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Mark S Soloway

Publications and source records attributed to Mark S Soloway.

At least 55 records · Page 3Linked to original sources
PubMed2003

Evaluation of the prognostic potential of hyaluronic acid and hyaluronidase (HYAL1) for prostate cancer.

Despite the development of nomograms designed to evaluate the prognosis of a patient with prostate cancer (CaP), the information has been limited to prostate-specific antigen (PSA), clinical stage, Gleason score, and tumor volume estimates. To improve our ability to predict prognosis, information regarding the molecular properties of CaP is needed. Hyaluronic acid (HA) is a glycosaminoglycan that promotes tumor metastasis. Hyaluronidase (HAase) is an enzyme that degrades HA into angiogenic fragments. We recently showed that in CaP tissues, whereas HA is localized mostly in the tumor-associated stroma, HYAL1 type HAase is exclusively localized in CaP cells (Lokeshwar et al. J. Biol. Chem., 276: 11922-11932, 2001). We evaluated the prognostic potential of HA and HYAL1 in CaP by immunohistochemistry. Archival CaP specimens were obtained from patients who underwent radical retropubic prostatectomy for clinically localized CaP. Group 1 (n = 25) included patients who showed biochemical recurrence (PSA >0.4 ng/ml; mean recurrence: 21.3 months). Group 2 included patients with no clinical or biochemical recurrence (n = 45; mean follow-up: 80.9 months). For HA and HYAL1 staining, a biotinylated HA-binding protein and an anti-HYAL1 antibody were used. The staining was evaluated on the basis of intensity (0 to 3+) and as dense or sparse (for HA staining only) and then grouped as low grade and high grade. In CaP specimens, HYAL1 was exclusively expressed in tumor cells. Although the stroma was stained positive for HA, 40% of tumor cells also expressed HA. HA, HYAL1, and combined HA-HYAL1 staining predicted progression with 96%, 84%, and 88% sensitivity, 55.5%, 80%, and 84.4% specificity, and 70%, 81.4%, and 85.7% accuracy, respectively. In the univariate analysis, preoperative PSA, Gleason sum, stage, margin, seminal vesicle, extra-prostatic extension (EPE), HA, HYAL1, and HA-HYAL1 were significant in predicting progression (P < 0.05). However, in the multiple logistic regression analysis, only EPE [odds ratio (OR) = 33.483; P = 0.002), HYAL1 (OR = 12.42; P = 0.009), HA-HYAL1 (OR = 18.048; P = 0.0033), and margin (OR = 26.948; P = 0.006)] were significant. Thus, in this 5-year follow-up study, HYAL1, together with EPE and margin, was found to be an independent prognostic indicator.

Adult↗
PubMed2003

An orally active Amazonian plant extract (BIRM) inhibits prostate cancer growth and metastasis.

PURPOSE: Poor efficacy of conventional chemotherapeutic drugs against metastatic hormone-refractory prostate cancer (CaP) drives patients to try "alternative medicine". The antitumor activity of one such agent, "BIRM" (biological immune response modulator; "Simple Ecuadorian Oral Solution: an extract of an Amazonian plant"), was characterized in vitro and in vivo using established CaP cell lines and a tumor model. METHODS: The cytotoxicity of BIRM in four human and one rat CaP cell line was evaluated using cell proliferation-inhibition and clonogenic survival assays. BIRM-induced apoptosis, alterations in cell cycle phase progression and inhibition of the extracellular matrix-degrading enzyme hyaluronidase were also investigated in these cells. The in vivo efficacy of BIRM was evaluated in rats with subcutaneous tumor implants of Dunning EGFP-MAT LyLu cells. The active species in BIRM were characterized by gel filtration chromatography. RESULTS: BIRM inhibited cell proliferation and clonogenic growth of the CaP cells (IC(50) about 8.0 microl/ml). It increased cell accumulation in the G(0)/G(1) phase by 33.8% and decreased the proportion of cells in S phase by 54.6%. Apoptotic cell death in BIRM-treated cells was associated with activation of cell death-associated caspases. BIRM inhibited the activity of hyaluronidase, a hyaluronic acid-degrading enzyme, at 1 microl/ml. Treatment of MAT LyLu tumor-bearing rats with BIRM by oral gavage resulted in a significant decrease in tumor incidence (50%), tumor growth rate (18.6+/-1.3 days for 1 cc tumor growth in control rats and 25.7+/-2.6 days in BIRM-treated rats), and only one out of six BIRM-treated rats versus four out of six in the control group developed lung metastasis. Three active ingredients in BIRM with a relative molecular mass (Mr) of >or=3500 were identified by ultracentrifugation and gel filtration chromatography and were found to be resistant to proteinase and heat (100 degrees C). CONCLUSION: The plant extract BIRM contains antitumor compounds of Mr >or=3500 with potent antiproliferative activity in vitro and in vivo against prostate cancer cells.

