Long-term conservative management of symptomatic bladder endometriosis: A case series of 17 patients.

OBJECTIVES: This study aimed to evaluate the course of long-term conservative management of bladder endometriosis (BE). MATERIALS AND METHODS: We retrospectively reviewed 17 cases of BE conservatively managed without surgery in our facility. The following factors were analyzed: age, medical history, lesion size, symptoms, hormonal treatment, and follow-up outcomes. RESULTS: In this study, 15 patients received hormonal therapy and 2 did not. Oral contraceptive (OC), dienogest (DNG), and gonadotropin-releasing hormone agonist (GnRHa) were administered as the first regimen in 7, 5, and 3 patients, respectively. Of the 7 patients, OC administration was effective in alleviating urinary symptoms in all but 2 patients. Of 3 patients who received GnRHa, 2 switched to OC and then DNG, and 1 patient discontinued the treatment because of adverse effects. Of 5 patients who received DNG, all experienced symptom relief. DNG, OC, and GnRHa administration were effective and tolerable in 9 of 10 patients (90.0%), in 5 of 9 patients (55.6%), and in 2 of 3 patients (66.7%), respectively. In particular, 3 patients completed DNG treatment until menopause. The size of the BE lesion significantly decreased after 3 months of DNG administration, and the reduction effect was maintained until 48 months thereafter. CONCLUSION: This study proposed that hormonal therapy for BE is an effective option for those who are not planning to conceive or to undergo surgery. Specifically, DNG may be suitable for patients refusing surgery, considering the effectiveness and tolerance for long-term use.

Elevated phosphorylation of estrogen receptor α at serine-118 in ovarian endometrioma.

OBJECTIVE: To evaluate the phosphorylation of estrogen receptor α at serine-118 (phospho-ERα S118) in the endometrium, ovarian endometrioma, and deep infiltrating endometriosis (DIE). DESIGN: Experimental study. SETTING: University-affiliated hospital and academic research laboratory. PATIENT(S): Twenty-five patients underwent a hysterectomy, 18 patients underwent surgical removal of ovarian endometrioma, and 6 patients underwent DIE. INTERVENTION(S): Tissue samples were obtained from patients who underwent surgical procedures. MAIN OUTCOME MEASURE(S): Immunostaining for phospho-ERα S118, ERα, or phosphorylated p44/42 mitogen-activated protein kinase (phospho-p44/42 MAPK) was performed to evaluate the endometrium with or without endometriosis, ovarian endometrioma, and DIE. For in vitro analysis, endometrial epithelial cells (Ishikawa cells) were stimulated with estradiol (E2) or tumor necrosis factor alpha (TNFα), and the expression levels of phospho-ERα S118 and phospho-p44/42 MAPK were evaluated via Western blotting. RESULT(S): First, phospho-ERα S118 level was significantly higher in the glands and stroma of ovarian endometriosis samples than in those of endometrial and DIE samples. Second, colocalization of phospho-p44/42 MAPK and phospho-ERα S118 was observed in the glands of ovarian endometrioma. The proportions of cells strongly expressing phospho-p44/42 and phospho-ERα were 87% in phosphor-p44/42 MAPK-positive cells and 79% in phosphor-ERα-positive cells. Third, E2 stimulation significantly enhanced phospho-ERα S118 after 15 and 30 minutes in in vitro analysis using endometrial epithelial cells. Fourth, TNFα stimulation modestly but significantly enhanced phospho-ERα S118 after 15 and 30 minutes. Fifth, in Ishikawa cells, treatment with a p44/42 inhibitor (PD98059) significantly reduced phospho-ERα S118 by TNFα but not by E2. CONCLUSION(S): ERα-S118 phosphorylation was increased in ovarian endometriosis. Our findings may provide a new perspective for understanding the mechanism of increased ERα action in the pathophysiology of endometriosis.

A Case of Nonpuerperal Uterine Inversion Caused by Cervical Cancer.

Uterine inversion is a rare puerperal event in the third stage of labor. Nonpuerperal uterine inversion is even rarer and is mainly caused by uterine fibroids, uterine sarcoma, or endometrial cancer. This is the first report of uterine inversion caused by cervical cancer. A 67-year-old woman presented with a 10 cm pelvic mass. Contrast-enhanced magnetic resonance imaging revealed uterine inversion, which was preoperatively diagnosed to be caused by endometrial cancer and was treated using an extended abdominal hysterectomy. Postoperative histopathological examination revealed that the primary tumor was a squamous cell carcinoma with coexistent high-grade squamous intraepithelial lesions and small-cell neuroendocrine carcinoma. Immunostaining was diffusely positive for p16 and negative for estrogen receptors. The postoperative diagnosis was cervical squamous cell carcinoma. Our observations suggested that cervical carcinoma can cause uterine inversion by invading the corpus.

