Biomedical subjects

T M Wheeler

Publications and source records attributed to T M Wheeler.

At least 109 records · Page 6Linked to original sources

PubMed1994

Prostate specific antigen and gleason grade: an immunohistochemical study of prostate cancer.

Prostate cancer is histologically heterogeneous as reflected in the 5 patterns of the Gleason grading system. Gleason grade correlates with volume, extent and prognosis. Serum prostate specific antigen (PSA) levels also correlate with tumor volume but the degree to which grade correlates with PSA has not been precisely defined. To quantify this relationship further, we prepared maps of each grade of cancer in 86 radical prostatectomy specimens from patients with clinical stage T2 cancer. The median per cent of the volume of cancer per prostate composed of grade 1 was 0%, while it was 1% for grade 2, 84% for grade 3, 5% for grade 4 and 0% for grade 5. We stained 95 cancer foci (grades 1 to 5) in 40 of these specimens for PSA. The presence and intensity (0 to 3+) of staining in more than 33,000 acini (or cells) correlated inversely with grade (p < 0.0001). Nearly all acini in grade 1 and most in grade 2 stained positive (2 to 3+) for PSA; 87% were positive but with less intensity in grade 3. While many grade 4 (79%) and grade 5 (49%) cells were positive, the intensity of staining was weak. Serum PSA levels correlated with total tumor volume (r = 0.67) but serum PSA levels per cm.3 of cancer decreased with increasing grade (r = -0.24 and p < 0.02). These studies confirm the strong inverse correlation between Gleason grade and the PSA content of prostate cancer. Since more than 85% of grade 3 acini stained for PSA and grade 3 made up the largest portion (84%) of cancer, the predominant contributor to serum PSA levels from prostate cancer was Gleason grade 3. The other grades contribute relatively little to the serum PSA levels either because of the small volume (grades 1 and 2) or the diminished PSA content (grades 4 and 5).

Adult↗

PubMed1994

Heterogeneity of prostate cancer in radical prostatectomy specimens.

OBJECTIVE: To understand the morphologic and spatial relationships of the various grades of prostate cancer, we investigated whether poorly differentiated cancer usually arises within the center of a large, well-differentiated tumor or more often forms the periphery or leading edge of the tumor. METHODS: In a series of one hundred and one completely sectioned whole-mount radical prostatectomy specimens removed from patients with clinical Stage T2 prostate cancer, we mapped the distribution of each of the five Gleason grades and assessed their frequency, proportion, and spatial distribution. RESULTS: The average number of different grades present in our patients was 2.7 (range 1-5). Over 50 percent of the prostates contained at least three different grades of cancer. The number of different Gleason grades present increased significantly with increasing tumor volume (p < 0.0001). Only 10 percent of the index cancers (largest tumor present) were composed of a single grade and these cancers were small (0.02-1.7 cm3). Among cancers with multiple grades, the most common finding (53%) was a high-grade cancer present within the core of a larger, more well-differentiated tumor; however, the opposite pattern, low-grade cancer present within a larger poorly differentiated cancer, was also common (30%) and predominated in very large cancers (> 10 cm3). CONCLUSION: Small prostate cancers are often composed of a single grade, usually Gleason grade 2 or 3. But most palpable cancers contain multiple grades which are arranged in heterogeneous and unpredictable geographic interrelationships.

Adult↗

PubMed1994

Tamm-Horsfall protein in bladder tissue. Morphologic spectrum and clinical significance.

