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Biomedical subjects

D A Swanson

Publications and source records attributed to D A Swanson.

At least 37 records · Page 2Linked to original sources
PubMed1997

Significance of downstaging in muscle-invasive bladder cancer treated with preoperative radiotherapy.

PURPOSE: The relationship between clinical-to-pathologic downstaging and patient outcome following preoperative radiotherapy was examined, focusing on the mechanism (selection vs. treatment effect) responsible for the benefit seen from such downstaging. METHODS AND MATERIALS: Three hundred and one patients were treated with preoperative radiotherapy plus cystectomy (PREOP) to a median dose of 50 Gy in 25 fractions between 1960-1983. These patients were compared to 225 patients treated with radical cystectomy, with or without chemotherapy (CYST), between 1984-1990. Multiagent chemotherapy was given to 68% of those in the CYST group and was not given to any in the PREOP group. Lymph node involvement was not formally evaluated in the PREOP group, while 20% had pathologic involvement in the CYST group. RESULTS: Clinical-to-pathologic downstaging (P < T stage) was found in 73% treated with PREOP and 29% treated with CYST (p < 0.0001, chi-square). The only factors that correlated with P < T staging for the PREOP and CYST groups when each was considered separately were clinical stage, blood urea nitrogen level, and creatinine level (p < 0.05, chi-square). Multivariate logistic regression revealed that treatment (PREOP vs. CYST) correlated independently with P < T staging (p < 0.0001). The relationship of actuarial local control to distant metastasis at 5 years in patients that were downstaged, as stratified by clinical stage and treatment, was then examined. Local control rates for P < T staged T2/T3a patients were independent of treatment (PREOP vs. CYST), while distant metastasis rates were significantly greater for those in the PREOP group. In contrast, P < T staged T3b patients in the PREOP group had significantly better local control and distant metastasis rates. CONCLUSIONS: Significantly higher P < T staging rates were observed with PREOP as compared to CYST, and this was a consequence of the radiotherapy given. The relationship of downstaging from radiotherapy to local control and distant metastasis was contingent on clinical stage. The results of Stage T2/T3a and T3b patients were divergent and supported treatment effect, rather than selection, as the mechanism consistent with the patient outcomes observed.

Adult↗
PubMed1997

Surgical management of renal cell carcinoma with inferior vena cava tumor thrombus.

BACKGROUND: The optimal management of patients with renal cell carcinoma with inferior vena cava tumor thrombus remains unresolved. Traditional approaches have included resection with or without the use of cardiopulmonary bypass. Chemotherapy has played a minor role except for biotherapeutic agents used for metastatic disease. METHODS: From January 1989 to January 1996, 37 patients with renal cell carcinoma and inferior vena cava tumor thrombus underwent surgical resection. The 27 men and 10 women had a median age of 57 years (range, 29 to 78 years). Thirty-six patients presented with symptoms; 21 had hematuria. Distant metastases were present in 12 patients. Tumor thrombi extended to the infrahepatic inferior vena cava (n = 16), the intrahepatic inferior vena cava (n = 16), the suprahepatic inferior vena cava (n = 3), and into the right atrium (n = 2). All tumors were resected by inferior vena cava isolation and, when necessary, extended hepatic mobilization and Pringle maneuver, with primary or patch closure of the vena cavotomy. Cardiopulmonary bypass was necessary in only 2 patients with intraatrial thrombus. RESULTS: Complications occurred in 11 patients, and 1 patient died 2 days postoperatively of a myocardial infarction (mortality, 2.7%). Twenty patients are alive; overall 2- and 5-year survival rates were 61.7% and 33.6%, respectively. For patients without lymph node or distant metastases (stage IIIa), 2- and 5-year survival rates were 74% and 45%, respectively. The presence of distant metastatic disease (stage IV) at the time of operation did not have a significant adverse effect on survival, as reflected by 2- and 5-year survival rates of 62.5% and 31.3%, respectively. Lymph node metastases (stage IIIc) adversely affected survival as there were no long-term survivors. CONCLUSIONS: Resection of an intracaval tumor thrombus arising from renal cell carcinoma can be performed safely and can result in prolonged survival even in the presence of metastatic disease. In our experience, extracorporeal circulatory support was required only when the tumor thrombus extended into the heart.

