FETAL SURGERY WHERE DO WE STAND

1. FETAL SURGERYWHERE DO WE STAND ? HESHAM SAFOURY A. PROF OF PEDIATRIC SURGERY AIN-SHAMS UNIVERSITY

2. THE FETUS AS A PATIENT Prenatal diagnosis improves perinatal care. Severe lesions detected early enough may lead to termination of pregnancy. Most correctable defects are best managed by maternal transport to an appropriate center and delivery near term. Some may benefit from change in the timing or mode of delivery.

3. THE FETUS AS A PATIENT Serial study of affected fetuses may help unravel the developmental pathophysiology of some surgically correctable lesions and thus lead to improved treatment before or after birth.

4. Diagnosis Ultrasonography/ MRI Alpha-Fetoprotein neural tube defects , omphalocele, gastroschisis and sacrococcygeal teratoma. Fetal Sampling karyotyping and DNA- based diagnosis, for genetic defects and inherited metabolic abnormalities

5. Fetal Sampling Chorionic villus sampling- first trimester Amniocentesis � second trimester PUBS percutaneous umbilical cord sampling ( rapid karyotyping 2 days versus 7 days for amniocentesis) Fetoscopy / ultrasound fetal skin or liver biopsies Risk of fetal loss from fetal sampling 1-5%.

6. Prenatal diagnosis and management DEFECTS USUALLY MANAGED BY ELECTIVE ABORTION DEFECTS DETECTED IN UTERO BUT BEST CORRECTED AFTER TERM DELIVERY DEFECTS THAT MAY LEAD TO CAESAREAN DELIVERY DEFECTS THAT MAY LEAD TO INDUCED PRETERM DELIVERY Defects that may benefit from Fetal intervention and Fetal surgery

7. DEFECTS USUALLY MANAGED BY ELECTIVE ABORTION Anencephaly, holoprosencephaly Severe chromosomal anomalies (trisomy 13) Bilateral renal agenesis, infantile polycystic kidney Severe untreatable inherited metabolic disorders (Tay-sachs disease) Lethal bone dysplasias (recessive osteogenesis imperfecta)

8. DEFECTS DETECTED IN UTERO BUT BEST CORRECTED AFTER TERM DELIVERY Oesophageal , duodenal, and Intestinal atresia Meconium ileus Enteric and Duplication cysts Small intact omphalocele, meningocele Unilateral, hydronephrosis, multicystic kidney Small sacrococcygeal teratoma, cystic hygroma, Benign cysts (ovarian, mesenteric, choledochal) Craniofacial, limb, and chest wall deformities

9. DEFECTS THAT MAY LEAD TO CAESAREAN DELIVERY Conjoined twins Giant omphalocele, ruptured omphalocele. Gastroschisis Severe hydrocephalus, large or ruptured meningomyelocele Large sacrococcygeal teratoma or cervical cystic hygroma

10. DEFECTS THAT MAY LEAD TO INDUCED PRETERM DELIVERY Obstructive hydronephrosis Obstructive hydrocephalus Gastroschisis or ruptured omphalocele Intestinal volvulus with ischemia Immune hydrops fetalis Intrauterine growth retardation Arrhythmias (supraventicular tachycardia with failure)

11. Malformations that may benefit from treatment before birth Potentially lethal defects those that interfere with fetal organ development and that if alleviated, would allow normal development to proceed. Nonlethal defects; myelmeningocele, cleft lip and palate Metabolic and cellular defects ; stem cell, enzyme defects, predictable organ failure.

12. Potentially lethal defects Urinary tract obstruction (urethral valves) Cystic adenomatoid malformation Diaphragmatic hernia Sacrococcygeal teratoma Twin-twin transfusion syndrome Aqueductal stenosis Complete heart block Pulmonary/ aortic obstruction Tracheal atresia /stenosis

13. Potentially lethal defects Rational for treatment / Type of procedure Urinary tract obstruction / Renal failure- pulmonary failure -percutaneous catheter placement -fetoscopic vesicostomy -open vesicostomy

14. Potentially lethal defects Rational for treatment / Type of procedure Cystic adenomatoid malformation Fetal hydrops �pulmonary failure -Open pulmonary lobectomy Diaphragmatic hernia Pulmonary failure - Open repair -Temporary tracheal occlusion

15. Potentially lethal defects Rational for treatment / Type of procedure Sacrococcygeal teratoma High output failure/ fetal hydrops -Open tumor resection -Fetoscopic vascular occlusion Twin-twin transfusion syndrome Vascular steal through placenta/ fetal hydrops -Open fetectomy -Fetoscopic division of placenta

16. Potentially lethal defects Rational for treatment / Type of procedure Aqueductal stenosis Hydrocephalus / brain damage -Ventriculoamniotic shunt -Open ventriculoperitoneal shunt Complete heart block Low output failure fetal hydrops -Percutaneous or open pacemaker implantation

17. Potentially lethal defects Rational for treatment / Type of procedure Pulmonary /aortic obstruction Ventricular hypertrophy- heart failure Percutaneous or open valvuloplasty Tracheal atresia , stenosis Overdistension by lung fluid- hydrops -Fetoscopic tracheostomy -Open tracheostomy -EXIT (Ex utero intrapartum treatment)

