Renal masses simulating primary renal cell carcinoma in patients with advanced malignancies

Most patients who present with a large solid renal mass and evidence of advanced malignancy will have primary renal cell carcinoma but a small subset with similar features have different and more treatable malignancies. We identified 7 patients with clinical and radiological findings suggestive of metastatic renal cell carcinoma who were ultimately diagnosed as have non-Hodgkin's lymphoma (5), germ cell tumor (1) or transitional cell carcinoma (1). Two of these patients presented with abdominal pain, gross hematuria and a flank mass. Computerized tomography was interpreted as showing renal cell carcinoma in all patients, although lymphoma and sarcoma were included in the differential diagnoses in 2. With the correct diagnosis and appropriate therapy, 4 of the 7 patients are currently disease-free. We emphasize the need for histological documentation in such patients in view of curative therapy available for possible underlying neoplasms simulating renal cell carcinoma.     

Evaluation and management of solid and cystic renal masses

PURPOSE: With the increasing detection of incidental renal lesions, the evaluation and management of solid and cystic renal masses are assuming greater importance in urological practice. A review of the techniques for evaluation and management is presented, with an emphasis on new and evolving procedures, along with recommendations for their selective use. MATERIAL AND METHODS: A MEDLINE computerized reference search and manual bibliographic review were performed to find pertinent peer reviewed articles published since 1985. Meeting abstracts were considered if they provided unique information. RESULTS: The primary means of evaluating renal masses is radiography (mainly ultrasonography and computerized tomography), although minimally invasive techniques such as percutaneous biopsy and laparoscopy are useful in selected situations. Nephron sparing surgery, minimally invasive surgery, alternative energy sources and other new techniques are being increasingly applied to the management of solid and cystic renal masses. CONCLUSIONS: Simple renal cysts can be defined ultrasonographically but more complicated masses require computerized tomography, other imaging modalities or rarely biopsy. Currently, minimally invasive techniques are commonly applied only to assist in the diagnosis of selected renal lesions and to treat benign simple cysts. The treatment of choice of solid renal masses remains open surgical radical nephrectomy and partial nephrectomy but alternative techniques will likely have a more significant role in the near future.     

Identification of nuclear matrix protein alterations associated with renal cell carcinoma

PURPOSE: Neoplastic transformation, including renal cell carcinoma (RCC), is always accompanied by changes in nuclear morphology. Nuclear grading of RCC is based on characteristic alterations in nuclear shape, size, area and other morphologic parameters. The nuclear matrix, which forms the skeleton of the nucleus, determines nuclear morphology. Alterations in nuclear matrix protein (NMP) composition specific to tissue and cancer type have been described in a variety of human cancers. We conducted a study to analyze the nuclear matrix protein composition of renal cell carcinoma and compare it to that of normal renal tissue and renal cell carcinoma cells grown in culture. MATERIALS AND METHODS: We analyzed the nuclear matrix protein composition of RCC tumor tissue and that of normal kidney tissue obtained from seventeen patients undergoing radical nephrectomy for RCC. We also analyzed the NMP composition of two renal cancer cell lines (A-498 and 769-P). RESULTS: We were able to identify five different and unique NMPs which were present only in the human RCC tumor samples and were absent in all normal kidney tissue. One NMP was found specifically in the normal kidney tissue. All five RCC specific NMPs were also identified in the nuclear matrix of the two cell lines analyzed. CONCLUSIONS: Five nuclear matrix proteins specific and unique to RCC were identified. These NMPs are different from those previously identified in other tissues and neoplasms. The RCC specific NMPs identified in this study can potentially be used as diagnostic markers for renal cell carcinoma and for therapeutic tumor targeting.     

Myositis associated with interleukin-2 therapy in a patient with metastatic renal cell carcinoma

BACKGROUND: Interleukin-2 (IL-2) has been used successfully in the treatment of some patients with metastatic renal cell carcinoma and melanoma, with a partial response rate of 15%-20%. It produces a well documented spectrum of side effects. Autoimmune diseases have been associated with IL-2 immunotherapy and the development of autoimmune thyroiditis may correlate with antitumor clinical response. METHODS: A patient with metastatic renal cell carcinoma is described who developed a polymyositis-like myopathy after an autologous tumor vaccine and IL-2 therapy. RESULTS: The patient had a delayed response for 15 months after developing this previously unreported toxicity. CONCLUSIONS: To the authors' knowledge, this represents the first reported case of necrotizing myositis in association with IL-2 therapy. Subsequent continuous partial response of the advanced malignancy was observed for 15 months. In this case, IL-2 may have broken tolerance to both normal muscle cells and tumor cells.     

