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Von Hippel-Lindau disease (VHL) is an autosomal-dominant inherited condition that predisposes patients to develop renal cysts and tumors, most commonly in the second to fourth decades of life. Renal cysts and tumors have historically been a major cause of disease-related morbidity and mortality, so urologists are often called on to manage patients with VHL. Knowledge of the extrarenal manifestations of VHL (hemangioblastomas of the central nervous system and retina, endolymphatic sac tumors, pancreatic cysts, epididymal and broad-ligament cysts, and pheochromocytomas) and integration of nonurologic specialties into management teams for VHL patients will help to achieve successful outcomes. Screening for renal manifestations of VHL, by regular imaging of the abdomen, begins late in the second decade of life. Because renal tumors in VHL can be multifocal and bilateral, management can be complex. Radical nephrectomy removes all tissue at risk for forming renal tumors; however, this necessitates renal replacement therapy. In an effort to control cancer effectively while preserving native renal function and minimizing intervention, some researchers have proposed an observational strategy. Patients are screened until the largest tumor reaches 3 cm in diameter, at which time operative intervention is recommended. Nephron-sparing surgery is undertaken, whenever technically feasible, with the goal of removing all tumors in that renal unit. The role of minimally invasive technologies is currently being evaluated in selected patients with VHL renal masses. Elucidation of molecular pathways associated with VHL renal tumors may facilitate development of effective medical treatments for these lesions in the future.

To perform a retrospective review in patients undergoing urologic operations during a 10-year period. Patient positioning is important before surgery to avoid pressure sores and other iatrogenic injuries. The reported risk factors have included a long operative time, diabetes, and malignancy. We have noted skin breakdown in patients placed on stabilizing devices and in patients with germline von Hippel-Lindau (VHL) gene mutations (a gene important in angiogenesis).We performed a retrospective review in patients undergoing urologic operations during a 10-year period. Patient sex, age, blood loss, position, use of belt or Vac Pac, and diagnosis of VHL were correlated with skin breakdown.During a 10-year period, 382 patients underwent primarily renal and adrenal surgery. Fifty-five patients (14.4%) developed skin breakdown after surgery. Ninety-six patients had VHL gene mutations. Patient position and operative time were both significantly related to skin breakdown (both P0.0001). The odds ratio for the position effect indicated that patients in the lateral position were at much greater risk than patients in the supine position (estimated odds ratio 8.1, P0.0001). The odds ratio for operative time confirmed that patients experiencing longer operative times were also at increased risk of skin breakdown (estimated odds ratio 3.7 for each doubling of the operative time, P0.0001). Patient sex, patient age, estimated blood loss, diagnosis of VHL, and use of belt or Vac Pac were not associated with an increased risk of skin breakdown.Patients with longer operative times were at greater risk of skin breakdown and required greater care during preoperative positioning. The other factors studied were not significantly associated with skin breakdown.

Nephron sparing surgery has become accepted surgical practice for removing of renal tumors. The resection of central lesions has been thought to be more surgically challenging than that of peripheral tumors. We analyzed our experience with renal preservation surgery in patients with small hereditary central renal tumors.From 1992 to 2000 we performed 116 partial nephrectomies with 44 kidneys (38%) demonstrating central renal masses. Central renal tumors were defined radiologically as those completely encircled by parenchyma or transgressing the interpapillary line on computerized tomography. We compared this group to a similar series of 67 patients with hereditary renal cancer with only peripheral based tumors.Mean tumor size was 3.2 cm (range 1.5 to 7.5). Mean operative time was 352 minutes (range 70 to 830). Renal hypothermia and vascular clamping were used in 19 of 44 procedures (41%). Mean ischemic time was 55 minutes (range 16 to 143). Mean blood loss was 4.6 l (range 0.1 to 23). The complication rate was 23% (10 of 44 cases) and with 18% (8 of 44) directly related to surgical technique. The mean transfusion requirement was 6.7 U (range 0 to 32) and 12 of 44 procedures (27%) required no blood products. Mean preoperative and postoperative serum creatinine was 1.05 (range 0.6 to 1.8) and 1.08 mg/dl (range 0.6 to 2.1), respectively. Mean followup was 33.7 months. No metastasis developed during followup.Central renal tumors are a common manifestation of hereditary renal cell carcinoma. There was no statistical difference found between common operative parameters when central and peripheral nephron sparing surgeries were compared. However, mean operative blood loss and transfusion requirements were increased in the central tumor group.

The types of epithelial renal tumors are clear cell, types I and II papillary, chromophobe and oncocytoma. We identified the genetic basis of these different types of kidney cancer to provide better methods for early diagnosis of this disease as well as provide the foundation for the development of molecular therapeutic approaches.To identify the genetic basis of kidney cancer we studied families with an inherited predisposition to kidney cancer. Families in which 2 or more individuals had kidney cancer underwent a comprehensive evaluation to determine whether they were affected with a hereditary form of renal carcinoma. Genetic linkage analysis was performed to identify the gene for inherited forms of renal carcinoma.The gene for the inherited form of clear cell renal carcinoma associated with von Hippel-Lindau gene was identified. This gene has been found to be a tumor suppressor gene. A new form of inherited renal carcinoma, hereditary papillary renal carcinoma, was identified. The gene for this condition was identified and found to be the proto-oncogene c-Met. A previously unidentified form of familial renal oncocytoma was found. A familial form of chromophobe renal carcinoma and oncocytoma associated with Birt Hogg Dubé syndrome was found. The gene for this condition was localized on the short arm of chromosome 17 and it has been identified. We studied families with cutaneous leiomyomas, uterine leiomyomas and papillary renal carcinoma. We identified mutations in the fumarate hydratase gene in patients affected with this disorder, namely hereditary leiomyoma renal cell carcinoma.Kidney cancer used to be considered a single disease. It is now known that there are a number of different types of cancers of the kidney with different histological patterns and different clinical courses that appear to respond differently to therapy. These different types of kidney cancer are caused by different genes, ie they each have a distinct genetic basis. Understanding the molecular pathways of these cancer genes should provide insight into their varying clinical courses and responses to treatment as well as provide the foundation for the development of disease specific molecular therapeutic strategies.

