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Pheochromocytoma is a rare but important tumor of chromaffin cells that is frequently considered in the evaluation of hypertension, arrhythmias, or panic disorder and in the follow-up of patients with particular genetic diseases. This report provides an update about the genetics, neurochemical diagnosis, localization by imaging, and surgical management of pheochromocytoma. Specific mutations of the RET proto-oncogene cause familial predisposition to pheochromocytoma in multiple endocrine neoplasia type II, and mutations in the von Hippel-Lindau tumor suppressor gene cause familial disposition to pheochromocytoma in von Hippel-Lindau disease. Recent findings demonstrating extraordinarily high sensitivity of plasma levels of metanephrines for detecting pheochromocytoma have led to an algorithm for clinical diagnostic steps. Nuclear imaging approaches, such as(123) I-metaiodobenzylguanidine scintigraphy and 6-[(18) F]fluorodopamine positron emission tomography, enhance both diagnosis and localization of the tumor, as described in an algorithm for patients with positive biochemical test results. Since pheochromocytoma is often benign, surgical resection by laparoscopic adrenalectomy can be curative. Areas requiring further work include determining appropriate follow-up of patients with familial pheochromocytoma, elucidating the bases for phenotypic differences, improving both specificity and sensitivity of biochemical tests, optimizing cost-effectiveness of diagnostic imaging, and testing the risk for tumor recurrence after partial adrenalectomy. [ABSTRACT FROM AUTHOR]

Objective: To describe the incidence of, clinical manifestations of, and risk factors for cyclophosphamide-induced urinary bladder toxicity in patients treated for nonmalignant disease.Design: Retrospective analysis of patients followed at the National Institutes of Allergy and Infectious Diseases from 1967 to 1993.Setting: The Warren G. Magnuson Clinical Center of the National Institutes of Health (NIH).Patients: 145 patients who received cyclophosphamide for the treatment of Wegener granulomatosis and were followed for 0.5 to 27 years (median, 8.5 years), for a total of 1333 patient-years.Measurements: Clinical characteristics, cystoscopic findings, results of cytologic examination of urine, surgical pathology, and total dose and duration of cyclophosphamide therapy were recorded and analyzed using a computer-based information retrieval system.Results: Nonglomerular hematuria occurred in 73 of 145 patients treated with cyclophosphamide (50%). Sixty of the 73 patients with nonglomerular hematuria (82%) had cystoscopy at the NIH. Forty-two of the 60 patients (70%) who had cystoscopy had macroscopic changes consistent with cyclophosphamide-induced bladder injury. Seven patients (5%) developed transitional-cell carcinoma of the urinary bladder. In 6 of these 7 patients, the total cumulative cyclophosphamide dose exceeded 100 g, and the cumulative duration of cyclophosphamide therapy exceeded 2.7 years. Before they were given a diagnosis of bladder cancer, all 7 patients had had one or more episodes of microscopic or gross nonglomerular hematuria. In contrast, none of the 72 patients who had never had nonglomerular hematuria developed bladder cancer. Cox proportional hazards regression analysis showed that only microscopic nonglomerular hematuria was a significant risk factor for the development of bladder cancer (P < 0.01).Conclusion: Long-term oral cyclophosphamide therapy is associated with substantial urotoxicity, including the development of transitional-cell carcinoma of the urinary bladder. In this cohort of patients, the estimated incidence of bladder cancer after the first exposure to cyclophosphamide was 5% at 10 years and 16% at 15 years. Nonglomerular hematuria was a frequent manifestation of cyclophosphamide-induced cystitis, and it identified a subgroup of patients at high risk for the development of bladder cancer. [ABSTRACT FROM AUTHOR]

