Preventive Effect of Hydrocolloid Dressings on Hypertrophic Scarring of Post-Cesarean Section Wounds: A Randomized Pilot Study.

OBJECTIVE: To determine the prophylactic effect of hydrocolloid dressings on hypertrophic scarring in post-cesarean section wounds. METHODS: Patients who underwent cesarean section (C/S) at the authors' hospital and provided informed consent to participate were randomly assigned to the intervention and control groups. The intervention group commenced applying hydrocolloid dressings to the wound on postoperative day 7 or 8 and continued with weekly dressing changes for 6 months. The control group refrained from any dressing application but was followed up. In each group, the condition of the wound was evaluated 6 and 12 months postoperatively using the Japan Scar Workshop Scar Scale 2015, the Patient and Observer Scar Assessment Scale version 2.0, the modified Vancouver Scar Scale, and patient-reported outcomes. RESULTS: During this period, 135 patients underwent C/S at the authors' institution, and 47 (23 in the intervention group and 24 in the control group) were included in the analysis. In all assessment methods, the intervention group scored lower than the control group at 6 and 12 months after C/S. Twelve months after C/S, hypertrophic scarring (Japan Scar Workshop Scar Scale 2015 score of 6-15) was found in 14 of the 47 (29.8%) patients: 11 of 24 (45.8%) in the control group and 3 of 23 (13.0%) in the intervention group. The intervention's relative risk was 0.623 (95% CI, 0.417-0.930). The risk factor for hypertrophic scarring was midline vertical incision, with an odds ratio of 20.53 (95% CI, 4.18-100.92). CONCLUSIONS: The study reveals that the application of hydrocolloid dressings to wounds reduces the risk of hypertrophic scarring after C/S.

Multidisciplinary perioperative management in dilatation and evacuation for a giant hydatidiform mole: A case report.

Gestational trophoblastic disease (GTD) is an abnormal pregnancy caused by the placenta, which can potentially metastasise. Suction evacuation is recommended for diagnosis and treatment, and dilatation and evacuation (D&E) is usually performed under intravenous anaesthesia due to the short operation time and minimal blood loss. We refer to the guidelines produced by the Japan Society of Obstetrics and Gynaecology (JSOG), and acknowledge that practices vary globally. However, to the best of our knowledge, there is no evidence on perioperative management and arrangements in D&E required for managing giant hydatidiform moles, such as preventing massive haemorrhage, respiratory dysfunction with a pathogenesis like ovarian hyperstimulation syndrome (OHSS), or intensive care needs. This case report describes perioperative considerations for managing a giant hydatidiform mole using D&E in a uterus enlarged to the third-trimester pregnancy size. A 28-year-old multiparous woman was clinically diagnosed with a hydatidiform mole after a spontaneous miscarriage due to abnormal genital bleeding, systemic oedema, and abdominal distention. Ultrasound and computed tomography showed a ballooning uterus with a third-trimester pregnancy size, a robust intrauterine mass, and ascites. Serum hCG levels were extremely high (>3,000,000 mIU/mL), confirming the clinical diagnosis of a hydatidiform mole. Emergency D&E was safely performed under multidisciplinary perioperative management, with careful preparation and support. This is a rare experience-based case report and valuable documentation detailing multidisciplinary perioperative management under general anaesthesia. To the best of our knowledge, this is the first report describing the considerations, details, and innovations required in the perioperative management of giant hydatidiform moles using D&E.

Incidental detection of retained oil-based hysterosalpingography contrast medium on postoperative postpartum radiography: A case report.

Hysterosalpingography is widely performed in assisted reproductive technology. We present a rare case of contrast medium retention which was incidentally found and mimicked a retained surgical instrument. A medical history of treatment for infertility can facilitate the differential diagnosis of abnormal findings on post-caesarean section radiography.

Eczema herpeticum subsequent to septic shock in early pregnancy: a first case report.