Purpose: Suramin is a polysulfonated naphthylurea that inhibits proliferation and DNA synthesis of transitional cell carcinoma cell lines. Its large molecular size and negative charge inhibit bladder absorption, making suramin an excellent candidate for intravesical chemotherapy. Intravesical suramin was evaluated in a phase I study to define dose limiting toxicity and systemic absorption, determine a starting dose and regimen for phase II studies and provide a preliminary assessment of in vivo antitumor activity.Materials and Methods: Intravesical suramin treatment was administered in 9 patients with histologically identified transitional cell carcinoma (Tcis, Ta or T1) in whom at least 1 course of standard intravesical chemotherapy (bacillus Calmette-Guerin, thiotepa or mitomycin C) had failed. Suramin was administered once weekly for 6 weeks. Patients were treated in groups of 3 using a 60 cc volume and intrapatient dose escalation schedule. Suramin doses of 0.3 to 614.4 mg./ml. were administer...

Purpose: Abdominal wall adhesions at laparoscopy may predispose patients to access related injuries and increase the complexity of the procedure. We have observed concern from referring physicians regarding the safety of laparoscopy in patients who previously underwent surgery because of the risk of abdominal adhesions. To assess the risk of adhesions at laparoscopy a retrospective cohort study was performed.Materials and Methods: All patients who underwent a transperitoneal urological laparoscopic procedure in a 6-year period at our institution were included in this study. A chart review was performed to obtain demographic/surgical data and identify preoperative risk factors for adhesions, such as previous abdominal or pelvic surgery, radiation and/or intra-abdominal inflammatory disease. Operative videotapes were reviewed to determine the presence and location of adhesions. Standard statistical analyses were performed.Results: During the study period 127 patients underwent transperitoneal laparo...

Purpose: Adrenal cortical sparing surgery is a relatively new approach to adrenal tumors. Laparoscopic partial nephrectomy is a technically feasible but challenging operation. We describe the use of intraoperative ultrasound to facilitate laparoscopic partial nephrectomy in a population with a hereditary predisposition to multifocal pheochromocytoma.Materials and Methods: All patients underwent a history, physical examination, serum and urine catecholamine determinations, abdominal computerized tomography-magnetic resonance imaging and metaiodobenzylguanidine scan. The adrenal gland was exposed using a standard 3 or 4 port approach. Intraoperative ultrasound was performed using a 7.5 MHz. 10 mm. transducer placed through a 12 mm. port. After imaging the whole gland and adjacent structures partial adrenalectomy was performed based on intraoperative ultrasound images using a harmonic scalpel or alternatively using a cut and sew technique that provided a 5 mm. margin. Tumors were removed intact and s...

Laparoscopic radical nephrectomy (LRN) is being increasingly offered for the management of renal-cell carcinoma (RCC). Specimen removal may be performed through a small or hand-port incision or by specimen morcellation. Limited studies exist addressing the accuracy of histopathologic diagnosis in morcellated renal tumors. Because of concerns about the lack of a diagnosis secondary to the morcellation process, we performed premorcellation needle biopsies to obtain nondisrupted tissue for pathologic analysis. Herein, we compare the histopathologic diagnosis achieved via needle biopsy prior to morcellation with that of the final specimen.Following successful laparoscopic resection, specimens were entrapped in a Lapsac. Needle biopsies were performed manually through the mouth of the Lapsac, and morcellation was then done in some patients using manual and mechanical methods. The histopathologic diagnoses in the needle biopsy specimens and the morcellated material were compared.Laparoscopic radical nephrectomy with specimen morcellation was performed in 15 patients. Nine patients had premorcellation needle biopsies. Eight of these biopsies had sufficient tissue for diagnosis of RCC. This finding correlated with final diagnosis from the morcellated material. Perinephric fat invasion was identified in three morcellated specimens.Needle biopsy prior to specimen morcellation confirmed the histologic diagnosis of the morcellated specimen. This finding suggests that such histopathology material is adequate for diagnosis and may make premorcellation needle biopsy redundant.

The management of advanced renal cell carcinoma (RCC) continues to evolve. With the advent of laparoscopic radical nephrectomy (LRN), minimally invasive approaches to kidney cancer have developed. Laparoscopic resection of locally advanced RCC yields a similar cancer-control rate with the advantage of decreased morbidity. Although cytoreductive LRN is a technically challenging procedure, it may be completed safely in selected patients. Further prospective study of the role of LRN for advanced RCC is warranted.

Purpose: Patients with metastatic renal cell carcinoma have a reported 5-year survival of 0% to 20%. The ability to predict which patients would benefit from nephrectomy and interleukin-2 (IL-2) therapy before any treatment is initiated would be useful for maximizing the advantage of therapy and improving the quality of life.Materials and Methods: A retrospective analysis of the x-rays and charts of patients treated at the National Institutes of Health Surgery Branch between 1985 and 1996, who presented with metastatic renal cancer beyond the locoregional area and the primary tumor in place, was performed. Preoperative computerized tomography or magnetic resonance imaging, or radiological reports if no scans were available, were used to obtain an estimate of the volume of retroperitoneal lymphadenopathy. Operative notes were used to evaluate whether all lymphadenopathy was resected or disease left in situ, or if any extrarenal resection, including venacavotomy, was performed. Mean survival rate was calcul...

Purpose: von Hippel-Lindau disease, hereditary papillary renal cell carcinoma, the Birt-Hogg-Dube syndrome and familial renal oncocytoma are familial renal tumor syndromes. These hereditary disorders are noteworthy for the development of multiple bilateral renal tumors and the risk of new tumors throughout life. One management strategy is observation of solid renal tumors until reaching 3 cm., then performing parenchymal sparing surgery. We present a 5-year update on our experience.Materials and Methods: From May 1988 to October 1998, 49 patients with hereditary renal cell carcinoma, including von Hippel-Lindau disease in 44, hereditary papillary renal cell carcinoma in 4 and the Birt-Hogg-Dube syndrome in 1, and 1 with familial renal oncocytoma underwent exploration to attempt renal parenchymal sparing surgery. Patients were followed prospectively with periodic screening for recurrence, metastasis and loss of renal function. Median followup was 79.5 months (range 0.7 to 205).Results: A total of 50 patien...

