Peter W. Dillon

Long-Term Outcome for Infants and Children With Sacrococcygeal Teratoma: A Report From the Childrens Cancer Group

BACKGROUND/PURPOSE Sacrococcygeal teratomas (SCT) are a relatively uncommon tumor affecting neonates, infants, and children. This study was designed to determine the effect of therapy on the long-term outcome of neonates and children with sacrococcygeal teratomas (SCT). METHODS The authors conducted a retrospective review of children with SCT treated at 15 Childrens Cancer Group institutions from 1972 to 1994. RESULTS One hundred twenty-six children presented with SCT diagnosed prenatally (n = 32), at birth (n = 79), or later in infancy (n = 15). For neonates, complete resection was performed except in two babies with lethal associated defects. All others (n = 15) underwent resection at the age of diagnosis. Six had a sacral mass identified at birth but had delayed surgery (1.5 to 11 months) and of these, two were malignant. Resection was via sacral (n = 96) or abdominosacral (n = 28) approach. Histology showed mature teratoma (MT, 69%), immature teratoma (IT, 20%), or endodermal sinus tumor (EST, 11%) at presentation. Seven neonates (5.6%) died of perioperative complications, whereas the remaining 117 were available for long-term follow-up. Between 6 and 34 months postresection, recurrent disease developed in 9 of 80 MT patients (11%) followed-up for a mean of 5 years. Recurrent disease was MT (n = 2) and EST (n = 7). The recurrent EST patients were treated with adjuvant chemotherapy. Six are alive with mean follow-up of 114 months, whereas one with metastatic disease was lost to follow-up. Recurrence (MT) developed in only 1 of 24 IT patients, and all are alive and well at mean follow-up of 39 months. Patients presenting with EST (n = 13) underwent excision, with two dying from non-EST causes. Six EST patients received no chemotherapy, with two of the six (33%) experiencing recurrence within 11 months and both disease free after salvage chemotherapy. The remaining five EST patients received adjuvant chemotherapy; four are alive and one died of metastatic disease. Of the 18 EST patients followed-up after resection (presentation, 11, recurrent teratoma, 7), 16 (89%) are free of disease with a mean follow-up of 91 months. CONCLUSIONS (1) Benign teratomas have a significant recurrence rate mandating close follow-up for more than 3 years. (2) Surgical resection alone is adequate therapy for nonmetastatic malignant tumors. (3) Survival for malignant lesions with metastases is excellent with modern chemotherapy.

Diagnosis, management, and outcome of cervicofacial teratomas in neonates: A Childrens Cancer Group study

The management of cervicofacial teratomas in neonates is often complicated and may result in significant morbidity and death. A Childrens Cancer Group (CCG) retrospective study was conducted to evaluate a multiinstitutional experience with the treatment of these extremely rare neoplasms. Twenty neonates with cervicofacial teratomas, presenting from 1971 to 1994, were identified from nine CCG institutions. Fourteen neonates had cervical teratomas, and six had orofacial teratomas. There were 12 males and eight females. A diagnostic prenatal ultrasound examination was performed in six cases. Life-threatening airway obstruction occurred in seven infants (35%) in the early postnatal period. Two neonates died in the delivery room without ever having their airway secured. Two other infants with a prenatal diagnosis survived only because tracheostomies were performed by pediatric surgeons who were in the delivery room. Three other patients were orally intubated, one after sustaining hypoxic cardiac arrest. Eighteen infants had their primary tumor excised. Three patients required tracheostomy. After resection, two patients had evidence of unilateral recurrent laryngeal nerve injury, and two required prolonged thyroid hormone replacement. Histological examination showed eight mature and seven immature teratomas. Four infants (20%) clearly had malignant lesions. Pulmonary metastases occurred in two patients and contributed to one late death at 6 months of age. The overall survival rate was 85%, and the mean follow-up period was 5 years (range, 2 months to 16 years). Twelve of 17 surviving patients (70%) have had an excellent functional and cosmetic outcome. Four children have varying degrees of developmental delay and mental retardation. Hypoxia at birth was believed to have contributed to these problems in two cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Anatomic and functional abnormalities of the esophagus in infants surviving congenital diaphragmatic hernia

