Efficacy of estrogen-progestogen therapy for women with vascular retained products of conception following miscarriage or abortion.

OBJECTIVE: To assess the clinical characteristics and endocrinological background of women with vascular retained products of conception (RPOC) after miscarriage or abortion and evaluate the effect of estrogen-progestogen therapy (EPT) as an initial treatment on this population based on their endocrinological background. MATERIALS AND METHODS: Women with vascular RPOC after miscarriage or abortion at less than 20 weeks of pregnancy who were given EPT (conjugated estrogen and norethisterone) were retrospectively reviewed. Their clinical characteristics, hormonal parameters, ultrasonographic findings, and outcomes were evaluated. RESULTS: Of 35 women with vascular RPOC, 30 (86%) presented with vaginal bleeding at a visit, and 6 (17%) required inpatient management due to heavy bleeding. Among women who presented with vaginal bleeding, serum progesterone levels were significantly lower (0.25 vs. 6.5 ng/mL, p = 0.004) than those in women who did not present with vaginal bleeding. There were no differences in serum hCG levels (10.5 vs. 3.1 mIU/mL) or serum estradiol levels (65.4 vs. 162.3 pg/mL). After withdrawal bleeding following the first course of EPT, vaginal bleeding was stopped in 27 of the 30 women (90%), and 23 (66%) of all women had a thin and linear endometrium. All women could be treated by up to two courses of EPT and did not require additional interventions. The median duration to hCG normalization after the initial EPT was 24.5 (9-88) days. CONCLUSION: Women with vascular RPOC who have no bleeding had significantly higher levels of serum progesterone, indicating that administration of progestogen may have an effect on hemostasis. Endometrial bleeding can be prevented or stopped, and retained tissues can be conservatively expelled by oral administration of EPT, including norethisterone, in women with vascular RPOC.

Advantages and limitations of estrogen replacement therapy on hypogonadal survivors of childhood cancer.

BACKGROUND: Hypogonadism is a significant late complication in childhood cancer survivors (CCS). The aim of this study was to elucidate the advantages and limitations of estrogen replacement therapy (ERT) for CCS with hypogonadism. METHODS: Seventeen CCS were divided into two groups: gonadal hypogonadism (GH) group (n = 8) and central hypogonadism (CH) group (n = 9). Pearson correlation coefficients were used to investigate the impact of cancer management on final height, bone density, and uterine development. RESULTS: Seven of GH group had hematologic malignancies, and all of them underwent total body irradiation before bone marrow transplantation. The GH group showed significant positive correlations between the onset age of disease treatment and final height (p < 0.05, R = 0.712) and uterine size following ERT (p < 0.05, R = 0.775). All CCS in the CH group had brain tumors, and seven of them received chemotherapy. There were trends towards positive and negative correlations between the onset age of disease treatment and final height (p = 0.09, R = 0.598) or uterine size (p = 0.07, R = - 0.669), respectively. A negative correlation trend was observed between the age at ERT initiation and final height (p = 0.07, R = - 0.769) or bone density (p = 0.18, R = - 0.626) in six CH patients who received growth hormone therapy. Five CCS in both groups experienced osteoporosis, despite receiving ERT. CONCLUSION: Individualized management strategies beyond ERT are essential to reduce long-term complications in CCS with hypogonadism, considering the type and timing of cancer treatment.

Mismatch repair protein deficiency in endometriosis: Precursor of endometriosis-associated ovarian cancer in women with lynch syndrome.

OBJECTIVE: We aimed to elucidate the pathogenesis of ovarian cancer through the loss of mismatch repair (MMR) proteins in women with Lynch syndrome (LS) in this report. CASE REPORT: Two women with LS underwent surgery for synchronous endometrial cancer and ovarian cancer. In both cases, immunohistochemical examination showed concomitant MMR protein deficiency in endometrial cancer, ovarian cancer, and contiguous ovarian endometriosis. In Case 1, the macroscopically normal ovary included multiple endometrioses with MSH2 and MSH6 expression, and FIGO grade 1 endometrioid carcinoma and contiguous endometriosis without MSH2 and MSH6 expression. In Case 2, all endometriotic cells contiguous with carcinoma in the lumen of the ovarian cyst showed loss of the expression of MSH2 and MSH6. CONCLUSION: Ovarian endometriosis with MMR protein deficiency may progress to endometriosis-associated ovarian cancer in women with LS. Diagnosing endometriosis in women with LS during surveillance is important.

