Biomedical subjects

A W Partin

Publications and source records attributed to A W Partin.

At least 127 records · Page 7Linked to original sources

PubMed1998

Prospective evaluation of percent free-PSA and complexed-PSA for early detection of prostate cancer.

Aims of the study: Retrospective studies investigating the use of percent free-PSA for early detection of prostate cancer were limited for various reasons: by their use of long-term stored sera, poor mix of non-cancer to cancer cases and the use of only men with PSA values between 4.0 and 10.0 ng/mL. This prospective study investigates the clinical utility of percent free-PSA and complexed-PSA for early detection of prostate cancer in 219 consecutive men presenting for prostate biopsy. Methods: Of 246 consecutive men who underwent ultrasound guided sextant biopsy of the prostate for PSA elevation and/or suspicious digital rectal exam, 219 men had serum total PSA levels between 2.0 and 20.0 ng/mL and were included in this study. Serum total, free and complexed (PSA-ACT) were measured (Hybritech Inc.). Results: Pathologic examinations demonstrated that 72% and 28% of the biopsies were non-cancer and cancer respectively. The mean percent free-PSA was statistically different between the groups (cancer 14%+/-6.4 and non-cancer 18+/-9%, P<0.001) and improved cancer detection. PSA-ACT provided only modest improvement in cancer detection over that of total PSA. Among this cohort of men, the optimal total PSA reflex range for percent free-PSA was 3.0-7.0 ng/mL (38% specificity) with a percent free-PSA cut-off of 20% (95% sensitivity) yet only affected 56% of the cases. Conclusions: PSA-ACT added very little additional value to the clinical utility of total PSA for early detection. Percent free-PSA performed well for all reflex ranges. A sensitivity and specificity of 95% and 20% respectively were obtained using a single cut-off of 25% for percent free-PSA for the group of men with total PSA values between 4.0 and 10.0 and correlated well with recently reported prospective analyses.

Journal Article↗

PubMed1998

Use of multivariate models to improve prediction of pathologic stage for men with clinically localized prostate cancer.

To benefit from definitive local therapy, men with clinically localized prostate cancer should have organ-confined disease. We discuss the use of multivariate analysis using serum PSA, biopsy Gleason score and clinical stage to improve the prediction of pathologic stage. Serum PSA, biopsy Gleason scores and clinical stage correlate with pathologic stage by univariate analysis are used in this study. However, each of these variables cannot accurately predict stage for the individual patient. Several investigators have proposed clinical algorithms based on multivariate analysis to enhance pretreatment staging. For men with clinically localized prostate cancer, multivariate algorithms are useful to determine the probability of a man having organ-confined disease, seminal vesicle invasion and lymph node involvement. This information will better enable clinicians and patients to make informed decisions about appropriate treatment options.

Journal Article↗

PubMed1998

Human Kallikrein 2 (hK2) and prostate-specific antigen (PSA): two closely related, but distinct, kallikreins in the prostate.

Recent studies on human kallikrein 2 (hK2) have revealed striking similarities and significant differences with the closely related kallikrein PSA. Both PSA and hK2 are primarily localized to the prostate and share close structural similarities. Although both kallikreins are produced by the same secretory epithelial cells in the prostate, hK2 is associated more with prostate tumors than PSA and is highly expressed in poorly differentiated cancer cells. The potent trypsin-like activity of hK2 contrasts with the weak chymotrypsin-like activity of PSA. The inactive precursor form of PSA, proPSA, is converted rapidly to active PSA by hK2, suggesting an important in vivo regulatory function by hK2 on PSA activity. The high homology between hK2 and PSA results in significant cross-reactivity to hK2 by polyclonal and some monoclonal antibodies to PSA. Future studies on both PSA and hK2 need to take into account this potential for cross-reactivity. Specific monoclonal antibodies to hK2 have now demonstrated that serum levels of hK2, like PSA, are correlated with prostate cancer. The production of hK2 protein in active protease form and specific monoclonal antibodies to the hK2 antigen will allow extensive future studies delineating the physiological and clinical utility of this new prostate antigen.

Humans↗

PubMed1998

Minilaparotomy radical retropubic prostatectomy: technique and results.

