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Renal cell cancer. From symptoms to therapy
Abstract
Renal cell cancer is one of the tenth most frequent tumor-dependent causes of death worldwide. In localized stages surgical therapy is the only curative option for the patient. If a renal cell carcinoma is diagnosed in late, i.e. advanced/metastasized stages a drug therapy with targeted agents following tumor burden surgery is nowadays the best option to increase patients progression-free survival. Whenever possible, a partial resection should be perform on regard to decrease rates of longtime renal failure.
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Epigenetic silencing of the RAS association domain family 1A (RASSF1A) tumor suppressor gene promoter has been demonstrated in renal cell carcinoma (RCC) as a result of promoter hypermethylation. Contradictory results have been reported for RASSF1A methylation in normal kidney, thus it is not clear whether a significant difference between RASSF1A methylation in normal and tumor cells of the kidney exists. Moreover, RASSF1A expression has not been characterized in tumors or normal tissue as yet.
Using combined bisulfite restriction analysis (COBRA) we compared RASSF1A methylation in 90 paired tissue samples obtained from primary kidney tumors and corresponding normal tissue. Bisulfite sequence analysis was carried out using both pooled amplicons from the tumor and normal tissue groups and subclones obtained from a single tissue pair. Expression of RASSF1A was analyzed by the use of tissue arrays and immunohistochemistry. We found significantly increased methylation in tumor samples (mean methylation, 20%) compared to corresponding normal tissues (mean methylation, 11%; P < 0.001). Densely methylated sequences were found both in pooled and individual sequences of normal tissue. Immunohistochemical analysis revealed a significant reduced expression of RASSF1A in most of the tumor samples. Heterogeneous expression patterns of RASSF1A were detected in a subgroup of histologically normal tubular epithelia.
Our methylation and expression data support the hypothesis that RASSF1A is involved in early tumorigenesis of renal cell carcinoma.
To define the rate of positive surgical margins (PSMs) and analyze the outcome of patients with PSMs. The outcome and proper management of patients with positive PSMs during nephron sparing surgery (NSS) are questionable. In this study we define the clinical outcomes of PSMs at NSS and suggest management.
Clinical records of 114 renal units who underwent open NSS for a renal mass between May 1995 and September 2005 were reviewed.
PSMs were suspected on frozen section in 17 of 114 renal units (15%). Tumors with suspected PSMs at frozen section were smaller (2.9 +/- 1.6) in comparison to those with negative surgical margins (3.4 +/- 1.8 cm) (P = .001). Nine of 17 (53%) cases underwent total nephrectomy (5 immediately, 4 delayed). In 4 (24%), immediate re-excision of the renal crater was performed. A total of 4 (24%) that were followed up clinically were with no evidence of disease. Therefore, in 13 of 17 (77%) cases, the presence of tumor cells at the remaining side of the kidney could be evaluated histologically. In 2 cases from the immediate response group, tumor cells were found in the side opposite to the resection. There was no residual tumor in any case subjected to delayed nephrectomy. At median follow-up of 71 months, 15 of 17 patients are alive and with no evidence of disease. Two patients died because of unrelated causes. The overall 5-year survival rate is 98.2% and there is no cancer-specific mortality.
The true PSM rate is in the range of 1.75%-5.26%. No disease progression or deaths attributable to renal cell carcinoma were associated with PSMs. Total nephrectomy should be avoided as a response to PSMs.
Laparoscopic-guided radiofrequency ablation (LRFA) has been introduced as a minimally invasive nephron-sparing management option for renal tumors. Many patients who desire treatment present with multiple comorbidities, which poses a therapeutic challenge. Our purpose is to determine if multipass LRFA is comparable, in terms of surgical risk and immediate postoperative outcomes, to laparoscopic partial nephrectomy (LPN).
A retrospective study identified 36 and 33 patients who underwent LRFA and LPN, respectively. Perioperative demographic data, tumor characteristics, and follow-up data were evaluated. Statistical analysis was performed using the Student t test and chi-square analysis.
Age, American Society of Anesthesiology score, and Charlson Comorbidity Index were significantly higher in the LRFA group than the LPN group (P < 0.001). Average tumor size was 2.8 cm and 3.1 cm for the LRFA and LPN groups, respectively. There were no significant differences in change between the preoperative and postoperative creatinine/glomerular filtration rate values or perioperative complication rates for the groups. Estimated blood loss and length of stay were significantly lower for the LRFA group than the LPN group (P < 0.05). Follow-up ranged 6 to 23 months and 6 to 58 months for the LRFA and the LPN groups, respectively. There has been no evidence of tumor recurrence in the follow-up period.
We present our initial report comparing patients undergoing LRFA v LPN for the management of renal tumors. Our preliminary results with our experience with multipass laparoscopic-guided RFA demonstrate that this technique can be safely used in an elderly, higher risk population. Long-term follow-up is needed to determine oncologic efficacy.
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.
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.
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.
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.