The role of renal biomarkers to predict the need of surgery in congenital urinary tract obstruction in infants.

INTRODUCTION: The diagnosis of renal function impairment and deterioration in congenital urinary tract obstruction (UTO) continues to be extremely challenging. The use of new renal biomarkers in this setting may favor early renal injury detection, allowing for a reliable choice of optimal therapeutic options and the prevention or minimization of definitive renal damage. OBJECTIVE: The aim of the study was to investigate a selection of promising biomarkers of renal injury with the intention of evaluating and comparing their profile with clinically based decisions for surgical intervention of infants with congenital obstructive uropathies. STUDY DESIGN: The first-year profile of renal biomarkers, serum creatinine (sCr), serum and urine cystatin C (CyC), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), transforming growth factor beta-1 (TGF-ß1), retinol-binding protein (RBP), and microalbuminuria (µALB), was analyzed in a cohort of 37 infants with congenital UTO, divided into three subgroups, 14 cases with grade III unilateral hydro(uretero)nephrosis, 13 cases with grade III bilateral hydro(uretero)nephrosis, and 10 cases with low urinary tract obstruction (LUTO), compared with 24 healthy infants matched by gestational age and birth weight. Serum and urine samples were stored at -70 °C and thereafter analyzed by quantitative enzymatic immunoassay. RESULTS: Compared with the control group (Figure), all renal biomarker values were significantly increased in patients (P ≤ 0.02). In the unilateral hydronephrosis and LUTO group, RBP (P ≤ 0.043), NGAL (P ≤ 0.043), KIM-1 (P ≤ 0.03), and TGF-ß1 (P ≤ 0.034) values dropped significantly after surgery. Neutrophil gelatinase-associated lipocalin alone and in combination with urine and serum CyC demonstrated the best performance in determining the need for surgery (area under the curve, 0.801 and 0.881, respectively). Biomarker profile analysis was suggestive of surgical intervention in 55.4% (7/13) of non-operated cases, and most of the biomarker values were above the cutoff levels within at least 3 months before the clinically based surgical decision in 58% (14/24) of all operated patients. DISCUSSION: To the best of the authors' knowledge, this is the first study to present the clinical use of selected group of serum and urinary biomarkers in the setting of UTO to distinguish between patients who would benefit from surgery intervention. The most promising results were obtained using NGAL, RBP, TGF-ß1, and KIM-1, especially in the unilateral hydro(uretero)nephrosis and LUTO subgroups when compared with the control group. CONCLUSIONS: Urine biomarkers, alone and in combination, demonstrated high potential as a non-invasive diagnostic tool for identifying infants who may benefit from earlier surgical intervention.

Cystoscopic placement of transurethral stent in a fetus with urethral stenosis.

We report the case of a fetus with severe megabladder, displaying the 'keyhole' sign on ultrasound imaging, that underwent cystoscopy at 22 weeks' gestation. There was a familial history of mild urethral atresia. Fetal cystoscopy revealed congenital urethral atresia. A guide wire was advanced through the fetal urethra and a transurethral vesicoamniotic stent was placed successfully. The fetus was delivered at 36 weeks' gestation and postnatal cystoscopy confirmed the absence of posterior urethral valves or urethral atresia. The infant was 5 years old with normal renal function at the time of writing. We conclude that fetal cystoscopic placement of a transurethral stent for congenital urethral stenosis is feasible.

Early fetoscopic tracheal occlusion for extremely severe pulmonary hypoplasia in isolated congenital diaphragmatic hernia: preliminary results.

