Assessment of surgical margins in renal cell carcinoma after nephron sparing: a comparative study: laparoscopy vs open surgery

PURPOSE: We compared the status of the peritumoral parenchyma after open and laparoscopic nephron sparing surgery for renal cell carcinoma. MATERIALS AND METHODS: The records of 64 consecutive patients who underwent nephron sparing surgery for renal cell carcinoma of 4 cm or less were reviewed retrospectively. Patients in group 1 underwent open retroperitoneal surgery (1998 to 2000) and patients in group 2 underwent laparoscopic (transperitoneal or retro peritoneal) surgery (2001 to March 2004). A single pathologist was employed to analyze the specimens, and comparative analysis included examination of tumor size, weight, histological cell type, intraoperative histological biopsies and margin status. RESULTS: The 2 groups were comparable in terms of clinical data, and mean lesion size was 31.4 mm in group 1 and 32 mm in group 2. Positive margins were found in 1 of 30 patients in group 1 and in 1 of 34 in group 2 (p = 0.9). An analysis of margins was performed by taking measurements at the minimum and maximum points of the section. The minimum mean measurement was 2 mm in group 1 and 2.08 mm in group 2 (p = 0.75). The maximum mean measurement was 4.56 mm in group 1 and 5.2 mm in group 2 (p = 0.09). The difference between minimum and maximum margin thickness was 2.56 mm in group 1 and 3.16 mm in group 2 (p = 0.04). Mean followup for group 1 was 50 months (range 30 to 72) and 16 months (range 2 to 35) for group 2. One local recurrence was recorded in group 1 and treated with radical nephrectomy, while no recurrence was recorded in group 2. CONCLUSIONS: In this study we further confirmed the efficiency of resectioning lesions using laparoscopy. In our experience there is no difference between the 2 procedures in terms of efficient surgical margins. However, despite these encouraging results it is necessary to obtain more extensive followup data, which will allow us to be more specific in reporting on laparoscopic margin quality.     

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.     

The accuracy of 250 fine needle biopsies of renal tumors

PURPOSE: In some cases of uncertain lesions in the kidney it would be helpful to perform biopsies for preoperative histopathological evaluation. In this study we evaluated the accuracy of and the impact on tumor management of core biopsy for histopathological evaluation of small solid renal masses. MATERIALS AND METHODS: After radical or partial nephrectomy 250 renal tumor biopsies were performed in 50 patients. All biopsies were performed by 1 urologist after preparation of the kidney ex situ on back table visually guided. Formalin fixed paraffin embedded biopsies were evaluated by 1 pathologist. RESULTS: In 49 of 50 cases (98%) we could define the malignant behavior of the tumor when performing 1 central and 4 peripheral biopsies of each tumor. In 85.2% the grading was correctly defined. A benign lesion was revealed in 4 cases (8%, all oncocytoma). In renal tumors 4 cm or smaller in diameter the accuracy of 1 central and 1 peripheral biopsy each regarding definition of tumor origin, tumor grading and cell type/growth pattern was 96% and 95.5%, 84% and 84.4%, and 87.5% and 89.5%, respectively. In renal tumors more than 4 cm in diameter the accuracy was 100% and 98.1%, 85% and 94.3%, and 71.4% and 88.7%, respectively. CONCLUSIONS: Core biopsy of renal lesions is accurate enough for histopathological evaluation and determination of therapeutic procedure. Additionally, biopsy could be used for identifying benign renal lesion for observation.     

Optical spectroscopy characteristics can differentiate benign and malignant renal tissues: a potentially useful modality

