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Martin I Resnick

Publications and source records attributed to Martin I Resnick.

45 records · Page 3Linked to original sources
PubMed2002

The accuracy of the increased prostate specific antigen level (greater than or equal to 20 ng./ml.) in predicting prostate cancer: is biopsy always required?

PURPOSE: Urologists are often referred patients who initially present with an extremely high serum prostate specific antigen (PSA) level. Despite a presumptive diagnosis of prostate cancer, many of these men undergo biopsy to obtain a tissue diagnosis before treatment with androgen ablative therapy. We examined a data base of men undergoing prostate biopsy to determine the accuracy of high PSA levels (greater than or equal to 20 ng./ml.) in predicting prostate cancer. MATERIALS AND METHODS: We reviewed the records of 1,250 consecutive patients undergoing transrectal ultrasound guided prostate biopsy at 1 institution. From this data base we identified all patients with PSA greater than or equal to 20 ng./ml. at the time of prostate biopsy. The accuracy of PSA in predicting cancer was determined by calculating positive predictive values for PSA ranges and PSA cutoffs. RESULTS: We identified 187 men (15%) presenting with PSA greater than or equal to 20 ng./ml. Of these 187 men 157 (84.0%) were diagnosed with prostate cancer on initial biopsy. Due to a negative initial biopsy, yet a high suspicion of cancer, 12 (6.4%) patients underwent at least 1 repeat biopsy. Of these 12 men 6 (50%) were diagnosed with cancer on repeat biopsy. Overall, 163 of the 187 men (87.2%) were diagnosed with prostate cancer by biopsy. Stratified by PSA ranges, positive predictive values were 73.6% for 20 to 29.9, 90.3% for 30 to 39.9, 93.8% for 40 to 49.9, 100% for 50 to 99.9, 95% for 100 to 199.9 and 100% for greater than or equal to 200 ng./ml. Using PSA cutoffs positive predictive values were 95.7% for PSA greater than or equal to 30, 97.6% for PSA greater than or equal to 40 and 98.5% for PSA greater than or equal to 50 ng./ml. CONCLUSIONS: Serum PSA, when increased above 50 ng./ml., is 98.5% accurate in predicting the presence of prostate cancer on tissue biopsy. Nonetheless, since transrectal prostate biopsy has a low complication rate and is relatively well tolerated, we recommend continuing to biopsy most patients with high PSA levels. However, carefully selected elderly patients on chronic anticoagulation, with severe co-morbidities or presenting with spinal cord compression may not require biopsy before androgen ablative therapy since PSA is highly accurate in diagnosing prostate cancer at levels greater than 50 ng./ml.

Aged↗
PubMed2002

Skeletal fractures negatively correlate with overall survival in men with prostate cancer.

PURPOSE: We assessed the correlation of skeletal fracture with survival in men with prostate cancer on chronic androgen suppressive therapy. MATERIALS AND METHODS: A total of 195 consecutive patients on chronic androgen suppression for prostate cancer were evaluated for the history and type of skeletal fracture. Correlation with overall survival was performed via multivariate analysis. RESULTS: Of these 195 men 24 reported skeletal fracture since the diagnosis of prostate cancer. Median overall survival was 121 and 160 months in men without and with a history of skeletal fracture since the diagnosis of prostate cancer, respectively (p = 0.04). A history of skeletal fracture was retained as a negative predictor of survival on forward stepwise regression analysis (RR = 7.4, p = 0.007). CONCLUSIONS: Our results suggest that skeletal fracture in patients with prostate cancer is an independent and adverse predictor of survival. Consideration for screening men at greatest risk via bone mineral density measurements and initiating empirical skeletal therapies (bisphosphonates, estrogens and so forth) may be warranted. This recommendation awaits validation through prospective randomized trials.

Adenocarcinoma↗
PubMed2002

Clinical predictors of androgen-independent prostate cancer and survival in the prostate-specific antigen era.

OBJECTIVES: To further characterize and identify novel predictors of androgen-independent prostate cancer (AIPC) and survival in the prostate-specific antigen (PSA) era. METHODS: A total of 184 consecutive patients with prostate cancer receiving chronic androgen suppression were assessed for the development of AIPC and overall survival. RESULTS: The median time to development of AIPC was 44 months (Stage M+ = 24 months; Stage M0 = 63 months, P = 0.000001). The 10-year overall survival rate for Stage M0 or M+ disease was 89% and 55%, respectively. AIPC developed significantly more commonly in patients with a higher nadir PSA level (greater than 1 ng/dL), a longer time to reach nadir PSA (greater than 3 months), a larger body mass index (greater than 27 kg/m2), greater pretherapy PSA level, and when evidence of metastatic disease was identified (logistic regression analysis). Overall survival was significantly associated with advanced stage (skeletal metastases), pretreatment PSA level, and history of skeletal fracture (multivariate Cox regression analysis). CONCLUSIONS: In the PSA era, longer intervals of androgen suppression therapy in nonmetastatic, biochemically recurrent prostate cancer have translated into a change in the duration of androgen-dependent prostate cancer. Although the duration of androgen dependence remains variable, prolonged--possibly "curative"--control exists in a subset of patients. Obese men developed AIPC significantly sooner than did slender men. A skeletal fracture was a significant negative predictor of overall survival. These observations form the basis for nomogram predictions of AIPC in the PSA era.

