Changes of lymphocyte subpopulation in advanced renal cell carcinoma patients with marked response to alpha-interferon therapy

At present, no sufficient therapy for advanced renal cell carcinoma is available. Interferon (IFN) therapy has been used to treat renal cell carcinoma, but the efficacy of it is low, with response rate being only about 20%. We experienced two patients with advanced renal cell carcinoma had marked response to IFN-alpha therapy in proximity effect. Using monoclonal anti-bodies of each subset of lymphocytes, the peripheral blood lymphocytes (PBL) in these patients were evaluated by two color flow-cytometry. And these results and clinical course were assessed. The lymphocyte subpopulation that change of clinical course is been similar to in these patients were Tc (CD11b-CD8+), TSI (leu8+ CD4+), ATS/C (CD8+ HLA-DR+) and ATH/SI (CD4+ HLA-DR+). And the pretherapeutic immunological status of these patients was characterized by significantly increased CD4+/CD8+ and TH/TS ratio. In conclusion, the clinical response of advanced renal cell carcinoma to IFN therapy might be found if CD4+/CD8+ and TH/TS ratio are increased at pretherapeutic immunological status. In addition, assessment of TSI, TC, ATH/SI, and ATS/C, as immune parameters for monitoring the actual immune status of patient is found to be necessary part of immunotherapy.     

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.     

Cytokine levels in cystic renal masses associated with renal cell carcinoma

PURPOSE: We compared cytokine levels in fluid from renal cysts with and without renal cell carcinoma. MATERIALS AND METHODS: Fluid was aspirated from 18 renal cysts without (benign) and 21 with renal cell carcinoma (malignant). Serum from patients with renal cell carcinoma and healthy controls was collected and cytokines were measured by enzyme-linked immunosorbent assay. RESULTS: Interleukin-6 (IL-6) and basic fibroblast growth factor concentrations were higher in malignant than benign cysts or serum (p <0.006). Epidermal growth factor levels were significantly higher in malignant cysts and serum than in benign cysts (p <0.01). IL-6 levels in malignant cysts positively correlated with the erythrocyte sedimentation rate (R=0.80) and C-reactive protein (R=0.86), and they were higher in grade 3 than in grade 2 tumors. Basic fibroblast growth factor levels were significantly higher in malignant cysts associated with hypervascular than hypovascular tumors (p=0.029). CONCLUSIONS: Cytokine levels in aspirated fluid may help to identify malignant renal cysts and indicate the characteristics of coexisting tumors.     

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.     

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.     

Clinicopathological study of incidental renal cell carcinoma

BACKGROUND: The objective of this study is to evaluate the clinicopathological features of incidental renal cell carcinoma, compared with non-incidental carcinoma. METHODS: Between July 1st, 1984 and June 30, 1994, 87 renal cell carcinoma patients were treated at our hospital; 56 had non-incidental renal cell carcinoma and 31 had incidental carcinoma. The clinicopathological features were examined. RESULTS: The incidence of incidental cancer ranges from 0 to 66%, and the incidence has increased in recent years. The median value of maximal tumor size was 4.0cm (1.5 approximately 8.0cm) for incidental cancer, and 8.0cm (3.0 approximately 16cm) for incidental cancer, and 8.0cm (3.0 approximately 16cm) for non-incidental cancer, i.e., the incidental cancer was significantly smaller than the non-incidental one (p < 0.001). The pathological stage of the resected non-incidental renal cell carcinoma (n = 47) was pT1, pT2, pT3 and pT4 in 0, 23, 21 and 3 patients, respectively. For the resected incidental renal cell carcinoma (n = 31) 3, 26, 2 and 0 patients showed pathological stages pT1, pT2, pT3 and pT4, respectively; the pathological stage of incidental renal cell carcinoma was significantly lower than that of non-incidental carcinoma (p < 0.001). Eighteen and 29 resected non-incidental renal cell carcinoma were grades 1 and 2, respectively, whereas 17 and 14 resected incidental renal cell carcinomas were in grades 1 and 2, respectively. Vascular invasion by tumor cells was shown in 31 (66.0%) and 8 (25.8%) patients with non-incidental and incidental renal cell carcinomas, respectively; the incidence of vascular invasion in incidental cancer being significantly lower than in non-incidental cancer (p < 0.001). The performance status and general condition in patients with incidental renal cell carcinoma were superior to those in patients with the non-incidental cancer. The 1, 3 and 5-year survival rate of all 87 renal cell carcinoma patients was 81, 62 and 57%, respectively. These rates for patients with non-incidental renal cell carcinoma were 72, 48 and 41%, respectively, and those for incidental cancer patients were 100%. The survival of patients with incidental renal cell carcinoma was significantly better than that of non-incidental carcinoma patients (p < 0.005). CONCLUSION: Our results suggest that the detection of incidental renal cell carcinoma will increase, and that the prognosis for renal cell carcinoma will improve. However, even in incidental renal cell carcinoma, careful long-term follow up may be necessary, since some tumors are comparatively large and exhibit vascular invasion.     

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.     

Laparoscopic enucleation of a renal cell carcinoma

The purpose of this study was to report on the feasibility of laparoscopic excision of renal cell carcinoma. An 81-year-old female with renovascular disease underwent a laparoscopic excisional operation for a 2-cm tumor localized in the left kidney. Pathological evaluation showed a low-grade tumor without any extension through the renal capsule (grade I Hand Broder, stage I Robson). The postoperative course was uneventful; there was minimal postoperative pain. The patient was discharged home on the sixth day. Laparoscopic excision would appear to be a safe and effective technique in selected cases.     

