Discussion

More than a decade after the advent of laparoscopic adrenalectomy, the worldwide accumulated experience indicates that the procedure is safe and successful, and it is now considered an established and preferred treatment for most endocrine and neoplastic disorders affecting the adrenal gland.

Comparison with Open Adrenalectomy

The results of laparoscopic adrenalectomy must be compared with those of conventional open surgery. There are no prospective, randomized studies comparing open with laparoscopic adrenalectomy. The excellent results, reported in the available retrospective comparative studies, make such research unnecessary and possibly unethical. In our own retrospective, comparative analysis,3 we have found no difference in operating time or dimensions of the adrenal gland. The estimated blood loss was 70 mL for the laparoscopic adrenalectomy versus 200 mL for the open adrenalectomy. The mean hospital stay for the laparoscopic surgery was 3 versus 9 days for the open group. TTie analgesia requirements and the mean time for ambulation were also significantly lower in the laparoscopic group. Other studies have reported similar outcomes.4"8'24,30 39 The Cleveland Clinic retrospective comparison of 110 laparoscopic and 100 open adrenalectomies showed the superior results of the laparoscopic approach.76 Open adrenalectomy was performed by various standard approaches. The laparoscopic group was superior in surgical time, blood loss, narcotic analgesic requirements, intensive care unit admissions, resumption of oral fluid intake, and mean hospital stay. Although intraoperative complication rate was similar, there were fewer postoperative complications in the laparoscopic group. Of special interest is the study by Thompson and coworkers6 from the Mayo Clinic, who compared the laparoscopic transabdominal laparoscopic approach in 50 patients with the open posterior approach in 50 well-matched patients. In addition to the other reported advantages of laparoscopy, late incision neuromuscular complications developed in 54% of the open group, chronic pain syndrome in 14%, and flank numbness in 10%. A recent meta-analysis of the English literature by Brunt77 compared the complications of laparoscopic with open adrenalectomy. Complications were tabulated from 50 studies of laparoscopic adrenalectomy involving 1522 patients and 48 studies of open adrenalectomy comprising 2273 patients. Among the reports, 22 compared laparoscopic with open adrenalectomy from within a single institution. They concluded that laparoscopic adrenalectomy resulted in fewer adrenalectomy-related complications than those seen historically with open adrenalectomy. Fewer wound and pulmonary complications and fewer incidental splenectomies are the primary reasons for this improved outcome. Finally, another variable of concern, addressed by several authors, is the cost of the procedure compared with that of open surgery.5,6,8,31,38 Although Thompson and coworkers6 found higher costs with the laparoscopic procedure, most other reports found no significant difference in overall cost between the two approaches. However, the earlier return to work in patients undergoing laparoscopic adrenalectomy would be associated with lower costs if is taken into consideration.

Choices of Approach

The technique of choice by most surgeons performing laparoscopic adrenalectomy is the transabdominal lateral approach. Several authors have successfully documented the feasibility, safety, and effectiveness of endoscopic adrenalectomy via the retroperitoneal approach in tumors less than 5 to 6 cm.14,15,17,78,79 Since the peritoneum is not violated and the bowel is not mobilized with the retroperitoneal approach, it was postulated to be less invasive and lead to better results, especially in small lesions and in obese patients.17,24 Siperstein and associates,15 in a series of 31 patients, concluded that although more demanding, the retroperitoneal approach should be considered in patients with tumors less than 6 cm, bilateral tumors, or extensive previous abdominal surgery. In another large series from the Netherlands, the procedure was described in 111 consecutive cases and showed comparative results with the transabdominal approach.78 These authors recommended the procedure for benign adrenal tumors less than 6 cm. Nevertheless, case history analysis has revealed no apparent difference in patient outcome, morbidity, or operative time for the two approaches.14,15,44,45,80 Moreover, in our experience and the experience of others,81 the transperitoneal approach has not caused bowel injury or other complications. Comparison between the two techniques has in fact indicated no real difference for small tumors, although for lesions larger than 5 to 6 cm, the transabdominal route is considered preferable.16 Disadvantages of the retroperitoneal approach include a lack of anatomic landmarks and a restricted working space. This combination of technical difficulties renders the retroperitoneal approach unsuitable for tumors larger than 6 cm. On the other hand, a major advantage of the transperitoneal approach is that the abdominal cavity, and particularly the liver, can be explored. In patients with pheochromocytoma, the liver can be examined by inspection and ultrasound and suspicious lesions may be biopsied. Moreover, in our personal experience with the retroperitoneal approach, the exposure was inferior to that obtained via the transperitoneal approach.

