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Paul Russo

Publications and source records attributed to Paul Russo.

65 records · Page 4Linked to original sources
PubMed2002

Phase II trial of thalidomide for patients with advanced renal cell carcinoma.

PURPOSE: To assess efficacy and toxicity of thalidomide in patients with advanced renal cell carcinoma (RCC). PATIENTS AND METHODS: Twenty-six patients with RCC were treated with thalidomide at a starting dose of 200 mg daily. Thalidomide was increased by 200 mg every 2 weeks until a maximum dose of 800 mg or prohibitive toxicity was reached. Fifteen patients had prior nephrectomy, 11 patients had no prior systemic therapy, and 15 had received one prior systemic regimen. RESULTS: A maximum dose of 800 mg, 600 mg, 400 mg, and 200 mg was reached in five, 10, eight, and three patients, respectively. Grade 2 and 3 dyspnea occurred in four and three patients, respectively. Grade 2 and 3 neurologic toxicity was observed in five and two patients, respectively. Of the 25 assessable patients, the best response was stable disease in 16 (95% confidence interval [CI], 43% to 82%) patients. The 6-month progression-free survival rate was 32% (95% CI, 14% to 50%). Three patients achieved prolonged stable disease of 16, 16+, and 18+ months, including two patients who were refractory to previous cytokine therapy. Fifty-seven percent were alive at 1 year (95% CI, 37% to 76%). CONCLUSION: This trial does not support the routine use of thalidomide to induce partial response for metastatic RCC. Because disease stabilization occurs as a part of the natural history of metastatic RCC, the potential effect of thalidomide on progression-free and overall survival for patients with advanced RCC is being addressed in a randomized phase III trial. New immunomodulatory analogs of thalidomide that have shown potentially greater antitumor effects in preclinical models warrant study in metastatic RCC.

Adult↗
PubMed2002

Charcot-Marie-Tooth disease and related neuropathies: mutation distribution and genotype-phenotype correlation.

Charcot-Marie-Tooth disease (CMT) is a genetically heterogeneous disorder that has been associated with alterations of several proteins: peripheral myelin protein 22, myelin protein zero, connexin 32, early growth response factor 2, periaxin, myotubularin related protein 2, N-myc downstream regulated gene 1 product, neurofilament light chain, and kinesin 1B. To determine the frequency of mutations in these genes among patients with CMT or a related peripheral neuropathy, we identified 153 unrelated patients who enrolled prior to the availability of clinical testing, 79 had a 17p12 duplication (CMT1A duplication), 11 a connexin 32 mutation, 5 a myelin protein zero mutation, 5 a peripheral myelin protein 22 mutation, 1 an early growth response factor 2 mutation, 1 a periaxin mutation, 0 a myotubularin related protein 2 mutation, 1 a neurofilament light chain mutation, and 50 had no identifiable mutation; the N-myc downstream regulated gene 1 and the kinesin 1B gene were not screened for mutations. In the process of screening the above cohort of patients as well as other patients for CMT-causative mutations, we identified several previously unreported mutant alleles: two for connexin 32, three for myelin protein zero, and two for peripheral myelin protein 22. The peripheral myelin protein 22 mutation W28R was associated with CMT1 and profound deafness. One patient with a CMT2 clinical phenotype had three myelin protein zero mutations (I89N+V92M+I162M). Because one-third of the mutations we report arose de novo and thereby caused chronic sporadic neuropathy, we conclude that molecular diagnosis is a necessary adjunct for clinical diagnosis and management of inherited and sporadic neuropathy.

Adolescent↗
PubMed2002

Partial nephrectomy: the rationale for expanding the indications.

BACKGROUND: We report preliminary results of partial nephrectomy for renal tumors of > or =4 cm in 39 patients with the intent of extending the indications for kidney-sparing surgery. METHODS: From July 1989 to October 2001, 39 patients underwent a partial nephrectomy for renal cortical tumors >4 cm in maximum diameter. Fourteen (36%) had the procedure performed for essential reasons, and 25 (64%) had an elective kidney-sparing operation. We evaluated tumor location and histology, perioperative renal function, and postoperative complications. RESULTS: There were 20 conventional clear-cell (51%), 13 papillary (33%), 4 chromophobe (10%), and 3 oncocytomas (8%) with a median tumor size of 5 cm. After a median follow-up of 13 months, 36 patients had no evidence of disease, 1 patient had died as a result of other causes, and 2 patients who had essential operations were alive with disease. Twenty-three patients (70%) maintained normal postoperative renal function. Of six patients with moderate preoperative renal dysfunction, five (83%) had no change in postoperative renal function and only one patient required short-term dialysis. CONCLUSIONS: With careful patient selection, partial nephrectomy can be effectively used to treat patients with renal cortical tumors >4 cm in diameter. The benefits of this approach include the effective local tumor control while at the same time preserving maximum renal function.

