Contemporary surgical management of pheochromocytoma

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The American Journal of Surgery 184 (2002) 621– 625

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Contemporary surgical management of pheochromocytoma David J. Bentrem, M.D., Sam G. Pappas, M.D., Yogesh Ahuja, Kenric M. Murayama, M.D., Peter Angelos, M.D., Ph.D.* Department of Surgery, Division of Gastrointestinal and Endocrine Surgery, Galter Pavilion 10-105, Northwestern University Medical Center, Chicago, IL 60611, USA Manuscript received July 31, 2002 Presented at the 54th Annual Meeting of the Southwestern Surgical Congress, Coronado, California, April 7–10, 2002.

Abstract Background: The availability of laparoscopic adrenalectomy led us to review our experience and management of adrenal and extraadrenal pheochromocytoma. Methods: Seventeen patients undergoing pheochromocytoma resection from January 1997 to August 2001 were categorized as open, laparoscopic, or laparoscopic assisted depending on the surgical approach. Hospital records were reviewed. Results: There was no significant difference between the groups in patient age, weight or preoperative blockade. Operative times for open, laparoscopic, and laparoscopic assisted adrenalectomies were 202, 218, and 260 minutes, respectively. Estimated blood loss was 562 cc, 187 cc, and 925 cc. The average hospital length of stay was 6.2, 3.0, and 5.8 days. Conclusions: Laparoscopic removal resulted in longer operative times than open, but less operative blood loss and a shorter hospital stay. The laparoscopic assisted approach did not save time nor did it lead to earlier discharge. Laparoscopic adrenalectomy was comparable to the open approach, and is preferential in tumors less than 6 cm. An open approach remains our choice for larger or extraadrenal tumors. © 2002 Excerpta Medica Inc. All rights reserved. Keywords: Pheochromocytoma; Laparoscopy; Adrenalectomy; Adrenal gland neoplasms

The management of adrenal and extraadrenal pheochromocytoma has challenged surgeons since 1926 when both Charles Mayo and Cesar Roux reported the resection of such tumors [1]. Pheochromocytoma is one of the few causes of hypertension that can be treated surgically. This neuroendocrine tumor is more likely seen in middle-age women. The majority of cases are sporadic, with only 16% having a history of associated endocrine disorders [2]. Surgical management has progressed through the years. Prior to 1980, the thoracoabdominal approach was utilized at some centers [2] to expose and resect large or invasive pheochromocytomas. More commonly the midline abdominal and flank approaches have been used to ensure adequate exposure [3]. Extensive abdominal exploration was also advocated because pheochromocytomas, the “10% tumor,” may be bilateral, multiple, extraadrenal, or malignant. An

* Corresponding author. Tel.: ⫹1-312-695-0641; fax: ⫹1-312-6951462. E-mail address: [email protected]

anterior transabdominal approach allows access to the contralateral adrenal gland and facilitates gaining proximal vascular control and early ligation of the adrenal vein [4]. The flank incision minimizes the risk of intraabdominal organ injury or adhesion formation, but limits exploration of even the ipsilateral adrenal gland. Both approaches have potential morbidity including pulmonary sequelae, postoperative ileus, postoperative pain, and prolonged hospital stay [5]. In 1989 laparoscopy was introduced for the management of cholelithiasis and allowed for therapeutic intervention with less postoperative morbidity. Since the first laparoscopic adrenalectomy for pheochromocytoma in 1992 [6], it has been used selectively for resection of pheochromocytomas and other lesions of the adrenal gland with success [4,6,7]. Laparoscopic adrenalectomy has become more commonplace as technical and safety considerations have been defined. Although laparoscopic resection of pheochromocytomas has been associated with more complications than open removal, for small adrenal cortical tumors this approach is becoming the standard surgical treatment [8,9].

0002-9610/02/$ – see front matter © 2002 Excerpta Medica Inc. All rights reserved. PII: S 0 0 0 2 - 9 6 1 0 ( 0 2 ) 0 1 0 9 7 - 8

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The adoption of laparoscopic adrenalectomy for the management of pheochromocytomas led us to examine the preferred surgical approach. We retrospectively reviewed our institutional experience to compare clinical outcomes and further individualize care of this rare tumor.

