PURPOSE:To evaluate the efficacy of a low-dose chemotherapy regimen in children with Epstein-Barr virus (EBV) -positive, post-transplantation lymphoproliferative disease (PTLD) after organ transplantation who have experienced failure with front-line therapy for PTLD.PATIENTS AND METHODS:Eligible patients received cyclophosphamide (600 mg/m2 intravenous for 1 day) and prednisone (2 mg/kg orally for 5 days) every 3 weeks for six cycles.RESULTS:Thirty-six patients treated on study were assessable for analyses. Front-line therapies for PTLD before study entry included immune suppression reduction or withdrawal (n = 36), antiviral therapy (n = 33), surgical resection (n = 8), rituximab (n = 2), and interferon alfa (n = 1). Reasons for failure of front-line therapy included progressive disease (PD; n = 33) and persistent disease with concurrent allograft rejection (n = 3). Thirty patients (83%) had stage III to IV disease, 92% had extranodal disease, and 75% had > or = three sites of disease. The overall response rate was 83% (75% complete response + 8% partial response). The relapse rate was 19%, with only one of five relapsed patients alive and disease-free. Four patients presented with fulminant, disseminated PTLD; only one of these four patients achieved a response, and all four died of PD. Two patients died of treatment-related toxicity. Three patients (8%) experienced allograft loss, but two of the three patients are alive and disease-free after a second transplantation. The 2-year overall, relapse-free, and failure-free (without PTLD and with functioning original allograft) survival rates were 73%, 69%, and 67%, respectively.CONCLUSION:This low-dose chemotherapy regimen is effective for children with EBV-positive, nonfulminant PTLD who have experienced treatment failure with front-line therapy, and this study represents the largest series of PTLD patients treated prospectively with a uniform chemotherapy regimen.

BACKGROUND: 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.STUDY DESIGN: From 1987 to 2002, 20 children with variceal bleeding after endoscopic therapy underwent PSS. Patient and database records were reviewed.RESULTS: 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 I patient died of hepatic failure while awaiting transplantation. The cause of portal hypertension was portal vein thrombosis (n = 13), billary 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.CONCLUSIONS: 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. (C) 2004 by the American College of Surgeons.

A 26-year-old woman presented with acute Budd-Chiari syndrome 18 weeks into a pregnancy. She was found to be heterozygous for the G20210A prothrombin gene mutation. She was treated with portacaval shunt placement and successfully completed the pregnancy, with a healthy baby delivered at 31 weeks' gestation. She developed progressive liver failure after delivery of the child, likely associated with clotting of the shunt, which occurred in the face of full anticoagulation. The patient subsequently underwent a technically complicated orthotopic liver transplantation, but died 10 months after transplantation. This case illustrates the challenges involved in the treatment of Budd-Chiari syndrome, in addition to difficulties balancing the health of a mother and an unborn child. It is the only case of surgical treatment of Budd-Chiari syndrome during pregnancy reported in the literature. (Liver Transpl 2003;9:976-979.)

BACKGROUND/PURPOSE:The aim of this study was to determine causes of late graft loss and long-term outcome after isolated intestinal transplantation in children at a single center. METHODS:All children who underwent primary isolated intestinal transplantation at our center with a minimum follow-up of 1 year were the subject of this retrospective study. RESULTS:Twenty-eight children underwent primary isolated intestinal transplantation. Median graft survival was 705 days (range, 0 to 2,630 days) and median patient survival was 1,006 days (range, 0 to 2,630 days). There were 6 deaths and 15 graft losses (including the 6 nonsurvivors). Seven of the losses occurred 6 or more months after transplant. Of these, 2 losses occurred because of death of the recipients of sepsis; both recipients had functioning grafts. The 5 remaining late graft losses occurred because of acute rejection in 2 patients, chronic rejection in 2 (1 with concomitant acute rejection) and a diffuse stricturing process without the histologic hallmarks of chronic rejection in the fifth. All late survivors with intact grafts are off total parenteral nutrition (TPN). CONCLUSIONS:Late graft loss remains a concern in a small percentage of patients after isolated intestinal transplantation. Nutritional autonomy from TPN is possible in the majority of these children after transplantation.

Liver TransplantationVolume 8, Issue 8 p. 667-669 Rapid CommunicationFree Access Deep blue polemics Byers W. Shaw Jr MD, Corresponding Author Byers W. Shaw Jr MD bshaw@unmc.edu Department of Surgery, University of Nebraska College of Medicine, Nebraska Medical Center, Omaha, NEDepartment of Surgery, University of Nebraska College of Medicine, 983280 Nebraska Medical Center, Omaha, NE 68198-3280. Telephone: 402-559-4632; FAX: 402-559-6749Search for more papers by this author Byers W. Shaw Jr MD, Corresponding Author Byers W. Shaw Jr MD bshaw@unmc.edu Department of Surgery, University of Nebraska College of Medicine, Nebraska Medical Center, Omaha, NEDepartment of Surgery, University of Nebraska College of Medicine, 983280 Nebraska Medical Center, Omaha, NE 68198-3280. Telephone: 402-559-4632; FAX: 402-559-6749Search for more papers by this author First published: 30 December 2003 https://doi.org/10.1053/jlts.2002.34676AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1 Freeman RB, Harper AM, Edwards EB. Redrawing organ distribution boundaries: Results of a computer-simulated analysis for liver transplantation. Liver Transpl 2002; 8: 659– 666. Volume8, Issue8August 2002Pages 667-669 ReferencesRelatedInformation