OBJECTIVE: To evaluate the effect of early fetoscopic tracheal occlusion (FETO) (22-24 weeks' gestation) on pulmonary response and neonatal survival in cases of extremely severe isolated congenital diaphragmatic hernia (CDH). METHODS: This was a multicenter study involving fetuses with extremely severe CDH (lung-to-head ratio < 0.70, liver herniation into the thoracic cavity and no other detectable anomalies). Between August 2010 and December 2011, eight fetuses underwent early FETO. Data were compared with nine fetuses that underwent standard FETO and 10 without fetoscopic procedure from January 2006 to July 2010. FETO was performed under maternal epidural anesthesia, supplemented with fetal intramuscular anesthesia. Fetal lung size and vascularity were evaluated by ultrasound before and every 2 weeks after FETO. Postnatal therapy was equivalent for both treated fetuses and controls. Primary outcome was infant survival to 180 days and secondary outcome was fetal pulmonary response. RESULTS: Maternal and fetal demographic characteristics and obstetric complications were similar in the three groups (P > 0.05). Infant survival rate was significantly higher in the early FETO group (62.5%) compared with the standard group (11.1%) and with controls (0%) (P < 0.01). Early FETO resulted in a significant improvement in fetal lung size and pulmonary vascularity when compared with standard FETO (P < 0.01). CONCLUSIONS: Early FETO may improve infant survival by further increases of lung size and pulmonary vascularity in cases with extremely severe pulmonary hypoplasia in isolated CDH. This study supports formal testing of the hypothesis with a randomized controlled trial.

Protective effects of human amniotic fluid stem cells in a model of aorta allograft vasculopathy in rats.

BACKGROUND: Chronic allograft vasculopathy (CAV) is an important cause of graft loss. Considering the immune inflammatory events involved in the development of CAV, therapeutic approaches to target this process are of relevance. Human amniotic fluid-derived stem cells (hAFSCs), a class of fetal, pluripotent stem cells with intermediate characteristics between embryonic and adult stem cells, display immunomodulatory properties. hAFSCs express mesenchymal and embryonic markers, show high proliferation rates; however, they do not induce tumor formation, and their use does not raise ethical issues. Thus, we sought to investigate the effect of hAFSC on CAV in a model of aorta transplantation. METHODS: Orthotopic aorta transplantation was performed using Fisher (F344) rats as donors and Lewis rats as recipients. Rats were divided into three groups: syngeneic (SYNG), untreated F344 receiving aorta from F344 (n = 8); allogeneic (ALLO), Lewis rats receiving allogeneic aorta from F344 (n = 8); and ALLO + hAFSC, ALLO rats treated with hAFSC (10(6) cells; n = 8). Histological analysis and immunohistochemistry were performed 30 days posttransplantation. RESULTS: The ALLO group developed a robust aortic neointimal formation (208.7 ± 25.4 µm) accompanied by a significant high number of ED1+ (4845 ± 841 cells/mm2) and CD43+ cells (4064 ± 563 cells/mm2), and enhanced expression of α-smooth muscle actin in the neointima (25 ± 6%). Treatment with hAFSC diminished neointimal thickness (180.7 ± 23.7 µm) and induced a significant decrease of ED1+ (1100 ± 276 cells/mm2), CD43+ cells (1080 ± 309 cells/µm2), and α-smooth muscle actin expression 8 ± 3% in the neointima. CONCLUSIONS: These preliminary results showed that hAFSC suppressed inflammation and myofibroblast migration to the intima, which may contribute to ameliorate vascular changes in CAV.

A randomized controlled trial of fetal endoscopic tracheal occlusion versus postnatal management of severe isolated congenital diaphragmatic hernia.