Surgical efficacy and quality of wide resection of the pelvic peritoneum in patients with epithelial ovarian cancer.

PURPOSE: The aim of the study was to evaluate the impact of adding an extensive pelvic peritoneal stripping procedure, termed "wide resection of the pelvic peritoneum," (WRPP) to standard surgery for epithelial ovarian cancer on survival effectiveness and to investigate the role of ovarian cancer stem cells (CSCs) in the pelvic peritoneum. METHODS: A total of 166 patients with ovarian cancer undergoing surgical treatment at Kumamoto University Hospital between 2002 and 2018 were retrospectively analyzed. Eligible patients were divided into three groups based on the surgical approach: standard surgery (SS) group (n = 36), WRPP group (standard surgery plus WRPP, n = 100), and rectosigmoidectomy (RS) group (standard surgery plus RS, n = 30). Survival outcomes were compared between the three groups. CD44 variant 6 (CD44v6) and EpCAM expression, as markers of ovarian CSCs, in peritoneal disseminated tumors were evaluated using immunofluorescence staining. RESULTS: With respect to patients with stage IIIA-IVB ovarian cancer, there were significant differences in overall and progression-free survival between the WRPP and SS groups, as revealed by univariate (hazard ratio [HR], 0.35; 95% confidence interval [CI], 0.17-0.69; P = 0.003 and HR, 0.54; 95% CI, 0.31-0.95; P = 0.032, respectively) and multivariate Cox proportional hazards models (HR, 0.35; 95% CI, 0.17-0.70; P = 0.003 and HR, 0.54; 95% CI, 0.31-0.95; P = 0.032, respectively). Further, no significant differences were observed in survival outcomes between the RS group and the SS or WRPP group. Regarding the safety of WRPP, no significant differences in major intraoperative and postoperative complications were found between the three groups. Immunofluorescence analysis revealed a high percentage of CD44v6/EpCAM double-positive ovarian cancer cells in peritoneal disseminated tumors. CONCLUSION: The present study demonstrates that WRPP significantly contributes to improved survival in patients with stage IIIA-IVB ovarian cancer. WRPP could result in eradicating ovarian CSCs and disrupting the CSC niche microenvironment in the pelvic peritoneum.

Maternal thrombocytopenia precedes fetal death associated with COVID-19.

Acute coagulopathy, specific placental pathology, and an increased risk of fetal death have been reported in pregnant women with COVID-19; however, the association between coagulopathy and fetal death remains unknown. We report two pregnant women with COVID-19 who showed acute coagulopathy prior to fetal death. Both pregnant women presented with thrombocytopenia after testing positive for SARS-CoV-2 (days 5 and 7). They had mild symptoms, but coagulopathy progressed, and their fetuses died on day 9 at 27 and 22 weeks of pregnancy. Their coagulability improved after delivery. Placental histology in both cases showed intervillous infiltration of histiocytes, necrosis of trophoblasts, and intervillous fibrin deposition, which were consistent with previously reported pathological findings related to SARS-CoV-2. In the management of pregnant women with COVID-19, thrombocytopenia may be a predictive marker of fetal death following coagulopathy and placental inflammatory changes due to SARS-CoV-2 infection.

Safety and Efficacy of a Single Local Methotrexate Injection for Cesarean Scar Pregnancy.

