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 nonHodgkin'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 nonHodgkin's lymphoma were the most common other primary malignancies. Men with renal cell carcinoma have an increased risk of subsequent bladder cancer.     

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.     

RENAL MEDULLARY CARCINOMA

Purpose

Renal medullary carcinoma is a rare and extremely aggressive neoplasm that almost always develops in young patients with sickle cell trait. To our knowledge all cases to date have been metastatic at surgical resection. Pathological examination reveals an aggressive tumor mainly involving the renal medulla with a varied morphology. The prognosis is dismal. Mean survival from the time of resection is 15 weeks (range 2 to 52). The disease course has not been altered by surgery, radiotherapy or various regimens of chemotherapeutic agents.

Materials and Methods

We add to the literature our experience treating renal medullary carcinoma in 2 cases and review the existing literature on this disease.

Results

Both patients whom we treated died of the disease, as have the other 35 patients described in the literature.

Conclusions

A high index of suspicion may lead to earlier diagnosis and treatment, and survival of patients with renal medullary carcinoma.     

MULTIFOCAL RENAL CELL CARCINOMA IN JAPANESE PATIENTS WITH TUMORS WITH MAXIMAL DIAMETERS OF 50 MM. OR LESS

Purpose

We determined the risk of local recurrence in 64 Japanese patients a median of 69 years old with renal cell carcinoma who were possible candidates for nephron sparing surgery and who underwent radical nephrectomy.

Materials and Methods

A total of 64 kidneys in which tumors 50 mm. or less were resected were prospectively examined pathologically in 3 mm. sections. The incidence of satellite tumors and the relationship between the pathological findings of the primary and satellite tumors were evaluated.

Results

Satellite tumors were identified in 10 of the 64 kidneys (15.6%), a rate similar to that reported in the United States. The correlation of histological findings between primary and satellite tumors was 70% for tumor grade. Satellite tumor grade was less than that of the primary lesion in 3 cases. In 60% of the specimens with multifocal renal cancer satellite tumors were within 10 mm. of the margin of the primary tumor. At this distance, if partial nephrectomy had been performed, the satellite lesions would have been missed in 4 of these 10 patients (40%). Of the 10 kidneys with satellite renal tumors 8 (80%) had vascular invasion of the primary tumor. Multiple logistic regression analysis demonstrated that vascular invasion was a significant predictor of multifocality of renal cell carcinoma.

Conclusions

Our results suggest that vascular invasion is a risk factor for multifocality in Japanese patients with renal cell carcinoma. Therefore, careful and long-term followup is necessary in patients with renal cell carcinoma who have undergone nephron sparing surgery, especially those with vascular invasion of the primary tumor.     

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.     

STAGE SPECIFIC GUIDELINES FOR SURVEILLANCE AFTER RADICAL NEPHRECTOMY FOR LOCAL RENAL CELL CARCINOMA

Purpose

We report stage specific followup guidelines based on our evaluation of the pattern of recurrence in 286 patients treated for local N0 or Nx renal cell carcinoma.

Materials and Methods

We retrospectively reviewed the clinical records of 286 patients with pT1 to pT3N0 or Nx renal cell carcinoma who underwent nephrectomy at our center between February 1985 and December 1994. In cases of later metastases the median interval to first metastasis, site of metastasis and method of diagnosis were correlated with the primary lesion stage.

Results

Metastases developed in 68 patients a median of 23 months after nephrectomy. Eight of the 113 patients with pT1 disease had metastases (median time to diagnosis 38 months), while 17 of 64 with pT2 disease and 43 of 109 with pT3 disease had metastases (medians 32 and 17 months, respectively). Of the 92 metastases 59 (64%) were asymptomatic, including 44 detected on routine chest x-rays (32) and blood tests (12). Isolated asymptomatic intra-abdominal metastases were diagnosed by surveillance computerized tomography in only 6 patients (9%). The remaining patients with metastases had associated clinical symptoms and/or abnormal results on interval tests that prompted further diagnostic studies.

