen was superior to cyclic regimen in reducing the dysmenorrhea.
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http://dx.doi.org/10.1002/rmb2.12373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022088PMC
April 2021

National survey of bladder endometriosis cases in Japan.

J Obstet Gynaecol Res 2021 Apr 4;47(4):1451-1461. Epub 2021 Jan 4.

Department of Obstetrics and Gynecology, University of Tokyo, Tokyo, 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.
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http://dx.doi.org/10.1111/jog.14656DOI Listing
April 2021

Plasma Oxytocin Concentrations During and After Gestation in Japanese Pregnant Women Affected by Anxiety Disorder and Endometriosis.

Yonago Acta Med 2020 Nov 5;63(4):301-307. Epub 2020 Nov 5.

Division of Health Administration and Promotion, Department of Social Medicine, Faculty of Medicine, Tottori University, Yonago 683-8503, Japan.

Background: Oxytocin has a key role in mother-infant bonding, maternal care, social interaction, and stress-related psychiatric disorders. However, the factors determining oxytocin concentrations during and after pregnancy such as medical history related to nursing or parental behavior are unknown. To elucidate these, we analyzed the relationships between oxytocin concentrations during and after pregnancy, and medical history assessed in the Japan Environment and Children's Study (JECS).

Methods: We then selected the pregnant women with a medical history of anxiety disorder and endometriosis as cases and pregnant women without medical history as controls adjusting the cohort for age and parity for a nested case-control study, after which 162 women remained for analysis. We evaluated 162 pregnant women from JECS using answers provided in a questionnaire and by measuring plasma oxytocin concentration by ELISA during the first (T1) and second (T2) trimesters of pregnancy, and after childbirth (T3).

Results: Oxytocin concentration increased in a time dependent manner, consistent with previous reports. There were weak negative correlations between oxytocin concentration at T1 and the mother's age and height, but no correlation with other factors. The mean oxytocin concentrations of pregnant women with a history of an anxiety disorder ( = 7) and endometriosis ( = 13) were significantly lower than those of pregnant women with no such history at T2 and T3.

Conclusion: These results suggest that oxytocin concentrations during and after pregnancy were affected by a past history of anxiety disorder and endometriosis. This is the first study of the relationship between oxytocin concentration and endometriosis. To elucidate the molecular mechanisms, further study is needed.
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http://dx.doi.org/10.33160/yam.2020.11.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683907PMC
November 2020

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

J Obstet Gynaecol Res 2020 Oct 20. Epub 2020 Oct 20.

Department of Obstetrics and Gynecology, University of Tokyo, Tokyo, Japan.

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.
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http://dx.doi.org/10.1111/jog.14522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756675PMC
October 2020

Animal models for research on endometriosis.

Front Biosci (Elite Ed) 2021 01 1;13:37-53. Epub 2021 Jan 1.

Department of Obstetrics and Gynecology, Tottori University Faculty of Medicine, Yonago, 683-8504, Japan.

Endometriosis results from the aberrant growth of endometrium outside the inner lining of the uterine cavity. Similar to humans, the primates also menstruate and hence, the primate models constitute the gold standard for studying the pathogenesis and potential treatment for this disabling disease in women. Due to the expense in carrying endometriosis research in primates, other models have been developed for understanding the pathobiology and potential treatment of endometriosis. This includes explanting human endometrial tissues in athymic nude mice or using homologous mouse models. Here, we examine the murine models of endometriosis, the impact of forced induced inflammation on its development, similarities in the gene expression profile in the endometriotic tissues in such models with that seen in human endometriosis, and the drugs that are being used in such models as potential new treatment for endometriosis.
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January 2021

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

J Obstet Gynaecol Res 2020 Nov 24;46(11):2280-2286. Epub 2020 Aug 24.

Department of Obstetrics and Gynecology, Tottori University Faculty of Medicine, Yonago, Japan.

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.
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http://dx.doi.org/10.1111/jog.14424DOI Listing
November 2020

Effects of pretreatment radiological and pathological lymph node statuses on prognosis in patients with ovarian cancer who underwent interval debulking surgery with lymphadenectomy following neoadjuvant chemotherapy.

J Obstet Gynaecol Res 2021 Jan 23;47(1):152-158. Epub 2020 Aug 23.

