Efficacy and safety of ASP1707 for endometriosis-associated pelvic pain: the phase II randomized controlled TERRA study.

Study Question: Does the GnRH antagonist, ASP1707, reduce endometriosis-associated pelvic pain?

Summary Answer: ASP1707 significantly reduced endometriosis-associated pelvic pain in a dose-related manner.

What Is Known Already: GnRH agonists are an effective therapeutic option for endometriosis that is refractory to non-steroidal anti-inflammatory drugs, oral contraceptives, and progestins. However, GnRH agonists cause complete suppression of estradiol (E2), resulting in hypoestrogenic side-effects such as bone loss that may increase the future risk of osteoporotic fractures.

Is it possible to diagnose malignancy from fluid in cystic ovarian tumors?

Objective: p53 gene mutations are frequently identified in ovarian cancer tissue. The aim of this study was to investigate whether wild type or mutated genomic DNA can be identified in ovarian cystic fluid specimens.

Study Design: Forty-eight Japanese patients with cystic ovarian tumors (30 benign cysts, 8 borderline malignant tumors, and 10 cancers) were investigated.

Detection of Merkel cell polyomavirus in cervical squamous cell carcinomas and adenocarcinomas from Japanese patients.

Background: Merkel cell polyomavirus (MCPyV) was identified originally in Merkel cell carcinoma (MCC), a rare form of human skin neuroendocrine carcinoma. Evidence of MCPyV existence in other forms of malignancy such as cutaneous squamous cell carcinomas (SCCs) is growing. Cervical cancers became the focus of our interest in searching for potentially MCPyV-related tumors because: (i) the major histological type of cervical cancer is the SCC; (ii) the uterine cervix is a common site of neuroendocrine carcinomas histologically similar to MCCs; and (iii) MCPyV might be transmitted during sexual interaction as demonstrated for human papillomavirus (HPV).

Role of NK cells and HLA-G in endometriosis.

Impaired natural killer (NK) activity in women with endometriosis is thought to promote implantation and progression of endometrial tissue, in accord with Sampson's hypothesis. However, the mechanisms responsible for decreased NK cell activity and the antigens recognized by NK cells are not clear.We focused on human leukocyte antigen (HLA)-G, a ligand of NK receptors, expression and its menstrual cycle changes by eutopic endometrium.

Prophylactic administration of melatonin to the mother throughout pregnancy can protect against oxidative cerebral damage in neonatal rats.

Objective: The purpose of this study was to investigate whether prophylactic administration of melatonin to the mother throughout pregnancy could protect against ischemia/reperfusion (I/R)-induced oxidative brain damage in neonatal rats.

Methods: The utero-ovarian arteries were occluded bilaterally for 30 min in female Wistar rats on day 16 of pregnancy to induce fetal ischemia. Reperfusion was achieved by releasing the occlusion and restoring circulation.

Therapeutic effects of maternal melatonin administration on ischemia/reperfusion-induced oxidative cerebral damage in neonatal rats.

Background: We have previously demonstrated that prophylactic administration of melatonin to pregnant rats can protect against ischemia/reperfusion (I/R)-induced oxidative cerebral damage in fetal rats. However, the effects of maternal administration of melatonin after an ischemic episode on the brains of neonatal rats exposed to oxidative stress in utero have not been evaluated.

Objectives: The purpose of the present study was to investigate whether maternal administration of melatonin after an ischemic episode can prevent oxidative cerebral damage in neonatal rats.

A long-survived case with solitary splenic metastasis from ovarian carcinoma.

A61-year-old postmenopausal woman with ovarian carcinoma was treated with two surgical operations and a series of platinum-based chemotherapy. A solitary metastasis into the splenic parenchyma was identified 33 months after the second surgery by abdominal computed tomography with an increased serum level of CA-125. She underwent a pancreaticosplenectomy and received platinum-based adjuvant chemotherapy continuously for 2 years.

Preoperative evaluation of pelvic masses with combined 18F-fluorodeoxyglucose positron emission tomography and computed tomography.

Objective: To prospectively evaluate the diagnostic value of combined 18F-fluorodeoxyglucose position emission tomography and computed tomography (FDG-PET/CT) to discriminate malignant or borderline malignant tumors from benign pelvic masses.

Methods: A prospective study of 30 women with suspected ovarian cancer who presented from July 2006 through August 2007. Selection was based on evidence from ultrasound, magnetic resonance imaging, and rising tumor marker levels.

Melatonin preserves fetal growth in rats by protecting against ischemia/reperfusion-induced oxidative/nitrosative mitochondrial damage in the placenta.

We have previously demonstrated that melatonin protects against ischemia/reperfusion-induced oxidative damage to mitochondria in the fetal rat brain. The purpose of the present study was to evaluate the effects of maternally administered melatonin on ischemia/reperfusion-induced oxidative placental damage and fetal growth restriction in rats. The utero-ovarian arteries were occluded bilaterally for 30 min in rats on day 16 of pregnancy to induce fetal ischemia.

