LAPAROSCOPIC RADICAL NEPHRECTOMY: CANCER CONTROL FOR RENAL CELL CARCINOMA

PURPOSE: We evaluated the clinical efficacy of laparoscopic versus open radical nephrectomy in patients with clinically localized renal cell carcinoma. MATERIALS AND METHODS: Between 1991 and 1999, 67 laparoscopic radical nephrectomies were performed for clinically localized, stages cT1/2 NXMX, pathologically confirmed renal cell carcinoma. During this period 54 patients who underwent open radical nephrectomy with pathologically confirmed stages pT1/2 NXMX disease were also identified. Medical and operative records were retrospectively reviewed and telephone followup was done to assess patient status. RESULTS: In the laparoscopic and open groups average tumor size was 5.1 (range 1 to 13) and 5.4 cm. (range 0.2 to 18), respectively, which was not statistically significant. No patient had laparoscopic port site, wound or renal fossa tumor recurrence in either group. All patients were followed at least 12 months. In the laparoscopic group 2 cancer specific deaths occurred at a mean followup of 35.6 months. In the open group there were 2 cancer specific deaths and 3 cases of disease progression at a mean followup of 44 months. Kaplan-Meier disease-free survival and actuarial survival analysis revealed no significant differences in the laparoscopic and open radical nephrectomy groups. Also, no differences were noted in the complication rate. CONCLUSIONS: Laparoscopic radical nephrectomy is an effective alternative for localized renal cell carcinoma when the principles of surgical oncology are maintained. Initial data show shorter patient hospitalization and effective cancer control with no significant difference in survival compared with open radical nephrectomy.     

PULMONARY NODULES IN PATIENTS WITH A HISTORY OF RADICAL NEPHRECTOMY FOR RENAL CELL CARCINOMA

Background:
Nine patients with a history of radical nephrectomy for renal cell carcinoma underwent surgical removal of newly detected pulmonary nodules at the Hiroshima University Hospital. Six patients had metastatic lung tumors two patients had bronchogenic primary carcinomas and one had a granulomatous infection.
Methods:
To determine if any characteristics can distinguish a new primary carcinoma from metastatic renal cell carcinoma, we reviewed the nine patients described above. The patients with pulmonary metastases and those with new primary lung cancers did not differ in age, sex, history of smoking, clinical stage and pathological findings of the renal primary site, on the location and size of the pulmonary nodules.
Results:
Only the interval between the nephrectomy and the appearance of the new pulmonary lesion may be a predictive factor. This interval was 48 and 51 months for the patients with new primary lung cancers but varied from 0 to 39 months for the patients with metastatic renal cell carcinoma. A solitary nodule had an equal chance of being metastatic or primary. Conclusions: These results indicate that a solitary nodule that is detected at a longer inferval after radical nephrectomy may be a new primary lung cancer. Once new pulmonary nodules are identified in a patient with a history of radical nephrectomy for renal cell carcinoma, surgical excision is required for a final diagnosis before initiating therapy for metastases.     

TIMELY DELIVERY OF BIOLOGICAL THERAPY AFTER CYTOREDUCTIVE NEPHRECTOMY IN CAREFULLY SELECTED PATIENTS WITH METASTATIC RENAL CELL CARCINOMA

Purpose

We determine whether cytoreductive surgery delays or precludes the administration of systemic biological therapy in patients with previously untreated metastatic renal cell carcinoma.

Materials and Methods

We evaluated 79 patients 22 to 73 years old with untreated renal cell carcinoma for possible cytoreductive surgery before the administration of systemic biological therapy. Based on performance status, overall disease burden and subjective clinical assessment 13 patients were referred for initial systemic biological therapy and 66 underwent cytoreductive surgery as initial treatment. We evaluated patient ability to receive postoperative biological therapy, time to therapy, surgical complications and mortality.