OBJECTIVE: Severe pulmonary hypoplasia and pulmonary arterial hypertension are associated with reduced survival in congenital diaphragmatic hernia (CDH). We aimed to determine whether fetal endoscopic tracheal occlusion (FETO) improves survival in cases of severe isolated CDH. METHODS: Between May 2008 and July 2010, patients whose fetuses had severe isolated CDH (lung-to-head ratio < 1.0, liver herniation into the thoracic cavity and no other detectable anomalies) were assigned randomly to FETO or to no fetal intervention (controls). FETO was performed under maternal epidural anesthesia supplemented with fetal intramuscular anesthesia. Tracheal balloon placement was achieved with ultrasound guidance and fetoscopy between 26 and 30 weeks of gestation. All cases that underwent FETO were delivered by the EXIT procedure. Postnatal therapy was the same for both treated fetuses and controls. The primary outcome was survival to 6 months of age. Other maternal and neonatal outcomes were also evaluated. RESULTS: Twenty patients were enrolled randomly to FETO and 21 patients to standard postnatal management. The mean gestational age at randomization was similar in both groups (P = 0.83). Delivery occurred at 35.6 ± 2.4 weeks in the FETO group and at 37.4 ± 1.9 weeks in the controls (P < 0.01). In the intention-to-treat analysis, 10/20 (50.0%) infants in the FETO group survived, while 1/21 (4.8%) controls survived (relative risk (RR), 10.5 (95% CI, 1.5-74.7), P < 0.01). In the received-treatment analysis, 10/19 (52.6%) infants in the FETO group and 1/19 (5.3%) controls survived (RR, 10.0 (95% CI, 1.4-70.6) P < 0.01). CONCLUSION: FETO improves neonatal survival in cases with isolated severe CDH.

Early fetal cystoscopy for first-trimester severe megacystis.

OBJECTIVES: To report the feasibility of early fetal cystoscopy for the prenatal diagnosis and therapy of severe first-trimester megacystis. METHODS: Between January 2008 and February 2010, early fetal cystoscopy at 16 weeks of gestation was offered to 15 patients whose fetuses presented with severe first-trimester megacystis. All infants were followed up for 6-12 months after birth. Autopsy was always performed whenever fetal or neonatal deaths occurred. RESULTS: Seven patients decided to undergo fetal therapy, and eight elected to continue with expectant observation. One fetus died before early fetal cystoscopy was performed. Therefore, six fetuses underwent early fetal cystoscopy. Urethral atresia was diagnosed in three fetuses during fetal cystoscopy and confirmed at autopsy following termination of pregnancy at 19-20 weeks in all cases. Posterior urethral valves were diagnosed and successfully fulgurated by laser during early cystoscopy in three fetuses, two of which survived with normal renal and bladder function after birth; the remaining fetus had a postnatal diagnosis of megacystis-microcolon intestinal hypoperistalsis syndrome and died neonatally. In the expectantly managed group, no survivals were observed, even among cases with 'isolated' posterior urethral valves. CONCLUSIONS: Percutaneous early fetal cystoscopy is feasible for prenatal diagnosis and therapy of severe megacystis.

Atelectasis observed by computerized tomography after Caesarean section.

BACKGROUND: Atelectasis after either vaginal or Caesarean delivery has not been adequately quantified. This study addresses the hypothesis that atelectasis may be worse in women who undergo Caesarean section when compared with vaginal delivery under regional anaesthesia. METHODS: Twenty healthy non-smoking women submitted to a chest computed tomography (CT) 2 h after delivery in a University Hospital, who had experienced vaginal delivery (n=10) under combined spinal-epidural analgesia or a Caesarean section (n=10) under spinal anaesthesia, were evaluated. The percentage cross-sectional area of atelectasis in dependent lung regions were measured from the CT images obtained at cross-section of the xiphoid process and the top of the diaphragm. RESULTS: The percentage cross-sectional area of atelectasis was 3.95% in the vaginal delivery group and 14.1% in the Caesarean group (P<0.001, Mann-Whitney rank sum test). CONCLUSIONS: These results suggested that pulmonary atelectasis is greater after Caesarean section delivery under spinal anaesthesia than after vaginal delivery with combined spinal-epidural analgesia.

Sonographic appearance of gestational trophoblastic disease evolving into epithelioid trophoblastic tumor.

