Adriamycin-induced Fetal Hydronephrosis

Introduction: At the end of pregnancy, the amniotic fluid (AF) depends basically on renal function, corresponding to fetal urine. Changes in AF, especially oligohydramnios, are reported in association with fetal hydronephrosis (FH). The experimental model using adriamycin in pregnant female rats has a teratogenic effect and has been classically employed to study esophageal atresia. Nevertheless, adriamycin promotes FH with high frequency as well. In the present study, using this animal model, we tried to identify the incidence and microscopic changes of FH, as well as its correlation with AF weight. Materials and Methods: Eight Spreague-Dawley pregnant female rats received adriamycin 2.2 mg/kg on the 8th and 9th gestational days (considering term gestation = 22 days). Those fetuses that received adriamycin (Adriamycin Group) were compared with fetuses from 2 female rats (Control Group), which received 0.9% saline solution. On the 21.5 gestational day, the fetuses were collected by cesarean incision, sacrificed, and examined for macro and microscopic changes in kidneys and ureters. Fetuses with bilateral hydronephrosis formed the Hydronephrosis Group. AF weight was determined as well. Results: Hydronephrosis occurred in 70 (95%) of the 74 fetuses in the adriamycin group against none of the 21 fetuses from the control group. The amniotic fluid weight was increased in the adriamycin group in relation to the control group (p < 0.001). The histomorphometric study revealed dilation of the renal pelvis and reduction of renal parenchyma in the hydronephrosis group in relation to the control group. Severe cortical atrophy, cortical tubular atrophy and medullar atrophy were observed in the hydronephrosis group. Conclusions: Slight renal lesions were in agreement with changes in AF weight, since they suggest that there was production of urine with the maintenance of AF.306508513Brace, R.A., Physiology of amniotic fluid volume regulation (1997) Clin. Obstet. Gynecol., 40, pp. 280-289Harrison, M.R., Nakayama, D.K., Noall, R., de Lorimier, A.A., Correction of congenital hydronephrosis in utero II. Decompression reverses the effects of obstruction on the fetal lung and urinary tract (1982) J. Pediatr. Surg., 17, pp. 965-974Chevalier, R.L., Thornhill, B.A., Chang, A.Y., Unilateral ureteral obstruction in neonatal rats leads to renal insufficiency in adulthood (2000) Kidney Int., 58, pp. 1987-1995Seseke, F., Thelen, P., Hemmerlein, B., Kliese, D., Zoller, G., Ringert, R.H., Histologic and molecular evidence of obstructive uropathy in rats with hereditary congenital hydronephrosis (2000) Urol. Res., 28, pp. 104-109Freedman, A.L., Bukowski, T.P., Smith, C.A., Evans, M.I., Johnson, M.P., Gonzalez, R., Fetal therapy for obstructive uropathy: Diagnosis specific outcomes (1996) J. Urol., 156 (2 PART 2), pp. 720-723. , [corrected]. discussion 723-4Erratum in: J Urol. 1996156: 1786Bernstein, J., Risdon, R.A., Gilbert-Barness, E., Renal System (1997) Potter's, Pathology of the Fetus and Infant, pp. 863-903. , Gilbert-Barness E (ed.), St Louis, MosbyBastide, A., Manning, F., Harman, C., Lange, I., Morrison, I., Ultrasound evaluation of amniotic fluid: Outcome of pregnancies with severe oligohydramnios (1986) Am. J. Obstet. Gynecol., 154, pp. 895-900Reddy, P.P., Mandell, J., Prenatal diagnosis. Therapeutic implications (1998) Urol. Clin. North Amer., 25, pp. 171-180Beasley, S.W., Diez Pardo, J., Qi, B.Q., Tovar, J.A., Xia, H.M., The contribution of the adriamycin-induced rat model of the VATER association to our understanding of congenital abnormalities and their embryogenesis (2000) Pediatr. Surg. Int., 16, pp. 465-472Merei, J., Hasthorpe, S., Farmer, P., Hutson, J.M., Visceral anomalies in prenatally adriamycin-exposed rat fetuses: A model for the VATER association (1999) Pediatr. Surg. Int., 15, pp. 11-16Merei, J., Batiha, A., Hani, I.B., El-Qudah, M., Renal anomalies in the VATER animal model (2001) J. Pediatr. Surg., 36, pp. 1693-1697Franca, W.M., Goncalves, A., Moraes, S.G., Pereira, L.A., Sbragia, L., Esophageal atresia and other visceral anomalies in a modified Adriamycin rat model and their correlations with amniotic fluid volume variations (2004) Pediatr. Surg. Int., 20, pp. 602-608Steinhardt, G.F., Liapis, H., Phillips, B., Vogler, G., Nag, M., Yoon, K.W., Insulin-like growth factor improves renal architecture of fetal kidneys with complete ureteral obstruction (1995) J. Urol., 154, pp. 690-693Steinhardt, G.F., Salinas-Madrigal, L., deMello, D., Farber, R., Phillips, B., Vogler, G., Experimental ureteral obstruction in the fetal Opossum: Histologic assessment (1994) J. Urol., 152, pp. 2133-2138Tewey, K.M., Rowe, T.C., Yang, L., Halligan, B.D., Liu, L.F., Adriamycin-induced DNA damage mediated by mammalian DNA topoisomerase II (1984) Science, 226 (4673), pp. 466-468Orford, J.E., Cass, D.T., Dose response relationship between adriamycin and birth defects in a rat model of VATER association (1999) J. Pediatr. Surg., 34, pp. 392-398Beasley, S.W., Diez Pardo, J., Qi, B.Q., Tovar, J.A., Xia, H.M., The contribution of the adriamycin-induced rat model of the VATER association to our understanding of congenital abnormalities and their embryogenesis (2000) Pediatr. Surg. Int., 16, pp. 465-472Kimble, R.M., Harding, J.E., Kolbe, A., Does gut atresia cause polyhydramnios? (1998) Pediatr. Surg. Int., 13, pp. 115-117Liu, M.I., Hutson, J.M., Cloacal and urogenital malformations in adriamycin-exposed rat fetuses (2000) BJU Int., 86, pp. 107-112Liu, M.I., Hutson, J.M., Zhou, B., Critical timing of bladder embryogenesis in an adriamycin-exposed rat fetal model: A clue to the origin of the bladder (1999) J. Pediatr. Surg., 34, pp. 1647-165

