Ex utero intrapartum treatment with extracorporeal membrane oxygenation for severe congenital diaphragmatic hernia

Purpose

The purpose of this study was to determine whether ex utero intrapartum treatment with extracorporeal membrane oxygenation (EXIT to ECMO) is a reasonable approach for managing patients antenatally diagnosed with severe congenital diaphragmatic hernia (CDH).

Methods

A 6-year retrospective review was performed on fetuses with severe CDH (liver herniation and a lung/head ratio <1.4, percentage of predicted lung volume <15, and/or congenital heart disease). Fourteen of the patients underwent EXIT with a trial of ventilation. Fetuses with poor preductal oxygen saturations despite mechanical ventilation received ECMO before their delivery. Maternal-fetal outcomes were analyzed.

Results

There were no maternal-reported complications. Three babies passed the ventilation trial and survived, but 2 of them required ECMO within 48 hours. The remaining 11 fetuses received ECMO before their delivery. Overall survival after EXIT-to-ECMO was 64%. At 1-year follow-up, all survivors had weaned off supplemental oxygen, but 57% required diuretics and/or bronchodilators.

Conclusion

This is the largest reported experience using EXIT to ECMO in the management of severe CDH. The EXIT-to-ECMO procedure is associated with favorable survival rates and acceptable pulmonary morbidity in fetuses expected to have a poor prognosis under conventional management.     

The ex utero intrapartum therapy procedure for high-risk fetal lung lesions

Background

Indications for the ex utero intrapartum therapy (EXIT) procedure have expanded to include any fetal anomaly in which resuscitation of the neonate may be compromised.

Methods

We reviewed the medical records of 9 patients after resection of lung lesions during the EXIT procedure.

Results

The mean gestational age at EXIT procedure was 35.4 weeks. All lung masses maintained large sizes late into gestation with mean mass volume/head circumference ratio of 2.5 at presentation and 2.2 at EXIT. Seven of 9 fetuses demonstrated hydropic changes (n = 6) and/or polyhydramnios (n = 5), and underwent prenatal intervention including thoracentesis, thoracoamniotic shunt placement, amnioreduction, and/or betamethasone administration. Overall survival after EXIT for lung mass resection was 89%. The average time on placental bypass was 65 minutes. Postnatal complications included reoperation for air leak (n = 1), reoperation for bleeding (n = 1), and death from sepsis and prematurity (n = 1). Venoarterial extracorporeal membrane oxygenation was used in 4 neonates for persistent pulmonary hypertension. Maternal prenatal complications included polyhydramnios (n = 5), preterm labor (n = 4), and chorioamnionitis (n = 1). One mother required perioperative blood transfusion.

Conclusion

The EXIT procedure allows for controlled resection of large fetal lung lesions at delivery, avoiding acute respiratory decompensation related to mediastinal shift, air trapping, and compression of normal lung.     

Severe pulmonary hypoplasia associated with giant cervical teratomas

Background

The use of the ex utero intrapartum treatment (EXIT) procedure has salvaged many fetuses with giant neck masses. Despite an adequate airway, a subset of these patients die from an inability to achieve adequate gas exchange.

Methods

We reviewed our experience with the EXIT procedure from 1996 to 2004. The EXIT was used to deliver 23 fetuses with giant neck masses.

Results

Three fetuses with giant cervical teratomas died of severe pulmonary hypoplasia. On postmortem, these patients had severe airway distortion by the mass. The carina was retracted superiorly to the first or second rib resulting in compression of the lungs in the apices of the chest and pulmonary hypoplasia. Hypoplasia was reflected in the lung weights of 24 vs 38 g and 17 vs 34 g for age-matched normal lung.

Conclusions

Unsuspected obstructive fetal neck masses can be fatal because of an inability to secure an airway. Prenatal ultrasonography can identify fetuses at risk, allowing the fetus to be salvaged using the EXIT procedure. Despite obtaining airway control, a subset of these patients will die because of pulmonary hypoplasia. When counseling patients with large cervical masses it is important to discuss potential pulmonary hypoplasia in these patients.     

