Clinical utility of temozolomide in the treatment of malignant paraganglioma: a preliminary report.

We report on the efficacy and safety of short-term administration of temozolomide, an inhibitor of nucleoside incorporation, in a 60-year-old woman with widespread hepatic metastases from a malignant paraganglioma. Temozolomide was orally administered in daily doses of 250 mg on days 1 to 5 and repeated every 28 days for five cycles. Clinical improvement was immediate and associated with weight gain, and further reduction in blood pressure without ortho-static intolerance. In addition, abnormal hepatic function was normalized and catecholamine production was significantly reduced. Except for mild nausea, adverse effects were virtually absent. Bone marrow function, renal function, and serum electrolytes remained normal; hemoglobin remained above 9 g/dl through treatment. The platelet count decreased but not to clinically meaningful levels. These responses allowed for a surgical debulking procedure to be performed safely without complications. The results suggest that temozolomide may be useful in presurgical preparation of patients with pheochromocytoma especially in those with widespread metastatic disease and poor physical condition. However, the present findings need confirmation in a larger study and the role of temozolomide in the long-term treatment of malignant paraganglioma/pheochromocytoma remains to be established.

Medical management of primary hyperaldosteronism.

Most forms of primary aldosteronism are surgically correctable. However, when surgery is not appropriate, medical management is just as effective in correcting the pathophysiologic abnormalities due to aldosterone excess. A prerequisite for the rational medical management of primary aldosteronism is an understanding of the mechanisms that sustain hypertension. Primary aldosteronism can be associated with severe and resistant hypertension, and persistent hypervolemia is the primary reason for resistance to therapy. Patients with overriding comorbidities or strong preferences have been medically treated over the intermediate term of 5 to 7 years without evidence of escape or evidence of malignant transformation of adrenal adenomas.

Laparoscopic right adrenalectomy after liver transplantation.

To our knowledge, laparoscopic right adrenalectomy has not been previously reported after orthotopic liver transplantation. The aim of this report is to demonstrate the feasibility of the laparoscopic approach in this technically challenging situation, and to outline some considerations unique to this clinical setting.

Pheochromocytoma coexisting with renal artery lesions.

PURPOSE: Physiologically significant renal artery lesions in the presence of a pheochromocytoma comprise a confounding factor which may impact on the hypertension cure following excision of the pheochromocytoma. We present 10 cases of these dual lesions and review the literature on this entity. MATERIALS AND METHODS: From 1952 to 1999, 269 patients were diagnosed with pheochromocytoma at our institution. Hospital charts of these patients were reviewed retrospectively to identify those with coexisting renal artery stenosis. A Medline search was performed to review the available literature. RESULTS: Of the 269 patients with pheochromocytoma 10 (3. 7%) had coexisting renal artery lesions, including renal artery stenosis in 8, renal artery aneurysm in 1 and postangiographic dissection occlusion in 1. Pheochromocytoma was adrenal in 8 cases and ectopic in 2. Of the patients 9 have been treated to date by adrenalectomy in 4, nephroadrenalectomy in 3, adrenalectomy plus lysis of renal artery adhesions in 1 and adrenalectomy plus renal autotransplantation with bench repair in 1. Both lesions were diagnosed preoperatively in 9 cases and a hypovascular adrenal lesion was missed preoperatively in 1. A review of literature revealed a total of 87 cases of coexisting pheochromocytoma and renal artery lesions. CONCLUSIONS: There are multiple mechanisms that can lead to renal artery stenosis and pheochromocytoma. A high index of suspicion is necessary to enable both entities to be diagnosed preoperatively and allow proper planning of surgical therapy. Incomplete diagnosis may lead to persistent hypertension postoperatively.

Laparoscopic adrenalectomy for large-volume (> or = 5 cm) adrenal masses.