Fetal Bilateral Obstructive Uropathies: Ultrasound Findings During Pregnancy And Postnatal Outcomes [uropatias Obstrutivas Bilaterais Fetais: Sinais Ultrassonográficos Durante Agravidez E Evolução Pós-natal]

Purpose: To verify the association between ultrasonographic signs during gestation and post-delivery evolution in fetuses with bilateral obstructive uropathies, followed up in an expectant way. Methods: Fetuses with bilateral obstructive uropathies presenting severe oligoamnios and narrow thorax have been compared with fetuses with bilateral obstructive uropathies without those alterations, concerning the presence or absence of cysts in both kidneys, and the presence or absence of parenchymal hyperechogenicity in both kidneys. Cases of neonatal death were compared with cases of neonatal discharge from the nursery, regarding the same renal echographic aspects mentioned above, the presence of severe oligoamnios and narrow thorax. The sensitivity, specificity, positive and negative predictive value of the presence of bilateral renal cysts, bilateral renal hyperechogenicity, severe oligoamnios and narrow fetal thorax for the neonatal death were calculated. RESULTS: severe oligoamnios and narrow thorax were more frequent (p=0.03; p<0.001) in fetuses with bilateral renal cysts, as compared to those with echographically normal renal parenchyma. Neonatal death was more frequent among cases with severe oligoamnios (p<0.001), narrow thorax (p<0.001) and bilateral renal cysts (p<0.002), when respectively compared with cases without those alterations. The best values of sensitivity, specificity, positive and negative predictive value for the death of neonatal/breastfeeding infants were obtained using the echographic aspect of narrow thorax, and were 81.8, 100, 100 and 79.3%, respectively. Conclusions: In cases of fetuses with bilateral obstructive uropathies followed up in an expectant way, the ultrasonographic signs more associated to bad prognosis are severe oligoamnios, narrow fetal thorax and presence of bilateral renal cysts.3111540546Helin, I., Persson, P.H., Prenatal diagnosis of urinary tract abnormalities by ultrasound (1986) Pediatrics, 78 (5), pp. 879-883Rosendahl, H., Ultrasound screening for fetal urinary tract malformations a prospective study in general population (1990) Eur J Obstet Gynecol Reprod Biol, 36 (1-2), pp. 27-33James, C.A., Watson, A.R., Twining, P., Rance, C.H., Antenatally detected urinary tract abnormalities: Changing incidence and management (1998) Eur J Pediatr, 157 (6), pp. 508-511Thomas, D.F., Prenatally detected uropathy: Epidemiological considerations (1998) Br J Urol, 81 (SUPPL. 2), pp. 8-12Dicke, J.M., Blanco, V.M., Yan, Y., Coplen, D.E., The type and frequency of fetal renal disorders and management of renal pelvis dilatation (2006) J Ultrasound Med, 25 (8), pp. 973-977Loirat, C., Ehrich, J.H., Geerlings, W., Jones, E.H., Landais, P., Mallick, N.P., Report on management of renal failure in children in Europe, XXIII, 1992 (1994) Nephrol Dial Transplant, 9 (SUPPL. 