PAX8: A Highly Sensitive Marker for the Glands in Extragenital Endometriosis.

In cases of extragenital endometriosis or microscopic endometriosis lesions, pathological diagnosis can be challenging because endometriotic stroma and glands represent only a minor component of fibrotic endometriotic lesions. For better accuracy of diagnosis, the development of a sensitive and specific epithelial marker is beneficial. Previous studies showed that PAX8 is a highly sensitive and specific marker for primary and metastatic Mullerian epithelial tumors. Therefore, we sought to examine whether PAX8 is a highly sensitive marker for glands in extragenital endometriosis. Eight and 47 samples of ovarian endometrioma and extragenital endometriosis, respectively, were evaluated in this study. We calculated the percentage of samples positively immunostained for PAX8, CD10, estrogen receptor (ER), and progesterone receptor (PR). PAX8 was positive for endometriotic epithelial cells in 95.7% (45/47) of extragenital endometrioses and in 100% (8/8) of ovarian endometrioses. CD10 was positive for endometriotic stromal cells in 97.9% (46/47) of extragenital endometrioses. PAX8 was strongly positive for glands, even in a CD10-negative case. The expression of PAX8, CD10, and PR was not affected by preoperative hormonal therapy, and the positive rate of ER staining was significantly reduced by preoperative hormonal therapy. In conclusion, PAX8 is a highly sensitive epithelial marker for extragenital endometriosis. This specific expression was maintained under hormonal therapy. It is noteworthy that extragenital endometriosis maintains the expression of this lineage marker, although it occurs at various sites, and its cause and mechanism of development might be different. PAX8 nuclear expression can be useful in detecting extragenital endometriosis in clinical practice.

IFITM1 is a Novel, Highly Sensitive Marker for Endometriotic Stromal Cells in Ovarian and Extragenital Endometriosis.

When the presence of endometriotic lesions are not evident by hematoxylin and eosin staining, CD10 is used to highlight and confirm the presence of endometriotic stroma. However, CD10 is not specific only to the endometrial stroma but is also expressed in many other cells. Recently, interferon-inducible transmembrane protein 1 (IFITM1) was reported as a highly specific immunohistochemical marker of normal endometrial stroma and endometrial stromal neoplasm. In this study, we examined the expression of IFITM1 and CD10 in 18 cases of ovarian endometriosis and 44 cases of extragenital endometriosis. Among the 62 patients, 62 (100.0%) were positive for IFITM1 and 60 (96.8%) for CD10, and CD10 was negative in 2 cases that were positive for IFITM1. Additionally, we found that IFITM1 sensitivity was unaffected by the presence or absence of hormonal therapy. To the best of our knowledge, this represents the first demonstration of IFITM1 as a highly sensitive stromal marker of ovarian and extragenital endometriosis.

Expression of ALDH1A Isozymes in Human Endometrium with and without Endometriosis and in Ovarian Endometrioma.

Human endometrium is a highly regenerative and dynamic tissue that undergoes cyclic changes during menstrual cycle. It has been reported that endometrial epithelium contains a population of progenitor/stem cells. Increasing amount of evidence indicates that progenitor/stem cells are involved in the pathogenesis of endometriosis. Proteins belonging to the aldehyde dehydrogenase 1 (ALDH1A) family have been reported to be markers of normal tissue stem cells and cancer stem cells. In this study, by using immunohistochemistry, we examined the expression of ALDH1A isozymes in human endometrial tissue, including that affected by endometriosis, and in ovarian endometrioma. Positive staining for ALDH1A isozymes was observed in the stroma of the endometrium and in endometriotic ovarian tissue. In the glands, expression patterns were distinct for different ALDH1A isozymes. ALDH1A1 and ALDH1A3 were highly expressed in the epithelium of stratum basalis of the endometrium and in the epithelium of ovarian endometrioma irrespective of the menstrual cycle, whereas ALDH1A2 was highly expressed only in the epithelium of endometrioma. Furthermore, ALDH1A1 co-localized with N-cadherin, which is a marker of endometrial epithelial progenitor cells, in the glands of stratum basalis. These findings support and reinforce the notion about the presence of progenitor/stem cells in endometrial glands in stratum basalis and in endometriotic glands, suggesting that these cells are involved in the physiology of the endometrium and in the pathology of endometriosis.

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.

