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T A Stamey

Publications and source records attributed to T A Stamey.

At least 19 recordsLinked to original sources

Multiple cancers in the prostate. Morphologic features of clinically recognized versus incidental tumors.

Multiple independent tumors were identified in specimens from 117 of 234 prostatectomies for clinical adenocarcinoma; there were 266 incidental cancers in these 117 prostates. The clinically detected carcinoma was the largest (or only) tumor in all 202 Stage B cases. However, among 32 Stage A cases (detection by transurethral resection), there were 8 prostates in which an incidental tumor was larger than the clinically manifest cancer. These were all small tumors except for two incidental cancers with a volume greater than 2cm3; roughly 80% of incidental carcinomas were smaller than 0.5 cm3, whereas fewer than 20% of manifest tumors were smaller than 0.5 cm3. Comparison with a series of cancers found incidentally at cystoprostatectomy for bladder cancer showed the same volume distribution as incidental (smaller) carcinomas in patients with prostate cancer. This distribution was thought to reflect the volume distribution of prostate cancer in the general population older than 50 years of age. It was concluded that additional incidental tumors are common in patients with prostate cancer, but their sum of volumes is seldom as large as the clinical cancer volume.

Adenocarcinoma

Morphologic analysis of surgical margins with positive findings in prostatectomy for adenocarcinoma of the prostate.

Apical invasion and positive apical margins were assessed in 165 consecutive radical prostatectomies. Apical invasion, defined as cancer in the distal 8 mm of the prostate, was evident in more than 80% of the cases, and apical margins occurred in 16% of the specimens with apical Clinical judgement was not effective in predicting apical cancer. Frequency of apical margins increased in proportion to greater cancer volume, from 9.8% in cancers smaller than 4 cc to 30.7% in cancers larger than 12 cc. However, most positive margins in the group with cancers smaller than 4 cc were caused by inadvertent incision into the prostate during the operation, whereas the vast majority of apical margins in cancers larger than 4 cc were caused by capsule penetration of the tumor. Although margins associated with capsule penetration occurred characteristically in the posterior (rectal) portion of the apex, margins caused by incision into the prostate were distributed over the entire apical surface of the gland. Positive margins at the urethral stump were quite uncommon (occurring in four cases). These findings suggest that modifications of surgical technique might reduce the frequency of this complication.

Adenocarcinoma

Detection of clinically significant prostate cancer by transrectal ultrasound-guided systematic biopsies.

Systematic biopsies are a useful, sensitive means to detect carcinoma of the prostate. However, multiple biopsies pose a risk for detecting clinically insignificant prostate cancer, that is those cancers less than 0.5 cc in volume, which occur in approximately 32% of all white men more than 50 years old. Systematic biopsies were positive for cancer in 442 of 816 patients and 60 (14%) demonstrated only a minute focus of cancer (3 mm. or less) in 1 of the 6 biopsy specimens. In 27 patients with these minute foci who underwent radical prostatectomy a wide range of cancer volumes was observed; 30% of these 27 cancers were less than 0.5 cc (15% less than 0.2 cc) and may not have required therapy. Thus, the overall risk of detecting an insignificant cancer is 4.0% with systematic biopsies. Performance of confirmatory biopsies in patients with a minute focus (3 mm. or less) of cancer on initial systematic biopsies resulted in cancers less than 0.5 cc being removed in only 1 of 10 radical prostatectomies (10%, none was less than 0.2 cc). Thus, with the addition of confirmatory biopsies the risk of detecting insignificant cancer is 1.4%. Conservative management is recommended for patients without significant cancer on repeat biopsies in whom initial biopsies have revealed only a minute focus of cancer in 1 of the biopsy cores. We believe that concern is also warranted for patients who have 3 mm. or less of cancer demonstrated by several nonsystematic biopsies directed at a suspicious hypoechoic lesion in whom the digital rectal examination is normal.

