Fetal surgery: interventional opportunitiesaium.s3.amazonaws.com/events/ann2015/fetus/14... · Fetal surgery: interventional opportunities “The area equaled the product of the longest

Full professor at the Department Obstetrics-Gynecology, Baylor College of Medicine, Houston, Texas, USA

Co-Director of the Texas Children’s Hospital Fetal Center, Houston, Texas, USA

Adjunct Professor of the Department of Bioengineering, Rice University , Houston, Texas, USA

Rodrigo Ruano, MD, PhD

Fetal surgery:

interventional opportunities

The Fetus: Five Top "Do Not Miss Diagnoses"

Definition of Maternal-Fetal Surgery

• Operating on two patients simultaneously where both incur risks

• Benefits to mother probably not medically definable

• Opportunity to correct a surgically-treatable lesion or diminish its sequalae

Fetal surgery: interventional opportunities

• Application of established surgical techniques to the unborn baby� During gestation� At end of gestation


Principles of fetal surgery• Correct and precise prenatal diagnosis• Absence of associated anomaly• Knowledge of the natural history• High perinatal morbidity/mortality• Absence of effective neonatal therapy• Animal studies showing favorable results• Procedures performed in specialized centers with

multidisciplinary approach• Not compromise the reproductive future• Should not increase maternal mortality

Harrison et al 2001


To avoid fetal death / Prolong fetal survival

To decrease fetal morbidity

To avoid maternal complications

Advantage: the uterus works as a perfect “ICU” for the fetus –

“FICU”, since the placenta gives oxygen and nutrition to the

fetus

It does not aim to fix/treat the defect, but to stop the

pathologic process, based on the physiopathology, and

therefore to increase the chance of the fetus survive

Harrison 2003

Objectives


Fetal Imaging and Prenatal Diagnosis

• Earlier detection of surgical problems

• Understand prenatal natural history

• Influence perinatal management (based on prognosis)


Fetoscopy

Open fetal surgery

Ultrasound-guided fetal shunts

Ultrasound-guided fetal fluid drainage

Intra-uterine fetal blood transfusion

Classification of fetal intervention


Open fetal surgeriesRisks

Bleeding and hemorrhage

Uterine rupture

Placental abruption

Histerectomy

Blood transfusion

Risks for future pregnancies

Harrison 2003

Fetoscopies

Less invasive procedures

Absence of hysterotomy

Under ultrasound-fetoscopic guidance


Fetal endoscopic surgery

(FETOSCOPY)


Malformations

• Twin-twin transfusion syndrome

• Congenital diaphragmatic hernia

• Lower urinary tract obstruction

• Open neural tube defect

• Amniotic band syndrome

• Lung lesions/Tumors w/ hydrops

• Fetal Anemia

• Bilateral hydrothorax

• Ao/Pu stenosis

• CHAOS

Procedures

• Fetoscopic Laser Ablation (FLA)

• Fetal Endoscopic Tracheal

Occlusion (FETO)

• Fetal vesicoamnitic shunt / fetal

cystoscopy

• Prenatal repair

• Amniotic band release

• Open resection / ablation

• Intra-uterine blood transfusion

• Fetal thoraco-amniotic shunt

• Fetal valvoplasty

• EXIT procedure

Twin-twin

transfusion

syndrome

Fetoscopic laser

ablation of placental

anastomoses

1 in 58 twin pregnancies or1 in 4,000 pregnancies

Definition Monochorionic twin pregnancy

Polyhydramnios (≥8cm or ≥10cm ) / oligohydramnios (≤2m)

Signs:

Same gender

Difference of weight

Dilated bladder in the recipient

Small or absent bladder in the donor twin


Twin-twin transfusion syndrome

Receptor� Polyhydramnios� Congestive heart failure� Brain hemorrhages� Hydropsy� Death

If no prenatal intervention (natural history)risk of death of both twin 70%

Risk of death of one twin 80%

risk of brain demage in the co-twin 30%

Donor�Olygohydramnios/Anyhydramnios� Vasoconstriction� Arterial hypertension� Tissue ischemia� Death


Classification

Stage I. Poly/Olygohydramnios with a present bladder in the donor

Stage II. Absent bladder in the donor

Stage III. Abnormal Doppler

Stage IV. Hydropsy in one twin

Stage V. Death of one twin

Quintero et al 1999


Indications*

*

Amnioreduction

Sepstotomy

Laser (Stages II-IV)

