THE PRACTICE of abdominal surgery was dramatically

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1 X/98/$03.00/0 Vol. 83, No. 9 Journal of Clinical Endocrinology and Metabolism Printed in U.S.A. Copyright 1998 by The Endocrine Society THERAPEUTIC CONTROVERSY The Role of Laparoscopic Surgery in Adrenal Disease* SAMUEL A. WELLS, DEBORAH P. MERKE, GORDON B. CUTLER, JR., JEFFREY A. NORTON, AND ANDRÉ LACROIX Therapeutic Controversies are an occasional feature of The Journal of Clinical Endocrinology and Metabolism. They present the opposing views of invited contributors on a topic. All reprints must include the complete Therapeutic Controversy, so that each section can be read in context. The Role of Laparoscopic Surgery in Adrenal Disease Samuel A. Wells, Jr. American College of Surgeons Chicago, Illinois THE PRACTICE of abdominal surgery was dramatically changed in 1987 when the technique of laparoscopic cholecystectomy was reported by Dubois and associates (1). The procedure was rapidly and widely adapted in Europe, the Americas, and Asia and quickly becoming the standard method of removing the diseased gall bladder. Over the last decade minimally invasive operations have been employed in the management of many surgical disorders, particularly in the abdominal and thoracic cavities and the retroperitoneum (2 4). With the initiation of each new laparoscopic technique there have been predictable cycles characterized by an introductory phase, where the surgical technique is perfected (virtually always associated with a learning curve), a definition phase with exploration of technical variations and clarification of the operative indications, and an educational phase, where the new technique is taught to house officers and surgical colleagues. This phase sequence is somewhat flexible, and there is often much overlap during the development, refinement, and maturation of a given procedure. Unfortunately, with the introduction of each new laparoscopic procedure there have been no prospective randomized controlled trials comparing the new technique to the standard open technique. Such comparative analyses were precluded by the clear demonstration, initially with laparoscopic cholecystectomy, that the minimally invasive procedures had advantages such as shorter hospital lengths of stay, less postoperative pain, and more rapid convalescence and return to work. Furthermore, the patients, the hospitals, the employers, and the health care providers found the minimally invasive techniques preferable to the standard operative procedures. There are no long-term reports of experience with any of the established laparoscopic procedures. Accepted May 19, * Address all correspondence regarding these controversies and requests for reprints to: Dr. Samuel A. Wells, Jr., American College of Surgeons, 633 N. Saint Claire Street, Chicago, Illinois In 1992 Gagner and associates (5) reported the first case of laparoscopic adrenalectomy (LA) in a patient with Cushing s syndrome due to an adrenocortical adenoma. The technique proved highly attractive to clinical endocrinologists, and within a short period of time several medical centers reported their clinical series of patients treated by this procedure (6 8). Currently, the technique has gained wide acceptance among endocrine surgeons as the procedure of choice for the resection of most adrenal tumors. However, there are some controversial issues among the experts, as demonstrated in this Round Table. We will review the most significant issues about LA and focus especially on the controversies evidenced in the current presentations. The technique of laparoscopic adrenalectomy: Even though there have been no prospective randomized trials comparing LA to open adrenalectomy (OA), there have been retrospective comparative evaluations. Thompson and associates (9) performed a matched case-control study comparing 50 patients having open adrenalectomy to 56 patients having adrenalectomy through a posterior approach. They found that LA, compared to OA, was significantly associated with shorter hospital stay, less postoperative narcotic use, more rapid return to normal activity, increased patient satisfaction, and less late morbidity. However, the laparoscopic procedure was associated, with longer operating room time and higher cost. Similar results have been reported by Prinz (10) and by Brunt et al (11), who found that LA had distinct advantages compared to OA. It has been noted by several authors that a posterior retroperitoneal LA is preferable to an anterior LA, especially in patients who have either bilateral adrenal tumors, prior to extensive abdominal procedures with resultant adhesions and scar tissue formation, or pre-existing cardiopulmonary disease (12 14). Posterior LA is not indicated in patients with large adrenal tumors. In laparoscopic adrenalectomy one sacrifices the tactile sense and must manipulate the fragile adrenal gland with instruments in a two-dimensional plane. This is a significant deficit for two reasons: 1) the adrenal gland is small and flat, and its true extent is often difficult to define, even under direct observation; 2) the adrenal gland is vascular and friable, and there is risk of damaging its capsule and the pa- 3041

2 3042 THERAPEUTIC CONTROVERSY JCE&M 1998 Vol 83 No 9 renchyma during instrumentation. This is a particular problem in patients with Cushing s disease, where adrenal cortical cells spilt at surgery may increase to nodules under constant endogenous ACTH stimulation. In the present report of Lacroix (in this discussion), 3 of their 100 patients had incomplete resection of adrenal glands, as evidenced by ACTH stimulation test in 2 patients and the recognition of a 1 mm remnant of adrenal cortex left in situ in the third. Only 1 of these patients had a functioning tumor and is at risk for recurrent disease. Ushiyama and associates (15) reported a case of adrenocortical carcinoma with recurrence 19 months after LA. At the original operation for Cushing s syndrome a 5-cm left adrenal cortical tumor was resected. The histologically benign tumor was removed intact. The patient developed recurrent symptoms and at reoperation had multiple metastases both in the previous resection bed and at other intraabdominal sites. It should be noted that there have been reports of tumor recurrence at abdominal port sites in patients treated laparoscopically for colon carcinoma or gall bladder carcinoma (16, 17). Also, one must also take great care not to damage the vasculature to the kidney, especially on the left side where adrenal tumors often overlie the renal hilus. The development of postoperative hypertension is often the manifestation of an ischemic injury to the kidney occurring at the time of adrenalectomy. The indications for laparoscopic adrenalectomy Laparascopic adrenalectomy was first performed in patients with benign tumors of the adrenal cortex, but it soon was used to resect pheochromocytomas. At present the procedure is used to resect a broad range of benign adrenal tumors and even the adrenal glands in some patients with nontumorous conditions, such as congenital adrenal hyperplasia (see Merke and Cutler in this Controversy). Laparascopic adrenalectomy