Tamm-Horsfall protein (THP) is a high-molecular-weight glycoprotein synthesized exclusively by the ascending loop of Henle and the distal tubule of normal kidney. In pathologic conditions, THP may accumulate in renal parenchyma, perirenal soft tissue, or renal hilar lymph nodes. Our recent finding of a cystectomy specimen showing large mural deposits of THP prompted a pertinent literature search, which uncovered only a single article in which THP deposition in bladder is briefly mentioned. In the current study, the clinical and morphologic features of THP were studied in 247 consecutive bladder biopsies and 15 cystectomies obtained in a 1-year period. A total of 18 cases were found (an incidence of 6.9%), with cystectomy specimens being much more frequently affected than biopsy specimens (60 versus 3.6%). Most patients were elderly men (45-78 years, with a mean 61 years; a male/female ratio of 16:2). In seven cases, THP appeared as large, "waxy," pale or weakly eosinophilic masses, so characteristic that the diagnosis could be readily made without any special studies. THP in these cases was strongly positive by periodic acid-Schiff, pale blue on Masson's trichrome stain, and ultrastructurally composed of nonbranching 4-nm-wide fibrils arranged in a parallel fashion. In 11 cases, THP appeared as inconspicuous flecks or interconnecting strands of eosinophilic material obscured by a large amount of adjacent fibrinous exudate or necrotic tissue. In these cases, the PAS and trichrome stains were not always helpful in the diagnosis. Immunostaining using an anti-THP antibody clearly identified even small amounts of THP in all 18 cases. This immunostaining was not only sensitive but also specific, giving a negative result for 64 control cases containing such materials as amyloid, fibrin, dense fibrosis, tissue necrosis, and edema fluid, all of which can potentially simulate THP. Although diagnoses for the specimens with THP were variable (nine transitional cell carcinomas, one squamous cell carcinoma, two nephrogenic adenomas, and five cases of cystitis), the areas where THP was deposited in each of these cases invariably showed necrosis, inflammation, fibrinous exudate, ulcer, or crystalline material. The mechanism for THP precipitation is not clear but is probably related to the mucosal changes, including inflammation and necrosis, which is always seen in areas of THP deposition. Follow-up study did not show any bladder abnormalities pertinent to THP deposition. In summary, THP is frequently seen in bladder tissue and most probably represents an incidental finding of morphologic interest but of no clinical significance.

Aged↗

PubMed1994

Detection of microscopic extracapsular extension prior to radical prostatectomy for clinically localized prostate cancer.

OBJECTIVE: To assess better techniques of clinical staging to identify the presence and location of extracapsular extension (ECE) and assist the surgeon in the selection of candidates for resection or preservation of neurovascular bundles during radical prostatectomy. PATIENTS AND METHODS: In a retrospective review of the records of 117 patients with clinically localized (31 T1 and 86 T2) prostate cancer treated with radical prostatectomy the results of digital rectal examination (DRE), real-time transrectal ultrasound (TRUS) and a retrospective review of static films were compared to assess their accuracy in the detection of ECE. The ultrasonic criterion for ECE was bulging or irregularity of the boundary echo adjacent to a hypoechoic lesion. On DRE, the criterion for ECE was palpable bulging of a nodule beyond the normal contour of the prostate. The reference standard was the presence and location of ECE in the whole-mount, serially sectioned radical prostatectomy specimens. RESULTS: Microscopic ECE was present in 64 of the specimens (55%). There was no significant difference between DRE, prospective TRUS and retrospective TRUS in the overall accuracy of detection of ECE. However, when the results of DRE and TRUS were combined (if either was positive the result was considered positive), the positive predictive value (PPV) was 79% and the sensitivity (91%), with the overall accuracy increased significantly (P < 0.05). CONCLUSION: The presence and precise location of microscopic ECE can be determined pre-operatively with reasonable accuracy using real-time ultrasound combined with the results of DRE.

Aged↗

PubMed1994

Clinical relevance of the individual prostate cancer focus.

