Pancreatic cancer and comparison of a hospital-based tumor registry with a National Cancer Data Base

BACKGROUND: The Commission on Cancer of the American College of Surgeons has called upon institutions providing cancer care to compare practice patterns and outcomes with the National Cancer Data Base (NCDB). Using data from the Virginia Mason Tumor Registry (VMTR), we sought to compare our pancreatic cancer care patterns with those reported nationally, while critically evaluating the accuracy and usefulness of our registry. METHODS: A review of the 906 computerized patient files in the VMTR from 1973 to 1995 was performed, with more detailed data on patients from the last 5 years retrieved from 224 manual abstracts. These data were compared with the 1991 NCDB for pancreatic cancer. RESULTS: The percent of cases according to AJCC stage in the NCDB (n = 9,715) versus the VMTR (n = 149), respectively, with cases of unknown stage excluded, were stage I 22% versus 22%, stage II 9% versus 12%, stage III 17% versus 28% (P <0.05) stage IV 52% versus 38% (P <0.05). One-third of the cases in the VMTR 1991 to 1995 were of unknown stage; number of cases with unknown stage for NCDB was 26.6%. The percent of surgical procedures for the NCDB (n = 7,802) versus the VMTR (n = 224), respectively, was pancreatectomy 14% versus 11%, local excision 1% versus 0%, no cancer-directed surgery 83% versus 89% (P <0.05), unknown 2% versus 0% (P <0.05). The actuarial relative survival rates for the 1991 NCDB versus 1987 to 1995 VMTR was 3-year 18% versus 38%, and 5-year 14% versus 35%. CONCLUSIONS: In comparison with the NCDB, VMTR may have fewer stage IV pancreatic cancers, but improvement is needed in decreasing the number of patients for whom the stage is unknown, as many of these likely represent late stage disease. We have a similar resection rate and a higher survival compared with the NCDB, but a mechanism is not in place to statistically compare our survival data with those of the NCDB. Even though all accredited hospitals are required to have a tumor registry, our data were difficult to compare with those of the NCDB because of coding and reporting deficiencies and inability to statistically compare survival data. Before our practice patterns and outcomes can be compared with national standards, both the VMTR and the NCDB must have standardized data collection and better access to the data.     

Fas ligand expression in islets of Langerhans does not confer immune privilege and instead targets them for rapid destruction

Fas ligand is believed to mediate immune privilege in a variety of tissues, including the eye, testis, and a subset of tumors. We tested whether expression of Fas ligand on pancreatic islets either following adenoviral or germline gene transfer could confer immune privilege after transplantation. Islets were infected with an adenoviral vector containing the murine Fas ligand cDNA (AdFasL), and were transplanted into allogenic diabetic hosts. Paradoxically, AdFasL-infected islets underwent accelerated neutrophilic rejection. The rejection was T cell and B cell independent and required Fas protein expression by host cells, but not on islets. Similarly, transgenic mice expressing Fas ligand in pancreatic beta cells developed massive neutrophilic infiltrates and diabetes at a young age. Thus, Fas ligand expression on pancreatic islets results in neutrophilic infiltration and islet destruction. These results have important implications for the development of Fas ligand-based immunotherapies.     

Information from time-varying vibrotactile stimuli

Experiments have been carried out to investigate the information transfer available via a single vibrator on the fingertip. In a first experiment, for stimuli with durations 80 to 320 ms, discrimination of a one-octave step change in frequency at the halfway point was investigated. Results were similar for three stimulus types--sinewave, monophasic pulse and tetraphasic pulse--suggesting temporal cues are more important than spectral cues in this task. In a second experiment, subjects were required to perceive changes in a sequence of stimulus elements. A presentation rate of 6.25 elements s-1 was found to give better results than a rate of 12.5 elements s-1. In the former case, the potential information transfer per element was estimated to be approximately 1.0 bits, corresponding to an information transfer rate of around 6 bits s-1. Implications for the design of a tactile aid to lipreading are discussed.     

