Electrical property sensing biopsy needle for prostate cancer detection.

BACKGROUND: Significant electrical property differences have been demonstrated to exist between malignant and benign prostate tissues. We evaluated how well a custom designed clinically deployable electrical property sensing biopsy needle is able to discriminate between these tissue types in an ex vivo prostate model. METHODS: An electrical impedance spectroscopy (EIS) sensing biopsy (Bx) needle was developed to record resistive (ρR) and reactive (ρX) components of electrical impedance from 100 Hz to 1 MHz. Standard twelve-core biopsy protocols were followed, in which the EIS-Bx device was used to gauge electrical properties prior to extracting tissue cores through biopsy needle firing from 36 ex vivo human prostates. Histopathological assessment of the cores was statistically compared to the impedance spectrum gauged from each core. RESULTS: The magnitudes of the mean resistive and reactive components were significantly higher in cancer tissues (P < 0.05). ROC curves showed that ρR at 63.09 kHz was optimal for discriminating cancer from benign tissues; this parameter had 75.4% specificity, 76.1% sensitivity, and ROC AUC of 0.779. Similarly, 251.1 kHz was optimal when using ρX to discriminate cancer from benign tissues; this parameter had a 77.9% specificity, 71.4% sensitivity, and ROC AUC of 0.79. CONCLUSION: Significant electrical property differences noted between benign and malignant prostate tissues suggest the potential efficacy an EIS-Bx device would provide for cancer detection in a clinical setting. By sensing a greater fraction of the prostate's volume in real-time, the EIS-Bx device has the potential to improve the accuracy of cancer grading and volume estimation made with current biopsy procedures.

Phase I pilot trial of the bispecific antibody MDXH210 (anti-Fc gamma RI X anti-HER-2/neu) in patients whose prostate cancer overexpresses HER-2/neu.

The goal of this study was to evaluate, in patients with prostate cancer, the toxicity profile and biologic activity of the bispecific antibody MDXH210, which has specificity for the non-ligand-binding site of the high-affinity immunoglobulin G receptor (Fc gamma RI) and the extracellular domain of the HER-2/neu proto-oncogene product. Patients with prostate cancer that expressed HER-2/neu were entered into a phase I dose-escalation trial of MDXH210. Patients received an intravenous infusion MDXH210 during a period of 2 h three times per week for 2 weeks and were monitored for toxicity. Pharmacokinetic and pharmacodynamic parameters were measured and included the biologic end points of monocyte-bound MDXH210, cytokine production, and clinical response. Seven patients were treated with MDXH210 doses ranging from 1 to 8 mg/m2. In general, MDXH210 was well tolerated, with only mild infusion-related malaise, fever, chills, and myalgias. No dose-limiting toxic effects were observed. Biologic effects included induction of low plasma concentrations of tumor necrosis factor-alpha and interleukin-6 observed immediately after MDXH210 infusion and 70% saturation of circulating monocyte-associated Fc gamma RI with MDXH210 at a dose level of 4 to 8 mg/m2. Five of six patients had stable prostate-specific antigen levels during the course of 40 days or more. Circulating plasma HER-2/neu levels decreased by 80% at days 12 and 29 (p = 0.03 and 0.06, respectively, by the Wilcoxon signed rank test). MDXH210 can be given safely to patients with HER-2/neu-positive prostate cancer in doses of at least 8 mg/m2. At the doses studied, biologic activity was demonstrated and characterized by binding of MDXH210 to circulating monocytes, release of monocyte-derived cytokines, a decrease in circulating HER-2/neu, and short-term stabilization of prostate-specific antigen levels.

A randomized phase II trial comparing two different sequence combinations of autologous vaccine and human recombinant interferon gamma and human recombinant interferon alpha2B therapy in patients with metastatic renal cell carcinoma: clinical outcome and analysis of immunological parameters.