Conclusions

We confirmed that the risk of metastatic renal cell carcinoma is stage dependent. Therefore, surveillance protocols should be based on the pathological stage of the primary tumor. We recommend an annual chest x-ray, and serum liver function and alkaline phosphatase level tests for patients with pT1 disease. These studies are indicated beginning at 6 and 3 months for pT2 and pT3 disease, respectively, continuing every 6 months for 3 years and then annually. Surveillance computerized tomography should be performed at 24 and 60 months in patients with pT2 and pT3 disease or earlier when the results of any routine study are abnormal or clinical symptoms are present. Bone and brain surveillance studies should be prompted by site specific symptoms, elevated alkaline phosphatase levels or the diagnosis of metastasis at another site.     

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.     

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.     

COINCIDENT RENAL CELL CARCINOMA AND NONHODGKIN'S LYMPHOMA: THE M.D. ANDERSON EXPERIENCE AND REVIEW OF THE LITERATURE

Purpose

We recently observed nonHodgkin's lymphoma and renal cell carcinoma occurring simultaneously in several patients. We determine whether the incidence of co-occurrence of the 2 malignancies is greater than expected based on the incidence of each disease in the general population.

Materials and Methods

Patients diagnosed with simultaneous renal cell carcinoma and nonHodgkin's lymphoma were identified through the medical informatics data base at our cancer center. Charts of all patients were reviewed to collect detailed demographic information and confirm both diagnoses. United States population based cancer statistics (Surveillance, Epidemiology and End Results Program data) were used to arrive at the expected age adjusted incidence of co-occurrence of these diagnoses, and statistical analysis was performed to ascertain any differences between expected and observed incidences.

Results

We identified 41 cases with both diagnoses between 1954 and 1995, including 21 diagnosed after 1987. The latter group was used for statistical analysis. The observed rates of renal cell carcinoma developing in the nonHodgkin's lymphoma population (1.86) and nonHodgkin's lymphoma developing in the renal cell carcinoma population (2.67) were greater than expected and both reached statistical significance.

Conclusions

There is a higher than expected incidence of co-occurrence of renal cell carcinoma and nonHodgkin's lymphoma. The cause remains speculative.     

ADJUVANT MITOMYCIN C FOLLOWING ENDOSCOPIC TREATMENT OF UPPER TRACT TRANSITIONAL CELL CARCINOMA

Purpose

A variety of topical agents have been used for transitional cell carcinoma of the upper tract. Mitomycin C has limited systemic absorption when given intravesically because of its high molecular weight. We reviewed our experience with mitomycin C following endoscopic treatment of upper tract transitional cell carcinoma.

Materials and Methods

Since 1991, 19 patients (21 renal units) have undergone a total of 28 treatments with mitomycin C for high volume, recurrent or multifocal transitional cell carcinoma. Of the 19 patients 12 had an absolute indication for nephron sparing treatment. Following ureteroscopic biopsy and treatment of upper tract transitional cell carcinoma, 40 mg. mitomycin C in 3 divided doses was instilled via a ureteral catheter, which was clamped between doses to give an exposure time of 30 minutes. Eighteen patients have undergone ureteroscopic surveillance following a total of 26 treatments.

Results

No systemic side effects occurred during or after treatment with mitomycin C. One patient had a prominent local inflammatory reaction following neodymium:YAG ablation and mitomycin C treatment of a renal pelvic tumor. The average size of the treated tumors was 17 mm. (range 5 to 30). The grade of the tumors (when known) was 1 in 5 patients, 1 to 2 in 2, 2 in 8 and 3 in 4. Most tumors were treated with either neodymium:YAG (6 cases) or holmium:YAG laser (8) or a combination of both (8). Following 1 to 4 treatments with mitomycin C 11 of 19 evaluable renal units (58%) were rendered free of disease. Six of those 11 renal units (54%) had an ipsilateral recurrence after a mean of 30 months of followup, 4 of which were treated endoscopically, and 7 (64%) are now disease-free without extirpative surgery. Four patients have undergone nephroureterectomy for persistent or recurrent disease. No patient has suffered local or distant progression of disease.