Purpose: With evolving radio frequency technology, the clinical application of radio frequency ablation (RFA) has been actively investigated in the treatment for small renal tumors. We present our intermediate patient outcomes after RFA., Materials and Methods: Since January 2001, 17 patients with a total of 24 hereditary renal tumors ranging from 1.2 to 2.85 cm were treated with RFA using the 200 W Cool-tip RF System (Radionics, Burlington, Massachusetts) under laparoscopic (9) or percutaneous (8) guidance and had a minimum 1-year followup. A percutaneous approach was considered unsuitable if kidney tumors were contiguous to bowel, ureter or large vessels. Treatment eligibility criteria included an average tumor diameter of less than 3.0 cm, tumor growth during 1 year and solid appearance with contrast enhancement (HU change greater than 20) on computerized tomography (CT). Postoperative followup consisted of CT with and without intravenous contrast, and renal function assessment at regular intervals., Results: Median patient age was 38 years (range 20 to 51). At a median followup of 385 days (range 342 to 691), median tumor or thermal lesion diameter decreased from 2.26 to 1.62 cm (p = 0.0013), and only 1 lesion (4%), which was located centrally near the hilum, exhibited contrast enhancement (HU change greater than 10) on CT at 12 months. Of the 15 renal tumors ablated laparoscopically, 13 were in direct contact with the bowel and 2 were abutting the ureter, necessitating mobilization before RFA. Laparoscopic ultrasound was used to guide radio frequency electrode placement and monitor the ablation process in these cases. Operative time and intraoperative blood loss (mean +/- standard mean of error) were 243 +/- 29 minutes and 67 +/- 9 cc, respectively. In 1 patient whose ureter was adherent to the tumor a ureteropelvic junction obstruction developed after laparoscopic RFA, requiring open repair., Conclusions: At the minimum 1-year followup 23 of 24 ablated tumors lacked contrast uptake on CT, meeting our radiographic criteria of successful RFA treatment. RFA treatment of small renal tumors using the Radionics system appears to result in superior treatment outcomes compared to those of earlier series with lower radio frequency power generators. A high wattage generator might attain more consistent energy deposition with subsequent cell death in the targeted tissue due to less convective heat loss.

Objective: Minimally invasive approaches to the management of renal tumors are being studied intensively in urology. Herein, we describe the use of multiple organ-sparing techniques for the management of tumors in a patient with von Hippel Lindau disease (VHL)., Materials and Methods: A 42 year-old woman with VHL underwent a right partial adrenalectomy and a left renal radiofrequency ablation (RFA) of two renal tumors., Results: A 2.2 cm solitary right adrenal pheochromocytoma was resected using a transperitoneal approach. A retroperitoneal approach to the left kidney was performed and RFA of the two renal tumors completed using sonographic guidance. On the 5-month follow-up CT scan, there was no evidence of residual adrenal tumors and both renal lesions lacked contrast enhancement. No complications occurred during the post-operative recovery., Conclusions: Multiple organ-ablative laparoscopic procedures may be performed in a single sitting. Laparoscopic partial adrenalectomy is an effective technique in patients with bilateral tumors or a familial syndrome predisposing to multiple adrenal tumors. Further study of renal RFA is required to assess the long-term durability of the procedure.

Purpose: Minimally invasive surgical approaches to renal and adrenal tumors have gained increasing use. The addition of robotic assistance and mechanical devices has decreased the number of assistants required for these often long cases. We describe an articulating arm retractor holder to aid in liver and spleen retraction during laparoscopic surgery., Materials and Methods: The articulating retractor holder consists of 4 components, including a base rod, flexible extension arm, stainless steel precision clamp and table attachment. During laparoscopy the abdomen is visualized using standard approaches. The articulating retractor holder is clamped to the table via the base rod and brought into the surgical field using sterile technique. A retractor is placed intracorporeally to elevate the liver or spleen and the handle is secured in place using the precision clamp., Results: The articulating retractor holder was used in all right and approximately 50% of left laparoscopic cases. Adequate visualization was obtained in all patients. There were no device failures or retractor related complications., Conclusions: The articulating retractor holder is a useful tool to aid in laparoscopic retraction that should be added to the urologist armamentarium.