PURPOSE: The clinical observation of spontaneous regression in patients with renal cell carcinoma (RCC) and the response to various immunotherapeutic therapies strongly suggest a role for the host immune system in this disease. Prior studies showed that sequential administration of interferon (IFN) gamma and IFN alpha to RCC patients was safe. Clinical responses as well as immune changes in the peripheral blood mononuclear cell compartment were observed. Autologous tumor cell vaccines (AV) have also demonstrated activity in renal cell carcinoma. We hypothesize that the addition of AV to sequential IFN gamma and a therapy might improve the tumor-specific immune response by providing an appropriate source of antigen in the appropriate cytokine environment. To our knowledge, this is the first trial using AV combined with IFN alpha and IFN gamma. The purpose of this study was to evaluate the feasibility of manufacturing and administering (AV) from resected tumor samples, and administration of AV with combination IFN gamma and IFN alpha therapy. Finally, the impact on immunological parameters of these treatment options was assessed. MATERIALS AND METHODS: Patients with metastatic RCC were randomly assigned to receive AV plus bCG along with a sequential administration of IFN gamma and a either together or after initiation of vaccine. Toxicity and clinical responses were evaluated. Modulations of the immune system were investigated by analyzing phenotype, cytokine mRNA expression, T cell proliferation and cytotoxicity in the peripheral blood mononuclear cell compartment. RESULTS: Fourteen patients with metastatic renal cell carcinoma were enrolled in this study; 9 were available for response evaluation. In a 70 day period, 3 (33%) showed mixed responses, 5 (56%) stable disease and 1 (11%) progression of disease. Toxicities were consistent with previous clinical reports. In the flow-cytometry phenotype analysis, stimulation of distinct subsets of circulating T-lymphocytes and a decrease of CD8+ T cell subsets was demonstrated. T-cell proliferation to allogeneic tumor cell stimulation improved following treatment. IL-4 and IL-5 mRNA levels were reduced in all patients after treatment. Patients who responded to treatment did not produce any IL-4 mRNA at all, before or after treatment. CONCLUSIONS: AV with IFNgamma and IFNalpha therapy might induce a MHC class-mediated cytotoxic T lymphocyte (CTL) response. We suggest that adequate therapy might direct T cell response toward a Th1 type response. We hypothesize a state of improved immune readiness in patients who might eventually respond to immunotherapy.

The effect of hospital volume on mortality and resource use after radical prostatectomy.

PURPOSE: The value of radical prostatectomy for patients with prostate cancer depends on low morbidity and mortality. We assessed whether patient outcome is associated with how many of these procedures are performed at hospitals yearly. MATERIALS AND METHODS: Using the Nationwide Inpatient Sample, which is a stratified probability sample of American hospitals, we identified 66,693 men who underwent radical prostatectomy between 1989 and 1995. Cases were categorized into volume groups according to hospital annual rate of radical prostatectomies performed, including low-fewer than 25, medium-25 to 54 and high-greater than 54. We performed multivariate logistic regression to control for patient characteristics when assessing the associations of hospital volume, in-hospital mortality and resource use. RESULTS: Overall adjusted in-hospital mortality after radical prostatectomy was relatively low (0.25%). However, patients at low volume centers were 78% more likely to have in-hospital mortality than those at high volume centers (adjusted odds ratio 1.78, 95% confidence interval 1.7 to 2.6). Overall length of stay decreased at all hospitals between 1989 and 1995. However, average length of stay was longer and total hospital charges were higher at low than at high volume centers (7.3 versus 6.1 days, p<0.0001, and $15,600 versus $13,500, p<0.0001, respectively). CONCLUSIONS: Hospital volumes inversely related to in-hospital mortality, length of stay and total hospital charges after radical prostatectomy. Further study is necessary to examine the association of hospital volume with other important outcomes, including incontinence, impotence and long-term patient survival after radical prostatectomy.

Vulvar metastases secondary to transitional cell carcinoma of the bladder. A case report.

BACKGROUND: Gynecologists are frequently asked to evaluate patients with vulvar lesions. Although the differential diagnosis of a vulvar lesion is varied, the main concern is to rule out a vulvar malignancy. Primary vulvar carcinoma is uncommon, and a metastatic cancer from an extragenital site involving the vulva is even more rare. CASE: A 78-year-old woman with a history of a transitional cell carcinoma (TCC) of the bladder presented with two painful vulvar lesions, which represented the first manifestation of metastatic disease. This is the fifth reported case of TCC from the bladder with metastases to the vulva. CONCLUSION: The differential diagnosis of a vulvar lesion, especially in a woman with a prior history of renal tract malignancy, should include metastatic lesions.

In vivo description of dendritic cells in human renal cell carcinoma.

