Laparoscopic Adrenal Surgery

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Sonia L. Sugg, Demetrius E.M. Litwin

Introduction 140

Preoperative Evaluation 140

Indications for Surgery 142

Surgical Techniques 145

Summary 149

INTRODUCTION

Since the introduction of laparoscopic adrenalectomy in 19921 its use has become increasingly widespread. The advantages of removing adrenal glands laparoscopically are related to the small incisions used in this procedure, resulting in decreased length of stay, decreased utilization of parenteral pain medication, and earlier return to functional status.

In this chapter, we will review the indications for laparoscopic adrenalectomy in surgical oncology, the clinical investigations required, the various surgical techniques, and discuss the controversies specifically related to approaching malignant adrenal lesions laparoscopically.

PREOPERATIVE EVALUATION

The preoperative evaluation of a patient with an adrenal mass begins with a thorough history and physical exam focusing on the signs and symptoms of excess hormonal secretion (Table 12.1), as well as those resulting from a mass effect of the tumor consisting of abdominal, back, flank pain, and a palpable mass. Symptoms may be episodic, and therefore the history must be carefully elicited. All patients with known adrenal masses must undergo biochemical evaluation for hormonal function. Functional tumors may be clinically occult.2,3 For example, some pheochromocytomas remain clinically silent until surgical stress or manipulation during surgery, or some asymptomatic cortisol producing adenomas can suppress contralateral adrenal function resulting in Addisonian crises after surgical removal.3 An initial screening of serum electrolytes, urinary catecholamines, and serum and urinary basal cortisol is indicated in all patients,4 and additional testing should be pursued as indicated (Table 12.2).

Table 12.1. Symptoms and signs of adrenal hormonal excess

Cortisol

Aldosterone

Sex Hormones

Catecholamines

Diabetes Truncal obesity Buffalo hump Moon facies Muscle wasting Osteoporosis Mood swings Hypertension Edema

Hypertension

Virilizing (in females)

Muscle weakness -amenorrhea Hypokalemia -hirsutism

Metabolic alkalosis -deepening voice Polyuria

Polydipsia Feminizing (in males)

-rare

-gynecomastia -impotence

Sustained or paroxysmal hypertension Palpitations Anxiety attacks Flushing

Excessive sweating

Table 12.2. Biochemical evaluation of adrenal mass

Cortisol

Aldosterone Androgens

Catecholamines

Screening tests

1 mg overnight dexamethasone suppression test

Urinary free cortisol

Plasma Plasma 12 or 24 hour potassium testosterone and urinary androstenedione metanephrines and VMA

Detailed AM and PM testing plasma cortisol

Urinary 17-hydroxy-corticosteroid and 17-ketosteroids Plasma corticotropin Exogenous CRH test

Plasma renin and aldosterone levels

Saline loading test Postural testing

Clonidine suppression test

The initial imaging test of choice is a computerized tomography CT scan with fine cuts through the adrenal glands.5 This test will detect with a high degree of accuracy tumors greater than or equal to 1 cm, possible involvement of other organs, metastatic disease, and extraadrenal disease. If there is concern of caval involvement, especially in large tumors suspicious for malignancy, a magnetic resonance imaging (MRI) scan should be obtained to rule out this possibility,6,7 which would preclude a laparoscopic approach. The functional status of the tumor can be evaluated by scintiscanning. MIBG (I123-meta-iodobenzylguanidine) scanning will detect most pheochromocytomas.8 It is especially helpful in determining the presence of bilateral pheochromocytomas, extraadrenal paragangliomas and metastatic disease. Biopsy will provide imaging of functional cortical adenomas (cortisol and aldosterone producing tumors),9,10 aid in the diagnosis of bilateral cortical hyperplasia, assess the functional status of the contralateral gland, and provide a guide for determining the malignant potential of a tumor (adrenocortical carci-

nomas usually display no or very low uptake of iodocholesterol).7 It may be necessary to perform venous sampling in some cases of hyperaldosteronism to determine the presence of unilateral or bilateral disease.11

INDICATIONS FOR SURGERY

Adrenal Cortical Tumors

Functional Adrenal Adenomas—Aldosteronomas and Cortisol Producing Adenomas

Aldosteronomas, producing the clinical syndrome known as Conn's, usually present between the ages of 30 and 50, and are twice as common in women than in men.12 Clinical symptoms are moderate to severe hypertension, and those related to hypokalemia such as muscle weakness, intermittent paralysis, and poly-uria. Preoperative preparation includes controlling the hypertension and correcting hypokalemia. Spironolactone is commonly used.13 The tumors are usually small, ranging from 1-3 cm in diameter.12 Removal results in cure of hyperaldosteronism and hypokalemia. However, patients who are male, older than age 40, and with longstanding hypertension are most likely to have residual persistent elevation in blood pressure.14