1), pp. 26-40Gauderer, M.W., Jassani, M.N., Izant Jr, R.J., Ultrasonographic antenatal diagnosis: Will it change the spectrum of neonatal surgery? (1984) J Pediatr Surg, 19 (4), pp. 404-407Mahony, B.S., Filly, R.A., Callen, P.W., Hricak, H., Golbus, M.S., Harrison, M.R., Fetal renal dysplasia: Sonographic evaluation (1984) Radiology, 152 (1), pp. 143-146Grignon, A., Filion, R., Filiatrault, D., Robitaille, P., Homsy, Y., Boutin, H., Urinary tract dilatation in utero: Classification and clinical applications (1986) Radiology, 160 (3), pp. 645-647Corteville, J.E., Gray, D.L., Crane, J.P., Congenital hydronephrosis: Correlation of fetal ultrasonographic findings with infant outcome (1992) Am J Obstet Gynecol, 167 (2), pp. 384-388McHugo, J., Whittle, M., Enlarged fetal bladders: Aetiology, management and outcome (2001) Prenat Diagn, 21 (11), pp. 958-963Muller, F., Dommergues, M., Mandelbrot, L., Aubry, M.C., Nihoul-Fekete, C., Dumez, Y., Fetal urinary biochemistry predicts postnatal renal function in children with bilateral obstructive uropathies (1993) Obstet Gynecol, 82 (5), pp. 813-820Miguelez, J., Bunduki, V., Yoshizaki, C.T., Sadek, L.S., Koch, V., Peralta, C.F., Fetal obstructive uropathy: Is urine sampling useful for prenatal counselling? (2006) Prenat Diagn, 26 (1), pp. 81-84Lee, R.S., Cendron, M., Kinnamon, D.D., Nguyen, H.T., Antenatal hydronephrosis as a predictor of postnatal outcome: A meta-analysis (2006) Pediatrics, 118 (2), pp. 586-593Keays, M.A., Guerra, L.A., Mihill, J., Raju, G., Al-Asheeri, N., Geier, P., Reliability assessment of Society for Fetal Urology ultrasound grading system for hydronephrosis (2008) J Urol, 180 (4 SUPPL.), pp. 1680-1682Moore, T.R., Cayle, J.E., The amniotic fluid index in normal human pregnancy (1990) Am J Obstet Gynecol, 162 (5), pp. 1168-1173Moore, T.R., Superiority of the four-quadrant sum over the single-deepest-pocket technique in ultrasonographic identification of abnormal amniotic fluid volumes (1990) Am J Obstet Gynecol, 163 (3), pp. 762-767Moore, T.R., Sonographic screening for oligohydramnios: Does it decrease or increase morbidity? (2004) Obstet Gynecol, 104 (1), pp. 3-4Johnson, J.M., Chauhan, S.P., Ennen, C.S., Niederhauser, A., Magann, E.F., A comparison of 3 criteria of oligohydramnios in identifying peripartum complications: A secondary analysis (2007) Am J Obstet Gynecol, 197 (2). , 207.e1-7discussion 207.e7-8Rudd, P.T., Hughes, E.A., Placzek, M.M., Hodes, D.T., Reference ranges for plasma creatinine during the first month of life (1983) Arch Dis Child, 58 (3), pp. 212-215Andreoli, S.P., Acute renal failure in the newborn (2004) Semin Perinatol, 28 (2), pp. 112-123Blyth, B., Snyder, H.M., Duckett, J.W., Antenatal diagnosis and subsequent management of hydronephrosis (1993) J Urol, 149 (4), pp. 693-698Gunn, T.R., Mora, J.D., Pease, P., Antenatal diagnosis of urinary tract abnormalities by ultrasonography after 28 weeks' gestation: Incidence and outcome (1995) Am J Obstet Gynecol, 172 (2 Pt 1), pp. 479-486Livera, L.N., Brookfield, D.S., Egginton, J.A., Hawnaur, J.M., Antenatal ultrasonography to detect fetal renal abnormalities: A prospective screening programme (1989) Bmj, 298 (6685), pp. 