Adult↗
PubMed2002

Natural history of chronic renal insufficiency after partial and radical nephrectomy.

OBJECTIVES: To compare the incidence of newly developed chronic renal insufficiency after partial nephrectomy (PN) and radical nephrectomy (RN). Elective PN for renal tumors is intended to preserve renal function; however, studies of transplant donors suggest normal renal function is also maintained after unilateral nephrectomy. METHODS: We retrospectively compared all patients undergoing PN or RN for renal tumors 4 cm or less in the presence of a normal contralateral kidney from 1989 to 2000. Creatinine failure was defined as a serum creatinine value greater than 2.0 mg/dL. Risk factors for renal insufficiency, including diabetes, hypertension, American Society of Anesthesiologists score, age, preoperative creatinine, and history of smoking tobacco, were compared between the two groups. We compared the two groups using the chi-square and Mann-Whitney U tests and the creatinine failure rates using the Kaplan-Meier method. RESULTS: One hundred seventy-three patients met the criteria for analysis after RN and 117 did so after PN (median follow-up 25 months). The 5-year freedom from recurrence rate was 96.4% and 98.6% for PN and RN, respectively (P >0.05). The mean preoperative serum creatinine was 1.0 mg/dL (range 0.4 to 1.4) and 0.98 (range 0.6 to 1.5) for RN and PN, respectively (P = 0.4, not significant). The incidence of risk factors for renal insufficiency did not differ between the two groups. The mean postoperative serum creatinine in the RN and PN groups was 1.5 mg/dL (range 0.8 to 3.8) and 1.0 mg/dL (range 0.5 to 1.9), respectively (P <0.001). The chance of creatinine failure over time was significantly greater in the RN group (P = 0.008). CONCLUSIONS: When controlled for preoperative risk factors for renal insufficiency, patients undergoing RN are at a greater risk of chronic renal insufficiency than a similar cohort of patients undergoing PN.

Adult↗
PubMed2002

Partial nephrectomy for renal cortical tumors: pathologic findings and impact on outcome.

OBJECTIVES: To review the experience with partial nephrectomy for the diagnosis and treatment of renal cortical tumors at the Memorial Sloan-Kettering Cancer Center with a particular focus on the histologic findings at the time of surgery. METHODS: The results of 292 consecutive partial nephrectomies were reviewed. Demographic data, perioperative complications, and disease status were recorded. The specimens were reviewed for histologic subtyping in accordance with the Heidelberg classification for renal cortical tumors. The probabilities of recurrence and disease-specific death were assessed with the cumulative incidence estimate. RESULTS: The median follow-up was 25.3 months (range 1 to 155). A total of 246 patients (87%) were diagnosed with a renal cortical tumor, 1 patient (less than 1%) was diagnosed with another cancer, and 34 (12%) were diagnosed with benign lesions. The most frequent histologic finding among the renal cortical tumor subgroup was conventional clear cell carcinoma in 148 cases (51%), followed by papillary carcinoma in 54 (18%), oncocytoma in 32 (11%), and chromophobe carcinoma in 21 (7%). Bilateral disease and multifocality were most prevalent in the conventional and papillary subtypes, respectively. The 5-year probability of recurrence and disease-specific death was 12% and 8%, respectively, for the conventional clear cell type. No local or distant disease recurrence was observed in any other renal cortical tumor subtypes. CONCLUSIONS: Partial nephrectomy should be considered a diagnostic and therapeutic surgical approach for renal cortical masses. Conventional clear cell carcinoma is the most frequent histologic subtype and is associated with a less favorable outcome compared with papillary carcinoma and chromophobe carcinoma. Radical nephrectomy for renal lesions that could be removed by partial nephrectomy will risk renal impairment in a substantial proportion of patients with benign disease.

Adult↗
PubMed2002

Allelic loss on chromosomes 8 and 9 correlates with clinical outcome in locally advanced clear cell carcinoma of the kidney.