Umbilical cord occlusion



TTTS II/III and IV – prenatal therapies Amnioreduction/S

eptostomy

Total 40%

One fetus 40%

Both fetus 30%

Survival rate

Total 15%

Vascular palsy 22%

Neurological delay

25%

Brain lesions

Cincotta et al 2000, Ling et al 2000, Frusca et al2003, Leung et al 2003, Jonhsen et al 2004,Rodeck et al 2006, van den Wijngaard et al 2007

Saade et al 1998, Johnson et al 2000, Adegbiteet al 2003, Moise et al 2005, Ross et al 2006

Total 80%

One fetus 80%

Both fetus 60%

Survival rate

Total 5%

Vascular palsy 5%

Brain lesions

Fetoscopic laser ablation

Ville et al 1995, Ville et al 1998, Lopriore et al 2003,Senat et al 2004, Duncan et al 2005, Nizard et al2006, Leclen et al 2007, Rossi et al 2008, Robert et al2008, Robert et al 2008


Fetoscopic laser ablation

Based on the physiopathology of the syndrome

Under ultrasound-fetoscopic guidance

“Cold coagulation”

Ruano et al 2013


Results of laser- Total survival rate= 68%

- Survival of at least one fetus = 89%

- Dual twin survival = 80%


TTTS– clinical research/trials(Texas Children’s Fetal Center – Pavilion for Women)


New fetoscopic techniques for posterior placental

Stem cell studies

Fetal cardiac evaluation prior and after FI

Congenital

Diaphragmatic Hernia

(CDH)

Fetal Endoscopic

Tracheal Occlusion

(FETO)

Congenital diaphagmatic hernia

Defect of the diaphragmatic formation

Herniation of abdominal viscera into fetal thorax

High mortality and morbidity (pulmonary hypoplasia and pulmonary hypertension)

During fetal life the respiratory function is supported by the placenta


Open fetal surgery

Initial resultsSurvival rate:

38% w/ postnatal therapy

15% w/ open fetal surgery

Purpose:Fetal endoscopic tracheal occlusion

(FETENDO)

Harrison et al.,1980

Harrison et al 1993


Principles Clinical observation from Congenital High Airway Obstruction Syndrome (CHAOS)

Harrison et al.,1980; Adzick et al.,1985; Di Fiori et al.,1994

Experimental studies


Less invasive procedure

Deprest et al., 2004


Ruano et al.,2010

Inclusion criteria: Isolated Left and right CDH

LHR < 1.0 (o/e-LHR<0.25)

Liver herniation

o/e-TFLV < 0.35

VI < 25%

Technical aspects: Maternal local anesthesia

Uterine puncture

Trocar 2.7-3.5 mm

Scope 1.0-1.3 mm

Detachable balloon

22-29 weeks


Indications*

*

Lung-to-head ratio (Standardization)


“The area equaled the product of the longest two perpendicular linear measurements (ie, 10 mm x 14 mm = 140 mm2). The right lung area to head circumference ratio (LHR) was calculated by a simple ratio of right lung area (in square millimeters) to head circumference (in millimeters)”

“to minimize lung size differences ow ing to gestational age”

Metkus et al 1996; Jani et al. 2007; Britto et al. 2015

Ultrasound Liver-to-thoracic ratio (US-LiTR)


Britto et al 2014

CDH– clinical research/trials(Texas Children’s Fetal Center – Pavilion for Women)

FETO for severe CDH (ClinicalTrials.gov Identifier: NCT00881660)

Hyperoxygenation study

Standardization of prenatal ultrasound evaluation


Lower Urinary Tract

Obstruction (LUTO)

Fetal Vesico-

amniotic shunt and

cystoscopy

LUTO - Etiology

Posterior urethral valves (PUV)

Urethral atresia (UA)

Urethral stenosis (US)

Prune-Belly syndrome

Anterior urethral valves (AUV) /

megalourethra

Obstructing ureterocele


No change in incidence of LUTO or PBS

(1:3000) between 1996 and 2009

Antenatal screening detects about 50%

LUTO - Etiology


PUV PredictorsFetal surgery: interventional opportunities

LUTO - Importance

Incidence: 1 in 2,000

High mortality (45-95%)

Secondary oligohydramnios

Pulmonary hypoplasia

Impairment renal function (50%)

Harrison et al.,1983; Freedman et al.,1999.