is contraindicated for malignant adrenal lesions because the tumors are often large, technically difficult to remove, and vulnerable to breakage or incomplete resection. Also the tumors may invade adjacent organs or regional lymph nodes, which also require resection. It is of interest that Merke and Cutler, in the present report, cite the use of LA in three infants with neuroblastomas found during a mass screening program in Japan (18, 19). Perhaps the generally good prognosis of neuroblastomas in this age group precludes this rule, but it will be very interesting to learn of the long-term evaluation of these patients. Size is the best indication that an adrenal tumor is malignant, a matter that was controversial among the Round Table participants. Lacroix and associates do not consider size of major importance and report laparoscopic resection of adrenal tumors as large as 10 or 13 cm. It is of interest that in their series, Lacroix refers to two patients with nonfunctioning adrenal tumors that met histological criteria for malignancy and two of four patients with cortisol secreting adenomas, who were later shown to have metastatic adrenal cortical carcinoma. There is no mention of the size of these four lesions. It has been reported by Page and associates (19) and Ross and associates (20) that tumors larger than 6 cm in diameter or weighing more than 100 g are highly likely to be malignant. Norton (in this Controversy) cites their work in recommending that such large lesions should be resected by an open technique. There is no reliable preoperative radiographic or biochemical test that indicates the biological nature of an adrenal tumor; even on histological examination it is very difficult, if not impossible, to tell if the neoplasm is cancerous. Often this only becomes evident when tumor spread is demonstrated beyond the confines of the adrenal capsule. The matter of resecting incidentally found adrenal tumors is also controversial. Lacroix and associates reported the removal of 15 nonfunctioning adrenal adenomas and 2 myelolipomas. Relatively clear guidelines have been developed for the management of patients who incidentally are found to have adrenal tumors (21 23). If these tumors have no endocrine function, are less than 6 cm in size, and do not enlarge with time, they can be left alone as virtually all such lesions are benign and harmless. The availability of a technique for easily removing these lesions is not necessarily an indication for doing so. Laparascopic adrenalectomy has clear applicability in the management of patients with benign adrenal neoplasms. Even though LA has distinct advantages compared with OA, much thought needs to be given to the indications for the application of the technique. There is still controversy in certain areas that will only be clarified as the definition phase matures and there is long term evaluation of large numbers of patients who have been treated by this technique. References 1. Dubois F, Icard P, Berthelot G, Levard H Coelioscopic cholecystectomy: preliminary report of 36 cases. Ann Surg. 211: Cuschieri A The spectrum of laparoscopic surgery. World J Surg. 16: Soper NL, Brunt LM, Kerbl K Laparoscopic general surgery. N Engl J Med. 6: Pellegrini C, Wetter LA, Patti M, et al Thoracoscopic esophagomyotomy: initial experience with a new approach for the treatment of achalasia. Ann Surg. 216: Gagner M, Lacroix A, Bolte E Laparoscopic adrenalectomy in Cushing s syndrome and pheochromocytoma. N Engl J Med. 327: Takeda M, Go H, Imai T, Nishiyama T, Morishita H Laparoscopic adrenalectomy for primary aldosteronism: report of initial ten cases. Surgery. 5: Fernandez-Cruz L, saenz A, Benarroch G, Astudillo E, Taura P, Sabater L Laparoscopic unilateral and bilateral adrenalectomy for Cushing s Syndrome transperitoneal and retroperitoneal approaches. Ann Surg. 6: Gagner M, Pomp A, Heniford BT, Pharand D, Lacroix A Laparoscopic adrenalectomy lessons learned from 100 consecutive procedures. Ann Surg. 3: Thompson GB, Grant CS, van Heerden J, et al Laparoscopic versus open posterior adrenalectomy: a case-control study of 100 patients. Surg. 6: Prinz RA A comparison of laparoscopic and open adrenalectomies. Arch Surg. 130: Brunt LM, Doherty GM, Norton JA, Soper NJ, Quasebarth MA, Moley JF Laparoscopic adrenalectomy compared to open adrenalectomy for benign adrenal neoplasms. J Am Coll Surg. 183: Walz MK, Peitgen K, Hoermann R, Giebler RM, Mann K, Eigler FW Posterior regroperitoneoscopy as a new minimally invasive approach for adrenalectomy: results of 30 adrenalectomies in 27 patients. Word J Surg. 20: Duh QY, Siperstein AE, Clark OH, Schecter WP, Horn JK, Harrison MR, Hunt TK, Way LW Laparoscopic adrenalectomy comparison of the lateral and posterior approaches. Arch Surg. 131: Bonjer HJ, Lange JF, Kazemier G, deherder WW, Steyerberg EW, Bruining HA Comparison of three techniques for adrenalectomy. Br J Surg. 84: Ushiyama T, Suzuki K, Kageyama S, Fujita K, Oki Y, Yoshimi T A case

3 THERAPEUTIC CONTROVERSY 3043 of Cushing s Syndrome due to adrenocortical carcinoma with recurrence 19 months after laparoscopic adrenalectomy. J Urol. 157: Ramos JM, Gupta S, Anthone GJ, Ortega AE, Simons AJ, Beart RW, Jr Laparoscopy and colon cancer Is the port site at risk? A preliminary report. Arch Surg. 129: Clair DG, Lautz DB, Brooks DC Rapid development of umbilical metastases after laparoscopic cholecystectomy for unsuspected gallbladder carcinoma. Surgery 113: Yamamoto H, Yoshida M, Sera Y Laparoscopic surgery for neuroblastoma identified by mas screening. J Pediatr Surg. 31: Ross NS, Aron DC Hormonal evaluation of a patient with an incidentally discovered adrenal mass. N Engl J Med. 323: Page DL, DeLellis RA, Hough AJ. Tumors of the adrenal. In: Atlas of Tumor Pathology, Washington: AFIP Angeli A, Osella G, Ali A, Terzols M Adrenal incidentaloma An overview of clinical and epidemiological data for the National Italian Study Group. Hor Res. 47: Mantero F, Masini AM, Opocher G, Giovagnetti M, Arnoldi G Adrenal Incidentoloma An overview of horomonal data from the National Italian Study Group. Hor Res. 47: Kasperlikzaluska AA, Roslonowska E, Slowinskasrzednicka J, Migdalska B, Jeske W, Makowska A, Snochowska H Incidentally discovered adrenal mass (incidentaloma) investigation and management of 208 patients. Clin Endocrin. 