PURPOSE: Promising results of optical signals have been reported in the literature for the diagnosis of Barrett's esophagus, oral cavity lesions, brain tumor margins, cervical intraepithelial neoplasia, skin cancer and bladder cancer. The potential usefulness of these techniques in renal tissues and neoplasms has not been described to date. This initial study examined the feasibility of using fluorescence and diffuse reflectance spectroscopy to differentiate between malignant and benign renal tissues. MATERIALS AND METHODS: An ex vivo study was conducted to identify optical characteristics of various renal tissue types. Pathologically confirmed benign and malignant renal samples were obtained from nephrectomy specimens from patients undergoing radical nephrectomy. Fluorescence and diffuse reflectance spectra were measured from benign and malignant renal tissues. RESULTS: All renal tissues, malignant or benign, contain 2 primary emission peaks-a strong one at approximately 285 nm excitation, approximately 340 nm emission (Peak A), and a weak one at approximately 340 nm excitation, approximately 460 nm emission (Peak B). Peak A of normal renal tissue typically locates at the shorter excitation wavelength region than that of malignant tissue. The intensity of Peak B from benign tissues tends to be greater than that from malignant renal tissues. Diffuse reflectance intensities from malignant renal tissues between 600 and 800 nm are markedly greater than those from normal renal tissue. Empirical discrimination algorithms developed based on selected fluorescence and diffuse reflectance spectral characteristics yields accurate differentiation between benign and malignant renal tissues. CONCLUSIONS: Highly accurate differentiation between normal human renal tissues and renal cell cancers is feasible using combined fluorescence and diffuse reflectance spectroscopy in an ex vivo setting. If successful in future clinical studies, optical spectroscopy could aid in margin detection and tissue discrimination while performing nephron sparing surgery.     

A phase 2 study of radio frequency interstitial tissue ablation of localized renal tumors

PURPOSE: Small renal tumors are frequently detected during the screening of patients with a hereditary type of renal cancer. The development of nonsurgical treatment modalities would greatly improve quality of life in these patients. We present our experience with radio frequency interstitial tissue ablation, a heating device approved by the Food and Drug Administration for treating soft tissue tumors. MATERIALS AND METHODS: Patients underwent radio frequency interstitial tissue ablation of small renal tumors just before surgical excision. Pathological examination of the renal tumors was done to evaluate the treatment effect. Computerized tomography and renal function testing were performed before and after therapy to evaluate toxicity. RESULTS: Four patients underwent treatment of a total of 14 tumors with the radio frequency interstitial tissue ablation device just before surgical removal of the tumors. All lesions were brown after ablation, in contrast to the normal pink appearance of untreated lesions that were resected. On color Doppler ultrasound blood flow to each tumor evident before was not visualized after treatment. The Wilcoxon rank sum test demonstrated no difference preoperatively and postoperatively in blood urea nitrogen, serum creatinine, creatinine clearance or differential renal function. We identified no toxicity associated with radio frequency interstitial tissue ablation. Of the excised tumors 11 were renal cell carcinoma and 3 fibrotic hemorrhagic cysts. For renal cell carcinoma the treatment effect involved the loss of nuclear detail and nonvisualization of nucleoli. These changes were not observed in any tumors resected without radio frequency interstitial tissue ablation. The treatment effect was noted in 10 of the 11 lesions, and in 1 case the treatment effect involved 35% of the tumor. CONCLUSIONS: No toxicity was associated with radio frequency interstitial tissue ablation. Percutaneous treatment of renal tumors is planned to evaluate the treatment effect better and further evaluate toxicity.     

Progression and long-term survival after simple enucleation for the elective treatment of renal cell carcinoma: experience in 107 patients

PURPOSE: We present our findings in a series of T1a renal cell carcinoma treated with elective simple enucleation, specifically reporting the incidence of local recurrence, and progression-free and disease specific survival rates. MATERIALS AND METHODS: A total of 107 patients who underwent elective nephron sparing surgery performed with simple enucleation from January 1989 to December 2000 were studied retrospectively. None of the patients had preoperative or intraoperative suspicion of positive nodes. All patients were free from distant metastases before surgery (M0). Patient status was last evaluated in July 2004. Mean (median, range) followup was 88.3 (84, 44 to 175) months. RESULTS: Pathological review according to the 2002 TNM classification showed that 95% (102 of 107) of tumors were pT1a, 4% (4 of 107) pT1b and 1% (1 of 107) pT3a. Mean (SD, median, range) tumor greatest dimension was 2.7 (0.93, 2.5, 0.6 to 5) cm. None of the patients died in the immediate postoperative period (within the first 30 days). There were no major complications such as bleeding and urinary leakage/urinoma requiring reoperation. The 5 and 10-year cancer specific survival was 99% and 97.8%, respectively. The 5 and 10-year progression-free survival was 98.1% and 94.7%, respectively. Overall 3 patients had disease progression (2.8%) of whom 2 (1.9%) were local recurrence, 1 alone and 1 associated with distant metastases diagnosed 12 months earlier. CONCLUSIONS: Simple tumor enucleation is a safe and acceptable approach for elective nephron sparing surgery. It provides excellent long-term progression-free and cancer specific survival rates, and is not associated with an increased risk of local recurrence compared with partial nephrectomy.     

