Search PubMed⌕ Search

Biomedical subjects

S B Malkowicz

Publications and source records attributed to S B Malkowicz.

At least 91 records · Page 5Linked to original sources
PubMed1996

The role of the Sertoli cell in active immunosuppression in the human testis.

OBJECTIVE: To define the involvement of Sertoli cells in immune suppression within the testis by identifying surface receptor molecules that describe or communicate with cells of the immune system. MATERIALS AND METHODS: Ten pairs of human testes obtained from orchidectomy were stained immunohistochemically with established monoclonal antibodies that identify common cells of the immune system. RESULTS: Patterns of staining were similar in all testes. Class I major histocompatibility complex (MHC) antigen, important for self/non-self recognition, was found on Sertoli cells. Class II MHC antigen, important for immune cell interaction and limited to immune cells, was absent. Leu M3, characteristically found on macrophages, was also seen on Sertoli cells but no receptor antigens defining basic T cell types (CD4, CD8), B cells (Leu 12) or natural killer cells (Leu 11) were seen on Sertoli cells. CONCLUSIONS: The Sertoli cell membrane lacks lymphocyte-cell surface markers but harbours somatic cell and macrophage markers. This suggests that immunosuppression within the testis is not maintained through classic lymphocyte receptors. The presence of a macrophage marker is consistent with the known phagocytic activity of the Sertoli cell.

Adult↗
PubMed1996

Critical analysis of the ability of the endorectal coil magnetic resonance imaging scan to predict pathologic stage, margin status, and postoperative prostate-specific antigen failure in patients with clinically organ-confined prostate cancer.

PURPOSE: To determine whether there is a role for endorectal coil magnetic resonance imaging (erMRI) in the prediction of pathologic stage, margin status, and/or postoperative prostate-specific antigen (PSA) failure in patients with clinically organ-confined prostate cancer. PATIENTS AND METHODS: Using erMRI, the radiologic-pathologic correlation of extracapsular extension (ECE) and seminal vesicle invasion (SVI) was evaluated in 445 surgically managed patients. Logistic regression multivariable analysis was applied to the clinical stage, PSA, biopsy Gleason grade, and erMRI findings to assess the outcomes of ECE, SVI, positive surgical margins (PSM), and postoperative PSA failure. RESULTS: The accuracy of erMRI to predict for ECE and SVI numerically decreased with both increasing PSA and biopsy Gleason score because of the increasing false-negative scans in cases of microscopic transcapsular or seminal vesicle disease. Of patients who could not be categorized into low or high risk for postoperative PSA failure on the basis of clinical stage, preoperative PSA, and biopsy Gleason score, a negative or positive erMRI for ECE or SVI stratified these patients into groups with a 78% versus 21% (P < .0001) 3-year rate of actuarial freedom from PSA failure. In this subgroup, the overall accuracy of the erMRI was 70% +/- 6% and 94% +/- 2% for ECE and SVI, respectively. The most significant predictor on multivariable analysis of PSM was the erMRI finding of ECE (P = .0001). CONCLUSION: This initial report suggests that a preoperative erMRI can identify clinically organ-confined prostate cancer patients at high risk for having ECE, SVI, and PSM that otherwise would be missed on the basis of the clinical stage, preoperative PSA, and biopsy Gleason score. Confirmatory studies are needed.

Adenocarcinoma↗
PubMed1996

Strategy for repeat biopsy of patients with prostatic intraepithelial neoplasia detected by prostate needle biopsy.

PURPOSE: We evaluated the strategy for repeat biopsy of patients with prostatic intraepithelial neoplasia without concurrent carcinoma detected on prostate needle biopsy. MATERIALS AND METHODS: Of 1,275 consecutive patients undergoing prostate needle biopsy 61 were identified with prostatic intraepithelial neoplasia but without concurrent prostate carcinoma. Of the 61 patients 53 had undergone repeat biopsy. The medical records, transrectal ultrasound, and operative and pathological reports of these patients were reviewed. RESULTS: Repeat biopsy was done in 53 patients with prostatic intraepithelial neoplasia, yielding carcinoma in 15, prostatic intraepithelial neoplasia without carcinoma in 8 and benign tissue in 30. The yield of carcinoma from repeat biopsy of a prostatic intraepithelial neoplasia site was 8.3% (7 of 84 sites). A total of 18 sites of carcinoma was detected by repeat biopsy of a previous random biopsy site (8), a prostatic intraepithelial neoplasia site only (5), a transrectal ultrasound nodule (3), a palpable nodule and prostatic intraepithelial neoplasia site (1), and a transrectal ultrasound nodule and prostatic intraepithelial neoplasia site (1). Carcinoma was as frequently detected by repeat biopsy of a prostatic intraepithelial neoplasia site (6 patients) as by random repeat biopsy (6 patients). CONCLUSIONS: Repeat prostate needle biopsy of patients with prostatic intraepithelial neoplasia should include random repeat biopsy and repeat biopsy of transrectal ultrasound abnormalities as well as previous sites of prostatic intraepithelial neoplasia.