BACKGROUND AND PURPOSE: Laparoscopic adrenalectomy has emerged as the standard of care at many centers for small surgical adrenal masses. However, the role of laparoscopic adrenalectomy in the treatment of large adrenal masses has not been specifically addressed. Our aim was to evaluate the outcome of laparoscopic v open adrenalectomy for large-volume (> or =5 cm) adrenal masses and to compare laparoscopic adrenalectomy for large- and small-volume (<5 cm) masses. PATIENTS AND METHODS: Data from 14 patients with large adrenal masses undergoing laparoscopic adrenalectomy between February 1998 and March 1999 (Group I) were retrospectively compared with 14 contemporary large-volume open adrenalectomies between December 1992 and May 1998 (Group II) and 45 small-volume laparoscopic adrenalectomies between July 1997 and November 1998 (Group III). RESULTS: In Group I and Group II, the mean surgical time (205 min v 216 min) and blood loss (400 mL v 584 mL) were similar. Although the mean adrenal size was also comparable (8 cm v 7.8 cm), the specimen weight of the en bloc adrenal gland and periadrenal fat was greater in Group I (168 g v 106 g). The hospital stay was shorter in Group I (2.4 days v 7.7 days). Minor complications occurred in 21.4% of Group I and 50% of Group II patients. On comparing Group I and Group III (laparoscopic <5 cm), Group I had larger specimen weight (168 g v 51.4 g), longer surgical time (205 min v 158 min), greater blood loss (400 mL v 113 mL), longer hospital stay (2.4 days v 1.5 days), a higher complication rate (21.4% v 8.9%), and a higher incidence of open surgical conversion (14.3% v 2.2%). Over a mean follow-up of 9.9 months, no local or port-site recurrences have been noted in Group I. CONCLUSIONS: Laparoscopic adrenalectomy for large-volume adrenal masses is technically feasible and seems to replicate open surgical oncologic principles of achieving a wide-margin, en bloc excision of the adrenal gland and periadrenal fat. Successful laparoscopic resection is not impacted by the large size of the adrenal mass per se but rather by the presence of local invasion and poorly defined tissue planes that may be encountered in adrenal malignancy. As such, laparoscopic adrenalectomy for large masses should be attempted only by experienced laparoscopic surgeons and then with a low threshold for open conversion.

Anesthetic aspects of laparoscopic and open adrenalectomy for pheochromocytoma.

OBJECTIVES: To compare the anesthetic aspects and intraoperative hemodynamic data and immediate postoperative outcomes in patients whose pheochromocytoma resection was performed either laparoscopically or by traditional open surgery. METHODS: Fourteen consecutive patients who underwent laparoscopic procedures (a single surgeon) were compared with 20 patients who underwent open surgery. The patients' records were reviewed for demographic information, preoperative medical history and therapy, intraoperative hemodynamic data, fluid balance, and immediate postoperative course. RESULTS: No differences between the highest intraoperative blood pressures and number of hypertensive episodes between the two groups were found. However, in laparoscopic patients, the intraoperative hypotension was less severe (mean lowest blood pressure 98/57 mm Hg versus 88/50 mm Hg, P = 0.05), and the hypotensive episodes were less frequent (median 0 versus 2, P = 0.005) and required fewer interventions with vasopressors (P = 0.02). Extreme high and extreme low heart rates did not differ between the two groups. The estimated blood loss was lower in the laparoscopic group (P = 0.0001), but the total intraoperative fluid requirement and operative times were similar in the two groups. Patients in the laparoscopic group resumed walking earlier (median 1.5 versus 4 days, P = 0.002) and resumed oral food intake sooner (median 1 versus 3.5 days, P = 0.0001). The median duration of hospitalization in patients who underwent laparoscopic and open adrenalectomy was 3 and 7.5 days, respectively (P = 0.001). CONCLUSIONS: Intraoperative hemodynamic values during laparoscopic adrenalectomy for pheochromocytoma were comparable to those of traditional open surgery, but the patients who underwent the laparoscopic procedure had a faster postoperative recovery.

Outpatient adrenalectomy.

PURPOSE: To our knowledge we report the initial experience with outpatient, same day laparoscopic adrenalectomy. MATERIALS AND METHODS: Nine select patients were entered into our ambulatory adrenalectomy protocol. Each patient fulfilled certain preoperative and postoperative inclusion criteria, including informed consent, age 70 years or older, body mass index 40 or less, adrenal tumor less than 5 cm., no pheochromocytoma, uncomplicated laparoscopic surgery that was completed by 12 p.m., perioperative hemodynamic stability and pain control by oral analgesics. RESULTS: All 9 patients successfully underwent outpatient laparoscopic adrenalectomy. Average patient age was 53 years and average adrenal tumor size was 2 cm. Mean surgical time was 2.3 hours and mean blood loss was 53 ml. The diagnosis was aldosteroma in 7 cases, enlarging adenoma in 1 and myelolipoma in 1. Average postoperative hospital stay was 416 minutes (range 300 to 570). Postoperative analgesia comprised 6 mg. morphine sulfate and 32 mg. ketorolac. The only complication was a local abscess requiring delayed drainage at 2 weeks. No other patient was rehospitalized for any reason. A followup questionnaire survey revealed excellent patient satisfaction. CONCLUSIONS: To our knowledge we report the initial series of outpatient laparoscopic excision of a solid organ, the adrenal gland. Ambulatory adrenalectomy is feasible and safe, and results in high patient satisfaction. However, ambulatory adrenalectomy should be restricted to highly select patients and performed by minimally invasive surgeons who have considerable experience with laparoscopic adrenal surgery.