The course of stage A prostate cancer is difficult to predict because some of the tumors sampled at TURP are histologically "latent" (resembling cancer discovered incidentally at autopsy) and others have the ability to progress clinically. TURP selectively samples cancer in the transition zone, but, as we noted, the pattern of cancer in the TURP was a limited predictor of residual cancer. Furthermore, peripheral zone cancer appeared histologically to have a higher grade, volume for volume, than transition zone cancer and, in our study, was more frequently associated with extraprostatic spread of cancer. Peripheral zone cancer, while sampled in a minority of TURPs (less than 20%), is associated with histological predictors of poor prognosis. In the ploidy study, peripheral zone cancer was sampled in 5 patients, 4 of whom had nondiploid residual cancer in the radical prostatectomy specimen. Three of these 5 had extracapsular extension and 2 had seminal vesicle invasion. The frequent pattern in stage A1 is, therefore, a low-volume, diploid, transition zone cancer in the TURP specimen. In most cases this was associated with one or more small diploid transition zone or peripheral zone cancers in the radical prostatectomy specimen. However, in some cases, a residual nondiploid cancer was present that could eventually cause progression. The pattern of cancer in stage A2 differs from that in stage A1 in that most large transition zone cancers are selected into this stage and some of these are nondiploid. Stage A2, therefore, includes the minority of transition zone cancers that are nondiploid as well as a considerable number of peripheral zone cancers that are nondiploid. In both stages A1 and A2 nondiploid peripheral zone cancers outnumbered nondiploid transition zone cancers. The relationship of tumor volume with ploidy is clearly different for peripheral zone and transition zone cancers. Eight peripheral zone cancers less than 2.0 cc were nondiploid but only 1 transition zone cancer less than 2.0 cc was nondiploid. Furthermore, all peripheral zone cancers greater than 2.0 cc were nondiploid whereas only 50% of transition zone cancers greater than 2.0 cc were nondiploid. There was a significant difference between tumor volume of diploid and nondiploid cancers. Presumably, nondiploid cell lines have a growth advantage and are more poorly differentiated than diploid cancers. Whether DNA ploidy changes occur as a consequence of tumor growth and tumor cell heterogeneity is unclear because of range in volume of tumors studied.(ABSTRACT TRUNCATED AT 400 WORDS)

Humans↗

PubMed1994

The most promising surrogate endpoint biomarkers for screening candidate chemopreventive compounds for prostatic adenocarcinoma in short-term phase II clinical trials.

Surrogate endpoint biomarkers (SEBs) are needed in clinical chemoprevention trials to avoid the excessively long study periods and high costs associated with the use of cancer incidence reduction as an endpoint, particularly with relatively slow-growing tumors such as prostatic adenocarcinoma. SEBs should be directly associated with the evolution of neoplasia, and develop with high frequency in abnormal cells of susceptible individuals. If SEBs can be modified by a particular intervention regimen in short-term studies, the rationale for carrying out long-term studies may be strengthened. The consensus panel identified a small and manageable group of biomarkers measured in tissue or serum as the most promising in prostate cancer chemoprevention, including (1) prostate specific antigen (PSA); (2) morphometric markers, such as nuclear size and roundness; (3) proliferation markers, such as MIB-1 and PCNA; (4) nuclear DNA content (ploidy); (5) oncogene c-erbB-2 (HER-2/neu) expression; (6) angiogenesis; and (7) high-grade prostatic intraepithelial neoplasia (PIN). Information regarding many of these and other biomarkers is limited, calling for further investigation. Also, these factors, chosen chiefly for their proven or proposed utility as prognostic factors, may be less useful as SEBs. It was agreed that concurrent study of numerous markers rather than single markers allows comparison of their relative utility, including assessment of ease of quantitation and the sensitivity, specificity, and positive and negative predictive value.

Anticarcinogenic Agents↗

PubMed1994

Apoptotic index as a biomarker in prostatic intraepithelial neoplasia (PIN) and prostate cancer.