Contraindications to Laparoscopic Adrenalectomy

MALIGNANCY

The available data suggest that there are few absolute contraindications for laparoscopic adrenalectomy. We consider invasive adrenal carcinoma to be the only absolute contraindication for the laparoscopic approach owing to the possible extent and complexity of the operation required. An open technique also may be more desirable for patients with malignant pheochromocytoma when metastatic nodes are present in the periaortic chain or close to the bladder. Several authors differentiate between the biologic behavior of adrenal metastasis and primary adrenal cancer as to their suitability for the laparoscopic procedure.51,71 Because solitary adrenal metastasis from an extra-adrenal primary is usually small and confined within the adrenal, the laparoscopic approach has considerable appeal for this specific indication.51 Conversely, adrenal cancer is usually larger and often locally invasive. An important limitation in this regard is that adrenal imaging and even fine-needle aspiration are often inaccurate to diagnose or exclude adrenal malignancy.71 Since no reliable and accurate preoperative diagnostic test to diagnose adrenal malignancy exists, it is difficult to determine when an open approach should be used. An initial laparoscopic approach can be used to establish the diagnosis with low morbidity and allows curative resection in most instances.71 Laparoscopic ultrasound is a simple and effective intraoperative technical adjunct that may be used to evaluate the nature and invasiveness of the suspected adrenal mass. Obviously, in patients who prove to have local invasion during surgery, the laparoscopic approach should be converted to an open procedure to allow curative, wide, radical resection. The limited experience to date with laparoscopic adrenalectomy in malignant disease is promising, with short-term results comparable with those of conventional surgery.6971 Thus, it appears that a laparoscopic approach is reasonable for metastatic adrenal disease, provided the primary cancer is controlled and there is no evidence of extra-adrenal disease. Similarly, for primary neoplasms, if complete resection is technically feasible and there is no evidence of local invasion, an initial laparoscopic approach is an acceptable option in experienced hands at selected centers.51'69,71

SIZE

The maximal acceptable size of a lesion appropriate for laparoscopic adrenalectomy is another unsettled issue. Although size per se is not a definite contraindication, laparoscopy is not advisable for masses larger than 12 to 14 cm because of the increased incidence of malignancy and the technical difficulties associated with their removal. The largest lesion that we have resected was 14 cm, but such a mass makes the dissection difficult and time consuming. The exposure also is problematic because of the limited space available in this area. Large masses frequently have unusual and numerous retroperitoneal feeding vessels that require tedious and lengthy dissection. Only surgeons with extensive laparoscopic experience should attempt resection of larger adrenal masses. Generally, the indications and contraindications for laparoscopic adrenalectomy, including the maximal size limit and other issues, are dictated largely by the experience of the individual surgeon.

Incidentaloma

Management of incidentally discovered adrenal masses is still controversial. Although adrenocortical carcinomas are usually larger than 6 cm, incidentally detected cancers 3 to 5 cm or even smaller have been reported.5182 Another confounding factor is that CT scanning underestimates by 20% to 40% adrenal tumor size compared with actual size on histopathology.82 Definite indications for adrenalectomy include sizes larger than 4 cm, hormonally active lesions, suspicious characteristics on imaging studies, and documented increase in size. Because of the excellent results of the laparoscopic procedure, we and others51 prefer laparoscopic adrenalectomy instead of observation for the young and low operative risk patients with 3- to 5-cm adrenal masses. Another argument against the watchful conservative policy in such cases is that most adrenal nodules increase in size with age51 and the need for imaging and biochemical testing continues throughout the patient's life. Moreover, the patient is spared the anxiety, expense, and time lost from repeated follow-up appointments and the associated studies needed.