BACKGROUND: Eczema herpeticum (EH) is a severe skin complication caused by human simplex virus (HSV) infection concomitant with immune dysfunction and dermatological conditions, mainly atopic dermatitis. We present the first case of EH subsequent to sepsis-related immunological suppression in pregnancy. CASE PRESENTATION: Septic shock developed in a 30-year-old primiparous woman at 14 weeks of pregnancy during admission for hyperemesis gravidarum. Although her life-threatening status due to sepsis improved by prompt treatment, on day 3 of treatment in the intensive care unit, blisters suddenly erupted on her face and neck and spread over her body. EH was diagnosed according to HSV type-1 antigen positivity and a past medical history of EH and atopic dermatitis. Antiviral agents were administered immediately, with positive results. Her general condition improved quickly, without central nervous system defects. This is the first report of EH following septic shock in early pregnancy. At present, we speculate that EH develops as a complication due to immunological changes in the late phase of sepsis because sepsis is mainly characterized by both an inflammatory state in the acute phase and an immunosuppressive state in the late phase. Pregnancy can also contribute to its pathogenesis, as it causes an immunosuppressive state. Mortality due to EH is relatively high; in this case, a history of EH and atopic dermatitis contributed to the initiation of prompt medical interventions for the former, with improvement in the patient's severe condition. The combination of immunological changes in sepsis and pregnancy can cause HSV reactivation, resulting in EH recurrence. CONCLUSIONS: In conclusion, if dermatological symptoms develop in a pregnant woman with a history of EH and/or atopic dermatitis treated for sepsis, EH should be suspected based not only on clinical features but also on immunological changes along with sepsis, and prompt medical interventions should be initiated.

Effectiveness of an Educational Video in Maternity Wards to Prevent Self-Reported Shaking and Smothering during the First Week of Age: A Cluster Randomized Controlled Trial.

This study aimed to investigate whether watching an educational video on infant crying and the dangers of shaking and smothering within 1 week after delivery at maternity wards reduces self-reported shaking and smothering, at a 1-month health checkup. A cluster randomized controlled trial, stratified by area and hospital function, was employed in 45 obstetrics hospitals/clinics in Osaka Prefecture, Japan. In the intervention group, mothers watched an educational video on infant crying and the dangers of shaking and smothering an infant, within 1 week of age, during hospitalization at maternity wards, without blinding on group allocation. Control group received usual care. A total of 4722 (N = 2350 and 2372 for intervention and control group, respectively) mothers who delivered their babies (still birth and gestational age < 22 weeks were excluded) between October 1, 2014, and January 31 were recruited. Outcomes were self-reported shaking and smothering behaviors, knowledge on infant crying and shaking, and behaviors to cope with infant crying, assessed via a questionnaire at a 1-month health checkup. In all, 2718 (N = 1078 and 1640) responded to the questionnaire (response rate: 58.3%), and analytic sample size was 2655 (N = 1058 and 1597 for intervention and control group, respectively). Multilevel analysis was used to adjust for correlation within the cluster. Prevalence of shaking was significantly lower in the intervention group (0.19%) than in the control group (1.69%). Intention-to-treat analysis showed an 89% reduction in the reported prevalence of self-reported shaking (OR: 0.11, 95% CI: 0.02-0.53) due to watching the educational video. However, self-reported smothering behavior showed no significant reduction (OR: 0.66, 95% CI: 0.27-1.60). No side effects were reported. Watching an educational video on infant crying and the dangers of shaking and smothering within 1 week after delivery at maternity wards reduced self-reported shaking at 1 month of age. UMIN Clinical Trial Registry UMIN000015558.

Horizontal Cervix as a Novel Sign for Predicting Adhesions on the Posterior Extrauterine Wall in Cases of Placenta Previa.

: We aimed to identify a magnetic resonance imaging (MRI) feature that can predict posterior extrauterine adhesion (posterior adhesion) antenatally, in patients with placenta previa. We retrospectively reviewed patients with placenta previa who underwent a preoperative MRI examination of placenta accreta spectrum. We categorized the patients into two groups based on whether the cervix was anterior or posterior to a line perpendicular to the anatomical conjugate on the MRI. We projected the perpendicular line toward a straight line through the broad of the back on T2-weighted sagittal MRI images and measured the angle between this line and the line passing through the cervical canal. We analyzed the correlation of the cervical canal angle with the presence of posterior adhesions. Of the 96 patients analyzed, 71 patients had an anteverted cervix and 25 patients had a retroverted cervix. There were 21 posterior adhesions. The adhesion rate was significantly higher in patients with a retroverted cervix than those with an anteverted cervix (8.5% vs. 60%; p = 0.00). The cervical canal angle was ≤10° in 25 patients; of these 17 had adhesions (sensitivity, 81.0%; specificity, 89.3%; area under the curve, 0.887; 95% confidence interval, 0.792-0.981). This finding, labeled "positive horizontal cervix sign," may be a promising indicator of posterior adhesions in patients with placenta previa.

