Liver transplantation

Linear and three-dimensional polymer composites were prepared on the basis of poly(2-hydroxyethyl methacrylate)--pHEMA--and collagen. Their biological properties were tested by in vitro as well as in vivo methods. The composite material (unlike pure pHEMA) supported myoblast adhesion as well as their fusion into multinuclear myotubes in vitro. The three-dimensional polymer composites stimulated a new bone formation after their intraosseal implantation in dogs and pigs. The biomaterial itself was degraded in the host organism, in contrast to stable pHEMA.     

Liver transplantation for metastatic neuroendocrine carcinoma: an analysis of 103 patients

BACKGROUND: Patients with neuroendocrine carcinoma often present with liver metastases not amenable to hepatic resection. For them, liver transplantation has been considered a viable treatment option, especially if hormonal symptoms and pain cannot be controlled medically. Still, little is known regarding potential prognostic factors and long-term survival after liver transplantation for neuroendocrine tumors. METHODS: A search of English, French, and German literature identified patients with liver transplantation for extensive metastases from neuroendocrine carcinoma for whom follow-up data were available. RESULTS: Overall, 2-year and 5-year survival for all 103 patients was 60% and 47%, respectively, but recurrence-free 5-year survival did not exceed 24%. Univariate analysis identified age less than 50 years, primary tumor location in lung or bowel, and pretransplant somatostatin therapy as favorable prognostic factors, whereas extended operations combining liver transplantation with upper abdominal exenteration or Whipple's procedure were associated with poor prognosis. Multivariate analysis identified age greater than 50 years (P<0.03) and transplantation combined with upper abdominal exenteration or Whipple's operation (P<0.001) as adverse prognostic factors. CONCLUSIONS: Liver transplantation may be justified in selected patients to provide immediate relief of otherwise intractable pain or hormone-related symptoms. Transplantation with curative intent appears worthwhile in young patients with only hepatic disease. In older patients with extrahepatic disease requiring extended operations, long-term results are discouraging, and the small benefit achieved by liver transplantation must be weighed against medical treatment options and the natural course of often slowly progressing disease.     

Structure and evolution of parallel beta-helix proteins

Three bacterial pectate lyases, a pectin lyase from Aspergillus niger, the structures of rhamnogalacturonase A from Aspergillus aculeatus, RGase A, and the P22-phage tailspike protein, TSP, display the right-handed parallel beta-helix architecture first seen in pectate lyase. The lyases have 7 complete coils while RGase A and TSP have 11 and 12, respectively. Each coil contains three beta-strands and three turn regions named PB1, T1, PB2, T2, PB3, and T3 in their order of occurrence. The lyases have homologous sequences but RGase A and TSP do not show obvious sequence homology either to the lyases or to each other. However, the structural similarities between all these molecules are so extensive that divergence from a common ancestor is much more probable than convergence to the same fold. The region PB2-T2-PB3 is the best conserved region in the lyases and shows the clearest structural similarity. Not only is the pleating and the direction of the hydrogen bonding in the sheets conserved, but so is the unusual alphaL-conformation turn between the two sheets. However, the overall shape, the position of long loops, a conserved alpha-helix that covers the amino-terminal end of the parallel beta-helix and stacks of residues in alphaR-conformation at the start of PB1 all suggest a common ancestor. The functional similarity, that the enzymes all bind alpha-galactose containing polymers at an equivalent site involving PB1 and its two flanking turn regions, further supports divergent evolution. We suggest that the stacking of the coils and the unusual near perpendicular junction of PB2 and PB3 make the parallel beta-helix fold especially likely to maintain similar main chain conformations during divergent evolution even after all vestige of similarity in primary structure has vanished.     

Liver transplantation: experiences and results of a program at the University of Liege

The orthotopic liver transplantation (OLT) program of the University of Liège was initiated in 1986. Between 1986 and December 1998, 150 adult OLT have been performed in our institution, including 18 liver retransplantations, 1 combined heart and liver transplantation and 3 combined liver and kidney transplantations. The aim of this study was to report the last 3 years of our experience. From January 1996 to November 1998, we performed 50 OLT on 49 patients. Three were retransplantations and two were combined liver and kidney transplantations. Fourty-three patients were transplanted for chronic liver disease and 6 for acute or subacute hepatopathy. Mean waiting time on the list was 4 weeks. Immunosuppression was based on triple therapy (cyclosporin A/tacrolimus, steroids, azathioprine), with steroid and azathioprine withdrawal in most of the patients after 3 months. In the chronic liver disease group, operative (< 30 days) survival was 95% (peroperative myocardial infarction in 2 patients). In the acute liver disease group, postoperative survival was 66%. No perioperative death occurred in 1997 and 1998. Actuarial one year survival was 87%. In our experience, OLT has become a safe procedure.     