Administration, Oral↗
PubMed2003

Biochemical and pathological predictors of the recurrence of prostatic adenocarcinoma with seminal vesicle invasion.

PURPOSE: We assessed biochemical and pathological factors as predictors of recurrence in men with seminal vesicle invasion. MATERIALS AND METHODS: A consecutive series of 812 men who underwent radical retropubic prostatectomy between 1992 and 2000 included 106 (13%) with seminal vesicle invasion. Disease recurrence was defined as prostate specific antigen (PSA) 0.4 ng./ml. or greater. Patients with less than 12 months of followup, salvage radical retropubic prostatectomy, lymph node metastases and adjuvant therapy were excluded from study. Data on the remaining 66 cases were analyzed using the chi-square test, bivariate logistic regression, Kaplan-Meier analyses and Cox proportional regression. Variables included demographics, recurrence, time from surgery to recurrence, positive margins, capsular invasion, extracapsular extension, Gleason score (2 to 6, 7 and 8 to 10), and dichotomized values of preoperative PSA (10 or less versus 10 ng./ml.) and tumor volume (20% or less versus greater than 20%). RESULTS: Mean patient age was 62 years (range 48 to 74). At an average followup of 47.7 months (range 13 to 109) 53% of the patients were free of biochemical recurrence. Mean time to recurrence was 18.6 months (range 1.7 to 51.6). Univariate analyses revealed a statistical significant increased risk of recurrence in patients with PSA greater than 10 ng./ml. (p <0.0001), capsular invasion (p = 0.01) and age (p = 0.036). When adjusting for potential covariates, Cox proportional regression analysis indicated that higher PSA (hazard ratio 7.33, 95% CI 2.57 to 20.95), larger tumor volume (hazard ratio 5.64, 95% CI 1.97 to 16.19) and higher age (hazard ratio 1.13, 95% CI 1.04 to 1.22) were significantly associated with shorter time to recurrence. CONCLUSIONS: PSA greater than 10 ng./ml., tumor volume greater than 20% and age are significant predictors of recurrence after radical retropubic prostatectomy in patients with prostate cancer and seminal vesicle invasion. Hopefully future randomized trials may show a survival benefit of adjuvant therapy in patients at high risk.

Adenocarcinoma↗
PubMed2003

Current bladder cancer tests: unnecessary or beneficial?

Bladder cancer is currently diagnosed using cystoscopy and cytology in patients with suspicious signs and symptoms. These same tests are used to monitor patients with a history of bladder cancer for recurrence. The recurrence rate for bladder cancer is high, thus necessitating long-term follow-up. Urine cytology requires an experienced cytopathologist and is costly. It has high specificity, but low sensitivity for low-grade bladder tumors. Recently many non-invasive bladder cancer tests, utilizing markers found in the urine, have been developed. The FDA has approved several of these for the use is bladder cancer diagnosis, and many others are undergoing development and investigation. An ideal bladder cancer test would be non-invasive, highly sensitive and specific, inexpensive, easy to perform, and yield highly reproducible results. Many of the tests reviewed meet some, but not all, of these criteria.

