Laparoscopic Adrenalectomy (LA): Keys to Success Correct Surgical Indications, Adequate Preoperative Preparation, Surgical Team Experience
Marco Lodin, MD, Antonio Privitera, MD, MRCSEd, and Giorgio Giannone, MD, FACS
Background: Laparoscopic adrenalectomy (LA) has become the surgical procedure of choice for the treatment of most adrenal lesions. Controversy still remains about the treatment for primary and secondary malignant lesions and for pheochromo- cytoma.
Materials and Methods: From September 1997 to December 2005, 77 patients were operated on for adrenal tumors in a single center. Three patients had bilateral lesion for a total of 80 adrenalectomies. Selection criteria for laparoscopic treatment included benign characteristics of the lesions regardless of size and absence of virilization syndrome. A multidisciplinary approach was used for adequate preparation of patients with functional lesions. Fifty-five patients were eligible for LA and 22 for open surgery.
Results: Mean operative time was 142 minutes (range 45 to 240) in the laparoscopic group (53 patients) and 161 minutes (range 90 to 300) for the open group (24 patients). In 2 patients (4%) conversion to open procedure was necessary for intraoperative bleeding. Laparoscopic surgery in patients with pheochromocy- toma was associated with a better intraoperative hemodynamic stability.
Conclusions: LA is the treatment of choice for benign adrenal tumors regardless of size. Appropriate selection of patients, adequate preoperative preparation of patients with functional lesions and expertise in adrenal surgery and advanced laparo- scopic skills are necessary to allow reduction of perioperative morbidity and early recovery.
Key Words: adrenal neoplasms, adrenocortical carcinoma, endocrine disorders, laparoscopic adrenalectomy, pheochromo- cytoma, minimally invasive surgery
(Surg Laparosc Endosc Percutan Tech 2007;17:392-395)
O ☐ ver the last 10 years, laparoscopic adrenalectomy (LA) has become the procedure of choice for the treatment of most adrenal tumors. The small size of the
From the Department of Oncology, Division of Surgical Oncology, Ospedale Garibaldi Nesima, Via Palermo, Catania, Italy.
Reprints: Dr Marco Lodin, MD, Oncologic Surgery, Istituto Oncologico del Mediterrano (IOM), Via Penninazzo 7, 95029 Viagrande (CT), Italia (e-mail: marcolodin2004@yahoo.it).
Copyright @ 2007 by Lippincott Williams & Wilkins
gland, its retroperitoneal location together with the rarity of malignant lesions, makes the use of the minimally invasive technique ideal. In fact, this allows easy access to the organ, magnified operative view, and possibility of working comfortably in a limited space. Since the first LA described by Gagner et al1 in 1992, an increasing number of studies have been reported. The widespread use of laparoscopy for adrenalectomy seems to follow a trend similar to laparoscopic cholecystectomy. Centers that have started to use laparoscopy for the treatment of adrenal lesions have found this to be a rewarding approach and have moved onto limiting the open method to more complex cases or to less experienced surgeons. Several studies have shown far better results with laparoscopy than open technique in terms of hospital stay, intraoperative blood loss, postoperative requirement of analgesics, early recovery, and short and long-term complications.2-5 Nevertheless, laparoscopic treatment of primary and secondary adrenal malignant lesions still remains controversial and treatment of pheochromocy- toma in consideration of the risk of intraoperative hemodynamic instability. The authors report their ex- perience with open and LA and discuss selection criteria for the choice of the most appropriate surgical approach.
MATERIALS AND METHODS
From September 1997 to December 2005, 77 patients affected by functional and nonfunctional adrenal neoplasms underwent surgical treatment at our Division for a total of 80 adrenalectomies (3 bilateral). The criteria used for the selection of patients eligible for a laparo- scopic procedure were benign characteristics of the adrenal lesions (unilateral and bilateral) assessed by ultrasound scan and computed tomography (CT) scan/ magnetic resonance imaging (MRI) (well-circumscribed mass lesions with homogeneous signal intensity and enhancement patterns),6,7 with particular attention to the presence of infiltration of the adrenal capsule and invasion of surrounding anatomic structures; absence of virilization syndrome. The size of the adrenal lesion was not an absolute contraindication to the laparoscopic procedure: 19 out of 54 lesions (35%) were greater than 6 cm.
