Minimizing risk through incident investigation and intervention.
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Hospital Administration↗
Biomedical subjects
M A Hudson
Publications and source records attributed to M A Hudson.
Early detection of prostate cancer.
Prostate cancer is unique among the potentially lethal human malignancies in the wide discrepancy between the high prevalence of histologic changes recognizable as cancer and the much lower prevalence of the clinical disease. Despite the availability of effective tests for early detection and of effective treatment for cancers so detected, the diagnosis usually is not established until the tumor is locally advanced or metastatic. Yet, physicians hesitate to use these tests for fear that many cancers found would be latent, of little threat to the life or health of the host, and treatment could introduce inappropriate morbidity. Latent or "clinically unimportant" cancers can be distinguished from those that are clinically important by the larger volume, higher grade, and greater invasiveness of the latter. The available tests can detect only those cancers large enough to be palpable, visible on ultrasound, or capable of elevating the serum level of prostate-specific antigen. Such cancers are clinically important and should be treated for cure if the life expectancy of the patient is sufficiently long and the morbidity rate of therapy is low. Early detection of prostate cancer using the tests that are available today may widen the window of opportunity so that treatment indeed becomes possible in those for whom it is necessary.
Antigens, Neoplasm↗
When intravesical measures fail. Indications for cystectomy in superficial disease.
The indications for intravesical therapy for superficial bladder cancer include multifocal or recurrent tumors, lamina propria invasion, CIS, and superficial involvement of the prostatic urethra. Tumor-free success rates approach 70% in most series. Intravesical therapy is usually administered as a 6-week course with a re-evaluation of the bladder at the 3-month interval. If disease persists, a second 6-week course of therapy is administered. If tumor recurs or persists at the 6-month evaluation, treatment is considered to have failed, and another form of therapy is instituted (Fig. 1). In the 30% of patients failing an adequate course of intravesical therapy, cystectomy may be indicated for uncontrollable superficial disease not amenable to transurethral resection, persistent grade III lesions, lamina propria invasion, persistent CIS, persistent involvement of the prostatic urethra, and persistence of tumor in a nonfunctioning bladder. Rarely, cystectomy may be indicated because of severe adverse effects related to intravesical therapy.
Administration, Intravesical↗
Modulation of fibronectin-mediated Bacillus Calmette-Guérin attachment to murine bladder mucosa by drugs influencing the coagulation pathways.
Adjuvant intravesical Bacillus Calmette-Guérin (BCG) has proved to be an effective treatment for superficial bladder cancer. Intraluminal attachment of BCG organisms via binding to the extracellular matrix protein, fibronectin (FN), appears to be required for expression of the antitumor efficacy of BCG against a murine bladder tumor. Initial studies demonstrated that radiolabeled FN localized to the acutely injured urothelium but not to intact urothelium. These studies also demonstrated that exogenous administration of FN enhanced BCG attachment to the injured but not to the intact urothelium. Because FN has been shown to be an integral part of clot formation at sites of urothelial injury, drugs known to affect fibrin clot formation were tested for their effects on BCG attachment and antitumor efficacy in a murine bladder tumor model. A stabilizer of fibrin clot formation was shown to enhance both BCG attachment and antitumor efficacy in the same model. An increased number of BCG organisms were also retained in the lymph nodes and spleens of mice receiving fibrin clot stabilizers, suggesting indirectly that immunological mechanisms are involved in the antitumor efficacy of BCG. The data presented herein provide further support for the hypothesis that BCG attachment to the injured bladder is mediated by FN. Furthermore, modulation of BCG-FN attachment is demonstrated to be possible with drugs influencing the coagulation pathway. This attachment is shown to be required for the antitumor efficacy in a murine bladder tumor model, and thus modulation of BCG-FN attachment appears to have significant influence on the antitumor efficacy of BCG in the murine bladder tumor model.
Aminocaproic Acid↗
Bilateral renal cell carcinoma with metastasis to thyroid.
A case of bilateral synchronous renal cell carcinomas with metastases to the regional lymph nodes and later to the thyroid gland was treated with aggressive surgical extirpation and adjuvant gamma interferon. The patient continues to have an excellent performance status sixteen months after initial diagnosis despite a large tumor burden at presentation.
