Laparoscopic compared with open adrenalectomy for resection of pheochromocytoma: a review of 47 cases

Abstract

Objective

We conducted a retrospective cohort study to determine whether laparoscopic adrenalectomy (LA) is a safe and effective therapy for the management of pheochromocytoma, as compared with open adrenalectomy (OA).

Methods

We collected pertinent data on 47 pheochromocytoma resections from 44 patient charts. Perioperative outcomes of 30 LAs were compared with 14 OAs.

Results

Median (and standard deviation [SD]) length of postoperative stay was shorter in the laparoscopic group (3.0, SD 3.3 d v. 6.0, SD 1.1 d; p < 0.05), and tumour size was smaller (3.9, SD 2.7 cm v. 5.0, SD 2.9 cm; p < 0.05). No statistically significant differences were found for operative time or rate of postoperative complications. There were no statistically significant between-group differences in intraoperative hypertensive episodes (systolic blood pressure > 180 and/or diastolic blood pressure > 90) or hypotensive episodes (systolic blood pressure < 100 and/or diastolic blood pressure < 60) or in the need for antihypertensive or vasopressive agents. There were no intraoperative complications related to extremes of blood pressure. There were no perioperative mortalities in this series, nor was there an increased risk of recurrent disease with the laparoscopic technique.

Conclusion

LA is safe and effective for the management of pheochromocytoma.

Since first described by Gagner and colleagues¹ in 1992, laparoscopic adrenalectomy (LA) has become the gold standard for surgical therapy for benign adrenal pathology.^1–3 Many advantages of this technique over open adrenalectomy (OA) have been shown, including decreased postoperative pain, shorter hospital stay and convalescence, reduced intraoperative hemorrhage and improved anatomic exposure.^1,2

However, adrenal pheochromocytomas have been considered a relative contraindication to laparoscopy.² The reasons often cited are increased risk of cardiovascular complications owing to intraoperative catecholamine surges and preoperative uncertainty about malignancy.^2,4–7 Controversy still exists regarding the optimal method for pheochromocytoma resections.^2,6

There is emerging literature on the role of laparoscopic surgery in the management of pheochromocytoma. Many of the existing studies are limited by small sample sizes.^2,3 The current study was therefore designed to determine whether laparoscopic adrenal resection is safe and effective for the management of pheochromocytoma. We conducted a retrospective cohort comparison of laparoscopic and open resections in terms of operative time, intraoperative hemodynamic parameters, complications and length of hospital stay.

Methods

Between 1998 and 2007, 3 surgeons at the University of Western Ontario surgically managed 47 pheochromocytomas. After ethics approval was obtained from the University Health Sciences Research Ethics Board, a single examiner conducted this retrospective chart review. Each hospital chart was reviewed for the following data: demographics, medical and surgical history, surgical procedure, operative time, perioperative blood pressure control, pathologic diagnosis and postoperative course.

Relevant history included modifiable cardiovascular risk factors (e.g., smoking and hypertension), history of inherited disorders related to pheochromocytoma and previous abdominal surgeries. Operative time was calculated independent of the time for anesthesia. Intraoperative hypertension was defined as systolic blood pressure (SBP) over 180 or diastolic blood pressure (DBP) over 90 mm Hg. Hypotension was defined as SBP under 86 or DBP under 60 mm Hg. The intraoperative use of vasopressors and antihypertensives was also recorded.

Preoperative blood pressure control was achieved primarily via α-blockade. Alpha-blocking agents (phenoxybenzamine, prazosin, terazosin and doxazosin) were titrated to achieve symptomatic orthostatic hypotension. Some patients were also treated with regimens including other antihypertensives, such as labetalol, metoprolol, propranolol and ramipril. Alpha-blocking regimens were often adjusted multiple times preoperatively to ensure adequate blood pressure control; therefore, we do not include a discussion of dosing in this paper.

Surgical technique

Preoperative selection of technique depended on the following criteria: tumour location, tumour size and previous abdominal surgery. Only tumours confined to the adrenal gland and not known to be invading adjacent structures were considered for laparoscopic resection. Although tumour size was considered in the preoperative planning, each of the 3 surgeons used different thresholds for laparoscopy.

The transabdominal lateral approach to LA was used for each procedure. For right adrenalectomies, the patient is prepped in the left lateral decubitus position. A 1-cm incision is made in the posterior clavicular line, and the trocar is inserted. A 10-mm, 30° laparoscope is inserted through this incision, and 3 other ports (midclavicular line, umbilicus and anterior clavicular line) are inserted under direct visualization. A Senn retractor is used to retract the liver. Using either electrocautery or a harmonic scalpel, the adrenal gland is exposed, and the adrenal vein is doubly clipped and divided. The remaining vessels are clipped and divided, and the gland is removed intact within a laparoscopic retrieval bag via the umbilical incision. The 1-cm fascial defects and skin incisions are primarily closed. For left-sided tumours, the procedure is similar, with the exceptions that only 3 ports are required and the spleen is partially mobilized to expose the gland.

