Differences in organ system of distant metastasis by renal cell carcinoma subtype.

PURPOSE: The majority of the published data regarding the rates of renal cell carcinoma metastasis to specific locations has examined renal cell carcinoma as a whole. We evaluated site of distant metastasis by renal cell carcinoma histological subtype. MATERIALS AND METHODS: We studied 910 patients treated with radical nephrectomy for clear cell, papillary or chromophobe renal cell carcinoma at the Mayo Clinic between 1970 and 2000 who had distant metastasis at nephrectomy or who had metastasis during followup. The sites of metastases were compared by histological subtype using the chi-square and Fisher exact tests. RESULTS: There were 853 (94%) patients with clear cell, 39 (4%) with papillary and 18 (2%) with chromophobe renal cell carcinoma. Median followup for the 65 patients who were still alive at last followup was 11.6 years. Patients with clear cell renal cell carcinoma were more likely to have metastasis to the lungs (53.6%) compared to those with papillary (33.3%) and chromophobe (33.3%) renal cell carcinoma (p = 0.012). Patients with chromophobe renal cell carcinoma were more likely to have metastasis to the liver compared to those with clear cell renal cell carcinoma (33.3% vs 9.7%, p = 0.007), but there was not a statistically significantly difference in the incidence of liver metastases between patients with chromophobe and papillary renal cell carcinoma (33.3% vs 18.0%, p = 0.308). CONCLUSIONS: Site of distant metastasis varies significantly by renal cell carcinoma histological subtype. Patients with clear cell renal cell carcinoma are more likely to have metastasis to the lungs while patients with chromophobe renal cell carcinoma are more likely to experience liver metastasis.

Case report: intraoperative anaphylactoid reaction and hydroxyethyl starch in balanced electrolyte solution (Hextend).

PURPOSE: To report a first case of probable anaphylactoid reaction to 6% hydroxyethyl starch reconstituted in balanced electrolyte and glucose solution (Hextend). CLINICAL FEATURES: A 22-yr-old man was admitted for a partial nephrectomy. Near the end of the four-hour operation, an infusion of Hextend was initiated. Shortly thereafter, mechanical ventilation became difficult, peak inspiratory pressure increased to 55 cm H2O with audible wheezing over the patient's lungs. Blood pressure suddenly decreased to 68/46 mmHg. Multiple doses of phenylephrine, ephedrine and epinephrine were required to restore the patient's blood pressure. Postoperatively, a diffuse urticarial rash was apparent on his upper torso. The patient recovered uneventfully. His postoperative serum tryptase was 26.3 ng x mL(-1) (reference range, < 11.5 ng x mL(-1)) and the urine N-methyl-histamine was 2448 microg x g(-1) creatinine (reference range, 30-200 microg x g(-1) creatinine). Two months after the event, skin testing was conducted to test for possible allergy to latex, lidocaine, propofol, cisatracurium, succinylcholine, vecuronium, midazolam, fentanyl, ondansetron, neostigmine, and cephazolin, and all were negative. Hextend was also tested, starting with a 1:100,000 dilution and the results were negative. CONCLUSIONS: The temporal relationship of severe hypotension, bronchospasm and skin rash within ten minutes from administration of Hextend in this patient suggests an immediate hypersensitivity reaction to hetastarch. The elevated levels of serum tryptase and urinary N-methyl-histamine suggest that this hypersensitivity was mediated from mast cell degranulation. Negative skin testing suggests that the reaction was anaphylactoid.

Costimulatory molecule B7-H1 in primary and metastatic clear cell renal cell carcinoma.