Department of Obstetrics and Gynecology, Tottori University School of Medicine, Yonago, Tottori, Japan.

Aim: To analyze whether radiological and pathological lymph node statuses affected prognosis in patients with epithelial ovarian cancer who underwent neoadjuvant chemotherapy followed by interval debulking surgery.

Methods: In total, 82 patients undergoing interval debulking surgery, including systematic retroperitoneal lymphadenectomy, were eligible for this study. We retrospectively analyzed the association among radiological diagnosed retroperitoneal lymphadenopathy by computed tomographic scan before (rLN) and after (yrLN) neoadjuvant chemotherapy, pathological lymph node metastasis (pLN) and prognosis. Patient survival distribution was calculated using the Kaplan-Meier method.

Results: There were 36 rLN+ cases (44%); there were no significant differences between rLN+ and rLN- with respect to progression-free survival and overall survival. Progression-free survival and overall survival did not differ between yrLN+ cases and yrLN- cases. Thirty-nine cases (47.5%) were pLN+, and both progression-free survival and overall survival were significantly shorter in pLN+ cases than in pLN- cases (P < 0.001 and P = 0.004, respectively). In univariate analysis, FIGO stage, pLN and surgical completion were prognostic factors for overall survival. Moreover, in multivariate analysis, pLN+ was the independent prognostic factor for progression-free survival (P = 0.001, 95% confidence interval: 1.911-15.69), and pLN and surgical completion were the only independent prognostic factors for overall survival (P = 0.046, P = 0.012).

Conclusion: Radiological lymph node status may not be a prognostic factor in patients with ovarian cancer who underwent neoadjuvant chemotherapy followed by interval debulking surgery. Pathological lymph node metastasis affects progression-free survival and overall survival.
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http://dx.doi.org/10.1111/jog.14446DOI Listing
January 2021

Long-term evaluation of renal function and neurogenic bladder following radical hysterectomy in patients with uterine cervical cancer.

J Obstet Gynaecol Res 2020 Oct 19;46(10):2108-2114. Epub 2020 Jul 19.

Department of Obstetrics and Gynecology, Tottori University School of Medicine, Yonago, Tottori, Japan.

Objective: This study aimed to determine whether radical hysterectomy (RH) affects renal function.

Methods: Renal function was followed up in 83 patients with stage IB1-IIB cervical cancer who underwent RH during 2006-2015. Serum creatinine (sCre) levels were measured preoperatively and every year postoperatively. Estimated glomerular filtration rate (eGFR) was calculated using sCre levels. Patients who were unable to urinate by themselves or whose residual urine was ≥100 mL were referred to a urologist with the diagnosis of neurogenic bladder (NB). The relationship between NB occurrence and changes in sCre level or eGFR was evaluated respectively.

Results: Urological intervention was required in 45 patients (54.2%), and self-urethral catheterization was performed in 41 (49.3%) patients. The NB and clean intermittent catheterization (CIC) groups exhibited significant increases in sCre levels, which were not observed in the non-NB or non-CIC groups. In the non-NB group, eGFR did not change following surgery. However, in the NB group, significant decreases in eGFRs were observed at postoperative 2 and 3 years and at final follow-up. There was no difference in the incidence of cardiovascular events between patients with and without NB.

Conclusion: In patients with NB following RH, a significant decrease in renal function was observed after postoperative 2 years.
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http://dx.doi.org/10.1111/jog.14394DOI Listing
October 2020

Efficacy of panniculectomy-combined surgery in superobese patients with endometrial cancer: A case report and literature review.

Int J Surg Case Rep 2020 6;72:99-103. Epub 2020 Jun 6.

Department of Obstetrics and Gynecology, Tottori University School of Medicine, 36-1 Nishicho, Yonago, Tottori, 683-5804, Japan.

Introduction: Panniculectomy is regarded as an effective approach in highly obese patients with endometrial cancer to improve surgical access or space of the surgical field.

