Luca Milone, MD, PhD, Michel Gagner, MD
Laparoscopy is now a well-established procedure for the surgical management of adrenal diseases, with laparoscopic surgical procedures having been used to treat adrenal diseases for over 15 years. This approach was first described in 1992 by Gagner et al,1 and since then thousands of cases have been reported in the literature. Both the patient and the surgeon experience advantages with this approach, which include reduced postoperative pain, decreased requirement for analgesics, shortened hospitalization with a faster convalescence, and fewer complications. From the point of view of the surgeon, the magnification of the laparoscopic approach provides improved visualization of an anatomically dangerous region, which is difficult to approach by open surgery, and it does not require any difficult reconstructive techniques. Gagner et al2 in 1997 reported on the first large series of laparoscopic adrenalectomy. They described the results of the first 100 cases in which the lateral transperitoneal approach was used. Mean operative time was 123 minutes with no mortalities and 12% morbidity, demonstrating the reproducibility and safety of this technique. These data are still comparable to reviews being published today. Park et al53 recently reported on 3144 adrenalectomies from a retrospective cohort analysis of hospital discharge information from 1999 through 2005 from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (HCUP-NIS) database. They reported a complication rate and length of hospital stay varying from 11.3% to 18.2% and 3.9% to 5.5%, respectively, depending on the volume of surgeries performed by each department.
Adrenalectomy is indicated for unilateral and bilateral diseases that include hypersecretory adrenal tumors and all suspected adrenal malignancies, as illustrated in Table 1.
Limitations of the laparoscopic approach include malignancy, tumor size, previous surgery, general status of the patient, and surgeon experience. The latter is probably considered the most important, because adrenal diseases are considered infrequent diseases; adrenalectomy should be performed only at a few high-volume centers by surgeons with a high level of experience.53
Despite the abundant literature on the subject, the best laparoscopic approach to the adrenals is still a controversial issue, because both the transperitoneal adrenalectomy anterior (ATA) or lateral (LTA) and the retroperitoneal adrenalectomy (REA) have specific advantages and disadvantages. Because no prospective randomized clinical trial has been conducted on this issue, there is no evidence in the literature indicating that one approach is superior to the other. The decision about which approach to use depends on personal preferences and probably has a lot to do with the surgical skills of each surgeon. Nevertheless, LTA is more universally used, because it may be applied in the vast majority of adrenalectomy cases, while tumor size may be a limitation for the REA.12 Another advantage of LTA is the possibility of exploring the entire abdomen and all areas of possible localization of extraadrenal tumors by means of intraoperative ultrasound and direct vision, reducing the risk of misdiagnosis of ectopic tissue, for instance in the case of pheochromocytoma. Moreover, the supine position allows the surgeon to perform associated surgical procedures during the same operation.9
On the contrary, in the hands of a skilled surgeon, the REA approach could result in less blood loss, because of the high pressure of the capnoretroperitoneum of 20mm Hg to 28mm Hg and a shorter operative time.4,13 Another favorable reason leading toward REA is the need for a small number of trocars compared with LTA; 3 ports are needed in REA while from 4 to 5 trocars are needed in LTA, because of the need for retraction or dissection of abdominal organs. Walz et al14 described their experience with single-access retroperitoneoscopic adrenalectomy (SARA) using 2 ports in a recent series of 5 patients. SARA was used through a 1.5-cm incision to remove five 1-cm to 4-cm adrenal tumors with an operative time of 35 minutes to 70 minutes and no need for conversion to laparoscopy.
Morbidity and Mortality
Large series with more the 100 cases have been reported in the literature over the last 5 years. Eight articles were found describing a total of 2047 adrenalectomies, including 124 cases of bilateral adrenalectomy. Transperitoneal adrenalectomy was used in 855 cases, while REA was used in 732. In the article by Lee et al8 about cases from 14 centers, no mention is made of the approach used. It is important to note that most REAs are being reported by one author only. This is important because even if REA is becoming more frequently utilized it is still restricted to a few surgeons. ATA was used in 25% of all the transperitoneal adrenalectomies.
The average operative time was 153.7 minutes, but when REA was performed the time dropped to 96.8 minutes. Conversion was described in 2.2% of the patients with a range from 0% to 5%, while the complication rate was 3.9% with bleeding being the most described complication in 40% of the cases. Of these cases, 68.7% required blood transfusion.4,6,7,9,11 Other reasons cited for conversion to the open technique include problems in establishing the posterior retroperitoneal space, arrhythmia during adrenalectomy for pheochromocytoma due to repeated arterial blood pressure peaks, and colonic tears.5,9
The other complication described in the literature includes damage to nearby organs, such as spleen, liver, colon, small bowel, vessels, diaphragm, and pleura (Table 2).