LUTO - Prenatal diagnosis

Fetal ultrasound

1st trimester (megacystis)

2nd trimester

Etiology CANNOT be determined by

ultrasound or MRI

Fetal cystoscopy


LUTO - Perinatal prognosis Associated anomaly – poor prognosis

Isolated LUTO Ultrasound findings

OligohydramniosHyperechogenic renal cortexGrade of hydronephrosisRenal cortical cystsRenal dysplasia

Borrelli et al.,2004; Craparo et al.,2007; Ruano et al 2015


Hydronephrosis - classification

Grignon et al 1986


Hydronephrosis - classification

Grignon et al 1986


Renal dysplasia

Grignon et al 1986


LUTO - Perinatal prognosis

Isolated LUTO Fetal urinary biochemistry Na urinary < 90mEq/L Cl urinary < 80mEq/L Osm urinary < 200mOsm/L Ca urinary < 7mg/dL β2-microglobulina (serium) < 6mg/L

Borrelli et al.,2004; Craparo et al.,2007

After 20 weeks


LUTO - Fetal Therapy

Ruano et al 2011

Vesico-amniotic shunting Fetal cystoscopy


Indications*- Severe LUTO with ‘favorable’ fetal renal function

Method: Maternal local anesthesia

Percutaneous - with either the King’s College/Rocket introducer, Harrison shunting set or Hakko double basket

Many case reports

Vesico-amniotic shunting


Ruano et al 2011

Fetal Cystoscopy

Method: Maternal epidural

Intramuscular fetal anesthesia (Fentanyl and Pancuronium)

Curved trocar 2,2 mm

1.0mm or 1.2 mm Fetoscope

Laser ND:YAG or Diode laser


LUTO – clinical research/trials(Texas Children’s Fetal Center – Pavilion for Women)

Standardized prenatal care for LUTO - database study (ClinicalTrials.gov Identifier: NCT02315521)

Fetal cystoscopy


Open neural tube

defect

Open and fetoscopic

repair


Fetal Surgery for Myelomeningocele

⇒Defect not life-threatening

⇒Evidence in support of “2 hit” hypothesis


Fetal Surgery Rationale

⇒ First hit: Congenital anomaly⇒ Second hit: Disability partly due to ongoing

damage from in utero environment� Ongoing CSF leak from open neural tube

defect leading to hindbrain herniation and compression of brainstem and spinal cord

� Direct mechanical damage� Inflammatory/ toxic effects of amniotic fluid

Heffez, et al. Neurosurgery 32:1005, 1993


MMC: Fetal Surgery

Reversal of Chiari Malformation




Fetoscopic repair of myelomeningocele

⇒ Experimental studies in sheep model

⇒ Research protocol in humans (TCH-PFW, BCM)

NTD– clinical research/trials(Texas Children’s Fetal Center – Pavilion for Women)

Fetoscopic repair of NTD- database study

(ClinicalTrials.gov Identifier: NCT02230072)


Thank you

[email protected];[email protected]

⇒ Maternal Fetal Medicine� Michael Belfort, MD, PhD� Rodrigo Ruano, MD� Alireza Shamshirsaz, MD� Jimmy Espinoza, MD� Wesley Lee, MD

⇒ Fetal/ Pediatric Surgery� Darrell Cass, MD� Oluyinka Olutoye, MD,

PhD� Timothy Lee, MD

⇒ Fetal Radiology� Chris Cassady, MD� Amy Mehollin-Ray, MD

⇒ Fetal Cardiology� Nancy Ayres, MD� Carrie Altman, MD� Shaine Morris, MD� Shiraz Maskatia, MD

⇒ Neonatology� Steve Welty, MD

⇒ Urology� David Roth, MD� Chester Koh, MD� Patricio Gargollo, MD

⇒ Nephrology� Michael Braun, MD

⇒ Interventional Cardiology� Henri Justino, MD

⇒ Nurse Coordinators� Carmen Watrin� Angel Krueger� Laura Mollett� Jayme Molohon� Florence Anyanwu

Texas Children’s Fetal Center – 832-822-2229

mailto:[email protected]

mailto:[email protected]

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Fetal surgery: interventional opportunitiesaium.s3.amazonaws.com/events/ann2015/fetus/14... · Fetal surgery: interventional opportunities “The area equaled the product of the longest