Human leukocyte antigen-G, a ligand for the natural killer receptor KIR2DL4, is expressed by eutopic endometrium only in the menstrual phase.

Objective: To investigate menstrual cycle changes in expression by eutopic endometrium of a nonclassic human leukocyte antigen, HLA-G, which binds to the killer immunoglobulin-like receptor (KIR) 2DL4 (CD158d) on natural killer (NK) cells. Such antigens have been linked to endometriosis.

Design: Case-control study.

Chemical zona pellucida thinning with acidified Tyrode's solution: comparison between partial and circumferential techniques.

Purpose: To compare effectiveness of two different chemical zona thinning techniques.

Method: We studied 163 patients who had experienced IVF or ICSI failures in two or more cycles. Patients were assigned to one of three groups: zona intact (n=72), partial thinning (n=59), or circumferential thinning (n=73).

Decreased human leukocyte antigen-DR expression in the lipid raft by peritoneal macrophages from women with endometriosis.

Objective: To investigate the macrophage response in endometriosis by determining the expression and localization of human leukocyte antigen (HLA)-ABC and HLA-DR by the peritoneal fluid (PF) macrophages and PF concentrations of interferon (IFN)-gamma that regulate HLA expression.

Design: Case-control study.

Setting: University hospital.

Primary yolk sac tumor concomitant with carcinosarcoma originating from the endometrium: case report.

Background: A primary yolk sac tumor (YST) with carcinosarcoma originating from the endometrium is extremely rare, to our knowledge, this is the third documented instance. Several hypotheses exist is to its histogenesis.

Case: A 65-year-old Japanese woman was diagnosed with a uterine malignancy and underwent surgical treatment and chemotherapy.

Killer immunoglobulin-like receptor and human leukocyte antigen expression as immunodiagnostic parameters for pelvic endometriosis.

Problem: We investigated host immunologic responses to endometriosis by comparing immune cell surface antigens in peripheral blood (PB) and peritoneal fluid (PF) from women with endometriosis with those in PB and PF from other patients.

Method Of Study: Japanese women with endometriosis (n = 56) were compared with controls with other laparoscopic diagnoses (n = 68). PB and PF were collected at the time of laparoscopy for flow cytometry.

Malignant müllerian mixed tumor (carcinosarcoma) of the fallopian tube: an immunohistochemical study of neoplastic cells.

The patient was a 65-year-old woman who complained of lower abdominal pain. Salpingo-oophorectomy and hysterectomy were performed due to suspicion of ovarian cancer. At surgery a polypoid mass was observed in the fimbria of the left fallopian tube.

Non-puerperal uterine inversion associated with endometrial carcinoma--a case report.

Background: Non-puerperal uterine inversion is rare, and a case associated with endometrial carcinoma is even rarer. It is difficult to diagnose the condition preoperatively and most cases are diagnosed at surgery.

Case: We describe a case of uterine inversion associated with endometrial carcinoma.

Expression of inhibitory-motif killer immunoglobulin-like receptor, KIR2DL1, is increased in natural killer cells from women with pelvic endometriosis.

Problem: We investigated inhibitory and activation motif expression of killer immunoglobulin-like receptor (KIR) by natural killer (NK) cells, which may be pathogenetically involved in endometriosis.

Method Of Study: We compared cells from 24 Japanese women laparoscopically diagnosed with endometriosis, to cells from 25 women with other laparoscopic diagnoses. KIR expression by NK cells was assessed in peripheral blood (PB) and peritoneal fluid (PF) by flow cytometry.

Human leukocyte antigen expression by peritoneal macrophages from women with pelvic endometriosis is depressed but coordinated with costimulatory molecule expression.

Objective: To investigate the macrophage response in endometriosis, we determined expression of human leukocyte antigen (HLA)-ABC, HLA-DR, and their costimulatory molecules by peritoneal fluid (PF) macrophages.

Design: Case-control study of immunologic markers.

Setting: University hospital.

MRI of endocervical glandular disorders: three cases of a deep nabothian cyst and three cases of a minimal-deviation adenocarcinoma.

The incidence of cervical adenocarcinoma is increasing. Nabothian cysts are a common gynecologic condition; if multiple and/or large cysts are present, it is difficult to differentiate them from a minimal-deviation adenocarcinoma (MDA), which is classified as a special type of cervical adenocarcinoma. We report three cases of deep nabothian cysts and three cases of MDAs.

Small low-density lipoprotein particles and endothelium-dependent vasodilation in postmenopausal women.

Low concentrations of estrogen may decrease endothelial function in postmenopausal women. Elevated plasma triglycerides after menopause are frequently associated with a small, dense low-density lipoprotein (LDL) phenotype. Small LDL particles that are more susceptible to oxidation can also inhibit endothelium-dependent vasodilation.