Aged↗
PubMed2002

Does the size of the surgical margin in partial nephrectomy for renal cell cancer really matter?

PURPOSE: Although many groups recommend a surgical margin of 1 to 2 cm., to our knowledge the amount of normal renal parenchyma that must be excised during partial nephrectomy for stages T1-2N0M0 renal cell carcinoma to ensure a safe margin has never been critically evaluated. We investigated whether the size of the surgical margin has any effect on recurrence. MATERIALS AND METHODS: All partial nephrectomies performed for localized renal cell carcinoma at our institution from 1988 to 1999 were retrospectively analyzed via a review of hospital records, pathology reports and histological slides. Parenchymal margin status was assessed and quantified by microscopy. Followup data were obtained via patient chart review and telephone interview. Average negative margin size and postoperative followup were determined, and renal cell carcinoma recurrence was assessed. RESULTS: A total of 44 partial nephrectomies were performed with a mean followup of 49 months (range 8 to 153). Mean tumor size was 3.22 cm. (range 1.3 to 10). Surgical margins were negative for malignancy in 41 cases and positive in 3. All patients with negative margins were without local recurrence at followup except 1 with a recurrent mass adjacent to the kidney at a site distant from the original lesion. Mean and median size of the negative margins was 0.25 and 0.2 cm., respectively (range 0.05 to 0.7). In the 3 cases with positive margins there was no evidence of disease at 39 and 62 months of followup in 2, while multiple local and metastatic recurrences developed in 1. CONCLUSIONS: No patient with negative parenchymal margins after nephron sparing surgery for stages T1-2N0M0 renal cell carcinoma had local recurrence at the resection site at a mean followup of 49 months. Margin size was irrelevant. Only a minimal margin of normal renal parenchyma of less than 5 mm. must be removed during partial nephrectomy for localized renal cell carcinoma.

Adult↗
PubMed2002

Decreased renal expression of the putative calcium oxalate inhibitor Tamm-Horsfall protein in the ethylene glycol rat model of calcium oxalate urolithiasis.

PURPOSE: Tamm-Horsfall protein is believed to inhibit calcium oxalate crystallization, aggregation or adhesion to the renal epithelium. We determined whether ethylene glycol induced urolithiasis changes the expression of renal and urinary Tamm-Horsfall protein. For comparison the expression of another calcium oxalate inhibitor, osteopontin, was also analyzed. MATERIALS AND METHODS: Male rats were treated with 0.75% ethylene glycol plus an AIN-76 diet (Dyets, Bethlehem Pennsylvania) (ethylene glycol group) or standard rat chow and water (control group) for up to 8 weeks (6 per group for 8 weeks and 3 per group for 3 days to 6 weeks). Kidneys and urine (8 weeks only) were harvested and analyzed by Northern and Western blot analysis, and immunohistochemistry. RESULTS: Tamm-Horsfall protein message and protein (membrane bound form) were decreased, while those of osteopontin were increased in the kidneys of rats treated with ethylene glycol for 8 weeks. As judged by immunochemistry Tamm-Horsfall protein and osteopontin were consistently present in a few tubules in rats in the ethylene glycol and control groups, respectively. In urine expression of the free form of Tamm-Horsfall protein (approximately 75 kDa.) was decreased but detectable in ethylene glycol treated rats. Although readily detected in tissue, osteopontin was not detected in the urine of control or ethylene glycol treated rats. In the time course experiment Tamm-Horsfall protein did not decrease until 4 weeks, when calcium oxalate crystals were detectable in the kidneys of treated rats. In contrast, osteopontin was increased, although inconsistently, beginning at 3 days. CONCLUSIONS: Unlike other calcium oxalate inhibitors, such as osteopontin, renal message and protein for Tamm-Horsfall protein was decreased in ethylene glycol treated rats. Tamm-Horsfall protein expression did not decrease until aggregates of crystals had been deposited in the kidneys, while osteopontin expression began to increase almost immediately. Comparisons of the data on kidneys and urine obtained by RNA or protein blot analysis and immunochemistry underscore the need to examine tissue and urine by multiple techniques to obtain the most accurate assessment of how protein expression is changed by a given treatment.

Animals↗
PubMed2002

Distribution of chronic prostatitis in radical prostatectomy specimens with up-regulation of bcl-2 in areas of inflammation.

