A case of cystic lymphangioma arising from the parauterine tissue.

A 57-year-old woman, gravida 3, para 3, with no complaints visited our hospital for right-sided adnexal tumor found incidentally in cancer screening. She had no medical history, surgical history, or gynecological disease. Imaging studies showed a 5-cm lobular cystic tumor on the right side of uterus. We suspected right hydrosalpinx and decided to perform diagnostic laparoscopy. During laparoscopy, the right adnexa was found to be atrophic, and the tumor was located in the broad ligament. The tumor was observed to be a multilocular cyst containing yellow fluid that developed from the right parauterine tissue. The tumor was resected from the surrounding tissue. Histological examination revealed that the multilocular cyst contained a vascular component surrounding the lymphatic endothelium and was decided to be a cystic lymphangioma. The patient was followed up and there was no evidence of recurrence at postoperative 7 months. We experienced a very rare case of lymphangioma arising from the parauterine tissue. The laparoscopic approach can assist with both diagnosis and treatment.

Porphyromonas gingivalis, a cause of preterm birth in mice, induces an inflammatory response in human amnion mesenchymal cells but not epithelial cells.

INTRODUCTION: Inflammation and infection, including dental infectious diseases, are factors that can induce preterm birth. We previously reported that mice with dental Porphyromonas gingivalis infection could be used as a model of preterm birth. In this model, cyclooxygenase (COX)-2 and interleukin (IL)-1ß levels are increased, and P. gingivalis colonies are observed in the fetal membrane. However, the mechanism underlying fetal membrane inflammation remains unknown. Therefore, we investigated the immune responses of human amnion to P. gingivalis in vitro. METHODS: Epithelial and mesenchymal cells were isolated from human amnion using trypsin and collagenase, and primary cell cultures were obtained. Confluent cells were stimulated with P. gingivalis lipopolysaccharide (P.g-LPS) or P. gingivalis. mRNA expressions of IL-1ß, IL-8, IL-6 and COX-2, protein expressions of nuclear factor (NF)-κB pathway components and culture medium levels of prostaglandin E2 were evaluated. RESULTS: Following stimulation with 1 µg/mL P.g-LPS, the mRNA expression levels of IL-1ß, IL-8, IL-6 and COX-2 in mesenchymal cells were increased 5.9-, 3.3-, 4.2- and 3.1-fold, respectively. Similarly, the expression levels of IL-1ß, IL-8, IL-6 and COX-2 in mesenchymal cells were increased by 7.6-, 8.2-, 13.4- and 9.3-fold, respectively, after coculture with P. gingivalis. Additionally, stimulation with P.g-LPS or P. gingivalis resulted in the activation of NF-κB signaling and increased production of IL-1ß and prostaglandin E2. In contrast, no significant changes were observed in epithelial cells. DISCUSSION: Our findings suggest that mesenchymal cells might mediate the inflammatory responses to P. gingivalis and P.g-LPS, thereby producing inflammation that contributes to the induction of preterm birth.

[Thrombocytopenia in pregnancy: a single-center retrospective analysis of 91 cases].

Thrombocytopenia is a relatively common complication in pregnancy, with a reported frequency of 7%-11%. The causes of this condition are diverse, although the most common etiology is gestational thrombocytopenia (GT) (70%-80%), followed by HELLP syndrome and immune thrombocytopenia (ITP). To investigate the clinical features of thrombocytopenia during pregnancy, we conducted a retrospective analysis of 69 women at our center with 91 pregnancies in which the platelet count was below 100×109/l. There were 38 cases in women with a prior diagnosis of thrombocytopenic diseases such as ITP or an inherited platelet disorder. In the remaining 53 cases, a diagnosis could be made only after delivery. We analyzed the disease course, maternal and perinatal characteristics, platelet count fluctuations, and pregnancy outcomes. The final diagnosis was GT in 38, ITP in 14, and other causes in 1. To distinguish between GT and ITP is not always feasible and can sometimes only be performed based on postpartum changes in the platelet count. In pregnant women with thrombocytopenia, careful follow-up of platelet count fluctuations after delivery is crucial to distinguish ITP from GT.

Fetal Membrane Inflammation Induces Preterm Birth Via Toll-Like Receptor 2 in Mice With Chronic Gingivitis.

