Prospective study of correlations between biopsy-detected high grade prostatic intraepithelial neoplasia, serum prostate specific antigen concentration, and race.

BACKGROUND: High grade prostatic intraepithelial neoplasia (HGPIN), a premalignant lesion of the prostate gland, is more common in black men than in white men. The influence of HGPIN on the serum prostate specific antigen (PSA) concentration is controversial, and correlations between HGPIN and PSA in black men and white men have not been investigated. METHODS: Between January 1992 and December 1998, 411 black men and 639 white men with suspected prostate carcinoma underwent an initial benign prostate biopsy at a single medical center. The presence or absence of HGPIN in the biopsy specimens was determined by one uropathologist. RESULTS: HGPIN was identified in 8.9% of the specimens. When stratified by PSA concentration (< 4.0 ng/mL, 4.0-9.9 ng/mL, and > or = 10.0 ng/mL), HGPIN was associated with an increased PSA concentration only among men with PSA concentrations < 4.0 ng/mL (P = 0.01). The prevalence of HGPIN in the black and white patients was 13.4% and 5.9%, respectively (P < 0.0001), and was significantly greater in black men than in white men with PSA concentrations < 4.0 ng/mL (P = 0.002). Among the patients with PSA concentrations < 4.0 ng/mL, black race was an independent predictor of an increased PSA concentration when adjusted for patient age, prostate volume, and the presence or absence of HGPIN (P = 0.03). CONCLUSIONS: HGPIN is more common in black men than in white men and may produce an increase in the PSA concentration. However, racial differences in the prevalence of HGPIN may not contribute to racial differences in PSA concentrations among men with no clinical or histologic evidence of carcinoma.

Prostate cancer detection in Black and White men with abnormal digital rectal examination and prostate specific antigen less then 4 ng./ml.

PURPOSE: Prostate cancer is more common in black than in white American men. Experience in a longitudinal prostate cancer screening program implies that cancer detection is greater in black than in white men with an abnormal digital rectal examination and prostate specific antigen (PSA) less than 4 ng./ml. We investigated potential racial differences in cancer detection in men treated in clinical practice who had an abnormal digital rectal examination and PSA less than 4 ng./ml. MATERIALS AND METHODS: Between January 1992 and December 1999 prostate biopsy was done at a Veterans Affairs Medical Center in 179 black and 357 white men with an abnormal digital rectal examination, PSA less than 4 ng./ml. and no history of prostate surgery. Significant racial differences in demographic and clinical parameters were limited to PSA, which was higher in black men (p = 0.01). RESULTS: Cancer was detected in 38 black (21%) and 65 white (18%) men (p = 0.42). There were no significant racial differences in the PSA adjusted cancer detection rate or in the Gleason score of detected disease. In men with PSA less than 1.0, 1.0 to 1.9, 2.0 to 2.9 and 3.0 to 3.9 ng./ml. the detection rate was 4%, 15%, 27% and 29%, respectively. CONCLUSIONS: In clinical practice prostate cancer detection appears to be equivalent in black and white men when an abnormal digital rectal examination is the only indication of malignancy.

The altered structure of renal papillary outflow tracts in obesity.

Weight gain is associated with an expanded renal medullary interstitium in humans and in animal models of obesity. In this study, the consequence of obesity and this expanded matrix on renal papillary structure was examined in 15 obese rabbits fed a high fat diet for 8-12 weeks compared to 21 rabbits fed a standard diet. When examined under a dissecting microscope, the tips of the renal papillae from formalin-fixed, methylene blue-stained kidneys showed patent ducts of Bellini in 5 of 5 instances from 2 lean rabbits, but in only 2 out of 12 ducts from 3 obese rabbits. The ostia of the remaining ducts were significantly distended (205 +/- 42 microns versus 56 +/- 8 microns) and occupied by lightly staining granular material. When examined with scanning electron microscopy, all ducts were patent in lean rabbits (6 ducts in 4 rabbits, averaging 104 +/- 12 microns across), whereas only 6 of 11 ducts were patent in papillae from 4 obese rabbits. Renal medullary parenchymal tissue appeared at the openings of the remaining 5 ducts of Bellini in the 4 rabbits. Not only were these 5 ducts significantly distended by the interstitial material (with openings averaging 248 +/- 56 microns across), but the associated collecting ducts were dilated relative to control (100 +/- 15 microns versus 75 +/- 7 microns). Since the ducts of Bellini are the only renal openings that are not corsetted by a fibrous capsule, the authors speculate that the expanded medullary interstitium and increased renal sinus lipid partially obstruct renal outflow and elevate renal interstitial hydrostatic pressure in obesity, causing a prolapse of parenchymal contents, further obstructing urine outflow and leading to distention of the collecting ducts and ducts of Bellini.