Mortality was described in 0.6% of cases (Table 3).4-11
Laparoscopic Adrenalectomy for Pheochromocytoma
Pheochromocytomas are uncommon tumors that cause hypertension and other symptoms attributable to increased catecholamine production. They most commonly arise in the adrenal medulla but may develop anywhere along the sympathetic ganglia. The hypertension may be episodic or sustained, and often is associated with spells of tachycardia, headache, anxiety, or sweating. Preoperatively, these patients should be prepared pharmacologically with the alpha-adrenergic receptor phenoxybenzamine to reduce the risk of intraoperative hypertensive exacerbations. Beta blockade is reserved for patients with tachycardia unresponsive to alpha blockade or for epinephrine-secreting tumors.15
Fifteen articles reporting laparoscopic adrenalectomy for pheochromocytoma were found in the literature with 532 patients undergoing 565 adrenalectomies. Pheochromocytoma is a tumor that can grow up to 15cm in size. Many authors prefer to approach the disease from the peritoneum. In the literature collected, LTA was reported to have been used 3 times more than REA. The only author preferring REA was Walz4 who demonstrated an operative time of 82 minutes, half of the average time for the other series. The author describes how the use of high gas pressure up to 24mm Hg and the absence of abdominal organs that must be pulled apart make this operation easy and feasible even for a large tumor.
Manipulation during surgery or even the pneumoperitoneum itself can induce a hypertensive attack, leading to either myocardial dysfunction or cerebral hemorrhage.4,26,27 Clamping the adrenal vein first without manipulating the tumor is important to prevent a hypertensive crisis secondary to excessive catecholamine excretion during the adrenalectomy.22 When this technique was used, operative hemodynamic changes were described in only 32% of the patients with a range of 9% to 55%. Some authors16 prefer an open approach if the size of the tumor is >5cm. This could be because the size of the tumor and malignancy are directly related.28 On average, malignant tumors were significantly larger than benign tumors were. However, the mean size of localized malignant tumors was similar to that of benign tumors. Consequently, if preoperative investigation confirms that the disease is grossly localized, the surgeon is justified in approaching even large (>6 cm) tumors laparoscopically.
Many others18,48 have, in fact, described no difference in complications, blood loss, and conversion rate when removing large tumors compared with small one. Average operative time was 162 minutes for a tumor size of 4.6cm and a blood loss of 95.3mL. Hospital stay after surgery varied a lot from series to series, ranging from 3 days to 9 days with an average of 4.1 days. Hypertension was cured in 91.7% of the patients. The others remained mildly hypertensive, with disease controllable with oral agents in the presence of normal catecholamine levels (Table 4).4,6,7,11,16-25,52
Laparoscopic Adrenalectomy for Aldosteronoma
Primary aldosteronism is an important cause of secondary hypertension, and it is estimated to account for between 5% and 20% of select hypertensive patients29 with hypertension often being severe and resistant to treatment. Primary hyperaldosteronism is classified into aldosterone-producing adenoma (APA), unilateral adrenal hyperplasia, and idiopathic hyperaldosteronism (IHA). Of these categories, more than 80% of primary hyperaldosteronism cases consist of APA, which is the only one that responds to surgery, whereas the other diseases are better managed with potassium-sparing diuretics or aldosterone-receptor antagonist. Aldosteronomas are ideally suited for laparoscopic excision, because they are small, almost always benign, and patients are usually slim, compared with those with Cushing’s disease or syndrome. Adrenal vein sampling to determine whether the source of increased aldosterone production is uni- or bilateral is recommended for all patients older than 40 years and for those with bilateral adrenal nodularity, normal adrenals, or a unilateral nodule <1cm. Also, adrenal vein sampling has been described as being superior to image-based techniques for subtype differentiation of primary aldosteronism.30,31
We reviewed 10 articles in which 809 adrenalectomies were described. The average tumor size was 1.7cm, which is more than half the size of the average pheochromocytoma; this could be the reason for the shorter adrenalectomy operative time for aldosteronoma compared with operative time for pheochromocytoma, 132.4 minutes versus 162.2 minutes, respectively. Blood loss was 64.2mL, and conversion rate was 0.6%. As previously mentioned, the slim body habitus of a patient in conjunction with the small size of the tumor makes the surgery easier to perform. Twenty-nine complications were described (0.3%), and even for the aldosteronoma the more described complication was bleeding, which was 31% of all the complications. The other complications described were approach related, such as chronic lumbar pain, retroperitoneal hematoma and lumbar fossa hematoma, colonic fistula, wound infection, or general, such as fever, pneumonia, urine infection, cardiac ischemic event, and ECG changes related to hypokalemia. This last one happened in only 1 patient, while normokalemia was described in 96.8% of the patients at the follow-up. Hypertension cure or improvement was reported in 77.3% of the patients (Table 5).6,11,13,31-37
Laparoscopic Adrenalectomy for Cushing’s Syndrome
Approximately 20% of all Cushing’s syndrome cases are attributable to a primary adrenal source (pituitary microadenoma is the most common cause of Cushing’s syndrome). The most common adrenal cause of Cushing’s syndrome is a cortisol-producing adenoma, although adrenal cortical carcinoma and primary adrenal hyperplasia account for some cases. The diagnosis of Cushing’s syndrome is established biochemically by demonstration of an elevated 24-h urine free cortisol and by failure to suppress plasma cortisol after administration of dexamethasone.15
Unilateral adrenalectomy is indicated for a cortisol-producing adenoma, whereas patients with primary adrenal hyperplasia and those who have failed treatment of pituitary Cushing’s syndrome require bilateral adrenalectomy. Another indication for adrenalectomy is subclinical Cushing’s syndrome in adrenal incidentalomas, which are usually clinically silent (5%) and nonfunctioning (20%). They may autonomically produce cortisol in mild quantities, not enough to cause clinically evident features of Cushing’s disease; however, they may have associated hypertension, diabetes, obesity, or osteoporosis.38 In these patients, perioperative administration of corticosteroids is essential to avoid postoperative adrenal insufficiency.