Adult↗
PubMed1997

Nephrectomy and vena caval thrombectomy in patients with metastatic renal cell carcinoma.

OBJECTIVES: To report out experience with performing nephrectomy and vena caval thombectomy in patients with metastatic renal cell carcinoma. METHODS: A retrospective review was performed of 15 patients who underwent surgical excision of the primary tumor and a caval thrombus and treatment of concurrent metastases between 1989 and 1995. The sites of metastases included lungs (n = 8), bone (n = 3), bulky retroperitoneal or mediastinal lymph nodes (n = 2), liver (n = 1), and contralateral adrenal (n = 1). The level of caval involvement was suprahepatic in 3 cases, retrohepatic in 2 cases, and infrahepatic in 10 cases. Three patients had an Eastern Cooperative Oncology Group performance score of 0, 11 had a score of 1, and 1 had a score of 2. Median follow-up was 17 months. RESULTS: Median operative time was 6.5 hours and median hospitalization was 10 days. Two patients required re-exploration for postoperative hemorrhage. There were no perioperative deaths. Four patients underwent surgery for resection of solitary metastases (1 lung, 2 spine, and 1 humerus); 2 of the 4 received adjuvant radiotherapy. Two patients received biologic therapy preoperatively, 3 received it both preoperatively and postoperatively, and 6 received it only postoperatively. The median time to initiation of postoperative biologic therapy was 48 days (range 25 to 110). Eleven patients are currently alive, 7 with no evidence of disease at a median follow-up of 17 months (range 6 to 66) and 4 with stable metastases at 14 months (range 4 to 22). Ten of the 13 symptomatic patients had improved performance scores after surgery. Four patients have died from metastatic disease: 2 from rapid progression at 2 and 5 months after surgery and the other 2 at 17 and 42 months. CONCLUSIONS: Nephrectomy and vena caval thrombectomy can be safely performed in selected patients with metastatic disease. Furthermore, in patients receiving biologic therapy, nephrectomy may enable a better quality of life and prolonged survival.

Aged↗
PubMed1997

A differential hybridization scheme to identify photoreceptor-specific genes.

Identification of genes expressed preferentially or exclusively in photoreceptors will facilitate the understanding of photoreceptor biology as well as provide candidate genes for inherited retinal degenerations. To achieve this goal we performed a differential hybridization screen of 3717 well-isolated phage clones from a human retinal cDNA library. Clones were selected for further study if they hybridized exclusively or strongly preferentially to a probe derived from RNA isolated from the cone-predominant retina of 13-line ground squirrels as compared to a probe derived from human fibroblast RNA. Twenty percent of clones (9/45) identified by this screen were derived from photoreceptor-specific genes and an additional 24.4% (11/45) were from neural-specific genes, demonstrating the utility of this strategy in identifying genes important for retinal biology.

Base Sequence↗
PubMed1997

Socioeconomic status, race and life expectancy in Arkansas, 1970-1990.

Earlier research found that high socioeconomic populations in Arkansas experienced an increase in mean life expectancy over low socioeconomic populations between 1970 and 1990. The possibility that these findings are spurious because of race is tested in this paper. Using multivariate analysis in conjunction with estimates of life expectancy by race and socioeconomic status (SES) we find that between 1970 and 1990: (1) Black populations with high SES gained more than three additional years of life expectancy over Black populations with high SES; and (2) White populations with high SES gained more than .5 years of life expectancy over White populations with low SES. These findings support earlier findings that SES plays an instrumental role in differential life expectancy. They also suggest that the effects of SES on life expectancy are moderated differentially for Blacks and Whites.

Black or African American↗
PubMed1997

The efficacy and complications of salvage cryotherapy of the prostate.