PURPOSE: Dendritic cells (DCs) are efficient and effective antigen-presenting cells that play a major role in initiating the primary immune response. They are the most potent stimulators of T-cell activation and would thus be expected to be of great importance in the antitumoral immune response. Although DC phenotype and function have been described under in vitro conditions, their in vivo characteristics are less well detailed. Human renal cell carcinoma (RCC) is an excellent model to explore tumor infiltrating dendritic cells (TiDCs) because of rare clinical spontaneous regressions and the association of high numbers of tumor infiltrating lymphocytes (TiLs), suggesting a strong immune response. MATERIALS AND METHODS: We determined the in situ phenotype of mature CD83+ TiDCs using monoclonal antibodies to known activation molecules (CD86 [B7.2], CD80 [B7.1], CD40, CD54, CD1a and HLA-DR). Seventeen primary RCCs, representing four distinct histologies, were evaluated using double-staining immunohistochemical techniques and light microscopy. RESULTS: CD83+ TiDCs were found in all tumors. Expression of CD40 correlated with expression of CD1a on CD83+ TiDCs. Expression of CD54 (ICAM-1) correlated with a lower expression of CD86 (B7.2) as well as a decrease in CD3+ and CD8+ TiLs. CONCLUSIONS: These data suggest a de novo lipid or sugar-based immunogenic antigen presentation by TiDCs. Also, the data support an impaired antigen-presenting capability for CD54+ TiDCs based on the decreased coexpression of CD86 (B7.2) and the decrease of associated CD8+ TiLs.

Trends in the use of radical prostatectomy for treatment of prostate cancer.

CONTEXT: The incidence of prostate cancer and rates of radical prostatectomy increased sharply in the Medicare population (men older than 65 years of age) after the introduction of prostate-specific antigen screening in the late 1980s. PRACTICE PATTERN EXAMINED: Trends in age-specific rates of use of radical prostatectomy in U.S. men between 1989 and 1995. DATA SOURCE: The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. RESULTS: Overall, rates of radical prostatectomy more than doubled between 1989 and 1992 (from 78 per 100,000 men to 206 per 100,000 men) but decreased by a third between 1992 and 1995 (to 146 per 100,000 men). The pattern in overall radical prostatectomy rates between 1992 and 1995, however, obscures changes that occurred for men in different age groups. Decreases in radical prostatectomy rates were most dramatic in elderly persons, dropping 51% in men 70 to 74 years of age and 71% in men 75 years of age or older. In contrast, rates in younger men continued to increase between 1992 and 1995, rising 42% in men 45 to 49 years of age and 18% in men 50 to 54 years of age. In each age group, trends in surgery rates mirrored trends in cancer detection rates. CONCLUSIONS: Surgical treatment of prostate cancer in older men is decreasing; however, surgery rates are increasing in younger men. These divergent trends reflect the pattern of prostate cancer detection in clinical practice.

Expression of Fas(APO-1/CD95) in tumor-infiltrating and peripheral blood lymphocytes in patients with renal cell carcinoma.

The functional expression of Fas-ligand on tumor cells reported in a variety of neoplasms has been proposed by several groups as a mechanism of tumor escape from immunological detection. To better support this hypothesis, we have evaluated and quantified for the first time the presence of the Fas(CD95)-R molecule on tumor-infiltrating lymphocytes and on matched peripheral blood lymphocytes (PBLs) of renal cell cancer patients. By two-color flow cytometry we have detected a significant increase in the Fas(CD95)-R expression on tumor-infiltrating lymphocytes compared with matched patient and normal volunteer PBLs. We also observed a decreased expression of the Fas(CD95)-R expression on PBLs from renal cell cancer patients compared with normal healthy controls. The Fas(CD95)-R expression was observed predominantly on the CD4+ subset in all three groups. These different distributions of the Fas(CD95)-R molecule support the hypothesis that the Fas(CD95)-R/Fas(CD95)-L pathway and tumor microenvironment play a major role in the modulation of T-cell function and differentiation to either memory and activation or apoptosis.

T-cell receptor zeta-chain expression on tumor-infiltrating lymphocytes from renal cell carcinoma.

Loss of the T-cell receptor-associated zeta chain in tumor-infiltrating lymphocytes (TILs) has been proposed as one mechanism of acquired immunosuppression in cancer patients. Recent reports suggest that zeta-chain loss may be related to contaminating monocyte/macrophage protease activity. Using flow cytometry and Western blot analysis, we have confirmed the expression of zeta chain in matched peripheral blood mononuclear cells and TILs from eight patients with primary renal cell carcinoma, when the cells were exposed to sufficient quantity of protease inhibitors. A small decrease in zeta-chain expression was found in three TIL samples. The loss of zeta-chain expression that was noted by others may be related to differences in laboratory method, and the small changes we have noted are unlikely to be sufficient in explaining the immunosuppression of TILs.

Adrenal insufficiency from bilateral adrenal hemorrhage after total knee replacement surgery.