A survey of public attitudes toward uterus transplantation, surrogacy, and adoption in Japan.

This study aimed to evaluate the attitudes of male and female members of the public toward uterus transplantation (UTx), surrogacy, and adoption in Japan via a web-based survey. One thousand six hundred participants were recruited with equal segregation of age (20s, 30s, 40s, and 50s) and gender. We assessed the association between ethical view and gender, age, infertility, and the knowledge level of UTx, using a questionnaire. The findings were as follows. First, 36.5% and 31.0% of respondents agreed that UTx and gestational surrogacy should be approved, respectively. Second, the respondents would potentially choose to receive UTx (34.4%), gestational surrogacy (31.9%), and adoption (40.3%), if they or their partners experienced absolute uterine factor infertility. Third, 10.1%, 5.8%, and 14.3% of the respondents chose UTx, gestational surrogacy, and adoption as the most favorable option, respectively. Fourth, if their daughters suffered from absolute uterine factor infertility, 32.3% of female respondents might want to be donors, and 36.7% of male respondents might ask their wives to be donors. These data were affected by age, gender, infertility, or the knowledge level of UTx. UTx was a more acceptable option than gestational surrogacy and adoption. The effects of gender, age, infertility, and the level of knowledge of UTx are important in understanding the attitude toward UTx. On the other hand, there were concerns about the safety of UTx for recipients, donors, and babies. It is important to continue to understand public attitudes to inform the development and safety of UTx, which will enhance the discussion on the ethical consensus on UTx.

Clinical aspects and management of inguinal endometriosis: A case series of 20 patients.

AIM: This study aimed to describe the clinical presentation, diagnostic evaluation, and operative or medical management of inguinal endometriosis. METHODS: In this study, we retrospectively reviewed 20 cases of inguinal endometriosis in our facility, particularly on the clinical characteristics, diagnosis, and surgical and medical treatment. RESULTS: We retrospectively investigated the following items for each patient: age at diagnosis, surgical history, presence of extragenital endometriosis, symptoms, imaging modalities, surgical therapy, hormonal therapy, follow-up period, postoperative recurrence and time to recurrence. We identified 20 cases of inguinal endometriosis in our facility. First, 75% of the patients had right inguinal endometriosis. Second, T1-weighted or fat-saturated T1-weighted images showed hyperintensity in the lesions in 17 patients (17/18 patients, 94.4%). Third, in 5 of 6 patients who underwent surgical therapy, we performed radical surgery to excise the inguinal lesion including the round ligament. One patient had disease relapse. Fourth, in 6 of 7 cases, dienogest effectively improved pain without significant adverse effects, but oral contraceptive was effective in 1 of 4 patients without significant adverse effects. CONCLUSION: We retrospectively reviewed 20 patients with inguinal endometriosis in our facility. We have shown that magnetic resonance imaging can be a useful imaging modality to obtain a specific diagnosis of this disease. In addition, inguinal endometriosis can be managed with radical surgery to resect lesions including the round ligament and with hormonal treatment. In particular, dienogest ameliorated symptoms, which can be an option for patients who do not want surgery.

Contralateral ovarian endometrioma recurrence after unilateral salpingo-oophorectomy.

BACKGROUND: The recurrence rate after unilateral salpingo-oophorectomy (USO) for unilateral endometrioma has not been reported. We evaluated the rate of and risk factors for endometrioma recurrence after USO. METHODS: In this retrospective observational study, we enrolled 110 women (age, 35-45 years) who underwent laparoscopic USO (n = 50) or cystectomy (n = 60) for unilateral ovarian endometrioma from January 2010 through December 2012. We compared patients' characteristics between patients who underwent USO and those who underwent cystectomy. We also compared patients with and without an endometrioma recurrence after USO using univariate and multivariate stepwise logistic regression models to identify recurrence risk factors. Endometrioma recurrence was defined as an ovarian cyst (> 2 cm) with features typical of an endometrioma identified by postoperative transvaginal sonography. RESULTS: Endometrioma recurred in 8 (16%) patients after USO (mean follow-up, 46.0 ± 12.9 months [range, 15-73]). The post-USO cumulative recurrence rates at 12, 24, 36, and 60 months were 8.0, 10.2, 12.7, and 24.7%, respectively (Kaplan-Meier analysis). In logistic regression analysis, a contralateral side adhesion score ≥ 4 was an independent risk factor for endometrioma recurrence after USO (odds ratio, 19.48, 95% confidence interval, 1.59-237.72). The post-USO cumulative recurrence rates at 12, 24, 36, and 57 months were 19.5, 24.1, 31.0, and 54.0%, respectively, in cases with contralateral side adhesion scores ≥4, and 0.0, 0.0, 0.0, and 5.9%, respectively, in cases with scores < 4 (log-rank test, P = 0.0023). CONCLUSIONS: To our knowledge, this is the first report on the recurrence rate and risk factors associated with recurrence after USO. Endometrioma recurrence rates were 24.7% during the first 5 years after USO. The post-USO recurrence rate increased significantly in cases with contralateral side adhesions. Our findings could improve the planning of USO and patient selection for postoperative hormonal therapy.