Chemoprevention trials in prostate cancer would involve excessively long follow-up if conventional endpoints of efficacy are used. Prostatic intraepithelial neoplasia (PIN) may be an appropriate surrogate endpoint for monitoring outcome during prostate cancer chemoprevention studies. To address the question of whether PIN could be stratified into "stable" PIN and PIN likely to progress to invasive cancer, we selected patients with a single focus of peripheral zone cancer with ipsilateral and contralateral high-grade PIN. Sixteen patients met these criteria from a series of 550 patients treated by radical prostatectomy. We examined the rate of apoptosis in PIN and prostate cancer tissues by quantifying the number of apoptotic bodies per hundred cells (apoptotic index) on hematoxylin and eosin stained histological sections. Significant differences (ANOVA: p < 0.05) were detected between foci of prostatic intraepithelial neoplasia contralateral to the cancer and the cancer itself. There was no difference in the apoptotic index between a given cancer and a focus of PIN ipsilateral to the tumor in the same section. However, the range of apoptotic indices overlapped in all categories. Apoptotic indices appear to parallel the biological activity of PIN and malignant prostatic tissue, but may be of little benefit when used alone in monitoring the outcome of chemopreventive therapy in an individual patient.

Analysis of Variance↗

PubMed1994

Paraganglia of the prostate. Location, frequency, and differentiation from prostatic adenocarcinoma.

In contrast to paraganglia of the urinary bladder, prostatic paraganglia have been largely unreported. Following the discovery of paraganglia in two separate radical prostatectomy specimens, we reviewed 100 randomly selected radical prostatectomy specimens to document the location and frequency of prostatic paraganglia. Twelve additional paraganglia were identified in eight resections, for a total of 14 paraganglia in 10 cases. Most paraganglia were located in or adjacent to lateral neurovascular bundles and, rarely, in lateral prostatic stroma. The size of paraganglia ranged from 0.1 to 1.7 mm (median 0.9 mm). Paraganglia consisted of clusters of cells in patterns that ranged from lobular to diffuse, usually with a prominent stromal vascular component. The cells contained bland oval nuclei and clear cytoplasm, which was often abundant. Occasionally, larger cells with larger nuclei were present. Immunohistochemical stains for chromogranin, neuron-specific enolase, and synaptophysin were positive; those for prostatic-specific antigen were uniformly negative. In one of our cases, histologic similarity was noted between a paraganglion and an adjacent prostatic adenocarcinoma with a "hypernephroid" pattern. Recognition of prostatic paraganglia, with appropriate immunohistochemical stains when necessary, will obviate the possibility of confusing these structures with prostatic adenocarcinoma.

Adenocarcinoma↗

PubMed1993

Comparison of the pathologic features and DNA ploidy value of prostate cancers detectable by sonography and by palpation.

Ultrasonography of the prostate detects some cancers that are not palpable, but the pathologic features of such cancers have not been well described. Since screening trials consistently find sonography more sensitive (though less specific) than digital rectal examination, nonpalpable cancers that are visible as hypoechoic lesions on ultrasound have been postulated to be early cancers of limited malignant potential and may not require aggressive treatment. To test this hypothesis, we determined the pathologic features and DNA ploidy value of prostate cancers in 63 radical prostatectomy specimens taken from patients with clinical stage T1 (n = 28) and T2 (n = 35) prostate cancer. In 40 patients (63%), the cancer appeared hypoechoic on ultrasound. The median volume of these cancers was 4.19 cm3 (range 0.45-19.22); 80% exhibited extra-capsular extension (ECE); 30% had seminal vesicle invasion (SVI); and 95% were nondiploid by nuclear image analysis (CAS 200 system). In patients with isoechoic cancer, tumor volume was significantly less (median 0.38 cm3) and ECE and SVI occurred less frequently (13% and 0%, respectively). Only seven (30%) had nondiploid tumors. In 35 patients, the tumor was palpable, and the pathologic features and DNA ploidy values (94% nondiploid) of these cancers were similar to those of the tumors that were visible on ultrasound. In seven patients, the cancer was visible by ultrasound but not palpable by digital rectal examination. Median tumor volume was 1.72 cm3 (range 0.45-18.98); four patients (57%) had ECE; one (14%) had SVI, and six (86%) had nondiploid cancers. We conclude that most cancers that appear hypoechoic on ultrasound are clinically important and exhibit aggressive pathologic features. Palpable cancers and sonographically visible cancers are similar and should be staged and treated similarly.