Presentation Of Case: A 66-year-old nulliparous woman was brought in from another hospital to our institute for newly diagnosed endometrial carcinoma. The patient was 158 cm in height and weighed 135.8 kg during the first visit to our hospital. Her body mass Index (BMI) was 54.4 kg/m. Unfortunately, the patient developed an umbilical hernia and strangulation before the surgery. Emergency partial ileal resection and simple closure of the umbilical hernia were performed. We were finally able to perform simple hysterectomy, and bilateral salpingo-oophorectomy with panniculectomy. Her weight at the time of surgery was 115.5 kg which had been reduced by 20 kg from the time she was first brought in, and the BMI decreased from 54.4 to 45.3 kg/m. The patient underwent follow-up without adjuvant therapy since she was in the low-risk group, and showed no signs of recurrence 12 months after surgery.

Discussion: There are various risks associated with surgery in highly obese patients. Diabetes mellitus, hypertension and smoking are reported to be risk factors of wound complication in panniculectomy, and it was reported that diabetes mellitus was an independent risk factor.

Conclusion: The combination of panniculectomy was considered as an effective approach to perform safe surgery for obese patients.
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http://dx.doi.org/10.1016/j.ijscr.2020.05.066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298323PMC
June 2020

Deep vein thrombosis and serum D-dimer after pelvic lymphadenectomy in gynecological cancer.

Int J Gynecol Cancer 2020 06 9;30(6):860-864. Epub 2020 Apr 9.

Obstetrics and Gynecology, Tottori University, Yonago, Tottori, Japan.

Introduction: Venous thromboembolism prevention during the perioperative period requires comprehensive risk-level assessment. The aim of this study was to evaluate the incidence of deep vein thrombosis and to assess the cut-off levels of serum D-dimer as a screening strategy for deep vein thrombosis during the perioperative period.

Methods: A total of 205 patients (ovarian cancer: 68, endometrial cancer: 76, cervical cancer: 61) who underwent gynecological surgery, including retroperitoneal lymph node dissection, were enrolled. We retrospectively analyzed the data on the cut-off value of D-dimer assessed using area under the receiver operating characteristic curve preoperatively, and 2 or 3 months, postoperatively. All patients underwent leg vein ultrasonography regardless of the serum D-dimer level. Furthermore, CT scans were performed to evaluate both disease status and venous thromboembolism, including pulmonary thromboembolism. Statistical analyzes were performed using the Mann-Whitney -test (D-dimer values of each cancer), Chi-square test, Fisher's exact test (incidence of deep vein thrombosis), and one-way analysis of variance (patient characteristics).

Results: A total of 205 patients (ovarian cancer: 68, endometrial cancer: 76, cervical cancer: 61) who underwent gynecological surgery, including retroperitoneal lymph node dissection, were included in the analysis. Deep vein thrombosis rates were significantly higher in patients with ovarian cancer (P<0.001). The postoperative D-dimer value was significantly higher than the preoperative value. Postoperative D-dimer values were also significantly higher in patients who received adjuvant chemotherapy (P=0.001). The cut-off value of D-dimer was 1.55 µg/mL preoperatively (sensitivity, 48.0%; specificity, 94.1%), and this value was higher postoperatively, at 1.95 µg/mL (sensitivity, 37.0%; specificity, 90.9%).

Conclusion: Postoperative D-dimer values are higher not only after surgery but also in patients who received adjuvant chemotherapy. The cut-off value of D-dimer at 2 or 3 months postoperatively was higher than preoperative value.
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http://dx.doi.org/10.1136/ijgc-2019-000914DOI Listing
June 2020

Ultralong administration of gonadotropin-releasing hormone agonists before in vitro fertilization improves fertilization rate but not clinical pregnancy rate in women with mild endometriosis: a prospective, randomized, controlled trial.

Fertil Steril 2020 04 5;113(4):828-835. Epub 2020 Mar 5.

Department of Obstetrics and Gynecology, Faculty of Medicine, Tottori University, Yonago, Japan.

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.
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http://dx.doi.org/10.1016/j.fertnstert.2019.12.018DOI Listing
April 2020

Changes in serum D-dimer level and effect of enoxaparin sodium after a cesarean section: a retrospective study.

J Matern Fetal Neonatal Med 2020 Feb 11:1-6. Epub 2020 Feb 11.

Department of Obstetrics and Gynecology, Japanese Red Cross Yamaguchi Hospital, Yamaguchi, Japan.