As more infants with congenital diaphragmatic hernia (CDH) survive by means of extracorporeal membrane oxygenation (ECMO), new clinical observations are being made. We report anatomic and functional abnormalities of the esophagus in these infants. Twenty-two of 30 infants with CDH survived. Three of 7 non-ECMO-treated infants and 14 of 17 ECMO-treated infants had an air- or fluid-filled mediastinal mass that was confirmed by an upper gastrointestinal series as ectatic esophagus. Contrast studies demonstrated severe gastroesophageal reflux. Intra-esophageal pH monitoring confirmed significant reflux (Euler scores greater than 50) in 69% of tested patients. Prolonged acid clearance in most patients implied abnormal peristalsis. Hydramnios was correlated to the observed esophageal abnormalities, being present in 13 of 16 infants with an available amniotic history. All patients had symptomatic gastroesophageal reflux managed without antireflux surgery and were discharged 36 +/- 2 days after initiation of feeding. Follow-up (range: 7 to 56 months; mean: 32 months) showed that weight gain in affected children was slower than in those not affected. All but one are asymptomatic. Repeat upper gastrointestinal series shows persistent ectasia but less gastro-esophageal reflux. Gastroesophageal reflux/ectasia is a new observation with CDH. The associated hydramnios may result from proximal foregut obstruction by kinking the gastroesophageal junction with CDH. The radiographic appearance can be quite unusual. Clinical manifestations of gastro-esophageal reflux are manageable without surgery but may account for the observed compromised growth.

Pediatric American College of Surgeons National Surgical Quality Improvement Program: feasibility of a novel, prospective assessment of surgical outcomes

PURPOSE The American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) provides validated assessment of surgical outcomes. This study reports initiation of an ACS NSQIP Pediatric at 4 childrens hospitals. METHODS From October 2008 to June 2009, 121 data variables were prospectively collected for 3315 patients, including 30-day outcomes and tailoring the ACS NSQIP methodology to childrens surgical specialties. RESULTS Three hundred seven postoperative complications/occurrences were detected in 231 patients representing 7.0% of the study population. Of the patients with complications, 175 (75.7%) had 1, 39 (16.9%) had 2, and 17 (7.4%) had 3 or more complications. There were 13 deaths (0.39%) and 14 intraoperative occurrences (0.42%) detected. The most common complications were infection, 105 (34%) (SSI, 54; sepsis, 31; pneumonia, 13; urinary tract infection, 7); airway/respiratory events, 27 (9%); wound disruption, 18 (6%); neurologic events, 8 (3%) (nerve injury, 4; stroke/vascular event, 2; hemorrhage, 2); deep vein thrombosis, 3 (<1%); renal failure, 3 (<1%); and cardiac events, 3 (<1%). Current sampling captures 17.5% of cases across institutions with unadjusted complication rates ranging from 6.8% to 10.2%. Completeness of data collection for all variables exceeded 95% with 98% interrater reliability and 87% of patients having full 30-day follow-up. CONCLUSION These data represent the first multiinstitutional prospective assessment of specialty-specific surgical outcomes in children. The ACS NSQIP Pediatric is poised for institutional expansion and future development of risk-adjusted models.

American College of Surgeons National Surgical Quality Improvement Program Pediatric: A Phase 1 Report

BACKGROUND There has been a long-standing desire to implement a multi-institutional, multispecialty program to address surgical quality improvement for children. This report documents results of the initial phase of the American College of Surgeons National Surgical Quality Improvement Program Pediatric. STUDY DESIGN From October 2008 to December 2009, patients from 4 pediatric referral centers were sampled using American College of Surgeons National Surgical Quality Improvement Program methodology tailored to children. RESULTS A total of 7,287 patients were sampled, representing general/thoracic surgery (n = 2,237; 30.7%), otolaryngology (n = 1,687; 23.2%), orthopaedic surgery (n = 1,367; 18.8%), urology (n = 893; 12.3%), neurosurgery (n = 697; 9.6%), and plastic surgery (n = 406; 5.6%). Overall mortality rate detected was 0.3% and 287 (3.9%) patients had postoperative occurrences. After accounting for demographic, preoperative, and operative factors, occurrences were 4 times more likely in those undergoing inpatient versus outpatient procedures (odds ratio [OR] = 4.71; 95% CI, 3.01-7.35). Other factors associated with higher likelihood of postoperative occurrences included nutritional/immune history, such as preoperative weight loss/chronic steroid use (OR = 1.49; 95% CI, 1.03-2.15), as well as physiologic compromise, such as sepsis/inotrope use before surgery (OR = 1.68; 95% CI, 1.10-1.95). Operative factors associated with occurrences included multiple procedures under the same anesthetic (OR = 1.58; 95% CI, 1.21-2.06) and American Society of Anesthesiologists classification category 4/5 versus 1 (OR = 5.74; 95% CI, 2.94-11.24). Specialty complication rates varied from 1.5% for otolaryngology to 9.0% for neurosurgery (p < 0.001), with specific procedural groupings within each specialty accounting for the majority of complications. Although infectious complications were the predominant outcomes identified across all specialties, distribution of complications varied by specialty. CONCLUSIONS Based on this initial phase of development, the highly anticipated American College of Surgeons National Surgical Quality Improvement Program Pediatric has the potential to identify outcomes of childrens surgical care that can be targeted for quality improvement efforts.