DNA, Neoplasm↗

PubMed1993

The mechanisms and prognostic significance of seminal vesicle involvement by prostate cancer.

To assess the mechanisms and prognostic significance of seminal vesicle involvement (SVI) by prostatic adenocarcinoma, we analyzed 312 radical prostatectomy specimens obtained from patients with T1-T3 prostate cancer. Detailed pathological examination demonstrated three patterns of SVI. Type I involvement was direct spread along the ejaculatory duct complex into the seminal vesicles. Type II involvement was spread outside of the prostate, through the capsule, and then into the seminal vesicle. Type III involvement was characterized by the finding of isolated deposits of cancer in the seminal vesicle with no contiguous primary cancer in the prostate. We found SVI in 64 patients (21%), who have been followed for a mean of 31 months (range 1-101). A defining criterion for progression was clinically apparent local or distant recurrence or a postoperative serum prostate specific antigen (PSA) > or = 0.4 ng/ml (Hybritech). Type I SVI was found in 17 (26%), Type II in 21 (33%), and Type III in 8 (13%) cases. In 18 patients (28%), the pattern of SVI appeared to be a combination of types I and II (categorized as Type I+II). Type III (isolated metastasis) SVI was associated with significantly smaller cancers (median, 3.13 vs. 6.7 cc; p < 0.0005) and fewer positive margins (0 vs. 32%; p = 0.05) than in other types. Type II SVI, with direct extension through the capsule, was associated with a significantly higher risk of lymph node metastasis (8 vs. 33%; p < 0.05). When patients with lymph node metastases were excluded, there was a trend toward a more favorable prognosis (p = 0.09) for patients with type III SVI than with other types. Overall, patients with type III SVI had a progression-free survival rate similar to that of 83 patients with extracapsular extension without SVI. We conclude that the prognostic significance of SVI may not be uniformly ominous; instead, it may depend on the specific mechanism of involvement and the pathologic features of the primary tumor.

Adenocarcinoma↗

PubMed1993

Ultrasonic detection of non-palpable seminal vesicle invasion: a clinicopathological study.

In an effort to identify reliable criteria for detecting seminal vesicle invasion (SVI) with transrectal ultrasonography (TRUS) in patients with clinically localised prostate cancer, we reviewed the pre-operative sonograms in 230 patients who underwent radical retropubic prostatectomy; 49 patients (21%) had pathologically confirmed SVI. Conventional sonographic criteria for SVI (asymmetry, distension, atrophy, abnormal echogenicity and irregularity in outline) were present in 58 patients, but only 16 (28%) had pathologically confirmed SVI. On the basis of the results of a preliminary comparison of radical prostatectomy specimens and TRUS, we had revised our criteria for the recognition of SVI: (1) a hypoechoic lesion at the base of the prostate (within 10 mm of the seminal vesicle); (2) an "adhesion sign" resulting from the loss of the echo reflections from the normal fat plane between the prostate and the seminal vesicle; (3) "posterior convexity" of the seminal vesicles. When we reviewed the 230 sonograms retrospectively, we found a hypoechoic tumour at the base in 70 patients, of whom 37 had SVI (positive predictive value (PPV) 53%). An adhesion sign was found in 16 patients, 12 of whom had SVI (PPV 75%). Posterior convexity was present in 4 patients, all of whom had SVI. If any one of our sonographic signs was present, the overall accuracy (83%), sensitivity (90%) and positive predictive value (51%) were significantly better than with any one of the conventional criteria. Patients with SVI were also more likely to have a high serum prostate specific antigen (PSA) level. The PPV for SVI of a PSA level > or = 10 ng/ml was 38%. If the PSA was > 10 ng/ml and TRUS was positive (> or = 1 of our sonographic criteria), 16 (62%) of 26 patients had SVI. If the PSA was < 10 ng/ml and TRUS was negative, only 3 (3%) of 86 patients had SVI. It was concluded that the conventional criteria for detecting SVI on ultrasonography are not accurate in patients with early stage prostate cancer. There are, however, reliable criteria that predict SVI with reasonable accuracy and these criteria, combined with the serum PSA levels, can stratify patients into those with a low risk and those with a high risk of SVI.