Open procedures were performed with the use of subcostal incisions in the supine position via the anterior transabdominal approach.

Statistical analysis

We used χ² analysis to compare parametric data. The Mann–Whitney U test was used to compare nonparametric data. Statistical significance was considered as p < 0.05. We used SPSS version 13.0 (SPSS, Chicago, Il.) for all statistical analyses.

Results

We reviewed the charts of 44 patients. In total, there were 44 procedures and 47 pheochromocytomas (Table 1); 30 (68%) subjects underwent laparoscopic resections, 13 (30%) underwent open procedures, and 1 (2%) required conversion because of failure to progress. For most variables, there were no differences at baseline between the groups. The laparascopic group, however, was found to have more bilateral tumours and tumours associated with multiple endocrine neoplasia type IIA.

Table 1

The open group was found to have more incidence of modifiable cardiovascular risk factors and extra-adrenal tumours. These extra-adrenal tumours were located in the organ of Zuckerkandl with associated pheochromocytomatosis, adjacent to the superior mesenteric axis, adjacent to the inferior vena cava and adjacent to the right adrenal gland. There were no extra-adrenal tumours in the laparascopic group because their presence was considered an absolute contraindication.

Open procedures were performed when tumours were large (5), when there was metastatic disease (2), when there had been a previous laparotomy (2), when there was an extra-adrenal tumour (1) and when a tumour adhered to the spleen and left kidney (1). No predetermined threshold was set for tumour size, and consequently, the surgical technique was left to the individual surgeon's discretion. Previous laparotomy was considered a contraindication to laparoscopy if the previous surgery had been extensive. In the 2 subjects for whom this applied, the first had undergone an open repair of a ruptured abdominal aortic aneurysm followed by a bowel resection for ischemic bowel, and the second had received a trauma laparotomy.

No statistically significant difference was found for median (and standard deviation [SD]) operative times between the laparoscopic and open groups, which were 138 (SD 59) minutes and 122 (SD 93) minutes, respectively (Table 2). We reanalyzed the data after excluding 4 unusually complex and long cases (2 bilateral LAs and 2 open debulking procedures for metastatic disease). After we excluded these outliers, the median operative times were 120 (SD 53) minutes for LA and 118 (SD 45) minutes for OA, which again, was not significantly different.

Table 2

The median postoperative stay was found to be significantly shorter in the laparascopic group when compared with the open group at 3.0 (SD 3.3) days and 6.0 (SD 1.1) days, respectively (p < 0.05) (Table 2).

The median tumour size in the open group was significantly greater than in the laparascopic group, at 5.0 (SD 2.9) cm and 3.9 (SD 2.7) cm, respectively (Table 2). In the laparascopic group, 4 (12%) tumours had malignant features (e.g., vascular invasion), although only 1 was found to be metastatic on follow-up. In the open group, 3 (21%) malignant tumours were found, 2 of which had metastases at surgery. This difference in malignancy was not statistically significant.

No statistically significant difference was found in the occurrence of intraoperative hypertensive (SBP and DBP) events between the groups or in the need for intraoperative antihypertensives (Table 3). As well, no statistically significant difference was found in the occurrence of intraoperative hypotensive (SBP and DBP) events between the groups or in the need for intraoperative vasopressors.

Table 3

No patient experienced a complication related to extremes of blood pressure in either group (Table 3 and Table 4). There were no perioperative mortalities in this series, although perioperative complications did occur in 12 (27%) procedures. Complications occurred in 6 (20%) laparoscopic and in 6 (43%) open procedures, which was not statistically significant.

Table 4

Discussion

Our data suggest that LA is a safe and effective technique for the management of pheochromocytoma. Shorter hospital stay was found to be a benefit of the laparoscopic technique. No between-group difference was found for operative time. It was found that even large tumours (e.g., a 14.5-cm cystic tumour) could be safely removed laparoscopically.

The first successful pheochromocytoma resections were reported in 1926 by Drs. Roux and Mayo.^6,8 In the early years of this surgery, the mortality rate approached 50% owing to perioperative cardiovascular complications.^4,6 Improved understanding of disease pathophysiology and advances in surgical and anesthetic techniques have resulted in reduced morbidity and mortality rates for this procedure.