Antigens, Neoplasm

Estimation of prostate cancer volume by transrectal ultrasound imaging.

Estimation of prostate cancer volume is a potentially important application of transrectal ultrasound imaging. Preoperative volume estimation was performed in 110 patients undergoing transrectal prostatic ultrasonography and subsequent radical prostatectomy. Several different methods for calculation of cancer volume were compared. Most of the sonographic methods that have proved to be useful for estimation of prostate gland volume were inaccurate in estimation of the cancer volume in the prostatectomy specimen. All methods underestimated the cancer volume in the majority of the cases. Step-section planimetry provided the highest correlation with cancer volume (r = 0.84) but the wide range of error makes clinical application impractical. With the current technology, ultrasound imaging alone does not appear to be a useful means to predict cancer volume.

Aged

The predictive significance of substaging stage A prostate cancer (A1 versus A2) for volume and grade of total cancer in the prostate.

Morphometric analysis was performed on 44 radical prostatectomy specimens for clinical stages A1 and A2 carcinoma of the prostate. The majority of stage A cancers (86%) were located in the transition zone of the prostate, while only 14% arose in the peripheral zone. The subclassification into stages A1 and A2 based on the percentage of cancer in the transurethral resection chips did not reliably distinguish those cancers of high volume (transurethral resection plus residual). All 6 cases with Gleason grade 4 elements in the transurethral resection chips had relatively high volume cancer. In 32 of the 44 cases (73%) unsuspected cancers unrelated to the tumor detected at transurethral resection were found in the radical prostatectomy specimen. Of these cancers 87% were nontransition zone tumors. Eight unsuspected cancers were larger than the stage A cancer but only 2 of them were larger than 1 cc. Post-resection serum prostate specific antigen (PSA) levels were elevated with increasing total residual cancer volume in the radical specimen. In 19 of 20 cases with a PSA of greater than 2.5 ng./ml. the total residual cancer volume was more than 0.9 cc, while in 7 of 8 with a PSA of less than 1 ng./ml. total residual tumor volume was lower than 0.4 cc.

Adult

Transrectal ultrasound imaging and ultrasound guided prostate biopsies in the detection of residual carcinoma in clinical stage A carcinoma of the prostate.

Planning treatment for patients diagnosed with stage A prostate cancer by transurethral resection or open enucleation can be difficult. Inability to determine the presence or absence of significant residual disease can result in unnecessary treatment for some individuals and inadequate treatment in others. Transrectal ultrasound imaging and systematic prostate biopsies offer a potential means of evaluating these patients. To determine the rate of residual cancer detection 3 groups of stage A prostate cancer cases were evaluated. Group 1 consisted of 39 patients who underwent radical prostatectomy. Preoperative ultrasound imaging revealed residual cancer in only 24%. Transrectal ultrasound guided systematic biopsies were performed in group 2 (25 patients) and revealed cancer in only 28%. Based on prior morphometric studies of prostatectomy specimens from stage A cases, a modification of the systematic biopsy method, which included anteriorly directed biopsies, was developed and applied to group 3 (47 patients). Cancer was detected in 47% of the patients, and it was detected by additional anterior biopsies alone in 11%.

Adenocarcinoma

Predictive value of contralateral biopsies in unilaterally palpable prostate cancer.