PURPOSE: A phase I/II study was done to evaluate the efficacy and complications of salvage cryotherapy as a treatment for locally recurrent prostate cancer following full dose radiation therapy and/or systemic therapy. The efficacy of single and double freeze-thaw cycles was compared using posttreatment prostate specific antigen (PSA) levels and prostate biopsies as end points. MATERIALS AND METHODS: A total of 150 patients with locally recurrent prostate cancer following radiation, hormonal therapy and/or systemic chemotherapy underwent salvage cryotherapy using a single (71 men, mean followup 17.3 months) or double (79 men, mean followup 10.0 months) freeze-thaw cycle. PSA was measured approximately every 3 months postoperatively and sextant biopsies were repeated 6 months postoperatively. Complications were assessed by retrospective chart review and a mailed quality of life survey. RESULTS: Overall, 45 patients (31%) had persistently undetectable PSA. Patients with a history of radiation therapy only who underwent a double freeze-thaw cycle had a higher negative biopsy rate (93 versus 71%, p < 0.02) and lower biochemical failure rate (defined as an increase in serum PSA of 0.2 ng./ml. above the nadir value, 44 versus 65%, p < 0.03) than those who underwent a single freeze-thaw cycle. The main complications of salvage cryotherapy were urinary incontinence (73% of the patients), obstructive symptoms (67%), impotence (72%) and severe perineal pain (8%). CONCLUSIONS: Salvage cryotherapy impacts local tumor control as evident by the high frequency of negative posttreatment biopsies. A double freeze-thaw cycle appears more effective than a single cycle. Like salvage prostatectomy, salvage cryotherapy causes significant morbidity.

Adult↗
PubMed1996

Renal cell carcinoma metastatic to the lung: potential benefit in the combination of biological therapy and surgery.

PURPOSE: We evaluated outcomes in cases of renal cell carcinoma metastatic to the lung treated with surgery or biological therapy followed by surgery. MATERIALS AND METHODS: We retrospectively evaluated 22 patients treated with surgical resection and 29 treated with biological therapy followed by surgery. RESULTS: At the time of this study 31 patients (61%) were alive, including 15 with no residual disease and 16 with disease. Of the 22 patients treated with surgery without initial biological therapy 12 (55%) were alive at a median followup of 57 months (range 17 to 148) and 19 of the 29 (66%) treated with combination therapy were alive at a median followup of 48 months (range 19 to 78). A total of 19 patients (37%) died of progressive disease. CONCLUSIONS: Our results suggest a role for an aggressive surgical approach in select patients with metastatic renal cell carcinoma, and demonstrate that patients who do not achieve a complete response to biological therapy may benefit from surgical resection of residual disease.

Actuarial Analysis↗
PubMed1996

Complications of radical cystectomy: impact of the timing of perioperative chemotherapy.

OBJECTIVES: To evaluate the impact of timing of perioperative chemotherapy on morbidity of radical cystectomy in patients with bladder cancer. METHODS: We compared the complications in patients randomized to neoadjuvant (n = 53) or adjuvant (n = 49) MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin) chemotherapy. RESULTS: In the 95 patients who underwent cystectomy, there were no significant differences in treatment compliance, surgical parameters, or postoperative recovery between the two groups. In patients who received neoadjuvant chemotherapy, there were more complications, and there was one perioperative death; however, these differences were not significant. The neoadjuvant group took longer to complete therapy (P < 0.001). Nine patients (3 neoadjuvant, 6 adjuvant) did not undergo cystectomy on time. CONCLUSIONS: Cystectomy following neoadjuvant MVAC chemotherapy is feasible. We were unable to demonstrate any difference between neoadjuvant and adjuvant chemotherapy in mortality, morbidity, or postoperative clinical course.

Adult↗
PubMed1996

A ubiquitin C-terminal hydrolase gene on the proximal short arm of the X chromosome: implications for X-linked retinal disorders.

We report the cloning of a novel human cDNA which encodes a 690 amino acid protein with high homology to ubiquitin C-terminal hydrolases. Northern blot analysis shows expression of a 3.3 kb transcript in all tissues examined, with 5- to 10-fold higher levels in retina than elsewhere. We mapped the structural gene to Xp21.2-p11.2. This gene's relatively high levels of retinal expression and recent work showing that perturbations in protein turnover and processing can lead to retinal disease make it an excellent candidate for several X-linked retinal disorders mapping within this interval. Additionally, there is evidence that members of the ubiquitin hydrolase family may play a role in oncogenesis and a locus implicated in ovarian cancer is also located within this region.

