Daniel von Allmen

Infliximab in pediatric ulcerative colitis: two-year follow-up.

Objectives: The role of infliximab in treating pediatric ulcerative colitis (UC) is not defined. The authors previously have described their experience with the open label use of infliximab in nine children with moderate to severe UC. The aim of this study was to describe the outcome of these patients after a minimum 2-year follow-up and to describe the responses of eight additional patients to this medication. Methods: The authors reviewed all pediatric patients with UC who received infliximab at The Childrens Hospital of Philadelphia from its first use until February 2003. Tolerance of the infusions and adverse events were recorded. Results: Follow-up information for a minimum of 2 years was reviewed for the nine initial patients. A total of 73 infliximab infusions were administered to these patients. Seven of nine (78%) patients were considered to be responders to the initial dose of infliximab. Two of these patients became nonresponders within 9 months of the first dose of infliximab and underwent colectomy. Of the remaining five (56%) patients with sustained response, two continue to receive infliximab infusions and three are doing well without infliximab. One patient experienced an infusion reaction, and one experienced herpes zoster infection. We have treated eight additional UC patients with infliximab. Seven (88%) patients were considered responders. One responder experienced relapse within 2 months. Overall, a short-term improvement was seen in 14 of 17 (82%) patients, and sustained improvement in 10 of 16 (63%) patients followed up for more than 9 months. All five patients with severe or fulminant UC, unresponsive to 2 weeks of intravenous corticosteroid therapy, experienced improvement with infliximab. Infliximab was well tolerated. Conclusion: Infliximab is associated with short- and long-term clinical improvement in children and adolescents with moderate to severe UC.

Laparoscopic-assisted bowel resection offers advantages over open surgery for treatment of segmental Crohn's disease in children.

BACKGROUND/PURPOSE Minimally invasive approaches have been shown to decrease hospital length of stay (LOS), decrease postoperative pain, and speed return to normal activity for a number of intraabdominal procedures. In this study, laparoscopic (LAP)-assisted bowel resection is compared with an open technique for patients undergoing an initial bowel resection. METHODS A retrospective review was conducted of 28 patients (12 LAP, 16 open) undergoing initial bowel resection for segmental Crohns disease. RESULTS Patients in the LAP group had decrease LOS (5.5 days v 11.5 days) decreased days of parenteral narcotics (3 days v 5 days) and more rapid return to regular diet (3 days v 5 days). CONCLUSIONS The data suggest that the laparoscopic approach may offer advantages to pediatric patients undergoing an initial bowel resection for segmental Crohns disease.

Primary tumor control in patients with stage 3/4 unfavorable neuroblastoma treated with tandem double autologous stem cell transplants.

Objective To assess the efficacy and toxicity of local radiotherapy in achieving local control in patients with stage 4 or high-risk stage 3 neuroblastoma treated with induction chemotherapy and tandem stem cell transplants. Methods Fifty-two children with stage 4 or high-risk stage 3 neuroblastoma were treated on a standardized protocol that included five cycles of induction chemotherapy, surgical resection of the primary tumor when feasible, local radiotherapy, and then consolidation with tandem myeloablative cycles with autologous peripheral blood stem cell rescue. Local radiotherapy (10.5–18 Gy) was administered to patients with gross or microscopic residual disease prior to the myeloablative cycles. Thirty-seven patients received local radiotherapy to the primary tumor or primary tumor bed. Two patients with unknown primaries each received radiotherapy to single, unresectable, bulky metastatic sites. The second of the myeloablative regimens included 12 Gy of total body irradiation. Results Of the 52 consecutively treated patients analyzed, 44 underwent both transplants, 6 underwent a single transplant, and 2 progressed during induction. Local radiotherapy did not prolong recovery of hematopoiesis following transplants, did not increase peritransplant morbidity, and did not prolong the hospital stay compared with patients who had not received local radiotherapy. Local control was excellent. Of 11 patients with disease recurrence after completion of therapy, 9 failed in bony metastatic sites 3 to 21 months after the completion of therapy, 1 recurred 67 months following therapy in the previously bulky metastatic site that had been irradiated, and 1 had local recurrence concurrent with distant progression 15 months following the second transplant. The three-year event-free survival was 63%, with a median follow-up of 29.5 months. The actuarial probability of local control was 97%. Conclusions The use of induction chemotherapy, aggressive multimodality therapy for the primary tumor, followed by tandem myeloablative cycles with stem cell transplant in patients with stage 4 or high risk stage 3 neuroblastoma has resulted in acceptable toxicity, a very low local recurrence risk, and an improvement in survival.