We review our 10-year experience with intraoperative ultrasound during renal parenchymal sparing surgery in patients with hereditary renal cancers.Between 1991 and 2000, 68 nephron sparing procedures were performed on 26 women and 27 men, all but 1 of whom had a hereditary predisposition to renal cancer, for example von Hippel-Lindau, hereditary papillary renal cancer. Intraoperative ultrasound was performed after the surgeon removed all visible or palpable lesions. High frequency transducers (7 MHz.) and color Doppler were used in all cases. Lesions were characterized as simple cysts, complex cysts or solid masses, and were recorded on a map.A total of 935 lesions (mean 12.8 lesions per kidney) were removed in 68 nephron sparing operations performed on 53 patients. Of these lesions 870 were removed without while 65 required intraoperative ultrasound. In 17 of 68 (25%) procedures intraoperative ultrasound identified renal cancers that were not detectable by the surgeon. Mean tumor size of ultrasound detected lesions was 1.0 cm. (range 2 mm. to 4 cm.). Of the 32 cystic lesions identified by intraoperative ultrasound 5 contained renal carcinoma, and 29 of the 33 solid renal masses were renal cell carcinomas. During reoperations ultrasound enabled the surface of the kidney to be evaluated even when it was inaccessible due to scar tissue or adherent perinephric fat.Intraoperative ultrasound can be performed after all visible lesions have been removed and identifies additional tumors in 25% of patients with hereditary renal cancer, thus ensuring that as many tumors as possible have been removed during renal parenchymal sparing surgery.

von Hippel-Lindau disease (VHL) is an autosomal dominant familial syndrome that predisposes to the formation of tumors in multiple organ systems, including adrenal and extra-adrenal pheochromocytomas. However, fewer than 30% of VHL families develop pheochromocytomas. In recent years, this clinical heterogeneity has been correlated with missense mutations. The VHL patient requires vigilant, lifelong biochemical and radiographic screening for pheochromocytoma. Half of VHL pheochromocytomas present bilaterally, and there is a high incidence of recurrence after surgery. Because of the morbidity of bilateral total adrenalectomy with subsequent steroid replacement therapy, the recent therapeutic trend has been toward observation and minimally invasive adrenal-sparing procedures.

Suramin has been shown to have an effect on bone resorption in in vitro models. It is not clear if a similar effect is seen in patients treated with suramin. The clinical effect of suramin treatment on total serum calcium was examined in two groups of patients with hormone-refractory prostate cancer. In all, 28 patients in group 1 were examined within 2 weeks before and 2 weeks after suramin treatment and 72 patients in group 2 were examined within 2 weeks before, during, and after treatment with suramin. In addition, calcium controls spiked with suramin were run in three different commercially available assays for evaluation of the effect of suramin dose on calcium determination. Group 1 patients showed a decrease in serum calcium after treatment with suramin. The mean uncorrected serum calcium level was 2.29 +/- 0.025 mmol/l before treatment and 2.09 +/- 0.025 mmol/l after treatment (P < 0.0001, paired Wilcoxon test). The mean serum calcium value corrected for albumin was 2.33 +/- 0.02 mmol/l before treatment and 2.24 +/- 0.02 mmol/l after treatment (P = 0.0022, paired Wilcoxon test). Group 2 patients also displayed a decrease in serum calcium after treatment with suramin. The mean baseline value was 2.23 mmol/l (median 2.26 mmol/l, range 1.20-2.54 mmol/l). The mean level of serum calcium corrected for albumin as determined at the end of treatment was 2.14 mmol/l (median 2.16 mmol/l, range 0.98 2.46 mmol/l). In all, 48 patients for whom pre- and post-treatment values were available for analysis displayed a median calcium decrease of 0.09 mmol/l (P = 0.0005, Wilcoxon signed-rank test for the null hypothesis of no change). For 68 patients in group 2, data on serial serum calcium measurements during treatment were available for analysis. A projected median decrease in serum calcium of 0.06 mmol/l (range 0.43 to 0.72 mmol/l) over an 8-week interval of suramin therapy was found. Overall, 47 of the 68 slopes were negative (P = 0.0022, Wilcoxon signed-rank test). Nine patients were treated with suramin for less than 6 weeks. These patients' calcium levels were significantly higher than those of 50 patients treated for longer periods (median value 2.24 versus 2.16 mmol/l, P = 0.035, Wilcoxon rank-sum test). No correlation was found between suramin dose and calcium level using the Kodak Ektachem, Hitachi 914, or Synchron Clinical System CX3 method. In conclusion, suramin treatment was consistently associated with decreases in serum calcium in two groups of patients with hormone-refractory cancer. Suramin placed in calcium controls did not affect calcium determination using three commercially available methods.

Purpose: Patients with von Hippel-Lindau disease are predisposed to multiple bilateral adrenal pheochromocytoma. In these patients partial adrenalectomy may preserve adrenocortical function and avoid the morbidity associated with medical adrenal replacement. We report our experience with such cases.Materials and Methods: Laparoscopic partial adrenalectomy was performed in patients with von Hippel-Lindau disease and pheochromocytoma when there was evidence of normal adrenocortical tissue on preoperative imaging or intraoperative examination. Suture ligature or a harmonic scalpel was used to excise the tumors, leaving a 2 to 3 mm. margin of normal tissue.Results: Two patients underwent laparoscopic partial adrenalectomy and 1 laparoscopic bilateral partial adrenalectomy with preservation of normal adrenocortical tissue. Seven pheochromocytomas were removed. Laparoscopic ultrasound was essential for localizing 2 pheochromocytomas that were not visualized by the camera. Median operative time was 324 minutes, ...

Purpose:: We review the literature and characterize the clinical findings of von Recklinghausen’sassociated pheochromocytoma.Materials and Methods:: A Grateful Med search for the years 1966 to 1999 was performed on the subjects, “von Recklinghausen” and “neurofibromatosis.” Articles from the Grateful Med search were then reviewed to identify older publications. Of 325 articles 118 are included in this review.Results:: Pheochromocytomas have been clinically identified in 0.1 to 5.7% of patients with von Recklinghausen’s disease. Mean patient age was 42 years (range 1.5 to 74) in 87 women and 61 men at presentation with pheochromocytoma. Of the 148 patients 84% had solitary adrenal tumors, 9.6% bilateral adrenal disease and 6.1% ectopic pheochromocytomas. Symptoms related to pheochromocytoma or hypertension were noted in 78% of the patients. Tumors secreted epinephrine and norepinephrine, and 87% demonstrated metaiodobenzylguanidine uptake. Of the 148 patients 6% died during pregnancy or a medical procedure...

Purpose: We characterize the genetic abnormalities associated with pathological subtypes of renal tumors, which may help diagnosis or prognostication.Materials and Methods: A comprehensive literature review of genetic abnormalities associated with different renal tumor subtypes was performed.Results: Studies of sporadic and hereditary forms suggest that abnormalities in the von Hippel-Lindau and met genes are the earliest changes in conventional (clear cell) and papillary basophilic renal cancers, respectively. Renal oncocytoma and chromophobe carcinoma have common genetic abnormalities, suggesting a relationship. A similar finding has been observed between papillary adenoma and papillary basophilic renal cancer.Conclusions: These findings suggest that molecular diagnostic testing will help determine histopathological diagnosis, identify tumor types with similar genetic abnormalities suggesting a common origin and indicate potential prognostic markers for future study.