Serum fibrinogen levels could be an index of successful use of balloon tamponade in postpartum hemorrhage.

OBJECTIVE: The object of our study was to determine whether serum fibrinogen levels could be used to predict the success rates of balloon tamponade and decrease the use of invasive methods. METHODS: This retrospective study, conducted at Rinku General Medical Center, was aimed to identify factors associated with high success rates in balloon tamponade. Forty-six patients with postpartum hemorrhage (PPH), non-responsive to uterotonics and treated with balloon tamponade between April 2008 and March 2015, were included. RESULTS: Forty-six women were included, of which 34 underwent vaginal delivery and 12 underwent cesarean delivery. There were no complications from balloon tamponade and its success rate was 73.3%. Seven women required additional procedures: One used gauze packing, three used uterine artery embolization, and five underwent peripartum hysterectomy. The cut-off line of serum fibrinogen level was 172.5 mg/dL (P=0.002) with its 77.4% sensitivity and 66.7% specificity. CONCLUSION: We recommend measuring serum fibrinogen level for predicting whether the balloon tamponade can be used successfully or not.

Perimortem cesarean delivery and subsequent emergency hysterectomy: new strategy for maternal cardiac arrest.

Cases: Perimortem cesarean delivery (PMCD) is the only way to resuscitate pregnant women in cardiac arrest, and has been found to increase maternal resuscitation rate by increasing circulating plasma volume. However, many obstetricians have not experienced a case of PMCD, as situations requiring it are rare. We report our strategy for cases of maternal cardiac arrest, on the basis of a review of published work, and present two case reports from our medical center. Outcomes: In case 1, PMCD led to death by massive bleeding. In case 2, PMCD and hysterectomy were carried out after the introduction of venoarterial extracorporeal membrane oxygenation, and both mother and baby survived. Conclusion: We find that rapid hysterectomy as a damage control surgery following PMCD can be life-saving for both mother and baby.

Long-term survival in small-cell carcinoma of the endometrium with liver and brain metastases.

Small-cell carcinoma (SmCC) of the endometrium is an extremely rare cancer and has a poor prognosis. Because long-term survival is rare, there is a paucity of data on the advanced disease stages. Thus, a standard treatment has not been established. We describe an extremely rare case of long-term survival in SmCC of the endometrium with liver and brain metastases. We provided multidisciplinary treatment, including brain surgery, subsequent whole-brain radiotherapy, gynecologic surgery, and adjuvant chemotherapy (irinotecan hydrochloride+cisplatin). The patient was treated successfully and has survived for more than 12 years with no evidence of the disease. Irinotecan hydrochloride+cisplatin chemotherapy was effective for controlling the liver metastases, and the resection of brain metastases and radiotherapy were effective for the treatment of brain metastases in our case. We reviewed the pertinent literature of advanced SmCC of the endometrium.

Clinical Significance of Atypical Squamous Cells of Undetermined Significance among Patients Undergoing Cervical Conization.

