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C D Zippe

Publications and source records attributed to C D Zippe.

32 records · Page 2Linked to original sources

Exclusion criteria enhance the specificity and positive predictive value of NMP22 and BTA stat.

PURPOSE: The limitation of current urinary tumor markers is the low specificity and positive predictive value, which clinically manifests as a high false-positive rate. We analyzed the false-positive data of 2 urinary tumor markers, NMP22 and the BTA stat tests. We examined the clinical categories of the false-positive results, established relative exclusion criteria, and recalculated the specificity and positive predictive value after using the exclusion criteria. MATERIALS AND METHODS: A total of 278 symptomatic patients who presented to a urology clinic were asked to submit a single voided urine sample. Each sample was divided into 3 aliquots of which 1 was stabilized with the NMP22 test kit stabilizer and assayed for NMP22, 1 was tested for BTA stat and 1 was sent for cytological examination. All patients subsequently underwent office cystoscopy and bladder biopsy if indicated. RESULTS: Of the 278 symptomatic patients 112 presented with microscopic hematuria, 77 gross hematuria and 89 chronic symptoms of urinary frequency or dysuria. Of 34 cases (12%) of histologically confirmed bladder cancer NMP22 detected 28 (82.4%), BTA stat 23 (67.7%) and cytology only 10 (29.4%). When atypical cytologies were considered positive, cytology then detected 19 cases (55.9%). Elevated NMP22 values were positive in 28 cases and false-positive in 44 for a specificity of 82% and a positive predictive value of 38.9%. Similarly, BTA stat test was positive in 23 cases and false-positive in 43 for a specificity of 82.4% and a positive predictive value of 34.9%. When atypical cytologies were considered positive, the specificity and positive predictive value were 93% and 55.9%. Greater than 80% of the false-positive results were clinically categorized as benign inflammatory or infectious conditions, renal or bladder calculi, recent history of a foreign body in the urinary tract, bowel interposition segment, another genitourinary cancer or an instrumented urinary sample. A category of "no known pathology" was included in analysis as a control. History of ureteral stents or any bowel interposition segment had a 100% false-positive rate. Exclusion of all 6 clinical categories improved the specificity and positive predictive value of NMP22 (95.6%, 87.5%) and BTA stat (91.5%, 69.7%), and was similar to urinary cytology. CONCLUSIONS: Awareness and exclusion of the categories of false-positive results can increase the specificity and enhance the clinical usefulness of NMP22 and BTA stat tests. Similarly, treating an atypical cytology as positive can enhance the sensitivity and usefulness of urinary cytology.

Antigens, Neoplasm↗

Combined nested RT-PCR assay for prostate-specific antigen and prostate-specific membrane antigen in prostate cancer patients: correlation with pathological stage.

Nested reverse transcription (RT)-PCR for prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSM) can detect circulating prostatic cells in patients with prostate cancer. We evaluated the role of a combined screening approach for PSA and PSM in prostate cancer staging. We examined the peripheral blood samples from 136 patients with adenocarcinoma of the prostate (PCA), 15 patients with benign prostatic hyperplasia, 15 normal male subjects, and 5 female subjects. The controls (benign prostatic hyperplasias, normal males, and normal females) were negative for both PSA and PSM. In patients with metastatic PCA (n = 11), 100% were positive by combined PSA/PSM (64% by PSA and 91% by PSM). In biochemical failure PCA patients (n = 18), 39% were positive by PSM, compared to only 6% by PSA. In patients with clinically localized PCA (n = 107), 48% were positive by combined PSA/PSM approach (43% by PSM and 14% by PSA). These results show that PSM is a more sensitive marker than PSA in detecting circulating prostatic cells (P < 0.0001). We correlated preoperative RT-PCR results with final pathological stages in 67 prostatectomy patients. RT-PCR positivity was 81.5% in patients with non-organ-confined disease versus 37.5% in organ-confined disease (P = 0.001). PSA/PSM RT-PCR had an odds ratio of 7.3 (95% confidence interval, 2.3-23.4; P = 0.001) in predicting tumor extracapsular extension. PSA/PSM RT-PCR was a better predictor of tumor extracapsular extension than initial serum PSA, clinical stage, and biopsy Gleason score. Our data show that PSA/PSM nested RT-PCR may provide the staging information unavailable from the current modalities. The ultimate impact of this technique in the management of patients with prostate cancer will require continued investigation.