Management of fetal mediastinal teratoma

Background/Purpose

Mediastinal teratomas are rare congenital germ cell tumors that prenatally can compress mediastinal structures and cause hydrops. Two possible presentations of massive fetal mediastinal teratoma include hydrops leading to fetal demise, or fetal esophageal and airway compression causing late-gestation polyhydramnios and preterm labor. The authors present 2 cases of fetal mediastinal teratoma that illustrate successful strategies for either of these presentations.

Methods

A 37-year-old woman carrying a fetus with a mediastinal mass and secondary hydrops at 23 weeks of gestation underwent in utero resection of the mass. Delivery was by cesarean delivery at 25 weeks because of preterm labor. A 24-year-old mother carrying a fetus with a mediastinal mass and severe polyhydramnios at 36 weeks of gestation underwent an ex utero intrapartum therapy procedure for establishment of an airway and tumor resection on uteroplacental support.

Results

These strategies resulted in physiologic improvement in the first case and controlled resection and resuscitation in the second. The first patient had significant sequelae of prematurity including bronchopulmonary dysplasia but is currently well at 9 months of age. The second patient is well at 1 year of age.

Conclusions

Massive fetal mediastinal teratoma can result in fetal or neonatal mortality by a variety of mechanisms. Optimal prenatal and perinatal management is required to salvage fetuses compromised by this lesion.     

Congenital high airway obstruction syndrome: natural history and management

Background

Congenital high airway obstruction syndrome (CHAOS) is a life-threatening condition with a poorly understood natural history.

Methods

A retrospective review of five patients with CHAOS between 1997 and 2002 was performed.

Results

All fetuses had large echogenic lungs, dilated airways, inverted diaphragms, and massive ascites. One fetus with a laryngeal cyst was terminated at 22 weeks. A twin fetus with findings suggestive of a tracheal web had progressive hydrops, which led to fetal demise. The remaining 3 patients delivered via the ex utero intrapartum treatment (EXIT) procedure survived. The first patient tolerated progressive hydrops for 12 weeks in utero. He had tracheal atresia but underwent laryngotracheoplasty successfully. He is the first long-term CHAOS survivor and is speaking at 5 years of age. The 2 patients with relatively stable lung volumes prenatally have laryngeal atresia with a pinpoint posterior laryngeal fistula. Their postnatal clinical courses were much more benign than the first survivor.

Conclusions

The prenatal natural history and postnatal course of CHAOS depends on whether the airway obstruction is complete. The EXIT procedure offers the potential for salvage of this otherwise lethal condition. Hydrops may be well tolerated prenatally for weeks with potential resolution if airway fistulization is present.     

Ex-utero intrapartum treatment procedure for giant neck masses--fetal and maternal outcomes

Background/Purpose

For fetuses with giant neck masses and tracheal obstruction, an ex-utero intrapartum treatment (EXIT) procedure allows for safe nonemergent airway management while on placental support. Our objective was to examine fetal and maternal outcomes after EXIT procedure specifically for giant neck masses.

Methods

The medical records of all patients referred to a comprehensive fetal center for a giant neck mass between 2001 and 2010 were reviewed retrospectively.

Results

Among 24 patients referred, an EXIT procedure was performed in 12 with evidence of tracheal compression. An EXIT procedure was not performed because of minimal tracheal involvement (n = 8), elective abortion (n = 2), fetal demise (n = 1), or obstetric complication (n = 1). In all fetuses, the airway was successfully secured; tracheal intubation was achieved with rigid bronchoscopy (n = 10), direct laryngoscopy (n = 1), and tracheostomy (n = 1). Eleven patients survived to discharge, whereas 1 patient with significant pulmonary hypoplasia died 8 days after emergency EXIT procedure. Of 11 surviving infants, 10 are neurodevelopmentally intact. All mothers who desired future pregnancies have subsequently had uncomplicated deliveries (n = 6).

Conclusions

Ex-utero intrapartum treatment procedure for giant neck mass can be performed safely for both mother and child. Most fetuses can be orotracheally intubated with minimal long-term morbidity. The potential for future pregnancies is preserved.     

