Biomedical subjects
M J Manyak
Publications and source records attributed to M J Manyak.
A comparison of urinary nuclear matrix protein-22 and bladder tumour antigen tests with voided urinary cytology in detecting and following bladder cancer: the prognostic value of false-positive results.
OBJECTIVES: To evaluate the diagnostic and prognostic value of the nuclear matrix protein-22 (NMP22) and bladder tumour antigen (BTAstat) tests compared with voided urinary cytology (VUC) in detecting and following bladder cancer, assessing particularly the prognostic value of false-positive test results in patients followed up for bladder cancer. PATIENTS AND METHODS: From 739 patients suspected of having bladder cancer, voided urine samples for the NMP22 and BTAstat tests, and for VUC and urine analysis, were collected before cystoscopy. All patients underwent transurethral resection of bladder lesions or mapping. and were followed for a mean (range) of 27.3 (3-65) months. RESULTS: In the 406 patients with bladder cancer, the overall sensitivity was 85% for NMP22, 70% for BTAstat and 62% for VUC. For histological grades 1-3 the sensitivity in detecting transitional cell carcinoma was 82%, 89% and 94% for NMP22, 53%, 76% and 90% for BTAstat, and 38%, 68% and 90% for VUC, respectively. Although the sensitivity in detecting invasive carcinoma was >85% for all the tests. NMP22 and BTAstat were statistically more sensitive than VUC for superficial tumours. The optimal threshold value for NMP22, calculated using the receiver operating characteristics curve was 8.25 U/mL. The specificity was 68% for NMP22, 67% for BTAstat, and 96% for VUC. The specificity of VUC remained >87% and was independent of benign histological findings. In contrast, in patients with no apparent genitourinary disease on histology, NMP22 and BTAstat had significantly higher specificity (94% and 92%, respectively: P=0.003) than in the group with chronic cystitis (52% for both tests). Forty patients having no bladder cancer at biopsy had a recurrence after a mean (range) follow-up of 7.7 (3-15) months: all had a previous history of bladder cancer. According to subsequent recurrence, the prognostic positive and negative predictive values were 18% and 91% for NMP22, 13% and 88% for BTAstat, and 79% and 91% for VUC. Both false-positive VUC and NMP22 tests predicted recurrence (log-rank test, P<0.001 and P=0.004, respectively), but the BTAstat test produced no similar correlation (P=0.778). CONCLUSION: The NMP22 and BTAstat tests are better than VUC for detecting superficial and low-grade bladder cancer but they have significantly lower specificity. After excluding diseases with the potential to interfere in these tests the overall specificity of both tests is increased considerably. False-positive results from NMP22 and VUC but not from BTAstat in patients followed up for bladder cancer correlate with future recurrences.
The enigma of prostatitis. Recent advances in classification and management.
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Cost effectiveness of microwave thermotherapy in patients with benign prostatic hyperplasia: part I-methods.
OBJECTIVES: To present the method used to evaluate the cost effectiveness, from the societal perspective, of transurethral microwave thermotherapy relative to medical therapy (alpha-blocking agents) and transurethral resection of the prostate (TURP) for a hypothetical cohort of 65-year-old men with moderate-to-severe benign prostatic hyperplasia (BPH) symptoms. METHODS: We constructed a decision-analytic Markov model with 25 health states describing the 3 treatments, 5 short-term clinical events, and 17 possible long-term outcomes. Each health state had an associated cost and utility. Utility weights, reflecting an individual's preference for a specific health outcome, range from 0, indicating death, to 100, indicating perfect health. Utility estimates were obtained by interviewing 13 men with moderate-to-severe BPH symptoms using the standard gamble preference measurement technique. On the basis of their risk attitudes, the patients were classified as risk averse or non-risk averse. The rates of remission, temporary and permanent adverse events, retreatment, and mortality were obtained from the Targis System (Urologix) randomized clinical trial, published reports, and a consensus panel. The costs during the 5 years after treatment initiation were estimated using national Medicare reimbursement schedules. The costs are reported in 1999 U.S. dollars. RESULTS: Eliciting utility values from patients with BPH was feasible and generated internally consistent and externally valid measures. In the non-risk-averse group, the utility value for significant remission, moderate remission, no remission, and worsening BPH symptoms without an adverse event was 99.1, 97.1, 94.4, and 87.3, respectively. As expected, the risk-averse individuals (n = 6) exhibited higher utility values than those in the non-risk-averse group (n = 7). In the non-risk-averse group, thermotherapy was the preferred treatment, and in the risk-averse group, medical therapy was preferred. In both groups, TURP was the least preferred therapy. The initial thermotherapy procedure costs without complications were estimated at $2629, and the initial TURP procedure costs without complications were estimated at $4597. Time-dependent probabilities were developed to reflect treatment durability. CONCLUSIONS: The resulting model parameters appear to be suitable for evaluating the cost effectiveness of thermotherapy relative to medical therapy and TURP in 65-year-old men with moderate-to-severe BPH symptoms.