Inflammation is associated with preterm birth. We previously described a mouse model of chronic inflammation-induced preterm birth after dental Porphyromonas gingivalis infection. The aim of this study was to employ this model system to investigate the mechanisms through which enhanced uterine contractility induces preterm birth. Messenger RNA (mRNA) encoding contraction-associated proteins, such as oxytocin receptors, was measured at various gestational time points by real-time polymerase chain reaction (PCR). Spontaneous and oxytocin-induced uterine contractile activity at gestational day 18 was assessed using a tissue organ bath. The expression levels of Toll-like receptor 2 (TLR2), TLR4, cyclooxygenase (COX)-2, nuclear factor-kappa B (NF-κB) p65, and p38 mitogen-activated protein kinase (MAPK) on gestational day 18 were also determined by real-time PCR or Western blotting. Messenger RNA encoding contraction-associated proteins was increased at gestational day 18, and the spontaneous contractile activity (1.6-fold greater area under the contraction curve) and sensitivity to oxytocin (EC50: 8.8 nM vs 2.2 nM) were enhanced in the P gingivalis group compared to those in the control group. In the P gingivalis group, COX-2 mRNA expression was not elevated in the placenta or myometrium but was upregulated 2.3-fold in the fetal membrane. The TLR2 mRNA levels in the fetal membrane were 2.7-fold higher in the P gingivalis group, whereas TLR4 levels were not elevated. Activation of the NF-κB p65 and p38 MAPK pathways was enhanced in the fetal membrane of the P gingivalis group. Thus, in mice with chronic dental P gingivalis infection, TLR2-induced inflammation in the fetal membrane leads to upregulation of uterine contractility, leading to preterm birth.

Two Case Reports of Intravenous Leiomyomatosis with Hyaluronan Expression.

Intravenous leiomyomatosis (IVL) is a rare benign neoplasm. Herein, we describe two cases of IVL at different levels of progression. The tumor in Case 1 was extensive, invading the right atrium after a hysterectomy for a uterine myoma. The tumor temporarily responded to hormonal treatment; however, tumor regrowth occurred. In contrast, the tumor in Case 2 extended only to the pelvic veins and was revealed preoperatively. Hysterectomy and bilateral salpingo-oophorectomy were performed, resulting in the complete surgical resection of the tumor. In Case 2, no recurrence has been observed. Tumor samples were evaluated for hyaluronan expression using Alcian blue staining (with and without hyaluronidase digestion). The tumor in Case 1 stained strongly positive for hyaluronan while the tumor in Case 2 stained weakly positive for hyaluronan. In contrast, a large non-IVL uterine leiomyoma (control) stained negative for hyaluronan. These results suggest a relationship between tumor hyaluronan expression and IVL progression, similar to that in other cancers.

Prenatal and Peripartum Management of Patients with Hypofibrinogenemia Resulted in Two Successful Deliveries.

Fibrinogen is an essential agent involved in maintaining pregnancy and coagulation. Since inherited fibrinogen disorders introduce greater risks for conditions such as placental abruption and postpartum hemorrhage, careful prenatal and perinatal management is essential for this patient population. We report two cases of successful deliveries in patients with hypofibrinogenemia. Case 1 is of a 26-year-old (gravida 1, para 1) woman. The patient's fibrinogen level increased spontaneously to higher than 300 mg/dL during pregnancy, without treatment. She delivered at week 38 of gestation, with no complications. Case 2 is of a 30-year-old (gravida 3, para 1) woman. We performed repeated infusions of fibrinogen to maintain the level higher than 100 mg/dL during pregnancy and at least 200 mg/dL in the perioperative period; the patient delivered a healthy infant. We identified a new mutation, Hiroshima I (γ278Tyr→His). It is important to maintain appropriate fibrinogen levels in cases of inherited fibrinogen disorders for successful prenatal and peripartum management.

Enhanced Expression of Contractile-Associated Proteins and Ion Channels in Preterm Delivery Model Mice With Chronic Odontogenic Porphyromonas Gingivalis Infection.

Inflammation and infection have been reported to induce preterm delivery. We have studied the relationship between inflammation and various ion channels, including the L-type Ca(2+) channel and P2X7 receptor, during acute inflammation of the pregnant rat uterus induced by lipopolysaccharides. Recently, we found that mice with odontogenic Porphyromonas gingivalis (P.g, an important odontogenic pathogen) infection delivered at day 18.3 of gestation (vs. day 20.5 in normal mice). The purpose of this study was to investigate the expression of myometrial contractile-associated proteins inducing contractions and confirm that these mice are useful as a model for preterm delivery induced by chronic inflammation. We examined the expression of the oxytocin receptor, connexin 43, prostaglandin F receptors, L-type Ca(2+) channel, and P2X7 receptor in the myometrium at day 18 of gestation by real-time PCR and western blot analyses. We also measured TNF-α and IL-1ß levels in the blood serum, placenta, fetal membrane and myometrium on the same day. mRNA expression of the oxytocin receptor, connexin 43, prostaglandin F receptors, L-type Ca(2+) channel, and P2X7 receptor was elevated by 5.4, 3.2, 2.4, 2.5, and 1.7 fold, respectively, in the P.g-infected mice. Protein levels of the oxytocin receptor and connexin 43 also increased. Serum levels of TNF-α and IL-1ß were elevated, showing that systemic inflammation continued during pregnancy. IL-1ß levels in the placenta and fetal membrane also increased, suggesting inflammatory reactions were induced. Thus, mice with odontogenic infection may be useful as a model of chronic inflammation-induced preterm delivery.