Amino Acid Sequence↗
PubMed1996

What to do if the lymph nodes are positive.

Lymph node metastases are common in patients with advanced bladder cancer. Survival rates have apparently improved from about 15% to 30% as management evolved from lymphadenectomy plus cystectomy to multimodal therapy, but investigators have not conclusively shown the benefit of adjuvant irradiation and/or chemotherapy. If clinical staging indicates nodal metastases, we recommend primary multiagent chemotherapy with subsequent exploratory laparotomy, lymphadenectomy, and possibly cystectomy for complete responders. Patients without clinical evidence of metastases undergo complete bilateral pelvic lymphadenectomy plus cystectomy if nodes are normal, or if grossly abnormal but resectable. Patients with nodal metastases may be candidates for adjuvant chemotherapy.

Combined Modality Therapy↗
PubMed1996

On the utility of population forecasts.

Many customers demand population forecasts, particularly for small areas. Although the forecast evaluation literature is extensive, it is dominated by a focus on accuracy. We go beyond accuracy by examining the concept of forecast utility in an evaluation of a sample of 2,709 counties and census tracts. We find that forecasters provide "value-added" knowledge for areas experiencing rapid change or areas with relatively large populations. For other areas, reduced value is more common than added value. Our results suggest that new forecasting strategies and methods such as composite modeling may substantially improve forecast utility.

Bias↗
PubMed1995

Local control of muscle-invasive bladder cancer: preoperative radiotherapy and cystectomy versus cystectomy alone.

PURPOSE: The role of preoperative radiotherapy for patients with muscle-invasive bladder cancer remains controversial. Since 1985, the primary modality for treatment of these patients at our institution has been radical cystectomy alone. Prior to that time, the use of preoperative and cystectomy had been the mainstay of treatment. In this retrospective review we compare the results of these treatments, focusing on local control. METHODS AND MATERIALS: The preoperative radiotherapy and radical cystectomy (PREOP) group was comprised of 338 patients with muscle-invasive (Stages T2-T4) transitional cell carcinoma of the bladder treated between 1960 and 1983. A mean total dose of 49.3 +/- 0.2 Gy (+/- SE) was administered at 2 Gy per fraction 4-6 weeks prior to cystectomy. The radical cystectomy alone (CYST) group was comprised of 232 patients treated between 1985 and 1990. The median follow-up for the PREOP group was 91 months and for the CYST group was 54 months. Only those patients who completed planned PREOP (n = 301) and CYST (n = 220) treatments were included in the analyses described below. RESULTS: The treatment groups were stratified by clinical stage and compared in terms of actuarial local control. There were no differences between the groups for Stage T2 or T3a patients, and there were not enough Stage T4 patients in the PREOP group with which to make a meaningful comparison. However, for those with T3b disease, actuarial 5 year local control for the PREOP group (n = 92) was 91%, compared to 72% for the CYST group (n = 43). This difference was significant at p = 0.003 (log rank). Patients with T3b disease who received PREOP also fared slightly better at 5 years in terms of freedom from distant metastasis (67% vs. 54%), disease freedom (59% vs. 47%), and overall survival (52% vs. 40%); although, these differences did not reach statistical significance. The distribution of prognostic factors in the groups was analyzed to determine if this could account for the differences in local control in Stage T3b patients. For patients with Stage T3b disease, the only significant difference was by grouped age (p < 0.05, chi-square), which was not a significant factor in the univariate analyses of local control. A multivariate analysis using Cox proportional hazards models revealed pretreatment hemoglobin, blood urea nitrogen (BUN) concentration, and treatment type (PREOP vs. CYST) to be independently predictive of local control. CONCLUSION: We document here in a large number of patients treated at a single institution that preoperative radiotherapy had a significant impact on local control for patients with clinical Stage T3b disease. Because the CYST patients were treated using modern-day surgical techniques and 80% of those with Stage T3b disease received multiagent chemotherapy, it is probable that any biases, if present, would favor the CYST group. Thus, the differences between PREOP and CYST described may be underestimated. Preoperative radiotherapy should be considered as an adjunct to chemotherapy and surgery for clinical Stage T3b patients.

