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ABSTRACT: BACKGROUND: Intestinal lengthening remains a treatment option in pediatric short bowel syndrome. However, clinical indications and nutritional outcomes from bowel lengthening are not well defined. METHODS: A retrospective review of a prospective database was conducted of patients who underwent bowel lengthening using serial transverse enteroplasty (STEP) at a single center. RESULTS: Sixteen children who underwent 19 STEP procedures were identified. STEP increased median small bowel length from 84 cm (range, 19 to 295 cm) to 103 cm (range, 24 to 375 cm) (P = .0001). Caloric provisions from parenteral nutrition were decreased after STEP (69% vs 0%, P < .01). Of 15 subjects in the nutritional analysis, 12 (80%) had improved enteral tolerance, and 9 (60%) achieved enteral autonomy after STEP. Six STEP procedures were not associated with improvements in enteral nutrition, and 5 (83%) were performed in children with gastroschisis. CONCLUSIONS: A majority of children with short bowel syndrome were weaned off parenteral nutrition after STEP. Gastroschisis may portend a less optimal outcome from the procedure.
American journal of surgery 03/2013; · 2.36 Impact Factor
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ABSTRACT: OBJECTIVE:: Recent data has demonstrated improved survival in children with intestinal failure. We hypothesized that thistrend would also be observed in children with ultra-short bowel syndrome. METHODS:: A prospective database from Seattle Children's Intestinal Failure Program was used to evaluate outcomes and morbidities of consecutive patients with ≤ 10 cm of small bowel enrolled in the program since 2005. Data are listed as median (range). RESULTS:: Five patients were identified with a bowel length of 6 (1-10) cm and follow-up of 54 (43-61) months. All children have survived and are currently between 3 ½ and 5 ½ years of age. One patient underwent isolated intestinal transplantation and one patient is currently listed for intestinal transplantation. The transplanted child is fully enterally fed. The other patients remain at least partially dependent on parenteral nutrition. None of these patients have current evidence of parenteral nutrition-associated liver disease. Patients have required extensive care after referral to our program, including 18 (15-32) visits to the emergency room, 152 (114-273) days of inpatient care, and 6 (5-9) central line-associated blood stream infections. CONCLUSION:: Long-term survival in children with ultra-short bowel length is possible after referral to an intestinal failure program although extensive medical management is required. These children may be reasonable candidates for longstanding intestinal rehabilitation as a bridge to intestinal transplantation.
Journal of pediatric gastroenterology and nutrition 06/2012; · 2.18 Impact Factor
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ABSTRACT: Hepatic artery thrombosis (HAT) remains a significant cause of graft failure and mortality after pediatric liver transplantation. Conditions not associated with hepatic failure, such as liver tumors, may be more prone to thrombotic problems after transplant. We hypothesized that liver transplant for hepatic malignancies may be associated with increased rates of HAT in the posttransplant period.
We conducted a retrospective review of pediatric patients (age, 0-21 years) who underwent primary liver transplantation at a free-standing children's hospital from 1990 to 2009. We reviewed cause of underlying liver disease, age, sex, weight, occurrence of HAT, use of antiplatelets and anticoagulants perioperatively, as well as reintervention, retransplant, and death.
A total of 129 children underwent 146 liver transplants, and 15 (12%) patients developed HAT. Nine liver transplants were performed for hepatic malignancy, and 4 (44%) of these patients developed HAT (relative risk, 4.85; 95% confidence interval, 1.9-12.2; P = .0015). All 4 children with hepatic malignancy and HAT required reintervention, including 3 retransplants (75%). One of these patients died.
Hepatic artery thrombosis occurs approximately 5 times more often and appears to be more morbid in children with hepatic malignancy after transplantation. Prospective evaluation of prophylactic anticoagulation regimens in the setting of hepatic malignancy requiring transplantation is warranted.
Journal of Pediatric Surgery 06/2012; 47(6):1255-60. · 1.45 Impact Factor
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ABSTRACT: Despite advances in pediatric nutritional support and a renewed focus on management of intestinal failure, there are limited recent data regarding the risk of parenteral nutrition (PN)-associated liver disease in surgical infants. This study investigated the incidence of cholestasis from PN and risk factors for its development in this population.