We studied 153 patients with tumors digitally localized to 1 prostatic lobe with transrectal ultrasound and bilateral biopsy. Of these patients 65 (42%) had tumor in the clinically benign lobe as well as the suspicious lobe. These patients had higher serum prostate specific antigen (PSA) levels (27.7 +/- 28.1 versus 14.3 +/- 16.7 ng./ml., p = 0.0001) than those with negative contralateral biopsies. Radical prostatectomy was done in 57 patients; the 25 with positive bilateral biopsies had larger tumors (6.3 +/- 6.0 versus 2.5 +/- 2.4 cc, p = 0.0008) and a much higher likelihood of capsular penetration into the periprostatic fat (72% versus 28%, p = 0.0025) than the 32 with unilaterally positive biopsies. Patients with bilaterally positive biopsies also were more likely to have nodal disease (8% versus 0%), seminal vesicle invasion (20% versus 6%), positive margins (32% versus 19%) and biochemical (PSA) evidence of recurrence (20% versus 3%), although none of these differences was statistically significant. Of the 25 patients with bilaterally positive biopsies 12 (48%) had nonpalpable extension of tumor into the other lobe; adverse findings and outcomes were concentrated in these patients as opposed to the 13 patients in whom small incidental tumors were sampled by biopsy. Finally, 2 of the 25 patients (8%) with bilaterally positive biopsies had a positive surgical margin in the area of the contralateral neurovascular bundle; this was not observed in any of the 32 patients with unilaterally positive biopsies. These findings demonstrate that contralateral negative biopsies in patients with unilaterally palpable disease predict low volume, localized tumor and a negligible likelihood of surgical margin compromise when using a contralateral nerve-sparing approach. Bilaterally positive biopsies suggest larger tumor volume with a greater likelihood of adverse pathological findings and recurrence.

Biopsy

Ultrasensitive radioimmunoassay of prostate-specific antigen.

We describe a modification of the Yang Pros-check radioimmunoassay for prostate-specific antigen (PSA) that increases the analytical sensitivity of the assay approximately threefold (from a working range of 0.3-50 to 0.1-1.2 micrograms/L). It can detect PSA added to zero-concentration diluent (bovine serum albumin solution) at 0.10 microgram/L or added to zero-concentration control female serum at 0.20 microgram/L (P less than 0.05). In 26 patients tested after cystoprostatectomy for bladder cancer (who had normal prostates without cancer on histologic examination), PSA values by this ultrasensitive assay were all less than 0.10 microgram/L. Therefore, we propose this value as the upper limit of the 95% reference interval. In a retrospective study of two patients who developed recurrent prostate cancer, serum PSA values increased above the 0.1 microgram/L detection limit 175 and 581 days before increasing above the 0.3 microgram/L detection limit of the standard Yang assay. This ultrasensitive radioimmunoassay of PSA should prove more useful than current methods for detecting early recurrence of prostate cancer.

Antigens, Neoplasm

[Systematic morphometry of radical prostatectomy samples. A guideline for general practice].

The predictive value of quantitated tumor volume for the prognosis of the individual patient with prostate cancer has been established in analysis of more than 500 radical prostatectomy specimens at Stanford Medical Center. The Stanford technique for detailed tissue sectioning involves considerable time and expense plus computer planimetry. Therefore we have developed two simplified protocols which are suitable to routine diagnostic pathology. Histologic slides of 145 radical prostatectomy specimens, as evaluated by the Stanford technique, were reviewed and a selection of slides was made in a systematic fashion according to two protocols ("bilateral" and "parasagittal"). Tumor volume was estimated manually from this reduced sample of slides by comparing cancer areas to a millimeter grid. The bilateral protocol used an average of 11.7 slides per case (range 8-20), the parasagittal protocol used an average of 8.8 slides per case (range 6-15) versus an average of 26.2 slides per case (range 16-67) by the original Stanford technique. Volume estimates were within +/- 20% of true (computer) volume in 96% and 89% of cases, respectively. A simplified tissue sampling technique can yield accurate cancer volume determinations in radical prostatectomy specimens with reduced time and expense.

Histological Techniques

Culture of prostatic epithelial cells from ultrasound-guided needle biopsies.

A protocol which was developed for the culture of epithelial cells from radical prostatectomy specimens was slightly modified to permit the culture of cells from ultrasound-guided prostatic needle biopsies. The collagenase digestion step of the standard protocol was omitted, and biopsies were simply minced and allowed to attach to collagen-coated dishes in serum-free medium. Cell outgrowths from biopsies were free of fibroblasts, and expression of keratin, prostate specific antigen, and prostatic acid phosphatase was maintained in vitro. The establishment of a bank of frozen cells from primary cultures permitted repetitive studies with individual cell strains, which could be serially passaged and were capable of clonal growth. The ability to derive cultures from biopsies will facilitate the biological characterization of cells from primary prostate tumors of high malignant grade, which are not commonly available from radical prostatectomy specimens.