Actuarial Analysis↗
PubMed1995

Sentinel lymph node dissection for penile carcinoma: the M. D. Anderson Cancer Center experience.

PURPOSE: We determined whether an extended sentinel lymph node dissection is effective for staging penile squamous carcinoma associated with clinically negative inguinal lymph nodes. MATERIALS AND METHODS: A retrospective review was done of 20 consecutive patients who underwent extended sentinel lymph node dissection between 1985 and 1994. RESULTS: Of the patients 14 underwent bilateral extended sentinel lymph node dissection, and 6 underwent ipsilateral extended sentinel lymph node dissection plus contralateral inguinal or ilioinguinal lymphadenectomy. All lymph nodes included in the extended sentinel node dissection were negative for metastases. Five patients had inguinal metastases at a median of 10 months (range 3 to 21) after negative extended sentinel lymph node dissection. CONCLUSIONS: Although it is a more extensive procedure than sentinel lymph node biopsy, extended sentinel lymph node dissection is still associated with a significant false-negative rate (25%). Thus, its routine use can no longer be recommended.

Adult↗
PubMed1995

The relationship of local control to distant metastasis in muscle invasive bladder cancer.

PURPOSE: We examined the relationship of local failure to distant metastasis in patients with muscle invasive bladder cancer. MATERIALS AND METHODS: This retrospective review included 240 patients treated with radical cystectomy with or without multiagent chemotherapy at our institution between 1984 and 1990 for clinical stage T2 to T4 transitional cell carcinoma of the bladder. The distribution of patients by clinical stage was 89 T2, 77 T3a, 51 T3b and 23 T4. Median followup was 55 months. RESULTS: The actuarial 5-year local control, freedom from distant metastasis and overall survival rates were 80%, 68% and 52%, respectively. There was a profoundly significant relationship between local failure and distant metastasis with distant metastasis in 56% of those with local failure. The actuarial 5-year freedom from distant metastasis rate for those with local control was 77% compared to 29% for those with local failure (p < 0.0001, log rank test). This relationship held when the group was subdivided by stage and when only cases of complete cystectomy were analyzed. The significance of this finding in light of the possible contribution of potential prognostic factors was examined. Univariate analyses revealed late clinical stage, abnormal pretreatment serum creatinine levels, the administration of chemotherapy, late pathological stage and lymph node involvement to correlate significantly with distant metastasis rates. Multivariate analyses using Cox proportional hazards models with freedom from distant metastasis as the end point revealed pathological stage, local failure and lymph node involvement to be the only significant covariates. CONCLUSIONS: Since local failure highly correlated with distant failure, treatment planning to optimize local control should be of foremost concern for those at high risk of failure by this mode (for example patients with T3b/4 disease). New treatment strategies, such as the use of preoperative radiotherapy as an adjunct to chemotherapy and radical surgery, should be considered in this high risk population.

Actuarial Analysis↗
PubMed1995

Cysteine conjugate beta-lyase activity in human renal carcinomas.

Cysteine conjugate beta-lyase, an enzyme that converts cysteine S-conjugates to free thiols, pyruvate and ammonia, is normally expressed primarily in the liver and kidney. In theory, this selective distribution affords the opportunity to target thiol-containing drugs to these organs and, perhaps, to tumors derived from them. To assess the potential for delivery of such drugs to kidney-derived tissue, we have used a typical beta-lyase substrate, S-(2-benzothiazolyl)-L-cysteine, to measure the beta-lyase activity in normal and tumor tissue of kidneys removed from patients with renal carcinoma. Although considerable heterogeneity in enzyme activity levels was observed in normal and tumor-derived samples, a high proportion of tumor samples had enzyme activity that was at least 50% of that observed in adjacent normal tissue. Frequently, hypoxanthine-guanine phosphoribosyltransferase activity was observed to be greater in the tumor than in normal tissue. These results may aid in the development of therapy for renal carcinomas.

Adult↗