BACKGROUND: Atypical squamous cells of undetermined significance (ASCUS) feature a wide variety of cervical cells, including benign and malignant examples. The management of ASCUS is complicated. Guidelines for office gynecology in Japan recommend performing a high-risk human papillomavirus (HPV) test as a rule. The guidelines also recommend repeat cervical cytology after 6 and 12 months, or immediate colposcopy. The purpose of this study was to determine the clinical significance of ASCUS. MATERIALS AND METHODS: Between January 2012 and December 2014, a total of 162 patients underwent cervical conization for cervical intraepithelial neoplasia grade 3 (CIN3), carcinoma in situ, squamous cell carcinoma, microinvasive squamous cell carcinoma, and adenocarcinoma in situ at our hospital. The results of cervical cytology prior to conization, the pathology after conization, and high-risk HPV testing were obtained from clinical records and analyzed retrospectively. RESULTS: Based on cervical cytology, 31 (19.1%) of 162 patients were primarily diagnosed with ASCUS. Among these, 25 (80.6%) were positive for high-risk HPV, and the test results of the remaining 6 patients (19.4%) were uncertain. In the final pathological diagnosis after conization, 27 (87.1%) and 4 patients (12.9%) were diagnosed with CIN3 and carcinoma in situ, respectively. CONCLUSIONS: Although ASCUS is known as a low-risk abnormal cervical cytology, approximately 20% of patients who underwent cervical conization had ASCUS. The relationship between the cervical cytology of ASCUS and the final pathological results for CIN3 or invasive carcinoma should be investigated statistically. In cases of ASCUS, we recommend HPV tests or colposcopic examination rather than cytological follow-up, because of the risk of missing CIN3 or more advanced disease.

Molecular analysis of parturition via oxytocin receptor expression.

In daily obstetric practice, oxytocin is one of the most frequently used drugs to stimulate uterine contraction. However, uterine sensitivity to oxytocin is profoundly different among pregnant women, which may reflect oxytocin receptor (OTR) expression in the uterus. We review here the literature focusing on OTR regulation in the human uterus. Recent progress in molecular biology has augmented our knowledge about OTR regulation in the uterus at the transcription level, although the totality of preparation for labor through OTR expression is still obscure.

Balloon tamponade during cesarean section is useful for severe post-partum hemorrhage due to placenta previa.

AIM: Severe post-partum hemorrhage during cesarean section due to placenta previa is still one of the leading causes of maternal mortality. The aim of this study was to evaluate the efficiency of intrauterine tamponade with a Sengstaken-Blakemore tube (SB-tube) for the treatment of severe post-partum hemorrhage in cases of placenta previa. MATERIAL AND METHODS: Data were collected from our departmental clinical records on all patients who underwent caesarian section due to placenta previa between 2007 and 2009. RESULTS: During the period analyzed, 37 patients underwent caesarian section due to placenta previa/low-lying placenta. Four (11%) underwent hysterectomy due to placenta accreta and 33 (89%) were treated conservatively. Of the 33 patients with conserved uterus, 10 (28%) patients required a SB-tube during the cesarean section because of continuous post-partum hemorrhage despite appropriate medical treatment. The median bleeding during the operation was 2030±860mL in the patients who used SB-tube. None of them presented severe complications related to these procedures or required any further invasive surgery. CONCLUSION: Intrauterine balloon-tamponade could successfully control severe hemorrhage from a lower uterine segment of a patient with placenta previa. This technique is simple to use, scarcely invasive, and available at a low cost to all maternity wards, and should be considered as one of the first management options to reduce the risk of undesirable hysterectomy.

Chemotherapy for endometrial carcinoma (GOGO-EM1 study): TEC (paclitaxel, epirubicin, and carboplatin) is an effective remission-induction and adjuvant therapy.

BACKGROUND: TAP chemotherapy (paclitaxel, doxorubicin, and cisplatin) is effective for advanced and recurrent endometrial carcinoma, but has occasional severe toxicity. TEC chemotherapy (paclitaxel, epirubicin, and carboplatin) has been suggested to have less toxicity; however, the optimal dosage has yet to be determined. PATIENTS AND METHODS: Phase I/II prospective study for TEC therapy was performed. A retrospective comparison of the prognosis between adjuvant TEC therapy and radiation for completely resected cases with risk factors was also performed. RESULTS: The recommended dose of TEC therapy was determined to be paclitaxel 150 mg/m(2), epirubicin 50 mg/m(2), and carboplatin AUC 4. A TEC regimen at this dose level was shown to be tolerable. The response rate and median overall survival were 74% and 37 months for those with advanced primary disease (Group B) and 50% and 26 months for recurrent tumors (Group C), respectively. A retrospective comparison showed that adjuvant TEC therapy for completely resected stage III cases improved their prognosis when compared to an adjuvant radiation therapy. CONCLUSION: TEC therapy was demonstrated to be a tolerable and effective treatment, not only as a remission-induction therapy for advanced and recurrent endometrial carcinomas but also as the adjuvant therapy.