Fifty-five patients were eligible for LA. Two patients required conversion to open surgery to control
intraoperative bleeding. They were both affected by right adrenal lesions and had received a preoperative diagnosis of pheochromocytoma and cortisol-secreting adenoma causing Cushing syndrome, respectively. In the laparo- scopic group 15 patients were males and 38 females, mean age 47.7 years ± 17.8 standard deviation (range 14 to 79 y). Fifty-four adrenalectomies were carried out: 34 right, 18 left, 1 bilateral (average size 5.8 cm, range 2.5 to 12 cm). All laparoscopic adrenalectomies were carried out or supervised by the same surgeon (G.G.). An anterior transabdominal approach in lateral decubitus was pre- ferred, because it allows a wide exposure and better control of vascular structures, of particular importance when operating on pheochromocytomas. Access was achieved through 3 port sites in left-sided lesions and 4 in right-sided lesions, the fourth port needed for liver retraction.
Twenty-two patients were eligible for open adrena- lectomy. Ten patients were males and 14 females, mean age 47.7 ± 18.4 DS (range 18 to 79 y). Selection criteria were adrenal lesions that were diagnosed as malignant or likely malignant (irregular margins, signs of tissue, or vascular invasion); adrenal tumors causing virilization; single metastatic lesions from an extra-adrenal tumor. A total of 26 adrenalectomies (2 after initial attempt at laparoscopy) were carried out: 12 right, 10 left, 2 bilateral. The 2 bilateral adrenalectomies were performed for carcinoma and pheochromocytoma, respectively. Adrenal lesions had a mean size of 8.7 cm (range 4 to 25 cm). An anterior transabdominal approach in lateral position was used. A subcostal incision was performed and magnifying glasses (2.5 x ) were routinely used.
Diagnosis of pheochromocytoma was achieved in all patients by measuring urinary catecholamines and radiologic imaging (ultrasound, CT, MRI, and iodine- 131-meta-iodobenzylguanidine scans). One patient pre- sented with pheochromocytoma in the context of MEN 2A syndrome. Before operation, patients were admitted to ICU to monitor blood pressure and assess response to phenoxybenzamine. In some cases, phenoxybenzamine treatment was suspended owing to the onset of important orthostatic hypotension. Blood pressure control was achieved with Doxazosin and was monitored by an endocrinologist. Intraoperative hypertension was con- trolled with infusion of sodium nitroprussiate. Beta- blockers were used in patients with tachycardia. From January 2003, a laparoscopic approach was preferred in patients with pheochromocytoma. Ligation of the adrenal vein was the first step of adrenal dissection in pheochro- mocytoma.
RESULTS
The mean operative time for LA was 142 minutes (range 45 to 240), with a mean hospital stay of 3.3 days (range 2 to 6d)-Table 1. The average operative time for LA for carcinoma was 133 minutes (range 45 to 210), with a mean hospital stay of 4 days (range 2 to 6 d). Histology showed adenoma (23), pheochromocytoma (15), myelo-
| TABLE 1. LA and OA: Operative and Perioperative Data | ||
|---|---|---|
| LA | OA | |
| Total patients | 53 | 24 |
| Male/female | 15/38 | 10/14 |
| Average age | 47.4 (14-79) y | 47.7 (18-79) y |
| Mean operative time | 142 min (45-240 min) | 161 min (90-300 min) |
| Hospital stay | 3.3 (2-6) d | 5.2 (3-12) d |
| Average size | 5.8 (2.5-12)cm | 8.7 (4-25)cm |
| Blood transfusion | 3 UI | 5 UI |
OA indicates open adrenalectomy.
lipoma (8), cyst (1), bilateral nodular hyperplasia (1), incidentaloma (5), metastases from melanoma (1)-Table 2. Histologic examination of the 5 patients (3 females and 2 males) operated on for right-sided incidentaloma (8, 6, 3.5, 6.5, and 4.5 cm) was reported as adrenocortical carcinoma: 1 patient aged 33 with a preoperative diagnosis of Cushing syndrome owing to a cortisol- releasing adenoma of 6 cm, died 2 years after operation with diffuse metastatic disease; 1 patient had preoperative diagnosis of Conn syndrome; the patient with corticoa- drenal carcinoma of 8 cm is still alive at 58 months with no evidence of recurrence.