Purpose: Patients with hereditary forms of renal cancer are at risk for new tumors and metastases. Renal parenchymal sparing surgery has been performed to preserve renal function and quality of life, and prevent metastases. We evaluated a 3 cm. threshold for performing renal parenchymal sparing surgery in patients with von Hippel-Lindau disease and hereditary papillary renal cancer.Materials and Methods: Patients with von Hippel-Lindau disease or hereditary papillary renal cancer and renal cancer were identified by screening affected kindred and by kindred history. Patients with small tumors were followed with serial imaging studies until the large renal tumor was 3 cm., when renal parenchymal sparing surgery was performed. Renal tumors greater than 3 cm. were resected without delay. Parenchymal sparing techniques were used when possible in each group.Results: The 3 cm. surgical threshold was evaluated in 52 patients with von Hippel-Lindau disease (group 1) at a median followup of 60 months (range...

Objectives. Cytoreductive nephrectomy is commonly performed in patients with metastatic renal cell carcinoma before systemic interleukin-2 (IL-2) therapy. Open nephrectomy is associated with prolonged recovery during which metastatic disease can progress. The feasibility of laparoscopic cytoreductive surgery in these patients with large renal tumors was examined. The role of tumor morcellation in reducing the recovery period and allowing earlier treatment with IL-2 was investigated. Methods. Patients with metastatic renal cancer underwent either open nephrectomy (group 1, n=19) or laparoscopic cytoreductive nephrectomy (n = 11; 6 with tumor morcellation [group 2], 5 with removal of the tumor through a small incision [group 3]). The three groups were compared to evaluate relative recovery, suitability for treatment with IL-2, and laparoscopic port site seeding. Results. A group of 19 patients underwent open nephrectomy (group 1). Eleven patients with a median tumor volume of 377 cm 3 (median tumor diameter 9 cm) underwent laparoscopic cytoreductive nephrectomy. Six of these patients underwent tumor morcellation (group 2) and 5 underwent laparoscopic assisted nephrectomy (group 3). There was no difference in patient age, sex, sites of metastatic disease, ECOG status, size of renal tumor, or surgical complication rates among groups. Patients whose tumor was morcellated had reduced postoperative parenteral narcotic requirements and were discharged sooner than patients undergoing open cytoreductive nephrectomy. Time to treatment with IL-2 was shortest in the morcellation group (median time to treatment 37 days). No port site seeding was observed. Conclusions. Laparoscopic cytoreductive nephrectomy in patients with bulky renal disease is a safe procedure in selected patients. This pilot study demonstrated a significant association of laparoscopic tumor morcellation with less postoperative pain, faster time to discharge, and shorter time to treatment with IL-2. A randomized study is warranted to determine the role of laparoscopic cytoreductive nephrectomy with tumor morcellation.

Purpose: In patients with von Hippel-Lindau disease multiple bilateral adrenal pheochromocytoma can develop, which has traditionally been treated with adrenalectomy. Partial adrenalectomy can preserve normal adrenal function and avoid the morbidity associated with medical adrenal replacement. We demonstrate whether adrenal function could be preserved by partial adrenalectomy in patients with von Hippel-Lindau disease.Materials and Methods: From 1995 to 1998, 13 consecutive von Hippel-Lindau disease patients with pheochromocytoma underwent 14 partial and 6 complete unilateral adrenalectomies. Function of residual normal adrenal and recurrence of adrenal pheochromocytoma were determined at followup.Results: Of the patients 2 had undergone unilateral adrenalectomy and 1 had undergone complete and partial adrenalectomy previously. Following surgery residual normal adrenal tissue consisted of 1 partial adrenal in 3 patients, bilateral partial adrenal in 5, partial and complete adrenal gland in 1, 1 com...

Purpose: We analyzed familial renal oncocytoma to provide a foundation for studies aimed at defining genes involved in the pathogenesis of renal oncocytoma.Materials and Methods: We describe 5 families with multiple members affected with renal oncocytoma. Tumors were analyzed pathologically, and affected and nonaffected members were screened clinically and genetically.Results: We identified 12 affected male and 3 affected female (ratio 4:1) individuals in the 5 families. In affected family members renal oncocytomas were often multiple and bilateral. No metastatic disease was observed. Most renal oncocytomas were detected incidentally in asymptomatic individuals or during screening of asymptomatic members of renal oncocytoma families. One identical twin pair was affected with bilateral multiple renal oncocytomas.Conclusions: Renal oncocytoma may be inherited in some families.

Purpose: After renal parenchymal sparing surgery, residual defects may persist on imaging studies at the sites of resection. These “pseudotumors” may lead to confusion as to whether a lesion was removed or has recurred. We describe the imaging appearances and behavior of renal pseudotumors following renal parenchymal sparing surgery.Materials and Methods: From 1988 to 1997, 32 patients underwent 46 renal parenchymal sparing surgeries for removal of renal cancers, including von Hippel-Lindau disease in 27, hereditary papillary cancer in 2 and sporadic disease in 3. A median of 14 tumors (range 1 to 114) were removed in each operation. Thrombin soaked absorbable gelatin sponge was placed in the tumor bed after resection to aid hemostasis. We reviewed all imaging studies performed after these operations to characterize these lesions and gain further understanding into the prevalence and etiology.Results: Of the patients, 9 had a total 13 pseudotumors on initial postoperative imaging studies, includin...

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%) wit...

To evaluate the use of dual-phase three-dimensional magnetic resonance (MR) angiography in the preoperative staging of renal cancer.MR angiography was performed in 18 patients before performance of partial (n = 7), radical (n = 10), or laparoscopic (n = 1) nephrectomy to treat renal cancer. Dynamic, three-dimensional MR angiograms were obtained with gadoteridol enhancement, breath holding, and a three-dimensional spoiled gradient-echo sequence. Images were obtained at 15-second intervals to achieve opacification of arteries and veins. Source, maximum intensity projection, and multiplanar reconstruction images were evaluated. Imaging results were compared with surgical findings.Renal arterial phase MR angiograms depicted 30 of 31 (97%) surgically confirmed renal arteries, with one false-positive result (an artery that arose from an early-branching single main renal artery, interpreted as a separate accessory artery). Renal venous phase MR angiograms depicted all seven instances of renal vein involvement, including extension to the inferior vena cava in two patients. Collateral vessels around the tumor, including prominent gonadal veins in three patients, were demonstrated. Additional findings included adenopathy and adrenal and pulmonary metastases.Dual-phase MR angiography of the kidney may be a useful technique in depicting renal vessels before nephrectomy.