Cost effectiveness of microwave thermotherapy in patients with benign prostatic hyperplasia: part II--results.
OBJECTIVES: To evaluate the cost effectiveness of transurethral microwave thermotherapy relative to medical therapy (alpha-blocking agents) and transurethral resection of the prostate (TURP) for patients with moderate-to-severe benign prostatic hyperplasia (BPH) symptoms. METHODS: A cost-effectiveness analysis was performed from the societal perspective for a hypothetical cohort of 65-year-old men with moderate-to-severe BPH symptoms. We calculated the incremental cost effectiveness of thermotherapy relative to medical therapy and TURP during 5 years after treatment initiation. Event probabilities were obtained from published reports, a consensus panel, and the Targis System (Urologix) randomized clinical trial. Costs were estimated using the national Medicare reimbursement schedules. Costs are reported in 1999 U.S. dollars. Total thermotherapy procedure costs were estimated at $2629. Quality-of-life and utility estimates were obtained by interviewing 13 patients with moderate-to-severe BPH symptoms. On the basis of their risk attitudes, patients were classified into risk-averse or non-risk-averse groups. The costs and health effects were discounted at 3% annually. RESULTS: In a hypothetical cohort of 10,000 non-risk-averse patients who were candidates for all three modalities, the 5-year costs were highest for patients undergoing TURP and lowest for those receiving medical therapy ($7334 and $6294, respectively). The thermotherapy group exhibited the highest 5-year utility value (53.52 quality-adjusted life-months). Compared with medical therapy, thermotherapy resulted in an additional 0.23 quality-adjusted life-months, with an incremental cost of $741. This yielded an incremental cost per quality-adjusted life-year gained of $38,664 for thermotherapy compared with medical therapy. Thermotherapy had a higher utility (difference of 1.71 quality-adjusted life-months) and lower cost (difference of $299) compared with TURP and thus was dominant over TURP. The results were similar for a hypothetical cohort of 10,000 risk-averse patients. CONCLUSIONS: From a societal perspective, thermotherapy appears to be a reasonable and cost-effective alternative to both medical and surgical treatment. However, the actual treatment decision should be based on multiple factors, only one of which is cost effectiveness.
Inhibitors of prostaglandin synthesis inhibit human prostate tumor cell invasiveness and reduce the release of matrix metalloproteinases.
Eicosanoids modulate the interaction of tumor cells with various host components in cancer metastasis. Their synthesis involves the release of arachidonic acid (AA) from cellular phospholipids by phospholipase A2 (PLA2), followed by metabolism by cyclooxygenases (COXs) and lipooxygenases (LOXs). This study aimed to identify the pathway(s) of AA metabolism that are required for the invasion of prostate tumor cells. DU-145 and PC-3 human prostate cancer cell lines were used to test the effect of inhibitors of PLA2, COX, or LOX on the invasion of prostate tumor cells through Matrigel in vitro using the Boyden chamber assay and fibroblast-conditioned medium as the chemoattractant. We used nontoxic doses that did not inhibit simple cell motility and did not decrease clonogenic survival. All of the inhibitors caused a significant reduction in AA release from treated cells compared with control cells, which indicated that the treatments were biochemically active. Invasion through Matrigel was inhibited by the PLA2 inhibitor 4-bromophenacyl bromide (4-BPB), the general COX inhibitor ibuprofen (IB), and the highly selective COX-2 inhibitor NS398. Inhibition of cell invasiveness by 4-BPB (1.0 microM), IB (10.0 microM), and NS398 (10.0 microM) was reversed by the addition of prostaglandin E2 (PGE2). PGE2 alone, however, did not stimulate invasiveness, which suggests that its production is necessary for rendering the cells invasive-permissive but not sufficient for inducing invasiveness. In contrast, we found no significant inhibition of invasion of prostate tumor cells treated with esculetin (1.0 microM) or nordihydroguiaretic acid (1.0 microM), which are specific inhibitors of LOX. We also tested the effect of 4-BPB, IB, NS398, and esculetin on the secretion of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), as key enzymes in the proteolysis of Matrigel during invasion, using gelatin zymograms and Western blots. Cells that received 4-BPB, IB, or NS398, but not esculetin showed a significant reduction in the levels of proMMP-2, MMP-9, and proMMP-9 in the culture medium. DU-145 cells did not secrete TIMP-1, and the drugs did not alter the secretion of TIMP-2. This work highlights the role played by COX in disturbing the balance between MMPs and TIMPs in prostate cancer cells, and it points to the potential use of COX inibitors, especially COX-2 selective inhibitors, in the prevention and therapy of prostate cancer invasion.
