Albert Shun

Chimerism and Tolerance in a Recipient of a Deceased-Donor Liver Transplant

Complete hematopoietic chimerism and tolerance of a liver allograft from a deceased male donor developed in a 9-year-old girl, with no evidence of graft-versus-host disease 17 months after transplantation. The tolerance was preceded by a period of severe hemolysis, reflecting partial chimerism that was refractory to standard therapies. The hemolysis resolved after the gradual withdrawal of all immunosuppressive therapy.

Structural and functional adaptation following jejunal resection in rabbits: Effect of epidermal growth factor

BACKGROUND/AIMS Remnant small intestine undergoes adaptation following massive resection. The aim of this study was to examine the effect of epidermal growth factor (EGF) on ileal adaptation following proximal resection. METHODS New Zealand white rabbits, aged 8 weeks, underwent 2/3 proximal resection, and ileal mucosal adaptation was assessed 10 and 21 days postsurgery. In a second series of experiments, animals with resection received oral EGF (40 micrograms.kg-1.day-1) for 5 days, and the effect on adaptation was assessed 10 days postsurgery. RESULTS Transection alone stimulated mucosal hyperplasia, intestinal sucrase specific activity, and glucose transport at 10 days but not at 21 days. Resection resulted in mucosal hyperplasia at both time periods and increased disaccharidase specific activity at 10 days postresection. In contrast, 3 O-methyl-D-glucose transport was significantly decreased compared with both groups at both time periods. EGF treatment in animals with resection did not alter mucosal proliferation but did stimulate maltase specific activity and caused a 3-4-fold increase in glucose transport and phlorizin binding. CONCLUSIONS Following proximal resection, adaptation of intestinal digestive and absorptive function does not parallel mucosal hyperplasia. Administration of EGF to resected animals enhances glucose absorption and may have a therapeutic role in the management of short gut syndrome.

Portosystemic shunting for paediatric portal hypertension

The records of 22 patients who received portosystemic shunting for portal hypertension from 1985 to 1995 inclusive at the Royal Alexandra Hospital for Children (RAHC) were retrospectively reviewed. There were 11 girls and 11 boys. The average age at operation was 8 years, 3 months (range, 2 years, 3 months to 16 years, 7 months). The aetiology was idiopathic portal cavernomatous transformation (n = 9), billiary atresia (n = 4), cystic fibrosis (n = 3), documented neonatal portal vein thrombosis (n = 3), congenital hepatic fibrosis (n = 2), and portal vein obstruction after liver transplant (n = 1). The major presenting problem was upper gastrointestinal haemorrhage. Two patients had recurrent melaena from Roux-en-Y jejunal loop and caecal varices, respectively. Before receiving shunts, 12 patients had endoscopic sclerotherapy, 1 had gastric transection, and 2 had gastric varices oversewn. Portal pressure at preoperative splenoportogram averaged 28 mm Hg (range, 20 to 41). Urgent shunts were performed on 13 patients. Two disadvantaged patients had prophylactic shunts for severe hypersplenism. The types of shunts used were reversed splenorenal (n = 13), splenoadrenal (n = 6), inferior mesenteric renal (n = 1), portocaval (n = 1), inferior mesenteric caval (n = 1), and superior and inferior mesenteric caval (n = 1). In all, 22 patients had 23 shunts. The patency rate was 96% on 6 months to 10 years follow-up (average, 5.8 years). No spleen was lost. There were 2 late deaths. Two cystic fibrosis patients and one child with extrahepatic portal hypertension experienced post-shunt encephalopathy. Three patients rebled in the early postoperative period despite a patent shunt. Two patients subsequently received liver transplantation without any additional difficulties. Thus, portosystemic shunting using a method appropriate for the patient is a reliable option for treating children with portal hypertension in whom variceal sclerotherapy is inappropriate or has failed.