Results

Cytoreductive surgery had a minimal impact on the administration of timely systemic biological therapy in these carefully selected patients. Of the 66 patients 54 (82%) received postoperative systemic biological therapy beginning a median of 40 days after nephrectomy. Two patients (3%) died postoperatively (within 30 days) and in 1 (1.5%) postoperative deterioration in performance status precluded the administration of systemic therapy. The other 9 patients did not have measurable residual disease postoperatively, did not need or refused systemic therapy, or were followed elsewhere.

Conclusions

Systemic biological therapy can be administered in a timely manner (median 40 days) to the majority of patients (82% treated) after cytoreductive surgery. Surgery alone does not preclude the administration of systemic biological therapy in carefully selected patients.     

METASTATIC RENAL CELL CARCINOMA WITH CONCURRENT INFERIOR VENA CAVAL INVASION: LONG-TERM SURVIVAL AFTER COMBINATION THERAPY WITH RADICAL NEPHRECTOMY, VENA CAVAL THROMBECTOMY AND POSTOPERATIVE IMMUNOTHERAPY

PURPOSE: We report our experience using aggressive multimodal therapy in a high risk group of patients with metastatic renal cell carcinoma and concurrent inferior vena caval extension. MATERIALS AND METHODS: We retrospectively reviewed the records of all patients in our kidney cancer database who had metastatic renal cell carcinoma and tumor thrombus extension into the inferior vena cava at the initial diagnosis. Patients were included in the study if they underwent radical nephrectomy and inferior venal caval thombectomy, and immunotherapy was planned for the postoperative period. Tumor size and grade, metastatic sites, level of vena caval extension, surgical complications and overall survival were obtained from the medical records. The primary end point analyzed was overall survival. RESULTS: We identified 31 cases of metastatic renal cell cancer with extensive disease and vena caval extension. Of the patients 23% had an isolated lung metastasis, and 53% had metastasis in the lung and at other sites. The remaining patients had involvement primarily at nonpulmonary metastatic sites, including lymph node in 38%, soft tissue in 13%, liver in 29% and bone in 10%. Average blood loss during nephrectomy was 3,200 cc (median 2,100) and the rate of major complications was 12%. Of the patients 80% underwent the full course of surgery and postoperative immunotherapy. At a mean followup of 18 months (34 for survivors) 26% of the patients are alive. Actuarial overall 5-year survival of the group was 17%. Tumor thrombus level did not correlate with overall survival, while immunotherapy, tumor grade and metastatic site provided significant prognostic information. In patients with an isolated pulmonary metastasis the 5-year survival rate was 43%, while in those with low grade tumors it was 52%. CONCLUSIONS: In contrast to the poor results of surgery only in patients with renal cell carcinoma and concurrent inferior venal caval invasion, reasonable 5-year survival may be achieved after combined aggressive surgery and immunotherapy. Patients in whom metastasis was limited to the lungs and those with grade 1 to 2 tumors had a better prognosis. With careful planning and experienced immunotherapists therapy may be completed in the majority of this high risk group of patients.     

PROGNOSTIC SIGNIFICANCE OF MICROVESSEL COUNT IN LOW STAGE RENAL CELL CARCINOMA

Background:
It has been postulated that tumors beyond a certain size are dependent on angiogenesis, which might also be related to distant metastasis. We therefore assessed the prognostic significance of tumor microvasculature in renal cell carcinoma.
Methods:
Tumor specimens from 84 patients with primary renal cell carcinoma were examined by immunohistochemical staining for factor VIII. Individual microvessels were counted in a 200 × field overlying the area of highest neovacularization.
Results:
The mean number of microvessels in patients with metastases was significantly higher than that in patients who were disease-free for more than three years ( P = 0.004). The survival of patients with less than 30 microvessels per 200 × field was significantly higher than that of patients with more than 30 microvessels per 200 × field ( P = 0.007). Multivariate analyses revealed that these microvessel counts were the only significant predictor of prognosis in 45 patients with T1-2 and MO tumors ( P = 0.028).
Conclusions:
Assessment of tumor microvasculature is therefore probably one of the most important prognostic predictors in renal cell carcinoma.     