Overexpression of c-met proto-oncogene associated with chromophilic renal cell carcinoma with papillary growth

The in vitro antiviral activity against picornaviruses (rhinovirus serotype 1B and 14, and poliovirus type 2) of new synthetic 3-hydroxyflavones, 3-acetoxyflavones, and substituted cinnamic and benzoic acid flavon-3-yl esters was evaluated. The maximum non-toxic concentration of compounds was determined in a human cell line (HeLa) suitable for the replication of the three viruses. Their antiviral potency was measured by a plaque reduction assay. Generally, rhinoviruses exhibited a higher sensitivity to the new flavonoids than poliovirus. Flavones, with sterically small substituents in position 3, showed good activity against both rhinoviruses tested. However, the introduction of bulky substituents in the same position resulted in analogues with a higher toxicity and often with a lower efficacy.     

Epidermal growth factor receptor expression is associated with rapid tumor cell proliferation in renal cell carcinoma

Epidermal growth factor receptor (EGF-r) expression and tumor cell proliferation rate have been proposed as potential prognostic parameters in renal cell carcinoma (RCC). In this study, immunohistochemical stains using antibodies to EGF-r and the cell proliferation marker Ki-67 (MIB-1) were used to study the relationship between EGF-r expression, tumor cell proliferation, and prognosis in 50 non-papillary RCC extending beyond the renal capsule (pT3). A high Ki-67 labeling index (LI) was associated with poor patient prognosis (P < .05). Thirty-eight cases (76%) expressed strong cell membrane immunoreactivity for EGF-r. There was a tendency toward a shortened survival for EGF-r-positive tumors (P = .08). Tumor growth fraction (Ki-67 LI) was significantly higher in EGF-r-positive tumors than in EGF-r-negative tumors (P < .05), suggesting that rapid tumor proliferation might be responsible for the poor prognosis associated with EGF-r-positive RCC.     

Early sCD8 plasma levels during subcutaneous rIl-2 therapy in patients with renal cell carcinoma correlate with response

Plasma sIl-2R and sCD8 levels of 12 patients with renal cell carcinoma were determined before and during subcutaneous rIl-2 therapy. Patients with a complete/partial remission showed a significantly stronger initial increase of sCD8 compared to patients with stable disease or tumour progression.     

Hereditary papillary renal cell carcinoma

We describe a 3 generation family with members affected with papillary renal cell carcinoma, an uncommon histological type of renal cell carcinoma. Multiple tumors of varying size were present in both kidneys of affected family members. The disorder was not linked to polymorphic markers on chromosome 3p and there was no loss of heterozygosity at loci on 3p in renal tumors. The results suggest the presence of a renal cell carcinoma gene not located on 3p that predisposes to renal cell carcinoma with a distinct histological appearance. The inherited disorder in this family appears to be different from recognized hereditary cancer syndromes.     

Immunotherapy of renal cell carcinoma

Immunologic approaches to the therapy of metastatic renal cell carcinoma have provided moderate improvement in response rates for a disease that is extremely resistant to all forms of treatment. This article reviews recent clinical efforts using immunotherapy for renal cell carcinoma, including the adoptive transfer of cytotoxic killer cells and/or the use of biologic response modifiers, such as interferon and interleukin-2.     

Lipid levels in adults with cystic fibrosis

The systemic treatment of soft tissue sarcomas is difficult due to the limited availability of active cytotoxic drugs. Combinations of cytotoxic drugs at standard doses do increase toxicity but do not improve response rates or survival. All combinations are limited by myelosuppression, mainly leukocytopenia. For at least two of the four active drugs (doxorubicin and ifosfamide) studies have shown a clear dose-response relationship. Recent studies have focused on increasing dose-intensity by increasing dosages or shortening treatment intervals, which is only possible by the use of hematological growth factors. This review will focus on the latter concept.     

Cytokine inhibition preserves renal hemodynamic function following mesangial cell immune injury

BACKGROUND: We assessed the effect of a cytokine inhibitor, compound SKF 86002 (a bicyclic imidazole), on changes in renal hemodynamics (renal blood flow and glomerular filtration rate) that occur acutely following immune injury of glomerular mesangial cells. METHODS: Injury was induced in Munich-Wistar rats by the administration of a monoclonal antibody against the mesangial cell membrane antigen Thy 1.1. An acute drop in renal blood flow (RBF) and glomerular filtration rate (GFR) occurred within one hour of injury. RESULTS: Pretreatment of animals with the cytokine inhibitor SKF 86002 prevented this drop. SKF 86002 had no effect on glomerular synthesis of vasoconstrictor eicosanoids. CONCLUSIONS: The observations indicate that in mesangial cell immune injury, cytokines mediate renal hemodynamic impairment.     