Developing a NSQIP module to measure outcomes in children’s surgical care: opportunity and challenge

Under the guidance of the American College of Surgeons (ACS) and in partnership with the US Department of Veterans Affairs (VA), the National Surgical Quality Improvement Program (NSQIP) has been developed to improve the quality of surgical care in adults on a national level. Its purpose is to provide reliable, risk-adjusted outcomes data so that surgical quality can be assessed and compared between institutions. Data analysis consists of reporting observed to expected ratios (O/E) for 30-day postoperative mortality and morbidity measurements. A surgical clinical nurse reviewer is assigned at each medical center to collect information on 97 variables, including preoperative, operative, and postoperative factors for patients undergoing major operations in the specialties of general and vascular surgery. Eligible operations are entered into the database on a structured 8-day cycle to ensure representative sampling of cases. Since the introduction of the program into the VA system, there has been a 47% reduction in 30-day postoperative mortality and a 42% reduction in 30-day postoperative morbidity. Over 160 institutions have enrolled with the ACS in its adult NSQIP. In 2005, a planning committee was formed by the ACS and the American Pediatric Surgical Association to explore the development of a childrens surgery NSQIP module. In conjunction with the Colorado Health Outcomes Program at the University of Colorado, a program potentially applicable to all childrens surgical specialties has been designed. This manuscript describes the development of that Childrens ACS-NSQIP module.

American College of Surgeons National Surgical Quality Improvement Program Pediatric: A beta phase report

PURPOSE The American College of Surgeons (ACS) National Surgical Quality Improvement Program Pediatric (NSQIP-P) expanded to beta phase testing with the enrollment of 29 institutions. Data collection and analysis were aimed at program refinement and development of risk-adjusted models for inter-institutional comparisons. METHODS Data from the first full year of beta-phase NSQIP-P were analyzed. Patient accrual used ACS-NSQIP methodology tailored to pediatric specialties. Preliminary risk adjusted modeling for all pediatric and neonatal operations and pediatric (excluding neonatal) abdominal operations was performed for all cause morbidity (other than death) and surgical site infections (SSI) using hierarchical logistic regression methodology and eight predictor variables. Results were expressed as odds ratios with 95% confidence intervals. RESULTS During calendar year 2010, 29 institutions enrolled 37,141 patients. 1644 total CPT codes were entered, of which 456 accounted for 90% of the cases. 450 codes were entered only once (1.2% of cases). For all cases, overall mortality was 0.25%, overall morbidity 7.9%, and the SSI rate 1.8%. For neonatal cases, mortality was 2.39%, morbidity 18.7%, and the SSI rate 3%. For the all operations model, risk-adjusted morbidity institutional odds ratios ranged 0.48-2.63, with 9/29 hospitals categorized as low outliers and 9/29 high outliers, while risk-adjusted SSI institutional odds ratios ranged 0.36-2.04, with 2/29 hospitals low outliers and 7/29 high outliers. CONCLUSION This report represents the first risk-adjusted hospital-level comparison of surgical outcomes in infants and children using NSQIP-P data. Programmatic and analytic modifications will improve the impact of this program as it moves into full implementation. These results indicate that NSQIP-P has the potential to serve as a model for determining risk-adjusted outcomes in the neonatal and pediatric population with the goal of developing quality improvement initiatives for the surgical care of children.