Biomarkers, Tumor↗
PubMed2003

A prospective study measuring penile length in men treated with radical prostatectomy for prostate cancer.

PURPOSE: Some patients report that the penis is smaller after radical retropubic prostatectomy for prostate cancer. We performed a prospective study which measured penile length before and after radical retropubic prostatectomy. MATERIALS AND METHODS: A total of 124 men consented to penile measurements before radical prostatectomy performed by the same surgeon. Repeat measurements were performed at 3-month intervals following surgery. Penile measurements (cm.) consisted of flaccid length, stretched length, depth of prepubic fat pad and circumference. Statistical analysis of penile measurements was performed using the paired samples and independent Student's t test, Pearson's correlation and analysis of variance. RESULTS: Mean patient age was 59.1 (range 42 to 76). No patient had a penile abnormality, for example Peyronie's disease, or history of penile or urethral surgery. The size of the penis was significantly smaller after prostatectomy, and there was a significant difference for flaccid (p <0.001), stretched (p <0.001), prepubic fat pad (p = 0.02) and circumference measurements (p <0.01). Twelve patients (19%) had a 15% or greater decrease in stretched penile length. When dichotomizing groups at the cut point of 15% decrease, the independent t test of prostate size was not significant (t[df 36.7] = -1.83, p = 0.076). Nerve sparing was not significant in relation to change in penile stretched length, (F[df 2, 62] = 0.501, p = 0.609). CONCLUSIONS: Our findings support observations of decreased penile length after radical prostatectomy. Men should be counseled before radical prostatectomy that penile shortening may occur.

Adult↗
PubMed2003

A pelvic drain may be avoided after radical retropubic prostatectomy.

PURPOSE: We reassessed the role of routine pelvic cavity drainage to prevent complications after radical retropubic prostatectomy (RRP). MATERIALS AND METHODS: RRP was performed in 116 consecutive patients with clinically localized adenocarcinoma of the prostate. Clinical and pathological information was recorded for each patient. After the prostate was removed and the anastomotic sutures were tied the bladder was filled with saline through the urethral catheter. If there was no significant leakage, a drain was not placed. RESULTS: We did not place a drain in 85 of the 116 patients (73%). There were 3 immediate postoperative complications. In a patient without a drain, a urinoma developed that required percutaneous placement of a drain on postoperative day 2. None of the 116 patients had clinical evidence of infection, lymphocele or hematoma. Two patients had hematuria 2 weeks after catheter removal and needed bladder irrigation. Neither patient had a drain. Three patients (drain and no drain in 1 each) were in urinary retention after catheter removal, which required catheter reinsertion for an additional week. None had an anastomotic stricture. CONCLUSIONS: The morbidity of RRP is low when performed by those who regularly perform this procedure. If the bladder neck is preserved or meticulously reconstructed, there may be little or no extravasation and, thus, routine drainage may be unnecessary. In properly selected cases morbidity is not increased by omitting a drain from the pelvic cavity after RRP.

Drainage↗
PubMed2003

Expectant management of small, recurrent, noninvasive papillary bladder tumors.