We have collected reports of 8 series from the literature of the last 5 years about laparoscopic adrenalectomy for Cushing’s syndrome. The comparison between these series and those for pheochromocytoma and aldosteronoma is more difficult, because of the high rate of bilateral disease in Cushing’s patients. Of 279 patients operated on, 186 underwent a bilateral adrenalectomy. This also accounts for the higher operative time. While the operative time for pheochromocytoma and aldosteronoma was respectively 162 minutes and 132 minutes, for Cushing’s syndrome, it was 242 minutes. The blood loss was an average of 91mL, which is comparable to that with other adrenalectomies, while conversion was reported to be higher and consequently the length of hospital stay was 5.3% and 5.3%.
The complication rate has been described as 7.9%, which is close to that for pheochromocytoma, probably because of the large dimensions that the organs and tumors can reach and biochemical hemodynamic abnormalities during and after the surgery.
Patients suffering from Cushing’ disease are more delicate and need more medical attention than others with adrenal disease because of their imbalanced equilibrium. Because most patients have lived with Cushing’s syndrome for many years, they are at a higher risk of perioperative complications, including poor wound healing, thromboembolic events, and bleeding, especially when a bilateral adrenalectomy is performed. These patients present with associated diseases, such as obesity, hypertension, osteoporosis, thyroid and cardiovascular disease. Resolution or improvement of comorbidities was achieved in 63.2% of the patients with bilateral disease and in 100% of the patients with adrenal adenoma (Table 6).6,11,27,39-44
Laparoscopic Adrenalectomy for Cancer
The role of laparoscopy in the setting of large or malignant adrenal tumors is controversial. Large tumors >6cm have a higher probability of malignancy. Fortunately, tumors of this size are a relatively small percentage of all the adrenal lesions. In general, however, a greater percentage of adrenal lesion in the >6cm range are malignant, compared with smaller tumors. Removing tumors as large as 15cm, although described in the literature,45 is technically challenging, because of the tumor bulk, increased vascularity, and greater difficulty with tumor manipulation and retraction. The risk of morcellating the specimen or making a large extraction incision is also present.
Also adrenal glands are relatively common sites for metastatic disease, being in many cases a manifestation of a more systemic process.46,47 We found 11 articles on malignant adrenal tumor (Table 7).4-6,8-10,16,19,23,51 The authors do not specifically describe the characteristics of the malignancy and the eventual different approach used by the surgeon. For this reason, it is more difficult for us to describe and compare these with the other lesions. Of 1904 adrenalectomies, only 8.1% of tumors were malignant, and of these 30% were metastatic disease. Moreover, many of the diagnoses were established based on the final histological report, and no more action was taken. In the articles48,49 in which adrenalectomy for malignancy was specifically described, no difference was found in operative time, complications, and morbidities between adrenalectomy for malignant or benign tumors.
In a study by Marangos et al,50 41 adrenalectomies were performed for metastatic diseases. The medium tumor size was 6cm with a range of 1.5cm to 15cm, with only 1 conversion and 1 case of resection margin not free. The authors concluded that laparoscopic adrenalectomy for metastatic adrenal tumors is feasible, regardless of the size of the tumor.
Laparoscopic adrenalectomy is the gold standard for removal of adrenal tumors, regardless of the approach used. The lateral transperitoneal approach compared with the retroperitoneal approach is easier and safer; it provides a surgical landmark for the young surgeon who wants to approach this operation and offers the possibility of exploring the entire abdomen and performing combined organ resections if needed. On the other hand, the retroperitoneal approach is faster and less invasive. Three instruments are needed instead of 5 as for the LTA, because of the lack of organs to retract to reach the glands. Also because of the high capnoretroperitoneum up to 28mm Hg, the bleeding rate is reduced. The size of the lesion matters when one is deciding on the laparoscopic or open approach, especially when a malignant tumor is present; nevertheless, the surgeon’s skill can overcome the technical difficulties. Malignancy is no longer considered an absolute contraindication to the laparoscopic approach, unless invasion of the nearby organs or the vasculature has occurred.
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