Epithelioid trophoblastic tumor is a distinctive but rare trophoblastic tumor. It derives from intermediate trophoblastic cells of the chorion laeve and is usually associated with a previous gestational event. We report the case of a patient who had undergone dilatation and curettage for a missed miscarriage. Three months later gestational trophoblastic disease was suspected because of persistent vaginal bleeding and high levels of beta-human chorionic gonadotropin (beta-hCG). Transvaginal ultrasound revealed irregular echolucent lacunae within the myometrium, some of them filled with low-resistance, turbulent blood flow on Doppler examination, emphasizing the diagnosis of gestational trophoblastic disease. The patient was treated with 12 courses of multiagent chemotherapy. After a 2-year remission, a low rise in serum beta-hCG was observed. Transvaginal ultrasound revealed a well-circumscribed echogenic lesion with a diameter of 1.8 cm in the uterine fundus, with no detectable blood flow on Doppler imaging. A diagnosis of tumor of intermediate trophoblastic cells was suspected and total hysterectomy was performed. On pathological examination, the histological and immunohistochemical features were characteristic of epithelioid trophoblastic tumor. Most reported cases of epithelioid trophoblastic tumor have solitary nodules with sharp margins, which is consistent with our ultrasound findings. Ultrasound may be helpful in differentiating epithelioid trophoblastic tumor from placental-site trophoblastic tumor, another tumor of intermediate trophoblastic cells, which shows infiltrative growth insinuating between muscle fibers.

Prenatal diagnosis of posterior mediastinal lymphangioma by two- and three-dimensional ultrasonography.

Lymphangioma is a rare benign tumor characterized by proliferating lymph vessels and composed of large cyst spaces with endothelium-lined channels of varying dimensions. The incidence of lymphangioma is approximately one in 6000 pregnancies. Less than 1% of lymphangiomas are purely mediastinal. The great majority of cases are of cystic lymphangioma, but very rarely there is a mixed lesion consisting of multiple cysts of dilated capillary and lymph vessels. We report a case of posterior mediastinal lymphangioma diagnosed at 28 weeks' gestation, in which three-dimensional ultrasonography was helpful in determining the precise location of the tumor. A Cesarean section was performed at 39 weeks and the tumor was resected on the 5(th) day postdelivery; histological examination revealed a mixed cystic lymphangioma.

Predictive factors of trophoblastic invasion into the ampullary region of the tubal wall in ectopic pregnancy.

BACKGROUND: Predictive factors of damage to the Fallopian tube may guide the treatment for patients with tubal pregnancy. The aim of this study was to assess the predictive value of the following parameters: gestational age, serum beta-hCG concentrations and ultrasound findings. METHODS: A total of 105 patients with ampullary pregnancy undergoing salpingectomy were analysed. Trophoblastic invasion was histologically classified as stage I when limited to the tubal mucosa, stage II when extending to the muscle layer and stage III in the case of complete tubal wall infiltration. We correlated the depth of trophoblastic infiltration into the tubal wall with gestational age, beta-hCG concentration on the day of surgery and the type and size of the ectopic mass upon ultrasound. RESULTS: No association was observed between the depth of trophoblastic invasion and gestational age (P = 0.53) or tubal mass diameter (P = 0.43). Trophoblastic invasion was, however, associated with beta-hCG concentration (P < 0.001) and with the type of ultrasonographic image (P = 0.001). Beta-hCG levels of 2400 mIU/ml showed 82.8% sensitivity and 85.5% specificity for stage I, and levels of 5990 mIU/ml showed 82.6% sensitivity and 74.6% specificity for stage III. CONCLUSIONS: Depth of trophoblastic penetration into the tubal wall of the ampullary region of Fallopian tube is correlated with beta-hCG concentration and the type of ultrasonographic image; serum beta-hCG is the best predictor of the depth of penetration.

Adeno-associated virus DNA in human gestational trophoblastic disease.