Calcineurin/NFAT pathway: a novel regulator of parturition.

PROBLEM: The oxytocin (OT)-oxytocin receptor (OTR) system plays an important role in mammalian parturition. However, we found OTR-deficient (OTRKO) mice are fertile and deliver at term without birth defects, thus alternative pathways inducing parturition can be hypothesized. METHODS OF STUDY: We tested the gene expression profile of OTRKO mice using suppressive subtractive hybridization, and focused on the calcineurin/nuclear factor of activated T cells (NFAT) pathway. We examined the expression and localization of this pathway in mouse parturition. RESULTS: Calcineurin and NFATc1 were detected in the decidua of pregnant uteri at term using immunohistochemistry (IHC). We identified higher activation levels of NFATc1 in wild type (WT) than in OTRKO mice and increased calcineurin A and NFATc1 mRNA levels during pregnancy. Moreover, injection of FK506, the inhibitor of this pathway, prolonged the delivery of the first pup. CONCLUSION: Our findings suggested that the calcineurin/NFAT pathway might play a substantial role in initiation of labor.

Immunisation with a plasmid DNA vaccine encoding gonadotrophin releasing hormone (GnRH-I) and T-helper epitopes in saline suppresses rodent fertility.

Research into active immunisation against gonadotrophin releasing hormone (GnRH-I) has gained widespread acceptance as a means of controlling reproduction and behaviour of farm, companion and wild animals. Many studies describe the use of multiple copies of the self-peptide in linear alignment and conjugation with a large carrier protein to increase the immune response to the peptide. However, problems resulting from carrier protein epitope suppression have seen a diversion of interest into the use of genetic materials to elicit an optimum immune response. In this study, a 533-bp long DNA vaccine was constructed in pcDNAV5-HisB coding for 18.871 kDa GnRH-I-T-helper-V5 epitopes fusion protein. COS1 cells transfected with the vaccine construct were found to release fusion protein into culture supernatant. The vaccine construct (100 microg/mice) in saline solution administered into the anterior quadriceps muscle of ICR male and female mice stimulated antigen-specific IgG antibody responses. Testosterone levels in the vaccinated male mice were significantly (p = 0.021) reduced. A significant reduction in uterine implants were noted following mating between immunised males and control females (p = 0.028), as well as between immunised females and control males (p = 0.004). Histological examination of both the male and female gonads in study week 13 showed atrophy of the seminiferous epithelium and suppression of folliculogenesis.

Immunisation of male mice with a plasmid DNA vaccine encoding gonadotrophin releasing hormone (GnRH-I) and T-helper epitopes suppresses fertility in vivo.

Immunisation against mammalian gonadotrophin releasing hormone (GnRH-I) linked to large carrier proteins has been shown to disrupt fertility. However, various studies have shown that the carrier protein causes epitope suppression of the hapten response, resulting in short-lived immunoneutralisation, followed by a return of fertility. A range of strategies has been used to resolve this, with limited success. The aim of this study was to construct a plasmid DNA vaccine encoding GnRH-I and T-helper epitopes. A 498 bp long vaccine construct in pcDNA3.1+ was administered to male mice in conjunction with a Hemagglutinating Virus of Japanese Envelop (HVJ-E) vector or in saline solution. The vaccine efficacy was evaluated in terms of GnRH-I specific IgG antibody response, serum testosterone levels, testicular spermatogenesis and the ability to produce offspring. The vaccine appeared to induce higher anti-GnRH-I IgG antibody response and insult the fertility axis, which was characterised by a drop of epididymal sperm counts, reduction of serum testosterone levels, suppressed testicular spermatogenesis and a significant decrease in litter numbers compared to control animals. The end-point vaccine efficacy was much higher in the HVJ-E vector mediated immunisation, than in saline alone.

Rapid detection of trisomy 21 by gene dosage analysis using quantitative real-time polymerase chain reaction.