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) (<.001). The D-dimer levels on POD1 were higher in patients aged ≥35 years and with a hospitalization history of threatened preterm labor. In addition, on POD6, patients aged ≥35 years and with a high body mass index had high D-levels. Following a multivariate analysis, the elderly represent an independent factor for high D-levels. DVT was not observed. 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.
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http://dx.doi.org/10.1080/14767058.2020.1725884DOI Listing
February 2020

Comparison of Total Laparoscopic Hysterectomy with Abdominal Total Hysterectomy in Patients with Benign Disease: A Retrospective Cohort Study.

Yonago Acta Med 2019 Dec 25;62(4):273-277. Epub 2019 Oct 25.

Department of Obstetrics and Gynecology, Japanese Red Cross Yamaguchi Hospital, Yamaguchi 753-0092, Japan.

Background: The present study aimed to determine whether total laparoscopic hysterectomy (TLH) is being implemented safely and appropriately compared with abdominal total hysterectomy (ATH) in our hospital.

Methods: We retrospectively reviewed clinical records of 102 patients who underwent total hysterectomy for benign gynecological disease at Japanese Red Cross Yamaguchi Hospital from January 2017 to August 2018. We examined periods of hospital stay, operation time, blood loss, weight of the uterus, frequency of perioperative complications, and the duration from the first visit to the date of surgery. < 0.05 was considered to be statistically significant indicated statistical significance.

Results: TLH and ATH were performed in 55 (53%) and 47 (46%) cases, respectively. The TLH group had significantly longer total operation time [133 (82-205) min vs. 87 (57-155) min, < 0.0001], lesser blood loss [5 (5-35) g vs. 100 (10-820) g, < 0.0001], shorter hospital stay [7 (5-14) days vs. 10 (9-26) days, < 0.0001], and lighter uterine weight [206 (27-658) g vs. 554 (79-2284) g, < 0.0001] than the ATH group. The frequency of perioperative complications did not differ between the two groups (3.5% vs. 8.0%, = 0.4103).

Conclusion: TLH had a longer operation time and a lesser excised uterine weight, but it had less intraoperative blood loss, shorter hospital stay, and no difference in perioperative complication frequency when compared with ATH.
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http://dx.doi.org/10.33160/yam.2019.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6872949PMC
December 2019

Juvenile Granulosa Cell Tumor with Elevated Peripheral Interleukin-6 Level Shows Prolonged Fever and Delayed Puberty.

Yonago Acta Med 2019 Sep 13;62(3):263-267. Epub 2019 Sep 13.

Division of Pediatrics and Perinatology, Department of Multidisciplinary Internal Medicine, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504, Japan.

Juvenile granulosa cell tumor (JGCT), classified as a sex cord-stromal tumor, is a rare neoplasm. This is an instructive case report of JGCT accompanied by augmented interleukin (IL)-6 secretion. A 13-year-old girl with prolonged fever and delayed puberty was diagnosed with JGCT of the left ovary based on an imaging study and pathological investigation. Although it was not clear whether IL-6 was secreted from the tumor cells, her serum level of IL-6 was very high. After tumorectomy, the patient's symptoms immediately disappeared, her IL-6 level decreased, and she entered puberty. Therefore, augmented IL-6 secretion production induced by tumors should be considered a potential cause of prolonged fever and/or delayed puberty.
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http://dx.doi.org/10.33160/yam.2019.09.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739248PMC
September 2019

Tokishakuyakusan, a Kampo medicine, attenuates endometriosis-like lesions and hyperalgesia in murine with endometriosis-like symptoms.

Am J Reprod Immunol 2019 11 10;82(5):e13182. Epub 2019 Sep 10.

Department of Obstetrics and Gynecology, Tottori University Faculty of Medicine, Yonago, Japan.

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.
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http://dx.doi.org/10.1111/aji.13182DOI Listing
November 2019

Adverse obstetrical outcomes for women with endometriosis and adenomyosis: A large cohort of the Japan Environment and Children's Study.

PLoS One 2019 2;14(8):e0220256. Epub 2019 Aug 2.

Department of Obstetrics and Gynecology, Tottori University Faculty of Medicine, Yonago, Japan.

