Efficacy of the Za self-expandable metal stent for palliation of malignant biliary obstruction

BACKGROUND: The efficacy and safety of the uncoated self-expandable Za metal stent for palliation of malignant distal biliary obstruction was prospectively analyzed. METHODS: Twenty-one patients with unresectable malignant tumors involving mid to distal common bile duct who presented with obstructive jaundice underwent endoscopic implantation of an uncoated self-expandable metal stent. Technical success with stent placement, adverse events, patient survival, duration of stent patency, and device performance were analyzed. RESULTS: Endoscopic biliary stenting was successful in all patients. No adverse events were encountered. The mean follow-up period of the 21 patients was 128 days (range, 3-263): 14 died of progressive disease at mean of 81 days (range, 3-210), 3 remain alive (at days 239, 250, and 263), and 4 were lost to follow-up (at days 90, 91, 92, and 116). The mean duration of stent patency was 249 days. Tumor ingrowth was observed in one patient (5%). Minor technical problems were encountered in 3 patients: 1 proximal deployment, 1 distal deployment, and difficulty associated with the delivery system in 1. CONCLUSIONS: The Za-metal stent provided effective palliation for patients with inoperable malignant biliary tumors. Although minor technical problems were encountered with stent deployment, the overall stent patency, efficacy, and safety profile appear satisfactory.     

Clinically significant differences between point-of-care analysers and a standard analyser for monitoring the International Normalized Ratio in oral anticoagulant therapy: a multi-instrument evaluation in a hospital outpatient setting.

The increasing number of patients requiring oral anticoagulant therapy has lead to an expansion in the use of point-of-care test (POCT) analysers for measuring the International Normalized Ratio (INR) for monitoring purposes. Availability of new technology inevitably leads to comparisons with standard methodologies, and studies to date have reached varying conclusions about the comparability of POCT INRs with conventional testing. We compared the performance of five POCT instruments (Hemochron Junior Signature, ProTime, CoaguChek S, INRatio and TAS) against Innovin thromboplastin on a Sysmex CA1500 automated analyser. The Hemochron Junior Signature, ProTime and CoaguChek S demonstrated strong correlation with the laboratory method (R2 > 0.94). These three analysers demonstrated higher percentages of paired results within 0.5 INR units (81.5, 92.0 and 74.0%, respectively); the INRatio and TAS demonstrated 54.2 and 62.2%, respectively. Within INR ranges of up to 2.0, 2.1-3.0, 3.1-4.0 and above 4.0, none of the POCT analysers demonstrated significant agreement with the standard method in every range. All POCT instruments showed a degree of bias and greater variation from the standard method at INR values above 3.0. These data indicate the potential for POCT analysers to generate INR values sufficiently different from conventional methods that they may impact on clinical decision-making.     

GSTM1 null polymorphism at the glutathione S-transferase M1 locus: phenotype and genotype studies in patients with primary biliary cirrhosis.

Studies were carried out to test the hypothesis that the GSTM1 null phenotype at the mu (mu) class glutathione S-transferase 1 locus is associated with an increased predisposition to primary biliary cirrhosis. Starch gel electrophoresis was used to compare the prevalence of GSTM1 null phenotype 0 in patients with end stage primary biliary cirrhosis and a group of controls without evidence of liver disease. The prevalence of GSTM1 null phenotype in the primary biliary cirrhosis and control groups was similar; 39% and 45% respectively. In the primary biliary cirrhosis group all subjects were of the common GSTM1 0, GSTM1 A, GSTM1 B or GSTM1 A, B phenotypes while in the controls, one subject showed an isoform with an anodal mobility compatible with it being a product of the putative GSTM1*3 allele. As the GSTM1 phenotype might be changed by the disease process, the polymerase chain reaction was used to amplify the exon 4-exon 5 region of GSTM1 and show that in 13 control subjects and 11 patients with primary biliary cirrhosis, GSTM1 positive and negative genotypes were associated with corresponding GSTM1 expressing and non-expressing phenotypes respectively. The control subject with GSTM1 3 phenotype showed a positive genotype.     

TEL gene is involved in myelodysplastic syndromes with either the typical t(5;12)(q33;p13) translocation or its variant t(10;12)(q24;p13)

A t(5;12)(q33;p13) translocation is a recurrent chromosome abnormality in a subgroup of myeloid malignancies with features of both myeloproliferative disorders and myelodysplastic syndromes (MDSs). The molecular consequence of a t(5;12) is a fusion between the platelet- derived growth factor receptor-B gene on chromosome 5 and a novel ETS- like gene, TEL, on chromosome 12. We report on three patients with a t(5;12)(q33;p13) diagnosed as chronic myelomonocytic leukemia, and one case of a t(10;12)(q24;p13) in a progressive MDS, with eosinophilia and monocytosis. Involvement of the TEL gene in these chromosome translocations was investigated by fluorescence in situ hybridization (FISH) with cosmid probes containing selectively the 5' end or 3' end of TEL. Hybridization of these cosmids to the der(5)/der(10) or a der(12), respectively, demonstrated a rearrangement of TEL in both translocations, showing that the t(10;12) is a variant translocation of the t(5;12). Cloning of the fusion cDNA of one case of t(5;12) showed that the breakpoint occurred at the RNA level at exactly the same position as reported by Golub et al (Cell 77:307, 1994). In addition, the TEL gene on chromosome 12 could be localized between two probes previously mapped to 12p13, namely PRB1 and D12S178, leading to a better definition of the position of TEL in this chromosome region. Moreover, in the case involving chromosome 10, the breakpoint occurred between cKTN206 and cKTN312/LYT-10 at 10q24. Clinicohematological data in these studies as well as the restriction mapping of chromosomal breakpoints strongly suggest that (1) common features in MDSs involving the TEL gene are monocytosis and eosinophilia, (2) chromosomes other than no. 5 may be involved and at least a t(10;12)(q24;p13) variant chromosome translocation does exist in these MDSs, and (3) both standard and variant 12p/TEL translocations may be identified by FISH with appropriate probes.     