Venovenous extracorporeal membrane oxygenation for cyanotic congenital heart disease

Background

Severe, refractory hypoxemia complicating uncorrected cyanotic congenital heart disease is a potentially lethal condition, even when urgent surgical intervention is undertaken. When a viral pneumonia initiates hypoxemia, the likelihood of a satisfactory outcome is further reduced. We examined our policy of venovenous extracorporeal membrane oxygenation support through the hypoxic event and performing delayed surgery, if required, to separate from extracorporeal membrane oxygenation.

Methods

A single institution, retrospective review of an Institutional Review Board approved database was undertaken. Over a 6-year period, 18 instances were identified for 17 patients who became acutely hypoxemic from either inadequate pulmonary blood flow (8 instances) or a viral pneumonia (10 instances) complicating their cyanotic heart disease. Demographics, duration of venovenous extracorporeal membrane oxygenation and outcomes are reported.

Results

The length of venovenous extracorporeal membrane oxygenation ranged from 13.5 to 362.5 hours (mean 130 ± 121 hours). During 10 supports, operations were performed to facilitate weaning from support. In 7 patients, extracorporeal support was weaned during this surgery. Follow-up was obtained in all patients over a period ranging from 4 months to 7 years (mean 39.0 ± 23.0 months). There were two late deaths due to sepsis 1.4 and 2.5 months after extracorporeal support.

Conclusions

Venovenous extracorporeal membrane oxygenation allows time for the recovery of acute hypoxic insult and resolution of some viral pneumonia processes. Palliative surgical procedures may be safely undertaken during extracorporeal support. Viral pneumonia is a risk for prolonged support. Venovenous extracorporeal membrane oxygenation is useful in these high-risk patients.     

The ex utero intrapartum treatment procedure: Looking back at the EXIT

Purpose

The ex utero intrapartum treatment (EXIT) procedure was developed originally for management of airway obstruction after fetal surgery, and indications have continued to expand for a variety of fetal anomalies. The authors review their single-institution experience with EXIT.

Methods

Retrospective review of all patients who underwent an EXIT procedure from 1993 to 2003 (n = 52) was performed. Variables evaluated include indication for EXIT, gender, gestational age at EXIT, birth weight, maternal blood loss, operative complications, operative time, and survival rate. Technique, personnel, and anesthesic management were reviewed.

Results

Long-term follow-up was available for all patients. Fifty-one of 52 patients were born alive; currently, 27 of 52 patients (52%) are alive. All deaths have been in patients with congenital diaphragmatic hernia. Forty-five patients underwent EXIT for reversal of tracheal occlusion for congenital diaphragmatic hernia. Of these patients, 30 underwent tracheal clip removal. Two patients had repair of tracheal injury from clipping at EXIT. Fifteen patients underwent bronchoscopy and tracheal balloon removal. Five patients underwent EXIT procedure for neck masses. Tracheostomy was performed in 3 of these patients. One patient was intubated successfully, and 1 patient underwent resection of the neck mass while on placental support. Two patients underwent EXIT procedure and tracheostomy for congenital high-airway obstruction syndrome. Average gestational age at delivery was 31.95 ± 2.55 weeks. Average birth weight was 1,895 ± 653 g. Average maternal blood loss was 970 ± 510 mL. Average operating time on placental support was 45 ± 25 minutes with a maximum of 150 minutes.

Conclusions

EXIT procedures can be performed with minimal maternal morbidity and with good outcomes. It is an excellent strategy for establishing an airway in a controlled manner, avoiding “crash” intubation or tracheostomy. Longer procedures on placental support allowing for definitive management of neck masses and airway obstruction have been realized. EXIT procedures have evolved from an adjunct to fetal surgery to a potentially life-saving procedure in fetuses with airway compromise at birth.     

Differential risk for neonatal surgical airway intervention in prenatally diagnosed neck masses

Purpose

We aimed to identify risk factors for neonatal surgical airway intervention among fetuses with prenatally diagnosed cervical masses.

Methods

An 8-year retrospective review identified 23 consecutive patients with a prenatal diagnosis of a neck mass, managed at a single tertiary center. Variables analyzed included anticipated diagnosis, extent of the mass, need for any surgical airway intervention in the neonatal period, final histopathology data, and survival. Statistical analysis was based on the Fisher and Fisher-Freeman-Halton exact tests (significance set at P ≤ .05) and exact 95% confidence intervals for risk differences.