Distribution of renal medullary hyaluronan in lean and obese rabbits.

BACKGROUND: Obese individuals have an expanded interstitium in the renal inner medulla (IM), which stains positively with periodic acid-Schiff and Alcian blue. In obese dogs, the IM is also expanded, with hyaluronan (HA) content being 2.4 times control. METHODS: We determined the anatomic pattern of renal HA deposition following weight gain, using an animal model of obesity consisting of young rabbits (N = 10), representing animals entering into the study, lean rabbits (N = 19), fed a control diet, and obese rabbits (N = 19), fed a high-fat diet (15% fat, by fortifying with corn oil and lard, in a ratio of 2:1) for two to three months. Tissue was papain digested, and HA was recovered in a phosphate or a Tris buffer and detected by an indirect immunoabsorbent competition assay. RESULTS: Rabbits fed a high-fat diet for 8 to 12 weeks gained weight (37%) and became mildly hypertensive (10 mm Hg). In lean rabbits, HA was low in the renal cortex (6 +/- 30 microg/g tissue), increased steadily across the outer medulla (OM; 79 +/- 28 microg/g tissue) and was uniformly high in the IM (192 +/- 28 microg/g tissue) when recovered in a Tris buffer; these levels of tissue HA did not change during the three-month period of dietary intervention. In obese rabbits, the renal medullary interstitium was expanded and stained intensely with periodic acid Schiff and Alcian blue, and tissue HA was elevated in the IM (448 +/- 25 microg/g tissue) but not the cortex (5 +/- 25 microg/g tissue) or the OM (85 +/- 25 microg/g tissue). The significant difference was due to those IM samples taken from the renal papilla; IM samples from the body of the kidney did not significantly differ among the lean, obese, and young rabbits. CONCLUSION: The elevated renal HA associated with weight gain is limited to the IM and occurs most consistently in the papilla, which is the region of the kidney that is most vulnerable to distention caused by elevated renal interstitial hydrostatic pressure.

Predictors of first repeat biopsy cancer detection with suspected local stage prostate cancer.

PURPOSE: We determine demographic and tumor related predictors of repeat biopsy cancer detection in men with suspected stage T1c-2 prostate cancer. MATERIALS AND METHODS: The study population included 298 consecutive men with suspected stage T1c-2 prostate cancer who had a benign prostate biopsy at 1 institution between January 1, 1992 and April 1, 1999 and underwent 1 repeat biopsy. Mean age plus or minus standard deviation was 66.8+/-6.7 years for 133 black (55%) and 165 white (45%) patients. Clinical measures included determination of high grade prostatic intraepithelial neoplasia in benign biopsy specimens, Gleason score of malignant biopsy specimens, prostate specific antigen (PSA), PSA density, annualized interbiopsy PSA change, percent free PSA (201 cases) and PSA velocity (171). RESULTS: Cancer was detected on repeat biopsy in 80 cases (27%). Significant differences between patients with benign and malignant repeat biopsies included age (p = 0.001), PSA density (p = 0.0001), percent free PSA (p = 0.0001) and PSA velocity (p = 0.009). High grade prostatic intraepithelial neoplasia in an initial benign biopsy was not predictive of cancer in repeat biopsy (p = 0.12). Multiple logistic regression analysis of all cases showed that age (p = 0.002) and PSA density (p = 0.0002) were independent predictors of cancer. Subset multiple logistic regression analysis modeled with age, PSA density and percent free PSA demonstrated that age (p = 0.002) and percent free PSA (p = 0.0001) were significant independent predictors of malignancy. Subset multiple logistic regression analysis modeled with age, PSA density, percent free PSA and PSA velocity revealed that age (p = 0.02) and percent free PSA (p = 0.0003) were significant independent predictors of cancer. There were no significant differences between the Gleason scores of cancers detected on repeat biopsy compared to 587 stage T1c-2 cancers detected on initial biopsy during the study period (p = 0.09). PSA, PSA density, percent free PSA and PSA velocity were not significantly different among men without a cancer diagnosis who had high grade neoplasia in 1 or 2 benign biopsies. CONCLUSIONS: Greater than 25% of this population of select patients with suspected stage T1c-2 prostate cancer had malignancy detected on repeat biopsy. Percent free PSA was the most powerful predictor of cancer. High grade prostatic intraepithelial neoplasia was not a predictor of repeat biopsy cancer detection and PSA functions were similar among men without cancer who did and did not have high grade neoplasia in 1 or more benign biopsies. This finding suggests that high grade prostatic intraepithelial neoplasia may not be a reliable indicator of clinically significant existing prostate cancer.