A POSTOPERATIVE PROGNOSTIC NOMOGRAM FOR RENAL CELL CARCINOMA

PURPOSE: Few published studies have combined prognostic factors to predict the likelihood of recurrence after surgery for renal cell carcinoma. We developed a nomogram for this purpose. MATERIALS AND METHODS: With Cox proportional hazards regression analysis, we modeled pathological data and disease followup for 601 patients with renal cell carcinoma who were treated with nephrectomy. Predictor variables were patient symptoms, including incidental, local or systemic, histology, including chromophobe, papillary or conventional, tumor size, and pathological stage. Treatment failure was recorded when there was either clinical evidence of disease recurrence or death from disease. Validation was performed with a statistical (bootstrapping) technique. RESULTS: Disease recurrence was noted in 66 of the 601 patients, and those in whom treatment was successful had a median and maximum followup of 40 and 123 months, respectively. The 5-year probability of freedom from failure for the patient cohort was 86% (95% confidence interval 82 to 89). With statistical validation, predictions by the nomogram appeared accurate and discriminating with an area under the receiver operating characteristic curve, that is a comparison of the predicted probability with the actual outcome of 0.74. CONCLUSIONS: A nomogram has been developed that can be used to predict the 5-year probability of treatment failure among patients with newly diagnosed renal cell carcinoma. The nomogram may be useful for patient counseling, clinical trial design and patient followup planning.     

RENAL OUTCOME 25 YEARS AFTER DONOR NEPHRECTOMY

PURPOSE: The extended outcome after kidney donation has been a particular concern ever since the recognition of hyperfiltration injury. Few published reports have examined donor renal outcome after 20 years or greater. Kidney transplantation has been performed at the Cleveland Clinic Foundation since 1963, at which there is extensive experience with live donor transplantation. We assess the impact of donor nephrectomy on renal function, urinary protein excretion and development of hypertension postoperatively to examine whether renal deterioration occurs with followup after 20 years or greater. MATERIALS AND METHODS: From 1963 to 1975, 180 live donor nephrectomies were performed at the Cleveland Clinic. We attempted to contact all patients to request participation in our study. Those 70 patients who agreed to participate in the study were mailed a package containing a 24-hour urine container (for assessment of creatinine, and total protein and albumin), a vial for blood collection (for assessment of serum creatinine) and a medical questionnaire. All specimens were returned to and processed by the Cleveland Clinic medical laboratories. Blood pressure was taken and recorded by a local physician. A 24-hour creatinine clearance and the Cockcroft-Gault formula were used to estimate renal function, and values were compared with an age adjusted glomerular filtration rate for a solitary kidney. RESULTS: Mean patient followup was 25 years. The 24-hour urinary creatinine clearance decreased to 72% of the value before donation. For the entire study cohort serum creatinine and systolic blood pressure after donation were significantly increased compared with values before, although still in the normal range. The overall incidence of hypertension was comparable to that expected in the age matched general population. There was no gender or age difference (younger or older than 50 years) for 24-hour urinary creatinine clearance, or change in serum creatinine before or after donation. Urinary protein and albumin excretion after donation was significantly higher in males compared with females. There were 13 (19%) subjects who had a 24-hour urinary protein excretion that was greater than 0.15 gm./24 hours, 5 (7%) of whom had greater than 0.8. No gender difference was noted in blood pressure, and there were no significant changes in diastolic pressure based on gender or age. CONCLUSIONS: Overall, renal function is well preserved with a mean followup of 25 years after donor nephrectomy. Males had significantly higher protein and albumin excretion than females but no other clinically significant differences in renal function, blood pressure or proteinuria were noted between them or at age of donation. Proteinuria increases with marginal significance but appears to be of no clinical consequence in most patients. Patients with mild or borderline proteinuria before donation may represent a subgroup at particular risk for the development of significant proteinuria 20 years or greater after donation. The overall incidence of proteinuria in our study is in the range of previously reported values after donor nephrectomy.     