Conclusions

Instillation of mitomycin C for upper tract transitional cell carcinoma appears to be safe and can be considered for adjuvant treatment in select cases. More data are necessary to determine its efficacy.     

Somatic Mutation of the Tuberous Sclerosis (Tsc2) Tumor Suppressor Gene in Chemically Induced Rat Renal Carcinoma Cell

Purpose

von Hippel-Lindau (VHL) gene mutations are detected in noninherited, sporadic human renal cell carcinomas (RCs) at a high frequency. We recently identified a germline mutation in the rat homologue of the human tuberous sclerosis (TSC2) predisposing RC gene in the Eker rat model, and in this study we searched for mutations of the Tsc2 gene in chemically induced non-Eker rat RCs.

Materials and Methods

Chemically [N-ethyl-N-hydroxyethylnitrosamine (EHEN)]-induced non-Eker rat RC lines (designated as BP13 and BP36B) were subjected to PCR-single strand conformation polymorphism (PCR-SSCP) analysis using specific primers covering entire exons of Tsc2 gene (41 coding exons and one non-coding exon). We simultaneously searched for mutations of Vhl gene, a rat homologue of von Hippel-Lindau disease gene (VHL) as well as Tsc2 gene.

Results

BP36B showed an abnormal mobility shift from the normal tissue of the same rat in exon 35 on analysis by PCR-SSCP. This mutation was confirmed by direct sequencing and found to be a T-to-C transition at the second position of codon 1470, resulting in an amino acid change from leucine to proline (missense mutation).

Conclusions

This is the first demonstration of Tsc2 gene somatic mutation in non-Eker rat RCs. Our present findings call attention to further investigation of the role of Tsc2 gene mutations in rat renal carcinogenesis and possible Tsc2 gene mutations in human RCs, especially of the non-clear cell type, which are not related to the VHL gene.     

USE OF THE HARMONIC SCALPEL FOR NEPHRON SPARING SURGERY IN RENAL CELL CARCINOMA

Purpose

The harmonic scalpel is a new tool for excising and coagulating tissue with ultrasound using higher frequencies than an ultrasonic aspirator. We evaluated the usefulness of the harmonic scalpel in nephron sparing surgery.

Materials and Methods

We used the harmonic scalpel to incise the renal parenchyma during nephron sparing surgery in 10 patients with renal cell carcinoma.

Results

Bleeding from the renal parenchyma was minimal but hemostasis of the larger vessels was not obtained even when the harmonic scalpel was used at maximal coagulation power. The cut surface of the kidneys, especially the vessels, were more clearly recognized than if an utrasonic aspirator had been used, enabling hemostasis by figure-of-8 suture.

Conclusions

The harmonic scalpel is useful for obtaining a clear parenchymal stump and hemostasis during nephron sparing surgery, although complete hemostasis of the arcuate or larger vessels cannot be achieved.     

SERUM INTERLEUKIN-6 LEVELS IN METASTATIC RENAL CELL CARCINOMA BEFORE TREATMENT WITH INTERLEUKIN-2 CORRELATES WITH PARANEOPLASTIC SYNDROMES BUT NOT PATIENT SURVIVAL

Purpose

We sought to determine the frequency of interleukin-6 (IL-6) expression in renal cancer cell lines, the frequency of the detection of IL-6 in the serum of patients with metastatic renal cell carcinoma, whether serum IL-6 level correlates with the development of paraneoplastic syndromes and whether serum IL-6 level in patients with metastatic renal cancer correlates with response to treatment with interleukin-2 (IL-2) or patient survival.

Materials and Methods

Conditioned media from 21 cell lines from 20 patients were examined for IL-6. We identified 2 matched groups of patients with metastatic renal cancer (30 responders and 29 nonresponders) to IL-2 based immunotherapy. Stored pretreatment serum specimens were evaluated for IL-6. Medical records were reviewed to determine the presence of paraneoplastic syndromes.

