SECTION ON SURGERY51ST ANNIVERSARY MEETING

October 8-10, 1999

SCHEDULE

FRIDAY, OCTOBER 8,1999

Section on Surgery3:00-5:00 p.m. Room 20, Washington Convention Center

Pediatric Oncology Group/Children's Cancer GroupAdvances In Surgery Techniques and Oncology

Moderator: Robert C. Shamberger, MD, FAAPCryotherapy and Radiofrequency Ablation of HepaticMetastasis

William Jarnigan, MDSentinel Lymph Node Mapping in Melanoma andRhabdomyosarcoma

Richard J. Andrassy, MD, FAAPLaparoscopic Techniques in Oncology

George W. Holcomb, III, MD, FAAPIntraoperative Radiotherapy

Michael P. LaQuaglia, MD, FAAP

Discussion

SATURDAY, OCTOBER 9,1999

Section on Surgery7:00 am-5:00 pmRooms 32 & 33, Washington Convention Center

7:00-8:00 a.m. Section Business Meeting and continentalbreakfastBreakfast tickets must be purchased through ad-vance registration.

8:00-9:30 a.m.

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Scientific Session #1(Please note that all abstract presentations are 8minutes except for those identified with a (3)which are 3 minutes. The abstracts asterisked arebeing considered for the Residents ResearchPrize).

Intermediate Term Results of the Free Tra-cheal Autograft for Long Segment Congen-ital Tracheal StenosisC.L. Backer, MD, FAAP; C. Mavroudis, MD,FAAP; M.E. Dunham, MD; L.D. Holinger,MD, FAAP. Chicago, IL

(3) Cervical Repair of Esophageal Atresiawith Tracheoesophageal FistulaA.M. Kosloske, MD, FAAP; P.F. Jewell, MD,FAAP. Lubbock, TX

One-Stage Soave Procedure for Hirsch-sprung Disease: A Comparison of theTransanal vs Open ApproachesJ.C. Langer, MD, FAAP; M. Seifert; R.K.Minkes, MD. St. Louis, MO

Immunolocalization of Gap Junction Pro-tein, Connexion-43, in the Interstitial Cellsof Cajal of the Normal and Hirschsprung'sDisease BowelL. Nemeth, MD; S. Maddur, MD; P. Puri,FRCS; Dublin, Ireland

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The Long-Term Follow-Up of Redo-Pull-through Procedures for Hirschsprung'sDiseaseK. van Leeuwen, MD; D.H. Teitelbaum, MD,FAAP; A.G. Coran, MD, FAAP. Ann Arbor,MI

(3) GDNF Signalling Pathway in InfantileHypertrophic Pyloric StenosisN. Guarino, MD; H. Shima, MD; T. Oue, MD;P. Puri, FRCS. Dublin, Ireland

(3) Complications of Ladd's Procedure forMalrotationR.C. Northrop, MD; C.W. Wagner, MD; S.D.Smith, MD, FAAP; R.I. Jackson, MD. LittleRock, AR

(3) Silo Decompression for AbdominalCompartment Syndrome in Three Chil-drenJ.M. DeCou, MD; R.S. Abrams, MD; R.S. Mill-er,MD; M.W.L. Gauderer, MD, FAAP. Green-ville, SC

(3) Routine Bedside Insertion of a SilasticSpring-Loaded Silo for Infants with Gas-troschisis.R.K. Minkes, MD; J.C. Langer, MD, FAAP;M.V. Mazziotti, MD; M.A. Skinner, MD, R.P.Foglia, MD, FAAP. St. Louis, MO

Failure of High Dose Intravenous ImmuneGlobulin Does Not Always Predict Re-sponse of Subsequent Splenectomy in Pe-diatric Patients with Idiopathic Thrombo-cytopenic PurpuraM.R. Hemmila, MD; D.S. Foley, MD; V.P.Castle, MD, FAAP; R.B. Hirschl, MD, FAAP.Ann Arbor, MI

9:30-11:15 a.m. Scientific Session #2

(3) Treatment of Inflammatory Bowel Dis-ease (IBD) With the Intestinal Growth Fac-tor Glucagon-Like Peptide-2 (GLP-2)K. Alavi, MD; R. Prasad, MD; J.P. Palazzo,MD; and M. Z. Schwartz, MD, FAAP. Wil-mington, DE

ANTI-TNFa But Not IL-10 Protects MurineNeonates From E.Coli SepsisK.P. Lally, MD; E. Cruz, BS; H. Xue, MD.Houston, TX

Salvage Laparotomy for Failure of Perito-neal Drainage in Necrotizing Enterocolitisin Extremely Low Birth Weight (ELBW)InfantsR.A. Dimmitt, MD, FAAP; A.H. Meier, MD,FAAP; E.D. Skarsgard, MD, FAAP; L.P. Hal-amek, MD, FAAP; B.M. Smith, MD, FAAP;R.L. Moss, MD, FAAP. Stanford, CA

(3) Cognitive Deficits In School-AgedChildren with Severe Short Bowel Syn-drome (SBS)S.R. Beers, Ph.D.; J.A. Yaworski, MSN, RN,CNSN; C. Stilley, PhD, RN; L. Ewing, PhD,

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RN; E.M. Barksdale, Jr, MD, FAAP. Pitts-burgh, PA

Fetal Wound Repair in Interleukin-10 (IL-10) Deficient Mice Results in Scar Forma-tionK.W. Liechty, MD; H.B. Kim, MD; N.S.Adzick, MD, FAAP; T.M. Crombleholme, MD,FAAP. Philadelphia, PA

Proinflammatory Cytokines DifferentiallyRegulate Hyaluronan Synthase Isoformsin Fetal and Adult FibroblastsC.I. Kennedy, MD; R.F. Diegelmann, PhD; J.H.Haynes, MD, FAAP; D.R. Yager, PhD. Rich-mond, VA

(3) Role of Preoperative Chemotherapy inthe Treatment of Infantile FibrosarcomaA.G. Kurkchubasche, MD; E.G. Halvorson,MD; W.S. Ferguson, MD, FAAP; E. Forman,MD, FAAP; Providence, RI

Growth Factor Receptor Tyrosine KinaseInhibition: An Effective Approach toTreatment of Wilms' TumorS. Naraghi, MD; D.W. Vane, MD; S. Khoshy-omn, MD; J.A. DeMattia, MD. Burlington, VT

16q Loss of Heterozygosity and Microsat-ellite Instability in Wilms TumorJ.E. Mason, MD; P.J. Goodfellow, PhD; P.E.Grundy, MD; M.A. Skinner, MD. St. Louis,MO

(3) The Occurrence of Wilms Tumor inHorseshoe Kidneys: A Report from the Na-tional Wilms Tumor Study Group(NWTSG)H. Neville, MD; M. Ritchey, MD, FAAP; R.Shamberger, M.D.; G. Haase, MD; S. Perlman;T. Yoshioka. Houston, TX

11:15 a.m. Presentation of the William Ladd Medal toLester Martin, MD, FAAP

11:30 a.m. Steven L. Gans Distinguished OverseasLectureJose Boix-Ochoa, MD"Congenital Anomalies of the Lung"

12:15- Poster Session and Luncheon2:15 p.m. (Advance registration required for lunch

tickets)Homeobox Gene Expression in CutaneousRabbit WoundsD.A. Lanning, MD; D.R. Yager, PhD; R.F.Diegelmann, PhD; 0. Bogler, PhD; J.H.Haynes, MD, FAAP. Richmond, VA

Pressure Induced Mucosal Growth in Neo-natal Small IntestineA.K. Knight, MD; M.Kanai, MD; T. Sablich,MD; A.W. Flake, MD, FAAP. Philadelphia,PA

Outcome of a Pediatric Congenital Anom-aly in a Rural Environment Compares Fa-vorably to Results in Urban CentersS. Rizvi, MD; R. Vaughan, MD; P. Ehrlich,MD. Morgantown, WV

Diagnosis, Pathology, Staging, Treatment,and Outcome of Epithelial Ovarian Carci-noma in Patients

Mesenteric Hyperperfusion During Hyp-oxia and ECMO in Newborn LambsJ. Lee, MD; B.L. Short, MD, FAAP; J.C. Gilbert,MD,FAAP; G.E. Hartman, MD, FAAP. Wash-ington, DC

GLP-2a Accelerates Recovery of MucosalAbsorptive Function Following IntestinalIschemia/ReperfusionR. Prasad, MD; K. Alavi, MD; M.Z. Schwartz,MD, FAAP. Wilmington, DE

Hepatocyte Nuclear Factor-6 is a NovelTranscriptional Activator in Cholangio-cytes and is Involved in the Bile Duct Pro-liferative Response to Obstructive Jaun-diceA.L. Holterman, MD; R. Costa, PhD. Chicago,IL

Sacral Agenesis: Clinimetric Experienceand OutcomeH.J. Suh, MD; H.P. Koo, MD, FAAP; A.C.Schwartz, RN; C.K. Garwood, RN; D.A. Bloom,MD, FAAP. Seoul, Korea

Mechanism of Cross-Species ProtectionAgainst Bacterial Translocation in Neona-tal Rabbits by Human Breast MilkE.P. Nadler, MD; X. Zhou, Ph.D.; K. Wong; P.Boyle; Y. Chen, MD, Ph.D.; H.R. Ford, MD,FAAP. Pittsburgh, PA

Adrenal Cortical Carcinoma in ChildrenH.L. Neville, MD; K.P. Lally, MD; C.A. Cor-pron, MD; R. Sawin, MD; R.J. Andrassy, MD.Houston, TX

Endothelin-Induced Pulmonary Vasocon-striction After Tracheal Ligation in Ratswith Nitrofen-Induced DiaphragmaticHemiaC.C. Coppola, M.D.; New Haven, CT

Risk Factors and Predictors of Mortality inChildren Following Ejection From MotorVehicle Crashes (MVC)H.R. Ford, MD, FAAP; B.L. Shultz, RN; L.Schall, MS; J. Tan, BA. Pittsburgh, PA

Gene Level of Pulmonary Vasoactive Me-diators During Artificial Ventilation in Ni-trofen Induced Congenital DiaphragmaticHernia in RatsH. Shima, MD; N. Guarino, MD; T. Oue, MD,P. Puri, FRCS. Dublin, Ireland

2:15- Into the Future: Pediatric Surgery in the4:15 p.m. 21st Century

The Scope of Practice in Pediatric Surgery:Past and PresentJames L. Talbert, MD, FAAP

Regional Variations in the Practice of Pe-diatric SurgeryC.D. Smith, MD, FAAP

A 25 year Perspective on the Pediatric Sur-gery WorkforceJames O'Neill, MD, FAAPFOPE II StudyRussell Chesney, MD, FAAP

Jill Josephs, MD, FAAP

Information Technology and the Practiceof Pediatric SurgeryThomas M. Krummel, MD, FAAP

Biotechnology and the Practice of PediatricSurgeryJoseph P. Vacanti, MD, FAAP

The Impact of Change on Initial and Re-current Training of Pediatric SurgeonsArnold G. Coran, MD, FAAP

4:15-5:00 p.m. Discussion

7:00 p.m. 51st Anniversary Reception and Banquet(Advanced registration requiredfor tickets)

SUNDAY, OCTOBER 10, 1999

Section on Surgery7:00 am-5:00 pmRooms 32 & 33, Washington Convention Center

7:00-7:30 a.m. Continental breakfastBreakfast tickets must be purchased through ad-vance registration

7:30-9:00 a.m. Scientific Session #3

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(3) Prenatal Consultation: Role and Per-spective of the Pediatric SurgeonM.T. Downing, MD; D.A. Caniano, MD,FAAP. Columbus, OH