Cortisol producing adenomas accounts for 10% of Cushing's syndrome. It occurs more frequently in females (3:1 female to male ratio), and commonly presents in the mid-thirties.15 The tumors usually range in size from 3-5 cm. Tumors larger than 6 cm have an increased likelihood of being malignant.16 Removal of the adenoma results in 100% cure, and the physical signs of Cushing's syndrome disappear within one year.17 Postoperative cortisol replacement therapy is required until the hypothalamic-pituitary-adrenal axis recovers, which may require 6-18 months.17

Nonfunctional Adrenal Masses—"Incidentalomas"

With the increasing use of imaging studies such as ultrasound, CT scanning and MRI, asymptomatic adrenal masses are being discovered with greater frequency, at about a 5% incidence.18 Most of these masses are benign nonfunctional cortical adenomas. However, the possibility of a functioning or malignant tumor must be ruled out. Possibilities include functional cortical adenomas, cortical carcinomas, pheochromocytomas, cysts, myelolipomas, ganglioneuromas, or adrenal metastasis.19 A complete biochemical evaluation for adrenal cortical and medullary function must be performed, and functioning tumors should be excised. MRI scanning may help distinguish between tumor types such as cysts, myelolipomas, or pheochromocytomas based on signal intensity.5 Iodocholesterol or MIBG scanning may detect subclinically functioning tumors.20 Needle aspiration may be useful in determining the nature of an adrenal cyst by analysis of the cyst fluid for catecholamines or cytology.21 It may also be useful for diagnosis in cases of adrenal metastasis from other tumors. Before attempting needle aspiration, pheochromocytoma must be ruled out by biochemical studies to prevent precipi

tation of catecholamine release by the aspiration.22 There is concern about needle aspiration possibly seeding tumor cells in cases of possible adrenocortical carcinoma, and cytology is unable to distinguish between adrenal adenoma and carcinoma.23 Therefore needle aspiration should be avoided in solid primary adrenal lesions, especially in operative candidates. The size of a biochemically silent adrenal mass has been used to determine operative strategy.7 Tumors larger than 6 cm are generally thought to have a higher chance of being malignant and should be removed. Tumors 3 cm or smaller may be followed with serial CT scans and biochemical studies. Enlargement or change in functional status should prompt operation. However, it should be noted that adrenocortical carcinomas as small as 3 cm have been found to metastasize.24 Management of masses between 3 and 6 cm is controversial, with some surgeons advocating operation in good risk patients,25 and some preferring observation with interval CT scanning and biochemical testing.19 However, with the advent of laparoscopic removal, it is likely that a more aggressive approach will be adopted and lesions larger than 3 cm in size will be removed.

Adrenal Cortical Carcinoma

This is a rare malignancy (0.5-2/million/year) with a poor prognosis (35% 5-year survival). The tumor more commonly affects females (female:male ratio of 2.5 to 1).24,26 Patients present with symptoms of mass effect, excess hormonal secretion, and systemic symptoms of malignancy. The tumor is generally large, with an average size of 12 cm (range 3-30 cm) and an average weight of approximately 600 gm (range 12-4750 gm).24,26 Metastasis occur most commonly in the liver, lung, and adjacent organs. Staging is based on the MacFarlane classification. Stages I and II are defined as local disease with no lymph node or distant metastasis, and no local invasion. Stage I tumors are less than 5 cm, and stage II tumors are larger than 5 cm. Regional disease with lymph node spread/local invasion is defined as stage III. Stage IV tumors have distant metastasis. At diagnosis, only 4% of patients have stage I disease. In contrast, approximately 40% are stage II, 26% are stage III and 30% are stage IV. Mean survival times correlate with stage: 34-40 months for stage I and II disease, 22 to 26 months for stage III disease and 8-9 months for stage IV disease. The overall mean survival is 21 months, and the overall 5 year survival rate is 35%.24,26 The survival rate for patients who underwent curative resection was significantly higher than patients with tumors that were unresectable.26 The lack of effective alternative therapies including radiation and chemotherapy for adrenal cortical carcinoma makes complete surgical resection the only option for potential cure. For this reason, not only should the initial lesion be aggressively resected, but local recurrence should be treated with re-resection if possible. Contiguous organs such as kidney, distal pancreas, colon, and spleen invaded with tumor should be resected en bloc.7 In patients without systemic metastasis, extension of the tumor into the vena cava may require venovenous or cardiopulmonary bypass for complete removal of the tumor thrombus.7 In patients with tumors producing significant clinical syndromes, efforts to remove all gross tumor should be attempted. Because of the extensive surgery often required, most surgeons therefore advocate laparotomy instead of

laparoscopic surgery for preoperatively diagnosed adrenocortical carcinoma.27 However, if the diagnosis is made postoperatively by the pathologist, and the tumor has been removed laparoscopically, open re-resection is probably unnecessary if the tumour capsule has not been breached by tumor and a margin exists.