PURPOSE: A small incision (minilaparotomy) radical retropubic prostatectomy is described and evaluated. A newly designed self-retaining retractor was used as a robot and functioned as a second operative assistant. MATERIALS AND METHODS: A total of 522 consecutive patients underwent minilaparotomy radical prostatectomy by a single surgeon (F. F. M.) between 1991 and 1997. The technique of minilaparotomy radical retropubic prostatectomy (a 7 to 8 cm. midline incision) is described in detail. RESULTS: A questionnaire was mailed to all 522 patients and there were 265 responses. Satisfactory continence was achieved in the short term in 85% of patients (0 to 1 pad). Of the patients 83% had a prostate specific antigen of less than 0.2 ng./ml. at average followup of 2.6 years. There was no operative mortality and the overall complication rates were similar to other patients treated by the same department staff with a larger incision. The typical patient was discharged home 3 days postoperatively. CONCLUSIONS: Minilaparotomy radical retropubic prostatectomy compares favorably with standard radical retropubic prostatectomy.

Equipment Design↗

PubMed1998

International surgical telementoring: our initial experience.

INTRODUCTION: Telesurgical laparoscopic telementoring has successfully been implemented between the Johns Hopkins Bayview Medical Center and the Johns Hopkins Hospital in 27 prior operations. In this previously reported series, telerobotic mentoring was achieved between two institutions 3.5 miles away. We report our experience in performing two international surgical telementoring operations. PURPOSE: To determine the clinical utility of international surgical telementoring during laparoscopic surgical procedures. METHOD: A laparoscopic adrenalectomy was telementored between Innsbruck, Austria (5,083 miles) and Baltimore, MD. As well, a laparoscopic varicocelectomy was telementored between Bangkok, Thailand and Baltimore, MD (10,880 miles) both over three ISDN lines (384 kbps) with an approximate 1 sec delay. RESULTS: Both procedures were successfully accomplished with an uneventful postoperative course. CONCLUSION: International telementoring is a viable method of instructing less experienced laparoscopic surgeons through potentially complex laparoscopic procedures, as well as potentially improving patient access to specialty care.

Adrenalectomy↗

PubMed1998

The use of percent free prostate specific antigen for staging clinically localized prostate cancer.

PURPOSE: The free-to-total serum prostate specific antigen (PSA) ratio (percent free PSA) has been demonstrated to have clinical use for early detection of men with prostate cancer with total PSA levels between 4.0 and 10.0 ng./ml. Several studies evaluating the usefulness of percent free PSA for the staging of clinically localized prostate cancer have provided conflicting results. We further investigate the usefulness of percent free PSA for staging of clinically localized prostate cancer. MATERIALS AND METHODS: In 263 men with clinically localized prostate cancer who underwent radical prostatectomy total PSA and free PSA were measured preoperatively. Pathological stages were classified as organ confined in 134 cases, capsular penetration in 92, seminal vesicle involvement in 7, involvement of the surgical margins in 20 and lymph node involvement in 10. RESULTS: Percent free PSA was significantly different between men with organ confined versus nonorgan confined tumors (p <0.0001) and between those with favorable versus unfavorable pathology (p <0.0001). A cutoff of 12% free PSA provided a 72% positive predictive value and 52% negative predictive value for favorable pathology. A cutoff of 15% free PSA provided a 76% and 53% positive and negative predictive value, respectively, for organ confined disease. CONCLUSIONS: These data demonstrate that the use of percent free PSA may be of additional value for the staging of clinically localized prostate cancer. The recommendations for cutoff levels of percent free PSA for detection and staging of localized prostate cancer are preliminary and can only be given for this particular assay. A large multicenter trial, controlling for age, stage and grade distribution, as well as for a uniform pathological evaluation and comparable total and free PSA assays, is required to elucidate this issue further.

Aged↗

PubMed1998

Differential nuclear matrix protein expression in prostate cancers: correlation with pathologic stage.

