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A W Partin

Publications and source records attributed to A W Partin.

At least 109 records · Page 6Linked to original sources
PubMed1999

Alpha 1-adrenoceptor antagonists terazosin and doxazosin induce prostate apoptosis without affecting cell proliferation in patients with benign prostatic hyperplasia.

PURPOSE: Recent evidence indicated that an alpha 1 blocker, doxazosin, induces prostate apoptosis in patients with benign prostatic hyperplasia (BPH). In this study, to determine whether this apoptotic response was mediated by alpha 1 adrenoceptor-dependent mechanism or was specific to doxazosin, we examined the effect of another alpha 1 blocker, terazosin, in addition to doxazosin, on the dynamics of prostate cell growth. MATERIALS AND METHODS: Cell proliferation and apoptosis were evaluated in BPH patients, an untreated (control) group (n = 31), and men treated with terazosin (n = 42) and doxazosin (n = 61) for the relief of the obstructive symptoms. Terazosin (1 to 10 mg./day) and doxazosin (2 to 8 mg./day) treatment varied from 1 week to 3 years. Ki-67 immunostaining and the TUNEL assay were used to evaluate the proliferative and apoptotic indices, respectively, in both the epithelial and stromal components of prostate (biopsy and prostatectomy) specimens. The smooth muscle cell content of the prostatic stroma was identified on the basis of smooth muscle alpha-actin immunoreactivity. RESULTS: A significant induction of apoptosis was observed in both the prostatic epithelial and stromal cells within the first month of terazosin and doxazosin therapy, as compared with untreated controls (p < 0.05). Furthermore, the marked induction of prostatic stroma apoptosis in response to both alpha 1 adrenoceptor antagonists was paralleled by a significant decrease in the smooth muscle alpha-actin expression. This loss of prostatic smooth muscle cells correlated with morphological stromal regression (as detected by trichrome staining) and BPH symptom improvement. Neither terazosin nor doxazosin therapy resulted in significant changes in prostate cell proliferation. CONCLUSIONS: These findings demonstrate that alpha-blockers as a class may regulate prostate growth by inducing apoptosis in both the epithelial and stromal cells, with little effect on cell proliferation. Apoptosis-mediated prostate stromal regression appears as a molecular mechanism underlying the therapeutic response to alpha 1 blockade in the treatment of BPH.

Adrenergic alpha-Antagonists↗
PubMed1999

Digital rectal examination and imaging studies are unnecessary in men with undetectable prostate specific antigen following radical prostatectomy.

PURPOSE: We determine the probability of local or distant recurrence following radical prostatectomy in men with an undetectable prostate specific antigen (PSA) level. MATERIALS AND METHODS: The clinical course of 1,916 consecutive men followed during a 14-year period after radical prostatectomy was reviewed. Average followup plus or minus standard deviation is 5.5+/-3.5 years, and 326 men (17%) have been followed for more than 10 years. In total this population of men has been followed for 10,540 patient-years. RESULTS: Of 1,916 men 56 (2.9%) had local recurrence an average of 6.1+/-2.7 years (range 1 to 12) after surgery. No man had local recurrence with an undetectable serum PSA. Mean serum PSA at the time of local recurrence was 5.8 ng./ml. Of the 56 men 13 (25%) who had local disease recurrence had an undetectable serum PSA at 5 years of followup but had progression to biochemical and local disease recurrence later. Of 1,916 men 118 had distant metastases with a mean serum PSA of 28.6 ng./ml. No man has had distant metastasis with an undetectable serum PSA. CONCLUSIONS: Disease can recur after radical prostatectomy even after an extended biochemical disease-free interval. None of the 1,916 men followed for an average of greater than 5 years after surgery had local recurrence or distant metastasis with an undetectable serum PSA. Based on these observations, we recommend no further evaluation, that is digital rectal examination or imaging studies, in men with an undetectable PSA following radical prostatectomy.

Follow-Up Studies↗
PubMed1999

Prediction of post-radical prostatectomy pathological outcome for stage T1c prostate cancer with percent free prostate specific antigen: a prospective multicenter clinical trial.