Hepatosplenic T-cell lymphoma: sinusal/sinusoidal localization of malignant cells expressing the T-cell receptor gamma delta

Peripheral T-cell lymphomas consist of a clinically heterogeneous group of malignant disorders whose immunophenotype usually corresponds to that of normal mature T cells. We describe and correlate the clinical, histopathologic, phenotypic, and genotypic findings in two patients with malignant lymphoma presenting with hepatosplenic disease. The morphologic pattern of lymphoma was that of a sinusal/sinusoidal infiltration in spleen, marrow, and liver. This morphologic characteristic was associated with the presence of a productive clonal rearrangement of the T-cell receptor (TCR) delta gene. Lymphoma cells expressed a CD3-TCR-gamma delta- phenotype. They were also double negative (ie, CD4-CD8-) and lacked the CD5 and CD7 antigens. In one patient, tumor progression was associated with phenotypic changes that resulted in a CD3-TCR-gamma delta- phenotype with the same delta-gene rearrangement as initially. These observations suggest the existence of a new type of peripheral T-cell lymphoma characterized by its hepatosplenic presentation, and by the sinusal/sinusoidal tropism and the TCR-gamma delta phenotype of the malignant cells.     

Further specificity characterization of von Willebrand factor inhibitors developed in two patients with severe von Willebrand disease

Circulating inhibitors against von Willebrand factor (vWF) that show the properties of heterologous IgG antibodies have been described in a few patients with severe von Willebrand disease (vWD). The present study provides further characterization of inhibitors from two patients with severe vWD. Inhibitors in both, like polyclonal rabbit antibody, detected all sizes of multimers and the complex structure of each multimer from platelets and plasma of normal individuals as well as from plasma of patients with IIA, IIB, and IIC vWD. Both inhibitors and the rabbit antibody reacted mainly with the intact 225-Kd vWF subunit and the 189-H and 140-Kd fragments in contrast to monoclonal antibodies specific for vWF fragments that detected a higher relative proportion of 176-Kd fragment. Furthermore, all these antibodies recognized fragment III, although one inhibitor and rabbit polyclonal antibody reacted poorly and the other inhibitor did not react at all with reduced fragment II of vWF digested with Staphylococcus aureus V-8 protease. These data suggest that although human inhibitors from severe vWD patients may behave, to some extent, as polyclonal heterologous antibodies against native vWF, the former show striking differences in their target specificity as well as a much broader specificity than that described for human factor VIII inhibitors.     

RFLPs of the phenylalanine hydroxylase gene in the Italian population

Summary Different mutations of the phenylalanine hydroxylase (PAH) gene leading to phenylketonuria (PKU) have been described associated with specific haplotypes in several European countries. In order to investigate the distribution of DNA haplotypes in Italy, restriction fragment length polymorphism (RFLP) analysis of the PAH gene was performed in nine Italian PKU patients from eight unrelated families, and in the available relatives. The analysis of eight polymorphic sites revealed haplotypes 1 and 6 in association with PKU. This pattern appears to differ from those reported for other European populations.The majority of the 14 PKU subjects studied showed compound heterozygosity for different haplotypes, as observed for other European series.RFLP analysis at the PAH locus allowed us to offer the possibility of prenatal diagnosis to six of the studied families. One prenatal diagnosis was performed and a normal fetus was diagnosed.     

Endoscopic biliary therapy using the combined percutaneous and endoscopic technique

Between September 1985 and December 1987, 74 patients underwent attempted endoscopic biliary therapy using a combined percutaneous transhepatic and endoscopic transpapillary approach (combined procedure). All patients had had failed endoscopy-alone procedures and had contraindications to surgery. The indication was palliation of malignant biliary obstruction in 66 cases (41 common bile duct, 25 hilar), assistance with sphincterotomy for the removal of common bile duct stones in 6 cases, and management of benign biliary stenosis in 2 cases. The initial procedure was percutaneous transhepatic access to the biliary tree, which was successful in all but 1 case (99%). The bile duct was drained externally for an average of 3.4 days before the combined procedure. One patient died during this period from hemorrhage associated with liver puncture. Combined procedure was performed in 72 cases and was successful in 60 [53 malignant stricture (53/66 = 80%), five common duct stone (5/6 = 83%), two benign stricture (2/2 = 100%)]. Procedure-related morbidity and mortality, respectively, were 12.5% and 0% for benign disease and 36% and 3% for malignant disease. The total (initial endoscopy included) morbidity and 30-day mortality were 33% and 0%, respectively, for benign disease and 62% and 27% for malignant disease. Subsequently, stent change has been required on 16 occasions, with endoscopy-only successful in 13 (81%) and repeat combined procedure being required in three (19%). The combined procedure improves the ability of endoscopy to offer nonsurgical therapy to poor risk patients with both malignant and benign biliary disease but is associated with significant morbidity and disease-related mortality.