PURPOSE: Nuclear Matrix Proteins (NMP) have been shown to be tissue and cell-type specific. Several unique NMPs have been investigated in various cancerous tissues, including prostate, bladder and kidney, and some are presently utilized as tumor markers. This study was aimed at characterizing the differential NMP expression in the pathologically more aggressive prostate cancers. METHODS: High resolution two-dimensional gel electrophoresis and silver staining was used to elucidate the NMP distribution of fresh prostate cancer nuclei, obtained from 39 radical prostatectomy specimens, surgically removed from men with clinically localized prostate cancer. Based on the final pathological grading, specimens were grouped according to predicted prognosis: poor--with seminal vesicle (SV) or lymph node (LN) involvement or established capsular penetration (ECP) with gleason score >7; intermediate--organ confined (OC) or focal capsular penetration (FCP) with gleason score 7 or ECP with gleason score 6; and good--with OC or FCP and gleason score <7. RESULTS: A specific charged protein (YL-1) of molecular weight 76 kD and isoelectric range 6.0-6.6 was found to be consistently present in 19 of 19 aggressive cancers. It was present only in 1 of 10 in the group with good prognosis and weakly positive in 9 of 10 in the intermediate group. CONCLUSIONS: Within this preliminary study, the expression of YL-1 appears to be related to aggressive prostate cancer, suggesting a potential marker of poor prognosis for clinically localized prostate cancer. Further characterization of the identity and function of this NMP is needed to fully ascertain its clinical potential.

Antigens, Nuclear↗

PubMed1998

Disease progression following radical prostatectomy in men with Gleason score 7 tumor.

PURPOSE: The long-term prognosis of men with Gleason score 7 adenocarcinoma of the prostate is uncertain. MATERIALS AND METHODS: We studied 488 men whose radical prostatectomy specimen showed Gleason score 7 tumor without involvement of the seminal vesicles or lymph nodes. Of the 400 men without progression 318 had been followed for 2 years or more and 93 for 7 years or more. RESULTS: Cases of organ confined disease and negative margins regardless of extent of extraprostatic extension had roughly similar and better prognoses than cases of focal and established extraprostatic extension with positive margins. The greater influence of margin status on progression (p <0.0001) compared to extent of extraprostatic extension (p = 0.023) was evidenced in the multivariate analysis. Of 30 men with established extraprostatic extension and positive margins 6 (20%) had progression to distant metastases, which was similar to 14 of 58 (24%) without established extraprostatic extension and positive margins. There was no difference in response to radiotherapy between men with established extraprostatic extension and positive margins compared to the other cases. CONCLUSIONS: Margins status greatly influences the risk of progression in men with Gleason score 7 tumors. Among men with Gleason score 7 tumors, except for those with established extraprostatic extension and positive margins, more than 50% appear to be cured at long-term followup. Because of the high risk of progression in patients with positive margins, clinical studies of adjuvant therapy in this population appear warranted.

Adenocarcinoma↗

PubMed1998

Influence of radical prostatectomy on serum hormone levels.

PURPOSE: The influence of radical prostatectomy on the hypothalamic pituitary axis has not been well studied. It is also unclear how alterations in serum androgen levels that result from surgical removal of the prostate might influence the recovery of libido and sexual function following radical prostatectomy. We determined the influence of radical prostatectomy on the hypothalamic pituitary testicular axis of 63 men with clinically localized prostate cancer treated only with radical prostatectomy. MATERIALS AND METHODS: A total of 63 healthy men 43 to 67 years old were enrolled in this prospective study. Phlebotomy was performed immediately before and 1 year following radical retropubic prostatectomy. Sera were stored frozen and analyzed as a group at the end of the study. We measured serum testosterone, percent free testosterone, dihydrotestosterone (DHT), estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone binding globulin and prolactin. RESULTS: Following radical prostatectomy there was a statistically significant increase in serum testosterone, free testosterone, estradiol, LH and FSH (p <0.0001), and statistically significant decrease in serum DHT (p <0.0001). No difference was noted in serum sex hormone binding globulin or prolactin levels. There was no statistically significant correlation between any serum hormone and sample storage time, patient age or prostate volume that could limit potential bias in study design. Serum hormone changes did not correlate with pathological stage or histological grade for this group of patients. CONCLUSIONS: Radical prostatectomy influences the hypothalamic pituitary axis by increasing serum testosterone, percent free testosterone, estradiol, LH and FSH while decreasing serum DHT levels. These findings suggest that the sexual dysfunction associated with radical prostatectomy cannot be explained by androgen deficiency alone. These data further suggest that the normal prostate and/or prostate neoplasm could secrete a substance or substances that give negative feedback control to pituitary gonadotropin secretion. Further investigation is warranted to identify this substance or substances.