Methods The medical records of the 17 patients at Northwestern Memorial Hospital who underwent pheochromocytoma resection between January 1997 and August 2001 were reviewed for demographic information, presenting signs and symptoms, medical history, tumor localization studies, preoperative preparation, operative length, blood loss, length of stay, and complications. Patients were categorized as open, laparoscopic, or laparoscopic assisted based on the initial surgical approach, and the outcomes were compared. All patients underwent a complete preoperative endocrinologic work-up and biochemical confirmation by either catecholamine and catecholamine metabolite concentration in a 24-hour urine collection or plasma catecholamine level. Preoperative localization was performed. The preoperative blockade consisted of an alpha-blocker with phenoxybenzamine with the addition of a beta-blocker in select patients. A single endocrine surgeon performed all of the resections. Our open approach for adrenal pheochromocytomas was transabdominal through a subcostal incision. For those patients with extraadrenal disease, a transverse incision was made centered over the tumor. Our laparoscopic approach was done in a transabdominal fashion with lateral decubitus positioning. A left adrenalectomy was performed with the patient in a right lateral decubitus position. A 10-mm trocar was placed in the midclavicular line just below the costal margin. A second 10-mm trocar was placed at least 5 cm medial to this, also below the costal margin. Then a 5-mm trocar was placed just below the costal margin in the midaxillary line 5 cm lateral to the first trocar. The lateral attachments to the spleen and the splenorenal ligament were divided, allowing the spleen and pancreatic tail to fall medially, exposing the retroperitoneum which was opened to isolate the adrenal gland. The medial border of the gland was dissected first, and the adrenal veins were then clipped and divided. The gland was dissected free using a harmonic scalpel and placed in a specimen bag for removal through a trocar site. For a right adrenalectomy a similar right-sided trocar placement was used, with an additional 5-mm port placed medially below the costal margin to the right of the xyphoid process for a liver retractor to elevate the right lobe of the liver. The right triangular ligament of the liver was dissected with laparoscopic scissors and forceps, exposing the inferior vena cava. The perinephric fat was dissected superiorly and close to the vena cava to reveal the adrenal gland. The gland was carefully dissected from the surrounding tissues, ensur-

Table 1 Patient demographics and tumor characteristics ⫾ standard deviation

Number of patients M:F Age (year) Mean tumor size (cm) Location (right:left:bilateral) Adrenal:extraadrenal

OA

LA

LAA

9 4:5 44.7 ⫾ 16 6.3 ⫾ 3.8 3:5:1 5:4

4 1:3 43 ⫾ 12 4.3 ⫾ 1.6 0:4:0 4:0

4 4:0 42.8 ⫾ 11 6.3 ⫾ 1.2 1:3:0 4:0

OA ⫽ open adrenalectomy; LA ⫽ laparoscopic adrenalectomy; LAA ⫽ laparoscopic assisted adrenalectomy; M ⫽ male; F ⫽ female.

ing control of the adrenal vein. As on the left side, the gland was placed in a bag prior to removal through a port site. For patients with larger tumors where the surgeon was unsure the operation could be completed laparoscopically, some patients had a laparoscopic assisted approach. In these cases, the initial dissection was begun laparoscopically with planned conversion to an open procedure to complete the dissection. The laparoscopic assisted approach was also done in the lateral decubitus position. After laparoscopic mobilization of liver or spleen, the retroperitoneum was entered and as much dissection as safely possible was performed laparoscopically with a harmonic scalpel. When it was not safe to proceed further laparoscopically, we converted to an open procedure by making a subcostal incision, but not changing from decubitus position.

Results Eighteen pheochromocytomas were removed from 17 patients, 9 in the open group, 4 in the laparoscopic group, and 4 in the laparoscopic assisted group. There was no significant difference between the groups with respect to patient age, weight, or preoperative blockade. Four of the 18 tumors were extraadrenal, all of which were resected through an open transabdominal approach. The predominance of extraadrenal pheochromocytomas in the open group reflects our practice preferences. The most common presenting symptom was hypertension, followed by headache, palpitations, sweating, and diarrhea. All patients had a preoperative abdominal computed tomography (CT) scan. The mean size of the lesions in the open group was 6.7 ⫾ 3.3 cm, in the laparoscopic group it was 4.2 ⫾ 1.6 cm, and in the laparoscopic assisted group it was 6.3 ⫾ 1.1 cm (Table 1). Therefore, the three groups were not equivalent: the laparoscopic group had a smaller mean tumor size than the other two groups and this reflects patient selection (larger tumors and extraadrenal tumors are more difficult to approach in a laparoscopic fashion). The mean operative time was 202 ⫾ 83 minutes for open removal, with a range of 105 to 380 minutes. This compared with a mean operative time of 218 ⫾ 74 minutes for laparoscopic adrenalectomy, with a range of 160 to 325 minutes,