STUDY OBJECTIVE: To investigate the safety and efficacy of a single local methotrexate (MTX) injection for the treatment of cesarean scar pregnancy (CSP), assess reproductive outcomes after treatment, and confirm clinical outcomes after the treatment of CSP patients according to the presence of fetal cardiac activity or serum human chorionic gonadotropin (hCG) levels. DESIGN: A retrospective cohort study. SETTING: A university hospital. PATIENTS: Women with CSP. INTERVENTIONS: Single local MTX injection under transvaginal ultrasound guidance. MEASUREMENTS AND MAIN RESULTS: A total of 45 CSP cases were identified; the mean (standard deviation, range) estimated gestational age was 7.7 (1.7, 5.4-12.5) weeks and the mean serum hCG level was 51 801 (40 761, 2307-187 898) mIU/mL. Three cases required additional treatment with MTX, and none of the cases needed uterine artery embolization or hysterectomy. The success rate for a single dose was 93.3%, and it was 100% if additional treatments with MTX were included. The mean time required for hCG normalization in those with fetal cardiac activity or with an initial level of hCG greater than 100 000 mIU/mL was not significantly longer than that in the controls (93.4 vs 77.1 days, p = .12; 113.7 days vs 83.6 days, p = .10). Of the 23 women who desired a subsequent pregnancy, 13 delivered 14 healthy newborns after treatment, 3 had an ongoing pregnancy, and 3 experienced recurrent CSP. CONCLUSIONS: A single local MTX injection is safe and effective for the treatment of CSP despite the presence of fetal cardiac activity or any initial level of hCG and may allow the possibility of a subsequent uneventful pregnancy.

Endometrial cancer with a POLE mutation progresses frequently through the type I pathway despite its high-grade endometrioid morphology: a cohort study at a single institution in Japan.

POLE-mutated endometrial cancer (EC) frequently shows high-grade endometrioid histology, which represents heterogeneity in the dualistic classification of EC. This study aimed to assess the clinicopathology and pathogenesis of POLE-mutated EC due to the scarcity of related information for Asian women. POLE variants were sequenced in tissues of Japanese women with EC. The tumor mutation burden (TMB) was assessed in tissues with a POLE variant of unknown significance. In the POLE-mutated EC tissues, the immunostaining expression of CD8, hormonal receptors, and p53 was evaluated, and the POLE variants in cancer and atypical endometrial hyperplasia (AEH) lesions were assessed by laser-capture microdissection. POLE variants were identified in five patients (3.9%) with high-grade endometrioid carcinoma among 127 patients with EC (S459F in two tissues and P441P in three tissues with a high TMB). The five cancer tissues coexisted with normal endometrium and/or AEH. Both AEH and cancer cells showed hormonal receptor positivity and harbored the same POLE mutation. Two patients showed a subclonal overexpression pattern of p53 in cancer and AEH lesions. In conclusion, POLE-mutated EC progresses through the type I pathway, even though it frequently shows high-grade endometrioid morphology. The common POLE mutation sites in EC might vary among races.

Prolactin Enhances the Proliferation of Proliferative Endometrial Glandular Cells and Endometrial Cancer Cells.

To elucidate the mechanism of endometrial cancer (EC) development in young hyperprolactinemic women, this study assessed the hormonal receptor expression, proliferation, and signaling induced by prolactin in endometrial glands (EG) and EC. Prolactin receptor (PRLR) and estrogen receptor alpha (ER-α) in EG were evaluated during the menstrual cycle by immunohistochemistry. The following parameters were compared between EM-E6/E7/TERT cells, which originated from proliferative EG and Ishikawa cells. The expression levels of PRLR, pJAK2 (phosphorylated Janus Activating Kinase 2), its downstream pathways (MAPK, PI3K, and STAT), and ER-α were assessed after adding prolactin by Western blotting. U0126 was used as a MAPK inhibitor. The proliferation caused by estradiol was also examined by MTS assay after adding prolactin. PRLR expression in the EG was significantly higher in the proliferative phase than in the secretory phase, and it was correlated with ER-α expression during the menstrual cycle. After adding prolactin, the expression of pJAK2, PRLR and ER-α was significantly increased in both cell lines, MAPK was activated after adding prolactin in both cell lines, and PI3K and STAT were activated only in EM-E6/E7/TERT cells. The increased proliferation induced by estradiol was enhanced after adding prolactin in both cell lines. All changes caused by prolactin were inhibited in Ishikawa cells pretreated with U0126. Long-term effects of serum prolactin on persistent proliferative endometrium in the presence of estradiol may induce abnormal proliferation of EG in hyperprolactinemic women. Prolactin-PRLR signaling via MAPK may play a crucial role in the progression of EC in hyperprolactinemic women.