Surgical management of renal tumors 4 cm. or less in a contemporary cohort

PURPOSE: We evaluated a patient cohort with renal tumors 4 cm. or less treated with partial or radical nephrectomy. We compared patient and tumor characteristics, and survival in these 2 groups. MATERIALS AND METHODS: We retrospectively analyzed the records of 670 patients with a median age of 63 years treated surgically for renal cell carcinoma between July 31, 1989 and July 31, 1997. Renal tumors 4.0 cm. or less were noted in 252 patients (38%) who underwent a total of 262 procedures, including 183 radical (70%) and 79 partial (30%) nephrectomies. Ten patients required 2 operations each because of bilateral renal cell carcinoma. Median followup was 40 months. We compared clinicopathological parameters in the partial and radical nephrectomy groups using chi-square or Wilcoxon analysis as appropriate. Survival analysis was determined by the log rank test and Cox regression model. RESULTS: The partial and radical nephrectomy groups were comparable with respect to gender ratio, tumor presentation, histological classification, pathological stage and complication rate. Median tumor size was 2.5 and 3.0 cm. in the partial and radical nephrectomy groups, respectively (p = 0.0001). Resection was incomplete in 1 patient (1.3%) in the partial and none in the radical nephrectomy group. There was no local recurrence after either procedure, and no significant difference in disease specific, disease-free and overall survival (p = 0.98, 0.23 and 0.20, respectively). CONCLUSIONS: Patients with a small renal tumor have similar perioperative morbidity, pathological stage and outcome regardless of treatment with partial or radical nephrectomy. Therefore, partial nephrectomy remains a safe alternative for tumors of this size.     

A scoring algorithm to predict survival for patients with metastatic clear cell renal cell carcinoma: a stratification tool for prospective clinical trials

PURPOSE: We developed a clinically useful scoring algorithm to predict cancer specific survival for patients with clear cell metastatic renal cell carcinoma (RCC). MATERIALS AND METHODS: We studied 727 patients treated with radical nephrectomy for clear cell RCC from 1970 to 2000 who had distant metastases at nephrectomy (285) or in whom metastases subsequently developed (442). A scoring algorithm to predict cancer specific survival was developed using the regression coefficients from a Cox proportional hazards model. RESULTS: There were 606 deaths from clear cell RCC at a median of 1.0 years (range 0 to 14) following metastatic RCC. Constitutional symptoms at nephrectomy (+2), metastases to the bone (+2) or liver (+4), metastases in multiple simultaneous sites (+2), metastases at nephrectomy (+1) or within 2 years of nephrectomy (+3), complete resection of all metastatic sites (-5), tumor thrombus level I to IV (+3), and the primary pathological features of nuclear grade 4 (+3) and histological tumor necrosis (+2) were significantly associated with death from RCC. All patients started with a score of 0 and points were added or subtracted as indicated in parentheses. Cancer specific survival rates at 1 year were 85.1%, 72.1%, 58.8%, 39.0%, and 25.1%, respectively, for patients with scores of -5 to -1, scores of 0 to 2, scores of 3 to 6, scores of 7 or 8, and scores of 9 or more. CONCLUSIONS: This scoring algorithm can be used to predict cancer specific survival for patients with metastatic clear cell RCC.     

