Growth of liver allografts over time in pediatric transplant recipients.

The liver's capacity to grow in response to metabolic need is well known. However, long-term growth of liver allografts in pediatric recipients has not been characterized. A retrospective review of pediatric recipients at a single institution identified patients who had cross-sectional imaging at 1, 5, and 10 years post-transplant. Using volumetric calculations, liver allograft size was calculated and percent SLV were compared across the different time points; 18 patients ranging from 0.3 to 17.7 years old were identified that had imaging at 2 or more time points. Measured liver volumes increased by 59% after 5 years and 170% after 10 years. The measured liver volumes compared to calculated %SLV for these patients were 123 ± 37%, 97 ± 19%, and 118 ± 27% at 1, 5, and 10 years after transplant, respectively. Our data suggest that liver allografts in pediatric recipients increase along with overall growth, and reach SLVs for height and weight by 5 years post-transplantation. Additionally, as pediatric recipients grow, the livers appear to maintain appropriate SLV.

First Attempt of Sequential Living Donor Liver and Hematopoietic Stem Cell Transplantation in a Child With Advanced Hepatocellular Carcinoma: Case Report.

Effective therapeutic options for advanced hepatocellular carcinoma are limited. Hematopoietic stem cell transplantation may offer a graft-versus-tumor effect. Combined liver and hematopoietic stem cell transplantation from the same donor with preparatory conditioning may promote tolerogenicity to the liver allograft and offers the potential for immunosuppression withdrawal. We report our experience with the use of this approach in a pediatric patient with invasive hepatocellular carcinoma and pulmonary metastases who underwent a living-donor liver transplantation followed by reduced-toxicity myeloablative conditioning and hematopoietic stem cell transplant from the same parental donor. Neutrophil engraftment and full donor chimerism was achieved without liver allograft dysfunction. Despite normal liver function and marrow engraftment, the patient succumbed to multisystem organ failure from disseminated toxoplasmosis. At autopsy, there was no histologic evidence of tumor recurrence. No pulmonary nodules were found. Regardless of the unfortunate overall result, this case demonstrates preliminary feasibility of sequential living-donor liver transplantation and hematopoietic stem cell transplantation for unresectable and metastasized hepatic tumors. Future studies in select pediatric patients require evaluation of the optimal conditioning regimen and prevention strategies for opportunistic infections to determine both graft-versus-tumor effect on hepatic tumors and durability of tolerogenicity and possible immunosuppression withdrawal.

Posttransplant metabolic syndrome in the withdrawal of immunosuppression in Pediatric Liver Transplant Recipients (WISP-R) pilot trial.

Posttransplant metabolic syndrome (PTMS)-obesity, hypertension, elevated triglycerides, low HDL and glucose intolerance-is a major contributor to morbidity after adult liver transplant. This analysis of the Withdrawal of Immunosuppression in Pediatric Liver Transplant Recipients (WISP-R) pilot trial is the first prospective study of PTMS after pediatric liver transplant. Twenty children were enrolled in WISP-R, at median age 8.5 years (IQR 6.4-10.8), and weaned from calcineurin-inhibitor monotherapy. The 12 children who tolerated complete immunosuppression withdrawal were compared to matched historical controls. At baseline, 45% of WISP-R subjects and 58% of controls had at least one component of PTMS. Calcineurin-inhibitor withdrawal in the WISP-R subjects did not impact the prevalence of PTMS components compared to controls. At 5 years, despite weaning off of immunosuppression, 92% of the 12 tolerant WISP-R subjects had at least one PTMS component and 58% had at least two; 33% were overweight or obese, 50% had dyslipidemia, 33% glucose intolerance and 42% systolic hypertension. Overweight/obesity increased the risk of hypertension in all children. Compared to controls, WISP-R tolerant subjects had similar GFR at baseline but did have higher GFR at 2, 3 and 4 years. Further study of PTMS and immunosuppression withdrawal after pediatric liver transplant is warranted.

Multivisceral ex vivo surgery for tumors involving celiac and superior mesenteric arteries.

Abdominal tumors involving both roots of the celiac and superior mesenteric artery are deemed unresectable by conventional surgical methods. We performed three cases of multivisceral ex vivo surgery involving temporary removal of the entire abdominal viscera followed by vascular reconstruction, ex vivo tumor resection and autotransplantation of excised organs. We achieved a complete tumor resection with negative margins in all cases. All patients have survived with no tumor recurrence to date at 17-, 27- and 38-month follow-up. Postoperative complications included diarrhea, sphincter of Oddi dysfunction and arterial stenosis; all responded to directed treatments. Multivisceral ex vivo surgery applying techniques of deceased donor multivisceral transplantation is feasible in achieving local control of otherwise unresectable abdominal tumors. This surgery is best suitable for locally invasive tumors unresectable because of location and vascular involvement.

Isolated liver transplantation for decompensated end-stage liver disease in children with intestinal failure.

Cholestasis progressing to end-stage liver disease (ESLD) is common in intestinal failure (IF) in infants. Isolated liver transplantation (OLT) is performed when eventual enteral sufficiency is expected. We reviewed our experience with OLT for ESLD in patients with residual IF. From 1998 to 2004, four IF patients underwent OLT for ESLD at our institution. Three were performed as UNOS status I for acute decompensation of chronic liver failure; one other with severe cholestasis with a living donor. The living donor recipient died within months after OLT of chronic respiratory failure despite normal liver function. One recipient remains on parenteral nutrition (PN) and continues to receive partial enteral feeds with normal liver function. Two other recipients became enterally sufficient after the OLT. Biliary complications occurred in two patients, one with late hepatic artery thrombosis. Resolution was achieved with serial balloon dilatations and the other by conversion from duct-to-duct anastomosis to a choledochoduodenostomy. The morbidity of OLT for this indication is higher than for others likely because of comorbidities like sepsis and pulmonary insufficiency. OLT is complicated further by the attempt to maximally preserve residual bowel length for the biliary reconstruction. OLT can be an emergent life-saving procedure in IF patients despite higher morbidity. Improved liver function and diminished portal pressures may shorten the time to enteral sufficiency. Management of parenteral nutrition after OLT can avoid ESLD and eliminate small bowel transplantation in selected patients.

Endoscopic considerations in children.

Endoscopy often is required in the management of patients with chronic liver disease. Endoscopy in this pediatric population is a safe and effective diagnostic and therapeutic modality for the appropriate clinical situation. The clear advantage afforded by reduced-sized equipment, new anesthetic agents, better operator training, and specialized pediatric endoscopy units have resulted in better outcomes and reduced risk to the patient. Advances in technical innovations will expand the currently offered diagnostic and therapeutic options for management of pediatric with portal hypertension. This article reviews specific considerations for endoscopy in this demanding patient population.