We defined the outcome of a strategy using cytoreductive surgery before high dose interleukin-2 (IL-2) therapy in patients with metastatic renal cell carcinoma.During an 11-year period, 195 patients underwent cytoreductive surgery as preparation for high dose IL-2 based therapy. The renal primary and locoregional metastatic disease that could be safely resected was removed.Because of the large size 176 of 195 renal tumors (90%) were resected through transabdominal incision and in 45 patients (23%) a second additional significant procedure was performed. Five cases (2.6%) were unresectable and 2 (1%) perioperative deaths occurred. After surgery 121 of 195 patients (62%) were eligible for treatment with high dose IL-2 based protocols. Overall response rate to IL-2 based protocols was 18%.Cytoreductive surgery can be performed safely in patients with metastatic renal cell carcinoma. Although the impact of cytoreductive surgery on response to immunotherapy remains undefined, this combination of primary debulking and systemic IL-2 can result in durable complete tumor regression in some patients with metastatic renal cell carcinoma.

Objectives Tumors are thought to metastasize by a process involving tumor cell attachment to extracellular matrix, degradation of matrix components by tumor-associated proteases, and cellular movement into the area modified by protease activity. Type IV collagen comprises the major element tumor cells must degrade to gain access to the rest of the body. Renal cancer cell line progelatinase A (E.C. 3.4.24.24; 72-kDa type IV collagenase; MMP-2) mRNA expression was correlated with patient survival. Methods Total cellular mRNA was extracted from tumor cell lines derived from patients with metastatic renal cell carcinoma. The results of the densitometric analysis of Northern blots were correlated with patient survival. Formalin-fixed, paraffin-embedded tissue sections of primary renal cancers were examined for immunohistochemical expression of MMP-2. Results Cell lines established from 23 primary renal tumors and six metastatic sites in 26 patients with metastatic renal carcinoma were studied. Variable expression of progelatinase A, relative to A2058 melanoma cells (mean ± SEM, 0.60 ± 0.21 ; median, 0.082; range, 0 to 4.78), was found. There was a significant inverse association between patient survival and the log of the MMP-2 expression (P = 0.045 by the Cox proportional-hazards model). Using a cutoff value of 0.10, the closest round number to the median expression of MMP-2, a significant difference between survival of patients with lower and higher MMP-2 expression in their primary renal cell line was found (P = 0.0054). Cell lines with low, intermediate, and high expression of MMP-2 mRNA all had primary tumors with high tissue immunohistochemical expression of MMP-2. Conclusions These studies demonstrate an inverse relationship between renal cancer cell line MMP-2 mRNA expression and patient survival. Immunohistochemical studies of the primary tumors from which the cell lines were derived uniformly showed high MMP-2 expression. Previous work suggests local renal factors upregulate cellular expression of MMP-2 in the primary tumor, and are not active at extrarenal sites.

BACKGROUND Combined androgen blockade (CAB) (medical or surgical castration plus antiandrogen therapy) is considered by many to be the optimal endocrine maneuver for patients with metastatic prostate carcinoma. When progression occurs after CAB, the discontinuation of the antiandrogen is recommended. The authors present a patient that had a clinical complete response to flutamide withdrawal plus hydrocortisone that, at last follow-up, had been maintained for more than 46 months. METHODS A 71-year-old man with a positive family history of prostate carcinoma presented in 1989 with urinary frequency and a suspicious digital rectal examination. He was found to have a poorly differentiated adenocarcinoma (Gleason 4+4). He was started on CAB and his prostate specific antigen (PSA) concentration declined from 96 ng/mL to the normal range and was maintained for the next 24 months. In 1991 his PSA began to rise, and reached 64 ng/mL by 1993. The patient was enrolled on a clinical trial that discontinued the flutamide administration and hydrocortisone was initiated. RESULTS Physical examination at the time of enrollment was unremarkable. His PSA declined to below the limits of detection after this maneuver and at last follow-up had been maintained there for more than 46 months. In 1995, the patient underwent a repeat biopsy of the prostate and all six tissue cores were negative for carcinoma. At last follow-up in December 1996, the patient had no evidence of disease and was being followed routinely; however, the authors were continuing treatment with testicular suppression (leuprolide) plus hydrocortisone. CONCLUSIONS The authors believe the residual androgens and steroids produced by the adrenal cortex play a meaningful role in prostate carcinoma cell proliferation. Based on this case and data from trials supporting the activity of flutamide withdrawal plus adrenal suppression, it appears reasonable to evaluate prospectively the discontinuation of antiandrogen versus antiandrogen withdrawal plus adrenal suppression in individuals failing CAB. Cancer 1997; 79:1964-8. © 1997 American Cancer Society.

Patients with von Hippel-Lindau disease are at risk for multiple, bilateral, recurrent renal tumors and metastases. We previously evaluated the relationship between tumor size and metastases in families with hereditary renal cancer. We update our findings with about twice the number of patients with von Hippel-Lindau disease.Screening affected kindred or retrospective review of medical records identified 181 patients with von Hippel-Lindau disease and renal cell carcinoma. Patients with small tumors were followed with serial imaging until the largest tumor reached 3 cm, at which point surgery was recommended. Surgical resection was recommended to patients with tumors larger than 3 cm. Patients not undergoing screening often had large renal tumors.A total of 108 patients with von Hippel-Lindau disease and solid renal tumors on computerized tomography imaging smaller than 3 cm (group 1) were followed a mean of 58 months (range 0 to 244). Metastatic disease did not develop in any of these patients. Renal tumors larger than 3 cm developed in 73 patients with von Hippel-Lindau disease (group 2). Mean followup of group 2 was 72.9 months (range 0 to 321). The proportion of procedures that were nephron sparing was higher in group 1 than in group 2 (120 of 125 [97%] compared to 85 of 125 [69%], Fisher's exact test p0.0001). Metastases developed in 20 of 73 (27.4%) patients in group 2. The frequency of renal tumor metastases increased with increasing tumor size.No renal tumor metastases were found in patients with renal tumors less than 3 cm in diameter. We advocate a 3 cm threshold for parenchymal sparing surgery in patients with von Hippel-Lindau disease to decrease the risk of metastatic disease while preserving renal function, avoiding or delaying the need for dialysis and/or renal transplant, and decreasing the number of operations which a patient may undergo. We stress the importance of early screening in the kindred of patients with von Hippel-Lindau disease and vigilant followup thereafter.