(3) > Prenatal Surgical Consul-tations: Does It Lead to Postnatal Increaseof Surgical Activity?A. Nahom, MD; C. Giolandino, MD; C. Gatti,MD; A. Trucchi, MD; E. Bilancioni, MD; V.Spina, MD; P. Bagolan, MD; A. Coran, MD,FAAP. Roma, Italy

Effect of Prenatal Dexamethasone on FetalIGF-1 ExpressionA. Thakur, MD; M. Sase, MD; J.J. Lee, MD; V.Thakur, M.D.; T.L. Buchmiller, MD. Torrance,CA

Prenatal Dexamethasone Reverses HeartHypoplasia in Fetal Rats with Experimen-tal Diaphragmatic HerniaL. Migliazza, MD; H. Xia, MD; A. Arnaiz; J.I.Alvarez; L.F. Alfonso, MD; A. Valls, MD, PhD;J.A. Diez-Pardo, MD, PhD; J.A. Tovar, MD,PhD. Madrid, Spain(3) Pulmonary Arterioles from Rat Pupswith Nitrofen Induced CDH Do Not Re-spond to Sodium NitroprussideZ. Vukcevic, MD; C. Coppola, MD; J.R. Gosche,MD, PhD, FAAP. New Haven, CTStretch-Induced Upregulation of VegfGene Expression in Neonatal Murine Pul-monary Culture. A Role for Angiogenesisin Lung DevelopmentC.S. Muratore, MD; M.M. Ziegler, MD,FAAP; J.M. Wilson, MD, FAAP. Boston, MA

In Vitro Effects of Growth Factors on LungHypoplasia in a Congenital DiaphragmaticHemia (CDH) ModelE.C. Jesudason, FRCS; D.G. Fernig, PhD; D.ALloyd, FAAP; P.D. Losty, FRCS. Liverpool,UK

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Expected Changes in the Demography ofChildhood Diseases in the US

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Perforated Appendicitis: Prospective Out-come Analysis in 150 ChildrenS.J. Fishman, MD, FAAP; L. Pelosi, RN, MS,PNP; S. Klavon, MSSW; E. O'Rourke, MD.Boston, MA

The Effect of Pediatric Surgical PracticeUpon the Management of Children withAppendicitisE.R. Kokoska, MD; R.K. Minkes, MD; M.L.Silen, MD; J.C. Langer, MD; T.F. Tracy, Jr.,MD; C.L. Snyder, MD; P.A. Dillon, MD; T.R.Weber, MD, FAAP. St. Louis, MO

9:00-10.30 a.m. Scientific Session #4

Laparoscopically-Assisted Anorectoplastyfor High Imperforate Anus-A New Tech-niqueT. Inge, MD, PhD; C.T. Albanese, MD, FAAP;K. Georgeson, MD, FAAP. San Francisco, CA

Cloacal Extrophy: A Unified ManagementPlanS. Soffer, MD; N. Rosen, MD; M. Alexianu,MD; A. Hong, MD, FAAP; A. Penia, MD,FAAP. New Hyde, NY

(3) Evaluation of Enuresis by a PediatricSurgeonP. Brisson, MD; H. Patel, MD; N. Feins, MD,FAAP. Boston, MA

(3) Non-Operative Management of Fistu-la-In-AnoN. Rosen, MD; D. Gibbs, MD; M. Sher MD; S.Soffer, MD; A. Hong, MD, FAAP; A. Penia,MD, FAAP. New Hyde Park, NY

(3) Characterization and Treatment of Bil-iary Anastomotic Stricture After Segmen-tal Liver TransplantD. Schindel, MD; S. Dunn, MD; A. Casas, MD;D. Billmire, MD; C. Vinocur, MD. Philadel-phia, PA

(3) Percutaneous Cannulation for Pediat-ric Venovenous Extracorporeal Life Sup-port (ECLS)D.S. Foley, MD; F. Swaniker, MD; T. Pranikoff,MD; R.H. Bartlett, MD; R.B. Hirschl, MD.FAAP. Ann Arbor, MI

Nonrhabdomyosarcoma Soft Tissue Sar-coma (NRSTS) in Children: Is Age at Di-agnosis an Important Variable?A.Hayes-Jordan, MD; S. Spunt, MD; C. Po-quette, MS; A. Cain, CRA; B. Rao, MD; A.Pappo, MD; S. Shochat, MD, FAAP. Mem-phis, TN

Differentiated Thyroid Cancer: ClinicalCharacteristics, Treatment, and Outcomein Patients Under 21 Years of Age WhoPresent With Distant MetastasesM.P. La Quaglia, MD,FAAP; T. Black, MD,FAAP; G.W. Holcomb, III, MD, FAAP; C.Sklar, MD; G.M. Haase, MD; K.D. Newman,MD, FAAP. New York, NY

Lymphatic Mapping with Sentinel NodeBiopsy in Pediatric PatientsH.L. Neville, MD; R.J. Andrassy, MD, FAAP;K.P. Lally, MD; C.A. Corpron, MD; MI. Ross,

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MD. Houston, TX

(3) Sentinel Lymph Node Biopsy for Mel-anoma in Young ChildrenK.A. Kogut, MD; M. Fleming, MD; A.S. Pappo,MD; K.P. Schropp, MD. Memphis, TN

Scientific Session #5

The Effects of Pre-Biopsy CorticosteroidTreatment on the Diagnosis of MediastinalLymphomaS. Borenstein, MD; T. Gerstle, MD; D. Malkin,MD; P. Thorner, MD; R. Filler, MD, FAAPToronto, Ontario-CANADA

Suppression of Primary Tumor Growth ina Mouse Model of Human NeuroblastomaD. Rowe, MD; J. Huang, MD; K. O'Toole, MD;C. Stolar, MD, FAAP; D. Yamashiro, MD,PhD; J. Kandel, MD, FAAP. New York, NY(3) Endorectal Pull-Through Abates Gas-trointestinal Hemorrhage From ColorectalVenous MalformationsS.J. Fishman, MD, FAAP; R.C. Shamberger,MD, FAAP; V. Fox, MD; P.E. Burrows, MD.Boston, MA

Changing Patterns of Treatment for BluntSplenic Injuries: A 10-Year Experience in aRural StateC. Frumiento, MD; D.W. Vane, MD. Burling-ton, VT

(3) Free Fluid on Abdominal CT AfterBlunt Trauma Does Not Mandate Explor-atory Laparotomy in ChildrenE.A. Beierle, MD; M.K. Chen, MD; T.V.Whalen, MD, FAAP; E.J. Doolin, MD, FAAPCamden, NJ

(3) Is the "Odontoid View" Necessary forClearing the Pediatric Cervical Spine?C. Buhs, MD; M. Cullen, MD; M. Klein, MD;D. Farmer, MD. Detroit, MI

(3) Supplemental Oxygen Improves Reso-lution of Injury-Induced PneumothoraxS.L. Lee, MD; D. Zierold, MD; J.J. DuBois,MD, FAAP. Sacramento, CA

Functional Outcome in Children with Pel-vic FracturesJ. Upperman, MD; M. Gardner, RN; B. Gaines,MD; L. Schall; H. Ford, MD, FAAP. Pitts-burgh, PA

11:45 a.m. Presentation of the Arnold M. SalzbergAward toLouise Schnaufer, MD, FAAP

12:00 noon Overseas GuestAgostino Pierro"The Metabolic Response to Neonatal Sur-gery"

12:45 p.m. Announcement of the Resident and Fac-ulty Prizes

1:00 p.m.- Lunch Symposium (Advance registrationrequired for tickets)

3:00 p.m. "Surgical Techniques: Contrasting Ap-proaches to Difficult Clinical Problems"

Bile Duct Size Does Not Predict Success ofPortoenterostomy for Biliary AtresiaS. Langenburg, MD; M. Goretsky, MD; J. Pou-lik, MD; M. Klein, MD, FAAP. Detroit, MI

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ABSTRACTS

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INTERMEDIATE TERM RESULTS OF THE FREETRACHEAL AUTOGRAFT FOR LONG SEGMENTCONGENITAL TRACHEAL STENOSIS

Backer CL MD FAAP, Mavroudis C MD FAAP, Dunham MEMD, Holinger LD MD FAAP; Children's Memorial Hospital, 2300Children's Plaza m/c 22 Chicago, IL 60614

Since 1996 we have used a new procedure-the free trachealautograft technique-to repair long segment congenital trachealstenosis (LSCTS). The purpose of this review is to examine theintermediate term results of that technique.Between January 1996 and February 1999, 8 infants underwent

repair of LSCTS using a free tracheal autograft. Age ranged from10 days to 12 months (mean age = 5.2 months). The number ofcomplete tracheal rings ranged from 6 to 20 (mean # rings = 15).On cardiopulmonary bypass the trachea was incised anteriorlythrough the area of stenosis. The midportion of the stenotic tra-chea was excised and an end-to-end anastomosis was made pos-teriorly. The excised tracheal segment was trimmed and thensutured in place anteriorly as a free autograft. In 5 patients theautograft was not long enough and the upper portion of thetracheal opening was patched with pericardium.There was one early death 26 days post-op in a 6 month old that

had simultaneous repair of Tetralogy of Fallot and requiredECMO for 7 days post-op for cardiac failure. The other 7 childrenare all alive and well at 2-40 months post-op (mean follow-up =26 months). Two children have tracheostomies at 2 and 32 monthspost-op. All children have had serial postoperative bronchoscopicexams. Current bronchoscopy shows a widely patent tracheallumen in all survivors.

Intermediate term follow-up of children having a free trachealautograft continues to support our use of this technique as theprocedure of choice for infants with long segment congenitaltracheal stenosis.

2CERVICAL REPAIR OF ESOPHAGEAL ATRESIA WITHTRACHEOESOPHAGEAL FISTULA

Ann M. Kosloske, MD, FAAP, and Patrick F. Jewell, MD, FAAP;Texas Tech University Health Sciences Center, Lubbock, TX 79415

Background/Purpose: Although a cervical approach is commonlyused for repair of isolated tracheoesophageal fistula (TEF), thisroute is not considered an option for repair of esophageal atresiawith TEF. The authors report 3 infants in whom both esophagealatresia and TEF were successfully corrected via the cervical ap-proach, without thoracotomy.

Methods: Tracheobronchoscopy was performed prior to repair ofesophageal anomalies. During a 10-year period, the authors encoun-tered 3 infants with the unexpected finding of a cervical TEF associ-ated with esophageal atresia. The level of the TEF was further doc-umented by transillumination and by palpation of the tip of thebronchoscope in the neck. Repair was carried out via a low rightcervical incision, with lateral retraction of the stemocleidomastoidmuscle. The recurrent laryngeal nerve was identified and preserved.The TEF was elevated with traction sutures, and divided. Trachealclosure and esophageal anastomosis were carried out. A strand ofmediastinal tissue was interposed between the two suture lines.

Results: The repair was successfully completed in all 3 cases. Tech-nical difficulties were not encountered. Two of the 3 children re-quired dilatation of a mild postoperative stricture. No recurrentnerve injury occurred. A videotape of the endoscopic diagnosis ofone of our patients will be shown.

Conclusions: Esophageal atresia with cervical TEF may be safelyrepaired through a cervical incision. In selected infants, the cervical

approach may be technically easier than, and preferable to, thoracot-omy. Tracheobronchoscopy is essential for identification of thisanomaly.