Pheochromocytoma

These are catecholamine producing neuroendocrine tumors of the adrenal medulla. Though this is a rare tumor, with an incidence ranging from 1.3/100,000 to 1/500,000, many pheochromocytomas remain undetected until autopsy.28 Extraadrenal pheochromocytomas, also known as paragangliomas, may be found along the sympathetic chain ganglia. Malignancy occurs in 10-20% of pheochromocytomas.29 There is an association with familial syndromes, such as multiple endocrine neoplasia II, neurofibromatosis, and Von Hipple Lindau disease.30,31 Prior to surgery, patients must be prepared by a-adrenergic blockade. After a-blockade is accomplished, p-adrenergic blockage may be added if the patient has tachycardia or arrhythmia. Intraoperative blood pressure needs to be monitored by arterial line and volume status by central venous pressure.32 Pheochromocytomas are usually at least 4 cm in diameter, and can be quite hypervascular with large veins on the surface. During operation, care must be taken to avoid manipulating or compressing the tumor, which can lead to sudden release of catecholamines and subsequent blood pressure fluctuations, even if the patient has been adequately blocked. The laparoscopic approach, with magnification and identification of tissue planes, allows for more gentle handling of pheochromocytomas. Traditionally, central vein clipped first to end efflux of catecholamines and blood pressure fluctuations. We have found it not necessary in most cases with adequate blockade. In our experience, clipping the central vein first often led to engorgement of the tumor with a more difficult resection as a result. Ten percent of pheochromocytomas are multifocal, and an even higher incidence is present in familial syndromes. Although it is possible to explore the potential areas of extraadrenal pheochromocytomas or paragangliomas laparoscopically, it can be time consuming. We recommend a good quality abdominal and pelvic CT scan and/or MIBG scan to screen for additional tumors prior to operation. Potential areas include the opposite adrenal, paraaortic regions from the celiac axis to aortic bifurcation, the organ of Zuckerkandl, and rarely, within the bladder. Postoperatively, patients with pheochromocytomas need to be monitored by urinary catecholamines for the development of malignant disease, which can occur as late as 7-10 years after resection of a primary tumor that appears benign on pathologic examination.33

Bilateral Adrenal Hyperplasia—Cushing's Disease, Ectopic ACTH Syndrome

Cushing's disease is the most common primary cause of hypercortisolism. Bilateral adrenal cortical hyperplasia is caused by excess adrenocorticotropic hormone (ACTH) secretion by a pituitary adenoma. The treatment of choice is transsphenoidal pituitary surgery or irradiation. Failure of surgery and subsequent medically uncontrollable Cushing's syndrome leads to bilateral adrenalec-tomy as the last resort, which will result in lifelong cortisol and mineralocorticoid

replacement.34 The surgical complication rate for this group of patients has been higher due to their excess corticosteroid secretion resulting in decreased immune function and delayed wound healing. The patients must be prepared for surgery with control of their diabetes, hypercortisolism, and hypertension. Though there have been no specific studies of laparoscopic adrenalectomy in these patients, the small surgical incisions, quicker mobilization and shorter length of stay associated with the laparoscopic approach should prove beneficial to this group of patients.

Ectopic ACTH syndrome is an uncommon cause of excess cortisol production. In a review of 41 patients by Zeiger et al, the source of ACTH in half of the patients was bronchial carcinoid, followed by pancreatic endocrine tumors, thymic carcinoid, medullary cancer of the thyroid, pheochromocytoma, small cell lung cancer, and occult disease.35 Bilateral adrenalectomy is indicated in patients with occult disease, or unresectable metastatic pancreatic ACTH producing tumors that fail medical therapy by cortisol-blocking agents.

Primary Nodular Adrenal Hyperplasia

This is a rare syndrome of hypercortisolism associated with multiple small hyperfunctioning adrenal nodules. It may be associated with Carney's syndrome with cardiac myxomas, hyperpigmentation of the skin and buccal mucosal and other endocrine disorders such as growth hormone producing pituitary adenomas.36 The treatment consists of bilateral adrenalectomy.

