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D F Paulson

Publications and source records attributed to D F Paulson.

At least 37 records · Page 2Linked to original sources
PubMed1996

Postoperative prostate-specific antigen as a prognostic indicator in patients with margin-positive prostate cancer, undergoing adjuvant radiotherapy after radical prostatectomy.

OBJECTIVES: To identify a population of patients within the group with positive surgical margins after radical prostatectomy who would benefit in terms of improved local control of disease by the administration of adjuvant radiation therapy to the prostate bed. METHODS: Postoperative prostate-specific antigen (PSA) values were evaluated in 45 patients with margin-positive (MP) disease who underwent adjuvant radiotherapy within 6 months of surgery. All patients were clinically T1-2 MO, and pNO. A cutoff of 0.5 ng/mL or less was used as the level below which PSA was considered undetectable. The mean follow-up time from date of radiation was 33 months. RESULTS: In 30 of 45 (67%) patients, PSA levels did drop to undetectable levels postoperatively. In 15 of 45 (33%) patients postoperative PSA levels did not drop to undetectable levels. In the group with detectable postoperative PSA, 12 of 15 (80%) failed adjuvant radiotherapy as determined by a progressive increase in PSA levels in a mean time of 0.95 years (range, 4 months to 2.02 years; median, 0.92 years). When postoperative PSA reached undetectable levels, only 10 of 30 (33%) failed treatment, with a mean time to failure of 2.1 years (range, 4 months to 7.8 years; median, 3.31 years). CONCLUSIONS: The data would suggest that patients who are MP, but attain an undetectable PSA level postoperatively accompanied by a progressive delayed increase in PSA, probably represent a group with local disease recurrence in the prostate fossa, whereas patients whose PSA levels are detectable postoperatively may represent a group with microscopic metastatic disease or a combination of local recurrence and distant disease or large volume local persistent disease. It is in the group of patients in whom the postoperative PSA decreased to undetectable levels that adjuvant radiotherapy may be effective in controlling local progression of prostate cancer through improved local control, as indicated by a durable decrease in PSA values to undetectable levels in roughly two thirds of these patients. Longer follow-up of these patients will be required to determine whether this improved local control will translate into improved survival.

Aged↗
PubMed1996

p53 immunohistochemical and genetic alterations are associated at high incidence with post-irradiated locally persistent prostate carcinoma.

PURPOSE: Several reports have shown that cells with p53 mutations display increased resistance to ionizing radiation, a treatment often used clinically for localized prostate carcinoma. MATERIALS AND METHODS: Totals of 18 post-irradiated locally recurrent prostatic carcinoma specimens and 25 (no radiation) stage D1 node-positive (TxN+MO) primary prostatic carcinoma specimens were tested for p53 immunoreactivity by immunohistochemistry. Of the 18 post-radiation locally recurrent prostatic carcinomas 10 were further analyzed by single strand conformational polymorphism to assess the validity of using this immunohistochemistry approach in irradiated tissue for detecting p53 alterations. Specimens showing p53 alterations by single strand conformational polymorphism were subjected to nucleotide sequence analysis or tested for loss of heterozygosity at a locus within the p53 gene. RESULTS: Of the 25 stage TxN+MO prostatic carcinomas without radiation 5 (20%) were immunoreactive (consistent with the reported incidence of positive immunoreactivity in clinical/surgical stage TxN+MO primary prostatic carcinomas). In contrast, 13 of 18 post-radiation locally recurrent prostatic carcinoma specimens (72%) were immunoreactive. Multivariate logistic regression analysis showed no dependence of p53 immunoreactivity to grade, stage or androgen status in the post-radiation locally recurrent prostatic carcinoma group, while 8 of 10 hormone naive prostatic carcinoma specimens (80%) were immunoreactive. The temporal relationship between p53 alterations and radiotherapy was assessed. Pre-irradiation prostatic carcinomas available from 5 patients with immunoreactive post-radiation locally recurrent disease were analyzed and all were immunoreactive. CONCLUSIONS: p53 Alteration in localized prostatic carcinoma is uncommon. Our study confirms others in that even aggressive locally advanced nonirradiated primaries (stage TxN+MO) contain only 20% incidence of p53 alterations. However, our study demonstrates that p53 alterations are found in the preponderant majority of post-radiation locally recurrent prostatic carcinoma specimens. Limited evaluation of pretreatment prostatic carcinoma biopsies uniformly documented the presence of p53 alterations before ionizing radiation, thereby demonstrating that p53 alteration was already present and was not radiation-induced or only correlated with late stage disease. This finding suggests a potential for p53 immunoreactivity to be used as a pretreatment marker that might predict local treatment failure with ionizing radiation. Large scale prospective trials would appear warranted to evaluate conclusively the potential prognostic applicability of p53 pre-screening before enrollment in definitive radiotherapy.