3ONE-STAGE SOAVE PROCEDURE FOR HIRSCHSPRUNGDISEASE: A COMPARISON OF THE TRANSANAL VSOPEN APPROACHES

Jacob C. Langer, Michael Seifert, Robert K. MinkesPurpose: We reviewed our experience with the transanal Soave

technique to determine: 1. If it is associated with any advantagesor disadvantages over the standard open approach, and 2.Whether routine laparoscopic visualization is necessary.

Methods: We reviewed 37 consecutive children

Methods: Full thickness bowel specimens were collected at pull-through operation from eight patients diagnosed as having HD.Normal control small and large bowel specimens were collected fromtwelve patients during bladder augmentation operation. Whole-mount preparation was performed on all of the specimens and dou-ble immunostaining using anti c-kit and anti connexin-43 antibodies.The immunolocalization was detected with the help of confocal laserscanning microscopy.

Results: Connexin-43 immunoreactivity appeared in and betweenthe c-kit cells and along the smooth muscle of the normal bowelspecimens and in the ganglionic part ofHD bowel. In the aganglionicpart of the HD there was no expression of connexin-43. In thetransitional zone of HD the connexin43 staining was weak endcolocalized only in the processes of the c-kit positive Cajal cells.

Conclusion: This study demonstrates for the first time that gap-junctional protein connexin-43 is present in the ICC interconnectionsas forming three-dimensional network in the bowel wall. The lack ofexpression of Connexin-43 in the aganglionic part and reduced ex-pression in the transitional zone of HD may explain the motilitydysfunction in HD.

5THE LONG-TERM FOLLOW-UP OF REDO-PULLTHROUGHPROCEDURES FOR HIRSCHSPRUNG'S DISEASE

van Leeuwen K. MD, Teitelbaum DH. MD, FAAP, Coran AG.MD, FAAP; University of Michigan-Mott Children's Hospital,Ann Arbor, MI 48109

Purpose: To review a 25-year experience with redo-pullthroughsfor Hirschsprung's including operative technique and long-termoutcomes.Methods: From 1974 to the present, over 325 patients with

Hirschsprung's have been treated at our hospital. This includes 28patients referred following an unsuccessful pullthrough at anotherhospital. All redo pullthroughs (N=17) were performed in theselatter patients, and their clinical courses were reviewed.

Results: Ten patients required reoperation secondary to a me-chanical problem with their first pullthrough and the other 7patients had evidence of residual segments of aganglionic bowelleading to functional failure of their initial operation. Five of thepatients requiring reoperation initially had a Swenson procedure,5 had an endorectal pullthrough (ERPT), 5 had a Duhamel proce-dure, 1 had a Rehbein procedure, and the remaining patient had apartial colectomy. An ERPT was carried out in any patient inwhom an adequate rectal cuff could be developed (N=6). Addi-tional redo procedures included a Swenson (N=5); a Duhamel(N=2) and other procedures in 4. Follow-up ranges from 6 monthsto 23 years (mean 6.3 years). There were no deaths in the seriesand no patient has required a third pullthrough. All patients overage 3 are continent, except for one child who developed a post-operative perirectal fistula requiring an ileostomy which has yet tobe closed. Stools per day range from 2 to 5 (mean 3.5.)

Conclusion: Redo-pullthrough operations for Hirschsprung'sdisease appear to be as effective as primary procedures in terms ofcontinence and stooling frequency. We found an ERPT to be theprocedure of choice if an adequate rectal cuff was present.

6GDNF SIGNALLING PATHWAY IN INFANTILEHYPERTROPHIC PYLORIC STENOSIS

Nino Guarino MD, Hideki Shima MD, Takaharu Oue MD,Prem Puri FRCS; Children's Research Centre, Our Lady's Hospi-tal for Sick Children, Dublin, Ireland

Purpose: The etiology of infantile pyloric stenosis (IHPS) isunknown. Recently, abnormalities of intramuscular innervationincluding enteric glia have been reported in IHPS. Experimentalmodels have shown that glial derived growth factor (GDNF) andits functional receptor RET are fundamental components of the

migration and survival of neuroblasts in the developing gut. Theearliest GDNF site of production is the mesenchyme and the outersmooth muscle cell (SMC) layer of the developing bowel. Only ata later stage of organogenesis and during adult life GDNF isproduced by the enteric glial cells. A mice GDNF knock-out modelhas shown that the gastric region is a critical passing site betweenGDNF/RET independent neuroblasts (colonizing the esophagus)and GDNF/RET dependent neuroblasts (colonizing the small andlarge bowel). The aim of this study was to analyze the expressionof GDNF and RET in IHPS.

Methods: Full-thickness muscle biopsy specimens were obtainedfrom eight IHPS patients (age range 23 to 41 days) at pyloromyo-tomy and from eight age-matched controls without gastrointesti-nal disease at autopsy performed within 4 hours after death.Indirect immunohistochemistry was performed using ABCmethod with anti-GDNF and anti-RET antibodies. Quantitativeanalysis was performed using sandwich-type ELISA for GDNF.

Results: The results are shown in the table:

GDNF Normal EHPS RET Normal EHPSPylorus Pylorus

Myenteric Plexus ++ + Myenteric ++ ++Plexus

Nerve Fibres ++ - Nerve Fibres ++ -or +SMCs - ++Concentration 5.61 8.38*

(pg/ng of TP)* p < 0.01.

There was lack or marked reduction in the number of GDNF andRET positive nerve fibers in IHPS compared to controls. GDNFwas strongly expressed by the smooth muscle cells of both mus-cular layers in IHPS, no expression was detected in controls. Thequantity of total GDNF in IHPS was significantly higher than incontrols (p

because of uncertainty of the original diagnosis. A Ladd's proce-dure was performed in 111 patients (95%). Twenty-three compli-cations occurred in 21 patients, and included small bowel obstruc-tion (15), prolonged ileus (4), wound infection (2), evisceration (1),and pancreatitis (1). Nine deaths occurred; only one was related toIM with necrotic midgut. Reoperation was required in 11 of 15patients with SBO, on average at POD 49 (range 3-289). Findingsat reoperation included adhesive SBO (7), small bowel intussus-ception (3), and volvulus (2). Preoperative symptoms persisted in16 patients. Ten had persistent vomiting secondary to GER; 3 ofthese required subsequent fundoplication.

Conclusion: A surprisingly high rate of postoperative complica-tions, particularly SBO, in children undergoing Ladd's procedurefor IM was identified. This occurred in the setting of an increasednumber of children with a radiographic diagnosis of malrotation.A prospective study correlating radiographic and operative find-ings is ongoing to better define the indication for operation inchildren with IM.

8SILO DECOMPRESSION FOR ABDOMINALCOMPARTMENT SYNDROME IN THREE CHILDREN

James M. DeCou, MD, Randel S. Abrams, MD, Richard S.Miller, MD, and Michael W.L. Gauderer, MD, FAAP; The Chil-dren's Hospital of Greenville Hospital System, Greenville, SC29605

Purpose: Abdominal Compartment Syndrome (ACS) is definedas a compromise of respiratory, renal, and/or hemodynamic func-tion as a result of an acute increase in intraabdominal pressure.Although well described in adults, little is known about ACS inchildren. We present three children with ACS treated by abdom-inal decompression.

Case Reports: Between April, 1995 and February, 1999, threegirls, ages 4, 5, and 5, were treated by temporary silo decompres-sion for ACS. Each required a massive fluid resuscitation and hadtremendous abdominal distention. The first sustained a thoraco-abdominal crush injury, underwent immediate celiotomy forsplenic avulsion and a liver laceration, and required abdominaldecompression 5 hours post-operatively. The second underwentligation of her bluntly transected inferior vena cava, and due tomassive edema, the abdominal wall could not be closed and thuswas decompressed to prevent ACS. The third presented withshock of unknown etiology and acutely developed ACS with abladder pressure of 26 mm Hg. Respiratory, renal, and hemody-namic function improved markedly in all three patients followingdecompression. Each girl underwent subsequent abdominal wallreconstruction and recovered uneventfully.

Conclusion: ACS is a potentially lethal complication of severetrauma and shock in children. Temporary abdominal decompres-sion led to improved cardiopulmonary and renal function in thesechildren, all of whom survived.

9ROUTINE BEDSIDE INSERTION OF A SILASTIC SPRING-LOADED SILO FOR INFANTS WITH GASTROSCHISIS.

RK Minkes MD, JC Langer MD FAAP, MV Mazziotti MD, MASkinner MD, RP Foglia MD FAAP; Washington University, St.Louis Children's Hospital, St. Louis, MO 63110

Purpose: Emergency closure (EC) of gastroschisis may lead toventilatory compromise and abdominal compartment syndrome.To avoid these complications, we recently began routinely insert-ing a spring-loaded silo (SLS) at the bedside shortly after birth,followed by gradual reduction of the viscera and elective closureseveral days later.

Methods: 43 consecutive neonates with gastroschisis were man-aged between 1993-1998. The first 30 underwent EC and the last13 were treated with SLS.

Results: There were no differences with respect to gestationalage, birth weight, gender, Apgar, matemal age, mode of delivery,or defect size. Median (range) values are presented below.(*Mann-Whitney U, +Chi-square, extb=extubated)

EC (n = 30) SLS (n = 13) pvalue

Length of stay (days) 32(11-244) 25 (17-70) .05*Days on ventilator 6 (1-44) 4 (0-5) .03*Peak airway pressure

(cm H20)Intraoperative 28 (16-36) 21 (18-30) .02*Immediate postop 24(16-35) 22 (extb-30) .04*Postoperative day 1 22 (extb-33) 20 (extb-20) NS*

Time to full feeds 27(7-134) 21 (13-56) .07*(days)

NEC/Perforation 6 0 .06+(# pts)

Ifections (# pts) 13 3 .05+Total hospital dcarges ($) 85,147 71,498 .05*

Complications tended to occur in the patients with the highestairway pressures.

Conclusion: SLS followed by elective repair permits gentle,gradual reduction of the viscera. When compared to EC, SLS isassociated with lower airway pressures, earlier extubation, fewercomplications, decreased length of stay and reduced hospitalcharges.

10FAILURE OF HIGH DOSE INTRAVENOUS IMMUNEGLOBULIN DOES NOT ALWAYS PREDICT RESPONSE OFSUBSEQUENT SPLENECTOMY IN PEDIATRIC PATIENTSWITH IDIOPATHIC THROMBOCYTOPENIC PURPURA

Mark R. Hemmila, MD; David S. Foley, MD; Valerie P. Castle,MD FAAP; Ronald B. Hirschl, MD FAAP

Background: A recent article by Law, et al., (N Engl J Med1997;336:1494-8) concluded that patients with idiopathic thrombo-cytopenic purpura (ITP) who have a poor response to intravenousIgG will not have a good or excellent response to subsequentsurgical splenectomy.

Methods: We retrospectively studied 22 pediatric patients age12 ± 4.7 years with ITP who had been treated with intravenousIgG prior to undergoing splenectomy. As in the article by Law, etal., the responses to the two treatments were classified on the basisof the platelet count as poor (150,000/mm3). For patientswho received multiple IgG treatments, both the initial and finaltreatment responses were analyzed. Data were compared by Fish-er's Exact Test with the good/excellent categories combined.

Results: Platelet count prior to initiation of IgG treatment was28 ± 22.

Initial IgG Treatment

Good/Exc Poor

Response to Good/Exc 14 4Splenectomy Poor 1 3

Final IgG Treatment

Good/Exc Poor

Response to Good/Exc 11 7Splenectomy Poor 1 3

There was a trend toward an improved response to splenectomygiven a good or excellent response to IgG, although it did not

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reach statistical significance (p = 0.077, Fischer's Exact Test). How-ever, in the group with a poor response to IgG, more than 50% ofpatients still had an excellent or good response to splenectomy.