46: Five-Year Experience with Laparoscopic Adrenalectomy at Hôtel-Dieu in Montréal: Endocrinologist s Perspective André Lacroix Centre Hospitalier de l Université de Montréal (CHUM) Montréal, Québec, Canada, H2W 1T8 THE WIDESPREAD use of high quality noninvasive adrenal imaging with ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) has greatly increased the detection of adrenal masses during the last 15 years. In addition, developments in hormonal investigations, in nuclear medicine scanning with 131 I-6-iodomethyl-19- norcholesterol (NP-59) or 131 I-metaiodobenzylguanidine (MIBG), and in fine needle aspiration (FNA) biopsies have facilitated the diagnosis and etiology of the adrenal masses (1). It has now become easier to identify the preclinical (1, 2) or overt hormone secreting adrenal tumors as well as the larger or progressing nonfunctional adrenal masses for which there is an indication of surgical removal. Surgery remains the basis of treatment, and major technical progress has also occurred in this field. Already available for years in gynecology, endoscopic surgery began enthusiastically with laparoscopic cholecystectomy in 1987 and is now widely practiced in general surgery and urology for the removal of several abdominal and pelvic organs. The growth of minimally invasive surgical approaches was stimulated by the advent of better instrumentation for dissection and hemostasis, improved video imaging, and the potential reduction in pain, duration of hospitalization, and cost of the procedures. Laparoscopic adrenalectomy at Hôtel-Dieu, Retroperitoneal exploration and laparoscopic nephrectomy were first performed in 1991 (3). A year later, Michel Gagner at Hôtel-Dieu hospital in Montréal successfully removed adrenals through the laparoscopic lateral transperitoneal approach in three patients (4). His first attempts for laparoscopic adrenalectomies in humans were preceeded by extensive experience with advanced laparoscopic abdominal surgery in humans and by experimental laparoscopic adrenalectomy in a porcine animal model. Several discussions between the endocrinology, anesthesiology, and surgery teams and our presence during experimental laparoscopic adrenalectomy in the porcine model preceeded the agreement to propose this approach to our first patient. A 52-yrold woman with Cushing s syndrome secondary to a left 3 cm adrenal adenoma developed an acute perforated diverticulitis that required a colostomy performed by laparoscopy by Dr. Gagner; the patient was treated with ketoconazole to control the hypercortisolism during the following 3 months. She agreed to undergo the first attempt at a laparoscopic adrenalectomy, which was successfully performed at the same time as the closure of the colostomy. Shortly thereafter, a bilateral adrenalectomy was performed in a 38-yr-old male patient with Cushing s disease that persisted after two pituitary surgeries and radiotherapy. I was present in the operating room during the entire procedure and was quite impressed not only by the technical skills of the surgeon, but mainly by the fact that the magnification of the anatomical structures through the laparoscope appeared to facilitate the identification and dissection of the various structures. Based on these two initial successful approaches, the medical, surgical, and anesthesiology teams agreed to use the same laparoscopic approach in a 60-yr-old male patient who presented with a 3.5 cm right pheochromocytoma; following medical preparation, the laparoscopic removal of the pheochromocytoma was performed without any complications. The transperitoneal lateral approach, developed and used in this center, is described in detail elsewhere (5, 6). From April 1992 to November 1996, a total of 100 adrenal explorations and resections were performed in 88 patients by laparoscopy by a team led by Michel Gagner, initially at Hôtel-Dieu hospital in Montreal until June 1995 (63 adrenalectomies), and then at the Cleveland Clinic Foundation (7, 8). The current surgical team in our center (Drs. Alfons Pomp, Gail Breton, and Daniel Pharand) have performed an additional 22 adrenalectomies since June 1995, for a total experience of 85 adrenalectomies in 74 patients at Hôtel-Dieu. The indications for the adrenalectomies included 25 (number of adrenals) pheochromocytomas, 17 adrenal Cushing s syndrome, 15 nonfunctioning adenomas, 13 aldosteronomas, 6 Cushing s disease, 3 macronodular adrenal hyperplasia, 2 ectopic ACTH syndrome, 2 metastasis, and 2 myelolipomas. Bilateral adrenalectomies were performed in 6 patients with bilateral pheochromocytomas, in 3 patients with persistent Cushing s disease, in 1 patient with an ACTH-producing pancreatic carcinoid tumor, and 1 patient with bilateral macronodular adrenal hyperplasia and vasopressin-dependent Cushing s syndrome (9); another patient with ectopic adrenal -adrenergic receptors, Cushing s syndrome, and bilateral macronodular adrenal hyperplasia underwent only a left adrenalectomy (203 gm), as his hypercortisolism was controlled by propranolol (10). Two of the nonfunctional tumors met pathology criteria of adrenal carcinoma without relapse to date; another was a medullary cyst, while one was a retroperitoneal sarcoma mimicking an adrenal mass, and others were corticoadrenal adenomas. In 4 cases of cortisolproducing adenomas, the patients presented with a preclinical syndrome (2), while the other cases had overt Cushing s syndrome; 2 of these cases eventually proved to be adreno-

4 3044 THERAPEUTIC CONTROVERSY JCE&M 1998 Vol 83 No 9 cortical carcinomas as they developed metastasis. In 2 cases operated for isolated lung cancer metastasis, dissection was difficult because of perirenal fat invasion. For the first 68 adrenalectomies, the overall mean operation time (anesthesia and surgery) was 2.1 h, with the right side requiring more time, an average of 138 min, compared with 102 min for the left side (7); this difference in operation time became negligible in recent cases (8). The time for bilateral adrenalectomies averaged 318 min. The mean diameter of the lesions removed was 4.1 cm (1 14 cm). Overall, the early mean postoperative stay was 3 days, with a range of 2 19 days (7). The mean number of postoperative narcotic injections was 5.5. Postoperative complications included 3 anemias not requiring transfusions, 2 wound hematomas, 2 exacerbations of renovascular hypertension without any evidence of renal vascular damage during the surgery, 2 urinary tract infections, 1 deep vein phlebitis with pulmonary embolus, 1 pulmonary edema, 1 subdural hematoma after a fall secondary to postural hypotension after removal of a pheochromocytoma, 1 cholecystitis, 1 colonic pseudo-obstruction, and 1 wound infection. Complete resection was performed in all but three patients. In the first patient undergoing bilateral adrenalectomy for refractory Cushing s disease, a small portion of the inferior left adrenal was not resected; this was not detectable by repeat CT or iodocholesterol scans, but low levels of cortisol were slightly increased by ACTH stimulation (20 50 nmol/l), and this has not progressed during 5 yr of followup. One patient who had previously undergone a left radical nephrectomy, including left adrenalectomy for renal cell carcinoma, underwent a right laparoscopic adrenalectomy following the appearance of a 4 cm adrenal lesion that was diagnosed as a nonsecreting cortical adenoma; resection of the right gland was later shown to be incomplete by a short ACTH stimulation test and by the limited requirement of only 10 mg of hydrocortisone in the morning and no mineralocorticoid replacement. There was no evidence of functional left adrenal on iodocholesterol scan, and there has been no evidence of progression of the residual portion of the right adrenal on CT scan. In one patient operated for a right medial nonfunctional adenoma, a small 1 mm rim of partially intrahepatic normal adrenal was left in place and has not progressed since. Conversion to open surgery was necessary in three patients including an early patient who had a 15-cm angiomyelolipoma where vessels could