Isolated Agnathia-Otocephaly Complex Diagnosed Prenatally for Ex-Utero Intrapartum Treatment: A Case Report.

BACKGROUND Agnathia-otocephaly complex (AOC) is a rare congenital malformation due to a first-branch arch disorder and has been considered lethal. However, milder variants of the isolated type of AOC have been reported as nonlethal. The ex-utero intrapartum treatment (EXIT) procedure is basically indicated for a fetus with a high risk of airway obstruction immediately after birth; it is not indicated for all AOC cases but is chosen to treat cases until the airway can be evaluated to achieve a better prognosis. CASE REPORT A 37-year-old woman was referred with reported fetal facial deformity and polyhydramnios at 27 weeks of gestation. Our fetal ultrasound scans showed agnathia, microstomia, and synotia, but not holoprosencephaly. Isolated AOC was diagnosed prenatally. Magnetic resonance imaging and microbubble tests revealed delayed fetal lung maturation, although it was not completely unmatured. With patient agreement, an emergency cesarean section with EXIT was performed because of clinical chorioamnionitis at 35 weeks of gestation. Tracheostomy was attempted for 16 min during EXIT and was completed 4 min after delivery. Despite this, the neonate died 12 h after delivery from severe respiratory failure and a tension pneumothorax caused by a hypoplastic lung. CONCLUSIONS There is controversy surrounding the non-lethality of all isolated AOC cases and the non-contraindication of EXIT procedures. Our case was estimated as the milder variant, and the EXIT procedure was indicated; however, the neonate died of the hypoplastic lung. The evaluation methods of lung maturation are inconsistent, and the indication of the invasive EXIT procedure must be carefully considered.

Does a cervical pessary reduce the rate of preterm birth in women with a short cervix?

OBJECTIVES: To evaluate neonatal outcomes after the use of a cervical pessary in Japanese women with short cervical length (CL) less than 25 mm. METHODS: This multicenter study involved women with singleton pregnancies between 20 and 29+6 gestational weeks and a CL of less than 25 mm. The primary outcome was preterm birth (PTB) before 34 weeks of gestation. This study was registered in the Japan Registry of Clinical Trials (JRCT: jRCTs042180102). RESULTS: Two hundred pregnant women were enrolled; 114 in the pessary group and 86 in the expectant management group as controls. In the pessary group, all 114 neonates were investigated for perinatal outcomes, and 112 pregnant women were investigated for primary, and secondary outcomes. In the control group, 86 pregnant women were investigated for primary and secondary outcomes and 86 neonates were investigated for neonatal outcomes. There were no significant differences in PTB in ≤34, ≤37, and ≤28 weeks of gestation or in preterm rupture of membranes (PROM) ≤34 weeks between the groups. The gestational weeks at birth and birth weight were significantly higher in the pessary group. Regression analysis demonstrated that the CL decreased without a pessary, whereas the shortening rate was suppressed during the intervention. No significant differences were observed in adverse neonatal outcomes, chorioamnionitis, or preterm PROM. CONCLUSIONS: The cervical pessary effectively reduced CL shortening during pregnancy resulting in an average increased gestational age, however, did not reduced the rates of preterm birth.

A case report of idiopathic pleuroparenchymal fibroelastosis with severe respiratory failure in pregnancy.

BACKGROUND: Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a rare lung disease that manifests as parenchymal fibrosis of the upper lung lobe and pleura. There have been no reports of IPPFE complicating pregnancy. Here, we report a case of IPPFE that deteriorated rapidly during pregnancy. CASE PRESENTATION: A 29-year-old woman presented with dyspnea and dry cough at 19 weeks of gestation. IPPFE with acute exacerbation was suspected on chest computed tomography (CT). Despite steroid treatment, her condition progressed. A cesarean section was performed at 28 weeks of gestation. On postoperative day 26, she underwent living-donor lung transplantation. She was discharged a year after transplantation. CONCLUSION: Our experience suggested that when pregnancy is complicated by PPFE, the disease may deteriorate rapidly. In this case, even though IPPFE with acute exacerbation was diagnosed during pregnancy, live birth was achieved, and the mother survived after lung transplantation. Lung transplantation should be considered in these patients because, once advanced, pulmonary lesions may be irreversible.