1421-1423Sairam, S., Al-Habib, A., Sasson, S., Thilaganathan, B., Natural history of fetal hydronephrosis diagnosed on mid-trimester ultrasound (2001) Ultrasound Obstet Gynecol, 17 (3), pp. 191-196Madarikan, B.A., Hayward, C., Roberts, G.M., Lari, J., Clinical outcome of fetal uropathy (1988) Arch Dis Child, 63 (8), pp. 961-963Hobbins, J.C., Romero, R., Grannum, P., Berkowitz, R.L., Cullen, M., Mahoney, M., Antenatal diagnosis of renal anomalies with ultrasound. I. Obstructive uropathy (1984) Am J Obstet Gynecol, 148 (7), pp. 868-877Reznik, V.M., Murphy, J.L., Mendoza, S.A., Griswold, W.R., Packer, M.G., Kaplan, G.W., Follow-up of infants with obstructive uropathy detected in utero and treated surgically postnatally (1989) J Pediatr Surg, 24 (12), pp. 1289-1292Wigglesworth, J.S., Desai, R., Is fetal respiratory function a major determinant of perinatal survival? (1982) Lancet, 1 (8266), pp. 264-267Barss, V.A., Benacerraf, B.R., Frigoletto Jr, F.D., Second trimester oligohydramnios, a predictor of poor fetal outcome (1984) Obstet Gynecol, 64 (5), pp. 608-610Bastide, A., Manning, F., Harman, C., Lange, I., Morrison, I., Ultrasound evaluation of amniotic fluid: Outcome of pregnancies with severe oligohydramnios (1986) Am J Obstet Gynecol, 154 (4), pp. 895-900Mandell, J., Peters, C.A., Estroff, J.A., Benacerraf, B.R., Late onset severe oligohydramnios associated with genitourinary abnormalities (1992) J Urol, 148 (2 Pt 2), pp. 515-518Prudente, A., Reis, L.O., França, R.P., Miranda, M., D'ancona, C.A., Vesicostomy as a protector of upper urinary tract in long-term follow-up (2009) Urol J, 6 (2), pp. 96-100Soliman, S.M., Primary ablation of posterior urethral valve in low birth weight neonates by visually guided fogarty embolectomy catheter (2009) J Urol, 181 (5), pp. 2284-2289Song, S.H., Lee, S.B., Park, Y.S., Kim, K.S., Is antibiotic prophylaxis necessary in infants with obstructive hydronephrosis? (2007) J Urol, 177 (3), pp. 1098-1101Yohannes, P., Hanna, M., Current trends in the management of posterior urethral valves in the pediatric population (2002) Urology, 60 (6), pp. 947-953Carvalho, M.H., Brizot, M.L., Lopes, L.M., Chiba, C.H., Miyadahira, S., Zugaib, M., Detection of fetal structural abnormalities at the 11-14 week ultrasound scan (2002) Prenat Diagn, 22 (1), pp. 1-4Souka, A.P., Pilalis, A., Kavalakis, I., Antsaklis, P., Papantoniou, N., Mesogitis, S., Screening for major structural abnormalities at the 11- to 14-week ultrasound scan (2006) Am J Obstet Gynecol, 194 (2), pp. 393-396Dane, B., Dane, C., Sivri, D., Kiray, M., Cetin, A., Yayla, M., Ultrasound screening for fetal major abnormalities at 11-14 weeks (2007) Acta Obstet Gynecol Scand, 86 (6), pp. 666-670Liao, A.W., Sebire, N.J., Geerts, L., Cicero, S., Nicolaides, K.H., Megacystis at 10-14 weeks of gestation: Chromosomal defects and outcome according to bladder length (2003) Ultrasound Obstet Gynecol, 21 (4), pp. 338-341Bunduki, V., Saldanha, L.B., Sadek, L., Miguelez, J., Miyadahira, S., Zugaib, M., Fetal renal biopsies in obstructive uropathy: Feasibility and clinical correlations - preliminary results (1998) Prenat Diagn, 18 (2), pp. 101-10

