Munekage Yamaguchi

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.

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.

Primary strumal carcinoid tumor of the ovary: A pregnant patient exhibiting severe constipation and CEA elevation

► We present a rare case of a PYY-positive primary strumal carcinoid tumor of the ovary during pregnancy. ► MRI was useful for the preoperative diagnosis, and the prenatal course was uneventful after the operation. ► Colitis due to severe constipation caused by PYY, which is an inhibitor of intestinal mobility, might induce serum CEA elevation.

Treatment of cervical pregnancy with ultrasound‐guided local methotrexate injection

Cervical pregnancy (CP) is a rare type of ectopic pregnancy. While methotrexate (MTX) is generally the first‐line method of choice for clinically stable women, there is still no consensus on the most appropriate treatment for this abnormal pregnancy. The aim of this study was to investigate the efficacy of a single local MTX injection under transvaginal ultrasound guidance for the initial treatment of CP and to assess post‐treatment fertility.

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

Abstract 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: PtenloxP/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.

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.

Human chorionic gonadotropin induces human macrophages to form intracytoplasmic vacuoles mimicking Hofbauer cells in human chorionic villi.

The most characteristic morphological feature of macrophages in the stroma of placental villi, known as Hofbauer cells, is their highly vacuolated appearance. They also show positive immunostaining for human chorionic gonadotropin (hCG) and express messenger ribonucleic acid of the luteinizing hormone/chorionic gonadotropin receptor with a deletion of exon 9 (LH/CG-R Δ9). Maternal hCG enters fetal plasma through the mesenchyme of the placental villi and promotes male sexual differentiation in early pregnancy; therefore, excess hCG may induce aberrant genital differentiation and hCG must be adjusted at the fetomaternal interface. We hypothesized that hCG is regulated by Hofbauer cells and that their peculiar vacuoles are involved in a cell-specific function. To assess the morphological modification and expression of LH/CG-R Δ9 in human macrophages after hCG exposure, the present study examined phorbol 12-myristate 13-acetate (PMA)-treated THP-1 cells, a human monocyte-macrophage cell line. hCG induced transient vacuole formation in PMA-treated THP-1 cells, morphologically mimicking Hofbauer cells. Immunocytochemistry showed that PMA-treated THP-1 cells incorporated hCG but not luteinizing hormone or follicle-stimulating hormone. Western blotting analyses demonstrated that PMA-treated THP-1 cells expressed an immunoreactive 60-kDa protein, designated as endogenous LH/CG-R Δ9. hCG induced a transient reduction in the LH/CG-R Δ9, which was synchronous with the appearance of cytoplasmic vacuoles. In conclusion, human macrophages regulating hCG via cytoplasmic LH/CG-R Δ9 mimic the morphological characteristics of Hofbauer cells. Their vacuoles may be associated with their cell-specific function to protect the fetus from exposure to excess maternal hCG during pregnancy.

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.

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 patients 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.

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.