A retrospective review was performed of all neonates in our institution who underwent abdominal surgery and required postoperative PN from 2001 to 2006. Cholestasis was defined as 2 conjugated bilirubin levels greater than 2 mg/dL over 14 days. Nonparametric univariate analyses and multivariate logistic regression were used to model the likelihood of developing cholestasis. Median values with range are presented.
One hundred seventy-six infants met inclusion criteria, and patients received PN for 28 days (range, 2-256 days). The incidence of cholestasis was 24%. Cholestatic infants were born at an earlier gestational age (34 vs 36 weeks; P < .01), required a 3-fold longer PN duration (76 vs 21 days; P < .001), had longer inpatient stays (86 vs 29 days; P < .001), and were more likely to be discharged on PN. The median time to cholestasis was 23 days. Cholestasis was an early development; 77% of cholestatic infants developed cholestasis by 5 weeks of PN exposure. On multivariate regression, only prematurity was significantly associated with development of cholestasis (P < .05).
In this analysis, the development of PN-associated liver disease occurred early in the course of exposure to PN. These data help to define the time course and prognosis for PN-associated cholestasis in surgical infants.
Journal of Pediatric Surgery 10/2011; 46(10):1913-7. · 1.45 Impact Factor
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ABSTRACT: Multidisciplinary treatment of pediatric intestinal failure has shown promising results. However, there are limited data as to the optimal time frame for referral of patients to intestinal failure programs. The aim of this study was to explore the relationship of hyperbilirubinemia at referral with patient outcomes in a multidisciplinary program.
A retrospective analysis was performed of a prospectively collected database from a multidisciplinary intestinal failure program. Multivariable logistic regression adjusted for age at referral was used to model the association between the conjugated bilirubin at referral and risk of mortality. Median values with range are reported.
Sixty-two patients were referred from 2005 to 2009. Patients presented at age 6.4 months (0.4-261.4 months) and were followed up for 16.8 (0.3-53.0) months. Nine subjects (14.5%) died, and 12 subjects (19.4%) were listed for combined liver-intestine transplant. A 50% mortality was seen in patients referred with a conjugated bilirubin ≥ 7.2 mg/dL (n = 12), whereas mortality at referral bilirubin levels <7.2 mg/dL was 6%. After adjusting for age at referral, patients with a conjugated bilirubin ≥ 7.2 mg/dL at referral were 15.4 times more likely to die than patients who presented with lower bilirubin levels (P = .001; 95% confidence interval, 2.8-83.4).
Within a pediatric intestinal failure program, mortality is associated with the degree of hyperbilirubinemia at time of referral. These data strongly suggest that these patients should be referred to a multidisciplinary program early in the evolution of their liver disease.
Journal of Pediatric Surgery 06/2011; 46(6):1052-6. · 1.45 Impact Factor
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ABSTRACT: The aim of this study was to evaluate the clinical experience of a regional multidisciplinary intestinal failure program for children established in 2005.
Data were collected from a prospective internal database. Univariate analyses were performed to compare pre- and post-treatment outcomes. Median values are reported.
Forty-nine children were referred at an age of 7 months. Remnant small bowel length was 29 cm. With follow-up of 14 months, overall patient survival was 88%. Thirteen bowel-lengthening procedures were performed, thereby increasing small bowel length from 83 to 132 cm (P < .05). Enteral autonomy was achieved in 22 patients (45%), and the caloric requirement for parenteral nutrition was decreased from 100% to 41% (P < .01). Conjugated bilirubin was reduced from 4.1 to 0 mg/dL (P < .05).
A multidisciplinary approach to pediatric intestinal failure that prioritizes intestinal rehabilitation can achieve successful enteral feeding advancement, improved liver function, and excellent survival in intermediate-range follow-up.
American journal of surgery 05/2010; 199(5):676-9. · 2.36 Impact Factor
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Simon P Horslen
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ABSTRACT: The lack of controlled interventional studies limits the ability to assess optimal management of intestine transplant recipients. This report aims to examine factors that probably impact on the quality of patient care in the setting of intestine transplantation. The specific practice in the most experienced intestine transplant programs in the United States was surveyed with regard to immunosuppressive regimens, treatment of acute allograft rejection, feeding, and viral surveillance and treatment. The most striking finding was in the level of agreement between the centers, particularly with regard to use of tacrolimus for maintenance immunosuppression, methylprednisone boluses for treatment of acute rejection, early postoperative enteral feeding, and ganciclovir prophylaxis.
