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Biomedical subjects

D A Swanson

Publications and source records attributed to D A Swanson.

At least 55 records · Page 3Linked to original sources

Management of transitional cell carcinoma involving von Brunn's nests.

We reviewed data collected from 371 patients with superficial transitional cell carcinoma of the bladder to determine whether carcinoma within von Brunn's nests is a risk factor for cancer progression and an indication for radical cystectomy. Cystectomy was done in 20 of 73 patients (27%) with transitional cell carcinoma in von Brunn's nests and in 42 of 298 patients (14%) without von Brunn's nest involvement. There was no significant difference in the Kaplan-Meier crude and disease-specific survival between patients with and without transitional cell carcinoma in von Brunn's nests, irrespective of whether radical cystectomy was performed initially. Of those patients with von Brunn's nest involvement none who underwent cystectomy died of bladder carcinoma, while 3 (6%) managed conservatively died of bladder cancer. Of those patients without von Brunn's nest involvement 1 (5%) managed with cystectomy and 9 (4%) managed conservatively died of bladder carcinoma. Furthermore, only 8 patients (15%) with and 29 (11%) without transitional cell carcinoma in von Brunn's nests showed disease progression after initial conservative management. Based on this analysis, our conclusion is that transitional cell carcinoma within von Brunn's nests is not a risk factor for disease progression or an absolute indication for radical cystectomy.

Aged↗

Preoperative radiotherapy for muscle-invasive bladder carcinoma. Long term follow-up and prognostic factors for 338 patients.

BACKGROUND: This study was performed to determine the importance of various potential prognostic factors in a large cohort of patients with transitional cell carcinoma of the bladder who were treated relatively uniformly at a single institution. METHODS: Between 1960 and 1983, 338 patients with muscle-invasive bladder carcinoma received preoperative radiotherapy (50 Gy in 25 fractions) followed 4-6 weeks later with radical cystectomy. Lymph node sampling was performed only when suspicious adenopathy was encountered. Ninety-eight percent of the patients completed the treatment as planned. The median followup for those living was 90 months. RESULTS: Actuarial 5-year pelvic control, disease free, and overall survival rates were 84, 51, and 44%, respectively, for all patients, and 88, 58, and 50%, respectively, for those who treatment completed. The overwhelming majority of failures were from distant metastases (43% at 5 years). The pathologic complete response rate was 42%, and downstaging was seen in 65% of the patients. Univariate actuarial analyses revealed clinical stage, clinical perivesical extension, tumor size, pretreatment hemoglobin level, pretreatment blood urea nitrogen (BUN) concentration, results of intravenous pyelography, sex, age, pathologic response, and pathologic complete response, correlated with disease outcome. A Cox proportional hazards model showed pathologic response (P < 0.0001), clinical stage (P = 0.01), hemoglobin level (P < 0.02), pathologic complete response (P < 0.05), and BUN concentration (P < 0.05), were correlated significantly with pelvic control. When only pretreatment factors were analyzed, clinical stage, hemoglobin level, and BUN concentration remained the only factors predictive of pelvic control. Similar results were obtained when overall survival was used as the endpoint, except that pathologic complete response and BUN concentration were replaced by sex as significant covariates. A Cox proportional hazards model using disease free status as the endpoint revealed pathologic response and tumor size to be independent predictors of patient outcome. Restricting this analysis only to pretreatment factors showed that pretreatment hemoglobin and tumor size were the only factors correlated with disease free status. CONCLUSIONS: The most significant prognostic factor was pathologic response, which correlated highly with all disease endpoints investigated. The most consistently significant pretreatment factors were hemoglobin level and clinical stage, although tumor size, sex, and BUN concentration also were independent predictors of patient outcome. These factors should be considered in patients receiving radiotherapy for bladder preservation.

Carcinoma, Transitional Cell↗

Muscle-invasive bladder cancer treated with external beam radiotherapy: prognostic factors.