Financial analysis of needlescopic versus open adrenalectomy.

PURPOSE: Needlescopic adrenalectomy, partially incorporating 2 mm. instrumentation, is currently our preferred technique for transperitoneal endoscopic adrenalectomy. Although this minimally invasive technique results in decreased morbidity and shorter hospital stay, to our knowledge financial implications vis-à-vis open adrenalectomy have not been elucidated. We retrospectively compared the costs of needlescopic adrenalectomy to traditional open adrenalectomy. MATERIALS AND METHODS: From September 1997 through March 1998, 15 patients underwent needlescopic adrenalectomy. Financial records of these patients were compared to those of 15 contemporary patients undergoing open adrenalectomy between January 1995 and May 1997. Adrenal pathology and tumor size were comparable between the 2 groups. Yearly costs were adjusted for inflation to 1998 dollars using a 4% annual rate. Needlescopic financial data are expressed as a ratio of open adrenalectomy costs, which are expressed as a unit of 1. RESULTS: Overall, needlescopic adrenalectomy resulted in a 17.9% decrease in total hospital costs compared to open adrenalectomy. While the needlescopic approach was associated with an 18.1% increase in intraoperative costs, postoperative costs were 63.4% lower. CONCLUSIONS: These data demonstrate that in addition to providing a shorter hospital stay, decreased morbidity and quicker recovery, needlescopic adrenalectomy also is 17.9% less expensive than open adrenalectomy.

Medical management of aldosterone-producing adenomas.

BACKGROUND: No data are available on the long-term medical management of aldosterone-producing adenomas. OBJECTIVE: To demonstrate the efficacy of medical management of aldosterone-producing adenomas in terms of blood pressure and serum potassium concentration and to discuss morbidity associated with medical management. DESIGN: Retrospective cohort study. SETTING: Large tertiary care referral center. PATIENTS: 24 patients with documented aldosterone-producing adenomas who were treated medically for at least 5 years. MEASUREMENTS: Aldosterone excretion rate, plasma renin activity, and size and location of adenomas (by computed tomography). Blood pressure and serum electrolytes were measured at the time of diagnosis and last follow-up. RESULTS: From the time of diagnosis to the time of last follow-up, systolic blood pressure decreased from 175 mm Hg to 129 mm Hg (95% CI for difference, 37.1 to 53.8 mm Hg) and diastolic blood pressure decreased from 106 mm Hg to 79 mm Hg (CI for difference, 20.8 to 33.9 mm Hg). Serum potassium concentration increased from 3.0 mmol/L to 4.3 mmol/L (CI for difference, 1.1 to 1.5 mmol/L). CONCLUSIONS: Medical management of aldosterone-producing adenomas is a viable option for controlling blood pressure and serum potassium concentration.

Successful outcomes in pheochromocytoma surgery in the modern era.

PURPOSE: We describe our experience with surgical management, complications and treatment outcome of histologically confirmed pheochromocytoma. MATERIALS AND METHODS: The records of 113 patients who underwent surgical excision of pheochromocytoma were reviewed and assessed for preoperative medical treatment, intraoperative findings, postoperative hospitalization and complications. RESULTS: There were no surgical mortalities. Average length of stay in the intensive care unit was 1.2 days. There were only 6 major cardiovascular complications all of which occurred in patients who received preoperative medications, including 5 with alpha blockade. Patients receiving no preoperative alpha blockade required an average of 956 cc less in total intraoperative fluids, which approached statistical significance, and 479 cc less fluids on postoperative day 1, which was statistically significant. CONCLUSIONS: Preoperative alpha-adrenergic blockade is not essential in pheochromocytoma patients. Calcium channel blockers are just as effective and safer when used as the primary mode of antihypertensive therapy. Surgery for pheochromocytoma is safe in the modern era.

Needlescopic adrenalectomy--the initial series: comparison with conventional laparoscopic adrenalectomy.