Adenocarcinoma↗
PubMed1996

Laparoscopic lymphadenectomy based on magnetic resonance imaging: is a unilateral dissection adequate for staging prostate cancer?

Laparoscopic pelvic lymphadenectomy is a satisfactory alternative to open lymphadenectomy for staging prostate cancer. Specific information obtained by endorectal coil magnetic resonance imaging may be used to predict the most likely side for lymph node metastases. These criteria may be used to define side selection for performing a unilateral laparoscopic lymphadenectomy without the risk of missing contralateral nodes that may be positive. A unilateral dissection when feasible reduces operative time and morbidity.

Aged↗
PubMed1995

A method for determining a prostate-specific antigen cure after radiation therapy for clinically localized prostate cancer.

PURPOSE: A method that allows the determination of a prostate-specific antigen (PSA) cure after definitive management for prostate carcinoma with radiation therapy is presented and tested. METHODS AND MATERIALS: The method involves a calculation of the patient's theoretical baseline PSA prior to the development of prostate cancer by using three serial rising PSA determinations obtained prior to the institution of therapy. The rate of rise of the PSA prior to therapy and the rate of decline of the PSA posttherapy are calculated, using an exponential model. Two criteria must be satisfied to define a PSA cure. First, the PSA nadir after treatment should be less than the calculated theoretical baseline PSA. Second, the rate of decline of PSA posttreatment should be greater than the rate of rise of the PSA prior to treatment. RESULTS: Applying these two criteria to the patient data base (n = 16) at a median follow-up of 19 months enabled the accurate prediction of 6 out of 6 (100%) of patients with documented PSA failure and 7 out of 10 (70%) of patients without PSA failure. Therefore, despite short follow-up, all six patients with PSA failure were predicted. Further follow-up is needed to ascertain if the seven patients predicted to be cured will remain PSA failure free and if the three patients currently without PSA failure in whom the model predicts failure, will subsequently fail. CONCLUSION: Therefore, using each patient's PSA history as the natural control may eliminate the error that is introduced with defining a PSA cure by using a single value for the PSA nadir at a specified time after radiation therapy.

Humans↗
PubMed1995

The impact of the inclusion of endorectal coil magnetic resonance imaging in a multivariate analysis to predict clinically unsuspected extraprostatic cancer.

BACKGROUND: The introduction of the endorectal coil magnetic resonance imaging (MRI) technique has improved the accuracy of preoperative staging for prostate cancer. This study quantifies the improvement in the ability to identify clinically unsuspected extraprostatic disease with the use of the endorectal coil MRI. METHODS: A retrospective review of the pathologic findings of 347 patients with prostate cancer treated with a radical retropubic prostatectomy was performed. The preoperative clinical indicators including prostate specific antigen (PSA), clinical stage, Gleason score, and endorectal coil MRI data were employed in a multivariate analysis to identify patients who were at high risk for seminal vesicle invasion (SVI) or extracapsular extension (ECE). The sensitivity, specificity, and positive and negative predictive values for predicting SVI and ECE were calculated using the significant clinical indicators found on the multivariate analysis. RESULTS: The clinical factors identified on multivariate analysis as significant predictors of SVI include the endorectal coil MRI data (P < 0.0001), PSA (P = 0.0096), and the Gleason score (P = 0.012). Endorectal coil MRI data (P < 0.0001), PSA (P = .0001), and Gleason score (P < .0001) were significant predictors of ECE. In the patient subgroup with PSA (> 10-20 ng/ml) and Gleason score of 5 to 7, the addition of the endorectal coil MRI data enabled an additional 71 and 27% of patients with SVI and ECE, respectively, to be correctly identified. These patients would have been missed based on the prediction obtained from the PSA and Gleason score alone. CONCLUSIONS: The use of the endorectal coil magnetic resonance imaging data, in addition to prostate specific antigen and Gleason score, provides a more accurate prediction of the pathologic outcome of seminal vesicle invasion and extracapsular extension than the PSA and Gleason score alone for the patient subgroup with a PSA of greater than 10 to 20 ng/ml and Gleason score of 5 to 7.

Adenocarcinoma↗
PubMed1995

Antiproliferative effects of tyrosine kinase inhibitors (tyrphostins) on human bladder and renal carcinoma cells.