Adenocarcinoma↗
PubMed1996

Natural history of renal cell carcinoma.

The survival of patients with renal cell carcinoma is directly related to the extent of malignancy at the time of treatment. Patients with T1 and T2 disease experience excellent survival independent of the grade of the disease. However, once the disease has extended from the kidney, survival is a function of whether the disease progresses by direct extension or has the ability to move through space and deposit at distant metastatic sites. When this occurs, survival is almost directly a function of the grade and degree of malignancy of the renal tumor.

Carcinoma, Renal Cell↗
PubMed1995

The impact of PSA on prostate cancer management. Can we abandon routine staging pelvic lymphadenectomy?

Despite a negative metastatic evaluation, up to 100% of patients with high-grade tumors are found to harbor metastatic disease within the pelvic lymph nodes at the time of surgery. This article reviews the literature regarding efforts to refine noninvasive preoperative staging through the use of serum tumor markers, improved radiologic imaging, and histologic analysis of the biopsy specimens. A discussion of the renewed controversy regarding the role of pelvic lymphadenectomy in the management of adenocarcinoma of the prostate follows.

Adenocarcinoma↗
PubMed1995

Prostate cancer.

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Humans↗
PubMed1994

Clinical variables which serve as predictors of cancer-specific survival among patients treated with radical cystectomy for transitional cell carcinoma of the bladder and prostate.

BACKGROUND: Studies have demonstrated conclusively that the stage and grade of transitional cell tumors at presentation are major determinants of survival for those with the disease in the bladder and prostate. The authors initiated a review of 531 patients with transitional cell carcinoma of the bladder and prostate treated with radical cystectomy between 1969 and 1990 to identify other clinical features predictive of cancer-specific survival. MATERIALS AND METHODS: Inpatient and clinical medical records were analyzed for age, race, gender, clinical T stage, medical history, and presenting symptoms and signs, and admission laboratory values were correlated with the patient's cancer-specific outcome. Both univariate and multivariate analyses of the various clinical factors were performed to identify variables predictive of cancer-specific survival. RESULTS: Univariate analysis indicated that clinical T classification, preoperative hemoglobin, tumor grade, irritative voiding symptoms, age, preoperative creatinine, obstructive hydronephrosis on preoperative excretory urography, a history of bladder tumors or nephrouretectomy for transitional cell cancer, prior urinary tract infections, prior pelvic irradiation, and obstructive symptoms were all predictive of poor cancer-specific survival. Multivariate analysis demonstrated that higher clinical T classification (T2, T3a, T3b, T4 versus Ta, Tis, T1) (P < 0.001), increasing age (< 65 years versus > or = 65 years) (P < 0.001), the presence of irritative voiding symptoms (P = 0.01), higher tumor grade, lower preoperative hemoglobin level (< or = 12 gm/dl versus > 12 gm/dl) (P < 0.001), higher preoperative creatinine level (> or = 1.5 mg/dl versus < 1.5 mg/dl) (P = 0.002), a history of nephroureterectomy for transitional cell cancer (P = 0.016), and a history of pelvic irradiation (P = 0.002) were all predictive of poor cancer-specific survival. CONCLUSIONS: Although clinical T classification and tumor grade remain the best predictors of survival in patients with transitional cell carcinoma of the bladder or prostate, clinical variables such as age, preoperative creatinine and hemoglobin levels, a history of nephroureterectomy or pelvic irradiation, and irritative voiding symptoms at presentation may provide additional prognostic information independent of tumor grade and stage.

