Hiroshi Tsujioka

A pure nongestational choriocarcinoma of the ovary diagnosed with DNA polymorphism analysis

BACKGROUND Choriocarcinoma arises in the ovary from gestational or nongestational origin. Nongestational choriocarcinoma of the ovary is extremely rare and the pure type is less frequent than the mixed type with other germ cell tumors. Diagnosis of pure nongestational choriocarcinoma is very difficult without genetic analysis. CASE We report a pure nongestational choriocarcinoma primarily arising in a 19-year-old womans ovary. Following abdominal operative procedure, careful examination of the tumor revealed pure choriocarcinoma without combination of other germ cell tumors. We confirmed its nongestational origin by DNA polymorphism analysis. Multiple courses of chemotherapy with an EMA/CO regimen were effective for this case. CONCLUSION Genetic analysis is useful tool in determining the origin of choriocarcinoma. We could distinguish the genetic origin of this tumor analyzing only two or three appropriate VNTR loci.

A normal uterus communicating with a double cervix and the vagina: a müllerian anomaly without any present classification

OBJECTIVE To report a rare uterine anomaly consisting of a normal uterus, a double cervix, and a double vagina. DESIGN Case report. SETTING University hospital. PATIENT(S) A 28-year-old nulligravida patient referred for evaluation of primary infertility and a suspected müllerian anomaly. INTERVENTION(S) Clinical and surgical evaluation of the anomaly. MAIN OUTCOME MEASURE(S) Description and treatment for a rare uterine anomaly and a subsequent literature search. RESULT(S) Successful resection of vaginal septum and subsequent pregnancy. CONCLUSION(S) This extremely rare anomaly is not explained by classic embryologic teachings, and it does not fit into the classification system currently used to describe müllerian anomalies.

K‐ras mutation in tamoxifen‐related endometrial polyps

K‐ras mutation is thought to occur at an early stage of neoplastic progression in the endometrium. The authors investigated mutations in codon 12 of K‐ras in tamoxifen (TAM)‐related endometrial polyps.

Small‐Cell Carcinoma of the Endometrium: An Immunohistochemical and Ultrastructural Analysis

Small‐cell carcinoma of the endometrium is a rare neoplasm, and its aggressive behavior has been reported. We report a case of small‐cell carcinoma occurring primarily in the endometrium of a 62‐year‐old woman with postmenopausal vaginal bleeding and lower abdominal pain. The excised uterus showed a necrotic polypoid mass and histologically displayed an endometrial small‐cell carcinoma. Immuno‐histochemically, the tumor cells were positive for cytokeratin, the epithelial membrane antigen, neuron‐specific enolase, and chromogranin, but were negative for the leukocyte common antigen and Grimelius stain. Ultrastructural analysis revealed the presence of dense core granules in the cytoplasm of tumor cells. The patient died 2 months after surgery because of aggressive behavior of the tumor. We wish to distinguish small‐cell carcinoma of the endometrium from conventional epithelial tumors of the endometrium, because of the formers distinctive histopathologic, immunohistochemical, and ultrastructural characteristics.

Critical Role of TRPC1-Mediated Ca2+ Entry in Decidualization of Human Endometrial Stromal Cells

Decidualization is an ovarian steroid-induced remodeling/differentiation process of uterus essential for embryo implantation and placentation. Here, we investigated the possible involvement of enhanced Ca²⁺ dynamics in the decidualization process in human endometrial stromal cells (hESC) in its connection with a recently emerging nonvoltage-gated Ca²⁺ entry channel superfamily, the transient receptor potential (TRP) protein. Combined application of 17β-estradiol (E₂) (10 nM) and progesterone (P₄) (1 μM) for 7-14 d resulted in morphological changes of hESC characteristic of decidualization (i.e. cell size increase), whereas sole application of E₂ exerted little effects. A 7- to 14-d E₂/P₄ treatment greatly increased the expression level of decidualization markers IGF binding protein-1 (IGFBP-1) and prolactin and also up-regulated the expression of TRPC1, a canonical TRP subfamily member that has been implicated in store-operated Ca²⁺ influx (SOC) in other cell types. In parallel with this up-regulation, SOC activity in hESC, the nuclear translocation of phosphorylated cAMP responsive element binding protein (p-CREB) and the expression of Forkhead box protein 01 were enhanced significantly. Small interfering RNA knockdown of TRPC1 counteracted the E₂/P₄-induced up-regulation of IGFBP-1 and prolactin and enhancement of SOC activity together with the inhibition of hESC size increase, p-CREB nuclear translocation, and FOXO1 up-regulation. Coadministration of SOC inhibitors SK&F96365 or Gd³⁺ with E₂/P₄ also suppressed the up-regulation of IGFBP-1 and hESC size increase. Similar inhibitory effects were observed with extracellularly applied TRPC1 extracellular loop 3-directed antibody, which is known to bind a near-pore domain of TRPC1 channel and block its Ca²⁺ transporting activity. These results strongly suggest that up-regulation of TRPC1 protein and consequent enhancement of SOC-mediated Ca²⁺ influx may serve as a crucial step for the decidualization process of hESC probably via p-CREB-dependent transcriptional activity associated with FOXO1 activation.