18. NON-LETHAL DEFECTS Rational for treatment / Type of procedure Myelomeningocele Spinal cord damage- paralysis, neurogenic bladder - Fetoscopic coverage -Open repair Cleft lip and palate Facial defect-persistent deformity -Fetoscopic/ Open repair

19. METABOLIC AND CELLULAR DEFECTS Rational for treatment / Type of procedure Stem cell or enzyme defects Hemoglobinopathy- anemia Immunodeficiency- infection Storage disease � retardation -Fetal stem cell transplant or gene therapy Organ failure Hypoplastic heart/ lung/ kidney -Induce tolerance for postnatal organ transplantation

20. Fetal stem cell transplantation rationale for treatment The preimmune fetus (< 15 weeks) will not reject the transplanted cells In utero transplantation allows treatment before fetal health is compromised by the underlying disease Disadvantage Fetus is difficult to access Delivering even a small volume (< 1ml) of cells to an early gestation fetus by intraabdominal or intravenous injection requires skill and carries risks

21. Fetal surgeryManagement of Mother and Fetus PRETERM LABOUR / FETAL SURGERY Preoperative indomethacin (Constrict fetal ductus arteriosus) Intraoperative deep halogenated anesthesia, nitric oxide and nitroglycerine (Fetal and maternal myocardial depression and affects placental perfusion). Postoperative indomethacin, magnesium sulfate, nitroglycerine and betamimetics (Maternal pulmonary oedema)

22. Videoendoscopic Fetal Surgery FETENDO Obviate need for uterine incision Obstacles Fix amniotic membranes Perfuse amniotic cavity with fluid rather than gas Position and stabilize the fetus

23. JPS December 2002 � Volume 37 � Number 12 Fetal endoscopic surgery: Lessons learned and trends reviewed HARRISON et al UCSF All fetal endoscopic cases performed at a single institution from January 1996 to August 2001 were reviewed (n = 66). Cases were examined with respect to year performed, type of operation, operative data, and outcome Twin-twin transfusion syndrome (26 cases) and congenital diaphragmatic hernia (35 cases) were the most common diseases treated. From 1996 to 2001, Three cases of myelomeningocele (MMC). One fetus with obstructive uropathy and one with tracheal atresia

24. JPS December 2002 � Volume 37 � Number 12 Fetal endoscopic surgery: Lessons learned and trends reviewed HARRISON et al UCSF There was a decrease in; average operating time (256 to 127 minutes [P = .0006]), number of ports utilized (3.8 to one [P = .00001]) pump volume (28.7 to 2.7 L [P = .00001]), estimated blood loss (408 to 29 mL [P = .008]). In addition, port size changed from 10 mm to 5 mm. COMPLICATIONS Chorioamniotic separation (31 of 66), premature rupture of membranes (32 of 66), chorioamnionitis (12 of 66), and fetal death (10 of 66) continued to be significant complications

25. JPS December 2002 � Volume 37 � Number 12 Fetal endoscopic surgery: Lessons learned and trends reviewed HARRISON et al UCSF TTTS has the shortest operating time, smallest pump volume, and least amount of blood loss. TTTS was responsible for 8 of 10 cases of fetal mortality among the patients. CDH had 25 cases of premature rupture of membranes, 19 progressed to preterm labor. Compared with TTTS, CDH had longer operating time, blood loss, and pump volume. Other cases of fetal endoscopic surgery comprising MMC, obstructive uropathy (OU), and congenital high airway obstructive syndrome (CHAOS) had significantly longer operating times, and blood loss

26. CONGENITAL DIAPHRAGMATIC HERNIA Mortality 58% despite best postnatal care including ECMO Fetal CDH repair , allows lung to grow while the fetus is on placental repair. Fetal surgery Open surgery (left liver lobe in chest) FETENDO CLIP of trachea (impeding egress of fetal lung fluid by tracheal obstruction, enlarges the hypoplastic lung, pushes the viscera back to abdomen) FETENDO BALLOON EXIT ex utero intrapartum treatment, removal of FETENDO CLIP, fetal airway obstruction

27. The past and future of fetal intervention The enterprise of fetal surgery has produced some unexpected spin-offs that have interest beyond this narrow therapeutic field. For pediatricians , neonatologists the natural history and pathophysiology of many previously mysterious condition of newborns have been clarified by following the development of the disease in utero.

28. The past and future of fetal intervention For obstetricians and fetologists Intensive effort to solve the vexing problem of preterm labour after hysterotomy for fetal surgery has yielded new insight into the role of nitric oxide in myometrial contractions and has spawned interest in treating spontaneous preterm labour with nitric oxide donors.

29. The past and future of fetal intervention The observation that the fetal incisions heal without scarring has provided new insights into the biology of wound healing and has stimulated efforts to mimic the fetal process postnatally.

30. The past and future of fetal intervention Finally fetal tissue seems to be biologically and immunologically superior for transplantation and for gene therapy, fetal immunological tolerance may allow a wide variety of inherited nonsurgical diseases to be cured by fetal hematopoietic stem cell transplantation Thank you