ATP-induced currents carried through P2X7 receptor in rat myometrial cells.

OBJECTIVE: The functional significance of purinergic P2 receptors in the myometrium is unclear. We previously reported the ATP-induced ionic currents in rat myometrial cells, causing uterine contractility. The aim of this study is to determine the main P2X receptors that carry the adenosine triphosphate (ATP)-induced currents. STUDY DESIGN: We cloned predominantly expressed P2X7 receptors from rat myometrium and transfected into cultured COS-7 cells. Reconstructed P2X7 receptor currents were characterized using the whole-cell patch clamp method. RESULTS: Extracellular ATP induced currents through P2X7 receptors with effective concentration (EC(50)) of 155 µmol/L, without desensitization. The myometrial P2X7 receptor was permeable to multiple monovalent cations with conductances ranked as K(+)>Cs(+)>Li(+)>Na(+). It was activated by P2X receptor agonists, with effectiveness ranked as 2',3'-O-(4-benzoylbenzoyl)-ATP (Bz-ATP)>>ATP>αß-methylene ATP (αß-MeATP)>2-methylthio ATP (2-MeSATP)>uridine triphosphate (UTP)>guanosine triphosphate (GTP)>adenosine diphosphate (ADP). These currents were blocked by selective P2X7 receptor antagonists and extracellular Mg(2+). CONCLUSION: P2X7 receptors carry ATP-induced currents in rat myometrial cells.

Functional expression of purinergic P2X7 receptors in pregnant rat myometrium.

ATP has been reported to enhance the membrane conductance of myometrial cells and uterine contractility. Purinergic P2 receptor expression has been reported in the myometrium, using molecular biology, but the functional identity of the receptor subtype has not been determined. In this study, ATP-induced currents were recorded and characterized in single myometrial cells from pregnant rats using whole cell patch clamping. Extracellular ATP was applied in the range of 10 muM-1 mM and induced currents with an EC(50) of 74 muM, with no desensitization, time dependency, or voltage dependency. The currents induced carried multiple monovalent cations, with conductances ranked as K(+) > Cs(+) > Li(+) > Na(+). They were activated by P2X receptor agonists, with their effectiveness ranked as 2',3'-O-(4-benzoylbenzoyl)-ATP >> ATP > alphabeta-methylene-ATP > 2-methylthio ATP > or = UTP > or = GTP > ADP. These currents were blocked by the selective P2X7 receptor antagonist 3-[5-(2,3-dichlorophenyl)-1 H-tetrazol-1-yl]methyl pyridine (A-438079). We therefore concluded that ATP-induced currents in rat myometrial cells crossed cell membranes via P2X7 receptors. We further showed that the ATP-induced currents were blocked by extracellular Mg(2+) (IC(50) = 0.26 mM). Clinically, administering extracellular Mg(2+) is known to inhibit uterine contraction. It therefore seems likely that uterine contraction may be induced by raised extracellular ATP and suppressed via Mg(2+) inhibiting P2X7 receptors. Further research is needed into the P2X7 receptor as a therapeutic target in abnormal uterine contraction, as a possible treatment for premature labor.

Enhanced expression of P2X4 and P2X7 purinergic receptors in the myometrium of pregnant rats in preterm delivery models.

The expression levels of P2X purinergic receptors were determined in the myometrium of pregnant rats using the quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR). The messenger RNAs (mRNAs) of P2X4 and P2X7 were expressed most strongly. The expression levels of these receptors increased during the late stages of pregnancy; at the time of delivery, the mRNA levels of P2X4 and P2X7 had increased to 1.9 and 3.2 times the day 19 values, respectively. We also explored the roles of P2X receptors in hormone-induced and inflammation-induced preterm delivery models. In the former, mifepristone caused the P2X4 and P2X7 mRNA levels to increase to 2.1 and 4.1 times the control values, respectively. In the latter, lipopolysaccharide (LPS) caused the mRNA levels of P2X4 and P2X7 to increase dramatically to 7.4 and 18.6 times the control values, respectively. These findings suggest that increased P2X4 and P2X7 receptor expression in pregnant rats is related to uterine contraction leading to term and preterm delivery.

P57kip2 immunohistochemical expression and ultrastructural findings of gestational trophoblastic disease and related disorders.