PURPOSE: The majority of patients with stage Ta or T1 bladder cancer will have a subsequent tumor. Many of these patients invariably undergo multiple transurethral resections to manage small subsequent tumors or recurrences. We report our experience monitoring patients whose subsequent tumors appear to be small, low grade and papillary. MATERIALS AND METHODS: A total of 32 patients with small, papillary, low grade appearing tumors and a history of Ta or T1 transitional cell carcinoma were monitored. The decision to delay resection or fulguration and observe these tumors was based on bladder cancer history, endoscopic appearance of the tumor and presence or lack of symptoms. All patients had a previous Ta tumor, and the tumor being observed was always papillary and appeared to be low grade. The decision to resect the tumor(s) was based on change in appearance (size or configuration) at followup endoscopy or hematuria. Patient records were reviewed, and bladder cancer history and tumor observation periods were recorded. Several patients underwent a number of observation periods. Tumor grade and stage before the observation interval were compared to the pathology of the observed tumor(s) after eventual resection. Tumor growth rate was calculated based on estimated tumor size documented at each interval. RESULTS: Mean patient age was 72 years (range 39 to 88). Mean time since diagnosis of bladder cancer (initial urothelial tumor event) was 71 months (range 12 to 139). Mean number of subsequent tumor episodes or recurrences per patient was 3.8 (range 1 to 10). Mean number of transurethral resections was 3.8. Mean tumor-free interval before development of a subsequent tumor or mean time to recurrence was 13.4 months based on 104 tumor episodes. Not all tumor recurrences were observed. Mean number of tumor observation periods per patient was 1.8 (range 1 to 5) with a mean duration of 10.09 months per period based on 56 observation intervals. Mean time since the beginning of the initial observation period was 38 months (range 6 to 126). Mean tumor growth rate for 37 tumors was 1.77 mm per month (range 0 to 5.8). Only 3 of 45 (6.7%) patients had tumor progression from a pre-observation, low grade, noninvasive (TaG1 to 2) to a high grade Ta or T1 tumor. In the 3 observation periods in which the patient's most recent tumor was T1, 2 (67%) patients had TaG1 on resection after observation. Every patient with a T1 tumor before observation of a small new tumor had a history of a Ta tumor. No disease progressed to muscle invasion. CONCLUSIONS: Small, recurrent, low grade appearing bladder tumors are slow growing and pose minimal risk. Therefore, as an alternative to in office fulguration to minimize morbidity and cost associated with repeat transurethral resection it may not be necessary to remove these tumors promptly at new tumor occurrence or recurrence.

Adult↗
PubMed2003

Visual estimate of percent of carcinoma predicts recurrence after radical prostatectomy.

PURPOSE: Tumor volume is an important prognosticator for predicting prostate cancer recurrence following radical prostatectomy (RP). We assessed the ability of the visual estimate of the percent of carcinoma (VEPC) to predict recurrence. METHODS AND MATERIALS: As performed by 1 surgeon (MSS), 1,114 men underwent radical prostatectomy between 1992 and February 2002. Patients who had less than 12 months of followup, who underwent salvage RP or in whom VEPC was not assessed in the pathology specimen were excluded. VEPC and other clinical variables were analyzed. We performed univariate analysis using the Kaplan-Meier log rank test. Multivariate analysis using Cox proportional hazards regression was performed. RESULTS: A total of 692 patients with a mean age of 61 +/- 7 years met the criteria for this analysis. Mean followup was 52 +/- 30 months. Of the patients 17% had biochemical recurrence. Mean VEPC was 25% and 13% in those with and without recurrence, respectively. On univariate analysis all variables were significant predictors of recurrence. However, multivariate analysis showed that the only significant predictors of recurrence were patient age, initial prostate specific antigen 10 ng/ml or greater, RP Gleason 8 to 10, extraprostatic extension, seminal vesicle involvement and VEPC. Based on disease-free survival curves patients were stratified into 3 broad groups, namely low, intermediate and high volume. The HR for biochemical recurrence was 2.1 for the intermediate VEPC group (9.1% to 20%) and 2.7 for the high VEPC group (greater than 20%). In the reference group it was less than 9% (low volume). CONCLUSIONS: VEPC is a simple and inexpensive method that is an independent predictor of recurrence after RP.

Follow-Up Studies↗
PubMed2003

[Future prospects for primary hormone therapy in localized and locally advanced prostate cancer].

The authors consider current and future prospects for primary hormone therapy in localized and locally advanced prostate cancer by comparing this form of treatment (hormone monotherapy) with neoadjuvant radiation therapy and radical prostatectomy. Neoadjuvant hormone therapy prior to radiation therapy has been proven effective in recent years, and currently the United States is showing a year-by-year increase in the use of androgen blocking agents during the early stage of prostate cancer. A survey of recent research findings, clearly showed that, for patients with localized prostate cancer, there is no significant difference in survival rate between hormone monotherapy and radical prostatectomy. In the future we can expect to see an increase in available treatment options for localized and locally advanced prostate cancer, with the optimal therapy for each individual patient to be selected by the attending physician in discussion with the patient.

