A. D. Mayer

Liver transplantation in patients over sixty years of age

Background. Although some centers have reported very good patient and graft survival in liver allograft recipients, reports from both North America (United Network of Organ Sharing) and Europe (European Liver Transplantation Registry) have failed to confirm this. Aim. We have reviewed our experience of liver transplantation in older recipients and compared their clinical outcome to a younger group. Methods. Retrospective analyses were conducted on 875 consecutive adult patients undergoing liver transplantation for chronic liver disease, between 1990 and 1999. Group I consisted of patients under 60 years of age (n=701; 80.2%) and group II of patients over 60 years (n=174; 19.8%). Results. The proportion of older patients transplanted increased from 10.15% between 1990–1991 to 20.85% (1997–1999). Actuarial graft survival at 1, 3, and 5 years was 78%, 74%, and 69% and 78%, 73%, and 66% for groups I and II, respectively (P =0.49). The overall actuarial patient survival tended to be better in the younger group (1-, 3-, and 5-year survival of 83%, 79%, and 76% for group I and 81%, 75%, and 69% for group II (P =0.07). Crude mortality probability shows a stable trend until 45 years, a gradual increase in mortality between 45 and 60 years, and then the risk of death is accelerated. The same analysis shows the risk of death is between 1.5 and 2 times greater in Child C patients; this is greater in patients aged more than 66 years. Conclusion. There is no statistically significant difference in patient or graft survival in patients aged over 60 compared to younger recipients. However, when age is assessed as a continuous variable, an adverse effect of older age is seen on outcome and this effect is more marked in sicker patients.

Outcome of liver resection and transplantation for fibrolamellar hepatocellular carcinoma

Abstract Fibrolamellar hepatocellular carcinoma (FL HCC) is an uncommon variant of hepatocellular carcinoma occurring usually in non‐cirrhotic livers. Hepatic resection or transplantation offers the only chance of cure. We reviewed our experience of surgery for FL HCC from 1985‐1998. Twenty patients with FL HCC (13 females and 7 males) median age 27 years (range 12‐69) were treated either by hepatic resection [n = 11; extended right hepatectomy (5), extended left hepatectomy (1), right hemihepatectomy (2), left hemihepatectomy (2), left lateral segmentectomy (1)] or, if the disease was non‐resectable, by transplantation (n = 9). The median follow up was 25 months (1‐63). The prognostic factors analysed included size [less than 5 cm (3 patients), more than 5 cm (17 patients)], number [solitary (16 patients), multiple (4 patients)], capsular invasion (6 patients), vascular invasion (11 patients) and lymph node invasion (6 patients). The overall survival at 1, 3 and 5 years was 89.5, 75 and 50 %, respectively. The liver resection survival was better than liver transplantation survival at 3 years 100 vs 76 %, respectively (P < 0.025). Although all prognostic factors analysed did not show a significant difference, there is tendency that tumour stage was the most significant for prognosis. Most of the patients in this study are young and presented without specific symptoms, with normal liver function range and had no tumour marker to help in diagnosis. As a result most of our patients were diagnosed late. However the outcome of surgical intervention was favourable.

Unresectable hepatic tumors in childhood and the role of liver transplantation

Liver transplantation has been performed in five children with unresectable hepatic tumors who did not have extrahepatic metastases at the time of surgery. Two of the children had hepatoblastomas, one had an infantile hemangioendothelioma, and two had a hepatoma. The two children who had hepatoblastoma are well (37 and 25 months posttransplant) and have no evidence of recurrence. The child with infantile hemangioendothelioma had a successful operation, with good quality of life, but died of tumor recurrence 41 months after transplantation. Both children with hepatomas died, one of graft failure owing to chronic rejection and the other of tumor recurrence 5 months posttransplant. These results suggest that liver transplantation may be successful in children with unresectable hepatic tumors without extrahepatic spread and should be considered particularly for the treatment of hepatoblastoma.

Long-term nutritional and neurodevelopmental outcome of liver transplantation in infants aged less than 12 months.