Growth factor receptors with tyrosine kinase activity mediate paracrine and autocrine growth regulation of normal and malignant cells. The epidermal growth factor receptor (EGF-R) is a tyrosine kinase transmembrane protein that is overexpressed by many epithelial malignancies, including transitional cell and renal cell carcinoma. Ligand-induced stimulation of cell growth depends on activation of the tyrosine kinase activity of the EGF-R. Tyrphostins are small molecular weight compounds that have been shown to preferentially inhibit the EGF-R tyrosine kinase and thus may inhibit EGF-R-dependent cell growth. We examined the effect of two tyrphostins, RG14620 and AG555, on the proliferation of three transitional cell carcinoma lines (RT4, J82, and T24) and three renal cell carcinoma lines (A-198, Caki-1, and Caki-2). Both tyrphostins inhibited proliferation of all six cell lines in a dose-dependent fashion. They were equally effective with IC50s ranging between 3 and 16 microM. Complete inhibition of growth was achieved at tyrphostin concentrations between 10 and 30 microM. Although both tyrphostins inhibited proliferation of T24 transitional carcinoma cells in growth assays, only RG14620 but not AG555 was found to specifically inhibit EGF-R autophosphorylation in this cell line. These results suggest that other intracellular targets in addition to the EGF-R are affected by these agents. In summary, tyrphostins are potent growth inhibitors for urological malignancies.

Adult↗
PubMed1995

The effect of cholinergic stimulation on cultured smooth muscle cells.

OBJECTIVE: To assess the role of cholinergic angonists and antagonists on the growth control of cultured rabbit detrusor smooth muscle cells. DESIGN: Dosage dependent growth curve analysis of smooth muscle cells in standard media to bethanechol and atropine at concentrations from 1 x 10(-5) to 1 x 10(-9) mMol. RESULTS: Exogenous exposure to bethanechol results in a significant dose dependent increase in total cell number over a 10 day period. At a concentration of 1 x 10-6 and 1 x 10-5 mMol a 20% to 50% growth increase is noted. Exogenous atropine at all concentrations decreased growth by approximately five fold. CONCLUSIONS: The exogenous application of muscarinic cholinergic agonists and antagonists can significantly effect bladder muscle cell growth in vitro. The mechanism of growth control through these pharmacological receptors remains to be elucidated.

Animals↗
PubMed1995

Cell saver and radical retropubic prostatectomy: analysis of cost-effectiveness.

OBJECTIVES: To determine the effectiveness of using cell saver suction during radical prostatectomy to decrease the risk of random donor transfusions in patients predonating blood, as well as to compare costs. METHODS: From March 1992 to October 1993, two consecutive groups of 86 patients underwent radical retropubic prostatectomy. The first group utilized predonated blood alone, and the second group utilized cell saver suction and predonated blood. The two groups were compared with respect to their transfusion records, preoperative and discharge hemoglobins, and estimated blood losses to determine the usefulness of cell saver suction during radical retropubic prostatectomy. RESULTS: There was no statistical difference in the rate of random donor blood transfusions between these two evenly matched groups of patients. The risk of receiving random donor transfusions was decreased to 5% by having 4 U of blood predonated by or for the patient prior to radical prostatectomy. CONCLUSIONS: For patients who are able to predonate blood, cell saver suction is neither cost-effective nor useful in decreasing the risk of receiving random donor blood transfusions.

Blood Transfusion, Autologous↗
PubMed1995

A multivariate analysis of clinical and pathological factors that predict for prostate specific antigen failure after radical prostatectomy for prostate cancer.

A Cox regression multivariate analysis was done to determine the clinical and pathological indicators that predict for prostate specific antigen (PSA) failure in 347 patients who underwent radical prostatectomy for clinically localized prostate cancer between 1989 and 1993. In the patient subgroups (PSA less than 20 ng./ml. and biopsy Gleason sum 5 to 7 or PSA more than 10 to 20 ng./ml. and biopsy Gleason sum 2 to 4) not classifiable into those at high and low risk for postoperative PSA failure using PSA and biopsy Gleason sum, the status of the seminal vesicles and prostatic capsule on endo-rectal coil magnetic resonance imaging (MRI) allowed for this categorization. Specifically, 2-year actuarial PSA failure rates were 84% versus 23% in patients with and without seminal vesicle invasion, respectively, on MRI (p < 0.0001) and 58% versus 21% in those with and without extracapsular extension, respectively (p = 0.0001). In patients with extracapsular extension but without pathological involvement of the seminal vesicle(s) or poorly differentiated tumors (pathological Gleason sum 8 to 10), the 2-year actuarial PSA failure rates were 50% (margin positive), 28% (margin negative with established extracapsular disease) and 9% (margin negative with focal microscopic extracapsular disease). Therefore, endo-rectal coil MRI showing seminal vesicle invasion or extracapsular extension when the PSA level is less than 20 ng./ml. and the biopsy Gleason sum is 5 to 7 or the PSA level is more than 10 but less than 20 ng./ml. and the biopsy Gleason sum is 2 to 4 predicted for PSA failure. In patients with extracapsular extension who had pathological Gleason sum less than 8 disease with uninvolved seminal vesicles, the margin status and extent of extracapsular disease predicted for PSA failure.