Adenocarcinoma↗

Treatment of erectile dysfunction after radical prostatectomy with sildenafil citrate (Viagra).

OBJECTIVES: To determine whether the response to the new oral medication, sildenafil citrate (Viagra), was influenced by the presence or absence of the neurovascular bundles, as recent reports on its success did not specify the efficacy of the drug in patients with erectile dysfunction after radical prostatectomy. METHODS: Baseline and follow-up data from 28 healthy patients presenting with erectile dysfunction after radical prostatectomy were obtained. Patients receiving any neoadjuvant/adjuvant hormones or adjuvant radiation therapy were excluded. Patients reported what their erectile status was before surgery, before sildenafil therapy, and after using a minimum of four doses of sildenafil. Both the patients and their spouses were interviewed using the Cleveland Clinic post-prostatectomy questionnaire, which includes questions about response to therapy, duration of intercourse, spousal satisfaction, side effects, and related topics. The patients were compared on the basis of the type of surgical procedure they had undergone-nerve sparing or non-nerve sparing. A positive response to sildenafil was defined as erection sufficient for vaginal penetration. RESULTS: Of the 15 patients who had bilateral nerve-sparing procedures, 12 (80%) had a positive response to sildenafil, with a mean duration of 6.92 minutes of vaginal intercourse. These 12 patients also reported a spousal satisfaction rate of 80%. All 12 of the responders had a positive response within the first three doses, and 10 of the 12 responded with the first or second dose. None of the 3 patients who had undergone a unilateral nerve-sparing procedure responded, nor did any of the 10 patients who had undergone a non-nerve-sparing procedure. The two most common side effects of the drug were transient headaches (39%) and abnormal color vision (11%). No patients discontinued the medication because of side effects. CONCLUSIONS: Successful treatment of erectile dysfunction in a patient after prostatectomy with sildenafil citrate may depend on the presence of bilateral neurovascular bundles. No patient who had undergone a non-nerve-sparing procedure responded. Whether patients who undergo unilateral nerve-sparing procedures will respond to sildenafil is still unclear because of the small number of patients in our study. These findings should encourage urologists to continue to perform and perfect the nerve-sparing approach. The ability to restore potency with an oral medication after radical prostatectomy will impact our discussion with the patient on the surgical morbidity of radical prostatectomy.

Enzyme Inhibitors↗

Stage T1-2 prostate cancer with pretreatment prostate-specific antigen level < or = 10 ng/ml: radiation therapy or surgery?