Gastroenterology 03/2006; 130(2 Suppl 1):S163-9. · 11.68 Impact Factor
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ABSTRACT: The rapid expansion of the volume of peer reviewed publications in recent years, including a large increase in the number of new biomedical journals, makes it difficult for the practicing clinician to stay up to date with the medical literature. This review is part of a new series that will provide succinct summaries of the recent medical literature in the field of pediatric transplantation. In this review, we summarize important articles in the field of pediatric intestine transplantation that have been published over the last 2½ years (2003–2005). The review is intended to be comprehensive but not exhaustive.
Pediatric Transplantation 01/2006; 10(1):7 - 16. · 1.48 Impact Factor
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ABSTRACT: The role of portosystemic shunt (PSS) in children with portal hypertension has changed because of acceptance of liver transplantation and endoscopic hemostasis. We report our experience with PSS, mainly the distal splenorenal shunt, to define its role in the management of variceal bleeding.
From 1987 to 2002, 20 children with variceal bleeding after endoscopic therapy underwent PSS. Patient and database records were reviewed.
There were 14 boys and 6 girls; mean age was 11 years (range 3 to 18 years). Seventeen distal splenorenal and three mesocaval venous interposition shunts were performed. There was no operative mortality, 19 patients were alive at a median followup of 31 months (range 4 to 168 months) without evidence of recurrent gastrointestinal bleeding. One patient underwent transplantation 2 years after PSS and 1 patient died of hepatic failure while awaiting transplantation. The cause of portal hypertension was portal vein thrombosis (n = 13), biliary atresia (n = 3), congenital hepatic fibrosis (n = 2), hepatitis C cirrhosis (n = 1), and Budd-Chiari syndrome (n = 1). Eighteen children were Child-Turcotte-Pugh class A and the remaining two were class B. One patient had two episodes of hematemesis after PSS. Two patients had worsening ascites. One patient had mild encephalopathy and one patient had shunt stenosis requiring angioplasty.
PSS is a safe and durable therapy for pediatric patients with portal hypertension. Liver transplantation should be reserved for children with poor synthetic function associated with variceal bleeding. PSS may also serve as a bridge to transplantation in patients with preserved hepatic function. PSS, in particular the distal splenorenal shunt, has produced excellent results. This experience challenges the need for alternative forms of portal decompression.
Journal of the American College of Surgeons 09/2004; 199(2):179-85. · 4.55 Impact Factor
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ABSTRACT: Isolated hepatocyte transplantation has long been recognized as a potential treatment for life-threatening liver disease. The basis for proceeding with clinical trials has been established by the extensive laboratory work in animal models. Human hepatocyte transplantation has been applied in individual cases and very small, uncontrolled series. Data, although sparse, demonstrate the safety and feasibility of this approach and are supportive, if less than conclusive, of effectiveness. The experience of hepatocyte transplantation in the laboratory and clinical arenas is reviewed and discussion will examine what is believed to be the primary cause for the slow growth of this technology in the clinical setting, namely a severe shortage of usable primary human hepatocytes. The potential of isolated hepatocyte transplantation remains largely untapped and awaits alternate sources of cells for transplantation other than those from discarded human cadaveric livers.
Transplantation 06/2004; 77(10):1481-6. · 4.00 Impact Factor
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ABSTRACT: The syndrome of multiple intestinal atresia with immunodeficiency is a rare, invariably fatal congenital disorder. At 16 months of age, a child with this syndrome underwent liver-small bowel transplantation from a 1-of-6 HLA-matched donor. He acquired full enteral tolerance and normal liver function and has never shown evidence of allograft rejection. After mild graft-versus-host disease developed, studies revealed that more than 99% of his CD3(+) lymphocytes and 50% of his CD19(+) lymphocytes were of donor origin, whereas granulocytes and monocytes remained of recipient origin. He synthesizes polyclonal immunoglobulin G (IgG), IgA, and IgM and has developed antibodies to cytomegalovirus (CMV) and parainfluenza 3. His T lymphocytes are predominately CD3(+)CD4(-)CD8(-) with T-cell receptor gammadelta heterodimers and CD3(+)CD4(-)CD8(+) with CD8alphaalpha homodimers, populations consistent with an intraepithelial lymphocyte phenotypic profile. We postulate that he has engrafted a donor intestine-derived immune system and is incapable of rejecting his engrafted organs.