Results

Eight patients underwent termination of pregnancy or were lost to follow-up. The imaging-based prenatal diagnosis was confirmed postnatally in 93% (14/15) of the remaining patients. Final diagnoses included lymphatic malformation (8), teratoma (6), and esophageal duplication (1). Teratomas were associated with a significantly higher risk for neonatal airway intervention than lymphatic malformations (67% vs 11%, P = .02). The majority of such procedures were performed under ex utero intrapartum treatment. Survival was 93% (14/15).

Conclusions

Cervical teratomas are significantly more likely to demand surgical airway intervention in the neonate, typically under ex utero intrapartum treatment, than cervical lymphatic malformations. These findings should be considered in the prenatal counseling for fetal cervical masses.     

Large fetal congenital cystic adenomatoid malformations: growth trends and patient survival

Purpose

The prognosis for fetuses with large congenital cystic adenomatoid malformations (CCAMs) remains uncertain. This study examined the natural history of large fetal CCAMs managed expectantly at a major referral center.

Methods

A 5-year retrospective review was conducted on fetuses diagnosed with a thoracic lesion (n = 59). Large CCAMs were identified on prenatal imaging and followed longitudinally. Perinatal outcomes were assessed.

Results

Twelve (20.3%) fetuses had large CCAMs in the absence of other congenital anomalies. Peak CCAM size occurred at 25.3 ± 3.6 weeks' gestation. Serial magnetic resonance volumetry demonstrated a trend toward decreasing CCAM mass volume relative to thoracic cavity volume over time. Overall, 6 patients, including 3 with signs of early hydrops, showed a marked regression of their lesions relative to estimated fetal weight. Five fetuses required an emergent intervention postnatally, including extracorporeal membrane oxygenation support (n = 1), cyst aspiration (n = 1), and lung resection (n = 5). Overall survival was 75%, with severe hydrops before 30 weeks seen in all 3 deaths.

Conclusion

Large fetal CCAMs tend to peak in size at 25 weeks' gestation and are characterized by in utero diminution relative to overall fetal growth. The prognosis for most fetuses with large CCAMs remains quite favorable under careful perinatal management.     

Successful in utero gene transfer using a gene gun in midgestational mouse fetuses

Background/Purpose

In utero gene therapy offers a number of potential advantages over postnatal gene therapy. A latest method of gene transfer to fetuses in utero uses a new tool called a gene gun. The gene gun is less invasive and simpler than other in utero methods. The current study was designed to determine whether the gene gun is an effective tool for transferring genes to mouse fetuses in utero.

Methods

Using a gene gun, we transferred plasmids that included enhanced green fluorescent protein (EGFP) genes and cytomegalo virus promoters to the abdominal skin of 40 A/J fetal mice at each of 3 gestational ages (13, 14, or 15 days). Four or 5 days after gene transfer, the number of surviving fetuses was counted, and a color image of EGFP in the skin was analyzed for gene transfer rates by fluorescence microscopy. Survival rates were analyzed using Fisher’s Exact test.

Results

The mean survival rate was 89.2% (107 of 120) in gene transfer fetuses and 91.7% (55 of 60) in controls. There is no difference in survival rate between gene transfer fetus and control. The highest gene transfer rate was 100% (37 of 37) at the gestational age of 14 days. The rate was 97.1% (34 of 35) at gestational ages of 13 and 15 days.

Conclusions

The results of this study show that in utero gene transfer by gene gun is a less-invasive technique, and the gene gun is an effective tool transferring genes to mouse fetuses in utero.     