Results

IL-6 was detected in 19 of 21 renal cancer cell lines (90%) obtained from 20 patients with metastatic renal cancer as well as in the serum of 33 of 59 patients (56%) with metastatic renal cell carcinoma. A significant association between serum IL-6 level and anemia (p = 0.0032), elevated platelet count (p = 0.01), decreased albumin (p = 0.034) and elevated alkaline phosphatase (p = 0.04) was found. A trend was noted of the association of increased serum IL-6 level and fever (p = 0.051). No correlation was found between pretreatment serum IL-6 level and survival or response to IL-2.

Conclusions

IL-6 was frequently secreted by renal cancer cell lines but it was only present in the serum of approximately half of the patients with metastatic renal cancer. Elevations of serum IL-6 were associated with paraneoplastic manifestations frequently seen in patients with renal cancer, including anemia, thrombocytosis, decreased albumin and elevations of alkaline phosphatase (Stauffer's syndrome). A weak relationship was noted between serum IL-6 level and fever but none was noted between that and survival or response to IL-2.     

INHIBITION OF TUMOR GROWTH AND ANGIOGENESIS BY VITAMIN D3 AGENTS IN MURINE RENAL CELL CARCINOMA

Purpose

To investigate the effect of active vitamin D3(VD) agents on tumor growth and metastasis.

Materials and Methods

BALB/c mice were inoculated with murine renal cancer Renca and graded doses of 1,25-dehydrovitamin D3 or 1- hydrovitamin D3 were given intraperitoneally every other day beginning on day 1, 3, or 7 and ending on day 9, 11, or 15. Direct cytocidal activity and angiogenic activity were evaluated by 48-hour MTT assay and by the colorimetric method, respectively.

Results

Both VD agents inhibited tumor growth and prolonged the life span of Renca-bearing mice in a dose-dependent manner and both suppressed tumor growth in athymic mice and euthymic mice with eliminated NK activity. Marginal body-weight loss without appreciable hypercalcemia was observed in mice given VD agents. When treatment was delayed on day 7, the VD agents failed to inhibit tumor growth. The MTT assay showed no direct cytotoxicity of VD agents on Renca. Tumor angiogenesis was inhibited to 46 to 30% of the control level by VD agents. Furthermore, VD agents reduced pulmonary and hepatic foci in the metastatic models.

Conclusions

These results suggest that VD agents may be effective as a treatment for renal cell carcinoma, especially when micrometastases are involved.     

GENITOURINARY SMALL CELL CARCINOMA: DETERMINATION OF CLINICAL AND THERAPEUTIC FACTORS ASSOCIATED WITH SURVIVAL

Purpose

We assessed the prognostic impact of genitourinary small cell carcinoma tumor and patient characteristics, and therapy.

Materials and Methods

We retrospectively reviewed the records of 180 patients with genitourinary small cell carcinoma in which patient and tumor characteristics, therapy, followup duration and survival status had been documented. Patient age, sex, primary site, histological features, tumor size, stage, locoregional therapy, systemic chemotherapy and hormonal manipulations were analyzed for association with survival.

Results

There were 106 cases of bladder, 60 prostatic, 8 renal and 6 ureteral small cell carcinoma. Median survival was 10.5 months overall, and 7 and 13 months for prostatic and bladder small cell carcinoma, respectively (p <0.0001 log rank analysis). In all cases metastatic disease at presentation (p <0.008, risk ratio 1.9) predicted poor survival on multivariate analysis. Radical surgery (p <0.0001, risk ratio 0.34) and cisplatin chemotherapy (p <0.0001, risk ratio 0.20) were the only factors that predicted improved survival on multivariate analysis. For prostatic small cell carcinoma primary surgical therapy (p <0.012, risk ratio 0.46) was the only parameter that predicted survival on univariate analysis. For bladder small cell carcinoma only cisplatin chemotherapy (p <0.0001, risk ratio 0.15) predicted survival on multivariate analysis.