Adult↗

PubMed1992

Detection of residual prostate cancer after radiotherapy by sonographically guided needle biopsy.

Detection of persistent or recurrent prostate cancer by digital rectal examination (DRE) after definitive radiotherapy is difficult. With the availability of transrectal ultrasonography (TRUS), the detection of prostate cancer has improved substantially. Since 1987 we have used TRUS to evaluate the prostate after definitive radiotherapy. A hypoechoic lesion suggestive of cancer was identified in 45 of 56 patients (80%) studied. Sonographically directed transrectal needle biopsies were performed in 27 of these (60%), and 16 (59%) were positive for cancer. The presence of a palpable nodule suggestive of cancer (present in 7 patients) was not predictive of a positive biopsy specimen. In 14 patients ultrasound-guided and digitally-guided biopsies were performed at the same time; 8 (57%) of the ultrasound-guided biopsy specimens were positive compared with only 4 (29%) of the digitally-guided biopsy specimens. In all 7 patients with an elevated serum level of prostate-specific antigen (PSA) an ultrasound-guided biopsy result was positive. Random biopsies of sonographically normal (isoechoic) areas of the prostate were performed in 8 patients, but only 2 specimens (25%) were positive for cancer. Ultrasound-guided transrectal biopsy of hypoechoic lesions was a safe and effective technique for identifying residual cancer in the irradiated prostate, regardless of the palpable findings. In the presence of an elevated PSA level, such biopsies invariably identified residual cancer. The use of TRUS, ultrasound-guided biopsy, and the measurement of PSA, in addition to DRE, may aid in the detection of residual cancer after definitive radiotherapy.

Antigens, Neoplasm↗

PubMed1992

Sonographic monitoring of prostate cancer after definitive radiotherapy.

Thirty patients who had transrectal ultrasonography before and after definitive radiotherapy were studied retrospectively to determine the effects of radiotherapy on the sonographic appearance of prostate cancer. Before therapy one or more discrete hypoechoic areas characteristic of cancer were present in 29 (97%) of the patients. In 10 patients (34%) the hypoechoic areas disappeared six to twenty-seven months (mean 11.4) after radiotherapy, but in 3 of these the hypoechoic lesion subsequently reappeared. Six months after radiotherapy a hypoechoic lesion could still be seen in the original area in 79 percent of 19 patients studied. Sonography showed persistent lesions in 65 percent of 17 patients at twelve months, in 79 percent of 14 patients at twenty-four months, and in 75 percent of 8 patients at thirty-six months. In 9 of the 29 patients (31%), there was a measurable increase in the size of the lesion, but overall, the size (maximum diameter) of the hypoechoic lesion had decreased by a mean of 41 percent when evaluated twelve months after radiotherapy. Previous studies from our laboratory have shown that persistent prostate cancer after definitive radiotherapy retains its hypoechoic appearance, and this study indicates that these characteristic hypoechoic lesions can be monitored by transrectal ultrasound.

Aged↗

PubMed1992

Unusual hyperechoic appearance of prostate cancer on transrectal ultrasonography.

A series of 157 patients with prostate cancer underwent transrectal ultrasonography prior to radical prostatectomy. In 112 patients (71.3%) the tumours appeared hypoechoic relative to the echo pattern of the normal peripheral zone; in 43 (27.4%) they appeared isoechoic, and in only 2 (1.3%) did they appear purely or predominantly hyperechoic. These 2 hyperechoic tumours were unusual ductal adenocarcinomas with central necrosis and dystrophic calcification within solid tumour nests, a pattern similar to that of comedo-carcinoma of the breast. Calcification within prostate cancer was found in 4 of the 157 radical prostatectomy specimens, including 2 other hypoechoic cancers which contained intraluminal or psammomatous calcification. Although the most common sonographic appearance of localised prostate cancer is hypoechoic, a predominantly hyperechoic pattern is seen occasionally and suggests the presence of a high grade ductal adenocarcinoma.