Gastrointestinal and nutritional problems in severe developmental disability

The aim of this study was to describe the experience of 452 children and adults with a severe developmental disability who presented to a multidisciplinary clinic with swallowing, nutritional, and gastrointestinal problems. Data were obtained by chart review. Two hundred and ninety‐four children (age range 7mo–19y, 173 males, 121 females) and 158 adults (age range 18–53y; 90 males, 68 females) were assessed over 5 years. One hundred and eighty‐two children and 86 adults had cerebral palsy. Approximately 90% were wheelchair dependent and totally dependent on caregivers for feeding; 60% had epilepsy. Pulmonary aspiration was identified by oesophageal videofluoroscopy in 41% of 174 children and 47% of 34 adults. Chronic oesophagitis and Helicobacter pylori were found in 57% of 182 children and 76% of 66 adults undergoing endoscopy. Chronic suppurative lung disease was identified by computerized axial tomography in 94% of 62 children and all six adults studied. Most patients improved with simple interventions. However, gastrostomy was recommended in 140 children and performed in 91, and in 10 adults but performed in seven, whereas fundoplication was recommended in 111 children and performed in 74, and in six adults but performed in two. In conclusion, chronic oesophagitis, pulmonary aspiration, and chronic lung disease were identified in many patients with a severe developmental disability.

Definitive abdominal wall closure using a porcine intestinal submucosa biodegradable membrane in pediatric transplantation

Abstract:  Abdominal closure in children less than 10 kg following liver or kidney transplantation can be challenging. Excessive pressure attained from a tight closure can result in abdominal compartment syndrome, graft compromise and loss. Concerns over using prosthetic patches are that of infection and dehiscence. We report a series of definitive abdominal wall closure using a biodegradable membrane from porcine intestinal submucosa (Surgisis®; Cook Biotech Incorporated, West Lafayette, IN, USA). A prospective collection and follow up of liver and kidney transplant patients weighing less than 10 kg who required abdominal wall augmentation with Surgisis® in order to achieve satisfactory closure. There were 10 liver and two renal transplant patients. The average weight of the liver transplant patients was 6.6 kg (5.4–8.5 kg) and the renal 9.8 kg. The average area of Surgisis® used was 71.2 cm2 (25–160 cm2) and length of follow up was 15.3 months (1–27 months). Concomitant measures to aid abdominal closure included bilateral recipient nephrectomy for the renal patients and reduction by 33% of the lateral segmental grafts in two liver transplant patients. Delayed closure occurred in all patients except one and the average days to closure from the first surgery was 3.75 days (0–6 days). Following liver transplantation one patient died from multiple organ failure at one month secondary to hemophagocytosis from underlying combined immune deficiency syndrome and one patient with hepatic artery thrombosis was salvaged at re‐exploration. There were two wound complications, one patient developed two small sinuses and some skin dehiscence which healed over four months and the second developed a skin sinus following trans‐patch liver biopsy which healed in three wk. Both had positive microbial cultures but neither necessitated removal of the graft. There were no incisional hernias. Surgisis® is a safe method for facilitating abdominal closure in pediatric transplant patients. It appears to have long‐term durability with no incisional hernias on short‐ and medium‐term follow up, and is fairly resistant to infection.

Hyperparathyroidism After Irradiation for Childhood Malignancy

PURPOSE To examine the occurrence of hyperparathyroidism in a cohort of patients undergoing combined parathyroid and thyroid surgery after previous head-and-neck irradiation for childhood malignancy. METHODS AND MATERIALS This is a retrospective cohort study for the years 1996 to 2007. The study group comprised patients undergoing surgery in the University of Sydney Endocrine Surgical Unit who had received previous head-and-neck irradiation in childhood and who were identified as having pathologic thyroid and parathyroid characteristics. RESULTS A total of 53 patients were identified in whom head-and-neck irradiation for the treatment of childhood malignancy had been documented. In each of the cases, thyroid disease was the primary reason for referral for surgery. Five of these patients (10%) were found to exhibit coexisting hyperparathyroidism. The latency period for hyperparathyroidism was less than 20 years in 4 of the 5 cases. There were four conventional parathyroid adenomas and one parathyroid lipoadenoma. All patients exhibited a significant decrease in postoperative calcium levels after surgery. CONCLUSIONS To our knowledge, this is the first study to document the significant risk of hyperparathyroidism after radiation exposure for childhood malignancy. The timeframe for development of disease is much shorter than that published for individuals who have undergone irradiation for benign diseases. High doses of therapeutic radiation at a young age make childhood survivors of malignancy at especially high risk for developing hyperparathyroidism.

Positron emission tomography in recurrent hepatoblastoma.

