Steven R. Potter

THE PATHOLOGICAL INTERPRETATION AND SIGNIFICANCE OF PROSTATE NEEDLE BIOPSY FINDINGS: IMPLICATIONS AND CURRENT CONTROVERSIES

PURPOSE The widespread use of prostate specific antigen testing and digital rectal examination has lead to the increasing application of prostate needle biopsy. A larger proportion of men undergoing biopsy have small foci of cancer, which coupled with the overall increase in needle biopsy has led to a surge in the number of equivocal biopsy specimens interpreted. MATERIALS AND METHODS We reviewed the literature with an overview of the topic of prostate needle biopsy pathology results with an emphasis on current controversies. RESULTS The diagnosis rendered on prostate needle biopsy pay be placed into 4 major categories, including 1) benign, 2) prostatic intraepithelial neoplasia, 3) atypical and suspicious for cancer, and 4) prostate cancer. Prostatic intraepithelial neoplasia or a diagnosis of atypical and suspicious for cancer mandates re-biopsy in a search for occult prostate cancer. Biopsy findings, including the location of positive cores, may help to guide re-biopsy strategies. Prostate cancer on needle biopsy may be evaluated by numerous techniques of quantifying tumor extent, Gleason score and perineural invasion. These modalities may help clinicians to assess the risk of extraprostatic disease and progression likelihood, and help men with prostate cancer choose among therapeutic options. CONCLUSIONS The pathology reports returned on needle biopsy specimens may provide a wealth of information beyond the simple presence or absence of prostate cancer that may aid clinicians in patient treatment and counseling.

Adenocarcinoma of the prostate invading the seminal vesicle: prognostic stratification based on pathologic parameters

OBJECTIVES To stratify the prognosis of lymph node-negative, seminal vesicle-positive tumors in men with prostate cancer after radical retropubic prostatectomy. METHODS Sixty cases were analyzed for multiple parameters and correlated with postoperative biochemical (prostate-specific antigen) progression. Variables included Gleason score, primary Gleason pattern, percentage of Gleason pattern 4, any presence of Gleason pattern 5, method of seminal vesicle invasion (SVI), margin positivity, SVI extent, SVI bilaterality, vascular invasion, extent of extraprostatic extension, length of tumor extending along the seminal vesicles, presence of intraductal carcinoma within the prostate, bladder neck margin positivity, and tumor volume. RESULTS We were able to stratify the prognosis based on the combination of a variation of the Gleason score and margin status and vascular invasion status. Using this stratification, a few patients had an excellent long-term prognosis, with most patients split into two groups, one experiencing rapid and the other slower progression. CONCLUSIONS SVI is not associated with a uniformly poor prognosis. Rather, tumors can be substratified by pathologic parameters into groups with differing prognoses based on routine histologic examination.

Ductal adenocarcinoma of the prostate diagnosed on needle biopsy: correlation with clinical and radical prostatectomy findings and progression.

Ductal adenocarcinoma of the prostate, previously referred to as endometrioid cancer, is typically diagnosed on transurethral resection. When treated by radical prostatectomy (RP), it pursues a more aggressive clinical course than usual acinar prostate cancer does. The significance of prostate cancer with ductal features found on needle biopsies from the peripheral zone is unknown. We reviewed 58 prostate needle biopsy cases with ductal adenocarcinoma for which we were able to obtain clinical information. Patients had a mean age of 69 years (range, 50-89 years) and had a wide range of levels of serum prostate-specific antigen (median, 7.9 ng/mL) and clinical stages. Six (10%) had metastases at the time of diagnosis. Cribriform or papillary structures or a mixture of the two patterns were seen in 86% of cases, whereas in the remaining cases, discrete glands composed of tall columnar cells were present. Stromal fibrosis accompanied the ductal carcinoma in 67% of the cases. A coexisting acinar carcinoma component was identified in 48% of the biopsy specimens. On biopsy, the ductal component composed a mean of 82% of the tumor. Of the 20 tumors treated by RP, 63% had extraprostatic spread of tumor and 20% had positive margins. Two (10%) cases showed seminal vesicle invasion, but none had lymph node metastases. The number of positive needle cores correlated with RP margin status (p<0.004) and with likelihood of clinical progression (p<0.02), but not with organ-confined status. Tumor volume calculated on the 11 extensively sampled RPs ranged from 0.15 cm3 to 20.3 mL (mean, 2.8 cm3). Two years after therapy, the actuarial risk of progression was between 34% (RP patients) and 42% (all patients). A shortened average time to progression was observed relative to a previous study group of men with acinar carcinoma. Serum prostate-specific antigen levels correlated with neither RP organ-confined status nor tumor volume. We conclude that prostatic ductal adenocarcinoma seen on needle biopsy implies more advanced cancer with a shortened time to progression.