PURPOSE: To determine the relationship of several potential prognostic factors to the outcome measures of pelvic control, freedom from metastases, and overall survival for bladder cancer patients treated with definitive external beam radiotherapy. METHODS AND MATERIALS: The records of 135 patients treated with high-dose, planned continuous-course, external beam radiotherapy for muscle-invasive transitional cell bladder cancer were reviewed. These patients were treated to an average total dose of 6588 +/- 475 cGy with an average fractional dose of 207 +/- 18 cGy using megavoltage. Median potential follow-up for all patients, including those who died, was 249 months. RESULTS: The actuarial results at 5 year were 31% pelvic control, 58% freedom from metastases, and 26% overall survival. In the univariate analyses, several factors were correlated with disease outcome including clinical stage, tumor morphology, gross total transurethral resection (TURBT), findings at bimanual exam after TURBT, clinical perivesical extension, age, and clinical complete response at first follow-up cystoscopy (Clinical-CR). A Cox proportional hazards model revealed that only Clinical-CR was independently predictive of pelvic control. In terms of freedom from metastases, only Clinical-CR and clinical stage were significantly associated with outcome in the multivariate analysis. When the multivariate analysis was restricted to T2 and T3 tumors only, then clinical perivesical extension replaced stage as being associated with freedom from metastases. The only factors significantly related to overall survival in the Cox proportional hazards model were Clinical-CR, age, and complete TURBT; stage was of borderline significance when only pretreatment factors were considered. CONCLUSIONS: Clearly, the most important prognostic factor was Clinical-CR. The pretreatment factors of stage, clinical perivesical extension, and gross total TURBT also correlated with outcome, but, to a lesser degree. For patients medically unfit for radical cystectomy radiotherapy is a viable option, particularly for selected patients. Patients with T4 tumors are poor candidates for definitive radiotherapy and should be treated palliatively if they cannot tolerate systemic therapy.

Aged↗

Gene order is conserved within the human chromosome 21 linkage group on mouse chromosome 10.

One hundred progeny from each of two intersubspecific mouse backcrosses were used to construct a comparative genetic map of a region of mouse chromosome 10 (MMU10) that is homologous to the distal tip of the long arm of human chromosome 21 (HSA21). The analysis included five genes and three simple sequence repeat markers, two of which flanked the HSA21-homologous cluster on either side. Analysis of 200 backcross progeny detected at least one crossover between each pair of adjacent genes and demonstrated that the proximal to distal orientation of the cluster was reversed between human and mouse. The order was determined to be Fyn-1-D10Mit20-S100b-Col6a1-Itgb2-Pfkl+ ++/D10Mit7-D10Mit11. Comparative mapping supports the order of corresponding markers on HSA21 determined using pulsed-field gel electrophoresis and radiation hybrid line data. However, sequence tagged site content mapping of human yeast artificial chromosomes (YACs) yielded conflicting data on the relative positions of human COL6A1 and S100B on HSA21. This discrepancy was resolved here by demonstrating that several key YACs used in the human contig analysis were mistyped for S100B. The murine map reported here provides a scaffold for construction of physical maps and yeast artificial chromosome contigs that will be useful in the development of mouse models for the study of Down syndrome.

Animals↗

Therapy and prognosis for male anterior urethral carcinoma: an update.

OBJECTIVE: The scarcity of reports evaluating the effect of current treatment strategies for male urethral carcinoma has prompted a review of our recent experience. Since our last report (1980), we have seen 23 patients with this disease. METHODS: We performed a retrospective chart review of 23 patients seen in our institution between 1979 and 1990 with this type of cancer. RESULTS: Fifty-two percent of our patients are alive without evidence of disease, after a mean follow-up of fifty months (range, 5 to 156 months). Treatment analysis indicates that distal urethrectomy and partial penectomy are adequate in controlling local disease for tumors arising in the fossa navicularis and penile urethra, respectively, and that en bloc excision of the penis, scrotum, prostate, and bladder together with resection of the inferior pubic rami, using myocutaneous flaps to cover the surgical defect, can provide long-term disease-free survival for patients whose tumor originates in the bulbomembranous urethra. Use of cisplatin-based chemotherapy resulted in a prolonged survival for patients who presented with metastatic disease. CONCLUSIONS: We conclude that the prognosis for patients with urethral carcinoma has improved, and some of the patients are having a prolonged disease-free survival due, in part, to more effective local and regional control and improved chemotherapy.

Adult↗

Increase in the ability of human cancer cells to induce cytotoxic T lymphocytes by ultraviolet irradiation.