Early detection of recurrent hepatoblastoma is not always possible with conventional imaging methods such as computed tomography (CT) and magnetic resonance imaging (MRI). This article describes three cases of recurrent hepatoblastoma in which positron emission tomography (PET) using F18-fluoro-deoxy-glucose (FDG-PET) was used to locate the site of recurrence. In the first two patients, FDG-PET accurately located recurrent disease where it was not detected by conventional imaging modalities, including CT and MRI. In the third patient, FDG-PET imaging also located the recurrent disease in an MRI-identified adrenal metastasis. The technique of “coregistration” using PET with CT and MRI scans was used in the cases described. This improves the anatomical localization of metabolically active sites and was particularly useful for determining the surgical approach. The difficulties of conventional imaging in locating early tumor recurrence or metastatic disease in hepatoblastoma make FDG-PET imaging an important investigation that may impact patient management.

Hepatocellular Carcinoma in Children: Does Modified Platinum- and Doxorubicin-Based Chemotherapy Increase Tumor Resectability and Change Outcome? Lessons Learned From the SIOPEL 2 and 3 Studies

INTRODUCTION The aim of this article is to present an experience of two prospective studies from the International Childhood Liver Tumor Strategy Group (SIOPEL 2 [S2] and SIOPEL [S3]) trials and to evaluate whether modified platinum- and doxorubicin-based chemotherapy is capable of increasing tumor resectability and changing patient outcomes. METHODS Between 1995 and 2006, 20 patients with hepatocellular carcinoma (HCC) were included in the S2 trial and 70 were included in the S3 trial. Eighty-five patients remained evaluable. RESULTS Response to preoperative chemotherapy was observed in 29 of 72 patients (40%) who did not have primary surgery, whereas 13 patients underwent upfront surgery. Thirty-three patients had a delayed resection. Thirty-nine tumors never became resectable. Complete tumor resection was achieved in 34 patients (40%), including seven of those treated with liver transplantation (LTX). After a median follow-up period of 75 months, 63 patients (74%) had an event (a progression during treatment, a relapse after treatment, or death from any cause). Sixty patients died. Twenty-three of 46 patients (50%) who underwent tumor resection died. Eighteen of 27 patients (63%) with complete tumor resection (without LTX) and 20 of 34 patients (59%) with LTX survived. Only one of seven patients (14%) with microscopically involved margins survived. Overall survival at 5 years was 22%. CONCLUSION Survival in pediatric HCC is more likely when complete tumor resection can be achieved. Intensification of platinum agents in the S2 and S3 trials has not resulted in improved survival. New treatment approaches in pediatric HCC should be postulated.

Pulmonary hypertension--a new manifestation of mitochondrial disease.

SummaryMitochondrial respiratory chain (RC) abnormalities in children can present as multiorgan disease, including liver failure, usually within the first year of life. Cardiorespiratory complications have previously been described in association with RC defects; however, to our knowledge no cases of pulmonary hypertension have been described. We discuss two patients with proven mitochondrial RC liver disease who developed severe pulmonary hypertension, one subsequent to cadaveric orthotopic liver transplantation, the second in the neonatal period. It is our contention that pulmonary hypertension should now be included as another potential manifestation of paediatric mitochondrial disease.

Inferior liver allograft survival from cadaveric donors >50 years of age?

The growing imbalance between the number of cadaveric organ donors and recipients has led to an increasing use of high‐risk donors as an option to expand the donor pool. The aim of this study was to evaluate our experience with the use of older liver (donor>50 yr of age) allografts. 
The medical records, postreperfusion biopsies and laboratory results were reviewed of the 393 patients who underwent orthotopic liver transplantation between 1986 and 1997. The outcome of the 61 patients who received older livers (OL) was compared to that of the other 332 recipients. 
Increasing use of OL was evident from 1992 onwards. Recipients of OL were older than recipients of younger livers (YL, p<0.001) and more commonly had underlying chronic viral hepatitis (CVH) or fulminant hepatic failure (p<0.05). Patient and allograft survival were only slightly less in recipients of OL versus YL (p=NS). Although postperfusion biopsies showed more damage in OL than YL allografts (p<0.05), this was not associated with increased primary graft failure. 
OL allografts can be transplanted with acceptable results into recipients without the concern of early allograft loss. 
Summary of Article: This report of one centres experience with 61 recipients of older donor liver allografts identifies recipient factors that may also have a negative impact on allograft outcome. These factors include a diagnosis of either CVH or fulminant hepatic failure at the time of transplantation. Postreperfusion biopsies of older donor allografts tend to show more damage, but this is not associated with primary non‐function.