PLAIN ABDOMINAL X-RAY VERSUS COMPUTERIZED TOMOGRAPHY SCREENING: SENSITIVITY FOR STONE LOCALIZATION AFTER NONENHANCED SPIRAL COMPUTERIZED TOMOGRAPHY

PURPOSE Urolithiasis followup with plain abdominal x-ray requires adequate visualization of the calculus on the initial x-ray or computerized tomography (CT) study. We compared the sensitivity of plain abdominal x-ray versus CT for stone localization after positive nonenhanced spiral CT. MATERIALS AND METHODS We evaluated 46 consecutive nonenhanced spiral CT studies positive for upper urinary tract lithiasis for which concurrent plain abdominal x-rays were available. X-ray and CT studies were compared for the ability to visualize retrospectively a stone given its location by CT. A consensus of 1 radiologist and 3 urologists was reached in each case. Cross-sectional stone size and maximum length were measured on plain abdominal x-ray. RESULTS Plain abdominal x-ray and scout CT had 48% (22 of 46 cases) and 17% (8 of 46) sensitivity, respectively, for detecting the index stone (p <0.00004). Of the 39 stones overall visualized on plain abdominal x-ray only 19 (49%) were visualized on scout CT. Mean cross-sectional area and length of the stones on scout CT were 0.34 cm.2 (approximately 6 x 5.5 mm.) and 6. 5 mm., respectively, while the average size of those missed was 0.11 cm.2 (approximately 4 x 3 mm.) and 3.6 mm. The mean size differences in the groups were highly significant (p <0.0009). CONCLUSIONS Plain abdominal x-ray is more sensitive than scout CT for detecting radiopaque nephrolithiasis. Of the stones visible on plain abdominal x-ray 51% were not seen on CT. To facilitate outpatient clinic followup of patients with calculi plain abdominal x-ray should be performed when a stone is not clearly visible on scout CT.

GENETICALLY ENGINEERED NEURAL NETWORKS FOR PREDICTING PROSTATE CANCER PROGRESSION AFTER RADICAL PROSTATECTOMY

OBJECTIVES To use pathologic, morphometric, DNA ploidy, and clinical data to develop and test a genetically engineered neural network (GENN) for the prediction of biochemical (prostate-specific antigen [PSA]) progression after radical prostatectomy in a select group of men with clinically localized prostate cancer. METHODS Two hundred fourteen men who underwent anatomic radical retropubic prostatectomy for clinically localized prostate cancer were selected on the basis of adequate follow-up, pathologic criteria indicating an intermediate risk of progression, and availability of archival tissue. The median age was 58.9 years (range 40 to 87). Men with Gleason score 5 to 7 and clinical Stage T1b-T2c tumors were included. Follow-up was a median of 9.5 years. Three GENNs were developed using pathologic findings (Gleason score, extraprostatic extension, surgical margin status), age, quantitative nuclear grade (QNG), and DNA ploidy. These networks were developed using three randomly selected training (n = 136) and testing (n = 35) sets. Different variable subsets were compared for the ability to maximize prediction of progression. Both standard logistic regression and Cox regression analyses were used concurrently to calculate progression risk. RESULTS Biochemical (PSA) progression occurred in 84 men (40%), with a median time to progression of 48 months (range 1 to 168). GENN models were trained using inputs consisting of (a) pathologic features and patient age; (b) QNG and DNA ploidy; and (c) all variables combined. These GENN models achieved an average accuracy of 74.4%, 63.1 %, and 73.5%, respectively, for the prediction of progression in the training sets. In the testing sets, the three GENN models had an accuracy of 74.3%, 80.0%, and 78.1%, respectively. CONCLUSIONS The GENN models developed show promise in predicting progression in select groups of men after radical prostatectomy. Neural networks using QNG and DNA ploidy as input variables performed as well as networks using Gleason score and staging information. All GENN models were superior to logistic regression modeling and to Cox regression analysis in prediction of PSA progression. The development of models using improved input variables and imaging systems in larger, well-characterized patient groups with long-term follow-up is ongoing.