Adult↗
PubMed1994

Does radical prostatectomy in the presence of positive pelvic lymph nodes enhance survival?

A retrospective review was performed on all patients with stage D1 prostate cancer treated at Duke University Medical Center between 1975 and 1989. A total of 156 patients underwent staging pelvic lymph-node dissection for clinically organ-confined prostate cancer (stage A or B) but were found to have disease metastatic to the pelvic lymph nodes (stage D1). Of this population, 42 patients also underwent radical prostatectomy (group 1), leaving 114 who did not have their prostate removed (group 2). The median cancer-specific survival was 11.2 years for group 1 versus 5.8 years for group 2 (P = 0.005). In patients with one or two positive lymph nodes the median cancer-specific survival was 10.2 years for group 1 versus 5.9 years for group 2 (P = 0.015). There was no difference in survival if three or more lymph nodes were positive. Adjuvant treatment with immediate androgen deprivation and/or postoperative radiation therapy failed to improve the survival experience. The incidence of local problems, including stricture formation, bleeding, or regrowth of cancer requiring dilation or surgical intervention (transurethral prostatectomy) averaged 9.5% in group 1 and 24.6% in group 2. These data show that patients with limited node-positive disease selected for radical prostatectomy experience a survival advantage over those denied such therapy and that this advantage is independent of adjunctive therapy.

Aged↗
PubMed1994

Expanding indications for conservative renal surgery in renal cell carcinoma.

OBJECTIVE: To more clearly define the selection criteria for conservative renal surgery in renal cell carcinoma. METHOD: The survival experience of 42 patients who underwent in situ partial nephrectomy (21), enucleation (18), or both (3) over an eighteen-year period was examined. The presence or a history of contralateral cancer, type of surgery, gender, grade, diameter of tumor, age at diagnosis, presenting symptoms, positive surgical margins, smoking history, and stage were examined with regard to prognostic significance. RESULTS: The five-year cancer-specific survival rates were 100 percent for those patients undergoing partial nephrectomy and 84 percent for those undergoing enucleation. The local recurrence rate was 4.8 percent (2/42) for the group, with both recurrences occurring in patients with von Hippel-Lindau disease. The mean diameter of tumor resected was 4.2 cm. Those patients found to have a positive surgical margin (6) had a significantly shorter disease-specific survival than those who did not (37) (p = 0.004), and those with a smoking history (23) had a significantly shorter survival than non-smokers (19) (p = 0.038). CONCLUSIONS: We conclude that both partial nephrectomy and enucleation are acceptable approaches to renal cell carcinoma in select cases, with survival rates that closely approximate those found in radical nephrectomy series. Renal carcinomas that are peripherally located and small in diameter (< or = 5 cm) are most appropriate for these procedures, and given the excellent results noted to date, the expanded use of these approaches to include very young patients and those with any disease process that may affect renal function is warranted. A positive surgical margin is an ominous pathologic finding and should be avoided by frozen section biopsy at surgery or possibly intraoperative ultrasonography. Additionally, smokers with renal cell carcinoma have a poorer disease-specific survival than non-smokers, further questioning a carcinogenic etiology in this disease.

Carcinoma, Renal Cell↗
PubMed1994

Differential immunoreactivity of transforming growth factor alpha in benign, dysplastic and malignant prostatic tissues.

Immunohistochemical examination of radical prostatectomy specimens from 57 patients was performed to determine the differential expression of transforming growth factor alpha in the human prostate. In addition, epidermal growth factor receptor (EGFr) immunoreactivity was assessed in each case. Stromal versus epithelial staining was determined for each histological subtype: benign prostatic hypertrophy (BPH), prostatic intra-epithelial neoplasia (PIN), and prostatic cancer (CaP) by a single pathologist reviewer. TGFa staining was predominant in stroma while EGFr was localized to the epithelial basal cell layer. Immunoreactivity of both TGFa (P = 0.002) and EGFr (P < 0.001) revealed a significant reduction in CaP compared to BPH or PIN. Autocrine stimulation of EGFr by TGFa or other unrecognized factors may be present in CaP. Conversely, altered stromal influence of CaP via TGFa may be present. These observations could form the basis for future cancer therapeutic strategies using antagonist factors.