not be clipped securely. In another patient believed to have a nonfunctional left adenoma, a retroperitoneal sarcoma originating from the posterior retroperitoneal muscles was identified at laparoscopy, which was converted to open surgery to perform an en bloc resection. During the removal of a right nonfunctional adenoma, an adrenal vein bleeding necessitated conversion to open surgery. Re-operations during the same admission were required in two patients and were performed by laparoscopy. One patient with asymptomatic gallstones developed acute cholecystitis 4 days post-adrenalectomy and underwent a cholecystectomy. A patient receiving anticoagulation for a mitral valve prosthesis required a laparoscopic evacuation of a retroperitoneal hematoma. Pheochromocytomas We performed 25 laparoscopic adrenalectomies on 19 patients with pheochromocytomas. Pheochromocytomas were unilateral in 13 patients and bilateral in 6 others. There were 5 multiple eudocrine neoplasia (MEN) 2 A patients and 2 MEN 2 B patients, 5 of whom underwent bilateral surgery; one patient with Von-Hippel-Lindau syndrome had a unilateral right pheochromocytoma removed. In the two MEN 2 B patients, unsuspected pheochromocytoma metastases were identified and removed at surgery; in both cases, a single small ( 2 mm) superficial liver capsule metastasis was present, and in one case, a3cmlarge metastatic node between the aorta and vena cava was resected; there is no evidence of recurrence of metastatic pheochromocytoma after 3 and 4 yr of follow-up. Seventeen patients received alpha-blocker preparation (mostly prazocin) and volume expansion in the preoperative period. The average tumor size was larger in pheochromocytomas (6.3 cm) compared with other tumors (3.5 cm). Operating time was longer in pheochromocytomas, on average 3.8 h in unilateral adrenalectomy, and 6.3 h in bilateral cases. Elevated blood pressure, with systolic over 200 mmhg or diastolic over 100 mmhg occurred in 11 patients and was well-controlled with various iv antihypertensive agents. Hypotension (systolic BP 80 mmhg) occurred after venous clamping in 3 bilateral and 7 unilateral cases and was corrected easily with volume expansion. Major complications included a megacolon requiring endoscopic decompression in a woman with MEN 2 B, alimentary tract ganglioneuromatosis, and a history of Ogilvy syndrome. Patients left the hospital on average 8.4 days after the operation. In the patients with uncomplicated courses, the average postoperative stay was 5.7 days. Of the four patients who remained hypertensive in follow-up, two required only monotherapy to control hypertension. One other patient with diffuse atherosclerotic disease, developed hypertension 8 months after right adrenalectomy, secondary to a left renal artery stenosis. In another patient with MEN 2 A and bilateral silent pheochromocytomas, severe hypertension occurred 2 3 weeks after bilateral laparoscopic adrenalectomy; investigation revealed anomalies in both renal arteries, with a stenosis in a polar renal branch on one side with a renal segmental perfusion deficit and an aneurysm of another renal arterial branch on the opposite side compatible with fibrous dysplasia. There was no evidence of inadvertently placed surgical clips on the renal arteries; the hypertension was easily controlled with -blockers. Should every patient requiring adrenalectomy be referred to a laparoscopic surgeon? Since the initial reports (4, 11), several other authors worldwide have published case reports of their experiences with a small series of patients using different laparoscopic approaches to treat various adrenal pathologies (partial review in ref. 7). The results of laparoscopic adrenalectomy should be compared with those of open surgery; there are no large prospective randomized trials that have been published to date comparing both approaches. Historical comparisons with standard open procedures (12 16) have indicated longer operative time for laparoscopic vs. open surgery, sim-

5 THERAPEUTIC CONTROVERSY 3045 ilar operative complication rates, earlier mobilization and oral feeding, shorter duration of hospitalization, and decreased requirement of pain medication in the laparoscopic approach. This has also been our experience; the patients indicate a high degree of satisfaction, and we have not seen patients with long-term postoperative pain, which was frequent in the previously used open posterior approach that included rib removal. In the hands of experienced surgeons, the procedure can be performed in an acceptable amount of time and can be used for a range of disorders affecting the adrenal glands; the morbidity remains as significant as open surgery. The need to convert to open procedure has been low to date. In initial editorials and reactions to adrenal laparoscopic surgery, caution concerning the use of this approach in pheochromocytomas and in larger lesions was expressed (17). In general, the size of the lesion is not a limitation in our experience; our surgeons successfully removed adrenals as large as 13 cms 6 cms 3.5 cms, weighing 203 g in a case of macronodular adrenal hyperplasia (10) or 99 g in a 10 cm pheochromocytoma. The concern with size is more a debate regarding neoplastic potential than technical feasibility of laparoscopic surgery. Only surgeons with great experience should approach pheochromocytomas and lesions larger than 6 8 cm by laparoscopy; larger lesions should be approached by laparoscopy only if known to be benign, as in macronodular hyperplasia with Cushing s syndrome. Laparoscopic adrenalectomy can be used for patients with bilateral diseases including pheochromocytomas. A major advantage of the transperitoneal adrenalectomy by laparoscopy is that the abdominal cavity and the liver, in particular, can be explored with the aid of magnification via the laparoscope. In our pheochromocytoma patients, we discovered two small metastatic lesions to the liver that had not shown up in the radiological and isotopic preoperative evaluation, and we also performed a liver biopsy for a suspect lesion. Through the retroperitoneal approach, open or laparoscopic, these lesions would not have been accessible. Now that the minimally invasive procedure of laparoscopic adrenalectomy is becoming more available and the techniques and surgical times are improving with experience, it has been suggested that management of nonfunctional adrenal masses could be reconsidered. Most primary malignant tumors are over 6 cms in diameter (1), and the general consensus previously was to recommend removal of all adrenal lesions of this size or greater. For lesions between 3 to 6 cms, there is, however, no clear consensus, and several authors were reluctant to recommend surgery because of the morbidity involved. With laparoscopic adrenalectomy, lesions that are relatively small but suspect, i.e. growing on follow-up CT scans or suspect in MRI (high signal intensity) or iodocholesterol scans (low uptake), could be removed and definite diagnosis obtained earlier, leading to cure for primary cancers and rapid diagnosis with possible impact on management in metastatic lesions. In our view, taking into account that morbidity rates remain similar