Two patients (4%) required conversion to open surgery to control intraoperative bleeding (both right- sided adrenal lesions): 1 patient had pheochromocytoma and Sturge-Weber syndrome and required 2 U of blood postoperatively; the other patient with a functional adenoma causing Cushing syndrome, did not need blood transfusion.
The mean operative time for open adrenalectomy was 161 minutes (range 90 to 300) with a mean hospital stay of 5.2 days (3 to 12d)- Table 1. Histology was reported as carcinoma (7), metastasis from extra-adrenal tumor (5), pheochromocytoma (4), adenoma (4), myelo- lipoma (1), vascular pseudocyst (1), ganglioneuroblasto- ma (1), neuroblastoma (1), paraganglioma (2)-Table 2. The patient with bilateral carcinoma underwent bilateral adrenalectomy with distal pancreatectomy for the in- volvement of the pancreatic tail. This patient developed pancreatic fistula that resolved spontaneously after 3
| LA | OA | |
|---|---|---|
| Adenoma | 23 | 4 |
| Pheochromocytoma | 15 | 6 |
| Carcinoma | 5 | 7 |
| Metastases | 1 | 5 |
| Myelolipoma | 8 | 1 |
| Pseudocysts | 1 | 1 |
| Hyperplasia | 1 | — |
| Ganglioneuroblastoma | — | 1 |
| Neuroblastoma | — | 1 |
| Paraganglioma | — | 2 |
| Total | 54 | 26 |
OA indicates open adrenalectomy.
weeks. One patient had carcinoma causing virilization syndrome (acne, hirsutism, oligomenorrhea, increase of muscular mass, lowering of voice). One patient with adrenal carcinoma of 12cm, received adjuvant che- motherapy with mitotane and died 16 months later with lung metastases. In 1 patient with 7.5 cm carcinoma, open adrenalectomy was associated with resection of hepatic metastases. The patient received adjuvant chemotherapy (mitotane associated to cytotoxic chemotherapy: adria- mycin, cisplatin, and etoposide) and died 9 months after operation. In the 5 patients who underwent open adrenalectomy for metastatic lesions, the primary site was kidney (1), liver (1), lung (2 nonsmall cell pulmonary carcinoma), melanoma (1). In 1 out of 5 patients, finding of adrenal metastases was concurrent with the diagnosis of nonsmall cell lung cancer. A pneumonectomy and adrenalectomy were carried out through a thoraco- abdominal incision. Postoperative bleeding occurred in 1 patient with ganglioblastoma (diameter 13 cm). This settled spontaneously and required transfusion of 5 U of blood.
DISCUSSION
Most unilateral and bilateral adrenal neoplasms, including the functional type and in particular pheochro- mocytomas, may be treated safely and effectively through a laparoscopic approach.8,9 In our experience, the conversion rate was 4% (2 cases) and this is comparable to other reports in the literature.10 The reason for conversion was intraoperative bleeding that is the most frequent complication of LA. This tends to decrease with surgical experience.11 Moreover, the incidence of a systemic inflammatory response syndrome seems to be reduced compared with open surgery.12 The size of the adrenal lesion was not a selection criteria for the choice of the surgical procedure. Nineteen out of 54 lesions (35%) treated with laparoscopy were equal or greater than 6 cm. Several studies have suggested that the size of the tumor cannot be considered as the only parameter to determine the biologic characteristics of adrenal tumors. 10,13-15 Although the prevalence of adrenocortical cancer is related to the size of the lesion with an overall positivity estimated in 25% to 29% for lesions with a diameter greater than 6 cm,10,16 accurate imaging (ultrasound, CT, MRI, and scintigraphy scan) is fundamental in the attempt of selecting lesions likely to be malignant (tumors with irregular margins and vascular infiltrations, dish- omogeneity, lymphadenopathy, etc.). However, despite the selection criteria adopted and the advancement in imaging techniques, it is not always possible to achieve a preoperative diagnosis of cancer. In our study, the 5 incidentalomas treated laparoscopically, were shown to be cancer at histology. This emphasizes the low sensitivity and accuracy of diagnostic investigations.17 As regard functional tumors, virilization was an indication for open surgery because it is more likely associated to a malignant lesion.