Aged↗
PubMed1994

Impact of radical prostatectomy in the management of clinically localized disease.

The cancer specific death rate following radical prostatectomy in patients with organ confined and specimen confined disease was 10% at 13.5 years, less than the noncancer death rate of 20% for patients in these disease extent categories. The median age of all patients in these categories was 65 years. Cancer remains the dominate cause of death in patients with margin-positive disease, being 40% at 13.5 years. Disease detected by prostate specific antigen (PSA) rather than digital rectal examination appears to be of smaller volume and to have a higher probability of negative margins. Data argue that early detection of PSA will shift patients to a more favorable disease category at surgical intervention. Disease recurrence or persistence by PSA detection seems to precede clinical detection of disease by 3 to 5 years. Disease recurrence by PSA detection does not predict survival outcome, probably does not differentiate between local and distant microscopic recurrence, and is not predictive of biological aggressiveness.

Adenocarcinoma↗
PubMed1994

Does of stage pT0 cystectomy specimen confer a survival advantage in patients with minimally invasive bladder cancer?

Controversy exists regarding the clinical significance of a pathological stage T0 (pT0) specimen found at cystectomy or after repeat transurethral resection for transitional cell carcinoma of the bladder. Many investigators cite this subpopulation of patients as a reason to consider more conservative management, based on the premise that the patient may have benefited from the original transurethral resection. However, we questioned whether outcome would be improved in stage pT0 cancer patients or whether outcome in stage pT0 cases would parallel that noted when the original stage was equivalent to the final pathological stage. To test this hypothesis, we examined the survival advantage occasioned by a stage pT0 finding in 66 of 433 patients who underwent radical cystectomy for transitional cell carcinoma of the bladder. Of the 433 patients studied 54 had clinical stage Tis or Ta, 166 clinical stage T1 and 213 clinical stage T2 disease. Within each of the 3 clinical groups (clinical stage Tis/Ta, clinical stage T1 and clinical stage T2) Kaplan-Meier survival projections were generated comparing patients with stage pT0 disease to those whose pathological stage was identical to the original clinical stage. Among the 54 clinical stage Tis/Ta cancer patients 11 with stage pT0 and 24 with stage pTis/pTa had survival projections of 90% of 5 years. Of 166 patients with clinical stage T1 disease 32 with stage pT0 and 78 with stage pT1 tumor had survival projections of 75% at 5 years. Among 213 patients with clinical stage T2 cancer 23 with stage pT0 and 71 with stage pT2 disease had survival projections of 68% at 5 years. The data suggest that a stage pT0 cystectomy specimen does not confer a survival advantage over that noted from the initiating population in which the final pathological stage and initial clinical stage are equivalent. A patient with a stage pT0 specimen functions, by survival analysis, in a manner similar to one with the stated clinical stage.

Adult↗
PubMed1994

Radical cystectomy for stages Ta, Tis and T1 transitional cell carcinoma of the bladder.

Between January 1969 and January 1990, 531 patients underwent bilateral pelvic lymph node dissection and radical cystectomy for the management of transitional cell carcinoma of the bladder. Of these procedures 220 were performed for clinical stage Ta (31 patients), Tis (23) or T1 (166) disease, which was either high grade or recalcitrant to transurethral resection and/or intravesical chemotherapy. This subgroup of patients was studied to evaluate the outcome of recurrent or chemotherapy resistant superficial transitional cell carcinoma of the bladder after radical cystectomy. The operative mortality rate for the group was 2.3% and the overall complication rate was 20.4%. The pelvic recurrence rate was 5.9%. The 5-year cancer-specific survival rates for patients with pathological stage Ta (11), Tis (19), T0 (43) and T1 (91) disease were 88%, 100%, 80% and 76%, respectively. The 10-year cancer-specific survival rates were 75%, 92%, 66% and 62%, respectively. A total of 74 patients received preoperative radiation therapy (2,000 rad) but they had no better 5-year cancer-specific survival rates than did nonirradiated patients. Transurethral resection and/or preoperative radiation therapy resulted in a pathological status of T0 in 43 patients but this did not confer a survival advantage. Although bladder preservation is preferable, low operative mortality and pelvic recurrence rates, as well as new methods of continent urinary diversion continue to make radical cystectomy the definitive form of therapy for patients with superficial disease recalcitrant to transurethral therapy.