Capromab Pendetide immunoscintigraphy: connecting the dots for prostate cancer imaging.
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Anastomotic calculus formation after side-to-side ureteroureterostomy in a patient with complete ureteral duplication.
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Comparison of clinical staging algorithms and 111indium-capromab pendetide immunoscintigraphy in the prediction of lymph node involvement in high risk prostate carcinoma patients.
BACKGROUND: The pretherapy prediction of occult lymph node involvement and the avoidance of otherwise futile and potentially morbid definitive local therapy is paramount in men with newly diagnosed prostate carcinoma. To identify patients with prostate carcinoma who likely have lymph node involvement and would benefit from staging lymphadenectomy prior to definitive local therapy, the authors compared the ability of several predictive staging algorithms and a radiolabeled monoclonal antibody scan to predict lymphatic metastases prior to treatment. METHODS: Between August 1991 and June 1994, 198 men with clinical T2 or T3 classified (TNM) prostate carcinoma (bone scan negative) who were at high risk of lymph node involvement underwent a 111In-capromab pendetide scan prior to staging lymphadenectomy. Several predictive models based on preoperative prostate specific antigen level, biopsy Gleason score, and clinical stage were selected to predict those men having a > or =20% probability of lymph node involvement. The ability to predict pathologic stage using several clinical algorithms and the monoclonal antibody scan was compared with pathologic examination of the lymph nodes. RESULTS: Overall, 39% of the pelvic lymph node specimens were positive for metastatic disease by pathologic analysis. Published algorithms predicting lymph node metastases had a positive predictive value (PPV) ranging from 40.5% to 46.6% and an area under the receiver operating characteristic curve (AUC) ranging from 0.52 to 0.61. The monoclonal antibody scan had a PPV of 66.7% and an AUC of 0.71. The differences between the PPV and the AUC for the individual clinical algorithms when compared with immunoscintigraphy were statistically significant. Combining the radiolabeled monoclonal antibody scan with clinical predictive models, a PPV of up to 72.1% could be obtained. CONCLUSIONS: These data suggest that the PPVs for the clinical predictive algorithms are similar and that the PPV of the radiolabeled monoclonal antibody scan alone or in combination with the algorithms has additional value in predicting lymph node involvement in prostate carcinoma patients at high risk of regional disease spread. These algorithms and the 111In-capromab pendetide scan may be used for the appropriate selection of candidates for definitive local therapy in men with clinically localized prostate carcinoma and significant risk of lymph node involvement.
Immunoscintigraphy with indium-111-capromab pendetide: evaluation before definitive therapy in patients with prostate cancer.
OBJECTIVES: No standard noninvasive diagnostic test reliably differentiates patients with organ-confined prostate cancer from those with lymph node metastases. The ability of a radiolabeled monoclonal antibody, indium-111 (111ln)-capromab pendetide, to identify sites of metastatic disease in patients at moderate to high risk of nodal involvement was investigated. METHODS: The study prospectively evaluated 160 patients with prostate cancer scheduled to undergo pelvic lymph node dissection (PLND) before or during definitive treatment. All were at relatively high risk of nodal involvement by virtue of significantly elevated baseline prostate-specific antigen (PSA) values, Gleason scores, and/or locally advanced clinical stages of disease. The histologic findings of the PLNDs were compared with the results of immunoscintigraphy, computed tomography, and magnetic resonance imaging. RESULTS: Among the 152 evaluable patientS studied with 111In-capromab pendetide before PLND, the sensitivity of immunoscintigraphy for lymph node detection was 62% and the specificity was 72%; the positive predictive value was 62% and the negative predictive value was 72%. In comparison, the sensitivity of computed tomography and magnetic resonance imaging was 4% and 15%, respectively, and the specificity was 100% for both procedures on the basis of a large number of negative interpretations. Logistic regression analysis revealed that immunoscintigraphy with 111In-capromab pendetide provided strong, independent evidence of the presence of lymph node metastases. Furthermore, the analysis indicated that certain combinations of PSA, Gleason score, and 111In-capromab pendetide were particularly effective at predicting the risk of nodal involvement. CONCLUSIONS: Immunoscintigraphy with 111In-capromab pendetide outperformed standard diagnostic imaging techniques in the detection of prostate cancer lymph node metastases and provided independent prognostic information that complemented PSA, Gleason score, and clinical stage.