Background: Because of the increased number of diagnosed cases of endometriosis or adenomyosis resulting in infertility, many women require assisted reproductive technology (ART) to become pregnant. However, incidences of obstetric complications are increased for women who conceive using ART. There has been no prospective cohort study examining the influence of endometriosis and adenomyosis on obstetric outcomes after adjusting for the confounding influence of ART therapy.

Objective: This study evaluated the impact of endometriosis and adenomyosis on the incidence of adverse pregnancy outcomes.

Study Design: Data were obtained from a prospective cohort study, known as the Japan Environment and Children's Study (JECS), of the incidence of obstetric complications for women with endometriosis and adenomyosis. The data of 103,099 pregnancies that resulted in live birth or stillbirth or that were terminated through abortion between February 2011 and July 2014 in Japan were included.

Results: Women with endometriosis or adenomyosis were at increased risk for complications during pregnancy compared to those without a medical history of endometriosis (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.23 to 1.41) or adenomyosis (OR, 1.72; 95% CI, 1.37 to 2.16). Our analysis showed that the adjusted ORs for obstetric complications of pregnant women who conceived naturally or after infertility treatment that did not involve ART therapy were 1.26 (CI, 1.17 to 1.35) for pregnant women with a history of endometriosis and 1.52 (CI, 1.19 to 1.94) for those with a history of adenomyosis.

Conclusions: The presence of endometriosis and adenomyosis significantly increased the prevalence of obstetric complications after adjusting for the influence of ART outcomes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0220256PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6677302PMC
February 2020

Evaluating Chemotherapy-induced Nausea and Vomiting and Food Intake in Patients With Gynecologic Cancer.

Anticancer Res 2019 Aug;39(8):4555-4560

Department of Obstetrics and Gynecology, Tottori University School of Medicine, Yonago, Japan.

Background/aim: Treatments for controlling delayed nausea after chemotherapy are inadequate, potentially inciting malnutrition. We sought to determine the incidence of nausea, anorexia, and food intake after chemotherapy.

Patients And Methods: Subjects were females with gynecological cancers who underwent chemotherapy between 2008 and 2013. Nausea, anorexia, and food intake in the acute (day 1) and delayed phases (days 2 and 3) were retrospectively evaluated.

Results: Subjects included 156 females. Chemotherapies were highly (HEC; n=24) and moderately emetogenic (MEC; n=132). There were no significant between-group differences for anorexia control during either the acute or the delayed phase and both groups demonstrated significantly worse control of nausea during the delayed phase. In the HEC group, food intake was significantly reduced on days 2 and 3 compared with day 1.

Conclusion: Rates of nausea, anorexia, and food intake significantly worsened over time, particularly in the MEC group. Current supportive therapies appear inadequate and should be improved.
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http://dx.doi.org/10.21873/anticanres.13633DOI Listing
August 2019

Re-evaluation of Urinary Trypsin Inhibitor on Pregnancy Course in Patients with Threatened Preterm Delivery: A Single-Center Retrospective Study.

Yonago Acta Med 2019 Jun 20;62(2):204-210. Epub 2019 Jun 20.

Department of Obstetrics and Gynecology, Japanese Red Cross Yamaguchi Hospital, Yamaguchi 753-0092, Japan.

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.
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http://dx.doi.org/10.33160/yam.2019.06.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584260PMC
June 2019

Training in the Departments of Urology and Surgery for Gynecologists in Japan.

Yonago Acta Med 2019 Jun 20;62(2):198-203. Epub 2019 Jun 20.

Department of Obstetrics and Gynecology, Japanese Red Cross Yamaguchi Hospital, Yamaguchi 753-0092, Japan.

Background: The authors wanted to understand the current situation concerning Japanese obstetricians' and gynecologists' ideas for and against training in other departments.

Methods: We sent questionnaires to obstetrics and gynecology (Ob-Gyn) specialists via a social networking service (SNS) in Japan. They answered anonymously using Google Forms over the internet.

Results: The respondents comprised 120 Ob-Gyn specialists, and their age ranges of 28-29, 30-39, 40-49, and 50 or more, were 5.8%, 73.3%, 15.8%, and 5.0%, respectively. Only five Ob-Gyn specialists (4.2%) had experience in other departments, specifically gastrointestinal and urology. Ninety percent of them responded that they thought training in other departments was useful for developing clinical and surgical skills. In addition, 91.0% of respondents thought that surgical knowledge and skills were necessary in the clinical practice of gynecology, while 94% stated training in urology was also necessary. However, 49.2% of respondents answered that they may feel stress training in other departments where there were many issues, including a lack of personnel and difficulties securing cases.