Gestational trophoblastic disease (GTD) is a unique spectrum of diseases ranging from complete hydatidiform mole (CHM), partial hydatidiform mole (PHM), and invasive mole (IM) to choriocarcinoma (CC). Placental site trophoblastic tumor (PSTT) and epithelioid trophoblastic tumor (ETT) have been classified as related disorders. Mesenchymal dysplasia (MD) may be misdiagnosed as PHM; however, it is said to have a quite different histogenesis from PHM. P57kip2 is the protein product of a paternally imprinted or maternal gene that inhibits cyclin-dependent kinases (CDK), thus serving to inhibit cell proliferation and to suppress tumor growth. Its lack of expression in trophoblastic disease plays a role in its abnormal proliferation and differentiation. In this study, P57kip2 immunostaining was absent in the trophoblastic layers of CHM and was positive in the trophoblast layer of nonmolar villi and MD. Ultrastructure of complete molar cystic villi showed tree-like branching of microvillous processes and intracytoplasmic lacunae without capillaries in the stroma, whereas MD contained many newly formed blood vessels and collagen. Also, large lacunae with microvilli and polymorphic nuclei of syncytiotrophoblast cells with well-developed organelles were observed in IM. Lung ETT following CHM and normal deliveries showed two types of large mononuclear cells and binuclear cells with abundant organelles and bundles of intermediate-type filaments in the stroma.

Epithelioid trophoblastic tumor of the lung.

Epithelioid trophoblastic tumor (ETT) is a rare type of gestational trophoblastic disease and only 25 cases have been reported so far. It was first proposed by Mazur and Kurman in 1994 as an unusual type of trophoblastic tumor that is distinct from placental site trophoblastic tumor and choriocarcinoma and has features resembling carcinoma. A case of ETT of the lung in a 38-year-old Japanese woman is reported. The patient had suffered from a hydatidiform mole at the age of 27 years, and had four normal deliveries at the ages of 24, 31, 35 and 37 years. Because no tumor lesions were detected in the uterus, the patient was suspected of having metastatic choriocarcinoma with multiple lesions in the lung accompanied by an elevated level of human chorionic gonadotropin (hCG). In order to make an exact diagnosis, a partial resection of metastatic foci in the lung was performed. Microscopically, the tumor showed hemorrhagic necrotic foci and was composed of mainly mononuclear tumor cells and some giant tumor cells resembling trophoblastic cells. Immunohistochemical examination showed that a few large cells were stained positively for hCG, and that other cells were positive for human placental lactogen, pregnancy-specific beta1-glycoprotein, cytokeratin 7 and inhibin-alpha. In the ultrastructure, the tumor cells contained large nuclei and rich organella with desmosomes and well-formed filaments. The diagnosis of ETT was confirmed from the findings as described above.

[Recurrent ovarian cancer with cancer peritonitis treated with weekly paclitaxel infusion--a clinicopharmacological study].

We treated a patient with recurrent ovarian cancer with cancerous peritonitis by weekly paclitaxel (w-TXL) therapy (65 mg/m2). Abdominocentesis was not performed to eliminate ascites, in order to maintain higher quality of life (QOL), and critical adverse reaction was not seen for 12 months. We measured the TXL concentration in blood plasma and ascites after TXL infusion by HPLC method. The TXL titer in plasma was 427 ng/ml after infusion, 23 ng/ml after 24 hours and under 10 ng/ml after 48 hours. The TXL titer in ascites was 41 ng/ml after infusion, 37 ng/ml after 6 hours, 18 ng/ml after 12 hours, 10 ng/ml after 24 hours and under 10 ng/ml after 48 hours. TXL transportation from blood to ascites was good. This result suggested that intravenous infusion of TXL was effective for cancerous peritonitis treatment.

[A case of ovarian cancer with Parkinson's disease treated by combined chemotherapy with paclitaxel and carboplatin followed by surgery].

It is well known that neuropathy, myelopathy, and arthropathy are specific adverse effects induced by paclitaxel administration. Parkinson's disease is neural degenerative disease, and the influence of paclitaxel administration on patients with Parkinson's disease is unknown. We have successfully treated an ovarian cancer patient with Parkinson's disease by paclitaxel/CBDCA combined chemotherapy after surgery. The patient was a 57-year-old woman with solid and cystic ovarian tumor. Among the tumor markers CA125, CA19-9, and SLX, only SLX was elevated. We operated and made a pathological diagnosis of the ovarian tumor as clear cell adenocarcinoma (FIGO stage Ic). After surgery, the patient was treated with paclitaxel (260 mg [175 mg/m2]) and CBDCA (600 mg [AUC = 5]) combined chemotherapy for 5 courses. Her status is complete remission. During chemotherapy, she had felt the decreased efficacy of her Parkinson's disease medication. We could continue chemotherapy by increasing the dose of the Parkinson's drug. There is only one case report on the influence of paclitaxel on Parkinson's disease, in which the course was similar to the present case.