Reduced expression of nm23 has been associated with increased metastases and decreased survival in a variety of malignancies. In the present study, the expression of nm23 was examined by Northern and Western blot analyses in a series of cell lines derived from patients with metastatic renal cell carcinoma. Two of twelve (17%) informative cell lines derived from 9 patients had loss of heterozygosity at Nm23-H1. Twenty-two renal cancer cell lines derived from primary tumors, 5 cell lines derived from metastatic tumors and 4 short-term cultures of normal proximal renal tubular cells all expressed Nm23 mRNA in varying amounts. On average, the level of expression of Nm23 mRNA in short-term cultures of benign proximal renal tubular cells was found to be similar to the level seen in renal cancer cell lines. Twenty-eight cell lines derived from renal primary tumors and 8 cell lines derived from metastatic tumors expressed both the Nm23-H1 and Nm23-H2 proteins. High or low relative expression of nm23 at the mRNA or protein level did not correlate with survival. The absence of any anomalous pattern of expression of the nm23 genes and the lack of correlation of expression with survival suggests that nm23 does not play a central role in the progression of this tumor type.

Tumor suppressor genes have been found to have loss of function in a number of malignancies. This loss of function is believed to contribute to malignant transformation or metastatic spread. In the present study, expression of the retinoblastoma (RB) tumor suppressor gene was examined in cell lines and tumor tissue obtained from primary renal and metastatic sites in patients with metastatic renal cell carcinoma.Three of fifteen (20 percent) of informative renal carcinoma cell lines had loss of heterozygosity (LOH) in the RB gene (intron 20) detected by polymerase chain reaction analysis. Using restriction fragment length polymorphism (RFLP) analysis, 7 of 22 (32 percent) informative cell lines had LOH centromeric to the RB gene at the D13S1 locus. No LOH (0 of 7) was seen telomeric to the RB gene at the D13S2 locus. None of the 28 cell lines examined had decreased RB mRNA expression compared with short-term cultures of proximal renal tubular cells. Western blotting demonstrated phosphorylated and ...

We recently described a 3-generation family with members affected with papillary renal cell carcinoma, an uncommon histological type of renal cell carcinoma. Possibly family 150 is an isolated occurrence, a reflection of some as yet unknown environmental factor. Alternatively, family 150 may represent a distinct class of inherited cancer. To distinguish between these 2 possibilities we sought additional families with papillary renal cell carcinoma and we identified 9 with members affected with papillary renal cell carcinoma. There were 29 affected male and 12 affected female subjects (ratio 2.41:1), including affected members of family 150. Papillary renal cell carcinomas were often detected incidentally in asymptomatic individuals or during screening of asymptomatic members of renal cell carcinoma families. The penetrance, the proportion of obligate gene carriers that showed clinical evidence of the disease, was reduced. The median survival of affected individuals was 52 years. The results suppor...

Suramin is polysulfonated naphthylurea which has a broad range of antitumor activity. The mechanism of action of suramin is not completely understood, although it is known to inhibit enzymes in all cellular compartments, inhibit steroidogenesis and interfere with ligand-receptor binding. Suramin's large molecular size and negative charge should make it poorly absorbed through the bladder mucosa, a desired characteristic for an intravesical chemotherapeutic agent. We examined the ability of suramin to inhibit thymidine uptake and decrease cellular proliferation in 4 transitional cell carcinoma cell lines grown in vitro to determine if suramin might be a new candidate drug of treatment for patients with superficial bladder cancer. Suramin inhibited cellular proliferation of all cell lines tested (MBT2, T24, RT4 and TCCSUP) in a dose-dependent fashion. Fifty per cent inhibition of cellular proliferation compared with controls was seen with suramin concentrations of 250 to 400 micrograms/ml. by, at most, 5 to 9 days of exposure. The cell line RT4 was the cell line most sensitive to the growth inhibitory effect of suramin, with 50% growth inhibition compared with controls achieved after 3 days' exposure to a suramin concentration of 100 micrograms/ml. Suramin inhibited DNA synthesis in a dose-dependent fashion, as measured by thymidine uptake, in 3 of the 4 cell lines tested (MBT2, T24, and RT4). Suramin inhibited thymidine uptake by TCCSUP in a dose-dependent fashion, but did not achieve statistical significance.

We describe a 3 generation family with members affected with papillary renal cell carcinoma, an uncommon histological type of renal cell carcinoma. Multiple tumors of varying size were present in both kidneys of affected family members. The disorder was not linked to polymorphic markers on chromosome 3p and there was no loss of heterozygosity at loci on 3p in renal tumors. The results suggest the presence of a renal cell carcinoma gene not located on 3p that predisposes to renal cell carcinoma with a distinct histological appearance. The inherited disorder in this family appears to be different from recognized hereditary cancer syndromes.

A reusable laparoscopic instrument consisting of a flexible deployment ring and a barrel was fabricated, and an impermeable sac was sutured to the flexible ring before entrapment of the specimen and morcellation. The laparoscopic specimen entrapment device facilitated placement of large renal tumors within a sac for morcellation.

Purpose: Laparoscopic radical nephrectomy is being performed more commonly. To our knowledge intentional resection of the diaphragm during laparoscopic radical nephrectomy for large renal tumors has not yet been described. We detail the laparoscopic management of diaphragmatic resection.Materials and Methods: From March 1996 to February 2001, 36 patients underwent cytoreductive laparoscopic radical nephrectomy at our institution in preparation for systemic immunotherapy. Charts and operative tapes were reviewed and cases were identified in which diaphragmatic resection was performed for locally invasive tumors.Results: In 3 patients a portion of the diaphragm was dissected via laparoscopy during debulking nephrectomy. All patients had renal cell carcinoma with documented metastatic disease. The diaphragm was repaired laparoscopically using intracorporeal suturing techniques in 2 of the 3 patients and a chest tube was placed in all 3. Transient systolic hypotension and hypercarbia in 1 case resolved with m...

Fewer than 1% of patients with renal cell carcinoma are reported to experience spontaneous regression of metastatic lesions after nephrectomy. We report on 4 of 91 patients (4.4%) with metastatic renal cell carcinoma who had spontaneous regression of all metastatic lesions after cytoreductive nephrectomy. These patients were carefully selected before surgery for the ability to receive high dose interleukin-2. One patient had recurrence at 2 months, 1 had recurrence at 11 months, and 2 had no evidence of disease at 3 and 4.5 years.