Blood 03/2004; 103(3):1171-4. · 9.90 Impact Factor
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ABSTRACT: Transplantation of isolated hepatocytes in animal models has been shown to correct inborn errors of metabolism. Based on these studies and our experience with hepatocyte transplantation in a child with Crigler-Najjar syndrome, isolated hepatocyte transplantation was performed to attempt metabolic reconstitution in a male infant with severe ornithine transcarbamylase (OTC) deficiency.
An infant with an antenatal diagnosis of OTC deficiency was managed intensively to prevent hyperammonemia. Isolated hepatocytes were obtained by collagenase perfusion of donated livers not used for transplantation. Hepatocytes were infused in batches over the first 4 weeks of life via an umbilical venous catheter positioned in the portal vein. Immunosuppression consisted of tacrolimus and corticosteroids.
Over 4 billion viable hepatocytes were transplanted during the first 3.5 weeks of life. A period of metabolic stability was achieved between days 20 and 31 during which normal protein intake was tolerated while phenylbutyrate was weaned. During this time, plasma ammonia and glutamine remained within normal limits. Hyperammonemia reappeared abruptly on day 31 of life. Protein tolerance diminished to baseline; metabolic stability was subsequently reattained only following successful liver transplantation at 6 months of age.
Isolated hepatocyte transplantation appeared to result in temporary relief of hyperammonemia and protein intolerance attributable to OTC deficiency. The metabolic stability achieved was lost after 11 days presumably because of rejection of the transplanted cells because of insufficient immunosuppression. Future attempts at isolated hepatocyte transplantation for inborn errors of metabolism in humans should include adequate immunosuppression and a liver biopsy as a means of proving hepatocyte engraftment and function.
PEDIATRICS 07/2003; 111(6 Pt 1):1262-7. · 4.47 Impact Factor
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ABSTRACT: To evaluate experience with isolated orthotopic liver transplantation in children with liver failure associated with short bowel syndrome (SBS).
Infants who have liver failure as a result of SBS are frequently referred for consideration for combined liver and small bowel transplantation. In a few patients the liver disease develops despite a seemingly adequate bowel, which if given time and appropriate management has the potential for full enteral adaptation. There is a limited literature suggesting the utility of OLT without replacement of the native bowel. The advantages over combined liver and small bowel transplantation are clear: organ availability is greater, liver-reduction techniques are well established, lower immunosuppression is required, and there is greater experience in the care of children after orthotopic liver transplantation.
Eleven infants, considered to have a good prospect of eventual gut adaptation to full enteral nutrition if it were not for their advanced liver disease, underwent isolated orthotopic liver transplantation. Age range was 6.5 to 17.7 months. All patients had been dependent on parenteral feeding but had also shown significant enteral tolerance at some time before listing for transplantation. Advanced liver disease was apparent both clinically and on histologic examination. All were jaundiced and had low albumin levels, and most had coagulopathy. As a group the infants had growth retardation. Estimated remaining length of small bowel beyond the ligament of Treitz was in the range of 25 to more than 100 cm. Six infants retained their ileocecal valve.
Thirteen liver transplants were performed in the 11 patients. A combination of whole livers (n = 6) and reduced-size grafts, of which three were from living-related donors, were used. Biliary anastomosis was duct-to-duct in eight instances and involved a short Roux limb in the others. Eight patients are alive with follow-up of 15 to 66 months. Three deaths have occurred after transplantation as a result of sepsis. Of eight surviving patients, only two continue to receive intravenous support and in both there is increasing enteral tolerance. Since transplantation, all surviving children have shown adequate growth with maintenance of pretransplant centiles.