In 1992, Gagner reported on his experience with 3 successful laparoscopic adrenalectomies.¹ The advantages of LA have been well documented in the literature and include decreased postoperative pain, shorter hospital stay and convalescence, decreased blood loss and improved anatomic exposure.^3,9–11

Pheochromocytoma has traditionally been considered a relative contraindication to the laparoscopic approach.¹² Preoperative uncertainty of malignancy and the theoretical risk of uncontrollable catecholamine surges with tumour manipulation are the reasons often cited.¹²

However, emerging evidence suggests that LA for pheochromocytoma can be safe and can achieve the same benefits as laparoscopy for benign adrenal pathology.^6,11–14 Further, intraoperative hemodynamic parameters have not been found to be significantly different when compared with open procedures.^11–15 As a result, the rate of cardiovascular complications has been found to be comparable to the rate for open surgery.^{11–14,16,17}

In the current study, LA was found to be safe and effective for the management of pheochromocytoma. There were no perioperative mortalities, and there were no complications resulting from intraoperative catecholamine surges. The rates of intraoperative hypertensive and hypotensive episodes were similar to rates for OA. As well, the need for intraoperative vasopressive and antihypertensive agents was similar for the laparoscopic and open groups. These findings are noteworthy because they lend support to the notion that, with proper patient selection and preoperative α blockade, adrenal pheochromocytomas can be managed laparoscopically.

The rate of complications was similar between the groups; however, those occurring in the laparoscopic group were less severe and resolved with medical management (Table 3). Three patients in the open group required splenectomy, 2 because extensive adhesion in the region of the spleen led to splenic hemorrhage and the need for removal and 1 because the splenic capsule was torn in the mobilization of the left adrenal gland, again necessitating removal. It is possible that the greater complexity of the tumours and the hostility of the abdomens in the open group could have accounted for this difference. Nonetheless, with proper patient selection, LA is safe and effective for the management of pheochromocytoma.

Operative time in most published series is longer for LA in comparison with OA, although there is a trend toward reduced time with surgeon experience.^18,19

In the current study, however, median operative time was not significantly different between the laparoscopic and open groups. We hypothesized that 2 factors account for this finding: patient selection and the operating surgeons' experience. In terms of patient selection, only tumours that were confined to the adrenal gland were considered for laparoscopy. Consequently, only a single procedure in 44 attempted required conversion to OA. With regard to the second factor, the procedures were performed by experienced laparoscopic surgeons, which has been shown to reduce operative time.^18,19

In the absence of obvious metastatic spread, there is currently no preoperative method to determine whether a pheochromocytoma is benign or malignant.⁷ Surgeons have therefore used tumour size as a surrogate marker of malignant risk, often using 6 cm as a cut-off.⁷ Shen and colleagues⁷ studied pheochromocytoma size and the risk of malignancy and found that, on average, malignant tumours were significantly larger than benign tumours. However, the mean size of localized malignant tumours was similar to that of benign tumours. Consequently, if preoperative investigations confirm that disease is grossly localized, the surgeon is justified in approaching even large (≥ 6 cm) tumours laparoscopically.^7,20 Nonetheless, a low threshold for conversion should be maintained to optimize patient outcomes.

In the current study, tumours in the laparoscopic group were smaller on average than those in the open group. All patients were followed postoperatively for evidence of recurrent symptoms. In the event of symptoms, further metabolic work-up and imaging were performed. Postoperative catecholamine levels were found to be elevated in only 1 patient in the laparoscopic group, and this was found to be due to metastatic disease. Three other patients were found to have malignant features on pathology, but in follow-up have not demonstrated any evidence of recurrence. Both patient selection and adequate postoperative follow-up are essential when using laparoscopic surgery for the management of pheochromocytoma.

Conclusion

LA was found to be safe and effective for the management of pheochromocytoma in this retrospective cohort series. The rates of complications and intraoperative hemodynamic fluctuations were similar to those for open resections. There were no complications related to intraoperative hypertension or hypotension in either group, and there were no perioperative mortalities. The patients who had laparoscopic resections had a shorter hospital stay. Oncologic outcomes were not compromised through the use of laparoscopic surgery. Proper patient selection and specialized surgical and anesthesia teams are required to achieve outcomes similar to those for open pheochromocytoma resections.

Preliminary data were published as an abstract in the Canadian Journal of Surgery (Can J Surg 2005;48[Suppl]:15), and this abstract was presented as a poster at the Canadian Surgery Forum in Montréal, Que., Sept. 8–11, 2005.

Contributors: All authors contributed to study design, data analysis and article review. Drs. Humphrey and Pautler acquired the data and together with Dr. Davies, wrote the article. All authors gave final approval for publication.

Competing interests: None declared.

Accepted for publication Sept. 6, 2007

Correspondence to: Dr. R. Humphrey c/o Dr. D. Gray, Victoria Hospital, London Health Sciences Centre, Room E2-217, 800 Commissioners Rd. E, London ON N6A 5W9; rhumphr2@uwo.ca