Hyperemesis gravidarum followed by refeeding syndrome causes electrolyte abnormalities induced rhabdomyolysis and diabetes insipidus.

Although hyperemesis gravidarum (HG), an extreme form of morning sickness, is a common complication during pregnancy, HG associated simultaneous onset of rhabdomyolysis and diabetes insipidus due to electrolyte abnormalities are rare. A 34-year-old woman with severe HG at 17 weeks of gestation complicated with appetite loss, weight reduction by 17 kg, general fatigue, myalgia, weakness and polyuria was identified to have simultaneous hypophosphatemia (1.6 mg/dL) and hypokalemia (2.0 mEq/L). Appetite recovery and the improvement of the hypophosphatemia (3.2 mg/dL) were observed prior to the first visit to our department. At the admission, she presented polyuria around 7,000~8,000 mL/day with impaired concentrating activity (U-Osm 185 mOsm/L), and abnormal creatine kinase elevation (4,505 U/L). The electrolyte disturbances and physio-metabolic abnormalities in undernourished state due to HG let us diagnose this case as refeeding syndrome (RFS). In this case, abnormal loss by vomiting, insufficient intake and previous inappropriate fluid infusion as well as the development of RFS may accelerate the severity of hypokalemia due to HG. Thus, as her abnormalities were considered as results of rhabdomyolysis and diabetes insipidus due to severe HG associated hypokalemia based on RFS, oral supplementation of potassium chloride was initiated. After 6 days of potassium supplementation, her symptoms and biochemical abnormalities were completely resolved. Severe HG followed by RFS can be causes of electrolyte abnormalities and subsequent complications, including rhabdomyolysis and renal diabetes insipidus. Appropriate diagnosis and prompt interventions including adequate nutrition are necessary to prevent electrolyte imbalance induced cardiac, neuromuscular and/or renal complications.

A 23-Year-Old Woman with Sudden-Onset Blindness of the Right Eye.

A 23-year-woman was presented for sudden-onset monocular blindness. Branch retinal artery occlusion in the right eye and multiple brain embolism were detected. Trousseau syndrome due to bilateral ovarian cancer was diagnosed; no embolic events were observed after anticoagulant therapy and surgical resection.

Serum Prolactin Contributes to Enhancing Prolactin Receptor and pJAK2 in Type I Endometrial Cancer Cells in Young Women Without Insulin Resistance.

Elevated levels of serum prolactin and a high expression of prolactin receptor (PRLR) in cancer cells was recently identified in patients with endometrial cancer (EC). However, the impact of prolactin on EC remains unknown. The aim of this study was to elucidate the clinical and immunohistochemical characteristics of hyperprolactinemic patients with EC according to the pathogenetic types, type I and type II. EC patients were retrospectively divided into a high prolactin (HP) group and a low prolactin (LP) group by a serum prolactin level of 20 ng/mL and were compared between 2 groups. The expression of PRLR, phosphorylated Janus-kinase 2 (pJAK2), estrogen receptor-α, progesterone receptor, and PTEN in cancer tissue were evaluated by immunohistochemistry. Ninety-nine patients were identified. In the type I group, HP group was significantly younger (45.2 vs. 52.2, P=0.028) and their insulin resistance was significantly lower (1.6 vs. 2.5, P=0.033) than those in LP group, and the expression of PRLR and pJAK2 in the HP group was significantly higher than that in the LP group (immunoreactive score: 6.8 vs. 3.9, P=0.003; 5.7 vs. 2.6, P<0.001, respectively). In the type 2 group, there were no differences between all the term. In the type I group, the rate of loss of PTEN in the HP group was significantly lower than the LP group (25.0% vs. 60.7%, P=0.024). Prolactin-PRLR signaling may play a crucial role for the progression of type I EC without involving the PTEN mutation in young hyperprolactinemic women without insulin resistance.

Sac-Type Congenital Diaphragmatic Hernia: A Case Report of Two Siblings.