PURPOSE: To detect differences in biochemical failure rates by treatment modality (radiation therapy or radical prostatectomy) in patients with early-stage prostate cancer presenting with pretreatment prostatic-specific antigen (PSA) levels < or = 10.0 ng/ml. METHODS AND MATERIALS: A total of 1467 consecutive patients with prostate carcinoma were treated with either radiotherapy (RT) or radical prostatectomy (RP) between January 1987 and June 1996. Patients with the following were excluded from the present study: initial PSA (iPSA) level > 10 ng/ml (n = 444), clinical Stage T3 disease (n = 73), adjuvant or neoadjuvant treatment (n = 173), no available iPSA level (n = 31), no available biopsy Gleason score (GS) (n = 33), incomplete pathologic information (n = 16), and no available follow-up PSA levels (n = 90). The analysis was performed on 607 cases: 354 treated with RP and 253 with RT (median dose 68.4 Gy). The outcome of interest was biochemical relapse-free survival (bRFS), with biochemical relapse being defined as either a detectable PSA level after RP or elevation in PSA levels of > or = 1.0 ng/ml above the nadir after RT. Proportional hazards were used to analyze the effect of treatment modality and confounding variables (i.e., age, stage, biopsy GS, iPSA levels) on treatment outcome. RESULTS: Seventy-nine percent of patients (n = 478) had clinical Stage T1 or T2A disease at presentation (RP vs. RT: 84% vs. 71%, p < 0.001). Twenty-one percent of patients (n = 127) had iPSA levels < or = 4 ng/ml (RP vs. RT: 24% vs. 17%, p = 0.027). Seventy-six percent of patients (n = 460) had biopsy GS < or = 6 (RP vs. RT: 79% vs. 71%, p = 0.014). The median follow-up time was 24 months (range 3-110). For the 607 patients, the 5-year bRFS rate was 76%. The 5-year RFS rates for RP versus RT were 76% versus 75%, respectively (p = 0.09). After adjustment for all confounding variables, iPSA levels (p < 0.001) and biopsy GS (p = 0.001) were the only independent predictors of relapse, whereas age, clinical stage, and treatment modality were not (p = 0.20; p = 0.09; and p = 0.10, respectively). CONCLUSION: In patients with clinical Stage T1-2 prostate cancer and pretreatment PSA < or = 10 ng/ml, there is no difference in biochemical failure rates between those treated with radiation and those treated with surgery.

Aged↗

Combined nested reverse transcription-PCR assay for prostate-specific antigen and prostate-specific membrane antigen in detecting circulating prostatic cells.

Accurate staging is an important issue in managing patients with prostate cancer. Current staging modalities are poor predictors for locally advanced disease. In the present study, we investigated the role of a peripheral blood-based, nested reverse transcription-PCR (RT-PCR) for prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSM) in prostate cancer staging. Our nested RT-PCR could detect both PSA and PSM mRNA in one LNCaP cell diluted in 10(6) mononuclear cells. None of the controls, including patients with benign prostate hyperplasia, normal male subjects, and female subjects, were positive for either marker, confirming the assay's specificity for prostate cancer. In patients with bony metastases, 100% were positive by combined PSA/PSM assays (64% by PSA and 91% by PSM). In patients with clinically localized prostate cancer, 29% were positive by combined PSA/PSM assays (13% by PSA and 23% by PSM). The combined PSA/PSM assay is more sensitive than the PSA assay alone in detecting circulating prostatic cells (P = 0.0071). PSM is a more sensitive marker than PSA (P = 0.042). We also correlated preoperative nested RT-PCR results with pathological findings in prostatectomy patients. Nested RT-PCR for PSA/PSM has an odds ratio of 20 in predicting tumor extracapsular penetration (P = 0.017). These results indicate that a nested RT-PCR result may provide the staging information unavailable from other modalities, including the clinical stage, initial serum PSA, and Gleason score. Additional investigation is needed to determine the ultimate role of this assay in the management of patients with prostate cancer.

Antigens, Neoplasm↗

Cryosurgery of the prostate: techniques and pitfalls.

The preliminary data on prostate cryosurgery encompass reports only on local recurrence rates. The procedure is too new to report any survival figures. For localized organ-confined disease, the initial reports at 1 year of positive biopsies following cryosurgery range from 8% to 33%. With clinical stage C disease, a review of the literature also shows a range of 16% to 33% for local recurrence at one year. The largest series of patients treated after failure from radiation therapy is from the M.D. Anderson Cancer Center, which reports a positive biopsy rate of 29% at 6 months. Reports of major complications have included a 2% to 5% incidence of rectourethral fistulas, a 7% to 15% incidence of urinary retention requiring a secondary TURP or prolonged catheter drainage, 2% to 7% incidence of stress incontinence, and a 50% to 80% incidence of impotence. While these overall results may not be optimal to many, they do give us optimism. It is important to recognize that knowledge of the cryosurgical technique is evolving rapidly, and present modifications are not reflected yet in our results. Because hypothermia is a modality proven to cause lethal injury to cancer cells, it would be unfortunate if clinicians dismissed this modality without rigorous review of the surgical technique. The detailed methodology described in this article expedites the learning curve of practicing cryosurgeons and helps to standardize the way cryosurgery is performed.