Modified laparoscopic cervicoisthmic cerclage in early pregnancy for refractory cervical incompetence: A case report.

Modified laparoscopic cerclage was developed as an easy laparoscopic approach during pregnancy, with sutures placed lateral to the uterine vessels. To the best of our knowledge, its successful use in the first trimester has not been reported in Japan. Additionally, there are no published data on chronological assessment of feto-placental circulation using Doppler. Here, we present the case of a 31-year-old Japanese woman (gravida 2, para 1) with refractory cervical incompetence who had a history of preterm birth at 32 weeks of gestation and cervical conization. Modified laparoscopic cervicoisthmic cerclage was performed. Doppler findings showed normal feto-placental circulation before and after the procedure. Her pregnancy progressed uneventfully with no significant feto-placental circulation or obstetric complications, and the baby showed normal growth. Elective cesarean section was performed at 37 + 0 weeks' gestation. Modified laparoscopic cervicoisthmic cerclage is suggested as one of the treatment methods for pregnant women with refractory cervical incompetence.

Coronary perfusion pressure and compression quality in maternal cardiopulmonary resuscitation in supine and left-lateral tilt positions: A prospective, crossover study using mannequins and swine models.

OBJECTIVE: The risk of maternal and fetal mortality is high if cardiopulmonary arrest occurs during pregnancy. To assess the best position for maternal cardiopulmonary resuscitation (CPR), a prospective randomized crossover study was undertaken, involving basic life support mannequin-based simulation (BLS-MS) and a swine model of pulseless electrical activity (an unstable cardiac state) incorporating a fetal mannequin (PEA-FM). STUDY DESIGN: The BLS-MS (performed by certified rescuers) served to evaluate the quality of chest compressions in 30° left lateral tilt (LLT) and supine positions. Based on a 5-point scale, each rescuer subjectively graded their experience. The PEA-FM model was used to compare coronary perfusion pressure readings during CPR in supine, supine with left uterine displacement, 30° LLT, and 30° right lateral tilt positions. Compression rate and correctness of hand position, compression depth, and recoil were measures of compression quality (BLS-MS). RESULTS: Compared with LLT position, supine position enabled correct hand position (rate: 0.99 vs 0.88; p<0.05) and compression depth (rate: 0.76 vs 0.36; p<0.001) significantly more often. Moreover, BLS-MS rescuers found chest compressions significantly easier to perform with the mannequin in supine (vs LLT) position (difficulty score: 1.75 vs 3.95; p<0.001). In the PEA-FM study arm, supine position with left uterine displacement and right lateral tilt positions had the highest and lowest recorded coronary perfusion pressure readings, respectively. CONCLUSION: Supine position with left uterine displacement is optimal for maternal CPR.

Intrapartum transperineal ultrasound for evaluating uterine contraction intensity in the second stage of labor.

PURPOSE: To clarify whether intrapartum transperineal ultrasound (ITU) can be used to evaluate uterine contraction intensity, and whether the intensity is associated with the duration of the second stage. METHODS: A prospective observational study was performed involving 86 women with a normal singleton term fetus and more than three contractions every 10 min. ITU was performed for contractile and non-contractile periods of labor at the beginning of the second stage, and one representative "angle of progression (AoP)" image was selected for each period. The Mann-Whitney U test was used to compare ∆AoP, the difference between the two angles, depending on the duration of the second stage. Receiver operating characteristic curves were used to evaluate the probability of duration of the second stage ≤50 min in nulliparous women. RESULTS: Among nulliparous women, ΔAoP differed significantly according to the duration of the second stage (52.5° ± 5.0° for ≤50 min vs. 30.9° ± 2.1° for >50 min; P < 0.001). Receiver operating characteristic curve analysis showed that approximately 85% of nulliparous women with ΔAoP greater than 40° delivered within 50 min. CONCLUSION: These findings could be utilized in the evaluation of uterine contraction intensity, and ∆AoP measurement could be used to predict the duration of the second stage of labor in nulliparous women.

Evaluation of transvaginal peritoneal surgery in young female patients.