Congenital diaphragmatic hernia (CDH), a herniation of the abdominal contents through a defect or hypoplasia of the diaphragm, is a relatively common, severe congenital anomaly. Here we present the first case of two siblings with possibly isolated sac-type CDH and with a suspected genetic etiology. Although sibling recurrence of isolated CDH is rare, the incidence is higher than in the general population. Additionally, the second child had a more severe respiratory disorder than the first child. It is to be noted that siblings of children having isolated CDH are at risk for CDH, and prenatal evaluation should be considered individually.

Administration of Cabergoline Contributes to Preserving Fertility in Young Hyperprolactinemic Patients With Endometrial Cancer Treated With Medroxyprogesterone Acetate.

BACKGROUND: An association between high levels of serum prolactin and endometrial cancer (EC) has been reported. However, the effect of antiprolactin drugs on hyperprolactinemic patients with EC has not been determined. The aim of this study was to confirm the effect of cabergoline on young hyperprolactinemic patients treated with medroxyprogesterone acetate (MPA) for the preservation of fertility. METHODS: A retrospective observational study was conducted to identify patients with atypical endometrial hyperplasia or early-stage EC aged 40 years or younger who were treated with oral MPA in Kumamoto University Hospital between 1998 and 2016. RESULTS: Thirty-four patients were identified and divided into two groups of 17 patients each, including a nonadministration of cabergoline group (noncabergoline group) and an administration of cabergoline group (cabergoline group). The ratio of pathological diagnoses of EC in the noncabergoline group was significantly lower than that in the cabergoline group (29.4% vs 70.6%, P = 0.016). The mean serum prolactin levels showed a significant decrease after the administration of cabergoline in the cabergoline group (25.2 [24.0] vs 5.2 [4.2] ng/mL, P = 0.003), and this decreased level was also significantly lower than that in the noncabergoline group (5.2 [4.2] vs 12.0 [5.0] ng/mL, P < 0.001). Kaplan-Meier analysis conducted for 150 months revealed that the estimated mean period until hysterectomy in the noncabergoline group was significantly shorter than that in the cabergoline group (83.5 vs 140.8 months, P = 0.007). Significant differences were observed in EC but not atypical endometrial hyperplasia based on histological classification (25.6 vs 138.0 months, P = 0.001). CONCLUSIONS: The administration of cabergoline may contribute to preserving fertility in young hyperprolactinemic patients with EC who were treated with MPA.

The clinical course and pathophysiological investigation of adolescent gestational diabetes insipidus: a case report.

BACKGROUND: Gestational diabetes insipidus (GDI) is a rare endocrine complication during pregnancy that is associated with vasopressinase overproduction from the placenta. Although increased vasopressinase is associated with placental volume, the regulation of placental growth in the later stage of pregnancy is not well known. CASE PRESENTATION: A 16-year-old pregnant woman was urgently transferred to our hospital because of threatened premature labor when the Kumamoto earthquakes hit the area where she lived. During her hospitalization, she complained of gradually increasing symptoms of polyuria and polydipsia. The serum level of arginine vasopressin (AVP) was 1.7 pg/mL, which is inconsistent with central DI. The challenge of diagnostic treatment using oral 1-deamino-8-D-AVP (DDAVP) successfully controlled her urine and allowed for normal delivery. DDAVP tablets were not necessary to control her polyuria thereafter. Based on these observations, clinical diagnosis of GDI was confirmed. Pathophysiological analyses revealed that vasopressinase expression was more abundant in the GDI patient's syncytiotrophoblast in placenta compared with that in a control subject. Serum vasopressinase was also observed during gestation and disappeared soon after delivery. Vasopressinase is reportedly identical to oxytocinase or insulin regulated aminopeptidase (IRAP), which is an abundant cargo protein associated with the glucose transporter 4 (GLUT4) storage vesicle. Interestingly, the expression and subcellular localization of GLUT4 appeared to occur in a vasopressinase (IRAP)-dependent manner. CONCLUSION: Because placental volume may be associated with vasopressinase overproduction in GDI, vasopressinase (IRAP)/GLUT4 association appears to contribute to the growth of placenta in this case.

Prognostic significance of CD169-positive lymph node sinus macrophages in patients with endometrial carcinoma.