PURPOSE: We examined the anatomical relationship of chronic prostatitis with prostate cancer and benign prostatic hyperplasia (BPH) based on the hypothesis that there may be an association of prostatitis with these other entities that may involve up-regulation of bcl-2. MATERIALS AND METHODS: We examined 40 whole mount radical prostatectomy specimens for the presence and distribution of chronic inflammatory infiltrate. Immunostaining for bcl-2 was done in 10 cases. RESULTS: Chronic prostatitis was identified in all 40 cases with peripheral zone inflammation in 95% and transition zone inflammation in 87.5%. In all cases of transition zone inflammation the infiltrate was noted within and/or around BPH. Inflammatory infiltrate was microscopically associated with prostate cancer in 23 of the 40 cases (57.5%). In these 23 cases, there was no association of inflammation with Gleason score, preoperative prostate specific antigen, positive margins, or seminal vesicle invasion. Patients with BPH unassociated with prostatitis had significantly smaller prostate weight (median 32 gm.) and were younger (mean age 54.4 years) than those with BPH associated with prostatitis (median weight 40 gm. and mean age 61.4 years, p <0.05). Bcl-2 staining was intensified in benign glands within areas of prostatitis in all 10 cases examined. CONCLUSIONS: Chronic prostatitis is a common finding in radical prostatectomy specimens. Inflammation was associated with BPH and cancer but had a greater tendency to be associated with BPH. Bcl-2 was prominently expressed in areas of prostatitis. Our findings indirectly support a potential role for prostatitis in the pathogenesis of BPH.

Aged↗
PubMedDate not supplied

Growth, immortalization, and differentiation potential of normal adult human proximal tubule cells.

Human proximal tubule epithelial cell lines are potentially useful models to elucidate the complex cellular and molecular details of water and electrolyte homeostasis in the kidney. Samples of normal adult human kidney tissue were obtained from surgical specimens, and S1 segments of proximal convoluted tubules were microdissected, placed on collagen-coated culture plate inserts, and cocultured with lethally irradiated 3T3 fibroblasts. Primary cultures of proximal tubule epithelial cells were infected with a replication-defective retroviral construct encoding either wild-type or temperature-sensitive simian virus 40 large T-antigen. Cells forming electrically resistive monolayers were selected and expanded in culture. Three cell lines (HPCT-03-ts, HPCT-05-wt, and HPCT-06-wt) were characterized for proximal tubule phenotype by electron microscopy, electrophysiology, immunofluorescence, Southern hybridization, and reverse transcriptase-polymerase chain reaction. Each of the three formed polarized, resistive epithelial monolayers with apical microvilli, tight junctional complexes, numerous mitochondria, well-developed Golgi complexes, extensive endoplasmic reticulum, convolutions of the basolateral plasma membrane, and a primary cilium. Each exhibited succinate, phosphate, and Na,K- adenosine triphosphatase (ATPase) transport activity, as well as acidic dipeptide- and adenosine triphosphate-regulated mechanisms of ion transport. Transcripts for Na(+)-bicarbonate cotransporter, Na(+)-H(+) exchanger isoform 3, Na,K-ATPase, parathyroid hormone receptor, epidermal growth factor receptor, and vasopressin V2 receptor were identified. Furthermore, immunoreactive sodium phosphate cotransporter type II, vasopressin receptor V1a, and CLIC-1 (NCC27) were also identified. These well-differentiated, transport-competent cell lines demonstrated the growth, immortalization, and differentiation potential of normal, adult, human proximal tubule cells and consequently have wide applicability in cell biology and renal physiology.

Animals↗
PubMedDate not supplied

Nuclear factor-kappaB/p65 (Rel A) is constitutively activated in human prostate adenocarcinoma and correlates with disease progression.

Aberrant nuclear factor-kappaB (NF-kappaB) activation has been implicated in the pathogenesis of several human malignancies. In this study, we determined whether NF-kappaB is constitutively activated in human prostate adenocarcinoma, and, if so, whether increased NF-kappaB activation and its binding to DNA influence tumor progression. Using tissue samples obtained during transurethral prostatic resection and paraffin-embedded sections of benign and cancer specimens, we determined the nuclear expression of NF-kappaB/p65 and NF-kappaB/p50, cytoplasmic expression of IkappaBalpha, its phosphorylation, and expression of NF-kappaB-regulated genes, specifically Bcl2, cyclin D1, matrix metalloproteinase-9 (MMP-9), and vascular endothelial growth factor (VEGF). A progressive increase in the expression of NF-kappaB/p65 (but not of p50) was observed in cancer specimens compared to benign tissue, which correlated with increasing levels of IkappaBalpha and its phosphorylation. NF-kappaB DNA-binding activity increased with increasing tumor grade and the binding complex mainly consisted of NF-kappaB/p65-p50 heterodimers. Immunohistochemical analysis showed enhanced nuclear staining for NF-kappaB/p65 in both high-grade (P <.0001) and low-grade (P <.003) cancer specimens, compared to benign tissue. The nuclear levels of NF-kappaB/p65 correlated with concurrent increase in cytosolic levels of IkappaBalpha along with NF-kappaB-dependent expression of Bcl2, cyclin D1, MMP-9, and VEGF. These results demonstrate that NF-kappaB/p65 is constitutively activated in human prostate adenocarcinoma and is related to tumor progression due to transcriptional regulation of NF-kappaB-responsive genes.

Adenocarcinoma↗