IFITM1 is a Novel, Highly Sensitive Marker for Endometriotic Stromal Cells in Ovarian and Extragenital Endometriosis.

When the presence of endometriotic lesions are not evident by hematoxylin and eosin staining, CD10 is used to highlight and confirm the presence of endometriotic stroma. However, CD10 is not specific only to the endometrial stroma but is also expressed in many other cells. Recently, interferon-inducible transmembrane protein 1 (IFITM1) was reported as a highly specific immunohistochemical marker of normal endometrial stroma and endometrial stromal neoplasm. In this study, we examined the expression of IFITM1 and CD10 in 18 cases of ovarian endometriosis and 44 cases of extragenital endometriosis. Among the 62 patients, 62 (100.0%) were positive for IFITM1 and 60 (96.8%) for CD10, and CD10 was negative in 2 cases that were positive for IFITM1. Additionally, we found that IFITM1 sensitivity was unaffected by the presence or absence of hormonal therapy. To the best of our knowledge, this represents the first demonstration of IFITM1 as a highly sensitive stromal marker of ovarian and extragenital endometriosis.

PAX8: A Highly Sensitive Marker for the Glands in Extragenital Endometriosis.

In cases of extragenital endometriosis or microscopic endometriosis lesions, pathological diagnosis can be challenging because endometriotic stroma and glands represent only a minor component of fibrotic endometriotic lesions. For better accuracy of diagnosis, the development of a sensitive and specific epithelial marker is beneficial. Previous studies showed that PAX8 is a highly sensitive and specific marker for primary and metastatic Mullerian epithelial tumors. Therefore, we sought to examine whether PAX8 is a highly sensitive marker for glands in extragenital endometriosis. Eight and 47 samples of ovarian endometrioma and extragenital endometriosis, respectively, were evaluated in this study. We calculated the percentage of samples positively immunostained for PAX8, CD10, estrogen receptor (ER), and progesterone receptor (PR). PAX8 was positive for endometriotic epithelial cells in 95.7% (45/47) of extragenital endometrioses and in 100% (8/8) of ovarian endometrioses. CD10 was positive for endometriotic stromal cells in 97.9% (46/47) of extragenital endometrioses. PAX8 was strongly positive for glands, even in a CD10-negative case. The expression of PAX8, CD10, and PR was not affected by preoperative hormonal therapy, and the positive rate of ER staining was significantly reduced by preoperative hormonal therapy. In conclusion, PAX8 is a highly sensitive epithelial marker for extragenital endometriosis. This specific expression was maintained under hormonal therapy. It is noteworthy that extragenital endometriosis maintains the expression of this lineage marker, although it occurs at various sites, and its cause and mechanism of development might be different. PAX8 nuclear expression can be useful in detecting extragenital endometriosis in clinical practice.

A survey of public attitudes towards third-party reproduction in Japan in 2014.

OBJECTIVE: The objective of this study was to examine public attitudes towards third-party reproduction and the disclosure of conception through third-party reproduction. METHODS: We conducted the web-based survey for the public attitude towards third-party reproduction in February 2014. Twenty-five hundred people were recruited with equal segregation of age (20s, 30s, 40s, and 50s) and gender. We analyzed the association between gender, age, infertility, and ethical view using a questionnaire regarding donor sperm, donor oocyte, donor embryo, gestational surrogacy, and disclosure to offspring. RESULTS: Of the respondents, 36.2% approved and 26.6% disapproved of gamete or embryo donation. The frequency of those who approved was lowest in females in the 50-59 year age group, and was significantly higher in males or females with infertility. Secondly, 40.9% approved and 21.8% disapproved of gestational surrogacy. The frequency of those who approved gestational surrogacy was higher in males or females with infertility. Thirdly, 46.3% of respondents agreed and 20.4% disagreed with "offspring have the right to know their origin". Those who disagreed were primarily in the 50-59 year age group of both genders, and disagreement was significantly higher in the infertility group compared with non-infertility group. CONCLUSION: In this study, public attitudes were affected by gender, age, and experience of infertility. These study findings are important in understanding the attitude towards third-party reproduction and disclosure to the offspring. Respondents having indecisive attitudes were >30%, which might indicate an increased requirement for information and education to enhance the discussion on the ethical consensus on third-party reproduction in Japan.