Adult↗

PubMed1998

The role of PSA and percent free PSA for staging and prognosis prediction in clinically localized prostate cancer.

Prostate-specific antigen (PSA) is the most important tumor marker for early detection, staging, and monitoring of men with prostatic cancer today. However, its sensitivity and specificity are not sufficient to use it as a single tool for screening for men with clinically localized prostate cancer. Recently, assays have become available that selectively detect several of the various molecular forms of PSA, especially the unbound or free PSA. Several studies have shown the clinical usefulness of percent free PSA (free PSA/total PSA) for the early detection of men with clinically localized prostate cancer. However, the use of percent free PSA for staging of prostate cancer remains controversial. Based on the case scenario presented, the value of total PSA and percent free PSA for the staging of men with clinically localized prostate cancer is reviewed.

Age Factors↗

PubMed1998

Multivariate models as predictors of pathological stage using Gleason score, clinical stage, and serum prostate-specific antigen.

The patient presented is a 58-year-old man with newly diagnosed prostate cancer who likely has at least a 10- to 15-year life expectancy. In staging this man's extent of disease, several preoperative clinical variables are provided to assess whether the patient has local disease before offering definitive surgical therapy. It has been demonstrated that the combination of several of these variables in a multivariate analysis has greater predictive power than any of these variables do alone. Multivariate analysis using clinical stage, prostate-specific antigen (PSA), and Gleason score will provide both the physician and patient with 95% confidence intervals for determining the probability of having organ-confined disease, extracapsular penetration, seminal vesicle involvement, and lymphatic metastases. Several of the clinical variables given indicate that this patient has advanced disease, such as a PSA of 12 ng/mL, a stage T2b lesion, Gleason sum 7 disease in 2 of 3 cores from the right side associated with perineural invasion, and an additional Gleason sum 7 biopsy from the contralateral apex. For a man with these preoperative variables, there is a 13% chance of organ-confined disease, an 18% probability of seminal vesicle invasion, and a 17% chance of positive pelvic lymph nodes based on a nomogram constructed from multivariate analysis. Using this information, this man should be counseled that he has a high probability (87%) of extracapsular disease and a significant risk (15% to 20%) of having either seminal vesicle or lymph node involvement. Recognizing the risks and benefits of various forms of definitive therapy for prostate cancer, the patient has additional information to make an informed decision.

Humans↗

PubMed1997

Heredity and prostate cancer: a study of World War II veteran twins.

BACKGROUND: Increased risk of prostate cancer among men with a family history of the disease has been observed in several epidemiological studies, and family studies have identified hereditary prostate cancer characterized by early onset and autosomal dominant inheritance. METHODS: In this study, we examine prostate cancer heritability among twins in the NAS-NRC Twin Registry, with cases ascertained from a number of sources: recent telephone interviews, Medicare and Department of Veterans Affairs hospitalizations, previous mail questionnaires, and death certificates. A total of 1,009 prostate cancer cases were identified among the cohort of 31,848 veteran twins born in the years 1917-1927. RESULTS: Probandwise concordance for prostate cancer was substantially higher among monozygous twin pairs, 27.1%, than among dizygous twin pairs, 7.1% (P < 0.001). CONCLUSIONS: These data suggest that genetic influences account for approximately 57%, and environmental influences for 43%, of the variability in twin liability for prostate cancer.

Aged↗

PubMed1997

Comparison of serum PSMA, PSA levels with results of Cytogen-356 ProstaScint scanning in prostatic cancer patients.

BACKGROUND: Stored serum from clinical trial cases undergoing ProstaScint (CYT-356) scanning were available for Prostate Specific Membrane Antigen (PSMA) assay. Prostate Specific Antigen (PSA) levels had already been determined. This provided an opportunity to see what correlations existed between the serum markers and the ProstaScint scan. A group of patients had the studies preprostatectomy, whereas another group had the studies postprostatectomy. METHODS: The scan results, serum PSA, serum PSMA, and clinical data were separately analyzed. PSMA serum levels were determined by Western blot. RESULTS: Preoperatively, radical prostatectomy patients showed a correlation between serum PSA or PSMA levels and the ProstaScint scan in the total group (n = 86), or in an untreated group (n = 38). Preoperatively, PSMA correlated with the pathological stage, whereas PSA correlated with the scan. Postoperatively, only PSMA serum levels correlated with the scan in an untreated group (n = 40). CONCLUSIONS: Preoperatively or postoperatively, Western blot PSMA serum levels predict the stage of disease or local, regional, or distant metastases, as shown by ProstaScint scan. Both the scan and the serum tests provide prognostic information and evaluate the extent of disease to a more significant degree than previously possible.