111Indium-capromab pendetide in the evaluation of patients with residual or recurrent prostate cancer after radical prostatectomy. The ProstaScint Study Group.
PURPOSE: Standard diagnostic methods are limited for detecting distant metastases in patients with prostate cancer in whom the only evidence of disease after radical prostatectomy is a detectable prostate specific antigen (PSA) level. We evaluated the role of immunoscintigraphy with the radiolabeled monoclonal antibody, 111indium ((111)In)-capromab pendetide, to differentiate between local and distant recurrence in this patient population. MATERIALS AND METHODS: We enrolled 183 men who had undergone radical prostatectomy in whom PSA later increased. Gamma camera images were acquired twice after infusion of a single dose of (111)In-capromab pendetide. RESULTS: Immunoscintigraphy revealed disease in 108 of 181 patients (60%) with interpretable scans. The antibody was localized most frequently to the prostatic fossa (34% of the cases), abdominal lymph nodes (23%) and pelvic lymph nodes (22%). Of the 181 men the scan localized the antibody outside the prostatic fossa in 42%. Half of the positive localizations in the fossa were confirmed by biopsy. CONCLUSIONS: These findings suggest that immunoscintigraphy with (111)In-capromab pendetide can assist in determining the extent of disease in patients who have increasing PSA after prostatectomy.
Subspecialization, recruitment and retirement trends of American urologists.
PURPOSE: Trends of urology workforce, subspecialization, recruitment practices, retirement planning, practice characteristics and managed care impacts in the United States were assessed. MATERIALS AND METHODS: In February 1996 the executive interviewing branch of The Gallup Organization selected randomly and interviewed by telephone 507 practicing urologists in the United States who had provided urological patient care for more than 20 hours per week, practiced in 1995 and completed a urological residency program. RESULTS: Several important issues emerged. Urologists think we may be training too many urologists, subspecialty board certification would be a divisive issue to urology as a whole and 90% of urologists have an active retirement plan, although 23% are not funding the plan fully. CONCLUSIONS: The American Urological Association Gallup Poll, as refined by the Health Policy Survey and Research Committee, continues to be a unique and valuable tool in assessing practice patterns, gathering demographic data and measuring opinions of the American urologist. This information will help us chart our way to the twenty-first century.
Oral bropirimine immunotherapy of bladder carcinoma in situ after prior intravesical bacille Calmette-Guérin.
OBJECTIVES: Bropirimine is an oral immunomodulator that has demonstrated anticancer activity in transitional cell carcinoma in situ (CIS) in both the bladder and upper urinary tract. Activity also has been documented in patients after prior therapy with bacille Calmette-Guérin (BCG). To more accurately estimate bropirimine's efficacy in BCG-resistant bladder CIS, a Phase II trial was performed. A separate analysis was performed in additional patients intolerant of BCG toxicity. METHODS: Patients received bropirimine 3.0 g/day by mouth for 3 consecutive days, weekly, for up to 1 year. Bladder biopsies and cytologic examination were performed quarterly. Complete response (CR) required negative biopsy and cytology results. RESULTS: Twenty-one of 86 patients entered were not evaluable. CR was seen in 21 (32%; 95th percentile confidence interval [CI], 21% to 44%) of 65 evaluable patients, including 14 (30%, CI 17% to 43%) of 47 BCG-resistant, and 7 (39%, CI 16% to 61%) of 18 BCG-intolerant patients. Overall, by intent-to-treat analysis, CR was thus seen in 21 (24%) of 86 subjects. Most BCG-resistant patients were failures to BCG without relapse, and had received 12 to 36 (median 12) BCG treatments; intolerant patients had received 4 to 11 treatments (median 6). Response duration ranged from 65 to 810 days, with median not yet reached (but greater than 12 months). Thirteen (15%) of 86 stopped bropirimine due to toxicity. Progression to invasive or metastatic disease during or immediately after therapy was documented in only 4 patients (6%), all nonresponders. CONCLUSIONS: Bropirimine may be an alternative to cystectomy for some patients with bladder CIS who have failed or have not tolerated BCG. Further evaluation to improve responses and durability is warranted.