The EXIT procedure: experience and outcome in 31 cases

Background: The EXIT (ex utero intrapartum treatment) procedure, although initially designed for reversal of tracheal occlusion in fetuses with congenital diaphragmatic hernias (CDH), has been adapted to treat a variety of fetal conditions. Methods: A retrospective chart review of all consecutive EXIT procedures since 1996 was conducted. Results: Thirty-one women underwent the EXIT procedure, with an average maternal age of 29 years (range, 20 to 38), and average gestational age of 34 weeks (range, 29 to 40). The indication was airway obstruction from fetal neck mass in 13, and reversal of tracheal occlusion from in utero clipping in 13. Singular indications included an EXIT-to-ECMO (extracorporeal membrane oxygenation) procedure for a fetus with CDH and a cardiac defect (n = 1), congenital high airway obstruction syndrome (CHAOS, n = 1), resection of a very large congenital cystic adenomatoid malformation of the lung (CCAM) on uteroplacental bypass (n = 1), unilateral pulmonary agenesis (n = 1), and thoracoomphalopagus conjoined twins. The mean duration on uteroplacental bypass (from uterine incision to umbilical cord clamping) was 30.3 [plusmn] 14.7 minutes (range, 8 to 66). No fetus experienced hemodynamic instability during uteroplacental bypass as recorded by fetal heart rate (FHR), pulse oximeter, and fetal echocardiography, except for one instance of reversible bradycardia from umbilical cord compression. The mean FHR and fetal saturation were 153.0 [plusmn] 38.5 beats per minute and 71.2% [plusmn] 19.9%, respectively. Five fetuses required a tracheostomy. Only 1 death occurred during an EXIT procedure because of inability to secure the airway secondary to extensive involvement by a lymphangioma. The average cord pH and pCO₂ were, respectively, 7.20 [plusmn] 0.11 and 63.2 [plusmn] 14.6. Two maternal complications occurred: bleeding from a hysterotomy site and dehiscence of an old hysterotomy scar noticed at a subsequent cesarean section. The average maternal blood loss was 848.3 [plusmn] 574.1 mL. Conclusion: The EXIT procedure was used successfully to ensure uteroplacental gas exchange and fetal hemodynamic stability during a variety of surgical procedures performed to secure the fetal airway or ensure successful transition to postnatal environment.     

Effects of early vesicostomy in obstructive uropathy on bladder development

Purpose

Creation of a vesico-amniotic shunt for obstructive uropathy removes the normal fetal urination cycle. It is unclear how this affects bladder function at term. The authors measured the bladder volume and reviewed the bladder histology after fetal vesicostomy.

Methods

The authors created an obstructive uropathy in fetal lambs at 60 days’ gestation by ligating the urethra and urachus. Vesicostomy (female) or urethrostomy (male) were performed 21 days after obstruction to release the obstruction. The fetuses were killed at term (145 days).

Results

Thirteen fetuses were shunted. Seven fetuses miscarried after shunting. Six survived, and 3 had a successful shunt with a very small bladder (5 to 7 mL). Two had incomplete shunts that failed some time after shunting. These both had huge bladders (399 mL). In one, the obstruction was unsuccessful. Histologic examination showed that the obstruction caused bladder muscle hypertrophy. Shunted lambs had severe fibrosis of the bladder wall and very poor bladder compliance.

Conclusions

Shunt operations after obstructive uropathy may salvage the kidney but fail to preserve bladder function. The fetus needs a normal urination cycle for normal bladder development. This requirement exists even when the obstruction is successfully bypassed.     

Impact of prenatal evaluation and protocol-based perinatal management on congenital diaphragmatic hernia outcomes

Background/Purpose

Although intuitive, the benefit of prenatal evaluation and multidisciplinary perinatal management for fetuses with congenital diaphragmatic hernia (CDH) is unproven. We compared the outcome of prenatally diagnosed patients with CDH whose perinatal management was by a predefined protocol with those who were diagnosed postnatally and managed by the same team. We hypothesized that patients with CDH undergoing prenatal evaluation with perinatal planning would demonstrate improved outcome.

Methods

Retrospective chart review of all patients with Bochdalek-type CDH at a single institution between 2004 and 2009 was performed. Patients were stratified by history of perinatal management, and data were analyzed by Fisher's Exact test and Student's t test.

Results

Of 116 patients, 71 fetuses presented in the prenatal period and delivered at our facility (PRE), whereas 45 infants were either outborn or postnatally diagnosed (POST). There were more high-risk patients in the PRE group compared with the POST group as indicated by higher rates of liver herniation (63% vs 36%, P = .03), need for patch repair (57% vs 27%, P = .004), and extracorporeal membrane oxygenation use (35% vs 18%, P = .05). Despite differences in risk, there was no difference in 6-month survival between groups (73% vs 73%).