Conclusion: Many Ob-Gyn specialists think training in other departments is necessary, but potential problems include proper training implementation and stress management for residents. If additional training is enforced, greater flexibility in each facility will be required.
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http://dx.doi.org/10.33160/yam.2019.06.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584265PMC
June 2019

Retroperitoneal Endometrioid Carcinoma Arising from Ureteral Endometriosis.

Case Rep Obstet Gynecol 2019 10;2019:9273858. Epub 2019 Jun 10.

Department of Obstetrics and Gynecology, Tottori University Hospital, Japan.

Primary ureteral endometriosis is considered to be an uncommon form with an incidence of less than 0.1% in endometriosis. We reported a case of retroperitoneal endometrioid carcinoma possibly arising from ureteral endometriosis. A 52-year-old woman complained left backache. A solid mass in left retroperitoneal cavity with hydronephrosis was found. Diagnostic laparotomy with bilateral salpingo-oophorectomy and biopsy of the mass were performed. Although the primary lesion was not defined in the surgery, the histopathological diagnosis of specimen was endometrioid carcinoma. In the interval debulking surgery after the chemotherapy, tumor adjacent the left iliac vessels was observed. We resected the mass together with 5 cm left ureter and performed ureterectomy and anastomosis. The patient was diagnosed as the malignant transformation of ureteral endometriosis. Adjuvant chemotherapy is now undergoing. In case of finding the cancer tissue in women, we should take into account the malignant transformation of less common endometriosis, including ureteral endometriosis.
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http://dx.doi.org/10.1155/2019/9273858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590549PMC
June 2019

Serum vascular endothelial growth factor A and vascular endothelial growth factor receptor 2 as prognostic biomarkers for uterine cervical cancer.

Int J Clin Oncol 2019 Dec 24;24(12):1612-1619. Epub 2019 Jun 24.

Department of Obstetrics and Gynecology, Tottori University School of Medicine, 36-1 Nishicho, Yonago, 683-8504, Japan.

Background: There are few studies on serum vascular endothelial growth factors and receptors (VEGF/VEGFRs) in patients with uterine cervical cancer (CC). The aim of this study was to determine whether VEGF/VEGFRs could be used as prognostic biomarkers in patients with CC.

Methods: A total of 107 patients with stage IB to IIB CC, who underwent radical hysterectomy at Tottori University Hospital between 2006 and 2015, were included in this study. Serum samples were collected prior to radical hysterectomy, and levels of VEGF-A, VEGF-C, VEGFR-1, and VEGFR-2 were analyzed by enzyme-linked immunosorbent assays. We evaluated the association between the levels of these angiogenic factors and clinicopathologic variables. Survival analysis of 93 patients treated between 2006 and 2013 was performed.

Results: The levels of VEGF-A in patients with bulky tumor, pelvic lymph-node involvement (PLNI), and parametrial infiltration (PI) were significantly higher than those in patients without these factors (P = 0.022, P = 0.020, and P = 0.0013, respectively). The overall survival (OS) of patients with high VEGF-A and VEGFR-2 defined by median levels was significantly lower than the OS of patients with low levels of VEGF-A and VEGFR-2 (P = 0.014, P = 0.012, respectively). Multivariate analysis revealed that PLNI, serum VEGF-A levels, and serum VEGFR-2 levels were independent prognostic factors for OS (hazard ratio for VEGF-A 3.42, 95% CI 1.07-13.2; hazard ratio for VEGFR-2 6.37, 95% CI 1.59-43.5).

Conclusion: Our results suggest that serum VEGF-A and VEGFR-2 may be promising prognostic biomarkers for CC.
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http://dx.doi.org/10.1007/s10147-019-01495-xDOI Listing
December 2019

lncRNA UCA1-Mediated Cdc42 Signaling Promotes Oncolytic Vaccinia Virus Cell-to-Cell Spread in Ovarian Cancer.

Mol Ther Oncolytics 2019 Jun 26;13:35-48. Epub 2019 Mar 26.