Ng and Libertino,13 in a review of the literature of 602 patients with adrenocortical carcinoma from 4 American institutes and 3 non-American institutes, report the presence of functional tumors in 62% of cases. Of these 39.5% had clinical evidence of Cushing syndrome and this was associated with virilization in 24%. Flack and Chrousos18 reported Cushing syndrome in 30% to 40% of patients affected by adrenocortical carcinoma. Bertagna and Orth19 reported that virilization is a distinctive characteristic of Cushing syndrome caused by adrenocortical carcinoma. Latronico and Chrousos20 reported virilization onset as the only presentation in 20% to 30% of the patients affected by functional adrenocortical carcinoma.
LA for primary and metastatic adrenal tumors is controversial. Because these tumors are rare, reports in the literature are limited only to small cohort studies. According to many authors, the current contraindication to LA is a definitive or suspected diagnosis of invasive adrenocortical carcinoma, where extensive complex sur- gery may be required (en bloc resection of the kidney with perirenal fat tissue, spleen resection, lymphadenectomy, etc.).21 Infiltration of surrounding tissues and the risk of implantation are factors that make open procedure preferable. LA for malignant adrenal lesions remains associated with high rates of local recurrence.17
We prefer open surgery when a lesion is suspicious for cancer because radical en bloc resection is needed. Although intraoperative finding of invasive carcinoma did not lead to conversion to open surgery in our study, we believe that conversion to open surgery should always be carried out in those cases in which a local invasion is present. In fact in these circumstances a radical laparo- scopic treatment may be difficult to achieve.
Some authors have shown that aggressive surgical treatment of single adrenal metastases in patients with complete resection of the primary cancer and a long disease-free interval, improves survival. This is particu- larly evident for renal and nonsmall cell lung cancer primary.22,23 Kebebew et al,17 showed that LA is safe and effective for single extra-adrenal metastases. In their study, no local-regional recurrence was detected at a mean follow-up of 3.3 years.17 In consideration of such results, starting from January 2005, we carried out a laparoscopic approach also for single adrenal metastases confined to the gland.
As regard pheochromocytoma, adequate preopera- tive preparation is a pivotal element for a successful treatment. Poor preparation is generally responsible for conversion to open surgery. Two of our patients operated on for pheochromocytoma had undergone a failed attempt of surgery in other nonreference institutions. Hemodynamic instability has been shown to be reduced with laparoscopic surgery.24 Reduced hospital stay and postoperative pain, rapid recovery are other advantages of the laparoscopic procedure.25,26 In hereditary and familial syndromes in which bilateral lesions are present, laparoscopy allows safe and effective cortical-sparing bilateral adrenalectomy.27
CONCLUSIONS
LA is safe and effective. Indications include benign functional (without virilization syndrome) and nonfunc- tional adrenal lesions, regardless of size. In our retro- spective study, the laparoscopic technique was shown to be practical even with lesions greater than 6 cm.
Accurate selection of patients, adequate preparation of patients affected by functional lesions and expertise in open and laparoscopic surgery are key elements to achieve a satisfactory outcome with reduction of perio- perative morbidity.
ACKNOWLEDGMENT
The authors thank Elizabeth Talamanca for editorial assistance.
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