Adrenal hemorrhage is a rare cause of adrenal insufficiency in adults. We examine the incidence, etiology, diagnosis, and therapy of adrenal insufficiency secondary to adrenal hemorrhage. This case illustrates the nonspecific presentation of adrenal insufficiency and the necessity of maintaining a high index of suspicion in a clinically confusing scenario.

Prospective development of a cost-efficient program for the pubovaginal sling.

OBJECTIVES: We designed and implemented a cost-containment program for patients undergoing a pubovaginal sling procedure. We sought to test the hypothesis that preoperative patient education could reduce the length of hospital stay in these patients. Our goal was to decrease hospital charges while maintaining quality of care. METHODS: A multidisciplinary group of clinic and hospital staff identified factors that contribute to a patient's hospital charges for a pubovaginal sling procedure. A program of preoperative patient education to teach intermittent self-catheterization was combined with the elimination or control of items considered unnecessary to the delivery of safe, efficient care. Patient care was standardized from the preoperative visit to discharge planning. The difference in the mean values of 38 prestudy patients was compared with 15 study patients with a Wilcoxon rank sum test. RESULTS: Length of hospital stay was reduced from a mean of 2.8 to 1.1 days after implementation of the program (P < 0.0001). This decreased length of stay, combined with a reduction in routine laboratory studies (97% decrease; P < 0.0001), operating room charges (11% decrease; P < 0.01), and medications (35% decrease; P < 0.01), led to significantly reduced hospital charges. Total hospital charges decreased by 35%, from a mean of $4862 to a mean of $3153 (P < 0.0001). There was no increase in morbidity. Patient satisfaction with length of hospital stay did not change significantly following implementation of the program. CONCLUSIONS: With a program of preoperative patient education combined with a critical review of the factors contributing to a patient's hospital charges, it is possible to implement a cost-efficient program for a pubovaginal sling, leading to a 35% reduction in mean total hospital charges. This approach directed toward other incontinence procedures could be expected to yield comparative results.

Tissue-shrinkage correction factor in the calculation of prostate cancer volume.

Many studies that have calculated prostate cancer volumes from microscopic slides have used correction factors, ranging from 1.22 to 1.5, to compensate for tissue shrinkage during tissue processing. We undertook a study to measure tissue shrinkage directly because our experience suggested less shrinkage than that reported by others. Ten prostatectomy specimens were processed in a uniform manner. Multiple identical linear measurements were taken at four stages of processing: in the fresh state, following fixation, following processing, and from the microscopic slide. Linear shrinkage following fixation was minimal (4.1%) but increased to 14.5% following tissue processing. With rehydration and expansion on the flotation bath, tissues swelled so that net linear tissue shrinkage was 4.3%, and net volumetric tissue shrinkage was 12.4%, which translates into a correction factor for tissue shrinkage of 1.14. The following variables had no statistically significant effect on shrinkage: concentration of formalin, whole-mount versus quadrant sections, thickness of tissue slices, length of time in the alcohol dehydration steps, and temperature of the flotation bath over a range of 35 to 45 degrees C. This study suggests that (a) tissue-shrinkage correction factors that have been used in some previous studies may not be applicable for all laboratories because of interlaboratory variations in tissue-processing procedures or differences in measuring shrinkage; and (b) some calculated tumor volumes that have been used for prognostic thresholds may be high because of inflated tissue-shrinkage correction factors.

5-fluorouracil and allopurinol combined with recombinant interferon-alpha 2b in the treatment of patients with advanced prostate cancer: a phase I/II study.

PURPOSE: We determined the toxicity and preliminary response rate of escalating doses of 5-fluorouracil (670 to 1,500 mg./m.2 per day) combined with a fixed dose of interferon-alpha 2b (5 million units) and allopurinol (300 mg. every 8 hours) in cohorts of patients with metastatic prostate cancer. MATERIALS AND METHODS: The trial included 11 men with metastatic prostate cancer. Cohorts of patients received a 5-day constant infusion of 5-fluorouracil combined with subcutaneous interferon-alpha 2b 3 times weekly and allopurinol for 1 week during 5-fluorouracil infusion. Treatment was repeat every 3 weeks. RESULTS: Of 10 patients evaluable for treatment response and toxicity 3 had a partial response as judged by significant decreases in prostate specific antigen measurements (mean followup 13.5 months). Significant dose limiting toxicities encountered included mucositis, diarrhea and leukoneutropenia. CONCLUSIONS: Further evaluation of this treatment to determine overall response rates and benefit should take into consideration the significant toxicity experienced.