Previous studies had shown a correlation between infection with the human adeno-associated virus (AAV) and spontaneous abortion in early pregnancy. Furthermore, AAV DNA had been detected in cells of the human trophoblast lines, Jeg-3, JAr, and BeWo, in cells of the human amnion line, FL, and in trophoblasts from amnion fluids. Infectious AAV virions could be isolated from amnion fluids. To further analyse AAV infection during pregnancy, we tested material from Gestational Trophoblastic Disease for the presence of AAV DNA. With 63 tissue samples from patients from Brazil, including 49 hydatiform moles and 14 choriocarcinomas, nested PCR was performed to detect the presence of AAV DNA. In addition, 15 samples from spontaneous abortions were analysed. AAV DNA was found in 43 samples (28/49 hydatiform moles, 4/14 choriocarcinomas, 11/15 miscarriage material). These findings confirm AAV infection of embryo-derived tissue in humans and further suggest a role of AAV in miscarriage and trophoblastic disease.

Phenotypic modulation of fibroblastic cells in the mucous layer of the human uterine cervix at term.

The uterine cervix is a dynamic structure with a high capacity to adapt to different, even opposing, roles during the sequence of physiological events of gestation (for example, acting as a barrier to retain the fetus during pregnancy and dilating to allow delivery at term). Histoarchitectural changes of the uterine cervix allow its successful adaptation. The aim of this study was to investigate whether fibroblastic cell plasticity, described in the lamina propria of the rat uterine cervix at term, could be observed in women too. Biopsy specimens of non-pregnant and intrapartum human cervices were studied under the transmission electron microscope, and cytoskeletal differentiation markers were identified by immunohistochemistry under the light microscope. Desmin-positive cells were present in the mucous layer of the cervix during labour. These cells displayed cytoplasmic processes (typical of myofibroblasts) that also stained positively for vimentin. The main ultrastructural features for defining the myofibroblast under the electron microscope were also observed in these cells. However, cervices of non-pregnant women contained resident fibroblasts at the same location. Examination of the differentiation repertoire of fibroblastic cells in the mucous layer of the uterine cervix resulted in the characterization of myofibroblasts at term. The implications of the plasticity of fibroblastic-myofibroblastic cells in the physiological changes displayed in the uterine cervix during pregnancy, labour and postpartum involution require further investigation.

Avaliaçäo da maturidade fetal em gestaçöes de alto risco: análise dos resultados de acordo com a idade gestacional / Assessment of fetal maturity in high risk pregnancies: analysis according to gestational age

OBJETIVO: Estudar a avaliaçäo da maturidade fetal em gestaçöes de alto risco e analisar os resultados neonatais. MÉTODOS: Entre julho de 1998 e agosto de 1999 foram realizadas, no Setor de Vitalidade Fetal da Clínica Obstétrica do HC-FMUSP, 180 amniocenteses para avaliaçäo da maturidade fetal, sendo realizados os testes de Clements em três tubos e a contagem de células orangiófilas coradas com Azul de Nilo a 0,1 por cento. Os resultados perinatais foram correlacionados com a maturidade fetal em 75 casos cujo parto ocorreu até sete dias após a punçäo. RESULTADOS: Na macroscopia, 91 por cento das amostras apresentavam líquido amniótico claro, 3,3 por cento meconial e 5,6 por cento hemorrágico. A maturidade foi observada em 28 por cento dos exames realizados. Na avaliaçäo dos resultados perinatais, quando a maturidade estava ausente, a necessidade de intubaçäo do recém-nascido ocorreu em três casos (13 por cento) e nos fetos maduros isto ocorreu em um caso (2,5 por cento) (p<0,05). A necessidade de internaçäo em UTI neonatal ocorreu em 65 por cento dos recém-nascidos que apresentavam líquido imaturo e em apenas 10 por cento dos maduros (p<0,0001). CONCLUSÖES: Os recém-nascidos das gestantes com maturidade fetal presente apresentaram com menor freqüência necessidade de intubaçäo na sala de parto e de internaçäo em UTI neonatal, demonstrando menor morbidade perinatal. Entre a 29ª e a 32ª semana de gestaçäo, foram observados cerca de 10 por cento de fetos maduros, demonstrando que, quando necessário, a avaliaçäo da maturidade pode ser realizada neste período da gravidez. Näo observamos casos com maturidade fetal abaixo de 29 semanas, limitando a realizaçäo deste exame neste período

Prenatal diagnosis and follow up of congenital splenic cyst: a case report.