BACKGROUND: The transvaginal approach is being used for natural orifice transluminal endoscopic surgery (NOTES), and reports of the clinical use of transvaginal NOTES have increased rapidly. However, hasty use of a transvaginal route may cause unexpected complications. Infertility or dyspareunia after transvaginal NOTES in young women is one of the most important issues to be resolved. The purpose of this study was to assess long-term complications, including infertility and dyspareunia, after transvaginal peritoneal surgery. METHODS: An anonymous questionnaire was sent to 73 young patients who had undergone ovarian cystectomy using a transvaginal approach from 2003 to 2011. The questionnaire contained 15 questions; 6 dealt with fertility, and 8 dealt with discomfort after surgery. A 5-point scale was used to evaluate patients' overall satisfaction with surgery. RESULTS: Forty-four (60 %) questionnaires were returned. The patients' mean age was 33.0 years, and the mean postoperative follow-up period was 16.5 months. Of responders younger than age 40 years, 24 did not use contraception, and 9 (38 %) conceived. The pregnancy rate among women younger than age 30 years was 60 %. Two (5 %) women reported temporary dyspareunia 1 month after surgery, but none developed permanent dyspareunia. The average patient satisfaction score was 4.12. CONCLUSIONS: There was no evidence to suggest that transvaginal peritoneal surgery causes infertility or dyspareunia. The majority of patients gave a high evaluation to vaginal ovarian cystectomy, suggesting the usability of a transvaginal approach for intraperitoneal surgery in young premenopausal women.

An alternative system for transvaginal removal of dermoid cyst and a comparative study with laparoscopy.

The objective was to introduce a new system for transvaginal removal of ovarian cyst and to evaluate its feasibility. With a new transvaginal system, ultrasound-assisted culdotomy, and laparoscopy supported cystectomy if vaginal procedure failed. The authors conducted a retrospective review in which 35 cases using new vaginal ovarian cystectomy were compared with 40 cases of laparoscopic cystectomy for the treatment of dermoid cyst. All cystectomies were completed without conversion to laparotomy and complications. In a case from vaginal group, laparoscopy was required. No differences existed in operating time, hemoglobin decrease, and C-reactive protein value between groups. Laparoscopically supported vaginal ovarian cystectomy with ultrasound-guided culdotomy was equivalent to laparoscopic cystectomy as to invasiveness and preserved the option of a completely vaginal approach. When a presumed benign dermoid cyst is located in cul-de-sac, this operation may represent a preferable alternative to an exclusively laparoscopic or exclusively vaginal ovarian cystectomy.

WT1 peptide vaccine stabilized intractable ovarian cancer patient for one year: a case report.

UNLABELLED: We report on Wilms tumor (WT1) peptide immunotherapy in a patient with intractable ovarian cancer patient over an extended period. CASE REPORT: Immunotherapy using WT1 peptide has been undergoing clinical trials for gynecological cancer. We used WT1 peptide vaccination to treat a 53-year-old woman suffering from ovarian cancer with peritoneal dissemination. After 2 months, her pleural and cardiac effusion had disappeared, and the sum of the longest diameter of the target lesion (in the pelvic mass) was reduced. There was a weak positive correlation between CA125 and mononuclear phagocyte/lymphocyte ratio (Spearman's ϱ=0.275, p=0.015). Intradermally administered WT1 peptide vaccination in a case of intractable ovarian cancer stabilized the disease over the course of one year. However, the immunotherapeutic mechanism of WT1 peptide and immunological escape mechanism for carcinoma cells remain to be elucidated.

Frequency of myeloid dendritic cells can predict the efficacy of Wilms' tumor 1 peptide vaccination.

BACKGROUND: The object of this study was to investigate the clinical predictive capability of peripheral myeloid dendritic cells (DCs) in Wilms' tumor 1 (WT1) vaccine therapy for patients with gynaecological cancer. PATIENTS AND METHODS: Six patients with WT1/human leukocyte antigen (HLA)-A*2402-positive gynaecological cancer were included in this study. The patients received intradermal injections of a modified 9-mer WT1 peptide every week for 12 weeks. Peripheral blood samples were obtained at 0, 4, 8 and 12 weeks after the initial vaccination. Circulating DCs were detected by flow cytometry. RESULTS: The frequencies of CD14(+)CD16(+)CD33(+)CD85(+) myeloid DCs were significantly higher in the therapeutically effective group than in therapeutically inert group (p<0.05). CONCLUSION: These results suggested that myeloid DCs, which should be associated with inducing cytotoxic T-cells, provided additional prognostic information in the use of cancer peptide vaccine.