AIM: Rapid detection of fetal aneuploidy helps inform a mother's choice about the course of her pregnancy. Obtaining results by fluorescent in situ hybridization (FISH) requires more than 24 h, and thus a more rapid method is needed. METHODS: Conventional G-banding and FISH for chromosome 21 were performed for cultured amniocytes. Genomic DNA was extracted from uncultured amniocytes obtained from 23 patients. TaqMan polymerase chain reaction (PCR) primers were designed to amplify the potassium voltage gated channel gene on chromosome 21q22.12 and the ribosomal phosphoprotein gene on 18q21.1. Quantitative real-time PCR was performed for these two gene fragments and the differences of the threshold cycle (Ct) of the two genes (Ct 18-Ct 21) were calculated for each sample. RESULTS: G-banding revealed that 19 patients had a normal karyotype and four had trisomy 21. FISH resulted in one case of a false positive. The Delta Ct values (Ct 18-Ct 21) of trisomy 21 patients were significantly higher than the values of individuals with normal karyotypes (P < 0.001) and there was no overlapping. CONCLUSIONS: Fetal trisomy 21 is rapidly detectable by gene dosage analysis from amniocytes using quantitative real-time PCR.

Mouse model of human infertility: transient and local inhibition of endometrial STAT-3 activation results in implantation failure.

Embryo implantation involves a series of biochemical reactions and its failure is an important therapeutic target of infertility treatment. We established an infertile mouse model using transient and local suppression of signal transducer and activator of transcription-3 (STAT-3) activity by STAT-3 decoy transfer into the uterine cavity during implantation, resulting in <30% implantation. This infertility is caused by suppression of decidualization, which is indispensable for implantation, and independent of progesterone. These conditions may mimic clinically unexplained infertility. Our results suggest that STAT-3 could be a useful target for diagnosis and therapy of human implantation failure.

Simple and highly efficient method for transient in vivo gene transfer to mid-late pregnant mouse uterus.

Up- and down-regulation of various genes in the placenta, decidua and amnion has been reported during the mid-late period of pregnancy and in pregnancy-related complications, such as preeclampsia and preterm labor. However, whether this gene regulation at the feto-maternal interface directly influences the physiology/pathophysiology of disease remains unknown. In order to study this problem, transient gene transfer into the pregnant uterus at mid-late term would be a useful tool. We injected exogenous plasmid entrapped using a commercially available Hemagglutinating Virus of Japan Envelope (HVJ-E) vector system (GenomONE Neo, Ishihara Sangyo) into the extra-amniotic space of the upper part of the pregnant mouse uterus on day 14.5 post-coitus (p.c.). Luciferase activity driven by the cytomegalovirus promoter was detectable for 3 days after transfection in the upper, middle and lower part of the uterus. beta-Galactsidase activity was localized in the basal lamina of the placenta, the decidual membrane and the fetal membrane. Exogenous plasmid was not transmitted to the fetus. The course of pregnancy was not disturbed by this procedure; rupture of membranes, intrauterine fetal growth restriction and preterm birth were not observed. Thus, we demonstrated that this transient gene transfer method is highly efficient and minimally invasive, and expect that this procedure will be a useful tool to analyze the pathophysiology of pregnancy-related disorders.

In vivo gene transfer into the mouse uterus: a powerful tool for investigating implantation physiology.

In vivo transient transfection of cDNA into uterine endometrium during the implantation period provides great opportunities to analyse the physiology/pathophysiology of implantation at the molecular level. We review here methodologies which have been applied for this purpose. Viral vectors are widely used for in vivo gene therapy models; however, there is no successful example of gene transfer into the uterus using such vectors. Cationic liposome-based technologies have produced some successful results, causing alterations in implantation physiology. We applied a haemagglutinating virus of Japan envelope (HVJ-E) vector system and showed that the transfection efficiency was much higher than that of methods based on cationic liposome. Commercial HVJ-E vector (GenomONE-Neo) is now also available. Several successful examples of in vivo gene transfer revealed that calcitonin, Hoxa 10 and NF kappaB play important roles in determining the efficiency or timing of implantation. Based on this knowledge, we should further analyse the pathophysiology of human implantation failure using human materials.