Laparoscopic radical nephrectomy is becoming increasingly utilized for localized renal tumors. We have applied this procedure to patients with metastatic disease for cytoreduction prior to systemic immunotherapy. Advantages of the laparoscopic approach include decreased parenteral narcotic requirement and decreased time to initiate systemic therapy. Herein, we describe the procedure with some technical pearls learned in our early experience.

PURPOSE Suramin is known to inhibit the growth of malignant prostate carcinoma cells in vitro. This led us to evaluate the effectiveness of suramin in the treatment of 38 patients with prostate carcinoma refractory to hormone therapy. PATIENTS AND METHODS Suramin was administered by continuous infusion at a rate designed to reach a peak of 300 micrograms/mL at the end of 14 days. Patients were given 8 weeks to recover from any toxicity before beginning the second cycle. Subsequent cycles were administered in the same manner except the starting dose rate was 280 mg/m2. RESULTS In 17 patients with measurable soft tissue disease, three had complete disappearance of soft tissue disease for 4, 5, and 11 months, whereas three patients had a greater than or equal to 50% decrease in the sum of the products of the diameters of all measurable disease for greater than or equal to 1 month. Of these 17 patients, pretreatment prostate-specific antigen (PSA) decreased by 75% or more in five (29%) and normalized in one (6%). The remaining 21 patients had disease limited to bone, and only one of these experienced resolution of more than 50% of all lesions on bone scan. Of these 21 patients, pretreatment PSA decreased by 75% or more in eight (38%) and normalized in five (25%). Median time to progression for all patients was 26.3 weeks, and median survival was 42.3 weeks. Patients with bone involvement alone exhibited a better survival than patients with soft tissue involvement (P2 = .02). Survival was strongly correlated (P2 = .0001) with a decline in the pretreatment PSA of greater than or equal to 75% by the eighth week on therapy, with nearly an 85% survival at 1 year compared with a 20% survival for those whose pretreatment PSA did not decline by that amount. CONCLUSION We conclude that suramin is an active agent in hormone-refractory prostate carcinoma.

A total of 12 patients with stage 4 renal cell carcinoma and primary renal tumors in situ was entered into a pilot study using treatment with interleukin-2 and α-interferon followed by radical nephrectomy. Of the patients 11 underwent nephrectomy after an initial course of immunotherapy. Ten patients were able to receive a second course of immunotherapy given after nephrectomy. One patient achieved a complete response of lung and mediastinal metastases without any change in the primary renal tumor but after nephrectomy the patient remained in complete remission for greater than 11 months. A total of 3 patients achieved a partial response at some extrarenal sites but they had progression elsewhere. Toxicity was similar to previous experience with this immunotherapy regimen. Therefore, we demonstrated that metastatic tumor regression is possible with primary renal tumors in situ and that aggressive interleukin-2-based immunotherapy can be tolerated in the presence of a large renal tumor.

Purpose: We describe the earliest renal lesions associated with hereditary papillary renal cancer and estimate the prevalence of microscopic papillary renal tumors.Materials and Methods: Grossly normal tissue was obtained from 12 kidneys during renal surgery in 9 patients with hereditary papillary renal cancer. Tissue was examined microscopically and findings were compared to those previously reported to be associated with von Hippel-Lindau disease and sporadic renal cell carcinoma.Results: A total of 92 microscopic papillary renal cell carcinoma lesions were identified on 46 of 88 slides (53%). No other lesions were identified. All tumors were solid and displayed the basophilic papillary histology characteristic of hereditary papillary renal cancer. Extrapolation of the data predicted the prevalence of 1,100 to 3,400 microscopic papillary tumors in a single kidney in a patient with hereditary papillary renal cancer.Conclusions: The basophilic papillary histology characteristic of clinically apparent rena...

Kidney cancer affects 36 000 Americans annually and is responsible for nearly 12 000 deaths every year in the US. Treatment with interleukin-2 (IL-2), the only FDA approved therapy for patients with advanced kidney cancer, is associated with a 10% complete response and a 12% partial response. To date, clear cell renal carcinoma has been the only histological type associated with response to IL-2-based therapy. In the current report, we describe a response to IL-2 therapy in a patient with type I papillary renal carcinoma.

The role of the HIF class of transcription factors has been implicated to be a critical step in clear cell kidney tumorigenesis. To assess if HIF over expression is a prominent feature of other renal cell carcinoma histological subtypes we characterized the expression of HIF-1alpha and HIF-2alpha in genetically distinct early renal cortical tumors.Nascent renal tumors of distinct histology from patients with a hereditary renal tumor syndrome were characterized for HIF expression using high amplification immunohistochemistry. In addition, indirect immunofluorescence and confocal microscopy were used for subcellular localization of HIF-1alpha and 2alpha in clear cell renal carcinoma cells.Clear cell RCC tumors from patients with von Hippel-Lindau disease strongly expressed HIF-1alpha and HIF-2alpha (10 of 12 and 12 of 12 tumors, respectively). Chromophobe tumors from patients with Birt-Hogg-Dubé syndrome expressed predominantly HIF-2alpha with weaker HIF-1alpha expression (12 of 12 and 6 of 12 tumors, respectively). Consistent HIF-1alpha expression was not seen in type I papillary tumors from patients with hereditary papillary renal carcinoma (3 of 12 tumors). However, half of the type I papillary tumors (6 of 12) expressed HIF-2alpha.Differential patterns of HIF-1alpha and HIF-2alpha protein over expression were found among the 3 human kidney tumor types associated with multifocal hereditary kidney tumor syndromes. Consistent, simultaneous over expression of HIF-1alpha and HIF-2alpha appears to be specific to VHL negative clear cell renal cell carcinoma. Consistent HIF-2alpha expression was found in all 3 renal cortical tumor subtypes, suggesting a pivotal role in renal cortical tumorigenesis. Differential function of HIF-1alpha vs HIF-2alpha is suggested by the distinct subcellular localization pattern of HIF-1alpha and HIF-2alpha in clear cell renal carcinoma cells.