Percent free prostate specific antigen and cancer detection in black and white men with total prostate specific antigen 2.5 to 9.9 ng./ml.

PURPOSE: The ratio of free-to-total prostate specific antigen (PSA), or percent free PSA, is a useful adjunct to total PSA for estimating the risk of prostate cancer when total PSA is 2.5 to 9.9 ng./ml. Relationships between cancer detection and total PSA are influenced by race but to our knowledge relationships between cancer detection and percent free PSA have not been studied. MATERIALS AND METHODS: A total of 222 black and 298 white consecutive and evaluable men with total PSA 2.5 to 9.9 ng./ml. underwent prostate biopsy for suspected cancer at a Veterans Affairs Medical Center. Clinical measurements included digital rectal examination, total and free serum PSA, prostate volume, PSA density and Gleason score of malignant biopsy specimens. RESULTS: Median percent free PSA was 14.1 (range 3.6 to 49.2) in 201 men with prostate cancer and 21.9 (range 5.7 to 83.3) in 319 without detectable cancer (p <0.0001). Significant racial differences in demographic characteristics and clinical measurements were limited to total PSA, which was higher in black men (p = 0.03). Cancer was detected in 156 black (47%) and 206 white (33%) men (p = 0.001). Areas under receiver operating characteristics curves for percent free PSA and total PSA were 0.66 and 0.58, respectively, for black men (p = 0.15), and 0.76 and 0.58, respectively, for white men (p <0.00001). Percent free PSA was 35.2 in black men and 29.2 in white men, and specificity was 9.1% and 28.7%, respectively, when sensitivity for percent free PSA was set at 95%. Of 156 black and 206 white men with percent free PSA less than 25, 83 (53%) and 85 (41%), respectively, had detectable cancer (p = 0.03). Of 66 black and 92 white men with percent free PSA 25 or greater 21 (32%) and 12 (13%), respectively, had detectable cancer (p = 0.005). CONCLUSIONS: Our study demonstrates racial differences in relationships between percent free PSA and cancer detection in men with suspected prostatic carcinoma and total PSA 2.5 to 9.9 ng./ml. Clinical application of the commonly used percent free PSA cutoff of less than 25 to determine the advisability of prostate biopsy may lead to under diagnosis of early stage prostate cancer in black men, who are at greater risk of morbidity and mortality from disease than white men.

Race and cause specific survival with prostate cancer: influence of clinical stage, Gleason score, age and treatment.