OBJECTIVES: To report the initial series of needlescopic transperitoneal adrenalectomy and to compare the results with a contemporary series of conventional transperitoneal laparoscopic adrenalectomy performed at the same institution. METHODS: Fifteen patients underwent needlescopic adrenalectomy over a 4-month period. Outcome data were retrospectively compared with 21 conventional laparoscopic adrenalectomies performed over the preceding 12-month period at the same institution. The needlescopic technique included three subcostal ports (two, 2 mm; one, 5 mm) and one umbilical port for ultimate specimen extraction (10/12 mm). The laparoscopic technique included four subcostal ports (all 10/12 mm). Endoscopic transperitoneal adrenalectomy was completed by the standard technique in both groups. RESULTS: Baseline demographics were comparable between the needlescopic (n = 15) and laparoscopic (n = 21) groups. The needlescopic group had a shorter surgical time (169 versus 220 minutes, P = 0.05), less blood loss (61 versus 183 mL, P = 0.002), and shorter hospital stay (1.1 versus 2.7 days, P < 0.001). Convalescence averaged 2.1 weeks in the needlescopic group and 3.1 weeks in the laparoscopic group (P < 0.001). No significant complications occurred in either group. One patient in the needlescopic group was converted to conventional laparoscopy because of marked obesity; hospital stay in this patient was 2 days. CONCLUSIONS: Reported herein is the initial series of needlescopic adrenalectomy. Compared with conventional laparoscopy, needlescopic adrenalectomy results in an overnight hospital stay, rapid recovery, and excellent cosmesis. However, prior experience with conventional laparoscopy is essential before embarking on needlescopic surgery.

Laparoscopic adrenalectomy: the preferred choice? A comparison to open adrenalectomy.

PURPOSE: We compare the effectiveness and efficiency of laparoscopic adrenalectomy to open surgical management of adrenal disorders. MATERIALS AND METHODS: A retrospective comparison was undertaken of 21 patients who underwent transperitoneal laparoscopic adrenalectomy between April 1996 and May 1997 with 17 patients who underwent open adrenalectomy between October 1994 and January 1996. Any patient suspected of having primary adrenal carcinoma and/or an adrenal lesion larger than 6 cm. was excluded from the study. RESULTS: Patient demographics were matched well. Mean laparoscopic surgical time was 79 minutes longer than for open surgery. After overcoming the learning curve, the surgical time decreased by 59 minutes in the last 10 laparoscopic adrenalectomies. All laparoscopic intraoperative complications were managed without the need for open surgical conversion. Postoperative characteristics demonstrated significant benefits in the laparoscopic group (p=0.001) with respect to days to return to full diet (1.7 versus 4.6), analgesic pain requirements and days of hospitalization (2.7 versus 6.2). CONCLUSIONS: Laparoscopic adrenalectomy offers significant postoperative benefits to patients with benign adrenal disease requiring surgical intervention. The surgical time is longer than that for open adrenalectomy but there was an encouraging reduction in time after overcoming the laparoscopic learning curve. Laparoscopic adrenalectomy is an excellent choice for tumors smaller than 6 cm. Its role for larger lesions and/or primary adrenal carcinoma is currently under investigation.

Technique of laparoscopic adrenalectomy.

Laparoscopic adrenalectomy by the transperitoneal route has been shown to be a safe and effective approach to select adrenal pathology. Although the specific indications will continue to be refined, it is clear that for adrenal masses of 6 cm or less, laparoscopy provides excellent access with little additional risk to the patient. In addition there appears to be an improved postoperative course when compared with open adrenalectomy. This latter point, however, requires careful prospective studies to confirm this impression objectively. The operative times are longer by the laparoscopic approach, but undoubtedly these times will decrease with increasing experience and improved laparoscopic instrumentation.

The role of nitric oxide in the regulation of aldosterone synthesis by adrenal glomerulosa cells.

The role of nitric oxide (NO) in the regulation of aldosterone synthesis in the adrenal glomerulosa is not known. In this study, we observed that liberators of NO such as S-nitroso-N-acetyl-penicillamine (SNAP), sodium nitroprusside (Snp) and spermine nonoate (SNO) could significantly inhibit angiotensin II (AII) and ACTH-induced aldosterone synthesis in isolated rat and cultured human adrenal glomerulosa cells. To evaluate more precisely whether glomerulosa cells express NO synthase, we performed immunoblotting experiments with antibodies specific for the endothelial type ecNO synthase as well as the neuronal NO synthase. This revealed the presence of the ecNO synthase in rat adrenal capsules, in normal and in adenomatous human adrenal glomerulosa tissue, as well as in freshly dispersed rat adrenal glomerulosa cells. Furthermore, on immunohistochemical analysis, rat adrenal glomerulosa cell sections showed strongly positive staining for ecNO synthase. These results suggest that NO may be an important negative modulator of adrenal glomerulosa steroidogenesis.

Renal pathology in patients with primary hyperaldosteronism secondary to an adrenal cortical adenoma.

