Successful delivery after transabdominal cerclage of uterine cervix for cervical incompetence after radical trachelectomy.

Pregnancy after radical trachelectomy (RT) has a high risk of prematurity and complications such as preterm premature rupture of the membrane and chorioamnionitis. Placing a cervical cerclage at the time of RT plays an important role in preventing such obstetrical complications. In patients who have trouble with the cervical cerclage, miscarriage during the second trimester seems to be inevitable. We have therefore started preconception transabdominal cerclage (TAC) for these patients. A 36-year-old Japanese woman who had a history of miscarriage due to trouble with the nylon thread used for cerclage, successfully delivered after TAC. TAC is a useful treatment modality to prevent miscarriage for patients who have trouble with cerclage after RT.

Importance of uterine cervical cerclage to maintain a successful pregnancy for patients who undergo vaginal radical trachelectomy.

BACKGROUND: We have performed 36 vaginal radical trachelectomies (RTs) for patients with early invasive uterine cervical cancer and experienced 10 deliveries. Pregnancy after RT has far higher risks of prematurity and complications such as preterm premature rupture of the membrane (pPROM) and chorioamnionitis. We report the significance of transabdominal cerclage in the follow-up of pregnancy after vaginal RT. METHODS: Our operative procedure is based on that of Dargent et al. We amputated the cervix approximately 10 mm below the isthmus. For the removal of the parametrium, we cut at the level of type II hysterectomy. A nylon suture is also placed around the residual cervix. Pregnancy courses after vaginal RT were studied in 9 patients (10 pregnancies) with respect to cervical length and several infectious signs. RESULTS: Obstetric prognosis after RT was improved with our follow-up modality. Four patients who were followed up with this modality were able to continue their pregnancies until late in the third trimester. However, it was not effective for four patients who showed cervical incompetence due to slack cerclage. They suffered from pPROM without any infectious signs and uterine contraction. Though we performed transabdominal uterine cervical cerclage for one patient in her 19th week of pregnancy, it was unsuccessful. CONCLUSIONS: Cervical cerclage placed at the time of RT played an important role in preventing dilatation of the uterine cervix and the subsequent occurrence of pPROM. Transabdominal cervical cerclage should be performed earlier in pregnancy or before pregnancy in patients who have experienced problems with cervical cerclage.

Low-dose SN-38 with paclitaxel induces lethality in human uterine cervical adenocarcinoma cells by increasing caspase activity.

Combination of anticancer drugs may provide a rational molecular basis for novel chemotherapeutic strategies. Paclitaxel and SN-38 (an active metabolite of CPT-11) are effective for many kinds of cancer. Therefore, we investigated the possibility that combination of these drugs could be effective against cervical adenocarcinoma cells. In this study, we examined cell growth inhibition after 96 h using the MTT assay and examined the release of fragmented DNA into the cytoplasm during apoptotic cell death by PI staining. Single and combined use of paclitaxel and SN-38 produced significant cytolethality against the cervical adenocarcinoma cell line CAC-1. Addition of a low concentration of SN-38 reduced the IC50 value of paclitaxel compared to that without SN-38, although the low concentration of paclitaxel did not enhance the cytotoxicity of SN-38. FACS scan analysis suggested that these drugs induced apoptosis and cell cycle arrest, and that caspase-3 and -7 were activated in the process. MTT assay and the IC50 demonstrated that paclitaxel had strong cytotoxicity against CAC-1 as well as other cancer cells. In this study, though only a single cell line was used for the experiment and the data are limited, our results suggest that paclitaxel together with low-dose CPT-11 is a promising basis for a new combination cancer chemotherapy.

Difficulty in the management of pregnancy after vaginal radical trachelectomy.

BACKGROUND: We have performed 26 vaginal radical trachelectomies (RTs) for patients with early invasive uterine cervical cancer since 2003 and, to date, have experienced 8 deliveries. The procedure has a high risk for preterm labor and the subsequent occurrence of preterm premature rupture of membranes (pPROM). We report the present situation and the limits of follow-up of pregnancy after vaginal RT. METHODS: Our operative procedure is based on that of Dargent et al. We usually amputate the cervix approximately 10 mm below the isthmus. To remove the parametrium, we cut at the level of type II hysterectomy. Pregnancy courses after vaginal RT were studied in 8 patients with respect to symptoms, cervical length, and several infectious signs. RESULTS: We recommended that patients enter hospital early in their second trimester, and prophylactic daily vaginal disinfection with povidone-iodine and an ulinastatin vaginal suppository were administered. Careful checking for vaginal infectious signs, as well as cervical length and abdominal tension of patients was also performed. Four patients followed up with this modality were able to continue their pregnancies until late in the third trimester. However, this follow-up modality was not effective for patients who showed cervical incompetence due to slack cervical cerclage. They suffered from pPROM at 26 and 19 weeks of gestation. CONCLUSION: We need a new approach for the management of pregnant patients after vaginal RT with cervical incompetence due to slack cervical cerclage to prevent cervical infection.

Hypermethylation in promoter region of retinoic acid receptor-beta gene and immunohistochemical findings on retinoic acid receptors in carcinogenesis of endometrium.