PURPOSE: Prostate specific antigen (PSA) exists in bound (complexed) and unbound (free) forms in serum. The percentage of free PSA enhances the specificity of PSA testing for prostate cancer detection. We evaluated the use of percent free PSA preoperatively to predict pathological stage. MATERIALS AND METHODS: A total of 379 men with prostate cancer and 394 with benign prostatic disease 50 to 75 years old were enrolled in this prospective study at 7 medical centers. All subjects had a palpably benign prostate gland, serum PSA 4.0 to 10.0 ng./ml. and a histologically confirmed diagnosis. The Hybritech Tandem PSA and free PSA assays were used. Of the 379 cancer patients 268 (71%) underwent radical prostatectomy. RESULTS: Higher percent free PSA levels were associated with more favorable histopathological findings in prostatectomy specimens. A value of 15% free PSA provided the greatest discrimination in predicting favorable pathological outcome. Organ confined cancer, Gleason sum less than 7 and small tumors (10% or less involvement of the prostate) were noted in 75% of patients with greater than 15% and only 34% with 15% or less free PSA (p<0.001). Multivariate logistic regression analysis revealed percent free PSA to be the strongest predictor of postoperative pathological outcome (odds ratio 2.25), followed by biopsy Gleason sum (2.06) and patient age (1.35). Total PSA was not predictive in this cohort but has been shown in prior studies to be predictive of outcome when a broader range of PSA values is evaluated. CONCLUSIONS: Percent free PSA may be used for risk assessment of the presence (diagnosis) and stage of prostate cancer in men with PSA between 4 and 10 ng./ml. Percent free PSA may be combined with PSA, digital rectal examination and biopsy findings to help predict postoperative pathological stage and grade, and may assist the patient and physician in making more informed treatment decisions.

Aged↗
PubMed1998

Use of the percentage of free prostate-specific antigen to enhance differentiation of prostate cancer from benign prostatic disease: a prospective multicenter clinical trial.

CONTEXT: The percentage of free prostate-specific antigen (PSA) in serum has been shown to enhance the specificity of PSA testing for prostate cancer detection, but earlier studies provided only preliminary cutoffs for clinical use. OBJECTIVE: To develop risk assessment guidelines and a cutoff value for defining abnormal percentage of free PSA in a population of men to whom the test would be applied. DESIGN: Prospective blinded study using the Tandem PSA and free PSA assays (Hybritech Inc, San Diego, Calif). SETTING: Seven nationwide university medical centers. PARTICIPANTS: A total of 773 men (379 with prostate cancer, 394 with benign prostatic disease) 50 to 75 years of age with a palpably benign prostate gland, PSA level of 4.0 to 10.0 ng/mL, and histologically confirmed diagnosis. MAIN OUTCOME MEASURES: A percentage of free PSA cutoff that maintained 95% sensitivity for prostate cancer detection, and probability of cancer for individual patients. RESULTS: The percentage of free PSA may be used in 2 ways: as a single cut-off (ie, perform a biopsy for all patients at or below a cutoff of 25% free PSA) or as an individual patient risk assessment (ie, base biopsy decisions on each patient's risk of cancer). The 25% free PSA cutoff detected 95% of cancers while avoiding 20% of unnecessary biopsies. The cancers associated with greater than 25% free PSA were more prevalent in older patients, and generally were less threatening in terms of tumor grade and volume. For individual patients, a lower percentage of free PSA was associated with a higher risk of cancer (range, 8%-56%). In the multivariate model used, the percentage of free PSA was an independent predictor of prostate cancer (odds ratio [OR], 3.2; 95% confidence interval [CI], 2.5-4.1; P < .001) and contributed significantly more than age (OR, 1.2; 95% CI, 0.92-1.55) or total PSA level (OR, 1.0; 95% CI, 0.92-1.11) in this cohort of subjects with total PSA values between 4.0 and 10.0 ng/mL. CONCLUSIONS: Use of the percentage of free PSA can reduce unnecessary biopsies in patients undergoing evaluation for prostate cancer, with a minimal loss in sensitivity in detecting cancer. A cutoff of 25% or less free PSA is recommended for patients with PSA values between 4.0 and 10.0 ng/mL and a palpably benign gland, regardless of patient age or prostate size. To our knowledge, this study is the largest series to date evaluating the percentage of free PSA in a population representative of patients in whom the test would be used in clinical practice.