OBJECTIVES: The cause of persistent hypertension following the removal of an aldosterone-producing adrenal adenoma is unknown. The purpose of this study was to determine whether this occurrence is due to existing renal histopathologic damage. METHODS: Thirty-two patients with primary hyperaldosteronism due to an aldosterone-secreting adrenal cortical adenoma underwent open renal biopsy at the time of unilateral adrenalectomy. Biopsy results were correlated with the duration and severity of hypertension before and after surgery. RESULTS: Nineteen patients were cured of their hypertension postoperatively, whereas 13 patients had persistent diastolic hypertension. Statistical analysis of these two groups revealed no difference when renal histopathologic variables, preoperative severity of hypertension, or preoperative duration of hypertension were compared. CONCLUSIONS: Persistent hypertension in these patients does not appear to be due to renal histopathologic changes; coexisting essential hypertension is a more likely cause.

Plasma volume and its regulatory factors in congestive heart failure after implantation of long-term left ventricular assist devices.

BACKGROUND: Congestive heart failure is associated with blood volume expansion caused by stimulation of the renin-aldosterone system and arginine vasopressin. The use of left ventricular assist devices as bridges to heart transplantation has improved the survival of patients during this critical period. In studying heart failure physiology on support devices, we hypothesized that improvement of cardiac function by a left ventricular assist device is associated with normalization of volume load secondary to normalization of its regulatory substances. METHODS AND RESULTS: We studied 15 patients (13 men, 2 women: age 51 +/- 8 years) with end-stage heart failure who were cardiac transplant candidates eligible for HeartMate implantation. We measured plasma volume and plasma levels of atrial natriuretic peptide, aldosterone, renin, and arginine vasopressin sequentially before HeartMate implantation (baseline), after HeartMate implantation (weeks 4 and 8), and after transplantation. Baseline plasma volume was 123 +/- 20% of normal; it was 122 +/- 22% at week 4 and decreased to 115 +/- 14% at week 8. Atrial natriuretic peptide was 359 +/- 380 pg/mL at baseline, 245 +/- 175 pg/mL at week 4, and 151 +/- 66 pg/mL at week 8. Plasma aldosterone fell from 68 +/- 59 ng/dL at baseline to 17 +/- 16 ng/dL at week 4 (P < .05 versus baseline) and was 32 +/- 50 ng/dL at week 8. Plasma renin activity decreased from 80 +/- 88 ng/dL at baseline to 11 +/- 12 ng/dL at week 4 and was 16 +/- 38 ng/dL at week 8 (both P < .05 versus baseline). Arginine vasopressin fell from 5.0 +/- 4.8 fmol/mL at baseline to 1.1 +/- 0.7 fmol/mL at week 4 and 1.2+/-0.8 fmol/mL at week 8 (both P < .05 versus baseline). CONCLUSIONS: The reduction of plasma renin activity, plasma aldosterone, and arginine vasopressin occurred earlier than the reduction of plasma volume and atrial natriuretic peptide after HeartMate implantation, possibly because of decreased pulmonary congestion and improved renal perfusion. The reduction of atrial natriuretic peptide cannot be responsible for the lack of adequate decrease of plasma volume; its reduction can be taken as a marker of improved cardiac pump function and decreased atrial stretch.

Malignant pheochromocytoma of the anterior mediastinum: PET findings with [18F]FDG and 82Rb.

A case of a malignant pheochromocytoma arising from the anterior mediastinum is presented. We report the use of positron emission tomography with 82Rb and [18F]fluorodeoxyglucose to successfully image this neoplasm.

Production, characterization, and expression of neuropeptide Y by human pheochromocytoma.

Neuropeptide Y (NPY) levels are increased in plasma and tumors of patients with pheochromocytoma. The present study was designed to evaluate plasma and tissue NPY levels simultaneously as well as to study its release and expression in patients with either adrenal or extraadrenal pheochromocytomas. Plasma NPY levels were higher (P < 0.01) in patients with adrenal tumors than in matched normal subjects and patients with extraadrenal tumors. NPY levels were also higher (P < 0.05) in adrenal than in extraadrenal tumors. Bioactive NPY (1-36) was the predominant form in plasma and tumors of patients with adrenal pheochromocytomas. In contrast, patients with extraadrenal pheochromocytomas had an abundance of NPY fragments. NPY mRNA was abundant in 11 of 13 adrenal tumors but in only 1 of 6 extraadrenal tumors. Moreover, NPY was coreleased with NE with manipulation of adrenal but not extraadrenal tumors. These findings indicate that increased NPY gene expression in adrenal pheochromocytomas accounts for the greater biosynthesis and storage of NPY in these tumors and that increased release of NPY results in elevated plasma NPY. Factors regulating NPY gene expression in pheochromocytoma and the role of NPY in the clinical manifestations of the disease remain to be elucidated.