Acid Phosphatase

Mucinous differentiation in prostatic adenocarcinoma.

Morphologic and histochemical analysis was performed on 33 carcinomas with mucin-secreting areas that were identified among 100 carcinomas from radical prostatectomy specimens. The most common mucin-secreting pattern was Gleason grade 3, which usually showed distinctive luminal distention. The "colloid carcinoma" pattern with mucinous lakes was the only histologic pattern that was unique to mucinous areas. Its frequent association with cribriform Gleason grade 4 carcinoma suggests that it is a variant of grade 4 cancer, whose deviant appearance is a consequence of mucus hypersecretion. Collagenous stromal micronodules, found in 13 cases, are a previously undescribed and distinctive pattern thought to be a stromal reaction to contact with acidic extraluminal mucin. In grade 3 carcinoma, glands that secreted into the stroma rather than the gland lumen accounted for the stromal mucin, which appeared to lead to micronodule formation. In the grade 4 "colloid cancer" pattern, collagenous micronodules sometimes completely obliterated mucinous lakes, isolating residual cribriform glands in a "pseudo-grade 3" pattern. Lectin histochemical staining showed similar sialated and/or sulfated acidic mucin in all cases. Immunohistochemical staining showed downregulation of several differentiation antigens accompanying the alteration to mucinous differentiation.

Adenocarcinoma, Mucinous

Microcarcinoma in the prostate: its association with duct-acinar dysplasia.

In a series of 100 prostatectomy specimens obtained for adenocarcinoma, 107 additional incidental microscopic (less than 0.05 cm3) carcinomas were identified. Their morphologic features including location, histologic grade, and associated premalignant changes were documented. In 51 cases there was strong evidence of transition between microcarcinoma and the premalignant lesion, duct-acinar dysplasia. Invasive cancer was usually related to dysplasia through a characteristic intermediate morphologic stage of transitive glands. These glands were smaller than prostatic ducts; they appeared to arise by budding from dysplastic duct walls and showed the same distinctive lining epithelium. They were distinguished from invasive glands by their pseudo-stratified epithelial lining and by consistent association with a sparse, discontinuous basal cell layer. Cytoplasmic differentiation at the point of junction of invasive cancer with transitive or dysplastic glands was studied by immunohistochemical staining for the differentiation markers prostate-specific antigen and pepsinogen II, and staining for mucin. Markedly reduced cytoplasmic differentiation was common in dysplastic and transitive glands. Invasion often coincided with an abrupt increase in cytoplasmic differentiation with expression of ectopic differentiation products. This sequence of biologic changes should be tested in other carcinomas where the exact point of invasion can be identified.

Adenocarcinoma

Efficacy of transrectal ultrasound for identification of clinically undetected prostate cancer.

A total of 51 patients underwent transrectal ultrasound of the prostate before radical cystoprostatectomy for transitional cell carcinoma of the bladder. Each had a normal prostate by digital rectal examination, no history of prostatic adenocarcinoma and no invasion of the prostate by transitional cell carcinoma. Real-time and step-sectioned ultrasound images were interpreted at the time of sonography and results were compared to pathological examination of the step-sectioned prostate specimen. When adenocarcinoma was identified in the specimen, cancer volume was determined. Positive ultrasound scans consisted of those exhibiting hypoechoic lesions. Hypoechogenicity due to transurethral resection defects, benign hyperplasia, vascular structures or shadowing from calcifications was not considered positive. Of 51 patients 27 (52.9%) exhibited no abnormality on ultrasound and were free of cancer in the prostate specimen, while 8 (15.7%) demonstrated a hypoechoic lesion that was proved to be prostate cancer. Seven patients (13.7%) with normal transrectal ultrasound scans had adenocarcinoma of the prostate, while 9 (17.6%) had lesions on ultrasound but no cancer. Based on these results, transrectal ultrasound has a sensitivity of 53.3% and a specificity of 75%. Further analysis reveals that transrectal ultrasound is more accurate in the detection of cancers of greater than 0.20 cc in volume than those of 0.20 cc or less. Transrectal ultrasound also is more accurate in the detection of peripheral zone than transition zone cancers.