PURPOSE: We assess the influence of race on stage stratified cause specific survival of men with prostate cancer, and Gleason score, age at diagnosis and treatment on potential racial differences in survival. MATERIALS AND METHODS: A total of 524 black and 396 white men were diagnosed with prostate cancer at a Veterans Affairs Medical Center between January 1982 and December 1992. Clinical stage was determined by retrospective review of the medical records and Gleason score of biopsy material as assigned by a single uropathologist. Of 611 patients who died the cause of death was determined by retrospective or prospective review of hospital records in 493 and by review of the death certificates in 102. In 16 cases the cause of death was indeterminate. Median potential followup was 112 months (range 60 to 182) and median period of observation was 61 months (range 1 to 182). RESULTS: Cause specific survival with stage T1b-2 cancer was lower in 231 black than in 264 white men of all ages (p = 0.02) and lower in 110 black than in 170 white men younger than in 70 years at diagnosis (p = 0.04). Gleason 7 to 10 cancer, which was associated with a less favorable cause specific survival compared to Gleason 2 to 6 cancer (p <0.0001), was more common in black than in white men with stage T1b-2 cancer of all ages (p = 0.01) and younger than 70 years at diagnosis (p = 0.04). No or unknown treatment status, which was associated with a less favorable cause specific survival compared to treatment (p = 0.05), was more common in black than in white men with stage T1b-2 cancer of all ages (p = 0.0005) but not significantly different when stratified by age. In men of all ages racial differences in cause specific survival were not significant when adjusted for age and Gleason score (p = 0.14) or age, Gleason score and treatment status (p = 0.17). In men younger than 70 years racial differences in cause specific survival were not significant when adjusted for age and Gleason score (p = 0.22). There were no significant racial differences in overall or age stratified all cause survival of men with stage T1b-2 cancer. There were no significant differences in overall or age stratified cause specific or all cause survival of 112 black and 58 white men with stage T3-4 cancer, or 181 and 74, respectively, with metastatic cancer. CONCLUSIONS: Our data indicate that local stage prostate cancer is more lethal in black than in white men and the difference is most pronounced in men younger than 70 years. The survival disadvantage of black men with local stage cancer is due in part to a propensity for development of less differentiated and more aggressive malignancies.

A prospective study of the serum prostate specific antigen concentrations and Gleason histologic scores of black and white men with prostate carcinoma.

BACKGROUND: The stage specific survival rates of black American men with prostate carcinoma are less favorable than those of white American men. The authors conducted a prospective study of the serum prostate specific antigen (PSA) concentrations and Gleason histologic scores of black and white men with newly diagnosed prostate carcinoma to determine whether there were racial differences in these prognostic variables. METHODS: At a Veterans Affairs Medical Center between January 1, 1992, and December 31, 1997, clinical stage, Gleason histologic score, serum PSA concentration, prostate volume, and PSA density were determined for 796 consecutive men (465 black and 331 white) who had biopsy-detected prostate carcinoma. RESULTS: The percentages, respectively, of black and white men with local, regional, and metastatic carcinoma were 58 and 72; 22 and 17; and 20 and 11 (P < 0.0001). Of 271 black and 329 white men with local stage cancer, 20% and 12%, respectively, had Gleason 8-10 tumors (P = 0.02), and the age-adjusted risk of Gleason 8-10 cancer was 1.39 times greater for black men (95% confidence interval [CI] = 1.09-2.93). Gleason 8-10 cancer was found in 12 of 68 black (18%) and 5 of 87 white (6%) men with local cancer who were age 65 years or younger (P = 0.02). Among black and white men with local stage cancer, the mean PSA was 12.9 (95% CI = 11.5-14.4) and 8.5 (95% CI = 7.6-9.4) ng/mL, respectively (P < 0.0001), and among black and white men with regional stage cancer the mean PSA was 53.3 (95% CI = 42.7-63.9) and 35.0 (95% CI = 27.3-42.6) ng/mL, respectively (P = 0.02). The mean PSA of black and white men with local cancer who were age 65 years or younger was 11.6 (95% CI = 8.8-14.4) and 6.9 (95% CI = 5.9-8.0) ng/mL, respectively (P = 0.0009). CONCLUSIONS: Disparities in the risk of Gleason score 8-10 cancer for black and white men with local stage disease and in the serum PSA concentrations of black and white men with local and regional stage disease help to explain racial differences in cancer survival. Racial differences in the risk of Gleason 8-10 cancer and in the serum PSA concentrations of men age 65 years or younger have implications regarding the potential benefits of screening for prostate carcinoma in the African American community.

Relationships between prostate-specific antigen and prostate volume in black and white men with benign prostate biopsies.