Liver transplantation: the death/life paradox

Chronic encapsulated intracerebral hematoma (CEIH) is a rare disease which is believed to be caused by angiographically negative vascular malformations. CEIH has the following characteristic findings: 1. It affects all age groups 2. Clinical symptoms progress slowly after sudden onset. Often there is a latency of months or years 3. There is no correlation with arterial hypertension 4. Imaging reveals a typical fibrous capsule with enclosed blood contents and signs of recurrent bleedings 5. Cavernoma was identified histologically as the cause of bleeding in 30% of cases. 6. All patients had a primary diagnosis of intracerebral tumor. To the best of our knowledge, 27 cases have been reported in the literature. We now add two cases, one of which is the first in the available literature which was not operated and could be followed by imaging.     

Liver graft bile duct necrosis--indication for retransplantation

The Herlitz type of junctional epidermolysis bullosa (H-JEB) is a severe blistering disease affecting the skin and mucous membranes, which is usually lethal within the first year of life. The laminin 5 genes have been implicated as candidate genes for most patients with H-JEB. Recently, two hotspot mutations were delineated in the LAMB3 gene, known as R42X and R635X, and have been noted in over 50% of mutant LAMB3 alleles. Here, we present a case of H-JEB of Hungarian origin with a neonatal lethal outcome. Monoclonal antibody staining showed a lack of expression of the laminin 5 beta 3 chain, as a possible result of a mutation in one of the laminin 5 genes. Screening of the family identified the previously described mutation R635X in exon 14 of LAMB3 in each of the parents and one healthy sibling in the heterozygous form, while proband was homozygous for R635X, and the other sibling proved to be genotypically normal. These results underscore the widespread prevalence of R635X in H-JEB cases from around the world.     

Liver transplantation for decompensated cirrhosis after jejunoileal bypass: a strategy for management

BACKGROUND: Although jejunoileal bypass results in end-stage liver disease in up to 100% of patients, little is known about outcome after liver transplantation. METHODS: The clinical courses of six patients who underwent liver transplantation at UCLA for decompensated cirrhosis owing to a jejunoileal bypass were reviewed. Liver function, allograft pathology, renal function, and nutritional status were assessed. RESULTS: Of the four patients with an intact jejunoileal bypass, two of the three who were biopsied had recurrent steatotic liver disease. The two patients whose jejunoileal bypass was reversed at the time of liver transplantation had lower alkaline phosphatase, lower creatinine, higher albumin, and higher cholesterol, and were more obese than their counterparts with intact bypasses. CONCLUSIONS: Patients undergoing liver transplantation for jejunoileal bypass-associated liver disease should, if possible, have their bypass reversed at the time of transplantation; otherwise, they must be followed closely and be biopsied routinely. Recurrent liver disease should prompt reversal of the jejunoileal bypass.     

Liver transplantation for hepatocellular carcinoma

Liver transplantation (LT) for hepatocellular carcinoma (HCC) has been controversial, however, with increasing experience the results of the procedure in these patients have improved. Earlier reports of poor result may have been secondary to advanced tumor and poor patient selection. Careful patient selection and preoperative assessment of tumor characteristic is essential before offering LT to these patients. Results of LT in carefully selected cases may be similar to patients receiving LT for other reasons. In cirrhotic patients LT may offer a better long-term survival than liver resection.     

Liver transplantation for Wilson's disease

BACKGROUND/AIMS: As has been the case with other metabolic diseases of the liver in the last decade, orthotopic liver transplantation has been applied to the treatment of Wilson's disease with increasing frequency. The experience at the University of Pittsburg with orthotopic liver transplantation for Wilson's disease is reported. METHODS: Between February 1981 and December 1991, 51 orthotopic liver transplants were performed on 39 patients (16 pediatric, 23 adults) with Wilson's disease. Twenty-two patients were transplanted because of a presentation co-existent with fulminant hepatic failure. Seventeen presented with chronic advanced liver disease with (n=9) or without (n=8) associated neurologic dysfunction. RESULTS: The rate of primary graft survival (n-39) was 73% and patient survival was 79.4%. No patient mortality occurred beyond 3 weeks post-orthotopic liver transplantation. Survival was butter for those with a chronic advanced liver disease presentation (90%) than it was for those with a fulminant hepatic failure (73%) presentation, but the difference was not statistically significant. CONCLUSIONS: 1) Currently, orthotopic liver transplantation is the treatment of choice for Wilson's disease presenting as fulminant hepatic hepatic failure; 2) orthotopic liver transplantation should be considered for patients with Wilson's disease with advanced, chronic liver disease for whom no other therapy is possible; 3)orthotopic liver transplantation only partially corrects the underlying metabolic defect of patients with Wilson's disease and converts the copper kinetics from that characteristic of an individual affected with a homozygous disease to that of an individual who is an obligate heterozygote, thereby effecting a phenotypic cure.     

Liver and kidney transplantation for polycystic disease

We conducted a double-blind, randomized, placebo-controlled study to investigate the effectiveness of P6 acupuncture on postoperative vomiting in children undergoing strabismus surgery. Acupuncture was performed by laser stimulation with a low-level laser. Laser stimulation of P6 was administered 15 min before induction of anaesthesia and 15 min after arriving in the recovery room. In the laser stimulation group, the incidence of vomiting was significantly lower (25%) than that in the placebo group (85%).