Aged↗

Ex vivo activated memory T-lymphocytes as adoptive cellular therapy of human renal cell tumour targets with potentiation by cis-diamminedichloroplatinum(II).

OBJECTIVE: To determine if cis-diamminedichloroplatinum(II) (CDDP) enhances, by immunomodulation, ex vivo anti-tumour cytotoxicity of autolymphocyte therapy (ALT) against a chemotherapy-resistant tumour, and if lysis is mediated through T-cells, NK-cells, or both. MATERIALS AND METHODS: Human renal cell carcinoma (RCC) target cells were derived from surgical specimens and incubated in complete medium (CM) with CDDP, or in CM alone (control group). ALT-cells were prepared from autologous whole peripheral blood mononuclear cells (PBMC) or NK-cell (CD56)-depleted PBMC obtained before surgery. Tumour cells from each group were labelled with chromium-51(51Cr) and used as targets for ALT-cells and PBMC in a standard (4 h) and delayed (18 h) 51Cr-release assay at varying effector/target ratios (E:T). RESULTS: Tumour cells incubated in CDDP showed enhanced lysis, as measured by the 51Cr-release assay, at all E:T tested. This lysis was significantly greater during the 18 h assay and when ALT-cells were used as the effector cells rather than PBMC. Depletion of CD45RO+ (memory) T-cells from the ALT cell population precluded both the 4 and 18 h tumour cell lysis. Depletion of NK-cells (CD56+) diminished the ex vivo lysis of autologous targets during the 4 but not the 18 h assay. ALT-cells derived from two patients demonstrated ex vivo tumour-specificity against autologous and allogeneic RCC. CONCLUSIONS: These data suggest that: (i) ex vivo activated memory T-cells are the principal component demonstrating significant tumour-specific cytotoxicity of ALT-cells against RCC tumour targets; (ii) CDDP may alter the physical properties of tumour cells rendering them susceptible to immune-mediated attack; (iii) the combination of ALT and CDDP may lead to increased therapeutic efficacy in patients with metastatic RCC.

Carcinoma, Renal Cell↗

Cryosurgical ablation for prostate cancer: a current review.

The available data on the efficacy of cryosurgery are still too immature to recommend this as a comparable option to radical surgery in the younger patient (< 72 years old) with organ-confined disease and at least a 10- to 15-year life expectancy. The available 3-month and 1-year positive biopsy figures of 10% to 20% are inversely comparable to the 10-year 80% to 90% disease-free survivals in contemporary radical prostatectomy series. While we wait for survival data to mature, it is unlikely that 10% to 20% local recurrence rates will translate into 80% to 90% disease-free survival rates. Only the data from the Crittendon Hospital group, which reports positive biopsies at 1 year of 3% to 4%, deserves special attention. Their protocol of optimal presurgical androgen ablation, use of thermosensors, and use of 2 to 3 freeze cycles may direct the way to a better cryosurgical technique. Conversely, the 2 to 8 months of presurgical androgen deprivation may just be prolonging the appearance of cryo-resistant cells. Regarding clinical stage C disease, the data looks promising with similar results as in organ-confined disease with a 10% to 20% positive biopsy rate at 3 months. One has to be cautious about what is really a stage C lesion, and comparison of preoperative PSA values enhance the comparisons between series. Overall, if the 1-year local recurrence rate does not exceed 30%, recommending cryosurgery as a viable option seems reasonable.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Phase II evaluation of coumarin (1,2-benzopyrone) in metastatic prostatic carcinoma.