The roles of ultraviolet-B (UV) radiation in the immunogenicity of human cancer cells have not been fully studied. We have investigated the effects of UV radiation on metastatic melanoma and renal cell carcinoma cells with regard to MHC antigen expression and the ability to induce cytotoxic T lymphocyte (CTL) activity in peripheral blood mononuclear cells (PBMC) or tumor-infiltrating lymphocytes (TIL) against untreated autologous tumor cells. UV radiation respectively decreased or increased MHC class I expression of freshly isolated tumor cells or cultured tumor cells, and also decreased MHC class I expression of starved cultured tumor cells. It increased the ability of both freshly isolated and cultured tumor cells to induce CTL activity from PBMC against untreated autologous tumor cells. UV-irradiated subclones that were more susceptible to CTL lysis were more potent for CTL induction from TIL than either an untreated parental clone or a UV-irradiated subclone that was resistant to CTL lysis. In summary, UV radiation increased the ability of tumor cells to induce CTL activity without a corresponding effect on MHC antigen expression.

Carcinoma, Renal Cell↗

Surgery following response to interferon-alpha-based therapy for residual renal cell carcinoma.

The role of aggressive surgery for metastatic renal cancer in the era of biological therapy is not clear. Therefore, we reviewed 17 patients who, between February 1987 and August 1990, underwent surgical resection of residual masses following initial response to interferon-alpha-based therapy. Viable tumor persisted in 15 patients (88%), whereas only inflammatory response was detected in 2. Of the patients 11 (65%) remained disease-free at a median of 12 months postoperatively (range 5 to 29), with an overall median survival of 26 months (range 6 to 34) from treatment initiation. These data suggest that surgery may be of therapeutic benefit in select patients with renal cell carcinoma who do not meet traditional criteria for surgical resection. Prospective trials are being performed to determine whether there is a role for aggressive surgical resection of persistent disease in patients with advanced renal cell carcinoma who have previously responded to interferon-alpha-based therapy.

Adult↗

Expression and processing of human ornithine-delta-aminotransferase in Saccharomyces cerevisiae.

Ornithine-delta-aminotransferase catalyzes the conversion of ornithine to glutamate-gamma-semialdehyde. In humans, deficiency of this mitochondrial matrix enzyme results in the progressive blinding disorder, gyrate atrophy of the choroid and retina. To explore yeast as an expression system, we introduced a cDNA encoding human ornithine-delta-aminotransferase into an ornithine aminotransferase-deficient strain of Saccharomyces cerevisiae. The human enzyme was expressed at high levels, with activity 20-fold greater than that of wild-type yeast and 10-fold higher than in human fibroblasts. Although the normal location of ornithine-delta-aminotransferase in S. cerevisiae is cytosolic, human ornithine-delta-aminotransferase expressed in S. cerevisiae was localized to the mitochondrial matrix with correct proteolytic processing of its mitochondrial leader sequence. Despite this anomalous location in yeast, human ornithine-delta-aminotransferase complemented the phenotype of the mutant strain, restoring its ability to utilize ornithine as a sole nitrogen source. We also expressed a vitamin B6-responsive missense allele of ornithine-delta-aminotransferase (V332M) and showed that the biochemical phenotype of this allele is easily demonstrated confirming the usefulness of this system for examining mutations causing gyrate atrophy.

Base Sequence↗

Stage B (P2/3A/N0) transitional cell carcinoma of bladder highly curable by radical cystectomy.

Seventy-one patients with pathologic Stage B (P2/3a/N0) transitional cell carcinoma (TCC) of the bladder underwent radical cystectomy alone without preoperative radiotherapy or perioperative chemotherapy between 1983 and 1987 and have been followed a median of fifty months. The five-year actuarial survival and disease-free survival rates were 82 percent and 77 percent, respectively, and only 13 patients (18%) have relapsed. Histologic parameters were evaluated as to prognostic impact; none correlated with disease-free survival rates although the presence of vessel involvement portended a worse disease-free survival rate (68% versus 80%). During this same period, an additional 15 patients underwent radical cystectomy for pathologic Stage B disease but received adjuvant chemotherapy on the basis of vessel invasion. Their disease-free survival rate at five years was 80 percent, comparable to the disease-free survival rate for patients with vessel invasion treated by surgery alone (68%). Although the role of systemic chemotherapy in the management of invasive bladder cancer remains under investigation, it would appear that patients with Stage B TCC are best treated with radical cystectomy alone. Continued analysis of modern surgical results grouped by current pathologic staging criteria is needed to identify patients who have a relatively low risk of relapse and thus little need for additional therapeutic intervention. These results demonstrate that Stage P2/3a/N0 TCC of the bladder is highly curable by surgery.

