Influence of hospital characteristics on operative death and survival of patients after major cancer surgery in Ontario.

BACKGROUND: There is a lack of information from Canadian hospitals on the role of hospital characteristics such as procedure volume and teaching status on the survival of patients who undergo major cancer resection. Therefore, we chose to study these relationships using data from patients treated in Ontario hospitals. METHODS: We used the Ontario Cancer Registry from calendar years 1990-2000 to obtain data on patients who underwent surgery for breast, colon, lung or esophageal cancer or who underwent major liver surgery related to a cancer diagnosis between 1990 and 1995 in order to assess the influence of volume of procedures and teaching status of hospitals on in-hospital death rate and long-term survival. For each disease site and before observing patient outcomes data, volume cut-off points were selected to create volume groups with similar numbers of patients. Teaching hospitals were those directly affiliated with a medical school. Logistic regression and proportional hazards models were used to consider the clustering of data at the hospital level and to assess operative death and long-term survival. We also used 4 measures to gauge the degree of procedure regionalization across the province including (1) the number of hospitals performing a procedure; (2) the percentage of patients treated in teaching hospitals; (3) the percentage of rural patients treated in higher volume procedure hospitals; and (4) median distances travelled by patients to receive care. RESULTS: The number of patients in our cohorts who underwent resection of the breast, colon, lung, esophagus or liver was 14 346, 8398, 2698, 629 and 362, respectively. Surgery in a high-volume versus a low-volume hospital did not have a statistically significant influence on the odds of operative death for patients who underwent colon, liver, lung or esophageal cancer resection. The risk of long-term death was increased in low-volume versus high-volume hospitals for patients who underwent resection of the breast (hazard ratio [HR] 1.2, 95% confidence interval [95% CI] 1.0-1.4, p < 0.05), lung (HR 1.3, 95% CI 1.1-1.6, p < 0.01) and liver (HR 1.7, 95% CI 1.0-2.7, p = 0.04). There were no significant differences in the odds of operative (in-hospital) death or risk of long-term death among patients treated in teaching compared with nonteaching hospitals. There was more regionalization of liver, lung and esophageal operations versus breast and colon operations. CONCLUSIONS: Increased hospital procedure volume correlated with improved longterm survival for patients in Ontario who underwent some, but not all, cancer resections, whereas hospital teaching status had no significant impact on patient outcomes. Across the province, further regionalization of care may help improve the quality of some cancer procedures.     

A multi-centre phase two study of intravesical epirubicin in the treatment of superficial bladder tumour

Epirubicin (4'-epi-adriamycin) was used in the treatment of widespread superficial carcinoma of the bladder. Thirty-seven patients received 50 mg in 50 ml of saline retained for 60 min. There was an overall response rate of 59% but this was of short duration. Thirty percent of patients progressed despite therapy. Therapy was associated with an incidence of side effects which necessitated therapy withdrawal in 12 (32.4%) patients. It is concluded that epirubicin, in the dose used in this study, cannot be recommended for routine intravesical chemotherapy and that further studies, at a reduced dosage, are necessary to evaluate this agent.     

Secretion of the mycobacterial 19-kilodalton protein by Escherichia coli, a novel method for the purification of recombinant mycobacterial antigens.

We have reported previously (R.G. Hewinson and W.P. Russell, J. Gen. Microbiol. 139:1253-1259, 1993) the secretion by Escherichia coli of a recombinant form of the immunogenic protein MPB70 of Mycobacterium bovis when the protein is translated from its native initiation codon. N-terminal sequence analysis of the purified protein revealed that the signal peptide of MPB70 was cleaved by an endopeptidase of E. coli at the same cleavage site as reported for the protein in M. bovis. Since both the B- and T-cell antigenicities of the purified recombinant protein were similar to that of the native protein, the 19-kDa antigen of M. bovis was used as a model to test whether the signal peptide of MPB70 could direct the secretion of heterologous proteins in E. coli and whether antigen produced in this way retained antigenicity superior to that of recombinant protein produced as a fusion to glutathione-S-transferase. A chimeric protein was produced in which the signal peptide of MPB70 was fused to the 19-kDa antigen of M. bovis at amino acid residue 23. This chimeric protein was found to be secreted into the periplasm and culture medium of recombinant E. coli, and the signal peptide was cleaved by an endopeptidase of E. coli during secretion. Secretion of the 19-kDa antigen facilitated purification of the antigen by two-stage preparative electrophoresis which gave yields of 2.5 mg of purified, soluble 19-kDa antigen from 2.5 g (wet weight) of E. coli. Antigen purified in this way retained both B- and T-cell antigenicities. Moreover, the nonspecific mitogenic activity of the purified 19-kDa antigen was low, while the magnitude of the T-cell response induced by the purified antigen was considerably higher than that observed with purified antigen produced as a fusion protein with glutathione-S-transferase.     

Role and regulation of interleukin-1 molecules in pro-asthmatic sensitised airway smooth muscle.

Interleukin (IL)-1beta is a pleiotropic, pro-inflammatory cytokine that has been importantly implicated in driving the inflammatory response and resultant changes in airway smooth muscle (ASM) responsiveness in asthma. IL-1beta belongs to a family of molecules, known as the IL-1 axis, which exert both pro- and anti-inflammatory effects. Since dysregulation of IL-1 axis molecules may be critical in the pathobiology of asthma, the present study examined the expression and activation of both the inhibitory and stimulatory IL-1 axis molecules in human ASM cells and their roles in modulating cytokine and immunoglobulin (Ig)E immune complex (IgE cx)-mediated changes in rabbit ASM constrictor and relaxant responsiveness. The results demonstrate the following. 1) Pre-treatment of isolated rabbit tracheal rings with the inhibitory IL-1 axis members, IL-1 receptor antagonist and IL-1 type-II receptor abrogated both IL-5- and IgE cx-induced changes in ASM responsiveness. 2) Administration of IL-5, IL-1beta and IgE cxs to human ASM cells increased mRNA and protein expressions of both stimulatory and inhibitory IL-1 axis molecules. 3) The time course of IL-5-induced IL-1 axis molecule expression preceded that of both IL-1beta and IgE immune cxs. Collectively, these findings suggest that modulation at the level of the interleukin-1 axis of molecules may have significant therapeutic potential in the treatment of asthma.