Conclusion: Response to IgG may be predictive of response tosplenectomy. However, a poor response to IgG does not precludea satisfactory response to splenectomy.

11TREATMENT OF INFLAMMATORY BOWEL DISEASE (IBD)WITH THE INTESTINAL GROWTH FACTOR GLUCAGON-LIKE PEPTIDE-2 (GLP-2)

Karim Alavi, MD*, Rajeev Prasad, MD, Juan P. Palazzo, MD,and Marshall Z. Schwartz, MD, FAAP; From the Departments ofSurgery and Pathology at the duPont Hospital for Children, Wil-mington, DE 19803; Thomas Jefferson University Hospital, Phila-delphia, PA 19107; and Washington Hospital Center, Washington,DC 20010*

Purpose: Microinjection of a Fisher (F344) rat zygote with hu-man HLA-B27 and 132-microglobulin genes induces spontaneouschronic gastrointestinal inflammation. Growth factors have beenproposed as treatment for certain intestinal disorders. This studywas designed to evaluate the potential therapeutic benefit ofGLP-2 in this newly developed transgenic rat model of IBD.

Methods: Five F344 (negative control) and 10 HLA-B27 (on aF344 background) rats aged 25 weeks were used. Rats were di-vided into the following 3 groups: Normal F344 rats-no treatment(n=5), HLA-B27-no treatment (n=5), and HLA-B27-treated with a14-day systemic infusion (via the jugular vein) of GLP-2 at 50,ug/kg/d (n=5). Following infusion, all rats underwent laparotomy,and the intestine from the Ligament of Treitz to the rectum washarvested. Total mucosal damage (% surface area) was measuredusing image analysis software (Sigmascan 2.0). Microscopic anal-ysis was performed by a blinded reviewer and scored as follows:0-no inflammation, 1-mild inflammation, 2-moderate inflamma-tion, and 3-severe inflammation. Colonic mucosal total RNA wasassayed for Tumor Necrosis Factor-a (TNF-a), Interferon-y(IFN-,y) and Interleukin-2 (IL-2) mRNA by reverse transcriptase/polymerase chain reaction. RNA levels were quantified usingGlyceraldehyde-3-Phosphate Dehydrogenase (GAPDH) RNA lev-els as a standard. Statistical analysis was performed usingANOVA and expressed as mean±SEM.

Results: ** p < 0.01

Group Mucosal HistologicDamage Lesion Score

(%)F344 0.0 0.6 ± 0.2HLA-B27 9.0 ± 0.7** 7.0 ± 0.6**HLA-B27 + GLP-2 0.9 ± 0.5** 4.2 ± 0.8**

Mean Band Intensity

TNF-a/GAPDH INF-,y/GAPDH IL-2/GAPDH

0.0 0.0 0.00.4 ± 0.04** 0.3 ± 0.02** 0.0

0.0** 0.0** 0.0

Conclusions: These data demonstrate for the first time that GLP-2significantly reduces gross (90% decrease) and histologic (40%decrease) lesions in this rat model of IBD. This is further sup-ported by a significant decrease in gene expression of the inflam-matory mediators TNF-a (100% decrease) and INF-,y (100% de-crease). These data suggest a therapeutic role for GLP-2 in IBD.

12ANTI-TNFa BUT NOT IL-10 PROTECTS MURINENEONATES FROM E. COLI SEPSIS

Kevin P Lally, MD, FAAP; Emmanuel Cruz, BS; Hasen Xue, MD;UT Houston & Hermann Children's Hospital-Houston, TX 77030

The neonate is at much higher risk for septic complications anddeath than the adult. Although some aspects of the infant's im-mune response are immature, others are fully functional. In fact,many models of septic death are due to an overexpression ofpro-inflammatory cytokines. We hypothesized that the high mor-tality rate of the newbom was due to over expression of tumornecrosis factor (TNFa) and that interleukin 10 (IL-10), whichdown-regulates TNFa expression, would attenuate this response.A dose response curve was determined for 1-day-old C3H/HENmice using 105 intraperitoneal E. coli, resulting in a 50 to 70%mortality. This dose caused no ill effect in adult mice. Timedpregnant mice were obtained and one-day-old pups from eachlitter were assigned to a control or treatment group. Four hoursbefore bacterial inoculation, half of each litter received eithersaline or one of two regimens: IL-10 (25mg/pup) or anti-TNFa(20ul/pup). At least 6 litters were used for each regimen. Theanimals were observed for seven days. Data were analyzed usingan unpaired t test. Pretreatment with anti-TNFa resulted in asignificantly improved survival, compared to controls (52% vs.100% p

and underwent "salvage laparotomy" 5-19 days following PPD.Indications included abdominal distention, requirement for vaso-active drugs, and failure of GI function. All four of these patientsdied. None of them were ever weaned from mechanical ventila-tion or tolerated any enteral feedings. These four non-survivingpatients had a mean post-operative hospital stay of 84±20 daysand a hospital cost of $660,000 compared to 34±11 days and$306,000 for the non-surviving PPD patients who did not havesalvage laparotomy.

Conclusions: PPD is often successful as definitive therapy forperforated NEC in ELBW infants. Patients undergoing PPD maymanifest persistent signs of sepsis for 6-10 days following PPD.This is not an indication for laparotomy as most recover fullywithout operation. "Salvage laparotomy" for failure of PPD wasineffective, costly, and only prolonged death. Appropriate selec-tion criteria for PPD versus LAP are not clear and await results ofa prospective study.

14COGNITIVE DEFICITS IN SCHOOL-AGED CHILDRENWITH SEVERE SHORT BOWEL SYNDROME (SBS)

Sue R. Beers, PhD, Jane Anne Yaworski, MSN, RN, CNSN,Carol Stilley, PhD, RN, Linda Ewing, PhD, RN, Edward M.Barksdale, Jr., MD, FAAP; Children's Hospital of Pittsburgh,University of Pittsburgh, Pittsburgh, PA 15213

Background: Improved therapies for managing of SBS have re-sulted in the prolonged survival of many children. By early child-hood, the physiological sequelae of severe SBS include delayedphysical development and metabolic imbalances. However, littleis known about how SBS affects brain development. Althoughmany parents report school problems, no controlled study hasevaluated the integrity of the CNS in SBS children. The purpose ofthis study was to investigate the neuropsychological status ofschool-aged SBS children to determine if there were characteristiccognitive impairments that might be amenable to early therapeu-tic intervention.

Methods: SBS children (n=8; mean age=116.9m±21m) werecompared to an age-matched Cystic Fibrosis (CF) control group(n=8; mean age=118.6±16m). Groups did not differ in age, grade,or school absences. Neuropsychological tests with established sen-sitivity to CNS integrity compared performance over 6 cognitivedomains. Emotional status was also measured. Analyses werecompleted with 2-tailed t-tests.

Results: Groups did not differ in tests of intellectual ability oremotional variables. Sensory-perceptual skills, language, memory,and problem solving testing indicated no significant group differ-ences. However, the SBS group performed significantly morepoorly on measures assessing visual-spatial ability, with p valuesranging from .002 to .045. In a subset of subjects, we noted signif-icantly slower performance on measures of finger dexterity andpsychomotor speed.

Conclusions: Although emotional status did not differ from thatof children with CF, SBS patients demonstrated visual-spatialimpairments in the company of preserved sensory function, lan-guage, attention and memory, and executive skills. The specificityand consistency of these findings suggests that right hemisphereCNS changes may occur in children with SBS. This unexpectedfinding, coupled with the indication of left-sided psychomotorslowing, raises the possibility that actual brain impairment, ratherthan developmental delay accompanying slowed physical growth,accounts for these findings. We speculate that early aggressivenutritional and surgical interventions may improve these deficits.We plan a longitudinal study to further clarify this issue.

15FETAL WOUND REPAIR IN INTERLEUKIN-10 (IL-10)DEFICIENT MICE RESULTS IN SCAR FORMATION

Kenneth W. Liechty, MD, Heung B. Kim, MD, N. Scott Adzick,MD, FAAP, Timothy M. Crombleholme, MD, FAAP.; The Chil-dren's Institute for Surgical Science at The Children's Hospital ofPhiladelphia, 34th Street and Civic Center Boulevard, Philadel-phia, PA, 19104.

Introduction: Fetal dermal wound healing is characterized by aminimal inflammatory response, restoration of normal dermalarchitecture, and scarless repair. We previously showed that theproduction of proinflammatory cytokines interleukin-6 (IL-6) andinterleukin-8 (IL-8) are diminished in fetal wound repair. IL-10 isan anti-inflammatory cytokine that deactivates macrophages, de-creasing production of IL-6 and IL-8. We hypothesized that thediminished IL-6 and IL-8 levels, and minimal inflammation seenin scarless fetal dermal wound repair may be due to increasedproduction of IL-10. To test this hypothesis, we developed a newmodel of fetal wound repair in normal and IL-10 "knockout" mice.

Methods: Fifteen day gestation fetal mouse skin was obtainedfrom either normal C57BL/6 mice or transgenic C57BL/6 mice inwhich the IL-10 gene has been "knocked out". The skin wasgrafted to the back of the same strain adult mice. After 1 week thegrafts were incisionally wounded and marked with India ink.Grafts were harvested at 1 week and histochemically analyzed forscar using Masson's Trichrome stain.

Results: At one week, the normal C57BL/6 fetal skin woundsdemonstrated minimal inflammation and the normal dermal re-ticular collagen pattem at the site of the wound, consistent withscarless repair. In contrast, the wounds in the C57BL/6 IL-10knockout fetal skin healed with significant inflammation and ab-normal collagen deposition at the site of the wound., consistentwith scar formation.

Conclusion: In a new murine model of fetal wound healing, fetalskin on adult syngeneic mice heals without scar, suggesting scar-less repair is intrinsic to fetal skin. The absence of IL-10 in fetalskin results in scar formation. Intrinsic lack of IL-10 in dermaltissue may permit continued amplification of the proinflammatorycytokine cascade, resulting in continued stimulation of fibroblastsin the wound, and abnormal collagen deposition. IL-10 is neces-sary for scarless wound repair to occur in normal fetal skin.

16PROINFLAMMATORY CYTOKINES DIFFERENTIALLYREGULATE HYALURONAN SYNTHASE ISOFORMS INFETAL AND ADULT FIBROBLASTS

Colleen I. Kennedy, MD; Robert F. Diegelmann, PhD.; Jeffrey H.Haynes, MD, FAAP; and Dome R. Yager, PhD.; Virginia Com-monwealth University, Richmond, VA 23298

Introduction: Fetal wound healing is a relatively scarless processthat occurs in an environment rich in hyaluronan (HA). Thisglycosaminoglycan is believed to facilitate cell movement duringperiods of rapid growth, repair and regeneration. Understandingthe regulation of the production of HA may provide insight intothe process of fetal wound healing. Three separate hyaluronansynthases (HAS) that are capable of synthesizing HA in humanshave been identified. The purpose of this study was to examinethe regulation of these enzymes and HA by the proinflammatorycytokines interleukin-l,B (IL-1g3) and tumor necrosis factor-a(TNF-a) in human adult and fetal dermal fibroblasts.

Methods: Quiescent low passage human fetal fibroblasts (gesta-tional age-50-80 days, 2 cell lines-n=8) and adult dermal fibro-blasts (6 cell lines, n=23) were exposed to IL-1,B (100 pM), TNF-a(1.2 nM), or medium alone (control). Cells and medium wereharvested at 24 hours. l215 I-HA binding protein was used todetermine the HA levels accumulated. RNA was extracted and

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ribonuclease protection assays used to quantitate transcript levelsof HAS-1, HAS-2 and HAS-3 relative to GAPDH. Results werecompared using analysis of variance.

