Management of Omphalocele: From Conception to Closure Terry L. Buchmiller, MD Brian Labow, MD February 13, 2013 Department of Pediatric Surgery Department of Plastic Surgery Advanced Fetal Care Center Boston Children’s Hospital

Conflict of Interest Disclosure We have no financial relationships with a commercial entity producing healthcare-related products and/or services.

Omphalocele Definition Central abdominal wall defect Herniation of abd contents into umbilicus Covered by membrane/ large peritoneal sac Not covered by skin Composed of fused peritoneum and amniotic membrane Delicate avascular wall, 1 mm thick Occasionally intervening compartment containing Wharton’s jelly Umbilical cord typically inserts slightly inferior on sac

Embryology of Abdominal Cavity Celomic cavity undergoes forward expansion into umbilical cord between wk 6-10 of fetal life Two lateral folds form pleuroperitoneal canals; destined to fuse with cranial and caudal folds

Embryology Omphalocele results from defect in migration of lateral folds very early in embryogenesis ~wk 3 Always occur at umbilicus Rectus muscles insert more laterally on costal margins Due to early event, often accompanied by other defects

History of Omphalocele Described in 16th Century by Ambrose Pare in printed works 1802: Hey reported first successful repair 1887: Olshausen described skin flap coverage after removal of membrane 1899: Alfield described painting sac with alcohol to produce eschar, awaiting contraction and epithelialization

History of Omphalocele 1953: Max Grob reported use of mercurachrome with toxic effects later described 1967: Schuster introduced staged reduction using prosthetic mesh as he noted abdominal cavity did not enlarge with skin flap coverage alone

History of Omphalocele 2013: Currently no closure technique universally accepted with ingenious methods still reported Tissue expanders VAC dressing Skin grafting Alloderm Partial hepatectomy Lateral relaxing incisions Division of rectus muscles Pneumoperitoneum

History of Omphalocele at BCH Chief of Surgery from 1947-1968 “The Surgery of Infancy and Childhood” Published in 1953 Exactly 1,000 pages “The green bible” Dr. Robert E. Gross

History of Omphalocele at BCH Abdominal organs “directly exposed to view as if exhibited in a showcase’ “Considerable judgment must be exercised in determining how perfect of a repair should be attempted” Dr. Robert E. Gross

Current Demographics Occurs in 1 in 3,000 fetuses 1 in 5,000 live births Slight male predominence No racial predilection Risk of preterm birth 25-65% IUGR in 6-35%

Remains unknown Etiology Several animal teratogenic models, but none truly recapitulate omphalocele Very rare familial occurrence, even more rare in twins No specific gene or environmental cause Potential assoc with EtOH in 1st trimester; heavy smokers (Natl Birth Defects Study) Can occur as part of syndromes Remains unknown

Associated Conditions Cardiac ~ 45% Chromosomal defects (T18, 21) in 30-40% Intestinal malrotation in 28% Cryptorchidism Increased incidence of inguinal hernias; Meckel’s diverticulum Pulmonary hypoplasia Musculoskeletal/ neural tube defects rare

Strongly consider prenatal Associated Syndromes Beckwith-Wiedemann Donnai-Barrow Gershoni-Baruch Fryns’ OIES Pentology of Cantrell Strongly consider prenatal genetics evaluation

Beckwith-Wiedemann Syndrome Macroglossia Gigantism Visceromegaly Pancreatic islet cell hyperplasia leading to hypoglycemia Predisposition to abdominal tumors Occurs in 1: 13,700

Genetic Testing for BWS ~85% cases are sporadic ~15 % inherited with 50% recurrence risk Dx by analysis of chromosome 11p15 by methylation-specific PCR to detect methylation errors, abnormal copy number If negative, sequencing of CDKN1C recommended 1-3 wk turnaround for prenatal dx on amniocytes only Children with features consistent with BWS, but with negative genetic test results should receive the same medical management as those with a confirmed genetic diagnosis