Aged↗
PubMed1998

Automated image analysis system for detecting boundaries of live prostate cancer cells.

Image analysis provides a powerful tool for quantifying cell motility and has been used to correlate motility with metastatic potential in an animal model of prostate cancer. However, widespread use of this image analysis method has been limited because earlier methods of quantitative analysis required time-intensive and subjective manual tracing of cell contours. In this report, we describe a fully automated image segmentation algorithm for detection and morphometric description of prostatic cells. The segmentation system was tested on prostate cell images generated from Hoffman modulation contrast microscopy (47 cells at 64 time points = 3,008 images) and differential interference contrast microscopy (29 cells at 64 times points plus 1 cell at 62 time points = 1,918 images). Morphometric measurements were derived from computer-determined cell boundaries and compared with the same measurements derived from manually traced cell boundaries. Final correlation coefficients for area and perimeter measurements for Hoffman and differential interference contrast microscopy were (0.76, 0.62) and (0.93, 0.93), respectively. Results with our differential interference contrast images demonstrate that our segmentation algorithm reliably and efficiently replaces the need for manually traced cell boundaries in addition to eliminating intraobserver variation. Our automated segmentation process will have immediate utility in our motility analysis system that relates cell motility with metastatic potential of prostate cancer.

Adenocarcinoma↗
PubMed1998

Biological aggressiveness of hereditary prostate cancer: long-term evaluation following radical prostatectomy.

PURPOSE: We answer the question of whether, following radical prostatectomy, prostate cancer in patients with a family history of prostate cancer relapses biochemically at the same rate as prostate cancer in appropriately matched patients with no family history. MATERIALS AND METHODS: The study was performed in 2 parts. In both parts prostate specific antigen (PSA) progression was defined as a postoperative elevation in serum PSA greater than 0.2 ng./ml. Part 1 included 656 patients who underwent radical prostatectomy by the same surgeon. Men with a family history of prostate cancer in a father or brother (94) were compared to those with no history of prostate cancer in a father or brother (562). Part 2 comprised 52 men with a family history of prostate cancer consistent with hereditary prostate cancer (HPC). HPC is defined as a family with 3 generations affected, 3 first-degree relatives affected or 2 relatives affected before age 55 years. Each member of this HPC group was matched by postoperative Gleason score and postoperative pathological stage with a patient who also underwent radical prostatectomy in the same time frame by the same surgeon but who reported no family history of prostate cancer by telephone interview and questionnaire. RESULTS: In part 1, 94 probands (14%) reported a history of prostate cancer in the father or in at least 1 brother. The remaining 562 probands (85%) reported no known history of prostate cancer in the father or brother(s). There was no statistically significant difference in the probability of maintaining an undetectable PSA between these 2 groups. In part 2, 45 of 52 pairs (87%) were matched identically for all matching criteria. Mean follow time for the sporadic and hereditary groups was 5.4 and 5.1 years, respectively. There was no statistically significant difference in the probability of maintaining an undetectable PSA between the 2 groups. CONCLUSIONS: Men with an affected father or brother, or those with a family history consistent with HPC have the same outcome following radical prostatectomy as men with no family history of the disease. Combined with our previous studies, these findings suggest that there is no biologically important difference between hereditary and sporadic prostate cancers.

Disease Progression↗
PubMed1998

Influence of finasteride on free and total serum prostate specific antigen levels in men with benign prostatic hyperplasia.