Carcinoma, Renal Cell↗
Comparison of the fibronectin-binding ability and antitumor efficacy of various mycobacteria.
Although the mechanism by which Bacillus Calmette-Guerin (BCG) exerts an antitumor effect on superficial bladder tumors is not fully understood, recent evidence has implicated binding of BCG organisms to fibronectin (FN) as requisite for this antitumor efficacy. Various substrains of BCG and other mycobacteria were tested in vitro for their relative capacities to bind both matrix and soluble FN. A substrain of Mycobacterium kansasii, designated the "high-binding strain," was found to bind FN more readily (P less than 0.05) in in vitro studies, when compared to commercially available substrains of BCG (Tice, Connaught, and Armand Frappier). The binding by the three commercial strains of BCG to FN in vitro appeared to be equivalent. The high-binding strain was further demonstrated to attach more readily in vivo to the acutely injured murine bladder (P less than 0.005) than the Armand Frappier substrain. Finally, using the MB49 murine bladder tumor model, an enhanced antitumor effect (P less than 0.05) was noted in mice treated with intravesical high-binding strain, in comparison to the Armand Frappier substrain, during five weekly treatments. It appears not only that the commercial substrains of BCG bind FN in an equivalent manner but also that the relative binding capacities of the substrains correlate directly with antitumor activity. A substrain of M. kansasii appears to have been identified which may prove more clinically effective than the currently available strains of BCG.
Animals↗
Adverse impact of fibrin clot inhibitors on intravesical bacillus Calmette-Guerin therapy for superficial bladder tumors.
Although intravesical bacillus Calmette-Guerin therapy has proved to be efficacious in the treatment and prophylaxis against tumor recurrence of superficial bladder tumors, its mechanism of action has not been fully elucidated. Previous work has suggested that bacillus Calmette-Guerin organisms attach to the matrix protein, fibronectin, during fibrin clot formation at sites of urothelial disruption and that this attachment was required for the antitumor effect of bacillus Calmette-Guerin to be expressed. Furthermore, drugs inhibiting clot formation were found to abrogate the antitumor effect of intravesical bacillus Calmette-Guerin therapy in a murine bladder tumor model. To examine the effect of inhibitors of fibrin clot formation on the results of intravesical bacillus Calmette-Guerin therapy, a retrospective analysis of 149 evaluable patients receiving intravesical bacillus Calmette-Guerin for superficial bladder tumors was performed. The over-all response rate free of tumor for 29 patients who concomitantly received inhibitors of fibrin clot formation with bacillus Calmette-Guerin therapy was 48%, as compared with 67% for 120 patients who were not receiving these medications (p = 0.0655, chi-square). The most striking difference was noted for patients who failed with recurrent superficial disease. Of the patients who received fibrin clot inhibitors during intravesical bacillus Calmette-Guerin therapy 35% had recurrent superficial tumors compared to only 8% of those who did not receive these drugs during a mean followup of 29.8 plus or minus 11 months (p = 0.005, chi-square). Our study suggests that inhibitors of fibrin clot formation may have an adverse influence on the results of intravesical bacillus Calmette-Guerin therapy for superficial bladder tumors.
Administration, Intravesical↗
Effect of adjuvant radiation therapy on prostate specific antigen following radical prostatectomy.
A total of 21 patients received adjuvant radiation therapy after radical prostatectomy for a persistently detectable prostate specific antigen value (more than 0.6 ng. per ml.) postoperatively. Adjuvant radiation therapy decreased serum prostate specific antigen values to the undetectable range in 6 of 21 patients (29%) all of whom have remained free of tumor recurrence with a mean followup of 12.6 months (range 6 to 30). Three patients initially showed a decrease in serum prostate specific antigen to undetectable levels but they subsequently demonstrated an increasing level within 12 months after adjuvant radiation therapy. Additionally, 7 of 13 patients whose prostate specific antigen values remained in the detectable range despite adjuvant radiation therapy have had clinical evidence of tumor recurrence. Further followup will be required to determine what ultimate impact adjuvant radiation therapy will have on survival free of tumor.