Adult↗
PubMed1993

Genetic risk and carcinogen exposure: a common inherited defect of the carcinogen-metabolism gene glutathione S-transferase M1 (GSTM1) that increases susceptibility to bladder cancer.

BACKGROUND: Numerous studies have associated bladder cancer with exposure to carcinogens present in tobacco smoke and other environmental or occupational exposures. Approximately 50% of all humans inherit two deleted copies of the GSTM1 gene which encodes for the carcinogen-detoxification enzyme glutathione S-transferase M1. Recent findings suggest that the GSTM1 gene may modulate the internal dose of environmental carcinogens and thereby affect the risk of developing bladder cancer. PURPOSE: We investigated whether the absence of the GSTM1 gene affects bladder cancer risk and whether there are racial differences in GSTM1 genotype frequency. METHODS: Using a polymerase chain reaction (PCR)-based method, we examined the frequency of the homozygous deleted genotype (GSTM1 0/0) in 229 patients with transitional cell carcinoma of the bladder and 211 control subjects who were enrolled from the Urology Clinics at Duke University Medical Center and the University of North Carolina Hospitals. Control subjects were urology clinic patients who primarily presented with benign prostatic hypertrophy or impotence, who had no history of any cancer other than nonmelanoma skin cancer, and who were frequency matched to case patients on race, sex, and age (10-year age intervals). In order to explore racial differences in GSTM1 gene frequency, genotype was also determined in a community-based sample of 466 paid, healthy, unrelated volunteers from Durham and Chapel Hill, N.C. The presence or absence of the GSTM1 gene locus was determined by using a differential PCR, a semiquantitative technique in which multiple genes are coamplified. RESULTS: Overall, the GSTM1 0/0 genotype conferred a 70% increased risk of bladder cancer (odds ratio [OR] = 1.7; 95% confidence interval [CI] = 1.2-2.5; P = .004). Absence of the GSTM1 gene encoding the glutathione S-transferase M1 enzyme significantly increased risk to persons with exposure to the carcinogens in tobacco smoke (OR = 1.8; 95% CI = 1.2-3.0; P = .01) but poses little increased risk to persons without such exposure. Persons with smoking exposure of more than 50 pack-years who had the GSTM1 0/0 genotype had a sixfold greater risk relative to persons in the lowest risk group (i.e., nonsmokers who were GSTM1 +/+ or +/0). In the pooled clinic control and community sample groups (677 individuals), the GSTM1 0/0 genotype occurred less frequently among Blacks (35%) than among Whites (49%, P < .001). CONCLUSIONS: These findings support a protective role for the GSTM1 gene in bladder cancer. From these findings, it is estimated that 25% of all bladder cancer may be attributable to the at-risk GSTM1 0/0 genotype.

Base Sequence↗
PubMed1993

The value of pathologic factors in predicting cancer-specific survival among patients treated with radical cystectomy for transitional cell carcinoma of the bladder and prostate.