for both surgical approaches, we have not modified our indications for surgery, which include all functional lesions and nonfunctional lesions larger than 3 cms and growing or suspect lesions in patients without other major comorbidity. Clearly malignant lesions should be removed by open surgery. This raises a controversy in that it is not possible to fully distinguish, before surgery, and even before long-term follow-up, whether certain lesions are benign or malignant; however, in the presence of elevated DHEAS or estradiol levels, of a very heterogenous high-density radiological lesion, we would now favor open surgery. In lesions not clearly malignant, a laparoscopic exploration is performed and converted to an open surgery if there is local evidence of malignancy. The absolute contraindications for laparoscopic adrenalectomy include primary or metastatic invasive adrenal malignancies because extensive en bloc surgery and node dissection will be necessary. Patients with malignant pheochromocytoma, as suggested by MIBG or MRI scans, would be better approached by open surgery. A coagulopathy that could not be controlled before surgery would also constitute a contraindication. Previous surgery or trauma in the area may create dense adhesions that will make dissection more difficult. Diaphragmatic hernias on the left side will elevate the splenic flexure of the colon and make dissection more difficult. An adrenal mass larger than 10 cm will have many blood vessels connecting to the retroperitoneal space, will require long dissections, and should not be approached by laparoscopic route unless the surgeon has extensive experience with the procedure. Finally, the most important factor in the surgical management of adrenal lesions is the experience of the surgical and anesthesiology teams involved. There is a delicate balance for the surgeon between the desire to perform glamorous new techniques and providing the best possible care for the patient. The endocrinologist can be faced with the human dilemma of an inexperienced surgeon who wishes to introduce the use of this surgical technique in their center. There are now numerous opportunities for qualified and well-trained laparoscopic surgeons to attend high quality advanced courses in specific surgical techniques, such as laparoscopic adrenalectomy including the use of animal models. The first interventions should be conducted in the presence of an experienced colleague. Hospitals where the number of these procedures are limited on a yearly basis should not perform laparoscopic adrenalectomies. The qualified surgeon should not hesitate to convert to open surgery if there is any such indication during the procedure. As laparoscopic techniques become more widely known and applied, as in other areas of medicine, the indications for the conventional open approaches will gradually decrease and the laparoscopic management of adrenal masses will become the standard of treatment for benign adrenal lesions. Acknowledgments The author wishes to thank the Hôtel-Dieu adrenal surgical team, including Dr. Michel Gagner for his pioneering contribution to this field, and Drs. Alfons Pomp, Gail Breton, and Daniel Pharand for their continued enthusiastic collaboration. The contributions of Dr. John S. Weisnagel in reviewing our initial patient s data and of all the other members of the Endocrinology and Nephrology Divisions in patient s evaluation and care are also greatly appreciated. References 1. Kloos RT, Gross MD, Francis IR, Korobkin M, Shapiro B Incidentally discovered adrenal masses. Endocr Rev. 16:

6 3046 THERAPEUTIC CONTROVERSY JCE&M 1998 Vol 83 No 9 2. Lavoie H, Lacroix A Partially autonomous cortisol secretion by incidentally discovered adrenal adenomas. Trends Endocrinol Metab. 6: Clayman RV, Kavoussi LR, Soper NJ, et al Laparoscopic nephrectomy. N Engl J Med. 324: Gagner M, Lacroix A, Bolte E Laparoscopic adrenalectomy in Cushing s syndrome and pheochromocytoma. N Engl J Med. 327: Gagner M, Lacroix A, Prinz RA, et al Early experience with laparoscopic approach for adrenalectomy. Surgery. 114: Gagner M, Lacroix A, Bolte E, Pomp A Laparoscopic adrenalectomy. The importance of a flank approach in the lateral decubitus position. Surg Endosc. 8: Weisnagel J, Gagner M, Breton G, Pomp A, Pharand D, Lacroix A Laparoscopic adrenalectomy. The Endocrinologist. 6: Gagner M, Pomp A, Heniford BT, Pharand D, Lacroix A Laparoscopic adrenalectomy: lessons learned from 100 consecutive procedures. Ann Surg. 226: Lacroix A, Tremblay J, Touyz RM, et al Abnormal adrenal and vascular responses to vasopressin mediated by a V 1 -vasopressin receptor in a patient with adrenocorticotropin-independent macronodular adrenal hyperplasia, Cushing s syndrome, and orthostatic hypotension. J Clin Endocrinol Metab. 82: Lacroix A, Tremblay J, Rousseau G, Bouvier M, Hamet P Propranolol therapy for ectopic -adrenergic receptors in adrenal Cushing s syndrome. New Engl J Med. 337: Higashihara E, Tanaka Y, Horie S, et al A case report of laparoscopic adrenalectomy. Nippon Hinyokika Gakkai Zasshi. 83: Guazzoni G, Montorsi F, Bocciardi A, et al Transperitoneal laparoscopic versus open adrenalectomy for benign hyperfunctioning adrenal tumors: a comparative study. J Urol. 153: Prinz R A comparison of laparoscopic and open adrenalectomies. Arch Surg. 130: Naito S, Uozomi J, Ichimiya H, et al Laparoscopic adrenalectomy: comparison with open adrenalectomy. Eur Urol. 26: Brunt LM, Doherty GM, Norton JA, Soper NJ, Quaserbarth MA, Moley JF Laparoscopic adrenalectomy compared to open adrenalectomy for benign adrenal neoplasms. J Am Coll Surgeons. 183: Takeda M, Go H, Watanabe R, et al Retroperitoneal laparoscopic adrenalectomy for functioning adrenal tumors: comparison with conventional transperitoneal laparoscopic adrenalectomy. J Urol. 157: Pertsemlidis D Minimal-access versus open adrenalectomy. Surg Endosc. 9: The Role of Laparoscopic Surgery in Adrenal Disease: A Pediatric Perspective Deborah P. Merke The Developmental Endocrinology Branch National Institute of Child Health and Human Development Bethesda, Maryland Gordon B. Cutler, Jr. Eli Lilly and Company Lilly Research Laboratories Indianapolis, Indiana LAPAROSCOPIC surgery is rapidly becoming the preferred approach for a variety of surgical disorders in both children and adults. The potential benefits of the laparoscopic approach include shorter length of hospitalization, more rapid convalescence, reduced postoperative analgesia, and fewer postoperative complications (1). In adults, laparoscopic adrenalectomy was first performed in 1992 (2). Since then, several institutions have compared laparoscopic versus open adrenalectomy retrospectively in adult patients (3 6), confirming that laparoscopic adrenalectomy is a safe and effective surgical modality with reduced morbidity. Proper training and familiarity with laparoscopic equipment and technique are essential. Operative time diminishes progressively with repeated experience (3, 5, 6), with a significant decrease in operative time after 10 procedures (5). Overall, Commissioned Officer in the United States Public Health Service. laparoscopic adrenalectomy is replacing open adrenalectomy as the standard surgical approach