Conclusions

Patients with CDH diagnosed prenatally are a higher risk group. Prenatal evaluation and multidisciplinary perinatal management allows for improved outcome in these patients.     

Low recurrence rate after Gore-Tex/Marlex composite patch repair for posterolateral congenital diaphragmatic hernia

Purpose

Many different prosthetic materials have been used for repair of large posterolateral congenital diaphragmatic hernias (CDH), with high recurrence rates for hernias that cannot be primarily repaired. Since 1993, we have used a composite patch of Gore-Tex/Marlex to repair large CDHs and hypothesized that this repair leads to fewer recurrences.

Methods

This is a retrospective review of 137 consecutive patients with CDH cared for at a single institution from 1993 to 2004. Data collected include timing and method of repair and use of extracorporeal membrane oxygenation. Outcomes include hernia recurrence, complications, and death.

Results

One hundred thirty-seven patients with CDH were analyzed. Repair was not attempted in 12 because of disease severity. Primary repair was accomplished in 79 and 46 required patch repair. Of the 46 patients with patch repairs, 32 required extracorporeal membrane oxygenation, and 18 died before discharge. Of the 28 patch repair survivors, 1 (3.57%) developed a recurrence over a median follow-up of 47 months (range, 2-115 months). Overall survival was 77%.

Conclusions

Gore-Tex/Marlex composite patch repair of large CDHs in this complex patient population results in a lower recurrence rate than has been reported for other types of prosthetic diaphragm repair.     

In utero repair of gastroschisis in the sheep (Ovis aries) model

Objective

Gastroschisis is associated with inflammatory changes in the exposed bowel which leads to intestinal dysmotility after postnatal repair. The insult is a combined effect of amniotic fluid exposure and mechanical constriction. We hypothesized that in utero anatomic repair is possible in a sheep model, and that it may halt the inflammatory damage caused by both mechanisms.

Methods

Gastroschisis was surgically created in mid-gestation (day 75) in 8 sheep fetuses. On gestational day 100, 2 fetuses underwent open fetal gastroschisis repair, where the eviscerated bowel was returned to the peritoneal cavity, and the abdominal wall was primarily closed. All fetuses were harvested at 135 days of gestation.

Results

Six fetuses survived the initial operation, and both fetuses that underwent gastroschisis repair survived to term. At 100 and 135 days of gestation, the eviscerated bowel showed progressive signs of inflammation and peel development. The gross and microscopic inflammatory changes in the gastroschisis bowel at 100 days of gestation were completely resolved at term following in utero repair.

Conclusion

In utero anatomic repair of gastroschisis is possible in mid-gestation in the fetal lamb model, and it appears to ameliorate the inflammatory process.     

Percent predicted lung volumes as measured on fetal magnetic resonance imaging: a useful biometric parameter for risk stratification in congenital diaphragmatic hernia

Purpose

This study was aimed at determining whether a new method of analyzing lung volumes on fetal magnetic resonance (MR) imaging could be used to predict the degree of pulmonary compromise in congenital diaphragmatic hernia (CDH).

Methods

Seventeen fetuses with CDH were prospectively evaluated by MR. Lung volumes were measured using an established technique and expressed as a percentage of the predicted lung volume (PPLV). Predicted lung volume was determined by subtracting measured mediastinal volume from total measured thoracic volume. The PPLV was correlated with postnatal outcomes. Statistical analyses were performed using the Mann-Whitney, Spearman correlation, or Fisher exact tests (P < .05).

Results

Of the 14 liveborn patients, the PPLV was 20.3±10.4 (gestational age at MR, 22.3 ± 5.7 weeks). The PPLV was significantly associated with extracorporeal membrane oxygenation (ECMO) use, hospital length of stay, and survival. All patients with a PPLV of less than 15 required prolonged ECMO support and had a 40% survival rate. In contrast, only 11% of patients with a PPLV of greater than 15 required ECMO, and survival was 100%.

Conclusion

The PPLV as measured by fetal MR imaging can accurately predict disease severity in CDH. A value of less than 15 is associated with a significantly higher risk for prolonged support and/or death, despite aggressive postnatal management.     