Results: At baseline, HAS-1 was not detectable in either cell line.In contrast, both fetal and adult cells expressed HAS-2 and HAS-3constitutively. There is an upregulation of HAS-1 and HAS-3mRNA transcript production in response to proinflammatory cy-tokines that is different between treatment groups as well as celltype (p50 cells) in controls.

Results: Genistein at 25 and 50 ,uM inhibited the tumorgenicityof G-401 by 37% and 79% (P=0.01 & 5E-06, two-tailed t test,respectively) and that of SK-NEP-1 by 44% and 74% (P=0.0001 &9.9E-07). The mean % growth inhibition was 57 ± 7.9% and 96 ±0.2% for G-401, and 47 ± 11.2% and 60 ± 2.7% for SK-NEP-1.AG1478 at 1000 and 5000 rqM inhibited tumorigenicity of G401 by75% and 78% (P=0.0005 & 7.38E-06 respectively) and that ofSK-NEP-1 by 19% and 40% (P=0.02 & 0.0001). The % growthinhibitions for G-401 were 53 ± 9.3% and 63 ± 6.3%, and forSK-NEP-1, 55 ± 14.5% and 65 ± 20.1% respectively.

Conclusion: Considering the growth factor receptor activity inWilms' tumor, inhibition of GFR-TKs should be investigated aseffective and potentially non-toxic treatment.

1916Q LOSS OF HETEROZYGOSITY AND MICROSATELLITEINSTABILITY IN WILMS TUMOR

Mason JE, Goodfellow PJ, Grundy PE, Skinner MAIntroduction: Wilms tumor is the most common renal malig-

nancy of childhood. Loss of heterozygosity (LOH) at 16q in Wilmstumor has been found in about 17% of cases and has been asso-ciated with a poor prognosis. To more precisely define the patternof deletion at 16q exhibited by Wilms tumor, we performed adetailed LOH analysis of 96 paired specimens of normal andtumor DNA using highly polymorphic microsatellite repeat mark-ers to assess allelic loss. We also evaluated the neoplasms for thepresence of microsatellite instability (MSI).

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Methods: 96 DNA samples were acquired from the NationalWilms Tumor Study Group. Tumor specimens were of uniformlyhigh neoplastic cellularity. Polymerase chain reaction-based LOHanalyses were performed by amplification of polymorphic micro-satellite repeats. For these studies, we used 6 PCR-amplified sim-ple sequence repeat markers spanning the long arm of chromo-some 16 and one 16p marker. Additionally, we used another tenmarkers to finely map particular regions of interest. The geneticmarkers BAT-26 and MLH-1 Exon 12 were also used to screen forMSI.

Results: We found unequivocal 16q LOH for at least onemarker in 14 of 96 specimens evaluated. In most cases there wasloss of at least the entire chromosomal arm. However, in onespecimen there was a complex pattern of allelic loss with twoareas of deletion flanking a retained segment. This specimenrevealed deletion in the 16ql2-q2l region and in a more distalarea at 16q23.2-q24.2. The distal region of deletion is very small,estimated to be approximately 2.0 megabases. In addition to theobserved LOH, two specimens were found to consistently ex-hibit MSI. MSI has not previously been reported in Wilmstumor. This pattern was noted in at least eight markers for eachspecimen.

Conclusions: We conclude that 16q LOH is a moderately fre-quent event in Wilms tumor and suggests the presence of atumor suppressor gene on the long arm of chromosome 16. Thesmallest consensus region of deletion at 16q23.2-q24.2 measures2.0 megabases. Additionally, MSI was present in a subset oftumor specimens suggesting that defects in DNA mismatchrepair may contribute to the pathogenesis of Wilms tumor.SPONSOR: Jacob C. Langer, M.D., Washington University

School of Medicine, Division of Pediatric Surgery, 660 S. EuclidAve., Box 8235, St. Louis, MO 63110. Tel (314) 454-6022, fax(314) 454-24421angerj@msnotes.wustl.eduPRESENTER: John E. Mason M.D., Washington University

School of Medicine, Department of Surgery, 660 S. Euclid Ave.,Box 8109, St. Louis, MO 63110. Tel (314) 362-2003, fax (314)362-8620, masonj@msnotes.wustl.edu

Paul J. Goodfellow, Ph.D., Washington University School ofMedicine, Department of Surgery, 660 S. Euclid Ave., Box 8109,St. Louis, MO 63110. Tel (314) 362-8106, fax (314) 362-8620,goodfellowp@msnotes.wustl.edu

Paul E. Grundy, M.D., Molecular Oncology Program, CrossCancer Institute, 11560 University Ave., Edmonton, Alberta,CA T6G 1Z2Michael A. Skinner, M.D., Duke University School of Medi-

cine, Division of Pediatric Surgery, PO Box 3815, Durham NC,27710. Tel (919) 681-5077, skinnO09@mc.duke.edu

20THE OCCURRENCE OF WILMS TUMOR IN HORSESHOEKIDNEYS: A REPORT FROM THE NATIONAL WILMSTUMOR STUDY GROUP (NWTSG)

Holly Neville, Michael Ritchey, Robert Shamberger, GeraldHaase, Sharon Perlman, Teri Yoshioka; University ofTexas-Houston Medical School Houston, TX 77030

Purpose: An increased incidence of Wilms tumor (WT) has beennoted in patients (pts) with a horseshoe kidney (HSK). These ptsrepresent a difficult diagnostic and therapeutic challenge. Thecharts of all NWTSG pts with WT occurring in aHSK were re-viewed. We report the diagnostic evaluation, surgical treatmentand outcome.

Methods: From 1969 to 1998, 8617 pts were enrolled in theNWTSG. The charts of all pts found to have WT arising in a HSKwere retrospectively reviewed.

Results: We identified 28 pts with tumor arising in a HSK. HSKwas not recognized preoperatively in 12 pts, 5 of whom hadpreoperative computed tomography (CT) alone, 5 had CT and US,

1 had CT and IVP and 1 had no preoperative imaging. WT wasdiagnosed preoperatively in 25 pts and intraoperatively in 3 pts, 2of whom had preoperative CT and 1 had no preoperative imaging.Stage at presentation was: stage 1-8 pts; stage 11-6; stage 111-8;stage IV-6. Primary surgical resection was performed in 17 pts (14nephrectomies, 3 partial nephrectomies). Eleven pts were treatedwith biopsy and preoperative chemotherapy. After all operations(excluding treatment of relapses), the mean total remaining renalparenchyma was approximately 75%. The collecting system wasentered and repaired in 7 pts. There were 7 surgical complicationsin 3 pts, including 2 small bowel obstructions, and one each:enterocutaneous fistula, urine leak, ureteral injury, wound dehis-cence and incisional hemia. Two pts developed transient renalfailure.

Conclusion: Wilms tumor in a HSK was seen in 0.32% of thepatients registered with the NWTSG. The diagnosis of HSK wasoften missed on preoperative imaging. Accurate preoperative di-agnosis may help reduce complications unique to the surgicalmanagement of the HSK. Specific complications related to tran-section of the calyceal system and division of the isthmus werefortunately uncommon.

21PRENATAL CONSULTATION: ROLE AND PERSPECTIVEOF THE PEDIATRIC SURGEON.

MT Downing, M.D., DA Caniano, M.D., F.A.A.P.; Ohio StateUniversity and Children's Hospital, Columbus, Ohio 43205

INTRODUCTION: This study assesses the role of pediatricsurgeons in the counseling of prospective parents whose fetus hasa major congenital anomaly.METHODS: A survey of 40 multiple-choice questions was

mailed to 479 North American pediatric surgeons. Factors evalu-ated included individual demographics, frequency and type ofconsults, educational background, approach to sessions, and bill-ing for services. Specific cases queried recommendations for tim-ing, type, and location of delivery, referral to high-risk and/orprenatal surgery centers, and advice about termination of preg-nancy for selected indications. Statistical analysis used the Chi-square test with significance at a p-value < 0.05.RESULTS: An 82% response rate demonstrated that academic

surgeons (51%) participated in more than 8 consults annually(p

22vREAL TIME>> PRENATAL SURGICAL CONSULTATIONS:DOES IT LEAD TO POSTNATAL INCREASE OF SURGICALACTIVITY?

A. Nahom MD, C. Giolandino* MD, C. Gatti MD, A. TrucchiMD, E. Bilancioni* MD, V. Spina* MD, P. Bagolan MD and A.Coran MD, FAAP.; Neonatal Surgery Unit-Bambino Gesii Chil-dren's Hospital-Artemisia Center*-00165-Roma-Italy

Objective The importance of prenatal pediatric surgical consul-tation has been recently emphasized. The impact of prenatal sur-gical consultations on the activity of a neonatal surgery unit andthe capacity of tertiary prenatal ultrasound centers to detect falsepositives diagnosed by primary centers were investigated.Methods Review of a seven year experience at a prenatal diag-

nosis center separate from our hospital. All women with sus-pected fetal anomalies were scanned at least three times duringpregnancy. Those anomalies assumed to be surgically correctable(except cardiac, urorenal and neurological ones) promptedmonthly consultations at the center. All consultations were ) ones, done onsite, together with a sonogram. The relation-ship between prenatal consultations and surgical activity wasanalyzed.

Results During the period 1992-1998, 4,123 scans were per-formed. Suspected anomalies were confirmed in 3120 fetuses (sen-sibility 75.6%, specificity 99.5%, false positive rate 24.3%). Of these,523 fetuses were referred for surgical consultation (1554 surgicalconsultations). Anomalies included: thorax 24.17% (sequestration,CDH,CCAM, esophageal atresia, pleural effusion); abdomen49.31% (cysts, intestinal atresia, echogenic bowel, calcifications);abdominal wall defects 9.16% (omphalocele, gastroschisis); tu-mors 8.79% (lymphangioma, teratoma, neuroblastoma); other de-fects 8.57%. Amniocentesis was performed in 89% cases. Fetalintervention was required in 12% (ovarian cysts > 4.5 cm andpleural effusions). Pregnancy was terminated in 7.1% cases(omphalocele and lymphangioma).Timing and mode of deliverywere planned in all cases. A steady increase in major anomaliesantenatally diagnosed and treated in our unit was observed. Werecorded a +371,6% increase in prenatal consultations and +415%increase in operation rate notwithstanding the natality decrease.Conclusion consultations increases the activity of neo-natal surgery referral centers. Prenatal ultrasound evaluations at atertiary center detects a considerable percentage of false positivesgenerated in primary centers.

23EFFECT OF PRENATAL DEXAMETHASONE ON FETALIGF-1 EXPRESSION

A. Thakur, MD, M. Sase, MD, JJ Lee, MD, V Thakur, MD, TLBuchmiller, MD; Division of Pediatric Surgery, UCLA MedicalCenter. Torrance, CA 90509.

Prenatal dexamethasone increases intestinal disaccharidase en-zyme activity and functional uptake in a rabbit model of intra-uterine growth retardation (IUGR), but the molecular signals pre-ceding this are unknown. Insulin-like growth factor-i (IGF-1), apotent mitogen for developing fetal tissues, is lowered in theserum of human IUGR infants. To determine if IGF-1 expression isincreased in vivo in response to maternal prenatal steroid admin-istration, a naturally occurring rabbit model of IUGR was used.