PURPOSE: We correlated allelic loss on chromosomes 8p, 9p and 14q with clinical outcome in locally advanced conventional renal cell carcinoma. MATERIALS AND METHODS: We analyzed radical nephrectomy specimens from 72 stage P3N0 conventional renal cell carcinomas by microsatellite loss of heterozygosity (LOH) analyses directed at chromosomes 3p, 8p, 9p and 14q (2 primers per chromosome). All patients were treated with surgery only. LOH results were correlated with disease-free survival using the Kaplan-Meier method. RESULTS: We detected LOH on chromosome 3p in 60 of 64 (94%), on chromosome 8p in 19 of 59 (32%), on 9p in 21 of 67 (31%) and on 14q in 18 of 70 (26%) informative cases. Of the 72 patients 24 (33%) had recurrence during followup. On univariate analysis patients with tumors demonstrating LOH on chromosomes 8p and 9q were at high risk for recurrence (p = 0.01). The correlation of recurrence with LOH approached significance for the individual chromosomes 8p and 9p (p = 0.10 and 0.14, respectively). No correlation was observed of LOH on chromosome 14q with recurrence (p = 0.42). The correlation of tumor grade with risk of relapse also approached significance (p = 0.12). On multivariate analysis LOH on chromosome 8p was a more powerful predictor of recurrence than tumor grade. When combinations of LOH on chromosomes were tested, LOH on chromosomes 8p and 9p was the most powerful predictor of recurrence (p = 0.006). CONCLUSIONS: LOH on chromosomes 8p or 9p may provide prognostic significance in patients with locally advanced renal cell carcinoma.

Carcinoma, Renal Cell↗
PubMedDate not supplied

Mode of presentation of renal cell carcinoma provides prognostic information.

PURPOSE: Broadened applications of imaging modalities have increased the incidental detection of renal cell carcinoma (RCC) over the past decade. Previous small series have suggested a prognostic benefit for incidental presentation. This study utilizes a large contemporary patient cohort to examine patterns of RCC presentation and their clinical implications. MATERIALS AND METHODS: Retrospective analysis was performed on 721 patients (260 women, 461 men) who underwent 750 nephrectomies for treatment of RCC between 7/1/89 and 12/31/97; 29 patients required two operations for bilateral RCC. Median age and follow-up were 63 years and 41 months, respectively. Indicators of symptomatic presentation included flank pain, flank mass, hematuria, varicocele, constitutional symptoms, paraneoplastic syndromes, and bone pain related to metastatic disease. Mode of presentation was compared with clinicopathologic parameters using Chi-square and t-test analyses. Survival analysis was performed using Kaplan-Meier estimates (log-rank test) and Cox regression modeling. RESULTS: Incidental and symptomatic presentation occurred in 57% and 42% of cases, respectively. When compared to incidental cases, symptomatic presentation was predominantly detected in younger patients (mean age, 59 years; P < .001), in males (P < .04), and in tumors with conventional (clear cell) histology (P < .001), larger size (mean, 8 cm; P < .001), and non-organ confined pathology (P < .001). In univariate analysis, symptomatic cases had a more adverse disease-free (P < .0001) and disease-specific (P < .0001) survival. In multivariate analysis, mode of presentation was an independent predictor of disease-free (P < 0.0001) and disease-specific survival (P < 0.005). CONCLUSIONS: Symptomatic presentation correlates with an aggressive histology and advanced disease. Incidental tumors may be frequently detected in female and elderly patients, as these groups traditionally seek general medical care more regularly. Mode of presentation can independently predict an adverse patient outcome and should be included in RCC-specific modeling systems.

Carcinoma, Renal Cell↗
PubMedDate not supplied

Conventional (clear cell) renal carcinoma metastases have greater bcl-2 expression than high-risk primary tumors.

Bcl-2 antagonizes p53-induced apoptosis and may contribute to chemoresistance. In renal cell carcinoma (RCC), the role of bcl-2 is not well-defined, though its expression is reportedly low in primary tumors and lacks prognostic value. This study evaluates patterns of bcl-2 expression in high-risk (pT(3)) primary tumors and in matched patient metastases. Immunohistochemical analysis of bcl-2 was performed on 149 cases of conventional (clear cell) RCC (112 pT(3) primaries, 37 metastases). Paraffin-embedded tissues were obtained from nephrectomies and metastatic resections. Median follow up was 48 months in the entire cohort and 69 months in living patients. We evaluated associations between bcl-2 expression and tumor recurrence or patient survival with the Cox regression test, and used the t-test and Pearson correlation methods to evaluate bcl-2 expression in primary and metastatic cases. Bcl-2 expression was observed at a higher frequency in metastases (21/37 cases; 57%) compared to primary tumors (24/112 cases; 21%; P < 0.001). The percentage of cells stained was greater in metastases than primary tumors (P = 0.003). This finding was also noted when expression in metastatic cases was compared with matched primaries (P = 0.05). Bcl-2 expression did not predict disease-free (P = 0.30), disease-specific (P = 0.90), or overall (P = 0.51) survival. Most RCC primary tumors have low-to-absent levels of bcl-2 protein, whereas most RCC metastases display greater protein levels. Bcl-2 expression in primary tumors does not predict clinical outcome. However, expression of bcl-2 protein occurs at a high frequency in RCC metastases when compared to primary tumors. It may be reasonable to target RCC patients displaying altered bcl-2 levels for molecular therapies, such as anti-bcl2, should metastatic disease develop.

Adult↗