The unavailability of effective treatment of metastatic hormone refractory prostatic carcinoma warrants trials of new and promising treatments. Coumarin is an investigational new drug that has produced objective tumor regression in some patients with metastatic renal cell carcinoma and malignant melanoma. Coumarin has shown activity against prostatic carcinoma in the Dunning R-3327 rat prostatic adenocarcinoma model. Forty-eight patients with metastatic hormone naive (5 stage D1 and 10 stage D2) or hormone refractory (33 stage D3) prostatic carcinoma of average age 67.6 years (range 46-86) and ECOG performance status of 2 or better were given 3 grams coumarin daily by mouth and evaluated monthly for toxicity and response by rigid criteria in a multicenter trial. Toxicity was limited to asymptomatic SGOT elevations in 3 patients and nausea and vomiting in 4 patients that required cessation of therapy in 2. Eligibility and protocol violations removed 6 additional patients from response evaluation. There were no complete responses. Partial responses (3 of 40 patients, 8%) occurred in 2 patients with bidimentionally measurable disease and 1 patient with disease evaluable by bone scan and elevated prostate specific antigen and prostatic acid phosphatase. The remaining patients progressed after 1 to 12 (average 4.4) months. Coumarin is a relatively nontoxic drug that may warrant further trials in a subset of patients with prostatic carcinoma.

Adult↗

Identification of carotid vascular receptors that control adrenal catecholamine secretion in dogs.

The role of carotid sinus and thyrocarotid mechanoreceptors in the reflex control of adrenal medullary function was assessed in anesthetized dogs with adrenal vein catheters. Dogs underwent carotid sinus, thyrocarotid junction, combined carotid sinus and thyrocarotid junction, or sham denervation. On the day after surgery, catecholamine secretion was measured after carotid occlusion proximal to the thyrocarotid junction, cervical vagotomy, and repeat carotid occlusion, each separated by 90 min. After combined carotid denervation, baseline norepinephrine secretion was increased, resulting in a decreased epinephrine-to-norepinephrine ratio. Carotid occlusion before vagotomy did not change the secretion of catecholamines or the epinephrine-to-norepinephrine ratio. After sham carotid denervation, acute vagotomy did not affect catecholamine secretion. However, after denervation of the carotid sinus or thyrocarotid junction, vagotomy resulted in small increases in catecholamine secretion without changing the epinephrine-to-norepinephrine ratio; the magnitude of the response was augmented after combined denervation. At 90 min after vagotomy in dogs with intact carotid baroreceptors, carotid occlusion increased adrenal secretion of catecholamines and decreased the epinephrine-to-norepinephrine ratio. After denervation of carotid sinus or thyrocarotid junction receptors, carotid occlusion increased secretion of catecholamines without changing the epinephrine-to-norepinephrine ratio; the response was abolished by combined denervation. These results show that both carotid sinus and thyrocarotid receptors contribute to the adrenomedullary response to carotid occlusion and to acute vagotomy. Also, reduction in the activity of carotid sinus and thyrocarotid junction receptors chronically (by denervation) or acutely (by carotid occlusion) results in preferential secretion of norepinephrine over epinephrine.

Adrenal Glands↗

Long-term efficacy and compliance of MUSE for erectile dysfunction following radical prostatectomy: SHIM (IIEF-5) analysis.