Multiple primary malignancies in renal cell carcinoma

PURPOSE: We determine the incidence and nature of multiple primary malignancies in patients with renal cell carcinoma, and whether these patients have an increased risk of a second primary malignancy. MATERIALS AND METHODS: Between July 1989 and January 1997, 551 patients underwent an operation for renal cell carcinoma. The incidence of other primary malignancies was determined and classified as antecedent, synchronous or subsequent. The observed number of subsequent malignancies after diagnosis of renal cell carcinoma was compared to the expected number based on age, race and sex specific 1990 to 1994 incidence rates from the United States Surveillance, Epidemiology and End Results data using the Poisson test. RESULTS: The number of primary malignancies, including cutaneous malignancies, was at least 1 in 148 patients (26.9%), at least 2 in 34 (6.2%), at least 3 in 6 (1.1%) and 4 in 1 (0.2%). Other malignancies were antecedent in 85 cases (45.0%), synchronous in 74 (39.4%) and subsequent in 30 (16.0%). The most common other primary malignancies were breast, prostate, colorectal and bladder cancer, and non-Hodgkin's lymphoma. Only men with renal cell carcinoma had an increased risk of bladder cancer (standardized incidence ratio 4.3, p = 0.0067). CONCLUSIONS: Breast, prostate, colorectal and bladder cancer as well as non-Hodgkin's lymphoma were the most common other primary malignancies. Men with renal cell carcinoma have an increased risk of subsequent bladder cancer.     

Expression of Fas in renal cell carcinoma

We have investigated whether the Fas-mediated cell death pathway is functional in renal cell carcinoma. The expression of Fas in surgical specimens and cell lines of renal cell carcinoma was examined. Fas expression was positive in six out of 18 tumors measured by flow cytometry and was prominent in advanced tumors. Three out of the six Fas-positive tumors had already metastasized at the time of surgery. A significant correlation was found between the tumor volume and the percentage of Fas-positive cells in a tumor (r = 0.70, P = 0.0007). Fas-positive tumors were larger than Fas-negative tumors [mean tumor volume (ml) +/- SD, Fas(+), 265.6 +/- 136.8; Fas(-), 65.8 +/- 80.9, P = 0.0012]. All human renal carcinoma cell lines tested (ACHN, Caki-1, SMKT-R-2, SMKT-R-3 and SMKT-R-4) expressed Fas abundantly, as Fas-positive cells accounted for > 50% in all cell lines by flow cytometry. Treatment with anti-Fas antibody caused apoptosis in Fas-positive renal cell carcinoma cell lines. However, the effectiveness of apoptosis induction in individual cell lines was not correlated with the level of Fas expressed. These data suggest that Fas targeting may be a therapeutic option for treatment of advanced renal cell carcinoma which is refractory to either chemotherapy or irradiation.     

Resection of metastatic renal cell carcinoma

PURPOSE: Resection of solitary metastases from renal cell carcinoma (RCC) is associated with a 5-year survival rate of 35% to 50%. Selection criteria are not well defined. PATIENTS AND METHODS: We retrospectively analyzed our experience with 278 patients with recurrent RCC from 1980 to 1993. RESULTS: One hundred forty-one of 278 patients underwent a curative metastectomy for their first recurrence (44% 5-year overall survival [OS] rate), 70 patients underwent noncurative surgery (14% 5-year OS rate), and 67 patients were treated nonsurgically (11% 5-year OS rate). Favorable features for survival were a disease-free interval (DFI) greater than 12 months versus 12 months or less (55% v 9% 5-year OS rate; P < .0001), solitary versus multiple sites of metastases (54% v 29% 5-year OS rate; P < .001), and age younger than 60 years (49% v 35% 5-year OS rate; P < .05). Among 94 patients with a solitary metastasis, lung (n = 50; 54% 5-year OS rate) was more favorable than brain (n = 11; 18% 5-year OS rate; P < .05). Survival rates after curative resection of second and third metastases were not different compared with initial metastectomy (46% and 44%, respectively, v 43% 5-year OS rates; P = nonsignificant). Favorable predictors of survival by multivariate analysis included a single site of first recurrence, curative resection of first metastasis, a long DFI, a solitary site of first metastasis, and a metachronous presentation with recurrence. CONCLUSION: Selected patients with recurrent RCC who can undergo a curative resection of their disease have a good opportunity for long-term survival, particularly those with a single site of recurrence and/or a long DFI.