WT1 expression correlates with angiogenesis in endometrial cancer tissue.

BACKGROUND: No direct comparison has been made of the relationship between the expression of Wilms' tumor gene WT1 within tumor cells and angiogenesis in vivo. MATERIALS AND METHODS: A series of 70 endometrial cancer patients who had undergone a curative resection was studied by immunohistochemistry to determine the correlation between WT1 expression, angiogenesis (proliferation of endothelial cell adhesion molecule-1, PECAM-1/CD31) and angiogenic growth factor (vascular endothelial growth factor, VEGF). RESULTS: A strong association was found between WT1 expression score and mean vascular density (p<0.001, n=70, ϱ=0.568). Immunohistochemistry of serial sections revealed that WT1 and VEGF were co-expressed in the same area of endometrial cancer tissue. CONCLUSION: Tumor-produced WT1, which may regulate the expression of VEGF, is found to be associated with induction of angiogenesis in endometrial cancer.

Wilms' tumor 1 (WT1) peptide immunotherapy for gynecological malignancy.

BACKGROUND: The object of this study was to investigate the safety and clinical response of immunotherapy targeting the WT1 (Wilms' tumor 1) gene product in patients with gynecological cancer. PATIENTS AND METHODS: Twelve patients with WT1/human leukocyte antigen (HLA)-A*2402-positive gynecological cancer were included in a Phase II clinical trial of WT1 vaccine therapy. In all the patients, the tumors were resistant to standard therapy. The patients received intradermal injections of a HLA-A*2402-restricted, modified 9-mer WT1 peptide every week for 12 weeks. Tumor size, which was measured by computed tomography (CT), was determined every 4 weeks. The responses were analyzed according to Response Evaluation Criteria in Solid Tumors (RECIST). RESULTS: The protocol was well tolerated; only local erythema occurred at the WT1 vaccine injection site. The clinical responses were as follows: stable disease (SD) in 3 patients and progressive disease (PD) in 9 patients. No patients had a complete (CR) or partial response (PR). The disease control rate was 25.0%. CONCLUSION: Although a small, uncontrolled, nonrandomized trial, this study showed that WT1 vaccine therapy for patients with gynecological cancer was safe and produced a clinical response.

Correlation between WT1 expression and cell proliferation in endometrial cancer.

BACKGROUND: The Wilms' tumor gene WT1 is overexpressed in endometrial cancer. Although recent studies have revealed that WT1 is a new prognostic factor, it remains unclear whether WT1 plays a pathophysiological role including cell proliferation. PATIENTS AND METHODS: A series of 70 endometrial cancer patients who had undergone a curative resection was studied by immunohistochemistry to determine the correlation between WT1 expression and cell proliferation (proliferating cell nuclear antigen; PCNA). RESULTS: WT1 expression was observed in 64 cases (91%). WT1 expression was associated with advanced FIGO stage (p=0.0228), myometrial invasion (p=0.0114) and high-grade histological differentiation (p=0.0004), indicating up-regulation of WT1 expression with tumor progression. A positive correlation between PCNA labeling index and score of WT1 expression was observed (p=0.0081, rho=0.319). CONCLUSION: These results showed that WT1 might regulate cell proliferation in endometrial cancer.

Immunohistochemical detection of WT1 protein in endometrial cancer.

BACKGROUND: The Wilms' tumor gene WT1 is overexpressed in various kinds of solid tumors. However, it remains unclear whether WT1 plays a pathophysiological role in endometrial cancer. PATIENTS AND METHODS: A series of 70 endometrial cancer patients who had undergone a curative resection was studied to determine the correlation between WT1 expression, clinicopathological characteristics and prognosis. Tissue specimens were evaluated for WT1 expression by immunohistochemistry. RESULTS: The expression of WT1 was strong in 31 patients (44%) and weak in 39 patients (56%). WT1 overexpression was associated with advanced FIGO stage (p=0.0266), myometrial invasion (p=0.0477) and high-grade histological differentiation (p=0.0049). The expression level of WT1 was found to be a significant predictor of disease relapse in univariate analysis (p=0.0233), but not in multivariate analysis (p=0.4757). CONCLUSION: These results suggested that tumor-produced WT1 provided additional prognostic information in endometrial cancer patients.