Adult↗

PubMed1997

Family history facilitates the early diagnosis of prostate carcinoma.

BACKGROUND: Although all men age >50 years are at an increased risk for the development of prostate carcinoma, 2 major factors increase this risk: family history and race. This article outlines the influence of family history on the risk of prostate carcinoma and current understanding of factors that increase this risk. METHODS: Published studies investigating the familial and hereditary link to prostate carcinoma are reviewed. The results of an investigation into the mendelian inheritance of prostate carcinoma are discussed as well as the relation between hereditary cancer syndromes such as breast and ovarian carcinoma and prostate carcinoma. RESULTS: A positive family history of prostate carcinoma increases the relative risk of prostate carcinoma in male first-degree relatives approximately twofold. Prostate carcinoma is inherited as an autosomal dominant trait. The relative risk of prostate carcinoma increases with multiple affected relatives. CONCLUSIONS: Hereditary prostate carcinoma is estimated to be associated with 43% of men in whom the diagnosis of prostate carcinoma is made at age <55 years, 34% of men in whom the diagnosis is made at age <70 years, and only 9% of men diagnosed before age 85 years. Hereditary prostate carcinoma should be suspected in families with an early age at onset of the disease and/or multiple affected family members. Because hereditary prostate carcinoma is characterized by an early age at onset, first-degree relatives in high risk families should begin screening before age 50 years.

Age Factors↗

PubMed1997

Combination of prostate-specific antigen, clinical stage, and Gleason score to predict pathological stage of localized prostate cancer. A multi-institutional update.

OBJECTIVE: To combine the clinical data from 3 academic institutions that serve as centers of excellence for the surgical treatment of clinically localized prostate cancer and develop a multi-institutional model combining serum prostate-specific antigen (PSA) level, clinical stage, and Gleason score to predict pathological stage for men with clinically localized prostate cancer. DESIGN: In this update, we have combined clinical and pathological data for a group of 4133 men treated by several surgeons from 3 major academic urologic centers within the United States. Multinomial log-linear regression was performed for the simultaneous prediction of organ-confined disease, isolated capsular penetration, seminal vesicle involvement, or pelvic lymph node involvement. Bootstrap estimates of the predicted probabilities were used to develop nomograms to predict pathological stage. Additional bootstrap analyses were then obtained to validate the performance of the nomograms. PATIENTS AND SETTINGS: A total of 4133 men who had undergone radical retropubic prostatectomy for clinically localized prostate cancer at The Johns Hopkins Hospital (n=3116), Baylor College of Medicine (n=782), and the University of Michigan School of Medicine (n=235) were enrolled into this study. None of the patients had received preoperative hormonal or radiation therapy. OUTCOME MEASURES: Simultaneous prediction of organ-confined disease, isolated capsular penetration, seminal vesicle involvement, or pelvic lymph node involvement using updated nomograms. RESULTS: Prostate-specific antigen level, TNM clinical stage, and Gleason score contributed significantly to the prediction of pathological stage (P<.001). Bootstrap estimates of the median and 95% confidence interval of the predicted probabilities are presented in the nomograms. For most cells in the nomograms, there is a greater than 25% probability of qualifying for more than one of the pathological stages. In the validation analyses, 72.4% of the time the nomograms correctly predicted the probability of a pathological stage to within 10% (organ-confined disease, 67.3%; isolated capsular penetration, 59.6%; seminal vesicle involvement, 79.6%; pelvic lymph node involvement, 82.9%). CONCLUSIONS: The data represent a multi-institutional modeling and validation of the clinical utility of combining PSA level measurement, clinical stage, and Gleason score to predict pathological stage for a group of men with localized prostate cancer. Clinicians can use these nomograms when counseling individual patients regarding the probability of their tumor being a specific pathological stage; this will enable patients and physicians to make more informed treatment decisions based on the probability of a pathological stage, as well as risk tolerance and the values they place on various potential outcomes.