Beckwith-Wiedemann Syndrome Tumor Screening 10% develop malignancy Wilms in 5-7% Most prior to age 4 US screen q 3 mo By age 8, 95% occur Hepatoblastoma AFP q 6 wk until age 4 US as above Adrenocortical www.beckwith-wiedemannsyndrome.org

Donnai-Barrow Omphalocele CDH Absent corpus callosum Hypertelorism Myopia Sensorineural deafness Likely autosomal recessive; LRP2 gene

Fryns’ Syndrome CDH Coarse facies Acral hypoplasia Often omphalocele Limited survival

OEIS Caudal Fold Defect Infraumbilical Omphalocele (usually not containing liver) Cloacal Exstrophy (with ileal prolapse) Epispadias Diastasis of pubic rami Imperforate anus Spinal anomalies

Limb Body Wall Complex (Body Stalk Anomaly) Severe multiple congenital anomalies ~ 250 cases reported Etiology remains unknown Incompatible with survival

Limb Body Wall Complex (Body Stalk Anomaly) Encephalocele Thoraco- and/or abdominoschisis Limb defects +/- Facial clefts Short umbilical cord Severe spinal curvature Fetus appears “stuck” to placenta

Pentology of Cantrell “Cephalic Fold Omphalocele” Supraumbilical abdominal wall defect typically containing liver Heart or ventricular diverticulum in sac through pericardial defect Central diaphragmatic tendon defect Lower sternal cleft Intracardiac anomaly

Prenatal Assessment of Omphalocele Elevated AFP (serum/AF); AChE (AF) US MRI ECHO Amniocentesis / CVS Abnormal karyotype in 30% More common in those with small defects

US Screening Increasing dx in 1st trimester due to nuchal translucency screening between 11-14 wks If seen very early in 1st trimester, repeat US in 7-10 d to assure not “physiologic” Stability of defect anticipated Study of choice in prenatal period to assess fetal growth, AF, delivery planning 13 wk US

Estroff, Buchmiller, et al. J Radiol In press MRI Preferred at >16 wk gestation Initial MRI exam useful in detecting underlying syndromes Not typically repeated unless concern for clinical change Estroff, Buchmiller, et al. J Radiol In press

Giant Omphalocele MRI Large omphalocele containing liver (L) and small bowel (SB) Note umbilical cord (UC) inserting into inferior aspect the omphalocele Assess hepatic vasculature ? stretched L 4039762 liver, gb, sb UC SB

Lakasing, Ciscero, Davenport, Patel, Nicolaides. JPS 2006 MFM Perspective Kings College London Referral Fetal Medicine Centre Retrospective study from 1991-2002 445 pts 3 cohorts formed based on karyotype assessment, if obtained Lakasing, Ciscero, Davenport, Patel, Nicolaides. JPS 2006

Lakasing, Ciscero, Davenport, Patel, Nicolaides. JPS 2006 MFM Perspective Group A: Abnormal karyotype N=250 (56%) Trisomy 18 most common in 63% Trisomy 13 in 17% Trisomy 21 in 4% Turner’s syndrome in 6% Triploidy in 5% Rare chromosomal deletions in 5% Additional structural anomalies in 73% Lakasing, Ciscero, Davenport, Patel, Nicolaides. JPS 2006

Lakasing, Ciscero, Davenport, Patel, Nicolaides. JPS 2006 MFM Perspective Group A: Abnormal karyotype 91% requested termination 8% fetal demise Only 2 live births (trisomy 18) with comfort care, ultimate neonatal death Lakasing, Ciscero, Davenport, Patel, Nicolaides. JPS 2006

Lakasing, Ciscero, Davenport, Patel, Nicolaides. JPS 2006 MFM Perspective Group B: Normal karyotype N=135 (30%) 54% had structural anomalies 47% TOP (usually not isolated anomaly) 14% fetal demise 31% live births 8% lost to F/U Lakasing, Ciscero, Davenport, Patel, Nicolaides. JPS 2006