Adult

Adjuvant radiation therapy in patients with detectable prostate specific antigen following radical prostatectomy.

Adjuvant radiation therapy following radical prostatectomy for adenocarcinoma of the prostate was given to 25 patients. Of these patients 8 had microscopic lymph node metastasis, 8 had seminal vesicle invasion without positive lymph nodes, 6 had positive surgical margins and 3 had only capsule penetration. Their only evidence of residual disease was detectable serum prostate specific antigen (PSA) by the Yang assay. A total of 15 patients (60%) had a subsequent decrease in PSA to less than 0.3 ng./ml. and an additional 5 (20%) had a decrease in PSA by more than 50%. Currently 8 patients have no detectable PSA after a median followup of 18 months (17 to 38 months) since initiating radiation therapy. Only 1 of 12 patients with detectable PSA immediately after radical prostatectomy has had a durable response to adjuvant radiation therapy. In contrast 7 of 13 patients with a delayed increase in PSA had a durable response. The ability of adjuvant radiation therapy to eliminate serum PSA in patients with a delayed increase in PSA after radical prostatectomy is encouraging. However, longer followup, including the use of nonradiated control subjects, is needed to assess the ability of adjuvant radiation therapy to control local disease and prolong patient survival.

Adenocarcinoma

Cytostatic effects of suramin on prostate cancer cells cultured from primary tumors.

Suramin is currently undergoing clinical trials as a chemotherapeutic agent for prostate cancer. The effects of suramin on cultured human epithelial cells derived from normal, benign hyperplastic, and malignant prostate tissues were examined. In serum-free medium, suramin inhibited the clonal growth of prostate cells at a half-maximal dose of approximately 10 micrograms/ml. Growth inhibition by suramin was completely reversible even after 24 hours of exposure. In conjunction, suramin did not alter cellular phenotype with regard to expression of keratins and prostate-specific antigens. Although suramin is reportedly an antagonist of growth factor-mediated mitogenesis, ten-fold excesses of growth factors did not appreciably suppress the cytostatic activity of suramin. In comparison to the activities of other possible chemotherapeutic agents, suramin would appear suboptimal because its inhibitory effects are reversible and it does not induce a terminally differentiated cellular phenotype.

Cell Division

Determination of prostate volume by transrectal ultrasound.

Estimation of prostate gland volume with transrectal ultrasound may provide important information in the evaluation of benign and malignant prostatic diseases. To determine the most accurate means of volume estimation 150 patients underwent transrectal ultrasound with 15 separate methods of volume estimation. All patients underwent subsequent radical prostatectomy or cystoprostatectomy. Prostate specimen weights were compared with the results of each volume estimation method. Step-section planimetry, previously assumed to be the most accurate means of volume measurement, exhibited a Pearson correlation coefficient of 0.93. The elliptical volume, widely used as an alternative to planimetry, demonstrated a correlation coefficient of 0.90. The most accurate method to estimate prostate weight (r = 0.94) was a variation of the prolate spheroid formula, expressed as pi/6 (transverse dimension)2 (anteroposterior dimension). When different volume ranges were considered, this prolate spheroid formula provided the closest estimate of weight in glands of less than 40 gm. and those in the 40 to 80 gm. range. The most accurate method to estimate prostates weighing greater than 80 gm. was the formula pi/6 (transverse dimension)3.

Adenocarcinoma