ADRENAL SPARING SURGERY DURING RADICAL NEPHRECTOMY IN PATIENTS WITH RENAL CELL CANCER: A NEW ALGORITHM

PURPOSE: Ipsilateral adrenalectomy is usually performed during radical nephrectomy because of renal cell cancer. Because renal tumors are detected more often in the earlier stages due to widespread use of ultrasound and computerized tomography, we define a subset of patients who would be eligible for adrenal sparing surgery. In a retrospective analysis we evaluated whether parameters obtained preoperatively are able to predict adrenal metastasis. MATERIALS AND METHODS: A total of 866 consecutive patients who underwent nephrectomy and ipsilateral adrenalectomy from 1983 to 1999 were evaluated. Preoperative parameters, including tumor size, location, clinical stage, number of tumors, and patient age and sex, were retrospectively compared with the histological results. Univariate and multivariate analyses were performed. RESULTS: A total of 27 (3.1%) adrenal metastases were noted in the 866 patients, and 63% were on the left side and 37% on the right side. Mean tumor size was 10 cm. with versus 6 cm. without adrenal involvement. Of the 27 patients 21 had multiple metastases at diagnosis and only 6 (0.7% of all 866) presented with solitary ipsilateral adrenal metastasis. Univariate and multivariate analyses revealed tumor size and M stage as best preoperative predictors of adrenal involvement. CONCLUSIONS: Adrenal sparing surgery is possible, and we suggest a new algorithm. If maximum tumor size measured by computerized tomography is less than 8 cm. and staging examination does not show organ or lymph node metastases, adrenalectomy is not necessary because of oncological reasons. This algorithm has to be validated by a prospective analysis.     

LAPAROSCOPIC NEPHRON SPARING SURGERY FOR SMALL RENAL CELL CARCINOMA

Purpose

In recent years the detection rate for small renal tumors has increased due to the widespread use of advanced diagnostic imaging techniques, which in turn has increased the need for nephron sparing surgery. We investigate whether laparoscopic surgery is a suitable approach to partial resection of small renal tumors.

Materials and Methods

Between June 1994 and October 1996, 7 patients underwent laparoscopic wedge resection of the kidney for renal tumors up to 2 cm. in diameter. Hemostasis was achieved mainly by bipolar coagulation. In addition, the resection surface was cauterized with an argon beam coagulator and then sealed with fibrin glue. In 1 procedure a novel ultrasonic dissector was tested.

Results

All procedures could be completed as planned. The only intraoperative complication was a pneumothorax that resolved spontaneously within 2 days. There were no postoperative complications. Histological examination yielded stage pT1 grade I renal cell carcinoma in 3, stage pT1 grade II in 2 and multilocular cysts in 2 cases. All patients had negative surgical margins. Postoperatively, renal function as assessed by serum creatinine was unchanged. Neither local recurrences nor metastases were observed during a followup of 7 to 35 months.

Conclusions

Our results indicate that laparoscopic partial nephrectomy is feasible for small renal cell carcinoma, and is associated with low morbidity and a low complication rate.     