Eight pregnant rabbits received either IM dexamethasone (Dex),.1 mg/kg/day, or normal saline (Cont) on days 26 and 27 of a31-day gestation. Fetuses were harvested on gestational day 28 or29 and were identified based on uterine position, as favored (Fav)or runt (Runt) generating four groups: Dex Fav, Dex Runt, ContFav, and Cont Runt. Fetal weights were recorded and serum,amniotic fluid, liver, kidney, proximal, middle, and distal smallintestine (SI) were collected. Reverse transcription-polymerase

chain reaction (RT-PCR) was performed to determine IGF-1/beta-actin mRNA densitometric band ratios in all tissues. Radioimmu-noassay (RIA) was done to determine IGF-1 protein levels inserum and amniotic fluid. Statistical analysis was performed usingANOVA and the paired Student's t-test.Weight was decreased in the growth-retarded fetuses at all time

points (p

25PULMONARY ARTERIOLES FROM RAT PUPS WITHNITROFEN INDUCED CDH DO NOT RESPOND TOSODIUM NITROPRUSSIDE

Z. Vukcevic MD, C Coppola MD, JR Gosche MD PhD FAAP;Yale University, New Haven, CT 06520

Background: Inhaled nitric oxide is an effective treatment formany forms of pulmonary hypertension in the newbom. Re-sponses to nitric oxide in infants with CDH have been inconsis-tent. We examined the vasodilator responses to a nitric oxidedonor, sodium nitroprusside (SNP), in third generation pulmo-nary arterioles from rats with nitrofen induced CDH.

Methods: Right sided CDHs were induced in fetal rats by feedingnitrofen (75 mg) to timed-pregnant rats on day 12 of gestation.Control rat fetuses were not pretreated. Newborn rats deliveredspontaneously and were allowed to breathe room air. Rat pupswere anesthetized at 3-12 hours of life. A 3rd generation pulmo-nary arteriole was isolated, cannulated and distended at a con-stant pressure that resulted in maximal responses to K+ inducedvasoconstriction. Vasodilator responses of K+ preconstricted arte-rioles were examined to increasing concentrations (10-15 to 10-3 M)of sodium nitroprusside.

Results: Control pulmonary arterioles (n=9) exhibited dose de-pendent vasodilation to sodium nitroprusside. In contrast, thearterioles from rats with nitrofen induced CDH (n=8) did notdilate. Differences between groups were statistically significant(p

Results: Over 120 fetal lung specimens were studied (n 2 4 pergroup). Significant increases in area, perimeter and bud countwere seen in normal lungs cultured with FGF1 + HEP comparedto control media (p

onto the perineum through the trocar. The anastomosis betweenrectum and anus is completed with absorbable sutures. The rec-tum is retracted laparoscopically and secured to the presacralfascia with two or three non-absorbable sutures. This fixed retrac-tion deepens the anal dimple and lengthens the skin-lined analcanal.

This strategy was used as a primary procedure in 3 newborninfants while 5 patients have been 2-12 months of age. In threepatients, diverting colostomy was not required after anorecto-plasty. Laparoscopic mobilization has been possible on all casesattempted. All of the patients have a brisk & symmetric anal winkwith perineal stimulation. Limited follow-up precludes accurateassessment of ultimate anorectal function.

31CLOACAL EXTROPHY: A UNIFIED MANAGEMENT PLAN

Samuel Soffer MD, Nelson Rosen MD, Mihai Alexianu MD,Andrew Hong, MD, FAAP, Alberto Pefia, MD, FAAP; SchneiderChildren's Hospital, New Hyde Park, NY 11040

Purpose: It is a common belief that patients with cloacal extro-phy have a short and therefore useless colon. In addition, thecolon is sometimes used for urinary or vaginal reconstruction, andthe possibility of a pullthrough is lost. In our experience with 25patients, the use of a unified management plan allowed mostpatients to undergo pullthrough and avoid a permanent stoma.

Methods: In all patients, bladder closure, omphalocele repair,and creation of a colostomy were performed at birth. An attemptto incorporate all available colon, no matter how small, was made.After at least one year, patients were assessed for the ability toform solid stool through their stoma. Normal colonic length, ca-pacity to form solid stool, or response to a bowel managementregimen through the stoma were considered indications for pull-through. The genitourinary reconstruction was contingent uponthe colorectal plan.

Results: Information on colonic length is available for 21 of the25 patients. Lengths ranged from normal in 12 pts, 40-70 cm in 3pts, 10-30 cm in 4 pts and

with an obvious male predominance. There are no reports ofexpanding cellulitis or toxemia due to conservative managementof perianal abscess or fistula in healthy infants.

34CHARACTERIZATION AND TREATMENT OF BILIARYANASTOMOTIC STRICTURE AFTER SEGMENTAL LIVERTRANSPLANT

David Schindel, M.D., Stephen Dunn, M.D., Adela Casas, M.D.,Deborah Billmire, M.D., Charles Vinocur, M.D.; St. Christo-pher's Hospital for Children, Erie Avenue at Front Street, Phila-delphia, PA 19134

Purpose: Biliary anastomotic strictures (BAS) following left lat-eral segment liver transplantation (LLST) may cause graft dys-function, sepsis and patient mortality. A review of our experiencewas performed to better characterize the risk factors and correc-tive management.Methods: The medical records of 9 children having received a

LLST who developed a BAS from 1989 to the present were retro-spectively reviewed.

Results: 75 of 199 liver transplants (38%) at our institution since1989 have been LLST. 4 boys and 5 girls (mean age at transplant=8.7 mos; range 6-15 mos) developed BAS (12% of patients). Theetiology of primary liver disease included biliary atresia (8) andtyrosinemia (1). BAS were diagnosed 12 mos in 5 children (mean=37 mos; range=14-72 mos). 5 chil-dren received living-related donor organs and 4 received cadav-eric grafts. Early strictures (

Age Group *Synovial sarcoma Peripheral Nerve sheath

'1 year>1-'5 years>5-'10 years>10-'15 years>15 yearsTOTALS

0 (O"t)4 (90,,)12 (26"',.)15 (330,o)15 (33%)46

1 (3%)3(10°/.)3 (10"'/)12 (41",)10 (34%')29

*MFH *Fibrosarcoma/Infantile fibrosarcoma *ASPS

1 (5°/,)2 (10",)10 (480/,,)6 (29%o)2 (10°/0)

21

6 (38°/.)3 (19'")4 (25"t,)3 (19")0 (0"S,)

16

0 (0"N')2 (150,,)5 (38"%)3 (23"N)3 (23")

13* Most prevalent histologies. (MFH = malignant fibrohistiocy-toma; ASPS = alveolar soft part sarcoma).

37DIFFERENTIATED THYROID CANCER: CLINICALCHARACTERISTICS, TREATMENT, AND OUTCOME INPATIENTS UNDER 21 YEARS OF AGE WHO PRESENTWITH DISTANT METASTASES

Michael P. La Quaglia M.D. FAAP, Thomas Black, M.D. FAAP,George W. Holcomb, III M.D FAAP, Charles Sklar, M.D, GeraldM. Haase, M.D, Kurt D. Newman, M.D. FAAP

Puirpose: Young patients with differentiated thyroid cancer typi-cally present with regional lymph node involvement (60-80'%) and10-20"%.. have distant metastases. This study characterizes the clin-ical presentation, treatment, and outcome in patients who presentwith distant metastases.

Methlods: A retrospective, multi-institutional database databaseof 327 patients in this age group with differentiated thyroid car-cinoma contained 83 (25%) with distant metastases. The medianfollow-up was 7.6 years.

Resullts: The median age at diagnosis was 14.6 years. A history ofprior head and neck irradiation was obtained in 12"%. Regionallymph nodes were positive in 90% and extrathyroidal extensionoccurred in 480,). The site of distant metastases included the lungsin all patients but some also had extension to mediastinal lymphnodes. Total thyroidectomy, subtotal thyroidectomy, lobectomy,and nodule excision was done in 66, 24, 3, and 8 percent of patientsrespectively. There was no residual cervical disease after surgeryin 750) while 14%. had microscopic and 11°/o had gross residual.Histopathologic subtypes included: papillary-follicular (48%)), fol-licular (10%), and papillary (42%). The median tumor size was 3.0cm. 100% of patients received adjuvant 1311 therapy and the overallsurvival at 10 years was 100%. The progression free survival was76" at five years and 66%/ at 10 years from diagnosis.

Couiclutsionis: A significant percentage of these patients presentwith distant metastases that will require radioiodine therapy. Thisshould be considered when planning the operative approach sincetotal or subtotal thyroidectomy facilitates '13I imaging and treat-ment. Although about one-third will relapse or develop diseaseprogression, the overall mortality is low.

38LYMPHATIC MAPPING WITH SENTINEL NODE BIOPSYIN PEDIATRIC PATIENTS

Holly L. Neville, M.D.; Richard J. Andrassy, M.D.*; Kevin P.Lally*, M.D.; Cyndy A. Corpron, M.D.; Merrick I. Ross, M.D.;University of Texas-M.D. Anderson Cancer Center and HermannChildren's Hospital Houston, TX 77030

Initrodiuctioni: Lymphatic mapping with sentinel node biopsy iswidely used in adult melanoma and breast cancer to determine

nodal status without the morbidity associated with elective lymphnode dissection. This technique can be used in children to deter-mine lymph node status with limited dissection and accurateinterpretation. Our initial experience is reported.

Metliods: The charts of patients who underwent lymphatic map-ping with sentinel node biopsy were retrospectively reviewed.Lymphoscintigraphy was performed in patients with truncal le-sions 24 hours preoperatively. The tumors were injected one hourpreoperatively with Technetium sulfur colloid and in the operat-ing room with Lymphazurin blue. The draining basin was exam-ined using a radioisotope detector. The blue nodes with highcounts were localized and removed. If nodal metastases wereidentified, lymph node dissection was recommended. Early in ourexperience, two patients were injected only with Lymphazurinblue.

Resuilts: Eleven children (5 males; mean age 8.3 years) under-went lymphatic mapping with sentinel node biopsy. The tumortypes were as follows: 8 malignant melanoma (6 extremity, 2truncal), 1 malignant peripheral nerve sheath tumor, 1 alveolarsoft part sarcoma, and 1 rhabdomyosarcoma. A mean of 2.4 nodes(range 1-6) was removed from each patient. Five patients had apositive sentinel node. Formal lymph node dissection was per-formed on 4 of the 5 patients, one of whom had further nodaldisease (2/13 nodes contained disease). Pulmonary metastasisdeveloped 26 months after diagnosis in a patient with alveolar softpart sarcoma and a negative sentinel node. This patient wasinjected only with Lymphazurin blue at the time of sentinel nodebiopsy and refused adjuvant therapy. There were no complica-tions related to lymphatic mapping or sentinel node biopsy.

Coniclutsionz: Lymphatic mapping with sentinel node biopsy, us-ing both technetium labeled sulfur colloid and Lymphazurin blue,can be performed safely in pediatric skin and soft tissue malig-nancies. Further study with long-term follow-up will determinethe utility and accuracy of this technique in pediatric malignan-cies.

39SENTINEL LYMPH NODE BIOPSY FOR MELANOMA INYOUNG CHILDREN

KA Kogut, MD, M Fleming, MD, AS Pappo, MD, KP Schropp,MD; St. Jude Children's Research Hospital and LeBonheur Chil-dren's Medical Center, University of Tennessee, Memphis, Mem-phis, TN 38105

Introductioni: Interferon-alpha-2b has been shown to increasesurvival in lymph node positive melanoma patients in whomdisease has been surgically removed. Lymphoscintigraphy andsentinel lymph node biopsy offer minimally invasive means todetermine lymph node status and are becoming the standard ofcare in adult and adolescent patients. In young children, palpablecervical adenopathy is common and does not necessarily indicatenodal disease. We report two cases of head and neck melanoma inyoung children in whom these techniques were successful inmapping lymphatic drainage and detecting nodal disease.