BACKGROUND Liver transplantation is established treatment for children with end-stage liver disease and has a 5-year survival rate of 80% to 85%, even in infants under 12 months. Long-term outcome in nutritional rehabilitation and normal development is unknown. This study aimed to prospectively evaluate growth and psychoneurologic performance of children who undergo liver transplantation in infancy. METHODS Twenty-five infants (18 girls, 7 boys) who underwent liver transplantation at less than 12 months of age (median age, 9 months) were evaluated for 4 years. Growth measurements were expressed as standard deviation scores (SDSs; mean +/- SEM), and psychoneurologic performance was assessed with the unrevised Griffiths Mental Ability Scales (normal range, 80-120). RESULTS Four children died during the study (4-year survival, 84%). The children were malnourished before transplantation (SDSs: weight, -1.9 +/- 0.2; midarm muscle area, -0.93 +/- 0.3; midarm fat area, -1.52 +/- 0.3; and height, -0.95 +/- 0.3). Nutritional rehabilitation for all parameters occurred within 12 to 24 months after transplantation, which was most significant for weight (-1.1 +/- 0.2, P = 0.001), midarm muscle area (0.74 +/- 0.3, P = 0.001), and midarm fat area (-0.44 +/- 0.3, P = 0.01). There was some improvement in height (-0.72 +/- 0.3, P = 0.14), which was not significant, although infants who were severely stunted before transplantation (mean height standard deviation score [SDS] -2.46) showed significant catch-up at 1 year after transplantation (mean height SDS -1.2, P = 0.003). Psychoneurologic scores were within normal limits before transplantation and were maintained for the 4-year follow-up period, although individual scores varied during this period. Improved nutritional status was associated with increased muscle bulk and subsequent improvement in motor scores from 90.6 at initial assessment to 97.3 at 4 years (P = 0.28). There was a temporary reduction in social skills and eye-hand coordination in the first year, which may have been an effect of the hospital environment or cyclosporine immunosuppression. Language abilities also regressed during the first year, possibly related to the effect of nasogastric tube feeding in delaying normal speech development. CONCLUSIONS Liver transplantation in infancy has not only a successful outcome but is also associated with long-term catch-up growth and nutrition and maintenance of normal development.

Favourable prognostic factors in a large UK experience of adenocarcinoma of the head of the pancreas and periampullary region.

Aims: To present the surgical experience in a regional unit, analysing the post-operative outcome, and determining risk factors for survival after pancreaticoduodenectomy for periampullary and pancreatic head carcinoma. Methods: Data were collected on 251 patients with pancreatic head adenocarcinoma (133), ampullary carcinomas (88) and distal common bile duct (30), between 1987 and 2002. Survival was calculated using the Kaplan-Meier method. Clinical, surgical and histopathological records were examined by univariate and multivariate analysis to identify the independent prognostic predictors of survival. Results: Median actuarial survival for carcinoma of the pancreatic head, ampulla and distal bile duct were 13.4, 35.5 and 16 months, respectively; p < 0.0001. On univariate analysis for the whole series, the age ≤60, tumour of the head of the pancreas, lymph node positive, resection margin R1, poorly differentiated tumours, and portal vein invasion significantly decreased survival. On multivariate analysis, poor tumour differentiation, surgical margin, lymph node metastases, and age independently influence survival. Mortality and morbidity were 4.8 and 29.9%, respectively. Conclusions: Pancreaticoduodenectomy for pancreatic and periampullary tumours is the only therapy that may cure patients and can be performed safely in centres with significant experience.

Neuroendocrine Tumours of the Pancreas: Predictors of Survival after Surgical Treatment

Aims: Neuroendocrine tumours of pancreatic and duodenal origin (NETP) are rare and we present a significant experience from a single centre. Methods: Data was collected on 44 patients who underwent surgery between 1988 and 2002. Since 1997, data have been recorded prospectively on a dedicated database. Results: Twenty-four patients had functioning tumours (16 insulinomas, 3 gastrinomas, 2 somatostatinomas, 1 vipoma, 1 glucagonoma and 1 carcinoid tumour). Nine functioning tumours and 13 non-functioning had a malignant phenotype. Twenty pancreaticoduodenectomies, 9 local excisions, 7 distal and 2 total pancreatectomies, 5 bypasses and 1 exploratory laparotomy were performed. Fourteen patients (31.8%) had surgical complications, 1 died peri-operatively (2.3%). The overall actuarial survival for resected cases was 74.4 and 42.5% at 5 and 10 years, respectively. Lymph node invasion and metastases were significant predictors of survival by univariate analysis and only the presence of metastases retained significance on multivariate analysis. Conclusion: Surgical resection is the only curative treatment for NETP. Resection can be safely carried out in a specialist centre and is associated with good long-term survival. The presence of metastases was a significant predictive factor for survival in patients with NEPT in this series.

Liver transplantation in babies and children with extrahepatic biliary atresia.

Orthotopic liver transplantation (OLT) is a life-saving procedure for end-stage liver failure. We reviewed 39 children (24 girls, 15 boys) who received OLT for biliary atresia from 1987 to 1991. Twenty had unsuccessful portoenterostomy, 6 were referred too late for a drainage operation, and the remaining 13 achieved bile drainage but developed portal hypertension. At transplant 37 had decompensated liver disease with varices (28), ascites (24), encephalopathy (17), and gastrointestinal bleeding (12). The median weight and age at transplant were 8 kg and 12.6 months, respectively. The median waiting time was 65 days. Forty-eight grafts (30 reduced and 18 whole) were performed; graft loss was 33% and 27%, respectively. Of the 30 segmental grafts, 15 were reduced conserving the left lateral segment and hepatic vein (Brisbane technique)--13 were from the left lobe and 2 from the right lobe. The overall subject survival rate is 72%. Eleven deaths occurred: primary nonfunction (3), sepsis (3), perioperative bleed (3), and other causes (2). Early complications included: hepatic artery thrombosis (5), hepatic vein thrombosis (2), bowel perforation (3), biliary leak (3), and acute rejection (8). Later complications were chronic rejection (4) and biliary stricture requiring reconstruction (3). Follow-up at 12 months confirms good quality of life for both child and family with catch up growth and normal development. Technical advances in reduction hepatectomy have allowed us to treat small babies under 1 year with an urgent requirement for OLT, with comparable results to those obtained with whole grafts. In conclusion, in the future size and age need not be a contraindication to OLT in children with biliary atresia.