BACKGROUND: Cancer cell expression of costimulatory molecule B7-H1 has been implicated as a potent inhibitor of T-cell-mediated antitumoral immunity. The authors recently reported that B7-H1 is aberrantly expressed in primary renal cell carcinoma (RCC). Blockade of B7-H1, as demonstrated in several murine cancer models, now represents a promising therapeutic target in RCC. However, the potential expression of B7-H1 in metastatic RCC has not been investigated. In the current study, the authors updated their primary RCC results with additional follow-up and investigated the potential role of B7-H1 in metastatic RCC. METHODS: Between 2000 and 2004, 196 patients underwent nephrectomy and 26 patients had resection of RCC metastases for clear cell RCC. Immunohistochemical analysis was performed on tumor cryosections using a B7-H1 monoclonal antibody (clone 5H1). A urologic pathologist quantified the percentage of B7-H1-positive tumor cells and lymphocytes. RESULTS: Variable levels of B7-H1 were expressed on primary RCC tumor cells (n = 130 [66.3%]) and primary tumor-infiltrating lymphocytes (n = 115 [58.7%]). Patients with high expression of B7-H1 on primary tumor cells and/or lymphocytes were significantly more likely to die of RCC compared with patients with low B7-H1 expression (risk ratio [RR] = 4.17; 95% confidence interval [95% CI], 1.97-8.84; P < 0.001) and this risk persisted in multivariate analysis after adjusting for the Mayo Clinic stage, size, grade, and necrosis score (RR = 2.63; 96% CI, 1.23-5.64; P = 0.013). Of the 26 metastatic specimens, cancer cell and lymphocyte B7-H1 expression were demonstrated in 17 (65.4%) and 18 (69.2%) specimens, respectively. In total, 14 (54.3%) metastatic specimens had high aggregate B7-H1 levels compared with 44.4% in primary RCC specimens. CONCLUSIONS: Patients with RCC with high B7-H1 expression were significantly more likely to die even after multivariate analysis. The authors also demonstrated that a high percentage of RCC metastases similarly harbored B7-H1. The authors surmised that B7-H1 blockade may augment current immunotherapy, including patients treated for metastases after cytoreductive nephrectomy.

Should the upper tracts be imaged for microscopic haematuria?

OBJECTIVE: To determine the relative prevalence of various definitions of microscopic haematuria (MH) in patients with renal neoplasms and controls, and to predict the likely outcome of renal imaging for those definitions. PATIENTS AND METHODS: In a retrospective case-control study 278 adult men and woman seen between 1998 and 2003 with untreated renal neoplasms were compared to controls matched for age and sex. All cases and controls had renal imaging within 6 months of a urine analysis. Patients were excluded for gross haematuria or other conditions associated with MH but not relevant to upper tract imaging. Adjusted odds ratios (OR) computed for 13 definitions of MH by conditional logistic regression were the primary outcome measures. Additional outcome measures were ORs in selected subsets. Hypothetical performance characteristics of a positive urine analysis were then derived to predict the likely results of detecting renal neoplasms for each definition of MH. RESULTS: The OR (95% confidence interval) for the entire series of cases and controls, both symptomatic and asymptomatic, was 2.0 (1.02-3.92, P = 0.04) for MH defined as > or = 4 red blood cells per high-power field (RBC/HPF) and 2.2 (1.09-4.52, P = 0.03) for > or = 5 RBC/HPF. No significant OR was calculated for < or = 3 RBC/HPF, nor for a subgroup of patients with MH in a routine urine analysis obtained during a periodic health examination. Symptomatic patients had an OR of 13.68 (1.6-117.1, P = 0.02) for MH defined as > or = 5 RBC/HPF. The sensitivity of a positive test decreased from 24.8% to 5.04% as the definition for MH became more stringent. The theoretical positive predictive value (assuming a prevalence of renal cell neoplasms of 0.25%) of the most stringent definition of MH was 0.58%. CONCLUSIONS: Patients with renal neoplasms have about twice the prevalence of MH with > or = 4 or 5 RBC/HPF in a single urine sample compared with matched controls, but this difference has little impact on the hypothetical detection rate of renal cancer. Imaging the kidney for low-grade MH in a routine urine analysis discovered at a periodic health examination in an otherwise asymptomatic patient is tantamount to screening without cause, and can be deferred for selected patients. The clinical context is as important as the degree of MH when deciding to image the kidneys.

Comparison of presentation and outcome for patients 18 to 40 and 60 to 70 years old with solid renal masses.

PURPOSE: We compared histological subtype, pathological features and outcome of patients with solid renal masses who were 18 to 40 years old vs patients who were 60 to 70 years old. MATERIALS AND METHODS: We conducted a retrospective review of the Mayo Clinic Nephrectomy Registry from 1970 to 2000, and identified 124 patients 18 to 40 years old and 1,067 patients 60 to 70 years old available for analysis. RESULTS: There was no significant difference in the incidence of benign solid renal masses between patients 18 to 40 years old and those 60 to 70 years old (13.7% vs 10.2%). Among patients with renal cell carcinoma (RCC), younger patients were more likely to have chromophobe RCC (13.1% vs 3.6%) and less likely to have clear cell RCC (70.1% vs 81.5%) than older patients. Among patients with clear cell RCC, younger patients were more likely to have stage pT2b or lower tumors (82.7% vs 69.9%) and a higher incidence of cystic clear cell RCC (10.7% vs 2.2%) than older patients. Younger patients had an improved cancer specific survival compared with older patients but this difference was not statistically significant (risk ratio 0.71, p =0.127). CONCLUSIONS: We found that patients 18 to 40 years old were more likely to have chromophobe and less likely to have clear cell RCC compared with patients 60 to 70 years old. We did not identify a higher incidence of papillary RCC in younger patients. Patients with clear cell RCC 18 to 40 years old had a higher incidence of low stage and cystic tumors compared with patients 60 to 70 years old, features which have been shown to have a favorable prognosis. These factors likely contributed to improved cancer specific survival for younger patients.