Outcome in Children Bridged and Nonbridged to Cardiac Transplantation

Background

Heart transplantation (HTx) in children with end-stage heart disease has become an accepted treatment option.

Objective

To evaluate our results of pediatric cardiac transplantation with vs without bridge methods.

Patients and Methods

The study included 31 patients (34 transplantations) younger than 18 years who underwent orthotopic HTx between March 1995 and December 2008. Ten patients were girls, and 21 were boys. Preoperative diagnoses included cardiomyopathy (n = 20), congenital heart disease (n = 7), hypertrophic cardiomyopathy (n = 2), restrictive cardiomyopathy (n = 1), and ischemic cardiomyopathy (n = 1). Mean (SD) ischemia time was 185 (72) minutes. Thirty-day mortality was 6%, and was due to primary graft failure (n = 2). Overall follow-up was 4.36 (3.93) years. Eleven patients underwent bridge techniques before HTx, and 11 patients required perioperative extracorporeal membrane oxygenation or ventricular assist device support.

Results

In the group that received extracorporeal membrane oxygenation, 8 patients (73%) were successfully weaned and discharged with excellent functional class. There were no differences in operative mortality, functional class, survival, rejection, and infection rates between the bridged and nonbridged groups. Overall actuarial 1- and 5-year survival rates were 93% and 83%, respectively. All survivors had good functional class.

Conclusion

Our findings demonstrate satisfactory medium-term outcome of HTx in selected pediatric patients with end-stage heart disease. Using bridge methods in children at high risk can increase the opportunity to receive a donor heart. These bridge methods achieve similar postoperative outcomes.     

Keyhole limpet hemocyanin potentiates standard immunotherapy for melanoma

Introduction

Our hypothesis was that keyhole limpet hemocyanin (KLH) would augment the effects of standard immunotherapies for melanoma including interferon-alpha (AIFN) and interleukin (IL)-2.

Methods

The HTB68 melanoma cell line was treated with KLH, AIFN, and IL-2 as single and combined agents. Cell viability, apoptotic activity, and vascular endothelial growth factor levels were all evaluated.

Results

Cell growth was reduced with KLH (28%), AIFN (54%), and IL-2 (29%) (all P < .001). KLH and IL-2 combined exhibited a 47% inhibition of cell growth, whereas KLH and AIFN combined yielded a 67% reduction in cell growth (both P < .001). KLH and AIFN combined significantly increased both early (10%) and late (14%) apoptotic activity compared with controls (5% and 7%, P < .001).

Conclusions

The additive effects exhibited by the combination of KLH with AIFN or IL-2 are encouraging and support combination therapy as an effective treatment for this aggressive disease.     

Extracorporeal membrane oxygenation support of the Fontan and bidirectional Glenn circulations

Background

Extracorporeal membrane oxygenation can provide effective mechanical circulatory support for the failing circulation in children. Patients with failing Fontan and bidirectional Glenn physiology present additional challenges both for extracorporeal membrane oxygenation cannulation and support. We report our institutional experience in patients with cavopulmonary connections who received extracorporeal membrane oxygenation.

Methods

We performed a retrospective review of 20 patients with cavopulmonary connections (14 Fontan and 6 bidirectional Glenn) who were supported with extracorporeal membrane oxygenation from a single, large pediatric tertiary care center.

Results

Of the 20 patients, ten were supported and decannulated successfully (50%) (two after cardiac transplantation), but only six (30%) are alive at follow-up. Of the 14 Fontan patients, seven (50%) were withdrawn from extracorporeal membrane oxygenation or died within 48 hours of decannulation due to lack of myocardial recovery or severe neurologic injury. All four adult-sized (> 40 kg) Fontan patients were withdrawn from extracorporeal support. The seven Fontan patients who were successfully decannulated survived to discharge, and five (35.7%) are alive at follow-up (median 35 months; range, 7 to 140 months). Of the six bidirectional Glenn patients, five died before hospital discharge and the lone survivor has neurologic injury at follow-up.

Conclusions

Patients with failing Fontan and bidirectional Glenn physiology present significant challenges to successful extracorporeal membrane oxygenation support. While the morbidity and mortality rates are high, there are select patients for whom extracorporeal support can be effective and lifesaving as a short-term resuscitative intervention.