Metastasis

Metastasis to the adrenal glands are relatively common. The most common types are lung carcinoma, renal cell carcinoma and melanoma.37 In most cases, the metastasis is a component of systemic disease and should not be resected. However, resection may be appropriate in certain cases where the adrenal lesion is the only site of recurrence in an otherwise healthy and disease free patient. The laparoscopic approach is ideal in this instance because it allows for inspection of peritoneal surfaces and intra-abdominal organs for occult metastasis prior to resection of the adrenal gland. Laparoscopic ultrasound may be used as an adjunct.

SURGICAL TECHNIQUES

In open surgery, there are three approaches to adrenalectomy—anterior, posterior, and lateral. The lateral approach is generally reserved for very large tumors, and may include a thoracic component. The posterior approach was advocated by many for smaller (< 6 cm) adrenal lesions, as the recovery times were less than those of the anterior approach because the peritoneal space was not entered.38 The anterior approach facilitated exposure and could exclude other tumors, and was preferred for larger adrenal masses and pheochromocytomas. Prinz compared three groups of patients who underwent adrenalectomy via the anterior and posterior open approaches, and lateral laparoscopic approach. The patients undergoing laparoscopic adrenalectomy had a significantly shorter length of stay and required less postoperative analgesia.39

Laparoscopically, there have also been three methods advocated which parallel the open approaches. The anterior approach40 provides difficult exposure to the adrenal glands and is not in widespread use.27 The lateral approach, developed by Gagner et al, has the advantage of allowing gravity to assist in the exposure by allowing the bowel, spleen, and pancreas to fall away from the operative field.41 It allows for the removal of very large tumors, and is easier to learn because of familiar anatomical landmarks. In the case of bilateral adrenalectomies, it requires repositioning of the patient, which can add at least 20 minutes to the operating time. We favor the lateral approach and will describe it in the following section.42 The posterior approach has been described in detail elsewhere. An initial balloon trocar is placed lateral to the 12th rib, and the retroperitoneal space is created by balloon expansion. Insufflation is maintained using CO2. Additional trocars are placed adjacent to the 10th, 11th and 12th ribs42 or positioned posteriorly between the costal margin and the iliac crest.27 The adrenal gland is identified, with the help of laparoscopic ultrasound, if necessary, dissected and removed. The advantages of this approach lies in avoiding entering the peritoneum, especially in cases with previous abdominal surgery, and obviating the need for repositioning in cases of bilateral adrenalectomy. Disadvantages include the size limitation of the lesion removed, due to the smaller potential space in the retroperitoneum for manipulation of instruments, occasional difficulty in identifying the gland within the retroperitoneal fat, limited access to the vena cava for vascular control, and a low incidence of postoperative neuralgia secondary to port placement adjacent to the intercostal nerves.27 Duh et al reviewed their experience with both methods and found them to be comparable in terms of operative time and length of stay.27 They especially favor the posterior approach for bilateral lesions.

Lateral Laparoscopic Approach

The patient is placed in the lateral decubitus position with the affected side facing up. The table is flexed for maximum exposure of the space between the costal margin and iliac crest. The patient is secured and pressure points are carefully padded (Fig. 12.1). The surgeon and assistant stands facing the patient. The peritoneal cavity is insufflated with CO2 to 15 mm Hg through a Veress needle placed inferior to the costal margin in the anterior axillary line. An 11 mm trocar is placed at this site and the peritoneal cavity is inspected with a 30°, 10 mm laparoscope. Another 11 mm trocar is placed along the costal margin in the posterior axillary line, and a 5 mm trocar is placed 5-8 cm cephalad to the first trocar also along the costal margin in the epigastrium. This positioning will allow for triangulation. Using forceps and scissors, exposure of the adrenal gland can begin.

On the left, the spleen is mobilized by incising the entire lateral peritoneum of the spleen to the level of the diaphragm. By grasping this edge of peritoneum, the operating surgeon can roll the spleen forward to expose the underlying kidney and adrenal gland. There is loose areolar tissue in this plane which can be both bluntly and sharply dissected. Gerota's fascia should not be entered. The spleen and tail of pancreas must be brought forward in this fashion, since this much mobilization is required to safely dissect the left adrenal vein. The adrenal gland is

Laproscopy Surgery Adrenalectomy

Fig. 12.1. Patient position for laparoscopic left adrenalectomy.