Split-thickness skin graft for the management of concealed penis.

PURPOSE: We review the use of split-thickness skin grafting in children with concealed penis. MATERIALS AND METHODS: Medical records were retrospectively reviewed for all patients younger than 20 years seen at our institution from 1995 to 2003 with a diagnosis of concealed penis. Patients were separated into "primary" and "secondary" groups based on the cause of concealment. Primary factors were prominent prepubic fat pad, dysgenetic dartos fascia or both. Secondary factors were post-circumcision phimosis and overzealous circumcision. RESULTS: A total of 26 patients 1 month to 19 years old were treated. In the primary group of 23 patients 11 underwent lysis of dartos fascia. Four of these 11 patients had insufficient skin, and split-thickness skin grafting was necessary to resurface the penile shaft. Five of the patients underwent excision of the fat pad only, and 2 underwent excision of the fat pad and lysis of fascia. Five patients are being observed. Of the 3 patients in the secondary group 1 underwent manual reduction of post-circumcision phimosis, 1 underwent scrotal flaps and 1 is being observed. Followup ranged from 2 weeks to 46 months (mean 13 months). Of 20 surgically repaired patients 19 (95%) had an excellent cosmetic result, were satisfied with penile length and reported no voiding complaints. CONCLUSIONS: The surgical approach for correcting concealed penis varies, depending on the cause. Of our 26 patients 4 (15%) had insufficient penile skin to resurface the penile shaft. In these select children split-thickness skin grafting provided a good cosmetic appearance and functional result.

Tissue ablation technologies for localized prostate cancer.

Traditional treatments for men with localized prostate cancer have included both surgical removal and radiation therapy, with their potential adverse effects on patient quality of life. Thus, there has been increasing interest in the development of minimally invasive procedures that use various technologies to deliver lethal doses of heat or cold to the prostate in an attempt to kill cancer cells. At the same time, it is vital that these newer techniques ablate prostate tissue and spare vital periprostatic organs essential for maintaining function and quality of life. In this article, we evaluate the current status of tissue ablation modalities in the treatment of clinically localized prostate cancer, focusing on the different methods, early results, and possible future directions. Although still in the beginning stages, these newer forms of treatment offer exciting potential for first-line and second-line treatment of this common urologic malignancy.

Costimulatory B7-H1 in renal cell carcinoma patients: Indicator of tumor aggressiveness and potential therapeutic target.

Expression of B7-H1, a costimulating glycoprotein in the B7 family, is normally restricted to macrophage-lineage cells, providing a potential costimulatory signal source for regulation of T cell activation. In contrast, aberrant expression of B7-H1 by tumor cells has been implicated in impairment of T cell function and survival, resulting in defective host antitumoral immunity. The relationship between tumor-associated B7-H1 and clinical cancer progression is unknown. Herein, we report B7-H1 expression by both renal cell carcinoma (RCC) tumors of the kidney and RCC tumor-infiltrating lymphocytes. In addition, our analysis of 196 clinical specimens reveals that patients harboring high intratumoral expression levels of B7-H1, contributed by tumor cells alone, lymphocytes alone, or tumor and/or lymphocytes combined, exhibit aggressive tumors and are at markedly increased risk of death from RCC. In fact, patients with high tumor and/or lymphocyte B7-H1 levels are 4.5 times more likely to die from their cancer than patients exhibiting low levels of B7-H1 expression (risk ratio 4.53; 95% confidence interval 1.94-10.56; P < 0.001.) Thus, our study suggests a previously undescribed mechanism whereby RCC may impair host immunity to foster tumor progression. B7-H1 may prove useful as a prognostic variable for RCC patients both pre- and posttreatment. In addition, B7-H1 may represent a promising target to facilitate more favorable responses in patients who require immunotherapy for treatment of advanced RCC.