Antigens, Neoplasm↗
Effect of tumor necrosis factor and interferon gamma on human renal carcinoma cell line growth.
Four human renal carcinoma cell lines (786-0, CaKi-1, TK-10 and TK-164) were studied in vitro for susceptibility to human recombinant interferon-gamma (IFN gamma) and/or human recombinant tumor necrosis factor (TNF). All four cell lines tested demonstrated a dose dependent sensitivity to the cytotoxic effects of TNF alone. The degree of sensitivity varied for each cell line. IFN gamma alone also mediated a dose dependent antiproliferative effect in three of the four cell lines. Combinations of IFN gamma and TNF produced diverse inhibitory effects. Preincubation of the cells for various time intervals with noninhibitory concentrations of IFN gamma prior to the addition of TNF resulted in distinct effects for each cell line. Pretreatment enhanced the cytotoxic effect of TNF for some cell lines; however, others became less susceptible and some demonstrated enhanced proliferation in the presence of both agents. Optimal pretreament times also varied from cell line to cell line. These results demonstrate variability in responsiveness by renal carcinoma cell lines to combination IFN gamma and TNF treatments and suggest that timing as well as concentration may be important in in vivo therapy.
Carcinoma, Renal Cell↗
Clinical use of prostate specific antigen in patients with prostate cancer.
The clinical use of prostate specific antigen as a screening test for prostate cancer, as a preoperative determinant for staging of prostate cancer and to monitor response to therapy in prostatic cancer patients was evaluated in 168 men with benign prostatic hyperplasia and 231 men with prostate cancer. Only 3% of the men with benign prostatic hyperplasia had prostate specific antigen levels greater than 10 ng. per ml. compared to 44% of the men with proved prostate cancer. Preoperative prostate specific antigen levels increased with higher clinical stages of prostate cancer but there was substantial overlap among stages. Among patients with stage A1 prostate cancer who were followed expectantly none had an elevated prostate specific antigen value or metastatic disease during a followup of 15 to 120 months. After radical prostatectomy serum prostate specific antigen values decreased to undetectable levels (less than 0.6 ng. per ml.) in 89% of the patients with organ-confined disease, in 87% of those with microscopically positive margins only but in only 34% with seminal vesicles or lymph node involvement. Failure of the prostate specific antigen levels to decrease to the undetectable range after radical prostatectomy was associated with a greater likelihood of subsequent tumor recurrence. Only 3 of 18 patients (17%) treated with definitive radiation therapy had post-irradiation prostate specific antigen values of less than 0.6 ng. per ml., while in 39% the prostate specific antigens values remained greater than 4 ng. per ml. and in 4 of 18 (22%) the values were greater than 10 ng. per ml. Of patients with previously untreated stage D2 prostate cancer the mean pre-treatment prostate specific antigen value was 63.7 ng. per ml. compared to a post-hormonal therapy mean value of 31.1 ng. per ml. Of 32 patients treated with hormonal therapy 14 had stable disease, including 13 with prostate specific antigen levels of less than 10 ng. per ml. In contrast, 18 patients had progressive disease, of whom 16 had prostate specific antigen levels of more than 10 ng. per ml. We conclude that the serum prostate specific antigen assay is most useful clinically to monitor the response to therapy of prostate cancer patients.
Acid Phosphatase↗
Choice of an optimal diluent for intravesical bacillus Calmette-Guerin administration.
The physical conditions, including diluent pH, salt concentration and duration of bacillus Calmette-Guerin attachment, were determined in in vitro binding assays for soluble and matrix fibronectin. Since soluble fibronectin may block attachment of bacillus Calmette-Guerin to matrix fibronectin in the bladder, the optimal conditions were determined under which matrix fibronectin-bacillus Calmette-Guerin binding was maximal and soluble fibronectin-bacillus Calmette-Guerin binding was minimal. These conditions, which were confirmed in vivo in the murine bladder model, included use of normal saline, pH 7 as diluent for bacillus Calmette-Guerin organisms, with retention of the bacillus Calmette-Guerin suspension for 2 hours.
Administration, Intravesical↗
Results of 6 weekly intravesical bacillus Calmette-Guerin instillations on the treatment of superficial bladder tumors.