Conclusions

Genitourinary small cell carcinoma has a poor prognosis, which is worse in prostatic than bladder disease. Patient and tumor characteristics were not determinants of survival when prostatic and bladder small cell carcinoma were analyzed individually. For prostatic disease only primary surgical therapy was associated with prolonged survival, while for bladder disease cisplatin chemotherapy was associated with a favorable prognosis. We recommend considering primary surgical therapy for prostatic and cisplatin based chemotherapy for bladder small cell carcinoma.     

Patterns of Tumor Recurrence and Guidelines for Followup After Nephron Sparing Surgery for Sporadic Renal Cell Carcinoma

Purpose

We delineated patterns of tumor recurrence and developed guidelines for followup after nephron sparing surgery for sporadic renal cell carcinoma.

Materials and Methods

Before December 1994, 327 patients underwent nephron sparing surgery for sporadic localized renal cell carcinoma at our clinic. Mean postoperative followup was 55.6 months. The course and outcome for patients with postoperative recurrent renal cell carcinoma were reviewed in detail.

Results

Renal cell carcinoma recurred after nephron sparing surgery in 38 patients (11.6%), including 13 (4.0%) who had local tumor recurrence with (7) or without (6) metastatic disease and 25 (7.6%) who had metastatic disease without local tumor recurrence. Recurrent renal cell carcinoma was detected by associated symptoms in 25 patients and by a followup chest x-ray or abdominal computerized tomography (CT) in 13. The respective incidences of postoperative local tumor recurrence and metastatic disease according to initial pathological tumor stage were 0 and 4.4% for stage T1, 2.0 and 5.3% for stage T2, 8.2 and 11.5% for stage T3a, and 10.6 and 14.9% for stage T3b disease. The peak postoperative intervals until local tumor recurrence were 6 to 24 months (7 of 10 patients with stage T3 renal cell carcinoma) and longer than 48 months (all 3 with stage T2 disease). Patients with isolated local tumor recurrence had better survival compared to those with local tumor recurrence and metastatic disease or metastases only.

Conclusions

Followup for recurrent malignancy after nephron sparing surgery for renal cell carcinoma can be tailored according to the initial pathological tumor stage. All patients should be evaluated yearly with a medical history, physical examination and select laboratory studies. Patients with stage T1 renal cell carcinoma require no additional monitoring, while those with stage T2 disease should also undergo a yearly chest x-ray and abdominal CT every 2 years. The same recommendations are offered for patients with stage T3 renal cell carcinoma except that abdominal CT should be done every 6 months for the first 2 years postoperatively.     

Von Hippel-Lindau disease and renal cell carcinoma in a 16-year-old boy.

Von Hippel-Lindau disease is a rare autosomal dominant disorder. Kidney lesions occur in the majority of cases, with renal cell carcinoma noted in 40% and renal cysts in 60%. Renal cell carcinoma in von Hippel-Lindau disease is usually bilateral and occurs at an earlier age than in patients with sporadic renal cell carcinoma. We report on a 16-year-old boy who, to our knowledge, is the youngest patient to present with von Hippel-Lindau disease and renal cell carcinoma. Controversy currently exists regarding the nature of renal cysts in von Hippel-Lindau disease and the optimal therapeutic approach (that is radical versus parenchymal sparing surgery). We review the histology of renal cysts and carcinoma, and discuss the rationale for selecting parenchymal sparing surgery.     