Epignathus: Report of a case with successful outcome

Epignathus is an extremely rare form of teratoma that arises from the palate or pharynx in the region of the basisphenoid (Rathke's pouch).(4) This condition is associated with a high mortality rate caused by severe airway obstruction in the neonatal period, thus requiring prenatal planning and prompt surgical treatment after birth. The authors describe a case of giant epignathus that was successfully resected followed by an uneventful recovery. Copyright (C) 1998 by W.B. Saunders Company.33352052

Lateral esophagostomy: An alternative in the initial management of long gap esophageal atresia without fistula

The authors report an alternative method of cervical esophagostomy that was used in a child with type A esophageal atresia. This method involved performing a lateral esophagostomy in the proximal pouch, preserving its distal end, allowing the child to swallow normally, without choking, while stimulating the spontaneous growth of the proximal esophagus. As a result, the infant could be discharged home on G-tube feedings while waiting for spontaneous growth of the proximal pouch to occur, There were no episodes of aspiration during this period, and definitive reconstruction through end-to-end esophageal anastomosis was accomplished successfully at the age of 18 months. The authors consider that this alternative might increase the possibility of a definitive correction through delayed primary anastomosis of the infant's own esophagus in children with this type of malformation. J Pediatr Surg 35:1827-1829. Copyright (C) 2000 by W.B. Saunders Company.35121827182

Beckwith-Wiedemann syndrome and virilizing cortical adrenal tumor in a child

The authors report a case of a virilizing adrenal tumor that developed in a 2-year-old child with Beckwith-Wiedemann syndrome (BWS), He had a fetal diagnosis of omphalocele and a history of neonatal adrenal cysts. The importance of prenatal diagnosis of BWS and postnatal follow-up of tumors is discussed. The differential diagnosis of adrenal pathologies occurring in BWS also is reviewed. J Pediatr Surg 35:1269-1277. Copyright (C) 2000 by W.B. Saunders Company.3581269127

Demographic Of Short Gut Syndrome: Increasing Demand Is Not Followed By Referral Of Potential Candidates For Small Bowel Transplantation

Background Despite improvements in small bowel transplantation (SBTx), early referral of patients with irreversible intestinal failure (IF) remains a major obstacle. In this study we evaluated the demand for SBTx among seven surgical pediatric centers located at least 200 km from our center. Methods From 1997 to 2001, 640 patients have been treated for neonatal diseases, including 248 who underwent a minor or major intestinal resection. Twenty-four patients with major resections presented with short gut syndrome, requiring total parenteral nutrition (TPN). The greatest demand was in postsurgical neonates with necrotizing enterocolitis, gastroschiesis, onphalocoeles, or midgut volvulus, and in three adults with postradiotherapy arteritis (n = 2) and mesenteric vein thromboses (n = 1). The median length of residual bowel after resection was 20 to 30 cm, without an ileocecal valve. Four patients were referred for SBTx evaluation; three died while awaiting a donor; 20 were not referred, among whom 14 died of TPN complications. Results Approximately 62 children per year require nutritional support for IF, most of whom develop complications related to TPN. Because many patients who are TPN-dependent develop complications, we believe that early referral would reduce mortality. Conclusions Greater medical awareness about the feasibility of SBTx procedures and earlier referral may improve results and quality of life after transplant.362259260Azuma, T., Nakai, H., Fukuzawa, M., (1998) Transplant Proc, 30, p. 2529Kato, T., Mittal, N., Nishida, S., (2003) J Pediatr Surg, 38, p. 14