Department of Biomedical Science, Graduate School of Medical Sciences, Tottori University, 86 Nishi-cho, Yonago 683-8503, Japan.

Oncolytic vaccinia virus (OVV) has demonstrated appropriate safety profiles for clinical development. Although designed to kill cancer cells efficiently, OVV sensitivity varies in individual cancers, and predictive biomarkers of therapeutic responses have not been identified. Here we found that OVV was much more efficient in KFTX paclitaxel-resistant ovarian cancer cells compared to that in KFlow paclitaxel-sensitive cells. Microarray analysis identified long non-coding RNA urothelial carcinoma-associated 1 (UCA1) upregulation, which contributed to both enhanced paclitaxel resistance and OVV spread. In addition, UCA1 expression correlated with efficient OVV spread in other ovarian cell lines and primary cancer cell cultures. When host pathways underlying OVV spread were analyzed, differences were detected in the activation of the Rho GTPase Cdc42, suggesting that filopodia formation enhances OVV cell-to-cell spread and tumor migration. Moreover, we established a clinically relevant mouse model of peritoneal metastasis using KFTX or KFlow cells. Paclitaxel exerted anti-tumor effects on KFlow, but not KFTX, tumors. In mice bearing KFTX cells after paclitaxel failure, OVV treatment induced the regression of residual tumors and improved survival. Our findings demonstrated that UCA1 promotes OVV cell-to-cell spread in ovarian cancer, resulting in enhanced therapeutic outcome.
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http://dx.doi.org/10.1016/j.omto.2019.03.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463205PMC
June 2019

A National Survey of Umbilical Endometriosis in Japan.

J Minim Invasive Gynecol 2020 01 6;27(1):80-87. Epub 2019 Apr 6.

Departments of Obstetrics and Gynecology (Drs. Hirata, Koga, Fukuda, Neriishi, and Osuga).

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.
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http://dx.doi.org/10.1016/j.jmig.2019.02.021DOI Listing
January 2020

Comparison of laparoscopic surgery and conventional laparotomy for surgical staging of patients with presumed low-risk endometrial cancer: The current state of Japan.

Taiwan J Obstet Gynecol 2019 Jan;58(1):99-104

Department of Obstetrics and Gynecology, Tottori University Fucluty of Medicine, 36-1 Nishimachi, Yonago, 683-8504, Japan.

Objective: National health insurance coverage for the laparoscopic staging surgery for patients with stage IA endometrial cancer started from April 2014 in Japan. We conducted this retrospective study to evaluate the surgical outcomes of the laparoscopic surgery for patients with low-risk endometrial cancer compared with those of the laparotomy.

Materials And Methods: A total of 120 patients with presumed low-risk endometrial cancer, who were treated at Tottori University Hospital between 2005 and 2016, were eligible for this study. The laparoscopic staging surgery included only the pelvic lymphadenectomy and not the para-aortic lymphadenectomy. We evaluated the discrepancy between preoperative presumption and postoperative diagnosis of recurrent risk factors.

Results: Forty patients underwent the laparoscopic surgery and 80 patients received the laparotomy. The laparoscopic surgery resulted in less intraoperative blood loss and shorter hospital stay. The operative time was significantly longer for the laparoscopic surgery compared with the laparotomy, but this difference was not seen in obese patients with a body mass index ≥30 kg/m. The type of the surgical procedure did not affect the incidence of perioperative complications. Among 120 patients, 104 (86.6%) were diagnosed as FIGO stage IA, 118 (98.3%) with endometrioid adenocarcinoma grade 1 or 2, and 107 (89.1%) with myometrial invasion depth <50%.

Conclusion: The laparoscopic staging surgery is a feasible and safe alternative to the laparotomy for patients with presumed low-risk endometrial cancer, especially for obese patients. To perform the laparoscopic surgery for patients with stage IA endometrial cancer under the current national health insurance system, it is important to limit the candidates to low-risk disease based on a precise diagnosis before the surgery.
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http://dx.doi.org/10.1016/j.tjog.2018.11.019DOI Listing
January 2019

GATA6 expression promoted by an active enhancer may become a molecular marker in endometriosis lesions.

Am J Reprod Immunol 2019 02 14;81(2):e13078. Epub 2019 Jan 14.