Metliods: The patients are a 30 month old male with a 6mm thickmelanoma located in the midline between the eyebrows and a 7year old male with a 3.5 mm thick melanoma located behind theleft ear. Both children had bilateral palpable anterior and posteriorcervical lymph nodes. Preoperative lymphoscintigraphy was usedto locate drainage basins for the primary cutaneous sites. Sentinellymph nodes were identified using both technetium-labeled sulfurcolloid and lymphazurin blue dye and were submitted for routinehistology and HMB-45 immunohistochemical staining. The pri-mary sites were re-excised to obtain adequate margins.

Resuilts: In the child with the midline facial lesion, no drain-age basin or sentinel node was identified on the right side, andbiopsy of a 2 cm right cervical node identified on CT scan wasnegative for melanoma. Lymphatic drainage was localized tothe left parotid and submandibular areas, and one sentinel node

778 SUPPLEMENT

was identified in each basin. Both sentinel nodes containedmicrometastatic disease. Left complete neck dissection and su-perficial parotidectomy were performed, and no additionalnodal disease was identified. In the child with the lesion behindthe left ear, a sentinel node was found in the left superiorcervical area and in the left posterior auricular area. Both werefound to harbor micrometastatic disease. Left complete neckdissection found one additional level II cervical node contain-ing 10-20 melanoma cells. Both children are receiving interfer-on-alpha-2b adjuvant therapy.

Conclusions: Lymphoscintigraphy and sentinel lymph nodebiopsy techniques can be successfully used in very young chil-dren with melanoma of the head and neck to detect nodaldisease. These results can be used to guide further surgical andadjuvant therapy.

40THE EFFECTS OF PRE-BIOPSY CORTICOSTEROIDTREATMENT ON THE DIAGNOSIS OF MEDIASTINALLYMPHOMA

Steven Borenstein MD', Ted Gerstle MD', David Malkin MD2,Paul Thorner MD3, and Robert Filler MD, FAAP1; 'Departmentsof General Surgery, 2Hematology/Oncology and 3Pathology, TheHospital For Sick Children, Toronto, Ontario M5G 1X8

Purpose: For children with probable mediastinal lymphoma andhigh risk of cardiorespiratory morbidity, many centers recom-mend that the diagnostic biopsy be delayed for 24-48 hours whilecorticosteroids are administered to reduce tumor size and mor-bidity. This study was undertaken to determine the effect ofpre-operative steroid use on the accuracy of the pathologic diag-nosis and incidence of peri-operative cardiorespiratory morbidity.

Methods: From 1988 to 1998, 86 children were treated for medi-astinal lymphoma. 23 received steroid prior to biopsy (studygroup) and the remaining 63 served as controls. Clinical parame-ters, steroid use, and detailed pathologic studies obtained at initialand subsequent biopsies were reviewed. Steroid treatment wasconsidered to have an adverse effect on the pathologic diagnosis if(1) definitive diagnosis was delayed more that 1 month, (2) defin-itive diagnosis could not be made or (3) the extent of disease couldnot be staged with certainty.

Results: Steroid treatment had an adverse effect on the patho-logic diagnosis in 5 of 23 (22%; 95% confidence interval, 7-44%)children: 1 diagnostic delay, 3 failures of a definitive diagnoses,and 1 failure of staging. A definitive diagnosis was made in allcontrol patients. Perioperative survival was 100% in both groups.At biopsy, only 3 children in the steroid treatment group and 2children in the control group had moderate, non-fatal cardiorespi-ratory instability. Parameters of steroid use among children whohad inaccurate pathologic diagnoses or cardiorespiratory morbid-ity were not significantly different from those who did not.

Steroid Use Pathologic Diagnosis

Inaccurate Accurate *P value

Dose 15.4 ± 7 12.5 ± 9 0.38Duration (hr) 31.4 ± 9 28.1 ± 10 0.50

Steroid Use Cardiorespiratory Morbidity

Present Absent *P value

Dose 12.6 ± 3 14.3 ± 10 0.56Duration (hr) 27.3 ± 13 31.1 ± 9 0.66

Dose is mg hydrocortisone equivalents/kg, * Student's t test.

Conclusions: Pre-biopsy steroids will adversely affect the patho-logic accuracy of the later biopsy in some cases. The dose and

duration of steroid use was not related to outcome. The use ofsteroids decreases the risks of cardiorespiratory morbidity in highrisk patients.

41SUPPRESSION OF PRIMARY TUMOR GROWTH IN AMOUSE MODEL OF HUMAN NEUROBLASTOMA.

Rowe, D, MD; Huang, J, MD; O'Toole, K, MD; Stolar, C, MD,FAAP; Yamashiro, D, MD PhD, Kandel, J, MD FAAP; ColumbiaUniversity, New York, NY.

Introduction: Neuroblastoma is the most common tumor of theabdomen in childhood. There is still no consistently effectivetreatment for children with aggressive disease. We have previ-ously reported a novel model of human neuroblastoma in thenude mouse, in which pattems of primary growth and metastasesresemble those seen in children with this disease. Vascular Endo-thelial Growth Factor (VEGF), a well-characterized angiogenicpromoter, is expressed at high levels by these experimental tu-mors. Since anti-VEGF strategies were highly effective in a similarexperimental model of Wilms tumor, we hypothesized that treat-ment with neutralizing antibodies to VEGF would have a similareffect in this model on 1) primary tumor growth and 2) distantmetastasis.

Methods: Tumors were induced in the right kidneys of nudemice (n=28) by injection of 106 cultured SY5Y neuroblastoma cells.After 1 week, treatment was begun with either vehicle (n=14) or100 mcg of monoclonal anti-VEGF antibody (n= 14) injected 2x perweek intraperitoneally. At 6 weeks animals were sacrificed andorgans were harvested. Tumor weights were compared by Stu-dent's T-test and metastases by chi square analysis.

Results: No ill effects were observed from the treatment.Grossly, tumors in the control group were bulky, with ectaticvessels crossing the surface of the tumor and intraparenchymaland intraperitoneal hemorrhage. In contrast, tumors in treatedanimals were significantly smaller than those seen in controls. Inaddition, they did not demonstrate hemorrhage and displayedless surface neovascularity than controls. There was a 65% reduc-tion in tumor weight in the treated group (p < .04). 5/14 liver and1/14 lung metastases were detected in controls, compared to 3/14liver and 3/14 lung metastases in the treated group (no significantdifference).

Conclusions: Treatment with specific anti-VEGF antibody signif-icantly reduces tumor size in our mouse model of intraabdominalneuroblastoma, although not to the same extent seen in a similarmodel of Wilms tumor. Interestingly, anti-VEGF treatment doesnot appear to affect the establishment of distant metastases in thismodel. Treated tumors qualitatively exhibit fewer features ofpathologic angiogenesis than control tumors. This suggests thatwhile VEGF plays a role in tumor growth in neuroblastoma, othergrowth factors and promoters mediate angiogenesis and metasta-sis in this tumor system. Nonetheless, anti-VEGF therapy mayprove a useful addition to the current agents available for thetreatment of neuroblastoma.

42ENDORECTAL PULL-THROUGH ABATESGASTROINTESTINAL HEMORRHAGE FROMCOLORECTAL VENOUS MALFORMATIONS.

SJ Fishman MD, FAAP; RC Shamberger MD, FAAP; V Fox MD,PE Burrows MD; Children's Hospital, Boston, MA 02115

Purpose: Lower intestinal venous malformations are rare anom-alies resulting from errors in vascular morphogenesis. These le-sions may cause significant chronic and acute gastrointestinalhemorrhage. Venous malformations are unresponsive to angio-genesis inhibitors. Though these anomalies are generally incom-pletely resectable due to diffuse pelvic and mesenteric involve-

SUPPLEMENT 779

ment, we sought to abate bleeding by excluding the lesion fromthe gastrointestinal lumen.

Methods: Three patients with circumferential transmural venousmalformations of the colorectum, pelvis and mesentery were iden-tified. Imaging findings were similar among the patients, andincluded circumferential septated bright signal on T-2 weightedMRI, contrast enhancement, and multiple phleboliths, seen best onCT. The lesion extended from the anus to the splenic flexure intwo patients and throughout the entire colorectum in the other.Each had daily hematochezia for many years and required trans-fusions (estimated over 100 units in one case) and chronic irontherapy. Though bleeding began in early childhood in each pa-tient, no therapy was successful until ages 7,24, and 45. Colec-tomy, anorectal mucosectomy (through the pelvic venous malfor-mation), and endorectal pull-through and anastomosis wasperformed (coloanal in two and ileoanal in one).

Results: Bleeding has been essentially eradicated in all threepatients with 5 to 52 month follow-up. One patient received athree unit transfusion intraoperatively and the other two receivednone. The most recently operated patient, who has residual ve-nous malformation in the remaining 1 cm of anal mucosa, hassome mild difficulty with fecal control if her diet results in loosestool.

Conclusion: Colectomy with mucosectomy and endorectal pull-through should be considered for diffuse venous malformations ofthe colorectum prior to the development of large transfusionrequirements.

43CHANGING PATTERNS OF TREATMENT FOR BLUNTSPLENIC INJURIES: A 10-YEAR EXPERIENCE IN A RURALSTATE

C. Frumiento, M.D., D.W. Vane, M.D.; The University of Ver-mont Dept. of Surgery, Burlington, Vermont 05401

Objective: To perform a population based study evaluating thetrend in management of pediatric blunt splenic injuries in a ruralstate and assess differences in the management of those injuries ata level I pediatric trauma center (PTC) and regional hospitals (RH)from 1985 through 1995.

Hypothesis: Educational programs increased the percentage ofpediatric splenic injuries treated with non-operative management(NOM) at both PTC and RH over the past ten years, but PTCcontinued to have a higher rate of NOM.

Methods: ICD-9-CM diagnosis and procedure codes for children(age

In only one patient in the 9-16 yr. old age group with a Type IIIodontoid fracture was this view deemed useful. The overall mor-tality in this series was 7.8% with all deaths secondary to associ-ated head injury.

Conclusions: In the 0 to 8-year-old age group, in whom theincidence of cervical spine injury is rare but frequently involvesthe upper cervical spine, the transoral "odontoid" roentgenogramis of little value in the evaluation of the spine and should not beconsidered necessary in "clearing" the pediatric cervical spine.Evaluation of these patients should include an initial lateral andAP radiograph, followed by CT scan if the patient has unex-plained neurologic deficit, neck tenderness, or radiographic find-ing.

46SUPPLEMENTAL OXYGEN IMPROVES RESOLUTION OFINJURY-INDUCED PNEUMOTHORAX

Steven L. Lee, MD, Dustin Zierold, MD, Jeffrey J. DuBois, MD,FAAP; Travis AFB, CA 94535 and UC Davis Medical Center,Sacramento, CA 95817

Purpose: Traditionally, supplemental oxygen is administered topatients with asymptomatic pneumothorax to accelerate resolu-tion. However, this is based on models that did not include injuryto the visceral pleura and ongoing pleural air leak. This studyevaluated the effects of increased inspired oxygen concentrationon pneumothorax resolution in a visceral pleural injury model.Methods: 27 NZW rabbits were randomly divided into three

groups: Room Air (RA), 40% FiO2 (40%), and 60% FiO2 (60%).Under thorascopic guidance, the visceral pleura was puncturedwith an 18-gauge needle to create a complete unilateral pneumo-thorax. The animals were housed in designated oxygen chambers.Cross-table AP chest radiographs were obtained pre-operatively,post-operatively, and twice a day until the pneumothorax re-solved. All radiographs were interpreted in a blinded-fashion bythe investigators.