Release of proinflammatory cytokines during pediatric cardiopulmonary bypass: heparin-bonded versus nonbonded oxygenators

BACKGROUND: Heparin bonding of the cardiopulmonary bypass (CPB) circuit may be associated with a reduced inflammatory response and improved clinical outcome. The relative contribution of a heparin-bonded oxygenator (ie, >80% of circuit surface area) to these effects was assessed in a group of pediatric patients. METHODS: Twenty-one pediatric patients undergoing CPB operations were assigned randomly to receive either a heparin-bonded oxygenator (group H, n = 11) or a nonbonded oxygenator (group C, n = 10) in otherwise nonbonded circuits. The two groups were similar in pathology, age, weight, CPB time, and cross-clamp time. Plasma levels of the cytokines tumor necrosis factor-alpha, interleukin-6, and interleukin-8, as well as terminal complement complex, neutrophils, and elastase, were analyzed before, during, and after CPB. RESULTS: Significant levels of tumor necrosis factor-alpha were not detected in either group. Plasma levels of all other markers increased during and after CPB compared with baseline. Plasma levels of interleukin-6 peaked in both groups 2 hours after the administration of protamine but remained significantly higher in group C 24 hours after operation. Plasma concentrations of interleukin-8 peaked at similar levels in both groups 30 minutes after protamine administration and returned to baseline thereafter. Levels of terminal complement complex and elastase peaked in both groups 30 minutes after protamine administration. Plasma levels of terminal complement complex were significantly higher at the end of CPB and after protamine administration in group C. Elastase levels were significantly higher 2 and 24 hours after CPB in group C. The ventilation time of patients in group H was significantly lower than that of patients in group C: 10 (range, 3 to 24) versus 22 (range, 7 to 24) hours, respectively (p < 0.01). CONCLUSIONS: The present study confirms the proinflammatory nature of pediatric operations and demonstrates a lessened systemic inflammatory response with the use of heparin-bonded oxygenators. This is achieved without bonding of the entire circuit, which could have significant cost-benefit implications by negating the need for custom-built heparin-bonded circuitry.     

Comparison of coronary vasodilator reserve in elite rowing athletes versus hypertrophic cardiomyopathy

Compared to normal volunteers, coronary vasodilation reserve is reduced in patients with hypertrophic cardiomyopathy but not in rowing athletes with left ventricular hypertrophy. Positron emission tomography can provide complementary information to distinguish between the athlete's heart and hypertrophic cardiomyopathy.     

Down-regulation of glial fibrillary acidic protein expression during acute lytic varicella-zoster virus infection of cultured human astrocytes

The effects of the varicella-zoster virus (VZV) OKA vaccine strain in producing morphologic and antigenic changes in dissociated cultures of human fetal brain was investigated. Cultures containing 80% glial acidic fibrillary protein (GFAP), GFAP+ (positive) astrocytes and 20% GFAP- (negative) fibroblastic-like cells were infected with cell-free VZV OKA at a multiplicity of infection of 0.1 plaque-forming units per cell. Cytopathic effects and significant viral antigen labeling with antibodies against VZV gpl and immediate-early (IE) protein 62 were first detected 6 to 7 days postinfection. Several observations indicated that astrocyte GFAP expression was altered and diminished as a result of VZV infection itself, thereby raising doubts about the utility of combining cell markers and viral antigenic labeling in assessing the susceptibility of neural cell types to viral infection. The down-regulation of GFAP expression by VZV appears to be mediated by early rather than late events in the viral replication cycle and may not be the result of virally induced global shut-off of host cell protein synthesis. Similar observations were made using VZV Ellen, a multipassaged, nonvaccine strain. These observations have potential in vivo implications related to histologic analysis of VZV-infected tissues and disease pathogenesis.     

Homocamptothecins: synthesis and antitumor activity of novel E-ring-modified camptothecin analogues

Homocamptothecin (hCPT), a camptothecin (CPT) analogue with a seven membered beta-hydroxylactone which combines enhanced plasma stability and potent topoisomerase I (Topo I)-mediated activity, is an attractive template for the elaboration of new anticancer agents. Like CPT, hCPT carries an asymmetric tertiary alcohol and displays stereoselective inhibition of Topo I. The preparation and biological screening of racemic hCPT analogues are described. The 10 hCPTs tested were better Topo I inhibitors than CPT. Fluorinated hCPTs 23c, d,f,g were found to have potent cytotoxic activity on A427 and PC-3 tumor cell lines. Their cytotoxicity remained high on the K562adr and MCF7mdr cell lines, which overexpress a functionally active P-glycoprotein. Fluorinated hCPTs were more efficacious in vivo than CPT on HT-29 xenografts. In this model, a tumor growth delay of 25 days was reached with hCPT 23g at a daily dose of 0.32 mg/kg, compared to 4 days with CPT at 0.625 mg/kg. Thus difluorinated hCPT 23g warrants further investigation as a novel Topo I inhibitor with high cytotoxicity toward tumor cells and promising in vivo efficacy.