Targeting the heparin-binding epidermal growth factor-like growth factor in ovarian cancer therapy.

Purpose of review Therapeutics targeting the ErbB protein family receptors have not always yielded favorable or successful results in present cancer therapy. This review discusses the possibility of the clinical adaptation of targeting against heparin-binding epidermal growth factor-like growth factor (HB-EGF), one of the ligands of the ErbB system, in ovarian cancer therapy. Recent findings We have previously described the results of studies concerning roles of HB-EGF in tumor formation in ovarian cancer. In brief, lisophosphatidic acid (LPA) and HB-EGF are predominantly expressed in advanced ovarian cancer, and LPA-induced, a disintegrin and metalloprotease-mediated ectodomain shedding of HB-EGF was found to be critical to tumor formation. We also noted that exogenous expression of HB-EGF enhanced tumor formation but inhibition blocked both extracellular signal-related kinase and serine/threonine protein kinase activation. Finally we investigated the antitumor effects of CRM197 – a specific HB-EGF inhibitor – on ovarian cancer cells by evaluating human ovarian cancer cell proliferation. Summary We discuss alternative strategies to develop the chemotherapeutic agent based on targeting ErbB family ligands rather than their receptors. A phase I study of CRM197 for advanced ovarian cancer has already begun, which is the first approved trial of ErbB-ligand-targeted therapy. We also discuss clinical adaptations based on combination of CRM197 with other conventional chemotherapeutic agents.

The efficacy of preoperative hormonal therapy before laparoscopic cystectomy of ovarian endometriomas.

Aim:  The aim of this study was to investigate the influence of preoperative hormonal therapy before laparoscopic cystectomy of ovarian endometriomas. We identified differences in follicle loss and surgical difficulties with or without preoperative hormonal therapy.

The Role of c-Jun Protein in Proliferation and Apoptosis of the Endometrium throughout the Menstrual Cycle

Proliferation and apoptosis of the endometrium throughout the menstrual cycle were evaluated. Sections from 30 premenopausal women were examined using antibodies of c-jun protein, c-fos protein, estrogen receptors alpha and beta (ER-α and ER-β), progesterone receptor (PR), and Ki-67. Apoptotic cells were identified using a modified terminal deoxynucleotidyl-transferase-mediated biotinylated deoxyuridine triphosphate nick-end labeling (TUNEL) method. The cyclic changes of c-jun protein, c-fos protein, ER-α, PR, and Ki-67 were shown in glandular epithelial cells. Although the stromal expression of ER-α decreased during the secretory phase, a high stromal expression of c-jun protein and PR was still observed during the late secretory phase. The expression of ER-β appeared lower as compared with that of ER-α, without a cyclic change. The apoptotic index was significantly elevated in the glandular epithelial cells of the late secretory phase, whereas a few apoptotic cells were detected in the stromal cells at any stage of the cycle. The cyclic change of c-jun protein probably plays an important role in proliferation and apoptosis of glandular epithelial cells. The persistent stromal expression of c-jun protein and PR is thus considered to prevent stromal cells from entering into apoptosis during the late secretory phase.

Amnioreduction in patients with bulging prolapsed membranes out of the cervix and vaginal orifice in cervical cerclage.

Abstract Objective: To determine whether an amnioreduction via bulging membranes (AVBM) and cerclage could be useful in 17 women with singleton gestations demonstrating hourglass membranes bulging out of the cervix or vaginal orifice. Methods: We used the following selection criteria for AVBM under ultrasonographic guidance using a peit needle because of undetectable cervical edges: (type 1) the bag of membranes protruded beyond the inlet of the vagina; (type 2) the bag of huge membranes completely occupied the vagina. Results: Eight patients (three cases of type 1 and five of type 2) were successful in AVBM and cerclage at 22.1±2.2 weeks gestation (range 19–24 weeks), and mean birth weight was 1,048.1±801.6 g (range 302– 2,688 g). Although the diameter of the forewater by transabdominal ultrasonography (cm) was higher than in the nine patients without AVBM (6.7±1.1 versus 4.1±0.7 cm, p=0.002), the prolongation of pregnancy (32.9±46.2 days; range 2–133 days) was the same as in patients without AVBM (36.9±39.3 day, p=1.000). Conclusion: It is important that every effort should be made to perform cervical cerclage at or before 26 weeks of gestation, even in women with type 1 or 2.

Involvement of anticentromere antibody in interference with oocyte meiosis and embryo cleavage.

The aim of this study was to investigate the clinical significance of anticentromere antibody (ACA) among types of antinuclear antibody (ANA) in the properties of oocytes retrieved from infertile women. The rate of metaphase II oocytes or embryo cleavage was significantly decreased in patients with positive ACA compared with patients with negative ACA, suggesting that ACA is an essential marker for flawed oocytes in infertile women with any type of ANA.