Epignathus: Report Of A Case With Successful Outcome.

Epignathus is an extremely rare form of teratoma that arises from the palate or pharynx in the region of the basisphenoid (Rathke's pouch). This condition is associated with a high mortality rate caused by severe airway obstruction in the neonatal period, thus requiring prenatal planning and prompt surgical treatment after birth. The authors describe a case of a giant epignathus that was successfully resected followed by an uneventful recovery.33520-

Demographic of short gut syndrome: Increasing demand is not followed by referral of potential candidates for small bowel transplantation

Background. Despite improvements in small bowel transplantation (SBTx), early referral of patients with irreversible intestinal failure (IF) remains a major obstacle. In this study we evaluated the demand for SBTx among seven surgical pediatric centers located at least 200 km from our center.Methods. From 1997 to 2001, 640 patients have been treated for neonatal diseases, including 248 who underwent a minor or major intestinal resection. Twenty-four patients with major resections presented with short gut syndrome, requiring total parenteral nutrition (TPN). The greatest demand was in postsurgical neonates with necrotizing enterocolitis, gastroschiesis, onphalocoeles, or midgut volvulus, and in three adults with postradiotherapy arteritis (n = 2) and mesenteric vein thromboses (n = 1). The median length of residual bowel after resection was 20 to 30 cm, without an ileocecal valve. Four patients were referred for SBTx evaluation; three died while awaiting a donor; 20 were not referred, among whom 14 died of TPN complications.Results. Approximately 62 children per year require nutritional support for IF, most of whom develop complications related to TPN. Because many patients who are TPN-dependent develop complications, we believe that early referral would reduce mortality.Conclusions. Greater medical awareness about the feasibility of SBTx procedures and earlier referral may improve results and quality of life after transplant

Inhibin α-subunit (INHA) gene and locus changes in paediatric adrenocortical tumours from TP53 R337H mutation heterozygote carriers

The R337H TP53 mutation is a low-penetrance molecular defect that predisposes to adrenocortical tumour (ACT) formation in Brazilian and possibly other populations. Additional genetic defects may be responsible for the variable expression of ACTs in these cases. The inhibin α-subunit gene (INHA) on 2q33-qter has been implicated in mouse adrenocortical tumourigenesis. We studied 46 pediatric patients with ACTs from Brazil for INHA genetic alterations; 39 of these patients were heterozygous carriers of the R337H TP53 mutation. We first mapped the INHA gene by radiation hybrid analysis and determined 10 linked microsatellite markers in an area flanked by D2S1371 and D2S206 on 2q33-qter. These markers were then used for loss of heterozygozity (LOH) studies in nine paired germline and tumour DNA samples. Mapping placed the INHA gene in close proximity to D2S2848 (SHGC11864) with a log of odds (LOD) score of 5.84. LOH for at least one marker in the region was identified in 8/9 tumours (89%). Six patients were heterozygous for three INHA mutations: one in exon 1, 127C>G, and two in exon 2, 3998G>A and 4088G>A, all leading to amino acid substitutions (P43A, G227R, and A257T, respectively). A257T is located in a conserved INHA region, highly homologous to transforming growth factor-ß; both G227R and A257T change polarity, and, in addition, G227R changes the pH. We conclude that these sequence alterations and the detected 2q allelic changes suggest that INHA may be one of the contributing factors needed for ACT formation in pediatric patient carriers of the R337H TP53 mutation