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 calculated from the time of nephrectomy to the time of death or last clinical followup. If patients received IL-2 therapy, the response to treatment was recorded. Mean survival and response rate for IL-2 were compared among patients in 3 separate analyses. Patients without preoperatively detected lymphadenopathy were compared with those with at least 1 cm.3 retroperitoneal lymphadenopathy. Also, the patients who had detectable lymphadenopathy were divided into subgroups consisting of all resected, incompletely resected, unresectable and unknown if all disease was resected. Each subgroup was compared with patients without detectable preoperative lymphadenopathy. Patients with less than were compared to those with greater than 50 cm.3 retroperitoneal lymphadenopathy. Patients undergoing extrarenal resection at nephrectomy (complex surgery) due to direct invasion of the tumor into another intra-abdominal organ were compared with those undergoing radical nephrectomy alone, regardless of lymph node status. Statistical analysis was done with the Mantel-Cox test for comparison of survival on Kaplan-Meier curves and with Fisher's exact test for response rates for IL-2., Results: A total of 154 patients with metastatic renal cell carcinoma underwent cytoreductive nephrectomy as preparation for IL-2 based regimens. There were 82 patients with metastatic renal cell carcinoma and no preoperative retroperitoneal lymphadenopathy who survived longer (median 14.7 months) than the 72 with lymphadenopathy (median 8.5, p = 0.0004). Patients with incompletely resected, unresectable or an unknown volume resected had decreased survival compared to those with no retroperitoneal lymphadenopathy. A multivariate analysis of survival was performed evaluating the known prognostic indicators, performance status and tumor burden, as represented by the number of organs involved with metastases, and the new prognostic factor, lymphadenopathy. Lymphadenopathy was more closely associated with survival than performance status, and appeared to be a new prognostic variable. Patients with and without retroperitoneal lymphadenopathy at initial presentation had similar rates for treatment with IL-2 (54% for both groups). Of the 82 patients with no lymphadenopathy 11 (13%) had long-term survival greater than 5 years. Of the 6 complete responses to IL-2, 5 occurred in this group. Only 1 other patient with incompletely resected retroperitoneal lymphadenopathy survived longer than 5 years. No significant difference in survival was seen between patients who did or did not undergo complex surgery., Conclusions: Patients who presented with metastatic renal cancer and retroperitoneal lymphadenopathy had a shorter survival than those with no detectable retroperitoneal lymphadenopathy. It is warranted to continue to perform complex extrarenal resection during nephrectomy since no significant difference in the response rate for IL-2 or mean survival compared with those of patients undergoing nephrectomy alone is currently detectable.

This study examined the mechanisms linking different biochemical and clinical phenotypes of pheochromocytoma in multiple endocrine neoplasia type 2 (MEN 2) and von Hippel-Lindau (VHL) syndrome to underlying differences in the expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis, and of phenylethanolamine N-methyltransferase (PNMT), the enzyme that converts norepinephrine to epinephrine. Signs and symptoms of pheochromocytoma, plasma catecholamines and metanephrines, and tumor cell neurochemistry and expression of TH and PNMT were examined in 19 MEN 2 patients and 30 VHL patients with adrenal pheochromocytomas. MEN 2 patients were more symptomatic and had a higher incidence of hypertension (mainly paroxysmal) and higher plasma concentrations of metanephrines, but paradoxically lower total plasma concentrations of catecholamines, than VHL patients. MEN 2 patients all had elevated plasma concentrations of the epinephrine metabolite, metanephrine, whereas VHL patients showed specific increases in the norepinephrine metabolite, normetanephrine. The above differences in clinical presentation were largely explained by lower total tissue contents of catecholamines and expression of TH and negligible stores of epinephrine and expression of PNMT in pheochromocytomas from VHL than from MEN 2 patients. Thus, mutation-dependent differences in the expression of genes controlling catecholamine synthesis represent molecular mechanisms linking the underlying mutation to differences in clinical presentation of pheochromocytoma in patients with MEN 2 and the VHL syndrome.