Lakasing, Ciscero, Davenport, Patel, Nicolaides. JPS 2006 MFM Perspective Group C: Karyotype declined N=60 (14%) 63% structural anomalies 55% TOP 13 % fetal demise 19% live births 13% lost to F/U Lakasing, Ciscero, Davenport, Patel, Nicolaides. JPS 2006

MFM Perspective: Take home points Less than 10% of antenatal diagnosed pts came to operative repair 55 live births 11 died preoperatively (anencephaly, major CHD) 44 repaired, all survived Pts cared for by pediatric surgeon/ tertiary care providers are a very select group Lakasing, Ciscero, Davenport, Patel, Nicolaides. JPS 2006

Preparation for Delivery Coordinated delivery with MFM, NICU Cognizant of travel plans should preterm labor occur Ave age of delivery 36.6 wks Ave birthweight 2.9 kg Unclear need for C section unless defect >5 cm Delivery at tertiary care center essential (if not opting for comfort care)

Delivery Room Management Surgical presence at delivery optimal Observe C section ABC’s Is sac intact? Place NGT Stabilize liver in extreme cases (Kerlix roll) Provide moist coverage of membrane Enable family celebration of birth

Initial NICU Management Maintain temperature Respiratory support PE to rule out associated (midline) anomalies Trisomy 13, 18, 21 Beckwith-Wiedemann Rectal exam R/O imperforate anus/ evacuate meconium Protect sac with xeroform/ moist gauze, especially under warming lights..... No urgency for repair unless sac ruptured

Ruptured Giant Omphalocele Majority born prematurely Typically fatal due to respiratory failure; sepsis

Subsequent Management Assess size of defect Small, medium, large, giant Is the hepatic vasculature at risk? Reassess potential for associated conditions, even if “cleared” during fetal period Prematurity may alter surgical closure plan Cardiac disease Urgent genetics consult if life threatening association suspected

Postnatal ECHO Still repeated even if prenatal study nl Most common defect VSD ECHO windows often compromised by inability to visualize in substernal area May need surgical presence to facilitate performance of study and protect sac

Role of Newborn US Abd US if ? about hepatic blood flow in giant defect Surgical presence paramount for effective study Assess in decubitus positions

Essential Management DOL 1 Continue ABC’s Protect membrane Assist bedside providers in understanding positioning concerns PICC Operative Planning

Historic Notes on Omphalocele Repair Gross noted postoperative condition after repair could be quite precarious; whenever a large portion of liver contained a grave outlook was expected Essential to devise a method to avoid intra-abdominal crowding of organs at first operation Diaphragm displaced upward causing respiratory disturbance, cyanosis, death Pressure on IVC impedes return of blood leading to circulatory collapse Pressure on stomach/intestine leads to partial / temporary obstruction (pre-PN)

When Considering Operative Repair “Primum non nocere” Avoid abdominal compartment syndrome at all costs ...........And provide a cosmetic umbilicus

Methods to Assess Potential Abdominal Compartment Syndrome Saphenous vein IV that will not drip with gravity Bladder pressure via foley or NG pressure > 20 mmHg PE Clinical judgment

Adjunctive Points to Consider During Closure Most do not recommend a Ladd procedure or appendectomy If testicle intraabdominal, place near ring; in most cases scrotal descent will occur by age one year; NO orchidopexy Consider gastrostomy if significant cardiopulmonary compromise Be gentle on liver; do not kink HV, PV, or rupture capsule....Budd Chiari reported

Omphalocele Closure Options Primary closure Immediate staged closure with mesh prosthesis for serial reduction Delayed closure Operative skin closure, period of waiting, later definitive closure with repair large ventral hernia “Paint and Wait”

Can Fetal MRI Predict Closure? N=9 (Mixed GS and omphalocele) MRI volumetry performed; manual 3D tracing Calculated Exteriorized Ratio= Exteriorized Viscera/Volume Abdominal Cavity ER 1.39 in staged closure, ER 0.33 in closure Quantifies clinical judgment Very limited study, but increasing interest Takada, Hamada, Kamiyama. JPS 2006