We evaluated 104 patients with superficial bladder tumors for response to intravesical bacillus Calmett-Guerin therapy. Patients received 6 weekly intravesical bacillus Calmette-Guerin instillations and they were followed for response every 3 months with urinary cytology, cystoscopy and bladder biopsy. Patients were considered treatment failures if either the cytology studies or biopsies were positive for tumor. Of 65 patients who failed the initial treatment course 57 were given an additional 6-week course of therapy. One 6-week course of bacillus Calmette-Guerin was successful in 20 of 55 patients (36 per cent) treated for prophylaxis, 12 of 32 (37 per cent) treated for carcinoma in situ and 7 of 17 (41 per cent) treated for residual tumor. The response rate for the total patient population treated with 1, 6-week course was 37.5 per cent (39 of 104). A second 6-week course was successful in 19 of 29 patients (65 per cent) treated for prophylaxis, 11 of 18 (71 per cent) treated for carcinoma in situ and 4 of 10 (40 per cent) treated for residual tumor. The response rate for all patients receiving a second course of bacillus Calmette-Guerin was 59.6 per cent (34 of 57). Of 6 patients who refused another 6-week course of bacillus Calmette-Guerin 4 had additional recurrences and 3 of these 4 suffered invasive disease. The over-all therapeutic response rate for patients treated with either 6 or 12 weeks of therapy was 70 per cent. These results suggest that 6 weeks of intravesical bacillus Calmette-Guerin do not provide optimal therapy for superficial bladder tumors. The data further suggest that more intensive regimens may increase therapeutic efficacy.
Administration, Intravesical↗
Single course versus maintenance bacillus Calmette-Guerin therapy for superficial bladder tumors: a prospective, randomized trial.
A total of 42 patients with recurrent superficial bladder tumors or carcinoma in situ entered a prospective, randomized trial to compare the efficacy of bacillus Calmette-Guerin therapy with and without quarterly maintenance instillations of bacillus Calmette-Guerin. Maintenance therapy did not reduce further bladder tumor recurrence rates or the interval to recurrence in patients who responded to the initial course of therapy. However, prolongation of toxicity was observed with maintenance bacillus Calmette-Guerin therapy.
Administration, Intravesical↗
Risks and benefits of repeated courses of intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer.
An actuarial analysis of the risks and benefits of repeated courses of intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer was performed for 100 consecutive patients treated for carcinoma in situ (29), prophylaxis against recurrent tumor (51) or residual superficial papillary tumor (21). The risk-to-benefit ratio at entry into bacillus Calmette-Guerin therapy (7 per cent risk of invasive cancer developing, 5 per cent risk of metastases and 77 per cent prospect for status free of tumor) and in patients who had failed only 1 course of bacillus Calmette-Guerin therapy (11 per cent invasive cancer, 14 per cent metastases and 58 per cent free of tumor) were highly favorable. However, among patients who had failed 2 or more courses of bacillus Calmette-Guerin therapy the risks of invasive (30 per cent) or metastatic (50 per cent) cancer developing exceeded the prospects for eradicating the superficial tumor present (20 per cent) with further therapy. The results suggest that patients who have failed 2 courses of bacillus Calmette-Guerin therapy (as given in our treatment protocol) should be considered for alternative treatment.
Actuarial Analysis↗
Emphysematous pyelonephritis: successful management by percutaneous drainage.
Emphysematous pyelonephritis is a life-threatening infection that usually requires open surgical drainage. We report a case of emphysematous pyelonephritis treated successfully with percutaneous drainage.
Diabetic Nephropathies↗
Can erythema nodosum and reactive arthritis be a sequel to Shigella flexneri gastroenteritis?
Erythema nodosum and seronegative arthritis associated with diarrhoea was previously regarded as implying the presence of inflammatory bowel disease. Recently, however, erythema nodosum has been described as a sequel to diarrhoea caused by infection with Salmonella typhimurium, Yersinia enterocolitica and Campylobacter jejuni. We report two patients in whom erythema nodosum and reactive arthritis followed acute Shigella flexneri gastroenteritis, a rare association.
Adult↗
Innovations in photo-reprographics.
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Copying Processes↗
Cross section of an embryonic eye.
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Eye↗