Fatal genitourinary mucormycosis in a patient with undiagnosed diabetes.

We present what we believe is the first report in the world literature of penile necrosis due to mucormycosis, a rare and often fatal fungal infection. This case of rhizopus mucormycosis began with a penile lesion in a 27-year-old patient with undiagnosed diabetes; it led to necrosis of the phallus, lower urinary tract, rectum, and pelvic musculature and finally to death. Despite repeated aggressive surgical debridement in conjunction with medical therapy, we were unable to halt the progression of the fungal and synergistic bacterial infections.

Staging of prostate cancer with endorectal MR imaging: lessons from a learning curve.

Endorectal magnetic resonance (MR) imaging is the most accurate noninvasive method of staging prostate cancer. However, inexperienced radiologists may lack the necessary technical and interpretative skills to use this technique, and both radiologists and referring urologists may become frustrated with this method because of its inaccuracy compared with analysis of the radical prostatectomy specimen. Meticulous pathologic correlation is necessary to evaluate endorectal MR imaging findings. The authors compare their initial experience using endorectal MR imaging for staging prostate cancer (25 cases) with their later experience (25 cases) to highlight the various diagnostic pitfalls and "pearls" one may encounter when using endorectal MR imaging. Knowledge of the pathways of tumor spread inside and outside the gland may be helpful in interpreting endorectal MR images. The authors achieved a substantial improvement in the overall staging accuracy of endorectal MR imaging by careful pathologic correlation and by considering the anatomic features of prostate cancer.

Surgical treatment of verrucous carcinoma of the bladder unassociated with bilharzial cystitis: case report and literature review.

Verrucous carcinoma of the bladder unassociated with bilharzial cystitis is rare with only 6 cases reported to date. Verrucous carcinoma of the bladder, like that involving the cervix, vagina, oral cavity, perineum and lower extremities, may invade surrounding structures but remain surgically curable. Although it is similar to condyloma acuminatum, verrucous carcinoma is considered malignant because of its invasive growth pattern and it should be treated accordingly. However, no evidence of metastases has been noted to date. To our knowledge we report the first case of extravesical extension of verrucous carcinoma of the bladder that was treated successfully by surgical removal.

Diuretic renal scan: is it always reliable?

The differentiation between significant mechanical obstruction and nonobstructive dilation of the kidneys and ureters is fundamental to patient management. The diuretic renal scan is a useful test in this situation because it usually is reliable and reproducible and is noninvasive and objective, providing information about the function of each kidney. However, this study has given variable results in a small number of patients. We report our experience with five such patients and recommend an algorithm for evaluating patients with equivocal scan results. This report emphasizes the importance of continued follow-up and the need for periodic reevaluation of patients with unexplained urinary symptoms or persistent flank pain, even when the initial diuretic renal scan is normal.

Metastatic renal cell carcinoma presenting as a skin nodule: case report and review of the literature.

Cutaneous metastasis from renal cell carcinoma is unusual. A patient is described who presented with a solitary skin metastasis 6 months after unilateral radical nephrectomy for renal cell carcinoma. In most instances, once cutaneous involvement is manifest the disease is widespread and has a poor prognosis. The skin should be examined during tumor evaluation as part of the physical examination and skin lesions in patients with renal cell carcinoma should be evaluated aggressively to rule out cutaneous metastasis.

Respiratory distress following cesarean section: cryptic presentation of bladder injury.

A case documenting the development of massive urinary ascites with associated pleural effusions and respiratory compromise due to an unrecognized cystotomy at the time of a tertiary low-vertical cesarean section is reported. The diagnosis was supported by elevated levels of serum blood urea nitrogen and creatinine and a peritoneal fluid to plasma creatinine ratio of 3:1. Imaging studies confirmed urinary extravasation into the peritoneum as well as bilateral pleural effusions and ascites. Primary intervention was to improve the patient's respiratory status and then to surgically repair the bladder wound.

Recurrent ileal conduit hemorrhage in an elderly cirrhotic man.

One recognized complication of portal hypertension in a patient with an ileal urinary conduit is variceal hemorrhage. The definitive treatment for this rare complication is controversial. Local measures, sclerotherapy, stomal revision and various operative portacaval shunts have been described but they have had limited long-term success. Using a recently developed interventional radiological technique, a transjugular intrahepatic portosystemic shunt was created in a cirrhotic man who had recurrent massive ileal conduit variceal hemorrhage. After the procedure the patient experienced no further life threatening stomal hemorrhage. He died of hepatic failure 6 months later.