Objective To evaluate experience with isolated orthotopic liver transplantation in children with liver failure associated with short bowel syndrome (SBS). Summary Background Data 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. Methods 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. Results 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. Conclusions 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.

ABSTRACT Background 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. Methods 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. Results 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. Conclusion 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.

Background. Initiated in 1995, the Studies of Pediatric Liver Transplantation (SPLIT) registry database is a cooperative research network of pediatric transplantation centers in the United States and Canada. The primary objectives are to characterize and follow trends in transplant indications, transplantation techniques, and outcomes (e.g., patient/graft survival, rejection, growth parameters, and immunosuppressive therapy.)Methods. As of June 15, 2000, 29 centers registered 1144 patients, 640 of whom received their first liver-only transplant while registered in SPLIT. Patients are followed every 6 months for 2 years and yearly thereafter. Data are submitted to a central coordinating center.Results. One/two-year patient survival and graft loss estimates are 0.85/0.82 and 0.77/0.72, respectively. Risk factors for death include: in ICU at transplant (relative risk (RR) = 2.63, P < 0.05) and height/weight deficits of two or more standard deviations (RR = 1.67, P < 0.05). Risk factors for graft loss include: in ICU at transplant (RR = 1.77, P < 0.05) and receiving a cadaveric split organ compared with a whole organ (RR = 2.3, P < 0.05). The percentage of patients diagnosed with hepatic a. and portal v. thrombosis were 9.7% and 7%, respectively; 15% had biliary complications within 30 days. At least one re-operation was required in 45%. One/two-year rejection probability estimates are 0.60/0.66. Tacrolimus, as primary therapy posttransplant, reduces first rejection risk (RR = 0.70, P < 0.05). Eighty-nine percent of school-aged children are in school full-time, 18 months posttransplant.Conclusions. This report provides one of the first descriptions of characteristics and clinical courses of a multicenter pediatric transplant population. Observations are subject to patient selection biases but are useful for generating hypothesis for future studies.

Introduction. The enterocyte-specific protein, intestinal fatty acid binding protein (I-FABP), is detectable in serum only after intestinal injury. Previous studies in animals suggest that I-FABP might be a useful marker of intestinal allograft rejection. Materials and Methods. I-FABP was repetitively measured in nine intestinal transplant recipients and correlated with findings of surveillance endoscopy. Results. Average interval between I-FABP determination and biopsy was 3.4 days (SD=4.2 days). Average number of rejection episodes per patient totalled 1.6±1.2. General linear modeling demonstrated no tendency for increases in serum FABP to precede histologic graft rejection (P =0.263). Restriction of the analysis to I-FABP determinations 1 day before or on the day of biopsy failed to affect these results. Minor increases in I-FABP were often associated with histologically normal grafts, whereas rejection often occurred when I-FABP was not detectable. Discussion. Serum I-FABP levels do not predict clinical intestinal allograft rejection.

The most common application of small bowel transplantation is for the patient with parenteral nutrition-induced liver failure. In this setting, the small intestine is transplanted simultaneously with the liver. We identified three technical problems that we believe contributed to complications in our first eight patients. First, pancreaticoduodenectomy was challenging in the infant donor. Second, the bowel graft was prone to volvulus around the skeletonized donor portal vein. Third, in the pediatric recipient, use of the donor bowel for Roux-en-Y biliary reconstruction was associated with biliary leaks in the early postoperative period. Our surgical technique of liver/small bowel (L/SB) transplantation has evolved since our early experience in 1990. Modifications in the L/SB operation, reported briefly in 1996 and 1997, have led to easier graft preparation and have reduced the incidence of technical complications.

Fristoe, Lance W.1; Sudan, Debra L.2; Fox, Ira J.2; Iyer, Kishore2; Shaw, Byers W. Jr.2; Langnas, Alan N.2 Author Information

The results of this investigation show that, in the absence of histologic or clinical indications of allograft rejection, pediatric intestinal transplant recipients do not have primary disaccharidase deficiencies. Similarly, absorption of usual dietary lipid content is adequate once weaning from parenteral nutrition is complete. In contrast, early assimilation of vitamin E is poor. Vitamin E absorption subsequently improves, but the mechanism is obscure.

Sudan, Debra1; Kaufman, Stuart1; Horslen, Simon1; Fox, Ira1; Shaw, Byers Jr.1; Langnas, Alan1 Author Information