Distance to care and relative supply among pediatric surgical subspecialties

BACKGROUND/PURPOSE The aim of this study is to describe geographic proximity to and quantify relative supply of 7 pediatric surgical specialties in the United States. METHODS Data from the 2005 American Medical Association Physician Masterfile and the Claritas Pop-Facts Database were used to calculate subspecialty-specific, population-weighted, straight-line distances between each zip code centroid and the nearest provider. These same data sources were used to calculate the percentage of hospital referral regions with a provider, the percentage of the younger than 18 years population living within selected distances of providers, and provider-to-population ratios for each of the pediatric surgical subspecialties. Further, we calculated the correlation between practice locations and childrens hospitals offering pediatric surgical services. RESULTS Across pediatric surgical specialties, average distances to the nearest provider ranged from 27.1 miles for pediatric surgery to 100.9 miles for pediatric cardiothoracic surgery. The average population-weighted distance to a provider was less than 30 miles for pediatric surgery and pediatric ophthalmology only. For 5 of the 7 pediatric surgical specialties studied, approximately one quarter of the younger than 18 years population lives more than 1-hour drive from a provider. Provider-to-younger than 18 years population ratios range across hospital referral region from 0.04 per 100,000 for pediatric cardiothoracic surgery to 0.97 per 100,000 for pediatric surgery. The correlation between pediatric surgeons and childrens hospitals offering services was 0.72. CONCLUSIONS Although the practice locations of pediatric surgical subspecialties parallel the geographic distribution of children in the United States, large percentages of the younger than 18 years population must travel long distance to receive care from these providers. Large coefficients of variation reveal substantial maldistribution. These findings lay the groundwork for workforce assessments of the pediatric surgical subspecialties and underscore the need for future studies that assess access barriers for children in need of surgical care.

Risk of incomplete pyloromyotomy and mucosal perforation in open and laparoscopic pyloromyotomy.

BACKGROUND Despite randomized controlled trials and meta-analyses, it remains unclear whether laparoscopic pyloromyotomy (LP) carries a higher risk of incomplete pyloromyotomy and mucosal perforation compared with open pyloromyotomy (OP). METHODS Multicenter study of all pyloromyotomies (May 2007-December 2010) at nine high-volume institutions. The effect of laparoscopy on the procedure-related complications of incomplete pyloromyotomy and mucosal perforation was determined using binomial logistic regression adjusting for differences among centers. RESULTS Data relating to 2830 pyloromyotomies (1802 [64%] LP) were analyzed. There were 24 cases of incomplete pyloromyotomy; 3 in the open group (0.29%) and 21 in the laparoscopic group (1.16%). There were 18 cases of mucosal perforation; 3 in the open group (0.29%) and 15 in the laparoscopic group (0.83%). The regression model demonstrated that LP was a marginally significant predictor of incomplete pyloromyotomy (adjusted difference 0.87% [95% CI 0.006-4.083]; P=0.046) but not of mucosal perforation (adjusted difference 0.56% [95% CI -0.096 to 3.365]; P=0.153). Trainees performed a similar proportion of each procedure (laparoscopic 82.6% vs. open 80.3%; P=0.2) and grade of primary operator did not affect the rate of either complication. CONCLUSIONS This is one of the largest series of pyloromyotomy ever reported. Although laparoscopy is associated with a statistically significant increase in the risk of incomplete pyloromyotomy, the effect size is small and of questionable clinical relevance. Both OP and LP are associated with low rates of mucosal perforation and incomplete pyloromyotomy in specialist centers, whether trainee or consultant surgeons perform the procedure.

The predictive value of head ultrasound in the ECMO candidate

Cranial ultrasound (US) examination is the screening technique of choice for assessing preexisting neurological damage in potential neonatal extracorporeal membrane oxygenation (ECMO) candidates. Currently, US evidence of intracranial hemorrhage greater than grade I in severity is a contraindication to ECMO at this ECMO center. In the current study, radiological findings were reviewed in 129 consecutive neonatal ECMO cases in an attempt to identify which pre-ECMO US findings were associated with the development of subsequent intracranial complications while on ECMO. Pre-ECMO head US, post-ECMO head US, and head computed tomography (CT) scans were reviewed retrospectively by one radiology team. Ventricular, parenchymal, and extraaxial fluid abnormalities were recorded for each case. Pre-ECMO US findings were then correlated with the subsequent development of significant intracranial radiological abnormalities noted on post-ECMO studies as well as with clinical data regarding ECMO course and outcome. Results showed that infants with evidence of severe edema or periventricular leukomalacia on pre-ECMO imaging had a 63% incidence of subsequent major intracranial complications. This represents a significantly higher risk than in candidates with a normal examination or evidence of grade I intracranial hemorrhage, subependymal cysts, or mild edema. These results suggest that infants with sonographic evidence of ischemic or anoxic damage on pre-ECMO US are at high risk for the development of significant intracranial complications if ECMO therapy is instituted.

Intestinal interleukin-13 in pediatric inflammatory bowel disease patients.

