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The Journal of Clinical Endocrinology & Metabolism Vol. 83, No. 9 3043-3046
Copyright © 1998 by The Endocrine Society


Special Articles

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


    Introduction
 Top
 Introduction
 Laparoscopic adrenalectomy at...
 Pheochromocytomas
 Should every patient requiring...
 References
 
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 131I-6-iodomethyl-19- norcholesterol (NP-59) or 131I-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, 1992–1997
 Top
 Introduction
 Laparoscopic adrenalectomy at...
 Pheochromocytomas
 Should every patient requiring...
 References
 
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-yr-old 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 ß-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 cortisol-producing 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 adrenocortical 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 follow-up. 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 3.5 x 3.7 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
 Top
 Introduction
 Laparoscopic adrenalectomy at...
 Pheochromocytomas
 Should every patient requiring...
 References
 
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, a 3 cm large 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 ß-blockers.


    Should every patient requiring adrenalectomy be referred to a laparoscopic surgeon?
 Top
 Introduction
 Laparoscopic adrenalectomy at...
 Pheochromocytomas
 Should every patient requiring...
 References
 
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, 13, 14, 15, 16) have indicated longer operative time for laparoscopic vs. open surgery, similar 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 x 6 cms x 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.

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
 Top
 Introduction
 Laparoscopic adrenalectomy at...
 Pheochromocytomas
 Should every patient requiring...
 References
 

  1. Kloos RT, Gross MD, Francis IR, Korobkin M, Shapiro B. 1995 Incidentally discovered adrenal masses. Endocr Rev. 16:460–484.[CrossRef][Medline]
  2. Lavoie H, Lacroix A. 1995 Partially autonomous cortisol secretion by incidentally discovered adrenal adenomas. Trends Endocrinol Metab. 6:191–197.
  3. Clayman RV, Kavoussi LR, Soper NJ, et al. 1991 Laparoscopic nephrectomy. N Engl J Med. 324:1370–1371.[Medline]
  4. Gagner M, Lacroix A, Bolte E. 1992 Laparoscopic adrenalectomy in Cushing’s syndrome and pheochromocytoma. N Engl J Med. 327:1033.[Medline]
  5. Gagner M, Lacroix A, Prinz RA, et al. 1993 Early experience with laparoscopic approach for adrenalectomy. Surgery. 114:1120–1125.[Medline]
  6. Gagner M, Lacroix A, Bolte E, Pomp A. 1994 Laparoscopic adrenalectomy. The importance of a flank approach in the lateral decubitus position. Surg Endosc. 8:135–138.[Medline]
  7. Weisnagel J, Gagner M, Breton G, Pomp A, Pharand D, Lacroix A. 1996 Laparoscopic adrenalectomy. The Endocrinologist. 6:1–10.
  8. Gagner M, Pomp A, Heniford BT, Pharand D, Lacroix A. 1997 Laparoscopic adrenalectomy: lessons learned from 100 consecutive procedures. Ann Surg. 226:238–247.[CrossRef][Medline]
  9. Lacroix A, Tremblay J, Touyz RM, et al. 1997 Abnormal adrenal and vascular responses to vasopressin mediated by a V1-vasopressin receptor in a patient with adrenocorticotropin-independent macronodular adrenal hyperplasia, Cushing’s syndrome, and orthostatic hypotension. J Clin Endocrinol Metab. 82:2414–2422.[Abstract/Free Full Text]
  10. Lacroix A, Tremblay J, Rousseau G, Bouvier M, Hamet P. 1997 Propranolol therapy for ectopic ß-adrenergic receptors in adrenal Cushing’s syndrome. New Engl J Med. 337:1429–1434.[Free Full Text]
  11. Higashihara E, Tanaka Y, Horie S, et al. 1992 A case report of laparoscopic adrenalectomy. Nippon Hinyokika Gakkai Zasshi. 83:1130–1133.[Medline]
  12. Guazzoni G, Montorsi F, Bocciardi A, et al. 1995 Transperitoneal laparoscopic versus open adrenalectomy for benign hyperfunctioning adrenal tumors: a comparative study. J Urol. 153:1597–1600.[CrossRef][Medline]
  13. Prinz R. 1995 A comparison of laparoscopic and open adrenalectomies. Arch Surg. 130:489–494.[Abstract]
  14. Naito S, Uozomi J, Ichimiya H, et al. 1994 Laparoscopic adrenalectomy: comparison with open adrenalectomy. Eur Urol. 26:253–257.[Medline]
  15. Brunt LM, Doherty GM, Norton JA, Soper NJ, Quaserbarth MA, Moley JF. 1996 Laparoscopic adrenalectomy compared to open adrenalectomy for benign adrenal neoplasms. J Am Coll Surgeons. 183:1–10.[Medline]
  16. Takeda M, Go H, Watanabe R, et al. 1997 Retroperitoneal laparoscopic adrenalectomy for functioning adrenal tumors: comparison with conventional transperitoneal laparoscopic adrenalectomy. J Urol. 157:19–23.[CrossRef][Medline]
  17. Pertsemlidis D. 1995 Minimal-access versus open adrenalectomy. Surg Endosc. 9:384–386.[Medline]




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