PURPOSE: Finasteride therapy for benign prostatic hyperplasia (BPH) results in a marked lowering of serum prostate specific antigen (PSA) levels. However, little is known about the effect of finasteride on unbound or free serum levels of PSA. Such information would be important since percent free PSA may substantially improve the cancer specificity of PSA testing. Thus, we prospectively studied the effect of finasteride therapy on total and free serum PSA levels. MATERIALS AND METHODS: In a randomized, placebo controlled, double-blind trial 40 men with histologically confirmed BPH (age range 52 to 78 years) were treated with either 5 mg. finasteride daily (26 patients) for 9 months or placebo (14) for 6 months. Prostate volume was assessed by transrectal ultrasound. Serum levels of free and total PSA were measured from archived serum samples stored at -70C at baseline and for as long as 9 months of treatment. RESULTS: In the finasteride group mean total PSA levels declined from 3.0 ng./ml. at baseline to 1.5 ng./ml. after 6 months of treatment (50% decrease, p <0.01). In the placebo group, with similar baseline levels, no significant change was observed. PSA density declined significantly in finasteride treated men (p <0.01) but not in men receiving placebo. The mean percent free PSA (13 to 17% at baseline) was not altered significantly by finasteride or placebo. CONCLUSIONS: Total PSA serum levels decreased by an average of 50% during finasteride therapy but percent free PSA did not change significantly. This information is potentially useful in the interpretation of PSA data used for early detection of prostate cancer in men receiving finasteride. However, further studies are required to demonstrate the use of percent free PSA to detect the development of cancer.

Aged↗
PubMed1998

Interpretation of free prostate specific antigen clinical research studies for the detection of prostate cancer.

PURPOSE: We reviewed the use of percent free prostate specific antigen (PSA) to enhance specificity of PSA testing and aid in the discrimination of benign and malignant prostate disease. We present proposed percent free PSA cut points and probability factors, and discuss factors that are believed to affect study outcomes and conclusions. MATERIALS AND METHODS: We reviewed the literature with respect to PSA and free PSA with particular emphasis on clinical use of percent free PSA and factors that may affect study outcomes. RESULTS: Percent free PSA may increase the specificity of PSA testing without sacrificing the cancer detection rate. Differences in study designs and subject populations may account for the confusion in the current literature. Specific factors that may influence study outcomes include sample size, PSA range, age, race, digital rectal examination findings, prostate size, tumor size and pathology, as well as treatment history, sample collection and storage conditions, and the particular assays used to determine free and total PSA values. CONCLUSIONS: The use of percent free PSA to enhance the specificity of prostate cancer screening is thought to provide useful information to aid in the differentiation of benign and malignant prostate diseases. There is evidence to suggest a benefit cost advantage to a tailored biopsy approach based on percent free PSA. However, statistically valid multisite clinical trials that take into account influencing factors are needed to set assay specific cut points and probability determinations.

Age Factors↗
PubMed1998

Long-term results of radiation therapy for prostate cancer recurrence following radical prostatectomy.

PURPOSE: Following radical prostatectomy, radiation therapy may be beneficial in select patients with isolated local recurrence. Pathological stage, Gleason score and the timing of prostate specific antigen (PSA) elevation are useful in distinguishing men with local recurrence from those with distant metastases. We test the ability of these criteria to predict long-term suppression of PSA recurrence following post-prostatectomy radiation therapy. MATERIALS AND METHODS: Of 1,699 men treated with radical prostatectomy from 1982 to 1995, 82 with an isolated PSA elevation or local recurrence following surgery underwent radiation therapy to the prostatic bed and were followed for at least 2 years. No patient had evidence of metastases at the time of radiation. RESULTS: Of the men 17 (21%) had an undetectable PSA (less than 0.2 ng./ml.) for 2 or greater years following radiation. The 5-year actuarial PSA recurrence-free rate after radiation was 10%. PSA remained at undetectable levels for 2 or greater years in no patients with Gleason score 8 or greater (12 cases), positive seminal vesicles (12) or positive lymph nodes (3), and in only 1 of 16 men (6%) who had a PSA recurrence within 1 year of prostatectomy. As the interval to PSA recurrence increased, the likelihood of responding to radiotherapy increased to 44% if initial disease detection occurred 5 or more years after prostatectomy. There was no demonstrated advantage to radiating men with an isolated PSA elevation before a documented local recurrence. CONCLUSIONS: Patients with Gleason score 8 or greater, positive seminal vesicles or lymph nodes, or a PSA recurrence within the first year following surgery rarely benefit from radiation therapy. As the interval to PSA recurrence increases, the likelihood of responding to radiation therapy increases substantially. These parameters are useful in the selection of patients with prostate cancer recurrences who are likely to benefit from radiation to the prostatic bed.