for uncomplicated benign adrenal tumors in adult patients. Indications include aldosteronoma, adrenal-dependent Cushing s syndrome, pheochromocytoma, and an enlarging nonfunctional adrenal mass. Patients with tumors greater than 6 8 cm or those suspected of having adrenal carcinoma are typically not candidates for laparoscopy and should be treated by open surgical excision. The recent availability of smaller instruments has expanded the application of laparoscopy to children and infants. Surgical applications include contralateral inguinal exploration in children with unilateral hernias, appendectomy, orchiopexy, cholecystectomy, splenectomy, Nissen fundoplication, and gastrostomy/jejunostomy. A recent retrospective review of 574 pediatric laparoscopic surgeries showed an overall complication rate of 2% (7), including significant hemorrhage controlled after conversion to laparotomy (n 4), unintentional esophagotomy during a Nissen fundoplication (n 1), technical errors (malpositioned Nissen fundoplication and improper gastrostomy tube placement) requiring repeat surgery (n 2), hernia at the umbilical trocar site used for contralateral inguinal exploration (n 2), and cellulitis at the trocar site used for gastrostomy tube placement (n 3). A change in surgical technique and the use of a separate site for gastrostomy tube and trocar placement prevented reoccurrence of the latter 2 complications. All episodes of hemorrhage occurred during the first 5 10 procedures. Similar to the adult experience, intraoperative complications occurred early in the use of laparoscopy and decreased with time. The two most serious potential intraoperative complications of laparoscopic surgery, including adrenalectomy, are hemorrhage and unintentional viscus injury. Overall, intraoperative blood loss has been less in laparoscopic adrenalectomy than open surgical procedures in adult patients (3, 4, 6), and a similar experience is expected in pediatrics. Unintentional viscus injury in both pediatric laparoscopic procedures and laparoscopic adrenalectomy in adults is rare, but risk is probably greatest in the smaller size child. In general, unintentional viscus injury during laparoscopic procedures in children has occurred primarily in the early surgical experience (7), reinforcing the importance of surgical expertise. Once the appropriate training and experience is achieved, advantages of the laparoscopic approach in children include faster recovery, less postoperative pain, and improved cosmetic appearance. Laparoscopic surgery is gaining acceptance at major pediatric medical institutions, however long-term follow-up is lacking because of the novelty of this approach, and laparoscopic adrenalectomy is rarely performed. Adrenalectomy is rarely indicated in children. The most common pediatric adrenal tumor requiring adrenalectomy is neuroblastoma, a neural crest cell tumor. Neuroblastoma in children less than 15 yr old occurs in approximately 1 in 100,000 per year, with the majority of cases occurring in the first 5 years of life (8). In general, a laparoscopic approach is contraindicated in the surgical resection of most carcinomas because of the need for extensive exploration and concern of tumor spillage. These concerns may not be applicable to a

7 THERAPEUTIC CONTROVERSY 3047 subset of neuroblastomas detected before 1 yr of age, which have a good prognosis and may not warrant aggressive therapy. In Japan, where a neuroblastoma screening program of 6-month-old infants exists, laparoscopic adrenalectomy was recently performed in 3 infants (8 9 months old) with screening-detected neuroblastomas who had a favorable prognosis (9). To our knowledge, this is the only report of laparoscopic adrenalectomy in infants. The child who has a neuroblastoma with a less favorable prognosis is not a good candidate for a laparoscopic approach. Endocrine tumors of the adrenal gland are rare in childhood. When present, the risk of cancer is greater in children than adults, and complete surgical resection is the treatment of choice. The annual incidence of childhood adrenocortical carcinoma below age 15 is estimated to be 0.3 per million children (10). Childhood adrenocortical carcinoma typically presents as virilization and/or Cushing s syndrome and, in children, Cushing s syndrome due to an adrenocortical tumor is suspicious for carcinoma. Rupture of the capsule and tumor spillage are potential complications of childhood adrenocortical tumor resection (10). Thus, a laparoscopic approach is contraindicated when adrenocortical carcinoma is suspected. Benign pediatric adrenal tumors that are amenable to a laparoscopic approach include pheochromocytoma and aldosteronoma. Aldosteronomas are extremely rare in children, with 15 reported cases to date (11). Pheochromocytoma is also rare in childhood and may be associated with familial syndromes such as neurofibromatosis and von Hippel Lindau disease. Pheochromocytoma associated with MEN2 syndrome is typically diagnosed later in life, in the 5th and 6th decades. Primary pigmented nodular adrenocortical disease (PPNAD), a rare cause of Cushing syndrome that often presents in childhood, is characterized by nonadrenocorticotropic hormone-dependent hypersecretion of cortisol by multiple pigmented nodules of adrenocortical cells. PPNAD occurs as part of the Carney complex, an autosomal dominant multisystem syndrome. Other manifestations of the Carney complex include spotty skin pigmentation, mesenchymal tumors (myxomas), endocrine neoplasias (growth hormone-producing pituitary adenoma, testicular Sertoli cell tumor, thyroid tumor), and schwannomas (12). Treatment for PPNAD consists of bilateral adrenalectomy. These patients should be good candidates for a laparoscopic approach. The use of adrenalectomy as a treatment option in classical congenital adrenal hyperplasia (CAH) has been proposed recently (13). Two treatment approaches have been suggested: adrenalectomy during the second 6 months of life, done concurrently with genitoplasty in girls, and adrenalectomy in select CAH patients that are difficult to manage with conventional medical treatment. To date, 4 cases have been reported in the literature (14 17), all in difficult to control cases. In addition, at the National Institutes of Health, we performed adrenalectomy on a 17-yr-old with virilization due to CAH that could not be controlled satisfactorily with medication, and other centers have begun performing this procedure on select cases. To our knowledge, adrenalectomy was performed via a laparoscopic approach in only one CAH patient, a 14-yr-old girl with 11 -hydroxylase deficiency (16). Adrenalectomy in CAH is an investigational procedure. A laparoscopic approach has the potential to minimize the surgical risks; however, sufficient numbers of patients are needed to acquire the necessary expertise, especially in infants. Modifications to the standard laparoscopic technique used in adults are necessary when the procedure is used on infants and small children because of the small peritoneal cavity (9). Ideally, laparoscopic adrenalectomy in children should be performed by surgeons with pediatric expertise in both adrenalectomy and laparoscopy, however, there is currently