We report a case of congenital splenic cyst that was identified by prenatal sonography at 25 gestational weeks. Serial scans demonstrated an increase in size during the prenatal period but after birth the cyst progressively decreased in size until its complete regression at 6 months of age.

Prenatal sonographic diagnosis of adrenal neuroblastoma.

Neuroblastoma is the most frequent extracranial solid tumor in childhood, but it is seldom diagnosed prenatally. We report a case of adrenal neuroblastoma identified at 39 weeks' menstrual age and successfully treated by postnatal surgery and chemotherapy. Sonography revealed a hyperechoic mass in the right upper quadrant of the fetal abdomen associated with hydramnios and hydronephrosis. Two days after delivery, the tumor was resected. No metastasis was identified. The infant received 6 cycles of chemotherapy, and at 2 years of age she was well, with no signs of recurrence.

Pancreaticoduodenectomy as treatment of adenocarcinoma of the papilla of Vater diagnosed during pregnancy. A case report.

BACKGROUND: Papillary adenocarcinomas are rare tumors of the gastrointestinal tract. There are few reports of this neoplasm diagnosed during pregnancy. CASE: A case of adenocarcinoma of the papilla of Vater was diagnosed by sonographically guided biopsy during pregnancy. The patient underwent radical resection of the tumor at 25 weeks' gestation; pregnancy termination was not indicated. At 39 weeks' gestation, a cesarean-section was performed. The postoperative period entailed total parenteral nutrition until intestinal motility stabilized. This ensured the mother and fetus' well-being until delivery. CONCLUSION: Papillary adenocarcinoma is associated with good prognosis since it is totally removed by radical resection, and pancreaticoduodenectomy can be performed successfully during pregnancy, but the patient must receive special prenatal care.

Prevalence of 'high risk' human papillomavirus in the lower genital tract of Brazilian gravidas.

The presence of high-risk human Papillomavirus types 16, 18 and 33 was examined in 125 pregnant patients with abnormal Papanicolau smears. Specimens of cervicovaginal cells were analyzed by a simplified method of slot-blot hybridization. The overall prevalence of those viral sequences was 48%, being: 22.4% of HPV16, 17.6% of HPV18, 4.0% for double HPV16 and 18 infestation and 4.0% of HPV33. Their prevalence in HPV positive cervical sample was alone respectively 46.6%, 36.6%, 8.3% and 8.3%. Besides the high incidence of those carcinogenic types and intense viral proliferation, a rapid progression from CIN to carcinoma was clinically observed in four pregnant patients. Our data may reinforce the idea that progesterone has a positive role to the persistence and transformation of 'high risk' HPV, particularly of HPV16. The enhanced detection of potentially malignant types during pregnancy should warn on the importance of early diagnosis and treatment of papillomatosis.

Prognostic factors associated with congenital cystic adenomatoid malformation of the lung.

This study presents 18 cases of prenatally diagnosed congenital cystic adenomatoid malformation (CCAM) to identify potential factors that could predict prognosis. Comparisons of prenatal parameters were made between fetuses that survived and those that died perinatally. It was found that microcystic lesion, bilateral lung involvement and hydrops were each highly correlated with poor prognosis, while neither polyhydramnios nor mediastinal shift was significantly associated with had outcome. Fetal interventions were indicated only in two of the surviving cases: a thoracocentesis and a cysto-amniotic shunt. A therapeutic amniocentesis was performed in one case of polyhydramnios. The diagnosis of CCAM was histologically confirmed in all cases by necropsy or by postnatal lobectomy.