Lymph node (LN) macrophages play critical roles in anti-tumor immunity, which develops via the activation of cytotoxic T cells (CTL) and NK cells. The present study aims to determine the prognostic significance of CD169(+) LN macrophages in patients with endometrial carcinoma (EC). The number of CD169(+) cells or the CD169(+) -to-CD68(+) macrophage ratio in regional LN (RLN), and the number of CD8(+) CTL or CD57(+) NK cells in tumor tissues were investigated by immunohistochemistry in paraffin-embedded tissue samples from 79 patients with EC. A high density of CD169(+) cells in the RLN of patients with EC was correlated with an early clinical stage or no LN metastasis. A high number of CD169(+) cells and a high CD169(+) -to-CD68(+) macrophage ratio were significantly associated with longer overall survival in EC. We also found that the density of CD169(+) macrophages was positively correlated with the number of CD8(+) CTL and CD57(+) NK cells that infiltrated into tumor tissues. A high density of CD57(+) cells in EC tissues was associated with a better prognosis, while a high density of CD8(+) cells was not linked to an altered prognosis. The present study showed that the density of CD169(+) macrophages in RLN was associated with an improved prognosis in EC patients. CD169(+) macrophages in RLN might represent a useful marker for assessing clinical prognoses and monitoring anti-tumor immunity in patients with EC.

Development of a mouse model for testing therapeutic agents: the anticancer effect of dienogest on endometrial neoplasms.

OBJECTIVE: As the number of younger women with endometrial carcinoma has increased, fertility-sparing treatments have received more attention. Although there have been several reports on conservative treatments with progestins for endometrial carcinoma, only medroxyprogesterone acetate (MPA) is available in Japan. Dienogest has been developed as a fourth-generation progestin for treating endometriosis. Because of its high progesterone activity, its antitumor activity has attracted attention. In this study, we investigated the anticancer effect of dienogest on endometrial neoplasms using mouse model of endometrial carcinoma. METHODS/MATERIALS: Pten(loxP/loxP) mice were injected with MPA or dienogest subcutaneously to evaluate the anticancer effect against endometrial neoplasms that developed in the mice. One week after injections, histopathological analyzes were performed. RESULTS: Endometrial neoplasms were found in one of the eight (12.5%) mice from each group treated with either dienogest or MPA. In contrast, they were found in seven of eight (87.5%) mice not treated with progestins. Each progestin treatment showed anticancer activity against endometrial neoplasms that developed in the mice compared to those without treatment. CONCLUSIONS: Dienogest and MPA showed potent anticancer activity against endometrial neoplasms in our mouse model. The present study demonstrated that dienogest might be a useful therapeutic agent for human endometrial neoplasms.

An Ovarian Carcinoid Tumor With Peptide YY-Positive Insular Component: A Case Report and Review of the Literature.

Ovarian carcinoid tumors are uncommon and account for 1% of all carcinoid tumors. The insular type of ovarian carcinoid tumor is common in western countries; in contrast, the strumal and trabecular types seem to be common in Asian countries. Strumal and trabecular types are associated with peptide YY (PYY) production, which may cause constipation. Here, we report the case of a 70-yr-old Japanese woman with chronic constipation who was referred to Kumamoto University Hospital because of a right adnexal mass. Imaging tests suggested that the solid mass might be malignant; therefore, abdominal total hysterectomy, bilateral salpingo-oophorectomy, and omentectomy were performed. A subsequent histopathologic examination confirmed an insular carcinoid tumor with a trabecular component in the right ovary. Both components were positive for PYY but not for serotonin. The patient complained of diarrhea instead of constipation soon after the surgery. Because PYY-positive insular carcinoid tumor in the ovary has not been previously reported, we reviewed 19 reported cases of patients with PYY-positive ovarian carcinoid tumors. The origins, common histologic types and symptoms caused by specific peptides secreted in ovarian carcinoid tumors differ between western and Asian countries.

Long-Term Outcome of Aromatase Inhibitor Therapy With Letrozole in Patients With Advanced Low-Grade Endometrial Stromal Sarcoma.

BACKGROUND: There has been no consensus on the indications for the treatment of advanced low-grade endometrial stromal sarcoma (LGESS), and the possible effects of hormonal treatment including progestins and aromatase inhibitors have been reported. The aim of this study was to investigate the efficacy of aromatase inhibitor therapy with letrozole for patients with residual or recurrent LGESS. METHODS: We retrospectively reviewed the clinical response of patients with advanced LGESS who had been treated with letrozole. We also analyzed the adverse effects after the administration of letrozole. The expression levels of estrogen receptor and aromatase in the tumors were immunohistochemically examined. RESULTS: In 5 patients who had been treated for unresectable LGESS lesions after initial or repeat surgical procedures, residual lesions in 3 patients and recurrence lesions in 2 patients were the indications for hormonal therapy with letrozole. The median duration of letrozole exposure at retrospective analysis was 53 (10-96) months. The clinical outcomes were classified as complete response in 2 patients, partial response in 1 patient, and stable disease in 2 patients. Myalgias, hot flashes, and arthralgias were not observed during the follow-up period in any patients. The median serum levels of estradiol were <5.0 (cutoff value, <0.5-11.8) pg/mL. The median age-matched bone mineral densities were 92% (79%-123%). The LGESS tissues in all 5 patients were positive for estrogen receptor and aromatase expression. CONCLUSIONS: Letrozole as well as progestins could be the first choice of treatment for patients with recurrent or residual LGESS, which is difficult to resect surgically because of its efficacy and minimal adverse effects.

A Giant Ovarian Tumor Causing Anasarca and Dyspnea Successfully Managed after Preoperative Drainage.

Serious complications are likely to accompany the treatment of giant ovarian tumors, and resection with or without preoperative drainage has been previously reported. Here, we report the case of a 27-year-old Japanese woman with a significant weight gain of 50 kg, who was referred to the Kumamoto University Hospital because of gait impairment and dyspnea. Imaging tests revealed an ovarian tumor, 37 cm in diameter, with two solid components. The patient's condition improved after the removal of 31.5 l tumor fluid by using a suprapubic urinary catheter for 3 days. The tumor was subsequently resected without complications, and was diagnosed as a left mucinous ovarian tumor with malignant components, weighing 37 kg (81.5 lb). The patient was discharged after her anasarca improved, and her body weight decreased from 100 to 50 kg with accompanying considerable urination within two weeks. She was in good condition with no evidence of recurrence at 15 months after surgery. Tumor resection after preoperative drainage was effective in the management of a patient with dyspnea induced by a giant ovarian tumor. We suggest the use of a suprapubic urinary catheter for preoperative drainage because of its ease of use in preventing fluid leakage from the possibly malignant tumor.

Transvaginal methotrexate injection for the treatment of cesarean scar pregnancy: efficacy and subsequent fecundity.

STUDY OBJECTIVE: To investigate the efficacy of local methotrexate (MTX) injections under transvaginal ultrasound guidance for treatment of cesarean scar pregnancy (CSP) and to assess fecundity after treatment. DESIGN: Retrospective review (Canadian Task Force classification II-3). SETTING: University hospital. PATIENTS: Eight women with CSP. INTERVENTION: Transvaginal MTX injection. MEASUREMENTS AND MAIN RESULTS: We retrospectively reviewed 8 CSP cases treated with local MTX injection under transvaginal ultrasonographic guidance. In all cases, the serum human chorionic gonadotropin concentration was monitored and the gestational sac was evaluated using ultrasonography after treatment. Magnetic resonance imaging was performed as necessary. Patient clinical characteristics, clinical course after treatment, treatment efficacy, and fecundity after treatment in patients desiring subsequent pregnancies were evaluated. All 8 women were successfully treated without the need for blood transfusions or surgical procedures, although 2 required additional MTX therapy via local injection or systemic administration. The mean (SD) time to human chorionic gonadotropin normalization was 78.5 (37.7) days (range, 42-166 days). Four of 5 patients desiring subsequent pregnancies after the treatment had uneventful parturition, and recurrent CSP was diagnosed in 1 patient. CONCLUSIONS: Transvaginal MTX injection was effective and safe as sole treatment of CSP. Although the treatment course tended to be long, this method can be considered the first choice of treatment in patients desiring future pregnancies. However, careful attention should be paid to the possibility of CSP recurrence.