Androgen Antagonists↗
PubMed2002

Bladder tumor markers for monitoring recurrence and screening comparison of hyaluronic acid-hyaluronidase and BTA-Stat tests.

BACKGROUND: One of the goals of a noninvasive test for bladder carcinoma screening would be to reduce surveillance cystoscopies among patients with a history of bladder carcinoma. In addition, an accurate bladder carcinoma marker could be used to screen a high-risk population. The authors examined the efficacy of the hyaluronic acid-hyaluronidase (HA-HAase) and BTA-Stat tests to detect and predict bladder carcinoma recurrence and tested their specificity for bladder carcinoma screening. METHODS: Over a four year period, the authors prospectively collected 225 urine specimens from 70 bladder carcinoma patients and analyzed them by the HA-HAase test. Tumors were identified during 178 visits, and in 47 specimens there was no evidence of disease (NED). Twenty six of these 70 patients were randomly selected to have the BTA-Stat test (111 surveillance visits). In a separate study, 401 former Department of Energy (DOE) workers, who are likely to be at a higher risk for bladder carcinoma, were screened by the HA-HAase and BTA-Stat urine tests. RESULTS: The HA-HAase test had an approximately 91.0% sensitivity, 70% specificity, 87% accuracy, 92% positive predictive value (PPV), and 67% negative predictive value (NPV) in the 70 bladder carcinoma patients. There were 14 false-positives; however, 6 of these had recurred in approximately 5 months. Only 4 out of 33 NED cases recurred in that time period (chi-square = 5.43; degrees of freedom [DF] = 1; P = 0.0198). Thus, a false-positive HA-HAase test carried a significant risk of recurrence within five months (relative risk [RR] = 3.5; odds ratio [OR] = 5.44). In a direct comparison, the HA-HAase and BTA-Stat had 94% and 61% sensitivity, 63% and 74% specificity, 87% and 64% accuracy, 89% and 88% PPV, and 77% and 38% NPV, respectively. While 6 of the 10 false-positive on the HA-HAase test recurred in 5 months (chi-square = 9.6; DF = 1; P = 0.004), only 1 of the 7 false-positives on the BTA-Stat test recurred in that time period (chi-square = 0.096; DF = 1; P = 0.756). The RR and OR for the HA-HAase test were 10.2 and 24, and for the BTA-Stat, 1.4 and 1.5, respectively. In the DOE worker screening study, the HA-HAase and BTA-Stat had 14% (56 out of 401) and 16.7% (67 out of 401) positive rates, respectively. Sixty three percent of the positives on the BTA-Stat test, but only 25% of the positives on the HA-HAase test, had benign urologic conditions. None of the biomarker positive cases with clinical follow-up (n = 29) had evidence of bladder carcinoma. CONCLUSIONS: The HA-HAase test is efficient and superior to the BTA-Stat for detecting and predicting bladder carcinoma recurrence. Noninvasive tests with low false positive rates could be used for bladder carcinoma screening in high-risk populations (e.g., those with occupational exposure to carcinogens or smokers).

Biomarkers, Tumor↗
PubMed2002

Regulation of hyaluronidase activity by alternative mRNA splicing.