OBJECTIVES: To determine whether the higher age-adjusted serum prostate-specific antigen (PSA) levels in black compared with white men with no clinical evidence of prostate cancer reflect racial differences in relationships between PSA and prostate volume. METHODS: The age, PSA, findings on digital rectal examination (DRE), prostate volume, and PSA density were assessed prospectively in 810 consecutive, evaluable men who underwent prostate biopsy for suspected cancer but who had benign histologic findings. RESULTS: Among the black and white patients, there were significant differences in age (mean 67.2 +/- 8.1 and 65.9 +/- 7.7 years, respectively, P = 0.02), PSA (median 4.7 and 3.9 ng/mL, respectively, P <0.0001), prostate volume (median 41 and 36 mL, respectively, P = 0.004), and PSA density (median 0.11 and 0.08 ng/mL/mL, respectively, P = 0.005). Multiple linear regression analyses showed that black race was significantly associated with increased prostate volume when controlled for age (P = 0.02), with increased PSA when controlled for prostate volume and age (P = 0.002), and with increased PSA density when controlled for age (P = 0.007). When controlled for prostate volume, PSA was not significantly different in black and white men 50 to 59 years old but was significantly greater in black men 60 to 69 and 70 to 79 years old (P = 0.02 and 0.002, respectively). CONCLUSIONS: On a volume/volume basis, the benign prostatic tissue of black men appears to contribute more PSA to the circulating blood than does the benign prostatic tissue of white men, and the difference increases with advancing age. These phenomena provide a reasonable explanation for the age-adjusted racial differences in the PSA of men with no clinical evidence of cancer.

Results of transition zone biopsy in black and white men with suspected prostate cancer.

OBJECTIVES: To determine whether biopsy-detectable transition zone tumors are more common in black than in white men with suspected Stage T1c and T2 prostate cancer. METHODS: We performed a prospective study of transition zone prostate biopsy (TZ biopsy) in 1 78 black and 261 white men who had not undergone previous prostate biopsy and in 61 black and 65 white men who had undergone one benign sextant peripheral zone prostate biopsy (PZ biopsy). RESULTS: The mean age of the 239 black and 326 white study patients was 68.6+/-7.4 and 67.2+/-7.2 years, respectively (P = 0.02), the mean prostate-specific antigen (PSA) was 8.4+/-7.4 and 6.4+/-5.4 ng/mL, respectively (P = 0.003), and the mean PSA density was 0.20+/-0.23 and 0.16+/-0.16 ng/mL/mL, respectively (P = 0.006). Overall, cancer was diagnosed by TZ biopsy only in 7 black men (3%) and in no white men (0%) (P = 0.003). However, cancer detection with a TZ biopsy only was not significantly different in the black and white men when controlled for age, PSA, or PSA density (P>0.90). A TZ biopsy only detected cancer in 1% of patients who had not undergone prior PZ biopsy and in 2% of patients who had undergone prior PZ biopsy. Of the seven cancers detected with TZ biopsy, six (86%) had a Gleason score of 2 to 6. CONCLUSIONS: Prostate cancer detection with a TZ biopsy only is not common and when controlled for confounding variables is the same in black and white men. The preferential use of TZ biopsies in black men is not warranted, and the low diagnostic yield argues against routine use of the biopsy technique in men of either race.

Clear-cell and papillary carcinoma of the kidney: an analysis of chromosome 3, 7, and 17 abnormalities by microsatellite amplification, cytogenetics, and fluorescence in situ hybridization.

Clear-cell and papillary renal cell carcinomas (RCCs) have specific genetic changes that allow them to be classified on the basis of histopathology and on the basis of cytogenetic and molecular genetic findings. Clear-cell carcinomas are characterized by a deletion of gene sequences on the short arm of chromosome 3 (3p). Papillary RCCs do not have 3p deletions but have an increase in chromosomal number that usually includes trisomies of chromosomes 7 and 17. This study was undertaken to determine whether PCR-amplified DNA microsatellites can be used to detect numerical abnormalities of chromosomes 7 and 17 and whether the numerical abnormalities and 3p deletions that are detected by microsatellite analysis can be correlated with histopathologic tumor types. A series of histologically unambiguous RCCs consisting of three papillary and ten clear-cell RCCs were studied by cytogenetics and by fluorescence in situ hybridization (FISH) with chromosome 7 and 17 centromeric probes. Microsatellites on the long and short arms of chromosomes 3, 7, and 17 were amplified in paired normal tissue and tumor samples, and the reaction products were analyzed for differences between the normal and the tumor allele ratios. Clear-cell carcinomas showed loss of heterozygosity (LOH) of 3p but not 3q alleles in eight of ten cases. LOH of 3p and 3q was seen in one case of papillary RCC that cytogenetically had two normal chromosomes 3. This indicated a nondisjunction duplication that could be confused with monosomy 3 if only microsatellite studies were performed. Differences in microsatellite allele ratios between normal tissue and tumor correlated with the presence of trisomy 7 that was identified in clear-cell and papillary RCCs by cytogenetics and by FISH. Microsatellite analysis did not detect numerical chromosome 17 abnormalities in the papillary RCCs but did show an abnormality in one clear-cell carcinoma that was markedly aneusomic for chromosomes 7 and 17 by FISH. In this collection of cases, microsatellite amplification genetically distinguished only clear-cell RCCs showing 3p but not 3q LOH as a separate class of tumors. The method detected abnormalities in chromosome number that were found in both clear-cell and papillary RCCs.

Prostate cancer detection in candidates for open prostatectomy.

PURPOSE: We determine the incidence of biopsy detectable prostate cancer in men with clinical benign prostatic hyperplasia (BPH) and prostate specific antigen (PSA) elevation who are candidates for open prostatectomy, and the histology of prostatic tissue of men who underwent surgery. MATERIALS AND METHODS: Sextant peripheral zone prostate biopsies were performed in 128 consecutive men with obstructive voiding symptoms who had digital rectal examination not suspicious for cancer, PSA greater than 4.0 ng./ml. and prostate volume 75 ml. or greater. Of the patients 59 also underwent transition zone biopsy. Median PSA was 9.9 ng./ml. (range 4.1 to 80.0), median prostate volume was 92 ml. (range 75 to 220), median PSA density was 0.10 ng./ml./ml. (range 0.03 to 0.80) and median percent free PSA in 43 patients was 23.6 (range 8.8 to 41.3). RESULTS: Of the 128 patients 16 (13%) had malignant biopsy including 1 who had cancer detected with transition zone biopsy only. Gleason score of tumors ranged from 4 to 8 (median 5). Of 57 patients who underwent prostatectomy 6 (11%) had stage T1a and 2 (4%) had stage T1b cancer. Among men without an indwelling urethral catheter due to acute urinary retention mean PSA, PSA density and percent free PSA were not significantly different in those with benign and malignant biopsies and/or prostatectomy specimens. CONCLUSIONS: Greater than 10% of men with PSA elevation who are potential candidates for open prostatectomy will have biopsy detectable prostate cancer. This diagnostic yield, while lower than that reported for unselect men with normal digital rectal examination and PSA elevation, may justify preoperative peripheral zone biopsy to avoid surgical misadventure during open enucleation. Among patients with benign peripheral zone biopsy there is a less than 5% prevalence of large volume tumors that may complicate open enucleation.

Renal cell carcinoma in native kidneys of patients with end stage renal disease.

OBJECTIVE: To determine prevalence of renal cell carcinoma in a cohort of patients with end stage renal disease who underwent nephrectomies for suspicious cysts or masses. METHODS: A retrospective review of patients with end stage renal disease who were receiving hemodialysis and underwent nephrectomies were identified and those charts were reviewed. RESULTS: Twenty patients, from a total of 400 patients with end stage renal disease, had nephrectómies preformed for various reasons. Of these twenty patients, four were found to have renal cell carcinoma with an occurrence rate of 5% in these patients. At followup from 1-9 years, all patients are alive without evidence of disease. CONCLUSIONS: Patients with end stage renal disease have an increased prevalence of renal cell carcinoma. While the patients in this series have a 100% survival at 1-9 year follow-up, the overall survival rate in published reports is 35%. The need is to identify patients at high risk for the development of this disease and perform annual screening.

Early results of a prospective study of hormone therapy for patients with locally advanced prostate carcinoma.

BACKGROUND: Locally advanced prostate carcinoma is usually not curable with surgery or radiation therapy. Primary hormone therapy is an alternative therapeutic option, but contemporary prospective studies of the outcomes of such therapy are not available. METHODS: The authors conducted a prospective, hospital-based study of gonadal androgen ablation with deferred antiandrogen therapy in 103 men with prostate carcinoma clinically classified as T3-4NXM0. The median potential follow-up was 51 months (range, 36-74 months), and the median period of observation was 43 months (range, 6-74 months). RESULTS: Each patient experienced regression of the primary tumor, and none experienced significant morbidity from the primary tumor during the study period. The projected 5-year cause specific, metastasis free, PSA disease free (no PSA elevation > 1.0 ng/mL after the beginning of antiandrogen therapy), and all-cause survival rates were 84%, 84%, 68%, and 58%, respectively. CONCLUSIONS: Primary hormone therapy is a reasonable treatment option for locally advanced prostate carcinoma in elderly men or in men with significant comorbid disease who request therapeutic intervention.

An 11-month-old with anti-glomerular basement membrane disease.

Anti-glomerular basement membrane antibody disease is an autoimmune disease that has rarely been described in children, and no cases have previously been described in a patient younger than 2.5 years of age. We report an 11-month-old infant girl who developed anti-glomerular basement membrane disease and progressed to end-stage renal disease and eventual renal transplantation. Although it has been suggested that this disease does not occur in infants, the possibility of anti-glomerular basement membrane disease must be considered in the differential diagnosis of acute renal failure and glomerulonephritis in an infant. The characteristic linear pattern of immunofluorescent studies for Immunoglobulin (Ig) G is important in suggesting the diagnosis, which can be confirmed by serologic testing for antibody titers.

Trends in diagnosis of stage T1a-b prostate cancer.

PURPOSE: Stage T1a-b prostate cancer comprised about 44% of newly diagnosed local prostate cancer cases in the United States before the advent of medical and minimally invasive treatments for symptomatic benign prostatic hyperplasia (BPH) and before the widespread use of prostate specific antigen (PSA) testing in men with BPH. Information about the impact of these advances on detection of T1a-b cancer is not available. MATERIALS AND METHODS: Prevalence of T1a-b prostate cancer was determined in 1,554 consecutive men who underwent surgical prostatectomy for suspected BPH at a Veterans Affairs Medical Center from 1985 through 1996. Since 1991 a PSA blood test was obtained routinely before surgery and patients with PSA greater than 4.0 ng./ml. usually underwent ultrasound guided prostate biopsy. RESULTS: The number of T1a-b cancer cases was relatively stable during 1985 to 1990 but declined from 36 in 1990 to 9 in 1996. There were no temporal trends in proportion of prostatectomy patients with T1a-b cancer and the decline in cancer detection paralleled less frequent use of surgical prostatectomy for treatment of BPH. The proportion of prostatectomy patients with T1a-b cancer was similar in 1985 to 1990 and in 1991 to 1996 but the percentage of Gleason 7 to 10 cancers declined from 26 in 1985 to 1990 to 10 in 1991 to 1996 (p < 0.0001). PSA and PSA density of evaluable patients with cancer were significantly greater than in evaluable patients with BPH. Of 105 patients with PSA greater than 4.0 ng./ml. who underwent preoperative prostate biopsy 16 (15%) had T1a-b cancer. CONCLUSIONS: The less frequent use of surgical prostatectomy at our institution has produced marked decline in detection of T1a-b cancer. If representative of national trends this experience suggests that many men with obstructive voiding symptoms and T1a-b cancer will remain undiagnosed and that periodic monitoring to identify unsuspected cancer is important in men who are treated with medical or minimally invasive therapies for BPH. Decline in detection of T1a-b cancer may also confound the accuracy of projected incidence rates of local prostate cancer in the United States.

Prostate specific antigen in black and white men after hormonal therapies for prostate cancer.

