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.     

Anticardiolipin antibodies in serum and cerebrospinal fluid from patients with systemic lupus erythematosus

Anticardiolipin antibodies were studied in serum and cerebrospinal fluid from 32 consecutive patients with systemic lupus erythematosus, admitted for the assessment of neuropsychiatric disease. Ten of the 16 patients with active neuropsychiatric complaints showed positive anticardiolipin antibodies in cerebrospinal fluid, including eight with the simultaneous presence of antibodies in their sera. By contrast, only 2 of the 16 patients with headaches, lacking further data of neurological disease, revealed anticardiolipin antibodies in their cerebrospinal fluid. The assessment of Q-albumin index showed abnormal values in a subset of patients with active neuropsychiatric changes who showed positive cerebrospinal anticardiolipin antibodies, suggesting that an impairment of the blood brain barrier function may lead to a leakage of intrathecal antiphospholipid antibodies from systemic circulation. Additionally, few patients revealed normal Q-albumin values with high IgG-cerebrospinal fluid index suggesting increased intrathecal synthesis of autoantibodies. The study of anticardiolipin antibodies in cerebrospinal fluid was useful to detect active neuropsychiatric disease in systemic lupus erythematosus.     

Clonal analysis of bilateral breast cancer

Forty-nine pairs of bilateral breast tumors (41 synchronous and 8 asynchronous cases) were examined for X-chromosome inactivation status and p53 mutations to address the issue of their clonality. Among 12 cases that were informative for the trinucleotide repeat polymorphism in exon 1 of the androgen receptor gene on the X chromosome, 3 cases were found to have different alleles of the locus inactivated in the right and left breast tumors, indicating that the two tumors arose from distinct transformed cells. Thirteen tumors (13%) from 11 women (22%) contained somatic mutations in exons 5-8 of the p53 gene. In two cases, both breast tumors harbored p53 mutations, but the specific mutations were not identical. Seven synchronous and two asynchronous cases had p53 mutations in one tumor only. A germ line p53 mutation at codon 248, one of the most common p53 mutations in Li-Fraumeni syndrome, was observed in one case. Immunohistochemical analysis of p53 protein with a monoclonal antihuman p53 antibody showed concordant positivity between the right and left tumors in three bilateral breast cancer cases. Our results suggest that at least some bilateral breast tumors originate from distinct cells, but that some bilateral breast tumors may be related through a common p53 abnormality.     

A shape-based machine learning tool for drug design

Building predictive models for iterative drug design in the absence of a known target protein structure is an important challenge. We present a novel technique, Compass, that removes a major obstacle to accurate prediction by automatically selecting conformations and alignments of molecules without the benefit of a characterized active site. The technique combines explicit representation of molecular shape with neural network learning methods to produce highly predictive models, even across chemically distinct classes of molecules. We apply the method to predicting human perception of musk odor and show how the resulting models can provide graphical guidance for chemical modifications.     

Simulation of austenitic microstructure in rod and wire rolling of quenched and tempered steel grades

The determination of the microstructural and forming parameters of rods and wire from low to medium-alloy quenched and tempered as well as spring steel grades is a prerequisite for the mathematical modelling and optimization of the technology on the basis of process and material criteria. Using the boundary, heat balance and finite difference methods as well as visioplastic investigations, the most important forming parameters were determined in high-speed rolling. The rolling of such steel grades allowed to determine the material constants for the dynamic and static equations of recrystallization. Due to the inhibitive effect of the alloying elements (Mo, V) the investigated steel grades display a comparatively pronounced recrystallization inertia. Accordingly, the austenitic post-recrystallization grain size is very fine and relatively independent of the temperature. Temperature control during rod and wire rolling allows to influence and adjust the austenitic microstructure prior to phase transformation.     

The role of anterior ectosylvian cortex in cross-modality orientation and approach behavior

Benzoporphyrin derivative (BPD), a sensitizer currently in clinical trials, was evaluated for the treatment of experimental Greene melanoma implanted in the rabbit iris. To improve tumor targeting, BPD was complexed with low-density lipoprotein (LDL) representing an endogenous carrier system for BPD as previously described. Twelve tumors were irradiated at a sensitizer dose of 2 mg kg-1 body weight using a dye laser at 692 nm. Tumor responses were documented by photography, angiography and light and electron microscopy. All tumors treated with 80 J cm-2 regressed irreversibly. The principal mechanism of tumor necrosis was thrombosis following disruption of endothelial membranes. Ultrastructure data suggested tumor cell damage, although evidence for this being the result of direct PDT-mediated tumor cell death was less clear. These data suggest that BPD-LDL may be used to improve the selectivity of photodynamic tumor therapy possibly by the increased uptake of lipoprotein-delivered sensitizer to neovascular endothelial cells.