Age, prostate-specific antigen, and digital rectal examination as determinants of the probability of having prostate cancer.

OBJECTIVES The decision to perform prostate biopsy has traditionally been based on an abnormal prostate-specific antigen (PSA) level or abnormal digital rectal examination (DRE) findings. For example, a 60-year-old man with a benign DRE and PSA level of 4.1 ng/mL would be counseled for biopsy, and the same man with a PSA level of 3.9 ng/mL might be counseled against biopsy. However, the difference in these PSA levels and in the likelihood of these two men having prostate cancer is not significant. We constructed a probability nomogram for the likelihood of detecting prostate cancer, thus aiding in the decision of whether to perform a prostate biopsy. METHODS Using multivariate logistic regression analysis and data from 2054 men (mean age 64 years) participating in the Tyrol Screening Project between January 9, 1993 and January 9, 1997, patient age, PSA level, and DRE findings were analyzed for their ability to determine the likelihood of finding prostate cancer on transrectal ultrasound-guided biopsy. RESULTS DRE was suspicious in 278 men (13.5%). Overall, 498 (24.5%) of 2054 men biopsied had prostate cancer. The probability of discovering cancer on biopsy was calculated using patient age, DRE findings, and PSA level. CONCLUSIONS DRE status had a large influence on the likelihood of positive biopsy across all PSA and age ranges. A combination of PSA, DRE result, and age better defined the probability of a positive biopsy than any factor alone. Using this nomogram, the decision to proceed with or defer prostate biopsy can be based on an actual probability of discovering prostate cancer rather than a single PSA-based cutpoint. These data may aid physicians and patients in decision-making.

Laparoscopic ileal conduit : Five-year follow-up

OBJECTIVES To report the techniques used for intracorporeal laparoscopic construction of an ileal conduit urinary diversion and long-term patient follow-up after this procedure. METHODS A 28-year-old man with cerebral palsy, a neurogenic bladder, and voiding dysfunction was referred for definitive management of his urinary tract after several episodes of pyelonephritis. A conduit urinary diversion was performed using a 5-port, transabdominal approach. An appropriate length of ileum was used for diversion, and ureterointestinal anastomoses were performed using a modified Bricker technique. All aspects of the procedure were performed intracorporeally, including isolation of conduit, bowel reanastomosis, ureteral mobilization, and ureterointestinal anastomosis. A 12-mm port site was enlarged and used as the stoma, which was constructed in routine fashion. RESULTS Five years after surgery, this patient had normal and stable renal function, with a serum creatinine of 0.8 mg/dL. Serial imaging studies continued to reveal prompt and symmetric renal function and no evidence of obstruction or reflux. CONCLUSIONS Laparoscopic ileal conduit construction is feasible and can provide durable results. Although technically challenging, ongoing technical refinements will make performance of reconstructive laparoscopy more widely applicable. Larger series with substantial follow-up will help illuminate the place of laparoscopic noncontinent urinary diversion in the surgical armamentarium.