Aged↗

PubMed1991

DNA ploidy by image analysis of individual foci of prostate cancer: a preliminary report.

The malignant potential of an individual focus of prostate cancer is difficult to determine. The established pathological features associated with malignant behavior include tumor volume, grade, and invasiveness (local extension or metastasis). We used nuclear image analysis to determine the DNA ploidy value of each cancer in a series of 30 radical prostatectomy specimens from patients with early stage prostate cancer in order to further explore the malignant potential of each separate focus of cancer. The volume, grade, invasiveness (extracapsular extension or seminal vesicle invasion), and zone of origin of each of the 63 separate cancers were determined. The DNA ploidy histogram of 200 cancer cells was compared with 50 normal epithelial nuclei on the same Feulgen-stained tissue sections. Sixty % of the cancers were diploid, and 40% were nondiploid. Ploidy correlated with volume and grade. All cancers less than 0.02 cm3 were diploid; 26% of foci 0.02 to 2.0 cm3 and 82% of foci greater than 2.0 cm3 were nondiploid. There were 16 cancers of transition zone origin ranging in size from 0.02 to 12.1 cm3 and only one (7.3 cm3) was nondiploid. There were 47 cancers of peripheral zone origin (range, 0.01 to 18.98) and 24 (51%) were nondiploid. Eight of the 24 nondiploid cancers were small (less than 1.0 cm3), and two were only 0.03 cm3. We conclude that some very small prostate cancers are nondiploid and that progression of prostate cancer is not a function of volume alone, whereby tumors only acquire full malignant potential at large volumes. Cancers of peripheral zone origin acquire a nondiploid cell population at a smaller volume than do cancers of transition zone origin, further supporting a fundamental difference between cancers arising in these zones.

Cell Differentiation↗

PubMed1991

Transrectal ultrasonography in stage A prostate cancer: detection of residual tumor after transurethral resection of prostate.

To evaluate the ability of transrectal ultrasonography to detect residual cancer in the prostate gland after transurethral resection in patients with stage A cancer, we studied 38 patients with stage A disease (11 stage A1 and 27 stage A2) in whom transrectal ultrasonography was done at least 3 weeks after resection. Each patient underwent radical prostatectomy, and residual cancer was present in 97% of the specimens (peripheral zone cancer in 95% and transition zone cancer in 61%). At sonography we identified hypoechoic areas suggestive of cancer in 10 patients (26%). In the pathological specimen residual cancer was present at the hypoechoic area in 8 of these cases (positive predictive value 80%). In a retrospective review of the sonograms we identified 25 hypoechoic lesions greater than 5 mm. in diameter, including 15 that corresponded to cancer in the radical prostatectomy specimens (positive predictive value 60%). Granulomas due to the transurethral resection were found in 92% of the radical prostatectomy specimens but none appeared hypoechoic on ultrasound. A total of 103 separate cancers was identified in the whole mount step sections of the radical prostatectomy specimens (2.7 cancers per patient). Of the 103 separate cancers 54 were less than 0.1 cc in volume and none of these could be identified in the retrospective review of the sonograms, 37 were 0.1 to 1.0 cc and 5 of these (14%) appeared hypoechoic, and 12 were greater than 1.0 cc and 10 of these (83%) appeared hypoechoic. Hypoechoic lesions greater than 5 mm. in diameter in the transition zone proved to be cancer in 47% of the cases, while 88% of similar lesions in the peripheral zone proved to be cancer. We conclude that suspicious-appearing hypoechoic lesions suggestive of cancer, whether in the peripheral zone or the transition zone, should be biopsied before expectant management of stage A prostate cancer is considered. Transrectal ultrasonography is useful for restaging after transurethral resection and for evaluating the extent of residual cancer in stages A1 and A2 prostate cancer.