Omphalocele Closure Options Primary closure Immediate staged closure with mesh prosthesis for serial reduction Delayed closure Operative skin closure, period of waiting, later definitive closure with repair large ventral hernia “Paint and Wait”

Small Omphalocele Occasionally small irregular liver segment in sac If bowel, can reduce and tie with umbilical tape if associated disease Genetics consult as associated syndromes more common

Schematic of Primary Closure Dr. Gross’ Skin edges freed Sac removed Leave on liver if difficult to peel off to avoid bleeding Viscera reduced Peritoneum closed Fascia closed Often difficult to oppose upper rectus Skin closed

Omphalocele Closure Options Primary closure Immediate staged closure with mesh prosthesis for serial reduction Delayed closure Operative skin closure, period of waiting, later definitive closure with repair large ventral hernia “Paint and Wait”

Silastic Silo If used, suture to abd wall Apply abx ointment at edges 0.007 in Dacron reinforced Silastic alternative Assess reduction 30 min post procedure Assess for tightening BID

MEDIUM OMPHALOCELE: Schuster approach DOL 1 DOL 2

Omphalocele Closure Options Primary closure Immediate staged closure with mesh prosthesis for serial reduction Delayed closure Operative skin closure, period of waiting, later definitive closure with repair large ventral hernia “Paint and Wait”

First Stage Skin Closure Liberate skin edges Can close skin over sac if adherent Never free up skin over chest further than necessary as to not displace viscera during reduction Dr. Gross

“Paint and Wait” Can be utilized if significant cardiac disease, prematurity, chromosomal anomaly to buy time, even in small defects Preferred in most giant omphalocele pts

Occasionally, brace used for protection... Eschar Formation 6 wks Occasionally, brace used for protection...

Epithelialization 3 mo Caloric needs often very “robust” Feeding tube supplementation Caloric needs often very “robust” Supplemental tube feeds often needed 3 mo

Potions to “Paint and Wait” Escharotic Agents Mercurachrome Silver nitrate solution Betadine Silvadene

Mecurachrome 2% Merbromin solution abandoned d/t mercury poisoning 0.25% solution used in Europe BID w/o complications Rare contemporary use

Silver Nitrate Solution Bacteriostatic Encourages epithelialization Hypotonic; draws Na into dressing; monitor serum Na Stains linens, skin No longer recommended

Whitehouse, Sato, Arca. JPS 2010 Betadine Promotes epithelialization and escharizaton 10 yr review; 6 GO pts 10% povidone-iodine used qD or qoD Diluted 1:4 with saline in 5, 1:10 in one TFT’s weekly inpt; mo as outpt Transient elevation TSH noted, normalized by following wk; Nl free T4, thyroxine No thyroid replacement therapy needed Frequency of dressing changes decreased in one Safe, but monitoring recommended Whitehouse, Sato, Arca. JPS 2010

Silvadene Bacteriostatic, used in burn sepsis prevention May impair G6PD Methemoglobinemia, hemolysis, hyperosmolality 2 pt with toxic serum levels (x200 adult) reported by Lander JPS 2010 No toxic sxs (incr LFT, seizures) Consider monitoring CBC, silver levels, very thin layer, or avoidance

Silvadene 20 infants with defect >10 cm 20 gm spread over thin layer, gauze cover qD Mean use 5 mo at cost $1/day Turns eschar black due to silver Silver levels not monitored, but no toxicity demonstrated Routine use supported Ein, Langer. JPS 2011

“Paint and Wait” Dr. Gross’ observations Mother apt to be apprehensive about potential rupture of protruding mass; reassure her this has never happened Considerable distension during crying or straining Child may be bathed A 4-6 inch Ace wrap serves admirably Wait until the abdominal cavity has grown large enough so that it can receive the organs without crowding

Dr. Gross’ Observations Plan final closure when.... the sac wall can be readily picked up between the examining fingers the viscera can be pushed back into the abdominal cavity

Skin Laxity

Epithelialized Sac Suspension Utilized to promote visceral reduction preoperatively to lessen time of mesh; potentially decrease infection risk

Silo Reduction

Final Closure Prepare for full complement of closure techniques Partnership with Plastic Surgery team in select cases

Surgical Management of Omphalocele: A Plastic Surgeon’s Perspective Brian I. Labow, MD, FACS, FAAP Department of Plastic Surgery Children’s Hospital Boston Harvard Medical School

Introduction Heterogenous population and associated anomalies common Many approaches, techniques and tools No single approach will suit all patients Outcome data based limited by numbers and confounding variables 73

Outline General considerations Tools/techniques Adjuvant procedures Summary

General Comments Usually not an emergency Most cases can be managed with “conventional approaches” Circumstances may mandate change in course…

Clinical Situation? Medically unstable Damage control (e.g. ruptured membrane, silo disruptions) Incomplete reduction Extreme visceral-peritoneal disproportion

Tools and Techniques

Negative-Pressure Wound Therapy NPWT/VAC™ hopefully not necessary! Decrease edema and bacterial colonization accelerate granulation Used with absorbable mesh, biological fascial substitute Bridge to definitive reconstruction (Kilbride et al. J Ped Surg (2006) 41, 212–215)

Tissue-Expansion Mechanical process to increase surface area of adjacent tissues Examples: Growth, Silo, External Skin closure devices Adjunct to flap transfer Progressive process takes time

Tissue-Expanders Tissue expanders require a clean field with minimal inflammation Epidermis thickens, dermis and fat atrophy, muscle thins, angiogenesis Multiple expanders, small, frequent fillings

Tissue-Expanders Subcutaneous, submuscular and intraperitoneal placement all reported Small case series, longest follow-up 3 yrs (Tanenbaum et al. Plas Rec Surg (2007)120,1564–7)

Tissue-Expanders Useful in a subset of patients Additional GA, time and good local tissue conditions required Judgment in rate of expansion Extrusion and infection most frequent complications

Component Separation Relaxing incision(s) separating rectus sheath from ext obliq aponeurosis Autologous tissue, 1-stage Skin deficit? Large experience in adults

Component Separation 1 series of 10 consecutive omphalocele patients (mean age 6.5 months) Van Eijck et al. J Ped Surg (2008) Mean defect size 8 cm Required temporary prosthetic in 1 case Complications in 3 patients (skin necrosis, hematoma, infection) Mean follow-up 2 years, no hernias

Absorbable Mesh Usually a lifeboat Allows egress of fluid, visualization of bowel Used with NPWT Lasts 3-4 months….hernia Cost Vicryl™ 15x 15” $1800* * BCH list price 2013

Non-absorbable, Meshed Allows tissue ingrowth, stronger Higher rate of enterocutaneous fistulae Onlay support Cost e.g. Marlex™ 10x14” $500

Non-absorbable, Non-meshed Temporary use silo construction (e.g. Silastic™) No ingrowth, minimal adhesions Permanent use (e.g. Goretex™) higher hernia rate? Cost* $600 for 10x15”Goretex™ * BCH list price 2013

Biological Materials Variety of freeze-dried, acellular dermal or intestinal products (e.g. Alloderm™, Surgisis™) Inlay graft or onlay above fascia Neovascularized, tissues replaced by native cellular ingrowth

Biological Materials Small series/case reports in pediatric literature (Alaish et al. J Ped Surg (2006) 41, E37–E39) Variable reports in adult abdominal wall reconstruction literature Cost has come down, 5x10” sheet of Alloderm™ ~$1800* * BCH list price 2013

Flaps Local tissues usually sufficient Mobilization wide undermining Can be facilitated with relaxing incisions Zama et al. Br Assoc Plas Surg (2004) 57, 749–753