Adult↗

The relationship between life expectancy and socioeconomic status in Arkansas: 1970 and 1990.

Life Expectancy at Birth is estimated for county populations in Arkansas in 1970, 1980 and 1990. Counties are grouped into quintiles at each time point according to the percent of persons below the poverty level. Comparisons are made between mean life expectancy in the highest and lowest socioeconomic group at each point in time as well as between the same group at 1970 and 1990. It is hypothesized that the high socioeconomic populations will experience an increase in mean life expectancy over the low socioeconomic populations between 1970 and 1990. Statistical analysis supports the hypothesis. These findings conform to those from earlier research in Ohio and may reflect a continuing deterioration in the relative standard of living of lower income groups in the United States subsequent to 1970.

Adolescent↗

Fibrin glue for partial nephrectomy.

Fibrin glue, a mixture of concentrated autologous fibrinogen and bovine-derived thrombin, was used to achieve hemostasis during 7 partial nephrectomies. After transected vessels were suture ligated, topically applied fibrin glue filled all renal defects with an adherent clot that resulted in immediate hemostasis. There was no case of delayed hematoma or abscess formation, and no complications were referrable to the use of fibrin glue. Although fibrin glue is no substitute for early vascular control and careful surgical technique, its ability to stop venous oozing from the cut surface of renal parenchymal tissue dramatically facilitates hemostatic control.

Fibrin Tissue Adhesive↗

Relationship of thyroid disease to renal cell carcinoma. An epidemiologic study.

Thyroid hormone participates in numerous cellular functions besides thermogenesis and metabolism. Several studies, including the recent identification of the product of an oncogene, c-erb-A, as a thyroid-hormone receptor, have shown possible involvement of thyroid hormone in the process of carcinogenesis. A recent anecdotal observation of an unusually high incidence of thyroid dysfunction in women with renal cell carcinoma led to a retrospective review of the incidence and distribution of thyroid disorders in women with renal cell carcinoma compared with a control group of women with transitional cell carcinoma of the renal pelvis, ureter, bladder, or urethra. Women with renal cell carcinoma had a statistically significantly higher percentage of hypothyroidism, thyroid disease in general, and the use of thyroid-hormone supplements as compared with the control group (P = 0.033, P = 0.005, P = 0.041, respectively). The nature of the relationship, however, could not be determined. These findings add a new dimension to renal cell carcinoma, and prospective studies are encouraged to define the contribution of thyroid hormone to renal cell carcinogenesis.

Adult↗

Preoperative irradiation and radical cystectomy for stages T2 and T3 squamous cell carcinoma of the bladder.

We treated 25 patients who had muscle invasive pure squamous cell carcinoma of the bladder with preoperative radiation and cystectomy. At operation the tumors in 10 patients (40%) were downstaged--3 of 5 from stage T2, 3 of 4 from stage T3a and 4 of 16 from stage T3b, while 6 patients (24%) had no residual tumor (pT0). The actuarial 5-year survival rate for all patients was 50%. Disease recurred in the pelvis in 7 patients, none of whose tumors had been downstaged (6 died of cancer). Median survival of patients with a pelvic recurrence was 9 months and without recurrence it was 86.7 months (p = 0.03). No patient whose tumor was downstaged had a recurrence or died of bladder cancer. We conclude that irradiation before cystectomy in patients with squamous cell bladder cancer may protect against pelvic recurrence, which is the predominant cause of death. Because effective adjuvant chemotherapy is not available to treat squamous cell carcinoma as it is for transitional cell carcinoma, we recommend irradiation before cystectomy for locally advanced squamous cell carcinoma of the bladder.

Adult↗