Prophylactic Urokinase in the Management of Long-Term Venous Access Devices in Children: A Children's Oncology Group Study

PURPOSE Infection and thrombosis are serious complications of long-term vascular access devices in children undergoing chemotherapy. Since routine fibrinolytic therapy may decrease these complications, the purpose of this study was to compare the efficacy of an every-2-week administration of urokinase with standard heparin flushes in reducing the incidence of device-related infections and occlusions. MATERIALS AND METHODS This study was a prospective, randomized phase III multicenter trial conducted by the Childrens Cancer Group, in which patients with implantable ports or tunneled catheters received either urokinase or heparin every 2 weeks for 12 months. Study end points were time to first occlusion or time to first device-related infection. RESULTS Five hundred seventy-seven patients from 29 institutions were enrolled, of whom 51% had external catheters and 49% had ports. Urokinase administration resulted in fewer occlusive events than heparin (23% v 31%; P =.02), a longer time to first occlusive event (log-rank analysis, P =.006), and a 1.6-fold difference in the rate of occlusive events (Poisson regression, P =.003). Similar results were noted when comparing ports and tunneled catheters. The urokinase group also had a 1.4-fold difference in the rate of infection (Poisson regression, P =.05) and longer time to first infection (log-rank, P =.07), but the difference was significant only in tunneled catheters. CONCLUSION Urokinase administration every 2 weeks significantly affects the rate of occlusive events in ports and tunneled catheters and of infectious events in external catheters compared with heparin administration.

The inflammatory response in pediatric biliary disease: Macrophage phenotype and distribution

PURPOSE Extrahepatic biliary obstruction in infants and children leads to ductal hyperplasia and portal fibrosis. Inflammatory mediators responsible for increased cellular proliferation and matrix deposition are hypothesized to result from the intrahepatic recruitment and activation of lymphocytes and macrophages (M phi). The authors previously showed components of this mechanism in studies that demonstrated increased adhesion molecule expression in biliary atresia, as well as evidence of altered hepatic M phi function during the course of experimental cholestatic liver injury. Therefore they sought determine the expression of macrophage receptor markers CD68 and CD14 in pediatric biliary disease. METHODS Sixteen liver specimens were snap-frozen and cryosectioned onto polylysine-coated slides. Sections were stained with murine monoclonal antibodies to CD68 (resident M phi) and CD14 (monocyte-M phi lipopolysaccharide [LPS] receptor) glycoproteins. The sections were analyzed using a semiquantitative scale of proliferation and were position-graded from 0 to 3 (maximal). RESULTS Blinded analysis showed that marked proliferation of CD68-positive cells occurred in five of the six patients with biliary atresia (BA) and in one patient who had severe cholestasis. Normal perisinusoidal liver M phi were found in specimens from patients with hepatitis (2), choledochal cyst (1), and congenital hepatic fibrosis (1). Similarly, expression of CD14 periportal M phi was found only in patients with BA or cholestasis (1.9 +/- 0.3 [mean +/- SEM]) and was absent in other diseases. Strong sinusoidal expression of CD14 was evident in all patients who had extrahepatic biliary obstruction. An early biopsy specimen from a premature infant with BA did not show cholestasis, fibrosis, CD68 Mø proliferation, or CD14 expression; however, another biopsy specimen, obtained further in the course of jaundice showed the progressive development of all features. CONCLUSION These findings suggest proliferation of resident M phi in association with cholestasis. The presence of the LPS receptor on periportal cells during cholestatic liver injury points to a potential source of cytokines responsible for the inflammatory reaction of biliary atresia.

Congenital Diaphragmatic Hernia and Eventration

A review of 52 consecutive cases of congenital diaphragmatic hernia composed of 36 cases of Bochdalek hernia (B.H.) 13 of diaphragmatic eventration (D.E.), and 3 of diaphragmatic agenesis (D.A.) is reviewed critically. The operative mortality rate in Bochdalek hernia was 8.3% but became 20% with reference to the 15 infants with B.H. operated in the first 24 hrs. of life and 31.5% with reference to all 19 infants requiring repair of the diaphragmatic defect during the first day after birth. The operative mortality in D.A. was 100% and was nil in D.E. The mortality appeared related directly to prematurity, early age at operation, preoperative hypoxemia (PaO2 less than or equal to 60), hypercarbia, (PaCO2 greater than or equal to 60), and acidosis (pH less than or equal to 7.0), association with life-threatening anomalies affecting the lungs and its vessels, the heart, the size of the diaphragmatic defect and of the celomic cavity, the postoperative development of NEC and of obstructing intestinal adhesions. Eight of the 33 survivors (24%) with B.H. developed intestinal obstruction secondary to adhesions 2 months to 14 years after operation, of whom 7 required surgical intervention, and 3 bowel resections. The total mortality rate in B.H. was 14% and the rate in this series of combined defects was 15%.