Hyaluronidase is a hyaluronic acid-degrading endoglycosidase that is present in many toxins and the levels of which are elevated in cancer. Increased concentration of HYAL1-type hyaluronidase correlates with tumor progression and is a marker for grade (G) 2 or 3 bladder cancer. Using bladder tissues and cells, prostate cancer cells, and kidney tissues and performing reverse transcription-PCR, cDNA cloning, DNA sequencing, and in vitro translation, we identified splice variants of HYAL1 and HYAL3. HYAL1v1 variant lacks a 30-amino acid (aa) sequence (301-330) present in HYAL1 protein. HYAL1v1, HYAL1v2 (aa 183-435 present in HYAL1 wild type), HYAL1v3 (aa 1-207), HYAL1v4 (aa 260-435), and HYAL1v5 (aa 340-435) are enzymatically inactive and are expressed in normal tissues/cells and G1 bladder tumor tissues. However, HYAL1 wild type is expressed in G2/G3 tumors and in invasive tumor cells. Stable transfection and HYAL1v1-specific antibody confirmed that the HYAL1 sequence from aa 301 to 330 is critical for hyaluronidase activity. All tumor cells and tissues mainly express HYAL3 variants. HYAL3v1 lacks a 30-aa sequence (299-328) present in HYAL3 protein, that is homologous to the 30-aa HYAL1 sequence. HYAL3v1, HYAL3v2 (aa 251-417 present in HYAL3 wild type), and HYAL3v3 (aa 251-417, but lacking aa 299-328), are enzymatically inactive. Although splicing of a single independent exon generates HYAL1v1 and HYAL3v1, internal exon splicing generates the other HYAL1/HYAL3 variants. These results demonstrate that alternative mRNA splicing controls cellular expression of enzymatically active hyaluronidase and may explain the elevated hyaluronidase levels in bladder/prostate cancer.

Adult↗
PubMed2002

Risk of positive margins and biochemical recurrence in relation to nerve-sparing radical prostatectomy.

PURPOSE: To assess the effect of nerve-sparing (NS) radical retropubic prostatectomy (RRP) on surgical margins and biochemical recurrence. PATIENTS AND METHODS: Location and incidence of positive surgical margins, recurrence, and time to recurrence were assessed in a consecutive series of 734 men who underwent RRP for localized prostate cancer from 1992 through February 2000. NS procedures were used in 33% (n = 240) of 734 patients studied. RESULTS: Surgical margins were positive for 24% (n = 58) and 31% (n = 152) of NS and non-NS patients, respectively (P =.06). No significant difference between the groups was found in location of positive margins (P =.92). Prostate-specific antigen level greater than 10 ng/mL, extraprostatic extension, tumor volume more than 20%, capsular penetration, Gleason score > or = 7, positive margins, and seminal vesicle invasion were associated with significantly increased risk of recurrence. However, NS patients were not at increased risk of recurrence compared with non-NS patients (hazard ratio, 0.96; 95% confidence interval, 0.53 to 1.72). The cumulative risk of recurrence within 3 and 5 years of surgery in NS patients was 9.7% and 14.4%, respectively, as compared with 17.1% and 21.1% for non-NS patients. CONCLUSION: In patients with localized prostate cancer, neither margin status nor biochemical-free survival within 5 years of surgery were altered by the nerve preservation technique. Given our experience, we recommend preservation of neurovascular bundles in these patients whenever the procedure is technically feasible.

Aged↗
PubMed2002

The procedure of transrectal ultrasound guided biopsy of the prostate: a survey of patient preparation and biopsy technique.

PURPOSE: We surveyed urologists in community and academic practice regarding their standard approach to patient preparation and their technique of transrectal ultrasound guided prostate biopsy. MATERIALS AND METHODS: We mailed 110 surveys to community urologists in Florida and urological oncologists at academic centers across the United States. Responses were calculated per group. RESULTS: Of the 88 respondents 34% were at academic centers and 66% were community urologists. Overall 79% of respondents prescribe an enema in preparation for biopsy, 81% administer an oral fluoroquinolone before biopsy, 50% give some type of analgesia, usually an oral agent, 63% obtain 8 or more cores per biopsy session, 36% biopsy the lateral and midline locations, and 83% do not use prostate specific antigen density to plan the biopsy strategy. CONCLUSIONS: The majority of urologists who responded to our survey ask their patients to use an enema in preparation for a transrectal biopsy procedure, prescribe an oral antibiotic and administer some type of analgesia. Few urologists administer a periprostatic nerve block. The majority obtain at least 8 biopsies and only 17% perform sextant biopsy. Some of these practices are not consistent with the literature. This survey provides insight into the practice patterns of urologists in regard to one of the most commonly performed office procedures.

Anesthesia, Local↗