BACKGROUND: A recent consensus conference on bladder carcinoma highlighted the need for pathologic predictors of outcome for patients with transitional cell carcinoma of the bladder. This review was undertaken to determine the pathologic features predictive of cancer-specific survival after a radical cystectomy and urinary diversion for transitional cell carcinoma of the bladder and prostate. METHODS: Between 1969 and 1990, 531 patients with transitional cell carcinoma of the bladder and prostate were treated with radical cystectomy at the Duke University Medical Center. Records and pathologic specimens were analyzed and correlated with outcome. Both univariate and multivariate analyses of the pathologic staging were performed to identify variables predictive of cancer-specific survival. RESULTS: Univariate analysis indicated that pathologic tumor (pT) stage, positive nodes, positive surgical margins, prostatic stromal involvement, grade, age, ureteral involvement, squamous cell carcinoma, and squamous cell differentiation in the specimen all were predictive of poor cancer-specific survival. Carcinoma in situ (CIS) in the specimen was not an adverse prognostic indicator. Multivariate analysis demonstrated that the pT stage, nodal involvement, positive surgical margins, patient's age at surgery, and loss of histologic differentiation were predictive of poor cancer-specific survival. CIS was found again not to have a negative influence on cancer-specific survival. CONCLUSIONS: If any of these features are noted in the final pathologic specimen, patients should be considered for some form of additional postoperative treatment such as chemotherapy or radiation therapy in an attempt to improve their chances for cancer-free survival. These factors will become more important in selecting which patients should be placed in developing adjuvant clinical trials.

Adult↗
PubMed1993

Stratification of pathologic features in radical prostatectomy specimens that are predictive of elevated initial postoperative serum prostate-specific antigen levels.

BACKGROUND: Prostate-specific antigen (PSA) is an important marker for adenocarcinoma of the prostate and is of clinical utility in assessment of residual carcinoma after radical prostatectomy. Although elevated postoperative serum PSA levels have been linked to pathologic stage in radical prostatectomy specimens, limited data are available on the relationship of postoperative PSA levels to margin positivity, intraglandular tumor extent, and histologic grade. METHODS: Initial postoperative serum PSA levels were related to pathologic features of 90 radical prostatectomy specimens with adenocarcinoma of the prostate. Logistic regression analysis was used to stratify pathologic stage, percentage intraglandular carcinoma, histologic grade, and margin positivity as predictors of elevated initial postoperative PSA levels. RESULTS: Pathologic stage, percentage carcinoma, and margin positivity were nearly equivalent in strength of prediction, whereas Gleason histologic grade was a significant but less reliable predictor of elevated initial postoperative PSA levels. Thirty-one of 51 (60.8%) patients with extension of carcinoma outside the prostate gland had an elevated initial postoperative PSA level, whereas only 5 of 39 (12.8%) patients with organ-confined carcinoma had an elevated postoperative PSA level. Intraglandular tumor extent greater than 10% was associated with a greater likelihood of an elevated postoperative PSA level. Additional predictive capacity was obtained with concurrent use of pathologic stage and percentage carcinoma or margin positivity in multivariate analysis. CONCLUSIONS: In radical prostatectomy specimens, pathologic stage, intraglandular carcinoma extent, and margin positivity are particularly important morphologic parameters because they are predictive of residual carcinoma that is detected early, as judged by an elevated initial postoperative serum PSA level.

Adenocarcinoma↗
PubMed1993

Possible mechanism for seeding of tumor during radical prostatectomy.

Prostatic adenocarcinoma sometimes recurs locally in the operative bed after radical prostatectomy. Having observed local recurrence in several patients who had a small tumor confined to the prostate on whole mount serial sections, we postulated that some instances of local recurrence could arise from malignant cells shed in prostatic secretions expressed during surgery. To evaluate whether prostatic secretions contain malignant cells and to estimate the frequency of this phenomenon, we collected fresh prostatic secretions from radical prostatectomy specimens immediately after removal. The secretions were analyzed by cytology for the presence of malignant cells. Of 76 samples collected from consecutive patients with clinical stages T1 and T2 prostate cancer at 3 institutions 11 (14%) contained malignant cells. Positive cytology results were most frequent in patients with poorly differentiated tumors. Of 11 cancers with a Gleason sum of 8 to 10 in the prostatectomy specimen 6 (55%) had a positive cytology result. However, of 63 tumors with a Gleason sum of 5 to 7 only 4 (6%) were positive (p < 0.0001). There was no significant correlation with either clinical or pathological stage of the tumor in this small series. Our findings suggest that malignant cells shed during prostatectomy may seed the surgical bed and could be responsible for some instances of local tumor recurrence. The rate of positive cytology results in our study is similar to the local recurrence rates reported in the literature. Surgeons should make prudent attempts to avoid seeding from this source.

Adenocarcinoma↗