Nephron sparing surgery for central renal tumors: experience with 33 cases

PURPOSE: Nephron sparing surgery is standard treatment for small, peripherally located renal cell carcinoma. In patients with a solitary kidney, bilateral tumors or impaired renal function nephron sparing surgery provides the only option to nephrectomy and subsequent hemodialysis or transplantation. We retrospectively investigated the value of nephron sparing surgery for centrally located renal cell carcinoma. MATERIALS AND METHODS: Between 1969 and 1997, 311 renal tumor enucleations were performed at our institution. The tumor was centrally located in 33 cases. The indication for enucleation was elective in 7 cases and imperative in 26, including bilateral tumor in 16 (metachronous in 9 and synchronous in 7), chronic renal failure in 4 and solitary kidney in 6. Four patients had metastasis at enucleation. RESULTS: Convalescence was unremarkable in 28 cases. Hemorrhage occurred in 1 patient, a urinary fistula in 2 and a local abscess secondary to a urinary fistula in 1. One patient died postoperatively of heart failure. Average serum creatinine was 1.25, 1.63 and 1.33 mg./dl. preoperatively, at hospital discharge and at a mean followup of 33 months, respectively. Hemodialysis was necessary transiently during convalescence in 1 patient and permanently starting 6 years after enucleation in another. Definitive histology revealed oncocytoma in 4 cases and renal cell carcinoma in 29. Disease was stages pT1 to pT3 in 9, 18 and 2 cases, and grades 1 to 3 in 6, 18 and 5, respectively. Local recurrence developed in 2 patients. Mean followup was 5.2 years (range 0.3 to 16.7). At a mean followup of 6.2 years (range 0.7 to 16.7) 20 patients were free of disease. In addition to the patient who died postoperatively, 9 died of renal cell carcinoma at a mean of 1.6 years (range 0.3 to 5.3) and 3 died of other causes at 5, 11 and 12 years postoperatively, respectively. No patient who underwent elective enucleation died. CONCLUSIONS: Nephron sparing surgery for centrally located kidney tumors is technically feasible and associated with an acceptable complication rate. Local tumor control is excellent, and the overall prognosis depends on contralateral disease and metastasis. Benign tumors may be diagnosed and removed without loss of the kidney. By avoiding hemodialysis quality of life is improved.     

Effect of dexamethasone on perioperative renal function impairment during cardiac surgery with cardiopulmonary bypass

Background. In cardiac surgery with cardiopulmonary bypass (CPB),corticosteroids are administered to attenuate the physiologicalchanges caused by the systemic inflammatory response. The effectsof corticosteroids on CPB-associated renal damage have not beendocumented. The purpose of this study was to evaluate the effectsof dexamethasone on perioperative renal dysfunction in patientsundergoing cardiac surgery with CPB. Methods. Renal damage was prospectively studied in 20 patientswithout concomitant morbidity undergoing coronary artery surgerywith CPB. Patients were randomized in a double-blind fashionto receive dexamethasone or placebo. Markers of glomerular function(creatinine clearance) and damage (microalbuminuria), and markersof tubular function (fractional excretion of sodium and freewater clearance) and damage (N-acetyl-ß-D glucosaminidase(NAG)) were evaluated in addition to plasma and urinary glucoselevels. Plasma and urinary specimens were obtained at the followingtime periods: (1) baseline, during the 12 h before surgery;(2) skin incision before heparinization; (3) from heparinizationuntil the end of CPB; (4) during the 2 h following weaning fromCPB; (5) in the intensive care unit from 2 to 6 h after weaningof CBP; (6) and from 36 to 60 h after weaning of CPB. Results. CPB was associated with an increase in markers in theplacebo group, which returned to baseline during the secondpostoperative day, demonstrating a transient impairment of glomerularand tubular renal function. Similar patterns were observed inpatients treated with dexamethasone. While postoperative glycosuriawas significantly higher in the dexamethasone-treated group,no other differences between groups were observed. Conclusion. Dexamethasone administration before CPB has no protectiveeffect on perioperative renal dysfunction in low-risk cardiacsurgical patients.     

Renal cell carcinoma 2005: new frontiers in staging, prognostication and targeted molecular therapy

PURPOSE: Renal cell carcinoma (RCC) has traditionally been staged using a purely anatomical staging system. Although current staging systems provide good prognostic information, data published in the last few years has led to significant controversies as to whether further revisions are needed and whether improvements can be made with the introduction of new, more accurate and predictive prognostic factors not currently included in traditional staging systems. This review highlights such controversies and provides an update on current staging modalities, prognostic factors and targeted molecular therapy for RCC. MATERIALS AND METHODS: A comprehensive review of the peer reviewed literature was performed on the topic of current staging modalities, validated prognostic factors, predictive nomograms, molecular markers and targeted molecular therapy for RCC. RESULTS: A staging system for malignant disease such as RCC uses various characteristics of tumors to stratify patients into clinically meaningful categories, which can be used to provide patients with counseling regarding prognosis, select treatment modalities and determine eligibility for clinical trials. The TNM staging system is currently the most extensively used one. However, it has undergone recent systematic revision due to rapidly emerging data from longer patient followup. The identification of various histological and symptomatic factors has led groups at many centers to develop more comprehensive staging systems that integrate these factors and include patients with metastatic and local disease. While integrated staging systems have improved RCC staging, the recent discovery of molecular tumor markers is expected to revolutionize RCC staging in the future and lead to the development of new therapies based on molecular targeting. CONCLUSIONS: Staging systems for RCC serve as a valuable prognostic tool. Several new patient and tumor characteristics have been reported to be important prognostic factors and they have been integrated into current staging systems. In addition, the field of RCC is rapidly undergoing a revolution led by molecular markers and targeted therapies. With this information urologists will be updated with the most current and comprehensive staging strategies, and be provided with a glimpse of the molecular and patient specific staging and treatment paradigms that will in our opinion transform the future management of this malignancy.     

Associations with contralateral recurrence following nephrectomy for renal cell carcinoma using a cohort of 2,352 patients

PURPOSE: We determined the incidence of and factors associated with the development of renal cell carcinoma (RCC) in the contralateral kidney after nephrectomy for localized RCC. MATERIALS AND METHODS: Between 1970 and 2000, 2,352 patients with sporadic, localized unilateral RCC and a normal contralateral kidney underwent nephrectomy for RCC. Cancer specific survival rates were estimated using the Kaplan-Meier method. Univariate Cox proportional hazards models were used to determine associations with outcome. RESULTS: Of the 2,352 patients studied 28 (1.2%) had RCC in the contralateral kidney, including 20 with clear cell and 8 with papillary RCC. Mean time from primary surgery to contralateral recurrence was 5.2 years (median 4.8, range 0 to 18) for clear cell RCC compared with 5.6 years (median 1.3, range 0 to 21) for papillary cell RCC. Positive surgical margins (risk ratio 14.23, p = 0.010) and multifocality (risk ratio 5.74, p = 0.019) were significantly associated with contralateral recurrence following nephrectomy for clear cell RCC, while nuclear grade (risk ratio for grades 3/4 vs 1/2, 4.78, p = 0.040) was significantly associated with contralateral recurrence following nephrectomy for papillary RCC. In patients with clear cell RCC estimated cancer specific survival rates 1, 3, and 5 years following contralateral recurrence were 93.8%, 80.2% and 72.9%, respectively. CONCLUSIONS: In patients with localized RCC and a normal contralateral kidney who underwent nephrectomy for RCC positive surgical margins and multifocality were significant predictors of contralateral recurrence for clear cell RCC, while nuclear grade was a significant predictor of contralateral recurrence for papillary RCC.     

Renal cell carcinoma with renal vein and inferior vena caval involvement: clinicopathological features, surgical techniques and outcomes

PURPOSE: We present a contemporary review of patients with renal cell carcinoma (RCC) in whom renal vein/inferior vena caval thrombus was treated with radical nephrectomy and thrombectomy. MATERIALS AND METHODS: A total of 220 patients underwent radical nephrectomy for RCC at our institution from 1998 to 2002. Of them 49 patients with renal vein/inferior vena caval involvement (T3b/c) were selected for review. We evaluated demographics, presenting symptoms, imaging modalities, clinical staging, pathological features, adjuvant treatment and clinical outcomes. We also evaluated surgical incisions, liver mobilization procedures, blood loss, transfusion requirements and perioperative mortality/morbidity. RESULTS: Gross hematuria was the most common presenting symptom, seen in 22 patients (45%), followed by constitutional symptoms in 8 (16%). Stage T3b/c was clinically diagnosed in 44 patients, while 2 had T2 and 2 had T4 disease. A subcostal incision was made in 30 patients, a chevron incision was made in 18, and a sternotomy and flank incision were made in 1. Liver mobilization was necessary in 13 patients and 2 required a Pringle maneuver. Cardiopulmonary bypass was performed in a single patient. Lymph node involvement was seen in 4 patients (8%) and distant metastases were present in 10 (20%). Median tumor size was 10 cm. Clear cell carcinoma was most common, as seen in 42 patients. Early (30-day) mortality in this series was 8%. At a median followup of 15 months 21 patients (43%) were without evidence of disease, 14 (29%) had disease, 8 (16%) had died of disease and 2 (4%) had died of other causes. None of the patients with lymph node involvement survived beyond 8 months after surgery. Tumor grade and T stage were found to be significant negative predictors of survival on univariate analysis. CONCLUSION: Most patients with RCC and tumor thrombus are symptomatic at presentation and metastatic disease at presentation is not uncommon. These results support the role of aggressive surgical treatment as the best initial management of these tumors. The majority of tumors can be approached and safely controlled without the need for a thoracoabdominal incision. While surgery provides modest disease-free survival, most patients should be offered immunotherapy, particularly those with advanced stage, grade, nodal involvement or metastases.