Treatment of Hydatid Disease of the Liver

Background: Hydatid disease of the liver though endemic in many countries, is rare in the UK. We evaluated a 16-year experience of treating hydatidosis using a management protocol combining surgery with anti-scolicidals. Patients and Methods: There were 30 patients. 14 (47%) males, median age 41 (range 25–72) years, of whom 21 (70%) were symptomatic. Diagnosis was by serological tests and imaging. All had disease confined to the liver and received peri-operative anti-scolicidal drug therapy. Results: The initial 4 (13%) patients received praziquantel combined with albendazole for 2 weeks and the following 26 (87%) patients received two cycles of albendazole 400 mg twice daily for 28 days, with a 14-day break in between. However, 2 (7%) patients could not tolerate albendazole, one due to GI side effects and the other developed deranged liver functions. These 2 patients subsequently received praziquantel for 2 weeks. All patients underwent surgery. Subtotal cystectomy was carried out on 29 (96%) patients and 1 patient required a segmentectomy. Cystobiliary communications were identified in 15 (50%) of patients which were oversewn using fine absorbable sutures. Of these, 7 had the bile ducts decompressed using a T tube, with only 1 developing a post-operative bile leak. In comparison, 8 were not drained of which 6 leaked (p = 0.03). The median post-operative hospital stay was 8 days (range 5–24). Patients who developed post-operative bile leaks, however, needed prolonged abdominal drainage for a median of 21 days (range 18–24). Two (7%) patients developed histologically proven recurrent disease. The median follow-up was 56 months (range 3–87). Conclusion: Surgery combined with anti-scolicidal therapy proved effective. Cystobiliary communications are common and, when identified, should result in the biliary system being drained, to avoid post-operative bile leaks.

Bile duct splintage in liver transplantation: is it necessary?

Abstract  The choledochochole‐dochal (duct‐duct, D‐D) anastomosis in orthotopic liver transplantation (OLT) is usually splinted by a T‐tube to facilitate easy cholangiog‐raphy, monitor bile quality and allow biliary decompression. T‐tubes, however, are a focus for sepsis and sludge deposition, and their removal may result in bile leakage. From January 1993 to December 1994, 199 consecutive adult OLTs in 183 patients (median age 50 years, range 16–69 years, 118 females) with a D‐D anastomosis were studied pro‐spectively with a median follow‐up of 16 (3–27) months. Of the 199 OLTs, 110 had an 8 Fr T‐tube (group 1) and 89 had no T‐tube (group 2). The two groups were similar for indication, preservation solution, median cold and warm is‐chaemia times and early graft function parameters. Biliary complications developed in 26/110 patients, including 10 with bile leaks on T‐tube removal in group 1 compared to 10/89 biliary complications in group 2 (P= 0.024). The use of T‐tubes is associated with increased morbidity and their routine use should be discontinued.

Role of Completion Pancreatectomy as a Damage Control Option for Post-Pancreatic Surgical Complications

Introduction: Management of pancreatic leak and haemorrhage is complex with high mortality rates. In this study, the results of completion pancreatectomy which was performed as a last resort option were analysed. Patients and Methods: 25 patients who had completion pancreatectomy from among 677 patients who had pancreatoduodenectomy or distal pancreatectomy over a period of 18 years were analysed in terms of the indications for completion pancreatectomy, outcome and survival data. Results: Indications for completion pancreatectomy include pancreatic leak in 12 patients (48%), both bleeding and pancreatic leak in 8 (32%), and haemorrhage alone in 5 (20%) patients. 18 (72%) patients also had splenectomy. Median ITU stay was 4 and 8 days for those who survived and died post-completion pancreatectomy, respectively. 36% patients had septicaemia and 32% patients had multiple organ failure. 12 patients survived the operation with a median survival of 52 months. Conclusion: 25 (3.6%) patients required surgical intervention for pancreatic complications. The incidence of splenectomy was 84.6% in those who died after completion pancreatectomy compared to 58.3% of those who survived (Fisher’s exact test two-sided 0.20). Despite significant morbidity and mortality, completion pancreatectomy has a role in the management of post-pancreatic surgical complications.