Background:Interleukin-13 (IL-13) is a multifunctional cytokine whose net principle action is to diminish inflammatory responses. Dysregulation of IL-13 production has been proposed to contribute to intestinal inflammation in inflammatory bowel disease (IBD) patients. Previous studies implicate IL-13 in IBD pathogenesis; however, they fail to accurately reflect in vivo intestinal IL-13 production. We evaluate IL-13, IL-6, and IL-1β elaborations from colonic organ cultures of pediatric IBD patients Methods:Endoscopic lamina propria biopsies or surgical specimens from pediatric patients with IBD were organ cultured and supernatants evaluated by enzyme-linked immunosorbent assay for IL-1β, IL-6, and IL-13. Results:IL-13 concentrations were significantly reduced in ulcerative colitis (UC) patients when compared with normal controls (P = 0.002) and Crohn disease (CD) patients (P = 0.001). End-stage UC patients at colectomy had lower intestinal IL-13 production than all other UC patients (P = 0.002). No significant correlation was found between IL-13 concentration and histologic disease severity (P = 0.134). Conclusions:Diminished intestinal IL-13 production is present in UC patients and wanes further with clinical disease progression. These findings suggest that UC patients may be differentiated from CD patients by intestinal IL-13 quantitation, and UC patients may benefit from IL-13 enhancing therapies.

Three-dimensional ultrasound guidance of autonomous robotic breast biopsy: feasibility study.

Feasibility studies of autonomous robot biopsies in tissue have been conducted using real-time three-dimensional (3-D) ultrasound combined with simple thresholding algorithms. The robot first autonomously processed 3-D image volumes received from the ultrasound scanner to locate a metal rod target embedded in turkey breast tissue simulating a calcification, and in a separate experiment, the center of a water-filled void in the breast tissue simulating a cyst. In both experiments the robot then directed a needle to the desired target, with no user input required. Separate needle-touch experiments performed by the image-guided robot in a water tank yielded an rms error of 1.15 mm. (E-mail: kaicheng.liang@duke.edu).

The genetics of Hirschsprung disease

Understanding the genetics of Hirschsprung disease will naturally expand our understanding of other neurocristopathies, the enteric nervous system, and autonomic system biology. As other disorders of gastrointestinal motility are investigated, genetics may resolve certain clinical questions. For example, isolated hypoganglionosis without aganglionosis has been reported as a primary cause of intestinal pseudo-obstruction. Is such hypoganglionosis merely a forme-fruste of Hirschsprung disease, or a result from an entirely different pathogenetic mechanism? Can irritable bowel syndrome or severe constipation be related to specific mutations, polymorphisms, or haplotypes? How might an understanding of derangements of the ENS be translated to understanding derangements of the CNS? Clearly, we should anticipate improved prognostication, counseling, and hopefully, therapies with future genetic insights.

Lung growth induced by tracheal occlusion in the sheep is augmented by airway pressurization

BACKGROUND/PURPOSE Prenatal tracheal occlusion (TO) has been shown to accelerate lung growth, yet the mechanism for this effect is poorly understood. Increased intratracheal pressure (ITP) with accumulation of lung fluid and secondary airway distension (stretch) may provide a mechanical stimulus for growth. In this study, ITP after TO is measured continuously, and the effect of altering ITP on lung growth is examined. METHODS Fetal lambs of 115 to 120 days of gestation (term, 145 days) underwent placement of an intratracheal catheter and an amniotic fluid reference catheter. First, ITP was monitored continuously in normal controls (n = 4) and in fetuses undergoing TO (n = 6). In a subsequent study, 2 groups of fetuses were compared. In the TO group (n = 5) ITP was monitored after TO. In the pressurized group (n = 5) ITP was maintained at 7 to 8 mm Hg by a continuous servo regulated pump that maintains a preset pressure by lactated Ringers infusion. The animals were killed after 4 days, and lung growth was compared. RESULTS In the control animals, ITP remained constant at 0.4 to 1.5 mm Hg. In the TO animals, ITP increased gradually during the initial 24 hours and plateaued at 4 to 5 mm Hg. In the second set of animals, ITP in the pressurized group was maintained at approximately 8 mm Hg using the infusion system. Lung volume (135.7+/-17.4 v. 95.2+/-14.8 mL/kg; P<.01), lung weight to body weight (6.70+/-0.73 v. 5.33+/-0.77%; P<.05), whole right lung dry weight (3.10+/-0.22 v. 2.63+/-0.20 mg/kg; P<.05), and right lung DNA and protein contents (87.3+/-6.0 v. 74.6+/-8.1 mg/kg, 2,310+/-248 v. 1,860+/-196 mg/kg, respectively; P<.05) were increased significantly in the pressurized group compared with the TO group. Morphometry confirmed greater volume of respiratory region and increased alveolar surface area in the pressurized lung. CONCLUSIONS TO results in a gradual increase in ITP over 15 to 24 hours, which plateaus at 4 to 5 mm Hg. Further increasing ITP by infusion of crystalloid significantly augments lung growth beyond that observed with TO alone. These data support the hypothesis that airway pressure and secondary mechanical stretch are the primary stimuli of TO induced lung growth.