Follow-Up Studies↗
PubMed1998

Ability of sextant biopsies to predict radical prostatectomy stage.

OBJECTIVES: There are few studies evaluating multiple variables on sextant biopsies with the intent to predict stage in radical prostatectomy specimens. METHODS: We studied 113 sextant biopsies with corresponding totally submitted radical prostatectomy specimens. Variables evaluated on sextant biopsies included total length and percent of cancer; maximum length and percent of cancer on one core; location (apex, mid, base); bilaterality; Gleason grade; number of cores involved; serum prostate-specific antigen (PSA) level; and serum PSA density (PSAD). Radical prostatectomy stage was classified as organ versus non-organ confined. RESULTS: The following variables individually correlated with radical prostatectomy stage: total cancer measured in millimeters (P <0.0001) or percent (P <0.0005); biopsy Gleason score (P <0.0001); number of involved cores (P <0.0001); maximum cancer on one core measured in millimeters (P = 0.0001); maximum percent of cancer on one core (P = 0.01); bilaterality (P = 0.01); PSA level (P = 0.03), and PSAD (P = 0.001). The most predictive sets of two variables that correlated with stage included high Gleason score (P <0.0001) combined with numbers of cores involved (P = 0.002). When biopsies had Gleason scores of 6 or less, two or fewer positive cores, and serum PSA of 0 to 4 ng/mL, 89% were organ confined. When biopsies had Gleason scores of 6 or less with two unilaterally positive cores, 87% were organ confined. In biopsies with Gleason scores of 7 or more and more than one positive core, only 10% were organ confined. CONCLUSIONS: The most important predictors of stage by sextant needle biopsy evaluation are numbers of cores involved with carcinoma and high Gleason score. Bilaterality and serum PSA values improved prediction in two small subgroups. In 37% of our population we were able to predict with a greater than 87% probability the organ-confined versus non-organ-confined status.

Biopsy↗
PubMed1998

A quantitative histologic analysis of collagen subtypes: the primary obstructed and refluxing megaureter of childhood.

OBJECTIVES: To analyze and identify collagen subtypes in the primary obstructed and refluxing megaureter of childhood. METHODS: Anticollagen monoclonal antibodies to collagen types I, III, and IV were used in control ureters (n = 4), obstructed (n = 7), and refluxing (n = 13) megaureters. Additionally, all were stained with Masson's trichrome to further define the extracellular matrix. After staining and serial sectioning, representative ureteral sections, focusing on the muscularis and lamina propria regions, were digitized and analyzed with a color image analysis system. RESULTS: Immunohistochemical studies demonstrated increases in collagen types I and III for both obstructed and refluxing megaureters compared with controls (P <0.05). Collagen type IV was not detected in statistically significant amounts in any ureter. In control ureters most was type I (83% +/- 9%) collagen. Obstructed megaureters produced similar results with virtually all collagen being type I (84% +/- 26%) with very little type III collagen present, 5.3% +/- 3%. Refluxing megaureters contained only 55% +/- 15% type I collagen. However, there was an increase in type III collagen (16% +/- 4%) versus (4.5% +/- 2%) in controls (P <0.05). CONCLUSIONS: These data suggest that the greater contribution of type III collagen may play a role in the pathophysiology of refluxing megaureters. Because type III collagen is a less distensible fiber, it may cause an intrinsically stiffer ureter and play a role in the lower surgical success in the reimplantation of refluxing megaureters.

Antibodies, Monoclonal↗
PubMed1998

An algorithm combining age, total prostate-specific antigen (PSA), and percent free PSA to predict prostate cancer: results on 4298 cases.