almost always obvious. Usually the dissection begins at the lateral aspect of the gland or the upper pole and numerous small vessels surrounding the gland are divided. Generally electrocautery is sufficient for hemostasis although occasionally clipping is required. Once the dissection around the gland has begun, the edge of the gland becomes obvious and it proceeds without difficulty. The adrenal vein is usually the last structure divided and is at the inferior and medial portion of the gland. It is always clipped prior to division. Rarely, an additional posterior trocar must be placed for retraction of the spleen. On the right, the first three trocars are placed as on the left, and an additional 5 mm trocar is always placed for medial retraction of the liver. The liver is mobilized by dividing the triangular ligament. This will swing the liver forward. The right adrenal is then exposed. It is dissected away from the surrounding perinephric fat in the same fashion as the left. The adrenal vein is identified at the superior and medial portion of the gland and it is doubly clipped and divided at its junction with the vena cava. The medial aspect of the gland is closely applied to the vena cava and care must be exercised separating the gland from that vena cava. The posterior attachments are avascular on both the right and left sides and can be easily and rapidly divided and the gland freed. After hemostasis is established, the adrenal gland or tumor is placed into a thick plastic extraction bag and removed through the anterior 11 mm trocar site. It may be necessary to fragment the tumor or enlarge the trocar site for removal of a large tumor.

Special Considerations for Malignant/Potentially Malignant Tumors

Malignant adrenal tumors, including pheochromocytomas and adrenocorti-cal carcinoma, often cannot be diagnosed preoperatively. Though these tumors are rare, every pheochromocytoma and adrenal cortical tumor must be handled as if potentially malignant because the consequences of tumor seeding can be fatal. Though there have been documented cases of tumor implantation in lap-aroscopic colon cancer resections,43 such cases have not yet been reported with adrenal tumors. The extraction of the adrenal tumor must be carefully done to avoid tumor spillage. A thick and sturdy plastic bag should be employed. If possible, the tumor should be extracted intact to aid in pathologic diagnosis. The difficulty lies in larger tumors, which have the highest chance of being malignant, and yet require fragmentation for removal without a large incision. Fragmentation can destroy histologic features used for the determination of malignancy by the pathologist such as capsular invasion and patterns of necrosis. We attempt to fragment the tumor into several large pieces in order to preserve as much architectural detail as possible. We approach all adrenal lesions laparoscopically unless there is evidence of gross invasion of adjacent organs. With the magnification achieved during laparoscopic examination, we are able to delineate tissue planes and identify gross evidence of tumor invasion. If major organ invasion is present, we advocate an open approach for complete radical resection of the tumor and adjacent invaded soft tissue and organs. Radical resection has been performed laparoscopically,44 but the increased time required may outweigh the benefits.

Results

In the past 2 years, we performed 20 right, 17 left, 2 partial and 2 bilateral laparoscopic adrenalectomies in 41 patients. The average patient age was 46 years (range: 15-74 years) and the female to male ratio was 2.7:1. Seventeen patients had Conn's syndrome, 9 had pheochromocytoma, 8 has Cushing's syndrome, 3 had adrenal metastases, and one each had myelolipoma, adrenal cyst, Cushing's disease and ectopic ACTH syndrome. There was one patient with a malignant pheochromocytoma (7 cm) and one case of adrenocortical carcinoma (8 cm) in a patient with Cushing's syndrome. In both cases the tumor was well encapsulated and removed without rupture. Two patients had adrenal metastasis from contralateral renal carcinoma, and one patient had a metastasis from colorectal carcinoma.

The average tumor size in the 41 patients was 3.9 cm (range: 1-10 cm). Our average operating time was 139 minutes and ranged from 80-295 minutes. The operating time correlated with tumor size. The average estimated blood loss was 127 cc (range: 10-400 cc), and did not correlate with tumor size. Intraoperative complications included one liver laceration and one splenic capsular tear, both easily controlled. There were no conversions to open surgery and no blood transfusions. Postoperative complications were minor and no deaths occurred. On average, patients were discharged on POD 2.9 (range: 1-9 days) tolerating a regular

diet. Increased length of stay was associated with increased age, but not with increased operating time or blood loss. Our results compare favorably with those of other published reports.

SUMMARY

Laparoscopic adrenalectomy has rapidly become many surgeons' method of choice for removing adrenal glands or tumors. The benefits of less postoperative pain and earlier discharge and return to functional status are clear. Although the procedure requires a high degree of technical expertise in laparoscopy, it can be performed with minimal morbidity and mortality by trained surgeons. In addition to the technical aspects, resection of adrenal glands and tumors requires detailed knowledge of the endocrine aspects of preoperative diagnosis, intraoperative and postoperative management. The laparoscopic approach is particularly suited to surgical oncology because of its ability to diagnose disease spread prior to resection with minimal morbidity. Malignant tumors may be encountered during laparoscopic adrenalectomy but can be appropriately managed as detailed above. This review covered aspects of laparoscopic adrenalectomy with special attention to its importance in the area of surgical oncology.

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