ISOLATED LOCAL RECURRENCE IS RARE AFTER RADICAL PROSTATECTOMY IN MEN WITH GLEASON 7 PROSTATE CANCER AND POSITIVE SURGICAL MARGINS: THERAPEUTIC IMPLICATIONS

PURPOSE We determined whether the high biochemical failure rate in men with Gleason score 7 disease and positive surgical margins after radical retropubic prostatectomy is secondary to distant metastasis or to local tumor recurrence that could be eliminated by immediate adjuvant radiation therapy. MATERIALS AND METHODS Between 1982 and 1997, 112 men with Gleason score 7 disease and positive surgical margins but no seminal vesicle or lymph node involvement underwent radical retropubic prostatectomy without immediate adjuvant radiation or hormonal therapy. Median followup was 8 years (range 1 to 16) and 45 men (40%) were followed 10 years or more. Kaplan-Meier actuarial survival estimates were used to determine the actuarial 5 and 10-year post-prostatectomy, and 5-year post-radiation recurrence rates. RESULTS The actuarial 5 and 10-year post-prostatectomy biochemical, local and distant recurrence rates were 40% and 52%, 6% and 6%, and 7% and 16%, respectively. For 20 men who received radiation therapy for isolated prostate specific antigen elevation actuarial 5-year post-radiation biochemical recurrence-free rate was 34%. For 5 men who received radiation therapy for local recurrence actuarial 5-year post-radiation biochemical recurrence-free rate was 20%. CONCLUSIONS Isolated clinical local recurrence is rare during long-term followup of men with Gleason score 7 disease and positive surgical margins at radical prostatectomy. Radiation therapy given at prostate specific antigen elevation poorly controlled the disease. Because patients with biochemical failure rarely had local recurrence at long-term followup, they most likely harbored subclinical distant metastasis. These data suggest that immediate adjuvant radiation therapy will not have a major impact on outcome because most men with Gleason score 7 disease and positive surgical margins in whom treatment fails most likely had distant metastasis at surgery. To improve the outcome in cases of Gleason score 7 disease and positive surgical margins a systemic approach to adjuvant therapy is necessary.

Urinary Stone Size: Comparison of Abdominal Plain Radiography and Noncontrast CT Measurements

BACKGROUND AND PURPOSE To compare urinary stone size as measured by abdominal plain radiography (AXR) with stone size as measured by noncontrast three-dimensional spiral CT in patients with acute renal colic. PATIENTS AND METHODS Patients presenting to the emergency room of a single institution with urinary stones that were visible on both AXR and noncontrast spiral CT were identified. Two radiologists blinded to the clinical outcomes separately and randomly reviewed all films and measured maximum longitudinal (craniocaudal) and transverse (anteroposterior) stone diameters. The two-tailed paired Students t-test was used to compare the sizes of each stone on AXR and CT. RESULTS Over a 1-year period, 22 patients were identified with a total of 31 urinary stones visible on both AXR and CT. Nineteen stones were located in the kidney, three in the midureter, and nine in the distal ureter. The mean stone size by AXR was 6.1 mm (range 2-13 mm; SD +/- 1.95) in the longitudinal axis and 5.3 mm (range 2-11 mm; SD +/- 1.50) in the transverse axis. The mean stone size by CT was 6.9 mm (range 3-12 mm; SD +/- 1.95) in the longitudinal axis and 6.1 mm (range 2-11 mm; SD +/- 1.50) in the transverse. The differences between AXR and CT measurements did not attain significance in either the longitudinal (p = 0.67) or the transverse (p = 0.25) axis. CONCLUSIONS A CT scan provides estimates of stone size that are consistently greater than those of AXR in both the longitudinal and transverse axes. However, for stones between 2 and 13 mm in maximum diameter, these differences do not attain significance. In patients with a history of radiopaque stones in this size range, therefore, AXR may provide useful size data for clinical decision-making without concern about significant disparities between the two modalities. As AXRs are more expeditiously obtained, incur less direct costs, and expose patients to significantly lower doses of radiation than CT scans, they remain a useful adjunctive study in the work-up of nephrolithiasis.

In vivo measurement of tumor conductiveness with the magnetic bioimpedance method

A noninvasive electromagnetic method has been developed that can effectively measure the in-vivo conductivity difference between rat tumor lines having a low and high metastatic potential. These tumor lines are used in the study of human prostate tumor.