little experience in this surgical modality in children. Alternatively, the larger child or adolescent may have laparoscopic adrenalectomy performed by surgeons with experience in this procedure in adults. Currently, in order to maximize operative experience, pediatric laparoscopic adrenalectomy is best done at a large tertiary care center. Prospective randomized clinical trials comparing new surgical procedures (i.e. laparoscopic adrenalectomy) to wellestablished surgical approaches (i.e. adrenalectomy by open laparotomy) do not exist, nor is there data on the community hospital experience. Based on available retrospective data of the adult experience at major medical centers, the laparoscopic approach appears to be the preferred surgical modality for adrenalectomy once the appropriate surgical expertise is achieved. We predict that this will also be observed in pediatrics. The incidence of classical CAH is estimated to be 1:15,000 (18), which is much more common than other pediatric indications for adrenalectomy. Thus, adrenalectomy may become a more commonplace pediatric procedure if the long-term follow-up of adrenalectomized CAH patients looks promising. As the adult experience with laparoscopic adrenalectomy expands, this approach will be applied more frequently in the pediatric population and will most likely become the preferred approach except when a potentially invasive malignancy is suspected. References 1. Soper N, Brunt L, Kerbl K Laparoscopic general surgery. N Engl J Med. 330: Gagner M, Lacroix A, Bolte E Laparoscopic adrenalectomy in Cushing s syndrome and pheochromocytoma. N Engl J Med. 327: Guazzoni G, Montorsi F, Bocciardi A, et al Transperitoneal laparoscopic versus open adrenalectomy for benign hyperfunctioning adrenal tumors: a comparative study. J Urol. 153: Brunt LM, Doherty GM, Norton JA, Soper NJ, Quasebarth MA, Moley JF Laparoscopic andrenalectomy compared to open adrenalectomy for benign adrenal neoplasms. J Am Coll Surg. 183: Vargas HI, Kavoussi LR, Bartlett DL, et al Laparoscopic adrenalectomy: a new standard of care. Urology. 49: Jacobs JK, Goldstein RE, Geer RJ Laparoscopic adrenalectomy: A new standard of care. Ann Surg. 225: Chen MK, Schropp KP, Lobe TE Complications of minimal-access surgery in children. J Pediatr Surg. 31: Gurney JG, Severson RK, Davis S, Robison LL Incidence of cancer in children in the United States. Cancer. 75: Yamamoto H, Yoshida M, Sera Y Laparoscopic surgery for neuroblastoma identified by mass screening. J Pediatr Surg. 31: Sandrini R, Ribeiro RC, DeLacerda L Childhood adrenocortical tumors. J Clin Endocrinol Metab. 82: Etker S Correspondence. J Pediatr Surg. 30: Stratakis CA, Carney JA, Lin JP, et al Carney complex, a familial multiple neoplasia and lentiginosis syndrome. J Clin Invest. 97: Van Wyk JJ, Gunther DF, Ritzen EM, et al The use of adrenalectomy as a treatment for congenital adrenal hyperplasia. J Clin Endocrinol Metab. 81:

8 3048 THERAPEUTIC CONTROVERSY JCE&M 1998 Vol 83 No Zachmann M, Manella B, Kempken B, et al Ovarian steroidogenesis in an adrenalectomized girl with 21-hydroxylase deficiency. Clin Endocrinol. 21: von Muhlendahl KE, Sippell WG Adrenalectomy as therapy in refractory adrenogenital syndrome. Monatsschrift Kinderheilkunde. 13: Nasir J, Royston C, Walton C, White MC hydroxylase deficiency: management of a difficult case by laparoscopic bilateral adrenalectomy. Clin Endocrinol. 45: Gunther DF, Bukowski TP, Ritzen EM, Wedell A, Van Wyk JJ Prophylactic adrenalectomy of a three-year old girl with congenital adrenal hyperplasia: pre- and postoperative studies. J Clin Endocrinol Metab. 82: Pang S, Clark A Congenital adrenal hyperplasia due to 21-hydroxylase deficiency: newborn screening and its relationship to the diagnosis and treatment of the disorder. Screening. 2: Laparoscopic versus Open Adrenalectomy Jeffrey A. Norton University of California San Francisco and San Francisco Veterans Affairs Medical Center San Francisco, California LAPAROSCOPIC surgery has dramatically reduced the morbidity of many abdominal surgical procedures resulting in less pain, shorter hospitalization, and more rapid return to work (1). An important guiding principle of laparoscopic surgery is to perform the same procedure laparoscopically as through open techniques. Incisional pain and discomfort are reduced by laparoscopy, because the operation is performed through multiple small incisions (1 2 cm) in the skin, muscle, and fascia rather than a solitary long incision (15 20 cm). Pain is not caused by dissection and mobilization of internal viscera, which is similar in both open and laparoscopic procedures, but rather by the magnitude of the abdominal wall incision. Larger incisions result in more pain that lengthens recovery time. Reduction in pain and rapid recovery has spurred patients and referring physicians to select minimally invasive techniques for common surgical procedures like cholecystectomy, splenectomy, and repair of hiatal hernias (2 4). Despite the fact that there is less pain associated with laparoscopic surgery (1 4), there have not been other clearly identified benefits. In fact, some studies indicate that laparoscopy results in an increased frequency of complications. For example, studies suggest that laparoscopic cholecystectomy has a higher incidence of bile duct injury than open cholecystectomy (2, 5). Prospective controlled studies assessing critical outcome parameters are essential before any procedure can be unequivocally recommended. Unfortunately, for most laparoscopic surgical procedures, these data are not available. This report will analyze the role of laparoscopic adrenalectomy in the management of patients with adrenal diseases. There are no prospective randomized trials with sufficient numbers of patients and meaningful follow-up data to convincingly compare open to laparoscopic methods of adrenalectomy. However, there are numerous recent retrospective studies comparing the two procedures (6 10). In general, these studies have been performed by advocates of the laparoscopic approach who compare recent laparoscopic methods to previous open techniques. These comparisons are limited scientifically, because the design is retrospective and nonrandomized. Nevertheless, each study suggests that laparoscopic adrenalectomy is associated with less pain, better functional status, and earlier return to full activity (6 10). These differences are consistent, meaningful, and readily apparent to anyone who has examined patients after these procedures. However, postoperative pain and recovery are not the only meaningful variables following surgery. Few studies have examined the results of adrenalectomy in these patients. Are the biochemical results similar following laparoscopic adrenalectomy? Are long term results similar? These questions are presently unanswered. It is possible that laparoscopic adrenalectomy is associated with a higher incidence of local recurrence of tumor, because of incomplete resection or spilled cells. Additional long-term follow-up studies will be necessary to address these issues. Before unequivocally recommending one approach, it will be critical to know that not only is pain less, but outcome is similar. Laparoscopic