Long-term dienogest administration in patients with symptomatic adenomyosis.

AIM: Adenomyosis is a common gynecological disorder that causes dysmenorrhea, hypermenorrhea and metrorrhagia. Previously, we reported that 24 weeks of dienogest treatment is highly effective for pain in symptomatic adenomyosis. Up to present, there is no report that describes treatment of adenomyosis with long-term dienogest administration for more than 2 years. In this retrospective cohort study, we investigated the course of long-term dienogest treatment in patients with symptomatic adenomyosis. METHODS: This is a retrospective cohort study. Dienogest was continuously administered at a dose of 2 mg daily for patients with symptomatic adenomyosis. The outcome of long-term administration of dienogest was investigated, and the characteristics of patients were compared between discontinued cases and long-term administration cases. RESULTS: Two patients were excluded from this study because of transfer to another hospital or discontinuation due to infertility treatment. Twelve of 18 patients (66.7%) received dienogest until menopause or for a period of >80 months. Four cases (22.2%) discontinued dienogest treatment because of severe metrorrhagia. In the discontinued cases because of severe metrorrhagia, the pain score for dysmenorrhea and serum CA125 level at baseline significantly elevated, and the hemoglobin level at baseline and the frequency of type 2 adenomyosis significantly decreased, compared to those with long-term use. Moreover, long-term dienogest use did not decrease the serum estradiol level. CONCLUSION: Our report suggests that dienogest is tolerable for long-term use until menopause and can be an alternative treatment option in some patients, especially those with type 2 adenomyosis, to avoid hysterectomy.

Thoracic endometriosis syndrome: Comparison between catamenial pneumothorax or endometriosis-related pneumothorax and catamenial hemoptysis.

OBJECTIVES: To evaluate the clinical features of thoracic endometriosis syndrome (TES) represented by catamenial pneumothorax (CP), endometriosis-related pneumothorax (ERP), and catamenial hemoptysis (CH). STUDY DESIGN: In this retrospective study, we enrolled 25 patients with TES, 18 of whom had CP/ERP and 7 had CH, to investigate the clinical presentation, effectiveness of treatment, and recurrence rates in these disorders. RESULTS: The age at onset was significantly lower in patients with CH than in patients with CP/ERP (P < 0.05). In 94.4% of patients with CP/ERP, pneumothorax was observed on either the right side or bilaterally, however there was no tendency toward laterality of CH among our cases. In our study, patients with CP/ERP predominantly underwent surgical management and the recurrence rate during treatment was higher in patients with CP/ERP than in those with CH. We found that the recurrence frequency of CP/ERP was lowest under the combination therapy with thoracic surgery and postoperative hormonal therapy. CONCLUSION: Our findings suggest that CP/ERP and CH are different pathological conditions and CP/ERP is more difficult to manage than CH.

Preoperative assessment of factors associated with difficulty in performing total laparoscopic hysterectomy.

AIM: Our objective was to determine the preoperative factors associated with difficulty in total laparoscopic hysterectomy (TLH). METHODS: This retrospective clinical study included 157 patients who underwent TLH for leiomyoma or adenomyosis between 2009 and 2013. All patients underwent magnetic resonance imaging (MRI) before surgery. We categorized patients as 'difficult' if the operation time was > 243 min, if total blood loss was > 500 mL, or if conversion to laparotomy was necessary. Preoperative information, including MRI findings, was compared between the difficult and 'other' patients. Stepwise logistic regression analysis was used to control for covariates that were significant on univariate analysis (P < 0.05). RESULTS: The presence of an endometrioma, a previous cesarean section (CS), a wide uterus, and a high body mass index were independent risk factors for being a difficult patient. For adenomyosis patients, the presence of an endometrioma, a prior CS, subtype II adenomyosis, and high body mass index were independent risk factors for being a difficult patient. For leiomyoma patients, the presence of an endometrioma, a prior CS, and having at least seven leiomyomas were independent risk factors for being a difficult patient. All laparotomy conversion patients had multiple risk factors. CONCLUSION: We have elucidated the factors associated with difficult TLH patients using patients' background and preoperative MRI findings. Awareness of these predictive factors may enable surgeons to prepare for the operation, minimize complications, or choose another more appropriate route of hysterectomy than TLH.