OBJECTIVES: To (1) determine if patient age and total prostate-specific antigen (PSA) levels could enhance the ability of percent free PSA to distinguish prostate cancer from benign prostate disease within the 4.0 to 20 ng/mL total PSA range; (2) define the probability of prostate cancer based on patient age, total PSA, and percent free PSA; and (3) define a probability cutoff that distinguishes benign from malignant prostate disease. METHODS: The 3773 urologically referred patients with serum PSA values between 4.0 and 20 ng/mL had a sextant biopsy diagnosed as either prostatic carcinoma (1234) or benign prostatic disease (2539) within 60 days of serum specimen collection. We created a logistic regression model, using patient age, total PSA, and percent free PSA, to assign a probability of prostate cancer, and tested the model on an additional data set (525 patients) to calculate sensitivity and specificity. RESULTS: An 18% probability cutoff detected 95% of malignant biopsies and identified 34% of negative biopsies in the validation set. This approach yielded an 11% percentage point increase in specificity over percent free PSA alone. A 20% probability cutoff detected 90% of malignant cases and identified 42% of negative biopsies. CONCLUSIONS: A prostate cancer probability based on age, total PSA, and percent free PSA is more effective than percent free PSA alone in differentiating benign prostate disease from prostate cancer. This model may assist physicians and patients regarding the need for biopsy.

Age Factors↗
PubMed1998

Frequent occurrence of metastatic disease in patients with renal cell carcinoma and intrahepatic or supradiaphragmatic intracaval extension treated with surgery: an outcome analysis.

OBJECTIVES: Previous reports indicate that up to 10% of patients with localized renal cell carcinoma have direct intracaval neoplastic extension. Many patients with locally confined tumors and small intracaval tumor extensions can be surgically cured. Few studies have documented long-term survival after radical surgery for renal cell carcinoma involving higher vena caval tumor extension. We report the follow-up of 34 consecutive patients undergoing radical nephrectomy and intrahepatic or supradiaphragmatic intracaval thrombectomy for renal cell carcinoma. METHODS: From October 1982 through January 1993, 34 consecutive patients with a mean age of 60 years were identified as having clinical Stage T3 renal cell carcinoma (mean diameter 9.5+/-4.0 cm) with intrahepatic (41%) or supradiaphragmatic (59%) intracaval neoplastic extension. Patients underwent radical nephrectomy with intrahepatic caval thrombectomy (38%) or supradiaphragmatic caval thrombectomy using cardiac bypass with hypothermia and circulatory arrest (62%). Clinical outcome was assessed during a mean follow-up of 30 months (range 1 to 182). RESULTS: A total of 24 (71%) of 34 tumors demonstrated capsular penetration, and 22 (65%) of 34 had significant perinephric extension into Gerota's fascia by pathologic analysis. Metastatic disease was identified in 35% of patients either at the time of surgery or by pathologic analysis. Using Kaplan-Meier actuarial analysis, the likelihood of survival for all 34 consecutive patients after surgery was 68% (95% confidence interval [CI] 49% to 81%) at 1 year, 32% (95% CI 18% to 48%) at 2 years, 14% (95% CI 5% to 28%) at 5 years, and 9% (95% CI 2% to 24%) at 10 years. Neither capsular penetration, perinephric extension, the level of intracaval extension of tumor, nor the use of cardiopulmonary bypass significantly affected survival. CONCLUSIONS: In patients with renal cell carcinoma and intrahepatic or supradiaphragmatic intracaval extension of tumor, the presence of metastases is a frequent occurrence and, if present, greatly diminishes survival. Improvements in the preoperative detection of occult metastases are needed if surgery alone is to improve survival.

Adult↗
PubMed1998

Elevated prostate-specific antigen, abnormal prostate evaluation on digital rectal examination, and transrectal ultrasound and prostate biopsy.

Prostate cancer screening for the early diagnosis of organ-confined, potentially curable prostate cancer has dramatically changed the practice of urology over the past 15 years. The introduction of prostate-specific antigen (PSA) testing, increased medical and public awareness for digital rectal examination (DRE), and transrectal ultrasound-assisted needle biopsy of the prostate (TRUS/PNBX) has been instrumental in these dramatic changes.

Adult↗