Malignant osteoclast-like giant cell tumor of the kidney.
Osteoclast-like giant cell tumors are rare mesenchymal tumors that typically present in osseous tissue and are remarkable because of their slow growth. We report the sixth documented case of a malignant osteoclast-like giant-cell tumor primary to the kidney of an 81-year-old man with a 5-month history of hematuria. Postnephrectomy analysis of the tumor, including immunohistochemical stains and electron microscopy, confirmed the diagnosis. Although the patient died of unrelated complications, metastatic disease was suspected.
The role of computerized tomography, magnetic resonance imaging, bone scan, and monoclonal antibody nuclear scan for prognosis prediction in prostate cancer.
The single most important issue in determination of treatment options for prostate cancer is accurate assessment of disease extent. Some prediction of probability is afforded by algorithms of patient and tumor characteristics, but definitive detection of disease extension before this decision often remains difficult. This is the critical issue in the healthy 58-year-old man depicted with relatively high-grade, high-volume prostate cancer and a moderately low serum PSA relative to these characteristics. Any combination of choices for evaluation and treatment of this patient is likely to generate some controversy. This article discusses both the changing trends in treatment patterns, which place more emphasis on noninvasive staging and the limited value of conventional radiographic evaluation to detect small volume or microscopic disease. Recent advances in imaging techniques with magnetic resonance and radiolabeled monoclonal antibodies may provide more precise localization of prostate cancer in these clinical circumstances. The relative merits and limitations of the current and selected emerging imaging technology for prostate cancer detection are provided in this article.
Loss of uteroglobin expression in prostate cancer: relationship to advancing grade.
We have shown previously that the secretory protein uteroglobin (UG) is highly expressed in normal human prostate tissue but this expression is either lost or altered in human prostate cancer cell lines. Treatment of these cell lines with recombinant human UG inhibits their ability to invade human reconstituted basement membrane by up to 90%, implying that the loss of normal UG expression may be related to the invasive potential of prostate cancer. Because invasion represents a critical step in metastasis, the expression patterns of UG could provide a unique and relevant indicator of cancer progression. In this study, we present the immunohistochemical analyses of fresh frozen prostate tissues from surgical specimens taken from 50 patients. Eight slides per patient were analyzed for UG staining. Slides from 26 patients showed evidence of prostate cancer, whereas slides from the remaining 24 patients showed only benign glands. The results demonstrate UG immunoreactivity in normal prostate, benign prostatic hyperplasia, and prostatic atrophy; low but clearly positive expression in prostatic intraepithelial neoplasia; positive expression in cancerous glands of Gleason's pattern </=2; and complete loss of UG immunoreactivity in cancerous glands of Gleason's pattern 3 or greater. In addition, in the one case of metastatic prostate cancer that we examined, the prostate cancer cells within the lymph node lacked UG expression. These findings suggest that the loss of UG expression may be an indicator of prostate cancer progression and possibly a component of the molecular natural history of prostate cancer, which may have prognostic value.
Bladder carcinoma--the good, the bad and the ugly.
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The cost of treating genital warts.
BACKGROUND: Genital warts is a common sexually transmitted disease treated by a variety of medical specialists. Standard therapies offer symptomatic relief but cannot ensure lasting remission. Using the clinical literature, claims databases, and a panel of experienced practitioners, the relative efficacy, cost, and cost effectiveness of five common treatments for genital warts were assessed in this study. METHODS: We reviewed the clinical literature for the following genital wart therapies: podofilox, podophyllin, trichloroacetic acid, cryotherapy, and laser therapy, focusing on their relative efficacy. Physicians experienced in treating genital warts defined standard treatment protocols for men and women patients with moderate wart burdens. Using national claims data and protocols developed by physicians, we derived three economic models based on provider charges, third-party payments, and a resource-based relative value scale, respectively. RESULTS: The literature review demonstrated highly variable success and recurrence rates among treatment methods and failed to show that one treatment provides consistently superior efficacy. In the economic models, treating women generally proved more costly than treating men per episode of care. This was due to the need for more extensive follow-up visits in the treatment of women. Total costs were highest for cryotherapy and lowest for a patient-applied therapy that reduced the need for follow-up visits. CONCLUSIONS: Clinicians should consider both clinical and cost issues when choosing the appropriate treatment for patients with genital warts.