The New Gold Standard

The accumulated evidence indicates that laparoscopic adrenalectomy in patients with hormonally active tumors is the new gold standard. This minimally invasive technique has become the procedure of choice for hyperaldostero-nism,37'63'64 Cushing's syndrome and disease,3,21,22,25,26,62.67 and pheochromocytoma.20'28'48'50'53,54'58

Bilateral laparoscopic adrenalectomy appears to be safe and effective in patients with pituitary-dependent Cushing's syndrome after failed transsphenoidal surgery and in cases with ectopic ACTH syndrome when the primary tumor cannot be identified or removed.62 After initial reluctance and skepticism, it is now obvious that laparoscopic resection of pheochromocytomas can be accomplished safely despite frequent episodes of hemodynamic variability equal to those of historical open control subjects. The earlier recovery, fewer complications, and lack of endocrine recurrence make this approach the procedure of choice for the management of pheochromocytoma.53'57 In addition, a recent publication by Brunt and colleagues52 has reported favorable results in cases of unilateral and bilateral familial pheochromocytoma (patients with MEN 2A, MEN 2B, von Hippel-Lindau disease, and neurofibromatosis type 1). Another large series from Germany55 has documented the successful outcome of endoscopic approach in 61 chromaffin neoplasms (52 pheochromocytomas and 9 paragangliomas). The patient population included a wide spectrum of this disease: unilateral, hereditary, bilateral, recurrent, and multiple tumors. In patients with bilateral disease, partial bilateral adrenalectomy was performed and achieved preservation of adrenocortical function in 86% of cases, without evidence of recurrence after 3 years of follow-up. Thus, in patients with hormonally active tumors of the adrenal, the procedure has proved feasible and safe and offered all the advantages of minimally invasive surgery. Additionally, it resulted in an excellent functional outcome and was associated with clinical and biochemical cure rates comparable with those of open surgery during long-term follow-up.3,52,53.55.57,62-64

Recent Advances

Recent advances and innovations in laparoscopic adrenalectomy have been introduced. Outpatient laparoscopic adrenalectomy has been performed in selected low-risk patients with small adrenal tumors (mainly hyperaldosteron-ism, excluding pheochromocytoma) with satisfactory results.65 83 To further minimize the morbidity of conventional laparoscopic procedures, needlescopic technique, using smaller ports, was reported by several groups.84"86 The limited experience to date with a small number of patients showed that the procedure was feasible and resulted in improved wound cosmesis. It decreased postoperative pain and hospital stay without prolonging operative time.84 The continued technologic advances, offering more effective 2-mm instruments, may convince more surgeons to try this new technique. Nevertheless, randomized, prospective trials comparing needlescopic with conventional laparoscopy are still needed to validate these favorable initial results.

Laparoscopic cortical-sparing surgery in selected patients with bilateral pheochromocytoma and well-circumscribed bilateral Cortisol or aldosterone-producing adenomas29'59'87 91 has been reported. This approach may be valuable in those who would otherwise require life-long adrenal replacement therapy after complete adrenal gland extirpation. It was also used in patients with unilateral aldosterone-producing adenomas.91 Our limited experience29 and that of others87 91 confirms the technical feasibility and safety of laparoscopic partial adrenalectomy. The recurrence rate after bilateral pheochromocytomas in patients with MEN syndromes approaches 20%.29,90 For this reason, some authors advise against adrenal-saving surgery in these instances. Intraoperative ultrasound is useful since one cannot rely solely on the direct laparoscopic view. Whenever tumor and normal parenchyma cannot be differentiated intraoperatively, total adrenalectomy becomes unavoidable. Total adrenalectomy is also undisputed in cases of suspected malignancy. There have been no studies showing failed adrenal function because of adrenal vein ligation; however, one should attempt to preserve the main vein during adrenal-sparing surgery. In case of severe hypertension during surgery for pheochromocytoma, it has been suggested to temporarily occlude the vein with a laparoscopic bulldog clamp.59 To preserve cortical response to stress, adrenal-sparing surgery may be valuable in selected patients. However, large prospective series with long-term follow-up are required before drawing definite conclusions.

Other technical advances include the thoracoscopic transdiaphragmatic approach to the adrenal gland,92 adrenal cryoablation,93 and robotic laparoscopic adrenalectomy.94'95

Finally, has the widespread introduction of laparoscopic adrenalectomy broadened the indications of adrenalectomy and changed the pattern of referral? Two recent publications99100 found that the introduction of laparoscopic adrenalectomy has resulted in an increase in the number of patients referred and, consequently, more adrenalectomies are performed. One study showed that the criteria for patient selection did not change but more patients with adrenal metastasis and incidentalomas were operated on laparoscop-ically.99 However, the other study indicated that this was due to an increased number of cases with hyperaldosteronism and pheochromocytoma, with no change in the number of operations for incidentalomas and metastasis.100

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