Aged↗

PubMed1991

A comparison of the morphological features of cancer arising in the transition zone and in the peripheral zone of the prostate.

To determine the characteristics of transition zone and peripheral zone prostate cancer, we examined a series of 42 stage A and 54 stage B radical prostatectomy specimens with particular attention to the number of separate foci of cancer, zone of origin, volume and grade of each focus, and presence of severe intraductal dysplasia (high grade prostatic intraepithelial neoplasia), extra-capsular extension and seminal vesicle invasion associated with cancer in each zone. We found that there were fundamental differences between transition zone and peripheral zone cancers, and that the features that characterize these tumors were apparent in stages A and B disease. Although the total tumor burden was similar in stages A (3.98 cc) and B (4.56 cc) disease, stage A cancer tended to be multifocal (3.1 tumors per prostate) and more diffuse. While 81% of stage A prostate specimens contained a tumor of transition zone origin and 93% had cancer of peripheral zone origin, transurethral resection of the prostate sampled a transition zone cancer in 77% and a peripheral zone cancer in 31% (8% had both types). Stage B cancer tended to be more focal (2.3 cancers per prostate). All stage B prostate specimens contained a peripheral zone cancer and 43% had a transition zone cancer as well. In only 1 stage B cancer patient was the transition zone tumor the palpable or index cancer. In stages A and B disease, peripheral zone tumors were less well differentiated (median Gleason sum 6 and 7) than transition zone tumors (5 and 5, respectively) and more likely to extend through the capsule (44% versus 11%). Seminal vesicle invasion arose from 19% of the peripheral zone but none of the transition zone cancers. Peripheral zone tumors were almost always (93%) associated with high grade prostatic intraepithelial neoplasia, while none of the transition zone cancers was so associated. For peripheral zone disease there was a moderate correlation between volume and grade (tau = 0.46, p less than 0.001) so that the larger the tumor the higher the Gleason sum but within transition zone disease this correlation was poor (tau = 0.23) and not statistically significant (p greater than 0.05). Extracapsular extension occurred at a smaller volume with peripheral zone cancer (mean 3.86, minimum 0.06 cc) than transition zone cancer (mean 4.98, minimum 0.39 cc). Cancer that arises in the transition zone appears to have a different histogenesis, is associated with more favorable pathological features and may have less malignant potential than tumors that arise in the peripheral zone.

Aged↗

PubMed1991

The distribution of residual cancer in radical prostatectomy specimens in stage A prostate cancer.

To assess the volume and distribution of residual cancer after transurethral resection of the prostate in stage A cancer patients 42 step-sectioned radical prostatectomy specimens were examined, and the volume, location, grade and extracapsular extension of the residual tumor were recorded. A total of 13 patients had stage A1 tumors (5% or less tumor in the transurethral resection specimen and a Gleason sum of 7 or less) and 29 had stage A2 disease. Residual cancer was present in the radical prostatectomy specimen in 41 patients (98%) with a mean volume of 1.28 cc. The location of residual cancer, that is multifocal (76%), peripheral (81%) and distal to the verumontanum (66%), makes complete removal or even identification of residual tumor (restaging) by repeat transurethral resection improbable. Of the stage A1 cancer patients 4 (30%) had more than 1 cc residual tumor volume, extracapsular extension or seminal vesicle invasion. On the other hand, 14 of the stage A2 cancer patients (48%) had less than 1 cc residual tumor completely confined to the gland. Foci of residual cancer were found in the transition zone in 67% and in the peripheral zone in 90% of the patients. The grade of the residual peripheral zone cancer was significantly higher than that of the transition zone cancer in the same gland (p = 0.0004). Eight of 13 instances of extracapsular extension and all 5 of seminal vesicle invasion were directly attributable to peripheral zone cancer. These observations imply that the greatest threat to patients with stage A prostate cancer may be a separate, associated cancer in the peripheral zone rather than the primary transition zone cancer incidentally removed at transurethral resection.

Carcinoma↗