Actuarial Analysis↗
PubMed1994

A multivariable analysis of clinical factors predicting for pathological features associated with local failure after radical prostatectomy for prostate cancer.

PURPOSE: A multivariate analysis is used to determine the predictive value of pretreatment clinical indicators on pathologic features associated with local failure after radical prostatectomy in patients with prostate cancer. METHODS AND MATERIALS: A retrospective review of the pathologic findings of 235 patients with adenocarcinoma of the prostate treated between 1990 and 1993 with a radical retropubic prostatectomy was performed. The preoperative clinical data including the serum prostate specific antigen, clinical stage, Gleason sum, and endorectal magnetic resonance scan findings are used to identify patients prior to definitive treatment who would be at high risk for having pathologic features associated with local failure at radical prostatectomy. Outcome prediction curves are constructed from a logistic regression multivariate analysis displaying the probability of pathologic involvement of the seminal vesicle, extracapsular disease, or positive surgical margins as a function of the preoperative prostate specific antigen and Gleason sum for the cases when the endorectal magnetic resonance scan is positive, negative, or not included in the multivariate analysis. RESULTS: Factors identified on multivariate analysis as significant predictors of seminal vesicle invasion include endorectal magnetic resonance scan findings (p < 0.0001), and preoperative prostate specific antigen (p = 0.017). Endorectal magnetic resonance scan findings (p = 0.0016), preoperative prostate specific antigen (p = 0.0002), and Gleason sum (p < 0.0001) were significant predictors of extracapsular extension and preoperative prostate specific antigen (p < 0.0001) and Gleason sum (p = 0.03) were significant predictors of disease extending to the margins of resection. Clinical stage was not a significant predictor (p > 0.05) of pathologic features associated with local failure on multivariate analysis. As a single modality, endorectal surface coil magnetic resonance imaging was accurate 93%, 69%, and 72% of the time for predicting seminal vesicle invasion, transcapsular disease, and final pathologic stage, respectively. Failure to recognize microscopic penetration of the capsule found at the time of pathologic evaluation in a prostate gland with a grossly intact capsule accounts for the majority (70%) of the staging inaccuracies. CONCLUSIONS: The use of the endorectal surface coil magnetic resonance scan findings in conjunction with both the serum prostate specific antigen and Gleason sum improves the clinical accuracy of predicting those patients at high risk for clinically unsuspected extraprostatic disease. In particular, for the subgroup of patients with moderately elevated prostate specific antigen (> 10-20 ng/mL) and intermediate grade clinically organ confined prostate cancer [Gleason sum: 5-7] where the specificity of these tests to predict for occult extraprostatic disease is suboptimal, the additional information obtained from the endorectal coil magnetic resonance scan allows the physician to definitively subgroup these patients into low and high risk for seminal vesicle invasion or transcapsular disease.

Adenocarcinoma↗
PubMed1994

Locally advanced renal cell carcinoma: low complication rate and efficacy of postnephrectomy radiation therapy planned with CT.

PURPOSE: To determine the usefulness of computed tomography (CT) in planning radiation therapy for locally advanced renal cell carcinoma after nephrectomy. MATERIALS AND METHODS: The authors retrospectively analyzed the treatment records and follow-up status of 12 consecutive patients who underwent radical nephrectomy and postoperative radiation therapy for locally advanced renal cell carcinoma. Records' of 12 consecutive patients who underwent only radical nephrectomy were also analyzed. RESULTS: None of the patients who received radiation therapy after nephrectomy had local-regional recurrence, despite disease at the surgical margins in six patients; the actuarial disease-free survival at 5 years was 75%. In contrast, the 5-year actuarial local failure rate in the surgery-only group was 30% (significant difference at P < .01) and the disease-free survival rate was 62% (mean and median follow-up was 4.6 and 5.1 years, respectively). CONCLUSION: With CT, radiation can be delivered to the renal bed safely and without undue morbidity. Given the lack of chronic complications associated with the side effects of radiation therapy and uniform local control of cancer in these patients, the role of radiation therapy in patients at high risk for local failure may be reconsidered.

Carcinoma, Renal Cell↗