adrenalectomy is a new approach to an old procedure. The surgeon performing it is responsible for understanding the indications. This is mentioned because some authors suggest that a nonfunctioning adenoma is an indication for laparoscopic adrenalectomy (11, 12). This is not the case because excellent data from long-term follow-up studies and autopies demonstrate that these tumors are clinically insignificant and do not warrant adrenalectomy (13). This leads to the notion that adrenal surgery requires more knowledge than simply how to do the procedure. It involves understanding the indications for the procedure and the postoperative management. Correct decision making is important in adrenal surgery. Interpretation of radiographs and data analysis may be critical in planning an operation. Further, prescribing the correct dose and duration of glucocorticoid replacement therapy following resection of an adenoma requires special knowledge (14). Adrenal surgery is best performed by a surgeon who is experienced and knowledgeable in both endocrine and laparoscopic surgery, and not simply laparoscopic methods. Large size of an adrenal tumor is a contraindication for laparoscopic adrenalectomy. Laparoscopic adrenalectomy should not be performed in patients suspected of having malignant neoplasms of the adrenal. For cortical tumors and pheochromocytomas, size of the tumor correlates with malignant potential. Weight greater than 100 g or size equal to 6 cm is highly suggestive of malignancy (13, 15). Laparoscopy is a limited approach to the adrenal, requiring manipulation of the gland to remove it. In patients with cancer, wide resection of the gland with contiguous structures provides the best chance for cure. Further, in patients with gall bladder and colon cancer, there has been an unusually high probability of port site recurrences following laparoscopic surgery (1). Therefore, in patients with adrenal tumors approximately 6 cm in size who have a significant likelihood of cancer, open adrenalectomy is recommended to avoid manipulation of the tumor and to maximize the chances of complete resection (9). Type of adrenal tumor is not a contraindication for laparoscopic adrenalectomy. Previously, some have suggested that a pheochromocytoma should not be removed laparoscopically. Recent reports indicate that this is not the case, and even pheochromocytomas as large as 5 cm have been successfully removed by laparoscopic methods (16, 17). Proper preoperative preparation with phenoxybenzamine or alpha-methyltyrosine has been effective at minimizing in-

9 THERAPEUTIC CONTROVERSY 3049 traoperative hypertensive episodes during insufflation with carbon dioxide, surgical manipulation, and resection. Laparoscopic adrenalectomy for pheochromocytoma in the setting of multiple endocrine neoplasia (MEN 2A and 2B) is the method of choice (Norton, JA; unpublished data). Patients generally have benign, small tumors within the adrenal. Recent technical advances make laparoscopic adrenalectomy safe and able to be performed by more surgeons. The lateral transperitoneal approach is preferred over the retroperitoneal approach because of improved working space and gland visualization (16). Operative identification of the adrenal gland is facilitated by the use of laparoscopic ultrasound (9, 17). The gland is identified as a hypoechoic mass, and relationships with other structures (inferior vena cava, the renal vein, and the adrenal vein) are clarified. The harmonic scalpel simplifies dissection and effectively controls bleeding from the small arteries that perfuse the gland along its medial borders. The adrenal vein is separately ligated with hemoclips to provide secure hemostasis. The resected gland is removed from the port site in an occlusive bag to decrease peritoneal implantation and port site recurrence. In fact, our analysis suggests that operative time and blood loss are not increased by laparoscopic methods (9). In summary, despite the unavailability of prospective randomized trials, laparoscopic adrenalectomy has become the method-of-choice to perform most adrenalectomy procedures, as it greatly reduces postoperative pain and shortens recovery. The surgeon should be aware of the indications for adrenalectomy. Laparoscopy has not changed the indications. Pheochromocytomas are not a contraindication to laparoscopic adrenalectomy, but malignant tumors are best removed by an open procedure. Procedural advances like lateral transabdominal approach, laparoscopic ultrasound, harmonic scalpel, clips and bags have shortened the operative time and reduced blood loss. Thus, for small ( 6 cm) functioning adrenal tumors and hyperplasia that require adrenalectomy, laparoscopic adrenalectomy appears to be the procedure of choice. Careful long-term follow-up of these patients is recommended to exclude recurrence from incomplete resection, ectopic tissue, or tumor spillage. References 1. Soper NJ, Brunt LM, Kerbl K Laparoscopic general surgery. N Engl J Med. 330: The Southern Surgeons Club A prospective analysis of 1518 laparoscopic cholecystectomies. N Engl J Med. 325: Farah RR, Rogers ZR, Thompson WR, Hicks BA, Guzetta PC, Buchanan GR Comparison of laparoscopic and open splenectomy in children with hematologic disorders. J Ped. 131: Laine S, Rantala A, Gullichsen R, Ovaska J Laparoscopic vs. conventional Nissen fundoplication. A prospective randomized study. Surg Endo. 11: Lee VS, Chari RS, Cucchiaro G, Meyers WC Complications of laparoscopic cholecystectomy. Am J Surg. 165: Mac Gillivray DC, Shichman SJ, Ferrer FA, Malchoff CD A comparison of open vs laparoscopic adrenalectomy. Surg Endo. 10: Linos DA, Stylopoulos N, Boukis M, Souvatzoglou A, Raptis S, Papadimitriou J Anterior, posterior, or laparoscopic approach for the management of adrenal diseases? Am J Surg. 173: Vargas HI, Kavoussi LR, Bartlett DL, et al Laparoscopic adrenalectomy: a new standard of care. Urol. 49: Brunt LM, Doherty GM, Norton JA, Soper NJ, Quasebarth MA, Moley JF Laparoscopic adrenalectomy compared to open adrenalectomy for benign adrenal neoplasms. J Am Col Surg. 183: Prinz RA A comparison of laparoscopic and open adrenalectomies. Arch Surg. 130: Gagner M, Lacroix A, Prinz RA, Bolte E, Albala D, Potvin C, Hamet P, Kuchel O, Querin S, Pomp A Early experience with laparoscopic approach for adrenalectomy. Surg. 114: Mugiya S, Suzuki K, Masuda H, Ushiyama T, Hata M, Fujita K Laparoscopic adrenalectomy for nonfunctioning adrenal tumors. J Endourol. 10: Ross NS, Aron DC Hormonal evaluation of a patient with an incidentally discovered adrenal mass. N Engl J Med. 323: Doherty GM, Nieman LK, Cutler GB, Chrousos GP, Norton JA Time to recovery of the hypothalamic-pituitary-adrenal axis following curative resection of adrenal tumors in patients with Cushing s syndrome. Surg. 108: Page DL, DeLellis RA, Hough AJ Tumors of the adrenal. In: Hartmann WH, Cowan WR, eds. Atlas of Tumor Pathology. Washington Armed Forces Institute of Pathology; pp Duh QY, Siperstein AE, Clark OH, et al Laparoscopic adrenalectomy: comparison of the lateral and posterior approaches. Arch Surg. 131: Gagner M, Breton G, Pharand D, Pomp A Is laparoscopic adrenalectomy indicated for pheochromocytomas? Surg. 120: