Long term prognosis after hepatectomy for hepatocellular carcinoma: a survival analysis of 204 consecutive patients

BACKGROUND: Intrahepatic recurrence continues to be the main cause of late death among hepatocellular carcinoma patients after hepatic resection. The aims of the current study were to identify the prognostic factors affecting long term survival and to evaluate the clinical value of pTNM classification as a prognostic factor for these patients. The identification of significant prognostic factors plays an important role in the selection of patients for postoperative adjuvant therapy and counseling. METHODS: From January 1989 to August 1995, 204 consecutive patients underwent hepatectomy for hepatocellular carcinoma. The overall cumulative and disease free survival rates for these patients were analyzed. Univariate and multivariate analyses of 16 clinicopathologic factors, including factors associated with pTNM classification, were performed to determine the significant prognostic factors. RESULTS: The median periods of overall cumulative survival and disease free survival were 35 months and 12.4 months, respectively. By univariate analysis, all factors associated with tumor (T) classification, namely, tumor size, vascular invasion, the number of tumor nodules, and tumor localization, were correlated with survival. By Cox regression analysis, preoperative indocyanine green retention value at 15 minutes, tumor size, and number of tumor nodules were independent prognostic factors of long term survival, whereas the number of tumor nodules, tumor size, and venous permeation were the most powerful predictors of tumor recurrence. The cumulative 5-year survival rates for patients with Stages I, II, III, and IVA tumors were 72%, 55%, 34%, and 8%, respectively. Significant differences in cumulative survival curves were observed among the categories of pTNM classification. CONCLUSIONS: The results of this study showed that pTNM classification correlated well with postoperative survival. Preoperative evaluation of hepatic functional reserve with an indocyanine green clearance test plays an important role in determining the long term prognoses of patients with hepatocellular carcinoma.     

Wound botulism in heroin addiction]

Botulism is a rare disease which usually is caused by preformed botulinum toxin in food. However, this article describes a case of wound botulism in a 29-year-old male heroin addict who developed progressive diplopia, dysphagia and proximal weakness of skeletal limb muscles. He needed mechanical ventilation for two weeks. The clinical diagnosis of botulism was supported by neurophysiological tests. Assays for detection of botulinum toxin and Clostridium botulinum were negative. The patient had not eaten any contaminated food the last two weeks before symptoms appeared, but he had multiple contaminated skin wounds. After treatment with botulinum antitoxins and antibiotics he gradually recovered, and six weeks later he was discharged from hospital in good condition. To the best of our knowledge this is the first case of wound botulism reported in Norway.     

Loss of cell adhesion in Xenopus laevis embryos mediated by the cytoplasmic domain of XLerk, an erythropoietin-producing hepatocellular ligand

The erythropoietin-producing hepatocellular (Eph) family of ligands and receptors has been implicated in the control of axon guidance and the segmental restriction of cells during embryonic development. In this report, we show that ectopic expression of XLerk, a Xenopus homologue of the murine Lerk-2 (ephrin-B1) transmembrane ligand, causes dissociation of Xenopus embryonic blastomeres by the mid-blastula transition. Moreover, a mutant that lacks the extracellular receptor binding domain can induce this phenotype. The carboxyl-terminal 19 amino acids of the cytoplasmic domain of XLerk are necessary but not sufficient to induce cellular dissociation. Basic fibroblast growth factor, but not activin, can rescue both the loss of cell adhesion and mesoderm induction in ectodermal explants expressing XLerk. Collectively, these results show that the cytoplasmic domain of XLerk has a signaling function that is important for cell adhesion, and fibroblast growth factor signaling modulates this function.     

Autoimmune manifestations of the Wiskott-Aldrich syndrome

OBJECTIVE: To describe and review the autoimmune features and typical manifestations of Wiskott-Aldrich syndrome (WAS). DESIGN: Case series and review of the literature. SETTING: Tertiary care medical center and pediatric referral center. PATIENTS: The presentation, diagnosis, and management of two cases are reported. In addition to the typical features of WAS, the first patient had hemolytic anemia, arthritis, leukocytoclastic vasculitis, and colitis. The second patient had colitis and arthralgias. Detailed review of features and therapeutic options in WAS as exemplified by these two patients are presented. Both patients had bone marrow transplantation, the only definitive treatment for WAS. CONCLUSIONS: WAS has variable clinical and autoimmune manifestations. Diagnosis must be suspected in a boy with small, decreased number of platelets and autoimmune problems or infections. Bone marrow transplantation is the only successful mode of treatment for all aspects of WAS.     

The treatment of chronic ischemic heart disease: the potentials for hypolipidemic correction using current drugs

The data obtained by the authors suggest that lipanor may correct those lipid metabolic disturbances that are most pronounced in each individual case. Moreover, the above drug is capable of lowering substantially the level of total blood cholesterol and atherogenic fractions of lipoproteins as early as at day 14 after its intake. Being associated with minimum adverse effects, and intended to be taken on a once-daily schedule, the drug will, we believe, come in wide use.     

Generation of specific deoxynojirimycin-type inhibitors of the non-lysosomal glucosylceramidase

The existence of a non-lysosomal glucosylceramidase in human cells has been documented (van Weely, S., Brandsma, M., Strijland, A., Tager, J. M., and Aerts, J. M. F. G. (1993) Biochim. Biophys. Acta 1181, 55-62). Hypothetically, the activity of this enzyme, which is localized near the cell surface, may influence ceramide-mediated signaling processes. To obtain insight in the physiological importance of the non-lysosomal glucosylceramidase, the availability of specific inhibitors would be helpful. Here we report on the generation of hydrophobic deoxynojirimycin (DNM) derivatives that potently inhibit the enzyme. The inhibitors were designed on the basis of the known features of the non-lysosomal glucosylceramidase and consist of a DNM moiety, an N-alkyl spacer, and a large hydrophobic group that promotes insertion in membranes. In particular, N-(5-adamantane-1-yl-methoxy)pentyl)-DNM is a very powerful inhibitor of the non-lysosomal glucosylceramidase at nanomolar concentrations. At such concentrations, the lysosomal glucocerebrosidase and alpha-glucosidase, the glucosylceramide synthase, and the N-linked glycan-trimming alpha-glucosidases of the endoplasmic reticulum are not affected.     

Clinical applications of detecting dysfunctional p53 tumor suppressor protein

The p53 gene encodes for a protein, p53, which plays a critical role in controlling the cell cycle, in DNA repair and in programmed cell death (apoptosis). p53 is one of the most frequently mutated genes in human neoplasms and a variety of techniques have been developed to detect these mutations. These range from advanced molecular-genetic analyses to immunohistochemical staining for the p53 protein. This review will summarize our current understanding of the function of p53 as well as current methods to detect dysfunctional p53 and the clinical value of such analyses.     

Correlation of chemiluminescent parameters of blood in non-irradiated animals with their survival after irradiation

Blood chemiluminescence is a reflection of the free radical oxidation process in every organism. The changes of its intensity, as a consequence of changes in the rate of this process, are connected, in its turn, with the changes, in the functional state of the organism. It is supposed that the differences in the radiosensitivity depend on the conditions in which free radical oxidation processes take place. Therefore, the indices of blood chemiluminescence of intact rats have been studied. The aim of the investigation is to find the correlations between these indices and the survival of animals irradiated with gamma-quantas in doses of 3.5, 7.0 and 9.0 Gr. It is established that the coefficients of the reaction rate (k1, k2 and k3) most reliably correlate with survival, whereas no correlation is observed between the other indices of chemiluminescence and survival.