LAPAROSCOPIC NEPHRECTOMY FOR INFLAMMATORY RENAL CONDITIONS

PURPOSE: Inflammatory and infectious renal conditions may result in severe perirenal fibrosis, making the laparoscopic approach challenging. The theoretical advantages of laparoscopy for managing inflammatory and infectious renal conditions have been questioned. We identified whether laparoscopy for inflammatory renal conditions is associated with higher morbidity than for other benign renal conditions. Furthermore, several technical modifications are discussed that may help to improve the outcome. MATERIALS AND METHODS: We retrospectively reviewed the records of all patients who underwent laparoscopic nephrectomy for inflammatory and infectious renal conditions between 1998 and 2000. The transperitoneal approach was used and specimens were removed after morcellation. Operative data were compared with those from a similar group of patients who underwent laparoscopic nephrectomy for other benign conditions. RESULTS: Laparoscopic nephrectomy done for inflammatory or infectious conditions in 12 cases and for other benign conditions in 9 matched cases was completed successfully in 10 (83%) and 9 (100%), respectively. In the inflammatory and benign groups mean blood loss plus or minus standard deviation was 155 +/- 163 and 59 +/- 23 ml. (p = 0.099), mean operative time was 284 +/- 126 and 226 +/- 62 minutes (p = 0.225), and mean postoperative hospital stay was 4.1 +/- 2 and 3 +/- 1 days (p = 0.157), respectively. CONCLUSIONS: Laparoscopic nephrectomy can be performed safely in most cases of inflammatory renal conditions. Although they were not statistically significant, a higher conversion rate and longer operative time should be expected. Early conversion may be required due to failure to progress. Similar advantages were observed in patients with inflammatory and other benign renal conditions via the laparoscopic approach.     

LONG-TERM SURVIVAL AFTER RESECTION OF A MEDIASTINAL METASTASIS FROM A RENAL CELL CARCINOMA

J Thorac Cardiovasc Surg 1998;115:1218-9     

LACK OF ASSOCIATION OF PROSTATE CARCINOMA NUCLEAR GRADING WITH PROSTATE SPECIFIC ANTIGEN RECURRENCE AFTER RADICAL PROSTATECTOMY

PURPOSE: Grading prostate cancer using the Gleason system relies only on architectural tumor growth, in contrast to other systems, such as the WHO system, which grade prostate carcinoma based on nuclear features as well as architectural patterns. The prognostic significance of nuclear grading remains controversial since most studies were performed before prostate specific antigen (PSA) screening became widely available. We evaluated the significance of nuclear grade for predicting PSA recurrence in a contemporary cohort of patients treated with radical prostatectomy for clinically localized prostate carcinoma. MATERIALS AND METHODS: Nuclear grades 1 to 3 were determined in 141 consecutive radical prostatectomies in 1995. Predominant and worst nuclear grade was determined by a consensus of 3 pathologists. Statistical analysis compared nuclear grade with Gleason score using the chi-square test. The Cox proportional hazards analysis was performed to calculate the ability of nuclear grade, Gleason score and other variables to predict PSA recurrence. RESULTS: We identified a significant association of Gleason score with worst nuclear grade (p = 0.007). All 6 cases with a Gleason score of 8 or greater had a worst nuclear grade of 3, in contrast to 36 of 60 (60%) with a score 6 or less, in which the worst nuclear grade was 3. Of the 141 patients 31 (21.9%) had PSA recurrence at a median followup of 3.7 years. The univariate Cox model revealed significant associations of PSA recurrence with Gleason score 8 or greater (hazards ratio 5.5, p = 0.005), extraprostatic extension (hazards ratio 3.4, p = 0.001), positive surgical margin (hazards ratio 2.6, p = 0.009), seminal vesicle involvement (hazards ratio 7.3, p <0.001), preoperative serum PSA (hazards ratio 1.03, p = 0.007), tumor stage (hazards ratio 3.6, p = 0.001) and maximal tumor dimension (hazards ratio 2.4, p <0.001). However, overall and worst nuclear grade did not predict PSA recurrence (p = 0.89 and 0.13, respectively). Nuclear grade did not fit any multivariate model tested, which otherwise included Gleason score, log(PSA), surgical margin status, extraprostatic extension, seminal vesicle status, tumor size and pathological stage. By varying sample fixation time we also showed that benign prostate tissue in the same section as prostate carcinoma had grade 2 or 3 nuclear changes, that is moderate to marked anaplasia. CONCLUSIONS: High nuclear grade is associated with high Gleason score. However, prostate carcinoma with a Gleason score of 6 or less shows extreme variability. Nuclear grade determined by light microscopy failed to predict PSA recurrence in a contemporary series of men with clinically localized prostate cancer treated with radical prostatectomy. Nuclear morphology is subject to tissue fixation and processing artifact. Any nuclear morphometric study must consider this artifact.