Decision Support Techniques↗

PubMed1997

Tumor angiogenesis correlates with progression after radical prostatectomy but not with pathologic stage in Gleason sum 5 to 7 adenocarcinoma of the prostate.

BACKGROUND: Prior studies have suggested that tumor angiogenesis (microvessel density [MVD]) may be of prognostic significance in patients with prostate carcinoma. METHODS: The authors examined the relationship of MVD in intermediate grade prostate carcinomas with stage at radical prostatectomy (RP) and progression after RP. For the former group, 109 RP specimens with Gleason sums of 6 and 7 were studied: 34 organ-confined tumors, 37 with capsular penetration, 21 with seminal vesicle involvement, and 17 with pelvic lymph node metastasis. For the latter group, 87 RP specimens were studied that had a Gleason sum of 5 to 7 for which the patients underwent follow-up of at least 7 years or until progression. Thirty-seven patients (43%) progressed at a mean of 3.5 years (range, 1-8 years). Representative sections of each tumor were stained for CD31 and "hot spot" microvessels were quantitated in a 3.14-mm2 area. RESULTS: In the first arm, there was no relationship between MVD and stage at RP. In the second arm, the mean MVD in tumors that progressed was significantly higher than in nonprogressors (43.0 +/- 26.1 vs. 29.0 +/- 13.1; P < 0.0001 by Wilcoxon-Gehan statistic). MVD and Gleason sum were independent statistically significant predictors of progression (MVD, P < 0.0001; Gleason sum, P < 0.0001 by Cox proportional hazards model). CONCLUSIONS: MVD is an independent significant predictor of progression after RP for tumors with a Gleason sum of 5 to 7. Because these comprise the majority of RP specimens, it is this group for which discrimination of biologic potential is most needed. Angiogenesis may be useful in the prognostic stratification of patients beyond that possible using stage and grade alone.

Adenocarcinoma↗

PubMed1997

Radical prostatectomy as treatment for prostate-specific antigen-detected stage T1c prostate cancer.

The use of serum prostate-specific antigen (PSA) measurement as a method for early detection of prostate cancer has increased the detection of clinically and pathologically localized prostate cancer. Clinical stage T1c was introduced to describe cancers discovered on prostate biopsy as a result of an abnormal serum PSA level without a palpable prostatic abnormality on digital rectal examination. The majority of men with stage T1c tumors have significant disease warranting treatment. We report the results of anatomic radical retropubic prostatectomy as therapy for PSA-detected stage T1c prostate cancer in 340 men treated at a single institution. In all, 17 men (5%) have had a recurrence with 2.3 +/- 1.2 years of follow-up, 15 of whom have experienced an isolated biochemical PSA recurrence only. The overall actuarial biochemical PSA recurrence-free rate at 6 years is 87%, with pathologic stage being the best single indicator of the likelihood of progression. Although a longer period of follow-up is needed, this interim report suggests that these men can be cured by surgery at rates equal to or better than those of previously reported radical prostatectomy series.

Actuarial Analysis↗

PubMed1997

Prostate-specific antigen in men born with bladder exstrophy.

OBJECTIVES: To determine serum levels of prostate-specific antigen (PSA) in men born with bladder exstrophy and to investigate the clinical utility of this test in the bladder exstrophy population. METHODS: Ten men aged 19 to 45 years with a history of bladder exstrophy underwent digital rectal examination and free and total serum PSA determinations. Immunohistochemistry for PSA and prostate-specific acid phosphatase (PSAP) was performed on archival prostate tissue from 1 man with bladder exstrophy. RESULTS: Free and total serum PSA levels for all patients were measurable and below the upper limit for established age-specific reference ranges for normal men. Both PSA and PSAP were detectable by immunohistochemistry in prostate epithelial cells of a man with bladder exstrophy. CONCLUSIONS: Men born with bladder exstrophy have detectable serum PSA levels. However, because prostate cancer in men with bladder exstrophy has not been reported, whether PSA will have a clinical role as a serum tumor marker for prostate cancer in this population remains to be determined. If so, the PSA reference range for men with the exstrophy condition will need to be defined. Because prostate histology in men with exstrophy resembles that of normal men, careful clinical monitoring for benign and malignant tumors should not be overlooked in this particular population.

Adult↗