PURPOSE: Prostate cancer deaths usually result from proliferation of the androgen independent malignant phenotype, and in the United States the survival of black men with metastatic cancer is less favorable than that of white men. We compared prostate specific antigen (PSA) functions after hormonal therapies in men of both races to investigate potential differences in the biology of androgen independent cancer. MATERIALS AND METHODS: The PSA nadir after gonadal androgen withdrawal was determined in 217 black and 188 white men with localized or metastatic cancer. The time to PSA elevation and PSA doubling time were determined in 62 black and 27 white men with biochemical relapse. Biochemical response to deferred flutamide treatment and flutamide withdrawal was assessed in 87 and 11 black and 30 and 10 white men, respectively. RESULTS: There were no significant racial differences in the PSA nadir when controlled for clinical stage and pretreatment PSA, or in PSA doubling time when controlled for clinical stage, PSA nadir and month of PSA elevation. The biochemical response to deferred flutamide therapy and flutamide withdrawal was the same in black and white men. CONCLUSIONS: The burden and growth rate of androgen independent cancer estimated from PSA functions after gonadal androgen withdrawal, and the impact of deferred antiandrogen therapy on the serum PSA are similar in black and white men. These findings suggest that racial differences in the biology of androgen independent carcinoma do not contribute to the inferior survival of black men with metastatic prostate cancer.

Characterization of a novel androgen-sensitive, prostate-specific antigen-producing prostatic carcinoma xenograft: LuCaP 23.

Prostatic carcinoma has proven extremely difficult to establish as cell lines or xenografts. In this article, we describe a new series of prostate cancer xenografts propagated in athymic mice, designated LuCaP 23, developed from prostate metastases harvested at autopsy shortly after death. Tumor from three separate metastatic deposits was developed into three xenograft sublines: two from lymph node metastases (LuCaP 23.1 and 23.8) and one from a liver metastasis (LuCaP 23.12). Fluorescence in situ hybridization analysis confirms the xenografts are human. Histologically, the xenografts are comprised of columnar epithelial cells arranged in a glandular pattern. Tumor doubling times range from 11 to 21 days for the three sublines. The cells secrete large amounts of prostate-specific antigen (PSA) with PSA indices of 1.27, 1.63, and 5.21 ng/ml/mm3 for the mice bearing the LuCaP 23.1, 23.8, and 23.12 sublines, respectively. Following androgen deprivation a temporary decrease in PSA secretion and a decrease in tumor size are noted in most tumors. Eventually, the tumors become androgen independent and resume growth in castrate hosts. The degree of PSA response to castration and time to PSA nadir correlate with time to progression. Thus, unlike most existing models of prostatic carcinoma, this novel xenograft exhibits many phenotypic characteristics of clinical prostatic carcinoma, including androgen sensitivity. These properties make this xenograft an excellent model for future study.

Synergistic renal protection by combining alkaline-diuresis with lipid peroxidation inhibitors in rhabdomyolysis: possible interaction between oxidant and non-oxidant mechanisms.

BACKGROUND AND PURPOSE: Heme-proteins, besides causing renal tubular obstruction, may contribute to rhabdomyolysis-induced renal injury through a heme-iron-mediated lipid peroxidation process. In the present study, we compared the combined therapy of a lipid peroxidation inhibitor, 21-aminosteroid (21-AS) and fluid-alkaline-mannitol (FAM) diuresis with either of them alone to determine the efficacy of the combination therapy and to delineate the roles of lipid peroxidation and cast formation. METHODS AND RESULTS: Employing Raman spectroscopy, we confirmed in vitro the ability of 21-AS to inhibit iron-induced fatty acid peroxidation. 21-AS was then administered to rats developing renal failure from glycerol-induced rhabdomyolysis. Although 21-AS inhibited rhabdomyolysis-induced plasma and renal lipid peroxidation, renal protection was incomplete. Administration of FAM to inhibit cast formation afforded a better renal protection. However, when these therapies were combined to inhibit both lipid peroxidation and cast formation, there was a synergistic renal functional protection. This was accompanied by a maximum inhibition of renal and plasma lipid peroxidation, as well as, renal tubular necrosis and cast formation. Compared to combination therapy, FAM therapy alone, despite identical volume, was accompanied by a higher tubular necrosis and cast formation. CONCLUSIONS: That combining a lipid peroxidation inhibitor with fluid-alkaline diuresis in rhabdomyolysis further lowers renal lipid peroxidation, tubular necrosis and cast formation and synergistically limits renal dysfunction (i) supports a role for lipid peroxidation in the pathophysiology of rhabdomyolysis ARF, (ii) underscores the role of the intratubular heme retention, a cause for tubular obstruction as well as a source for prodigious amount of iron, likely involved in the lipid peroxidation, and (iii) raises the possibility of interactions between non-oxidant and oxidant mechanisms.