Baseline and follow-up data of 54 patients from a single surgical series (1998-2001), who used medicated urethral system for erection (MUSE) for the erectile dysfunction (ED) associated with radical prostatectomy (RP), were obtained. Patients were surveyed using the abridged five-item version of the International Index of Erectile Function (IIEF) questionnaire, commonly referred to as the Sexual Health Inventory of Men (SHIM), to determine presence and severity of ED and efficacy of ED treatment modalities. The mean patient age was 63.7+/-5.6 y and the mean follow-up period was 2.3+/-1.2 y. All patients experienced ED for at least 6 months after their surgery before starting MUSE therapy. Overall, 55% of the patients achieved and maintained erections sufficient for sexual intercourse while on MUSE and 48% continued long-term therapy with a mean use of 2.32+/-1.2 y. The mean presurgery SHIM score in these patients was 19.2+/-1.3, which decreased to 5.2+/-0.5 after surgery and increased to 16.3+/-1.3 after MUSE treatment. A total of 28 patients (52%) discontinued treatment after a mean use of 8+/-1.4 months. The reasons for discontinuation were insufficient erections (n = 16, mean SHIM score of 10.5+/-4.4), switch to other ED therapies (n = 4), natural return of erections (n = 4) and urethral pain and burning (n = 4). Excluding the patients (n = 8) who preferred other therapies and return of natural erections, the compliance to MUSE was 63%. There were no significant differences in the IIEF-5 responses between the patients who had a nerve-sparing technique (n=34) and those who did not (n = 20) or among patients who used different doses (250, 500 or 1000 microg) of MUSE. The results of the current trial indicate that MUSE is a successful treatment option in RP patients with established ED. It appears that a post-treatment SHIM score of > or = 16 defines a successful outcome with MUSE therapy.

Aged↗

Early use of vacuum constriction device following radical prostatectomy facilitates early sexual activity and potentially earlier return of erectile function.

To assess the efficacy of vacuum constriction devices (VCD) following radical prostatectomy (RP) and determine whether early use of VCD facilitates early sexual activity and potentially earlier return of erectile function. This prospective study consisted of 109 patients who underwent nerve-sparing (NS) or non-nerve-sparing (NNS) RP between August 1999 and October 2001 and developed erectile dysfunction following surgery. The patients were randomized to VCD use daily for 9 months (Group 1, N=74) or observation without any erectogenic treatment (Group 2, N=35). Treatment efficacy was analyzed by responses to the Sexual Health Inventory of Men (SHIM) (abridged 5-item International Index of Erectile Function (IIEF-5)), which were stratified by the NS status. Patient outcome regarding compliance, change in penile length, return of natural erection, and ability for vaginal intercourse were also assessed. The mean patient age was 58.2 years, and the minimum follow-up was 9 months. Use of VCD began at an average of 3.9 weeks after RP. In Group 1, 80% (60/74) successfully used their VCD with a constriction ring for vaginal intercourse at a frequency of twice/week with an overall spousal satisfaction rate of 55% (33/60). In all, 19 of these 60 patients (32%) reported return of natural erections at 9 months, with 10/60 (17%) having erections sufficient for vaginal intercourse. The abridged IIEF-5 score significantly increased after VCD use in both the NS and NNS groups. After a mean use of 3 months, 14/74 (18%) discontinued treatment. In Group 2, 37% (13/35) of patients regained spontaneous erections at a minimum follow-up of 9 months after surgery. However, only four of these patients (29%) had erections sufficient for successful vaginal intercourse and rest of patients (71%) sought adjuvant treatment. Of the 60 successful users, 14 (23%) reported a decrease in penile length and circumference at 9 months (range, 4-8 months) compared to 12/14 (85%) among the nonresponders. However, in control group 22/35 reported decrease in penile length and circumference. Early use of VCD following RP facilitates early sexual intercourse, early patient/spousal sexual satisfaction, and potentially an earlier return of natural erections sufficient for vaginal penetration.

Aged↗

Benign prostatic hyperplasia: an approach for the internist.

In benign prostatic hyperplasia, urodynamic testing and the many available drugs and surgical procedures have complicated the issue of what to do for whom. Although the severity of a patient's symptoms and his informed preferences should be the driving forces, specialized tests can help tailor treatment to the individual patient.

Adrenergic alpha-Antagonists↗