Flaps Br Assoc Plas Surg (2004) 57, 749–753

Adjunctive Procedures Skin closure: secondary but important part of reconstruction Umbilicoplasty if possible Secondary procedures: hernias, bulges, hypertophic/depressed scar

Adjunctive Procedures

Rijwani, Davenport, Dawrnat. et al. J Pediatr Surg 2005 Long-Term Follow Up Postnatal survival rates 70-95% Mortality related to associated cardiac and chromosomal anomalies Rijwani, Davenport, Dawrnat. et al. J Pediatr Surg 2005

Incidence of Bowel Obstruction 170 abd wall defects; 111 w/ omphalocele 10 yr median F/U 12/92 (13%) incidence of adhesive SBO 85% occurred in 1st yr 88% underwent laparotomy Sepsis and fascial dehiscence risk factors in entire cohort Van Eijck, Wijnen, van Goor. JPS 2008

Danzer, Flake, Adzick, Hedrick. JPS 2010 Neurodevelopmental Cohort from CHOP with GO 31 pts Overall survival 81% 20 survivors enrolled in prospective F/U Age > 6m, had Bayley (BSID-II,-III) Danzer, Flake, Adzick, Hedrick. JPS 2010

Danzer, Flake, Adzick, Hedrick. JPS 2010 Neurodevelopmental Median age at evaluation 12 mo Motor skills: Normal 40% Mildly delayed 13% Severely delayed 47% Cognitive/Language skills: Ave 40% Mildly delayed 13% Severely delayed 40% Of 6 with severe delays: 2 autism 4 tracheostomy 1 Williams syndrome Danzer, Flake, Adzick, Hedrick. JPS 2010

Pulmonary Hypoplasia Definition nebulous, often based on clinical course Require long-term vent support ? “permanently limited” reserve High postoperative mortality 30-60%

Assessment of Early Pulmonary Function in GO N=14, mean age 19 mo PFT’s Spirometry Fractional lung volume assessment Bronchodilator responsiveness Passive respiratory mechanics Danzer, Hedrick, Panitch. JPS 2012

Assessment of Early Pulmonary Function in GO FVC, mean Forced Exp Vol, TLC FRC normal Restrictive pattern demonstrated responsiveness to bronchodilators Reduced lung compliance Undetermined clinical significance Danzer, Hedrick, Panitch. JPS 2012

Can Pulmonary Function be Predicted Prenatally? Fetal MRI assessed at ~26 wks (N=17) Observed/Expected TLV calculated vs. age-matched fetal nomograms Mean O/E TLV 52% (+/- 17%) Age at delivery 37 wk Survival 94% Danzer, Victoria,Hedrick. JPS 2012

Can Pulmonary Function be Predicted Prenatally? 88% staged reduction Infants <50% O/E TLV Lower Apgar scores Prolonged ventilatory support Delayed oral intake Longer hospitalization Fetal MRI predictive of postnatal morbidity Numbers small, but.....a start Danzer, Victoria,Hedrick. JPS 2012

QOL Studies Tunell series of mixed abd wall defects 88% reported good health; 80% good QOL 40% concerned about height, inadequate in sporting/ social activities Educational levels equal to general population Many report absence of umbilicus caused psychologic distress

Long Term F/U Challenges Most case reports, small series, single center F/U Typically includes gastroschisis Definition of giant omphalocele diverse Are defects containing the whole liver/all viscera different?

Parental Perspective “People turn to social media for answers which can be greatly helpful, but also dangerous as parents generalize their experience and their child's condition in counseling other parents. I think the world, is in need of some really good long term follow up on these kids to change the perspective surrounding survival and short/long term complication statistics.”

Long-Term F/U Needed

Summary No single “right way” to manage but optimistic outcome in absence of severe congenital heart disease/chromosomal anomalies Situation dependent Numerous tools/techniques available Outcome data needed

Thank You!