Metastasis of renal cell carcinoma to the contralateral renal pelvis

A young woman with syphilids resembling borderline lepromatous (BL) leprosy is being described. This is yet another addition to its already well-documented manifestations. The high prevalence of leprosy and syphilis augments the epidemiological significance of the case.     

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.     

Efficacy of recombinant alpha-interferon 2a and 13-cis-retinoic acid in the treatment of squamous cell carcinoma

BACKGROUND: Recent in vitro and in vivo studies hypothesize a synergistic effect of 13-cis-Retinoic Acid (13cRA) and recombinant alpha-IFN 2a (alpha-IFN) in the treatment of squamous cell carcinoma (SqCC). PATIENTS AND METHODS: 35 patients with SqCC in several sites were treated with 13cRA (0.6-1 mg/kg/day) combined with alpha-IFN (6 x 10(6) I.U./day), continuously for 3 months. RESULTS: We observed an objective response in 41% of cases (13/32 evaluable patients) with 5 complete and 8 partial responses. Toxicity was mild and always rapidly reversible, with no haematological side effects. CONCLUSIONS: These preliminary data confirm the feasibility and effectiveness of the combination of 13cRA and alpha-IFN in the therapy of SqCC, also in pre-treated patients, with acceptable toxicity and good compliance.     

Prevalence, morphology and biology of renal cell carcinoma in von Hippel-Lindau disease compared to sporadic renal cell carcinoma

PURPOSE: Renal cell carcinoma occurs as a sporadic tumor but may be part of the autosomal dominant von Hippel-Lindau disease, characterized by retinal and central nervous system hemangioblastoma, pheochromocytoma, pancreatic cysts and renal cell carcinoma. We determine the prevalence of von Hippel-Lindau disease in a series of unselected renal cell carcinoma cases by molecular genetic analysis, and compare sporadic to von Hippel-Lindau renal cell carcinoma with respect to morphology and biology. MATERIALS AND METHODS: We established registers comprising 63 subjects with von Hippel-Lindau renal cell carcinoma, belonging to 30 distinct families (register A), and 460 unselected patients operated on for renal cell carcinoma in an 11-year period (register B). Molecular genetic analysis of the von Hippel-Lindau gene was performed for living patients of register A, representing 80% of von Hippel-Lindau families, and register B, 62% living patients, to identify von Hippel-Lindau germline mutations. In addition, register B was evaluated by a questionnaire (95% response) for familial occurrence of von Hippel-Lindau disease. RESULTS: The prevalence of von Hippel-Lindau renal cell carcinoma was 1.6% in 189 consenting unselected renal cell carcinoma patients. Risk factors for occult germline von Hippel-Lindau gene mutations in register B included familial renal cell carcinoma in 3 of 3 patients (100%), multifocal or bilateral renal cell carcinoma in 1 of 10 (10%) and age younger than 50 years at diagnosis in 1 of 33 (3%). Compared to sporadic von Hippel-Lindau renal cell carcinoma was characterized by an occurrence 25 years earlier, association with renal cysts, multifocal and bilateral tumors, cystic organization and low grade histology, and a better 10-year survival (p < 0.001 each). In von Hippel-Lindau disease metastases occurred only in tumors larger than 7 cm. CONCLUSIONS: von Hippel-Lindau differs from sporadic renal cell carcinoma in morphology and biology. Our data provide arguments for planning surgery for von Hippel-Lindau renal cell carcinoma and should stimulate future investigations.     

Treatment of cutaneous T cell lymphoma with low doses of interferon alpha-2b

Pseudomona vasculitis is an exceptional disease. Only a few cases have been reported, non with oropharyngeal involvement. The case of a 30-year-old, HIV-positive man who suddenly developed septicemia and necrotizing lesions with tissue destruction of the oropharynx is reported. Histological study confirmed vasculitis. Pseudomona aeruginosa was isolated in peripheral blood and in the biopsy of the palatal lesion. Antibiotic treatment produced satisfactory results.     

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.     

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.     

Histopathologic prognostic indicators for renal cell carcinoma

Abstracts of scientific papers and posters that are presented at annual scientific meetings of professional societies are part of the broader category of conference literature. They are an important avenue for the dissemination of current data. While timely and succinct, these abstracts present problems such as an abbreviated peer review and incomplete bibliographic access. METHODS: Seventy societies of health sciences professionals were surveyed about the publication of abstracts from their annual meetings. Nineteen frequently cited journals also were contacted about their policies on the citation of meeting abstracts. Ten databases were searched for the presence of meetings abstracts. RESULTS: Ninety percent of the seventy societies publish their abstracts, with nearly half appearing in the society's journal. Seventy-seven percent of the societies supply meeting attendees with a copy of each abstract, and 43% make their abstracts available in an electronic format. Most of the journals surveyed allow meeting abstracts to be cited. Bibliographic access to these abstracts does not appear to be widespread. CONCLUSIONS: Meeting abstracts play an important role in the dissemination of scientific knowledge. Bibliographic access to meeting abstracts is very limited. The trend toward making meeting abstracts available via the Internet has the potential to give a broader audience access to the information they contain.