Department of Obstetrics and Gynecology, Tottori University Faculty of Medicine, Yonago, Japan.

Problem: Genome-wide profiling of DNA methylation in endometriotic cells has shown a distinct facet of epigenetic backgrounds; however, specific DNA methylation sites responsible for aberrant gene expression in endometriosis were unknown. Are there specific endometriosis-associated DNA methylations that can be used as molecular markers in endometriosis lesions?

Method Of Study: This study used endometriotic tissues from the chocolate cyst lining of the ovaries of patients with endometriosis, and endometrial tissues from disease-free patients. For analysis, stromal cells were collected from endometrial and endometriotic tissues. Using endometrial cells as control, differentially methylated cytosine-phosphate-guanine (CpG) characteristic in endometriotic cells was extracted. Among these CpGs, we focused on a stretch of hypomethylated CpGs within GATA6 gene and examined the potential role as enhancer in endometriotic cells and tissues.

Result(s): We identified a stretch of hypomethylated CpGs within the GATA6 gene body in endometriotic cells. Because GATA6 mRNA was highly expressed in endometriotic cells but not in endometrial cells, we then hypothesized that the hypomethylated sequence may function as an enhancer in GATA6 gene expression. Chromatin immunoprecipitation analysis predicted the presence of active enhancer within the gene body sequence in endometriotic cells. Immunohistochemistry showed a positive staining of GATA6 in ovarian chocolate cysts, while in endometrial tissues and in some peritoneal tissues with endometriosis, GATA6 staining was at a marginal level.

Conclusion: This is the first implication showing a link between an aberrant DNA methylation of cis element and gene expression in endometriosis. GATA6 expression may become a molecular marker to diagnose endometriosis lesions.
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http://dx.doi.org/10.1111/aji.13078DOI Listing
February 2019

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

J Obstet Gynaecol Res 2019 Jan 23;45(1):168-175. Epub 2018 Sep 23.

Obstetrics and Gynecology, Tottori University Faculty of Medicine, Yonago, Japan.

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.
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http://dx.doi.org/10.1111/jog.13807DOI Listing
January 2019

Treatment preferences among Japanese women with dysmenorrhea: results from a discrete choice experiment study.

Patient Prefer Adherence 2018 31;12:1627-1640. Epub 2018 Aug 31.

Department of Obstetrics and Gynecology, Tottori University, Tottori, Japan.

Purpose: To examine patient preferences for oral and intrauterine system treatments for dysmenorrhea in Japan.

Patients And Methods: A discrete choice experiment was conducted to assess the willingness to accept trade-offs among hypothetical treatment profiles. An internet-based survey was administered to women 18-49 years of age who self-reported a dysmenorrhea diagnosis or experienced dysmenorrhea at least once in the past 6 months (N=309). Choice questions included pairs of treatments presented with different attributes: mode of administration, reduction in bleeding after 6 months, chance of symptoms becoming "improved", nausea, weight gain, irregular bleeding, and risk of venous thromboembolism. Relative importance (RI) estimates were computed.

Results: The mean respondent age was 35.8 years (standard deviation =7.0), and 85 women (27.5%) reported that they had previously used hormonal therapy for dysmenorrhea. Treatment preference was most strongly associated with mode of administration (RI=49.8%), followed by chance of irregular bleeding (RI=17.3%). In contrast, treatment preference was most weakly associated with chance of weight gain (RI=2.4%) and reduction in bleeding after 6 months (RI=0.8%). Respondents preferred oral treatments: for twice-daily regimen, odds ratio (OR)=4.90; for once-daily fixed cyclic regimen, OR=4.20; and for once-daily flexible extended regimen, OR=2.44; whereas for intrauterine system, OR=0.02 (<0.001 for all). Those with prior hormonal therapy experience exhibited the same pattern.

Conclusion: Mode of administration factored heavily in dysmenorrhea treatment preferences. Women of reproductive age preferred oral medication, especially twice-daily regimen and once-daily fixed cyclic regimen. Findings can potentially help to improve physician-patient communication and treatment decision making. Physicians should consider factors that can influence patient preference to optimize treatment acceptance and adherence.
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http://dx.doi.org/10.2147/PPA.S166332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6124802PMC
August 2018