In selected infants with liver failure secondary to short bowel syndrome in whom complete enteral autonomy is anticipated, isolated liver transplantation can offer long-term survival.
Annals of Surgery 04/2002; 235(3):435-9. · 7.49 Impact Factor
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Stuart S Kaufman,
Elizabeth Ruby Lyden,
Cindy R Brown,
Carolyn K Davis,
Deborah A Andersen,
Keith M Olsen,
Kimberly L Bergman, Simon P Horslen,
Debra L Sudan,
Ira J Fox,
Byers W Shaw Jr,
Alan N Langnas
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ABSTRACT: Proton pump inhibitors such as omeprazole are increasingly used to prevent stress-related gastric bleeding in critically ill patients. In this investigation, the acid-suppressive potency of omeprazole was assessed in one at-risk group, pediatric patients undergoing liver or intestinal transplantation, or both.
Twenty-two patients ranging in age from 0.9 to 108 months (23.8 +/- 6.5) underwent isolated liver (n = 10) or intestinal (11 with composite liver allografts) transplantation. Omeprazole was delivered in bicarbonate suspension through a nasogastric tube. Therapy was started after surgery at 0.5 mg/kg every 12 hours. Gastric pH monitoring was performed approximately 2 days later.
For the entire group, mean gastric pH equaled 6.1 +/- 0.3, the same in recipients of isolated liver and intestinal allografts. Twelve of the 22 patients demonstrated a discontinuous omeprazole effect, that is, dissipation of acid reduction before the next dose. Five of the 12 patients with discontinuous omeprazole effect had mean gastric pH of less than 5 (3.9 +/- 0.4). In 4 of these 5, the omeprazole dosing interval was shortened to every 8 or every 6 hours, resulting in an increase in mean pH to 6.6 +/- 0.2 ( P < 0.01). In the remaining 10 of 22 patients, acid suppression was uninterrupted until the next dose. No patient experienced bleeding attributable to gastric erosion.
Omeprazole suspended in sodium bicarbonate is an effective acid-suppressing agent in pediatric recipients of liver or intestinal transplant, or both. A dosage of 0.5 mg/kg every 12 hours is sufficient for most patients, but dosing every 6 to 8 hours is required to assure maximal acid suppression in all.
Journal of Pediatric Gastroenterology and Nutrition 03/2002; 34(2):194-8. · 2.30 Impact Factor
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Simon P. Horslen,
James M. Hammel,
Lance W. Fristoe,
Jeff A. Kangas,
Dean S. Collier,
Debra L. Sudan,
Alan N. Langnas,
R. Stephen Dixon,
Ernest D. Prentice,
Byers W. Jr. Shaw,
Ira J. Fox
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ABSTRACT: Background. Patients with fulminant hepatic failure (FHF) often die awaiting liver transplantation.Extracorporeal liver perfusion (ECLP) has been proposed as a method of bridging such patients to transplantation. We report the largest experience to date of ECLP using human and porcine livers in patients with acute liver failure.
Methods. Patients with FHF unlikely to survive without liver transplantation were identified. ECLP was performed with human or porcine livers. Patients underwent continuous perfusion until liver transplantation or withdrawal of support. Two perfusion circuits were used: direct perfusion of patient blood through the extracorporeal liver and indirect perfusion with a plasma filter between the patient and the liver.
Findings.
Fourteen patients were treated with 16 livers in 18 perfusion circuits. Nine patients were successfully bridged to transplantation. ECLP stabilized intracranial pressure (ICP) and cerebral perfusion pressure (CPP). Arterial ammonia levels fell from a median of 146 to 83 μmol/liter within 12 hr and this reduction was maintained at least 48 hr. Pig and human ECLP lowered ammonia levels equally. Serum bilirubin levels also fell from a median of 385 to 198 μmol/liter over the first 12 hr but the response was not sustained as well with porcine livers. There was no immunological benefit to using the the filtered perfusion circuit.
Interpretation.
These data demonstrate that ECLP is safe and can provide metabolic support for comatose patients with fulminant hepatic failure for up to 5 days. While labor and resource intensive, this technology is available to centers caring for patients with acute liver failure and deserves wider evaluation and application.
Transplantation 11/2000; 70(10):1472-1478. · 4.00 Impact Factor