Metachronous bilateral renal cell carcinoma: risk assessment, prognosis and relevance of the primary-free interval

PURPOSE: We evaluated the prognosis, risk factors and relevance of the primary-free interval in a large cohort with metachronous bilateral renal cell carcinoma. MATERIALS AND METHODS: We studied 120 patients with metachronous, bilateral renal cell carcinoma who were treated at 12 international academic centers. Logistic regression was performed to evaluate risk factors for contralateral metachronous renal cell carcinoma during followup. Disease specific survival was evaluated with univariate and multivariate analysis. RESULTS: Median age at diagnosis of the first and second renal cell carcinomas was 54 and 62 years, respectively. The most common histological subtype was bilateral clear cell renal cell carcinoma (89% of cases). Familial renal cell carcinoma was found in 14% of patients, von Hippel-Lindau disease was found in 4% and nonfamilial renal cell carcinoma was found in 81%. The 15-year disease specific survival rates for the first and second renal cell carcinomas were 66% and 44%, respectively. Logistic regression revealed von Hippel-Lindau disease, a family history of renal cell carcinoma, multifocal first renal cell carcinoma and young patient age as independent risk factors for contralateral renal cell carcinoma after surgery for unilateral renal cell carcinoma. A longer primary-free interval was associated with a better prognosis. When calculating disease specific survival from the diagnosis of the first renal cell carcinoma, the primary-free interval was an independent prognostic factor. CONCLUSIONS: Long-term survival rates of metachronous, bilateral renal cell carcinoma are moderate. von Hippel-Lindau disease, a family history of renal cell carcinoma, multifocal first renal cell carcinoma and young patient age are independent risk factors for contralateral renal cell carcinoma. These risk factors support close and extended abdominal surveillance following nephrectomy for unilateral renal cell carcinoma. Patients with a longer primary-free interval have a more favorable prognosis.     

Report of aggressive renal cell carcinoma in two patients with von Hippel-Lindau disease

Renal cell carcinoma is relatively common in patients with von Hippel-Lindau disease, yet characteristically follows a less aggressive course compared with sporadic renal cell carcinoma. We report on 2 patients with von Hippel-Lindau disease and atypically aggressive renal tumors. In these patients, more rigorous screening guidelines may help to identify the more aggressive variants.     

RENAL LESION GROWTH IN CHILDREN WITH TUBEROUS SCLEROSIS COMPLEX

Purpose

Renal lesions, including angiomyolipoma, renal cysts (simple and polycystic kidney disease) and renal cell carcinoma, develop in patients with tuberous sclerosis complex. While there is limited information that these lesions may grow in adults with tuberous sclerosis complex, the incidence, characterization and growth rate in children have not been reported. Also, the age at which these lesions first appear, thus providing insight into their natural history, is unknown. We present our data from a longitudinal renal surveillance study of children with tuberous sclerosis complex.

Materials and Methods

Since 1985 children with tuberous sclerosis complex at our hospital have undergone periodic renal imaging by ultrasonography or computerized tomography to monitor renal lesions. A total of 35 girls and 25 boys 1 to 18 years old have undergone at least 2 or more annual renal ultrasounds.

Results

On initial evaluation 33 of 60 children (55%) (mean age 6.9 years) had an identifiable renal lesion, which increased to 48 of 60 (80%) at followup (mean age 10.5 years). Angiomyolipoma was the most frequent lesion (75%) followed by simple renal cysts (17%). Angiomyolipomas increased in size and/or number in 10 of 18 boys (56%) and 18 of 27 girls (66%). The largest growth rate in 1 year was from 0 to 4 cm. and from 5 to 9 cm. in diameter. The youngest patient demonstrated lesions at age 2 years. The average age at which a normal ultrasound became abnormal was 7.2 years. While a total of 27 patients had a normal ultrasound on entering the study, lesions had developed in 15 at followup (11 with angiomyolipomas, 4 with cysts). Five patients had cysts that had disappeared at followup. A 7-year-old boy had a 9 cm. renal cell carcinoma removed. One patient has renal lesions characteristic of autosomal dominant polycystic kidney disease.

Conclusions

Renal involvement in patients with tuberous sclerosis complex begins in infancy, and angiomyolipoma is the most common lesion (75%). Angiomyolipomas are more likely to grow than remain stable, although the rate of growth varies. Simple renal cysts may appear or disappear with time but angiomyolipomas do not disappear. An initially normal renal ultrasound does not rule out future development of lesions. Periodic surveillance is indicated in children with tuberous sclerosis complex.