In the present study, we analyzed the immunohistochemical findings for the RA receptor (RAR), retinoic X receptor (RXR) and hypermethylation of promoter-region CpG island methylation of RAR-beta2. Immunohistochemistry indicated that though RXR-alpha and -gamma were present in endometrial hyperplasia and cancer, other retinoid receptors were only weakly detected. The hypermethylation of RAR-beta2 was found in 75.0% of endometrial hyperplasia samples and 92.2% of carcinomas. No normal endometria had methylation. This evidence may point to one of the reasons why endometrial hyperplasia acquires high proliferative capacity without differentiation, and the hypermethylation of RAR-beta2 may occur in the early stage of endometrial carcinogenesis.

Preservation of fertility and subsequent childbirth after methotrexate treatment of placenta percreta: a case report.

INTRODUCTION: Placenta percreta is associated with maternal morbidity and mortality. A hysterectomy is often needed to control the bleeding in such cases. However, it has been advocated that placenta percreta be managed conservatively to avoid massive pelvic bleeding and to preserve the patient's fertility. Here, we present a case of placenta percreta diagnosed by magnetic resonance imaging, and treated with systemic administration of methotrexate. CASE PRESENTATION: A 27-year-old nulliparous Japanese woman at 39 gestational weeks had an uncomplicated vaginal delivery of a 3244-g infant. However, her placenta was not delivered, and we could not remove it manually. Contrast-enhanced magnetic resonance imaging indicated deep myometrial invasion by placental tissue and the whole placenta was strongly enhanced. Seven days post-partum, her serum human chorionic gonadotropin level was 12,656IU/L. Our patient hoped to preserve her uterus for a future pregnancy. She therefore received 13 courses of methotrexate (50mg/week, intravenous injection). Her serum human chorionic gonadotropin level was undetectable 97 days after the first methotrexate injection. At 117 days post-partum, she had a labor-like pain every three minutes and delivered the placenta. Our patient regained normal menses and at follow-up remained in good health. Two years later, she delivered a healthy daughter. CONCLUSION: We should try to detect placenta percreta in high-risk patients by any means. For low-risk patients, we should give a diagnosis swiftly and control any intrauterine infection and massive bleeding.

The tight-junction protein claudin-6 induces epithelial differentiation from mouse F9 and embryonic stem cells.

During epithelialization, cell adhesions and polarity must be established to maintain tissue assemblies and separate the biological compartments in the body. However, the molecular basis of epithelial morphogenesis, in particular, a role of cell adhesion molecules in epithelial differentiation from stem cells, remains unclear. Here, we show that the stable and conditional expression of a tight-junction protein, claudin-6 (Cldn6), triggers epithelial morphogenesis in mouse F9 stem cells. We also demonstrate that Cldn6 induces the expression of other tight-junction and microvillus molecules including Cldn7, occludin, ZO-1α+, and ezrin/radixin/moesin-binding phosphoprotein50. These events were inhibited by attenuation of Cldn6 using RNA interference or the C-terminal half of Clostridium Perfringens enterotoxin. Furthermore, similar results were obtained in mouse embryonic stem cells. Thus, we have uncovered that the Cldn6 functions as a novel cue to induce epithelial differentiation.

A case of congenital toxoplasmosis whose mother demonstrated serum low IgG avidity and positive tests for multiplex-nested PCR in the amniotic fluid.

We encountered a woman whose infant developed congenital toxoplasmosis. Serum Toxoplasma gondii antibody titers (320x) at 12 weeks of gestation increased to 5120x at 25 weeks. Toxoplasma immunoglobulin M was 2.8 index, and immunoglobulin G avidity index was 23%. Cyclic administration of acetylspiramycin was maintained from 22 weeks until delivery. Multiplex-nested polymerase chain reaction of maternal blood and amniotic fluid at 28 weeks both tested positive for Toxoplasma DNA. A male neonate weighing 2916 g was born at 38 weeks via cesarean section. No abnormalities were detected by physical and funduscopic examinations, whereas a head computed tomography of the neonate revealed three independent intracranial calcifications. The infant underwent therapy with pyrimethamine and sulfadiazine for one year. Serum titers of Toxoplasma gondii antibodies were all less than cut-off values between 5 and 12 months after birth, but all increased up to positive levels 18 months after birth.

Expression patterns of claudin family of tight-junction proteins in the mouse prostate.

Claudins are the transmembrane proteins forming the backbone of tight junctions, and consist of over 20 members of a gene family. Claudins are expressed in a tissue- and cell-type specific fashion, and changes in their abundance and/or distribution are proposed to play important roles in the pathophysiology of numerous disorders. In the prostate, claudin-1, -3, -4 and -7 transcripts are known to be expressed, but it is unknown regarding mRNA expression of other claudins or concerning expression and localization of claudin proteins in this organ. We herein show, by RT-PCR and Western blotting analyses, that not only these four claudins but also claudin-5, -8 and -10 are expressed in the normal mouse prostate. Claudin-3, -4, -5, -8 and -10 were primarily localized at the apicalmost sites of lateral membranes of luminal epithelial cells in the prostate gland, whereas claudin-1 and -7 were distributed along the basolateral membranes of the epithelium. These findings provide basic information for elucidating the significance of claudins in prostate diseases, including prostate cancers.