Purpose: Herein we describe the evaluation and management of renal tumors in Birt-Hogg-Dube (BHD), an autosomal dominant disorder predisposing to cutaneous fibrofolliculomas, pulmonary cysts, spontaneous pneumothorax and renal tumors. Materials and Methods: A total of 124 affected individuals underwent comprehensive clinical evaluation, including body computerized tomography, to determine cutaneous, pulmonary and renal manifestations of BHD. Of these individuals 14 had their renal tumors managed at our institution. Results: Of the 124 BHD affected individuals 34 (27%) had renal tumors of various histologies, most commonly hybrid oncocytic tumor and chromophobe renal carcinoma. Average age at renal tumor detection was 50.4 years and multiple tumors were found in a majority of patients. Some patients with renal tumors were identified that did not have the characteristic cutaneous hallmarks of BHD. In 4 of the 14 patients treated at our institution small (less than 3 cm) renal tumors were observed, while 10 others underwent a total of 12 renal procedures, including 4 radical and 8 partial nephrectomies. At a median of 38 months of followup 5 of these 10 patients remained free of disease, 3 had small renal tumors and 2 died of metastatic renal cancer. Conclusions: Patients with BHD are at risk for multiple renal tumors that are often malignant and can metastasize. Individuals at risk or affected by BHD should be radiographically screened for renal tumors at periodic intervals and they are best treated with nephron sparing surgical approaches. Genetic testing for this syndrome is now available.

Purpose: Transureteroureterostomy has primarily been performed for benign disease in children with reflux or undergoing undiversion, and in adults with lower ureteral injury. We report the use of transureteroureterostomy for other than these traditional indications, including malignant disease.Materials and Methods: Transureteroureterostomy was performed in 6 patients at the time of tumor resection to bypass large ureteral defects and in 4 as a secondary operation, usually associated with a ureteral leak after previous surgery.Results: Complications related to transureteroureterostomy included 1 ureteral stricture and 1 ureteral leak. Good renal function was maintained with a mean followup of 77.9 months.Conclusions: Our experience suggests that transureteroureterostomy can be useful for urinary diversion when a segment of lower ureter is involved with malignant disease.

Hereditary papillary renal carcinoma (HPRC) is characterized by a predisposition to multiple, bilateral papillary type 1 renal tumors caused by inherited activating missense mutations in the tyrosine kinase domain of the MET proto-oncogene. In the current study we evaluated the clinical phenotype and germline MET mutation of 3 new HPRC families. We describe the early onset clinical features of HPRC.We identified new HPRC families of Italian (family 177), Spanish (family 223) and Cuban (family 268) descent. We evaluated their clinical features, performed MET mutation analysis by denaturing high performance liquid chromatography and DNA sequencing, and estimated age dependent penetrance and survival using Kaplan-Meier analysis. We characterized renal tumors by histology and fluorescence in situ hybridization.Identical germline MET c.3522G --A mutations (V1110I) were identified in families 177 and 268 but no evidence of a founder effect was found. Affected members of family 223 carried a germline c.3906G --C.3522G --A MET mutation (V1238I). Age dependent penetrance but not survival was significantly earlier for the c.3522G --A mutation than for the c.3906G --A mutation in these HPRC families. Trisomy of chromosome 7 and papillary renal carcinoma type 1 histology were detected in papillary renal tumors.HPRC can occur in an early onset form. The median age for renal tumor development in these 3 HPRC families was 46 to 63 years. HPRC associated papillary renal tumors may be aggressive and metastasize, leading to mortality. Median survival age was 60 to 70 years. Families with identical germline mutations in MET do not always share a common ancestor. HPRC is characterized by germline mutations in MET and papillary type 1 renal tumor histology.

Renal tumors are being detected at increasing rates because of widespread use of modern imaging techniques such as ultrasonography and computed tomography. Typically, these tumors, many of which are discovered incidentally, tend to be small and are confined to the kidney. Advances in ablative and imaging technology have led to the application of minimally invasive therapy in the treatment of small renal tumors. Although still evolving as a cancer treatment, minimally invasive treatment potentially offers several advantages over conventional open renal surgery: shorter convalescence, improved cosmesis, reduced postoperative pain, and renal preservation. This article reviews the status and recent progress of minimally invasive approaches to renal neoplasm.

Significant advances have been made in the understanding of the genetic basis of familial renal neoplasia. Identification of key genes in the pathogenesis of various hereditary renal cancer syndromes has provided opportunities to screen family members at risk and to explore the significance of these genetic abnormalities in the development and genesis of much more common sporadic counterparts. As researchers continue to delineate critical carcinogenic pathways and accumulate expansive knowledge on oncogenic mechanisms driving cancer initiation and progression at the cellular and molecular levels, this information will be integrated and translated into effective diagnostic and therapeutic strategies that will dictate clinical management of all renal cancers.

Laparoscopic management of extra-adrenal pheochromocytoma presents a unique surgical challenge due to variable anatomical presentation and potential catecholamine surge during operative manipulation. We report our experience with laparoscopic removal of extra-adrenal pheochromocytomas.Between 1999 and 2002, 5 patients presented with retroperitoneal extra-adrenal pheochromocytomas. Of the patients 2 had a history of von Hippel-Lindau disease, and the remaining 3 patients were diagnosed with sporadic extra-adrenal pheochromocytoma during hypertension evaluation. Although 4 patients had a history of hypertension, only 2 reported symptoms (episodic flushing, headaches, blurred vision) associated with excess catecholamine production. All patients had markedly increased preoperative urinary and plasma normetanephrine and/or norepinephrine levels, and 3 had positive I131 metaiodobenzylguanidine scan. In each case tumor was accurately identified on computerized tomography before surgery.Laparoscopic resection of extra-adrenal pheochromocytoma was successful in 4 patients. Open conversion was required in 1 patient, who also had von Hippel-Lindau related bilateral adrenal pheochromocytomas due to significant adhesion of the extra-adrenal tumor to the aorta and renal hilum, and a concern for possible local invasion. Mean laparoscopic operative time and blood loss were 273 minutes (range 240 to 350) and 119 cc (range 75 to 200), respectively. Three 10 mm ports in a standard triangular fashion were used for the left side tumors, in which the tumors were found lateral to the aorta. For the right side tumors located either in the inter-aortacaval or para-caval region, a fourth port (10 mm) was inserted for liver retraction as needed. Laparoscopic ultrasound was used to localize the tumor and to assess the retroperitoneum for possible metastasis (none detected) in 3 cases. None of the patients had a hypertensive crisis intraoperatively, and all had unremarkable postoperative recovery with an average hospital stay of 3.8 days (range 3 to 4). Plasma and/or urinary norepinephrine and normetanephrine levels returned to normal range postoperatively in all cases. One patient was noted to have left lower extremity lymphedema and gluteal hematoma due to a positional injury related to prolonged pressure from the operating table and was treated conservatively. There has been no tumor recurrence at a median followup of 14 months (range 9 to 36).With careful surgical planning and appropriate preoperative pharmacological blockade, laparoscopic surgery can be safely performed in patients with extra-adrenal pheochromocytomas with minimal morbidity. Laparoscopic ultrasound may be helpful in precise localization and evaluation of tumor extension.