Results: 20/27 of the animals completed the study successfully(3 died from tension pneumothorax and 4 from anesthetic com-plications). Mean time to resolution was longer in the RA groupcompared to the 40% group and in the RA group compared to the60% group. Time to resolution was also longer in the 40% groupthan in the 60% group. Data is summarized below.

Inspired Oxygen Concentration Time to Resolution (hours)

Room Air (n = 7)40% FiO2 (n = 6)60% FiO2 (n = 7)

111.2 + 30.8*71.8 + 22.3*39.4 + 14.2*

* P < 0.05 one-way analysis of variance, RA vs 40%, RA vs 60%,40% vs 60%.

Conclusion: Supplemental oxygen improves resolution of injuryinduced pneumothorax. The tradition of administering supple-mental oxygen to patients with asymptomatic pneumothoraxshould be continued even in the face of ongoing pleural air leak.

47FUNCTIONAL OUTCOME IN CHILDREN WITH PELVICFRACTURES.

Jeffrey Upperman, MD, Mary Gardner, RN, Barbara Gaines,MD, Laura Schall and Henri Ford, MD, FAAP; Department ofPediatric Surgery, Children's Hospital of Pittsburgh, Pittsburgh,PA.

Background: Although the mortality, morbidity and spectrum ofassociated injuries in children with pelvic fractures have beenextensively studied, little is known about the functional outcomes

in these patients. Since children with pelvic fractures often survivetheir injuries, early rehabilitation may improve functional out-come. We retrospectively examined functional independence mea-surement (FIM) at discharge in children with pelvic fractures todetermine how it should influence our management protocol.

Methods: We reviewed the records of all patients who sustainedpelvic fractures between 1993 and 1998 in the trauma registry of alevel I pediatric trauma center. Patients were stratified accordingto demographics, type of pelvic fracture (Torode radiographicclassification), FIM and discharge disposition. Fractures graded 1,2 or 3 were defined as stable, while grade 4 fractures were deemedunstable. Differences in FIM between patients with stable andunstable pelvic fractures were compared using chi-square test ofproportions.

Results: 88 children sustained pelvic fractures. 74% (65) hadstable fractures whereas 26% (23) sustained unstable fractures.There was no difference in age or sex between the groups: maleswere more commonly injured than females. Motor vehicle crashesaccounted for most injuries. The mean injury severity score (ISS)for patients with a stable fracture was 17±+14 and 20+13 forunstable fractures. There was no difference in overall hospitaliza-tion nor ICU stay. Of the 20 patients with an unstable pelvicfracture in whom FIM was recorded, 80% were categorized asdependent based on locomotion, compared to 52% of the 44 stablepatients with a recorded FIM (p=0.04). There was a higher num-ber of dependent patients in the unstable group compared to thestable group based on the transfer category (75% vs 55%), howeverthis difference was not statistically significant (p=0.12).

Conclusion: Short-term function appears to be significantly im-paired in greater than 50% of children with stable pelvic fractures.Therefore, aggressive rehabilitation should be instituted early in allchildren with pelvic fractures to achieve optimal functional outcome.

48BILE DUCT SIZE DOES NOT PREDICT SUCCESS OFPORTOENTEROSTOMY FOR BILIARY ATRESIA

Scott Langenburg, M.D., Michael Goretsky, M.D., Janet Poulik,M.D., Michael Klein, M.D., F.A.A.P; Children's Hospital of Mich-igan, Detroit, Michigan 48201

Presence of bile ducts at the porta hepatis larger than 200microns has been suggested to predict success following portoen-terostomy. It has been our experience that the size and presence ofbile ducts at the porta hepatis does not predict outcome of por-toenterostomy. We reviewed our patients with biliary atresia totest the hypothesis that bile duct size at the porta hepatis insuccessful portoenterostomy patients was no different than in theunsuccessful patients.We retrospectively reviewed the patients at our institution from

1989 to 1998 who had the diagnosis of biliary atresia (n=38).Information was gathered from our office charts, the medicalrecords, and the pathology reports. In addition, a pathologistblinded to the results of the operation confirmed the measure-ments of the bile duct remnants. We considered a successfuloutcome a patient who had a bilirubin level less than 1.5 mg/dl atleast one year out from the operation with no evidence of endstage liver disease. Data was analyzed using Student's t-test.

Five of our 38 patients did not have a portoenterostomy. Theyunderwent cholangiogram and liver biopsy and were evaluatedfor liver transplantation. All patients who underwent surgery(n=33) had a Roux-en-y hepaticojejunostomy. There were 17males and 16 females. Twenty-one patients were successes (64%)and twelve patients (36%) were failures. The average age at oper-ation in the successful group was 50.9 ± 3 days and in the failures,57.9 ± 4 days (p =0.16). The age range in successes was 32-78 days.The range of failures was 39 to 76 days. Duct size was not differentbetween the successes and failures. The size in successes was107.6 ± 27 microns. The size in failures was 135 ± 54 microns(p=0.6). Two of our successes had no evidence of bile ducts

SUPPLEMENT 781

grossly or histologically.We conclude that a child presenting less than 80 days of life

with biliary atresia should undergo a portoenterostomy regardlessof the size of the bile ducts at the time of exploration.

P1HOMEOBOX GENE EXPRESSION IN CUTANEOUS RABBITWOUNDS

David A. Lanning, MD, Dome R. Yager, PhD, Robert F. Di-egelmann, PhD, Oliver Bogler, PhD, and Jeffrey H. Haynes, MD,FAAP; Department of Surgery, Medical College of Virginia/Virginia Commonwealth University, Richmond, VA

Background: The genes that regulate the mechanisms responsi-ble for open wound contraction have not been elucidated. Ho-meobox genes direct cellular differentiation and tissue migrationduring embryogenesis and may play a role in the process ofwound contraction. The purpose of this study was to test thehypothesis that homeobox genes are expressed in a differentialpattem in noncontractile fetal excisional wounds compared withwounds induced to contract with TGF-f33.

Methods: Cellulose discs (3mm in diameter) were formulatedwith either 1.0,ug of TGF-133 or its carrier protein alone, bovineserum albumin (BSA), for sustained-release. Each disc was im-planted into a subcutaneous pocket on the back of a fetal NewZealand White rabbit in utero on day 24 of gestation (term=31days). A full-thickness, 3-mm excisional wound was then madenext to the implanted cellulose disc. A 2-mm ring of tissue washarvested from around the wound at day one and the mRNA wasextracted. This was followed by RT-PCR using degenerate oligo-nucleotide primers corresponding to regions located within thehighly conserved homeodomain region. PCR products were thenligated into a pT7Blue-2 cloning vector prior to being transformedinto E. Col cells. Positive clones were sequenced using standardtechniques and compared to the gene bank. Adult rabbit exci-sional wounds without implants were also harvested and pro-cessed in a similar manner. At this time, no rabbit homeoboxgenes have been submitted to the gene bank. Therefore, genesegments that had a >90% match to previously cloned homeoboxgenes from other species were taken to represent rabbit homeoboxgenes.

Results: Fifteen gene segments were found to meet this criteriaranging from 91 to 94%. Matches included those with humanhoxA5, A10, C4, C6, C8, and sheep hoxC6.

Conclusions: This study demonstrates that homeobox genes arepresent at the site of excisional wounds induced to contract withTGF-f33 in the fetal rabbit. Furthermore, these genes were ex-pressed in a varied pattem when compared to the BSA and adultgroups. These findings suggest that homeobox genes may regulatethe mechanisms responsible for wound contraction. Grant supportby NIH GM08695-01, Jeffress Memorial Research Trust, and thePlastic Surgery Educational Foundation.

P2PRESSURE INDUCED MUCOSAL GROWTH INNEONATAL SMALL INTESTINE

Adina Kay Knight, MD, Masaki Kanai, MD, Timothy Sablichand Alan W. Flake, MD, FAAP; Children's Institute for SurgicalScience, The Children's Hospital of Philadelphia, Philadelphia, PA19104.

Introduction: Short bowel syndrome is a lifelong problem forneonates who have had massive intestinal resections for NEC orcongential bowel defects. Based on clinical and experimental ob-servation that hypertrophic segments of bowel are often presentupstream of sites of partial intestinal obstruction, we hypothesizedthat increasing the pressure in an isolated loop of ileum wouldlead to growth of that segment of bowel.

Methods: 7 day old piglets were anesthetised, and a 40 cm loopof ileum beginning 2 cm proximal to the ileocecal valve and wasisolated, catheterized and secured to the abdominal wall. Theremaining bowel was reanastamosed in continuity. Animals wereallowed to recover and Go-lytely (10 cc/hr) was infused throughthe intestinal loop. On post-operative day 3, experimental animalshad the loop pressurized to 40 cm water with the Go-lytely infu-sion (n = 3), while control animals were maintained withoutpressurization with Go-lytely infusion alone (n = 3). On post-operative day 12 the control and experimental animals were sac-rificed. The isolated loop and a length of ileum proximal to theanastamosis were analyzed. Mucosal dry weights per cm andcircumferences were measured in triplicate for each animal. Stu-dent's T-test was used to compare groups.

Results: There were no statistical differences in body weightsbetween the groups. A significant (p

Materials and Methods: A review (1989-98) of children with gas-troschisis bom and/or treated at a rural Children Hospital wasconducted. Birth records confirm this accounts for 70% of allbabies bom with gastroschisis in the state. Matemal (age, smok-ing, drug use, etc), prenatal (complications, diagnosis), obstetrical(gestational age, birth weight, mode of delivery), surgical (time toOR, type of repair), hospital (ventilation, TPN, oral feeding), mor-bidity and mortality data was extracted. A literature review iden-tified studies published within similar time parameters from ur-ban centers in North America and Europe to which we comparedour outcomes. Means were analyzed by the student's t test.

Results: 30 infants with gastroschisis were identified from hos-pital records. A brief summary is shown in the data below. Aprenatal diagnosis was known in 79%. 63% were delivered vagi-nally with an average birth weight of 2.46 kg. The median time tosurgery was 6.8 hours and 64% were primarily repaired. Hospitalcourse included an average of 5.9 days for post op ventilation, and18.5 days from repair to first feeding. There was 1 death. Compli-cations occurred in eight neonates. Wound infection (5) was themost frequent followed by central line infection (4). Short gut (1),post op bowel obstruction (1), and NEC (1) were the other com-plications Comparison of this data to previously published datafrom urban centers did not reveal any statistical difference(p

P6NEUROBLASTOMA-DERIVED FACTORS INHIBITDENDRITIC CELL (DC) GENERATION FROM CD34+HEMATOPOIETIC PRECURSORS

Edward M. Barksdale, MD, FAAP, Galina V. Shurin, MD, Mi-chael T. Lotze, MD; University of Pittsburgh, Pittsburgh, PA15213

Introduction: Dendritic cells (DC) play a critical role in the initiationof the host immune response to cancer by stimulating nalve T andNK cells to recognize tumor antigens. Previous studies in our labsuggest that prognosis may be correlated with the degree of DCinfiltration in neuroblastoma (NB) and other tumors. Impairments inDC function may provide a mechanism for evasion of these tumorsfrom immune detection. We hypothesize that NB secretes solublefactors that inhibit DC maturation and function.

Methods: CD34+ progenitor cells isolated from cord blood weregrown in the presence of GM-CSF a