D.J. Bentrem et al. / The American Journal of Surgery 184 (2002) 621– 625 Table 2 Comparison of average operating room time, average estimated blood loss, and average hospital stay

Average OR time (min) Average EBL (mL) Average hospital stay (days)

623

OA

LA

LAA

P value

assisted adrenalectomy (Fig. 1B). No deaths were recorded. When comparing mean operating time, estimated blood loss, and length of hospital stay, the differences were not statistically significant given the small sample size.

202 550 6.2

218 188 3.0

260 925 5.8

0.262 0.183 0.361

Comments

P values generated using a one-tailed analysis of variance. OA ⫽ open adrenalectomy; LA ⫽ laparoscopic adrenalectomy; LAA ⫽ laparoscopic assisted adrenalectomy; OR ⫽ operating room; EBL ⫽ estimated blood loss.

and 260 ⫾ 47 minutes for the laparoscopic assisted group, with a range of 230 to 330 minutes (Table 2). The mean estimated blood loss was 550 ⫾ 528 mL, range 100 to 1700 mL for open removal; 188 ⫾ 85 mL, range 100 to 300 mL for laparoscopic adrenalectomy; and 925 ⫾ 763 mL, range 200 to 1800 mL for laparoscopic assisted adrenalectomy (Fig. 1A). The mean hospital stay after open removal was 6.2 ⫾ 4.8 days, range 4 to 18 days. This compared with 3.0 ⫾ 1.4 days, range 2 to 5 days for laparoscopic adrenalectomy; and 5.8 ⫾ 1.2 days, range 4 to 7 days for laparoscopic

Fig. 1. A. Comparison of mean ⫾ standard error for estimated blood loss among open, laparoscopic, and laparscopic assisted adrenalectomy. B. Comparison of mean ⫾ standard error for hospital stays among open, laparoscopic, and laparscopic assisted adrenalectomy.

During surgery for pheochromocytoma there is a risk of hypotensive or hypertensive crisis due to excessive catecholamine release, which cannot be completely precluded even with preoperative alpha-blockade. There are concerns that laparoscopy may increase the risk of such crises [10]. Others have shown that the catecholamine release during laparoscopic removal is lower than with open surgery [11,12]. Because of difficulty in obtaining adequate exposure, several different surgical approaches have been used. The absolute contraindications for laparoscopic adrenalectomy are few. We do not recommend laparoscopic adrenalectomy for suspected primary malignant lesions, but this is very difficult to determine preoperatively. If malignancy is suspected based on magnetic resonance imaging or metaiodobenzyl guanidine nuclear scan results showing metastatic nodes present in the periaortic chain or close to the bladder, an open approach is more desirable due to the possible extent and complexity of the operation. Laparoscopic adrenalectomy is becoming a preferred method of surgically treating patients with pheochromocytoma [4,13–15]. Prinz et al [5] compared conventional transabdominal and posterior adrenalectomy with the laparoscopic approach in lesions less than 10 cm. The operating time for the laparoscopic and anterior adrenalectomy were similar, while the hospital stay was shorter for the patients undergoing laparoscopy (2.1 days versus 6 days). This difference was not statistically significant due to the limited numbers of this rare tumor. Laparoscopic resection can be a technically demanding procedure, complicated by poor exposure and difficulty identifying the adrenal gland, but the magnification afforded by the laparoscope and the lateral approach aids in identifying the adrenal vasculature facilitating adrenalectomy. Although the three groups are not identical in our retrospective study, these data may help surgeons select the most appropriate operative approach for their patients. This study, though limited by a small number of patients, is one of the few to make comparisons among patients undergoing adrenalectomy for only pheochromocytoma. Most other series with larger numbers have included other adrenal lesions in the comparisons made. Furthermore, this review compares the laparoscopic assisted approach to laparoscopic and open approaches. Our retrospective comparative study found laparoscopic removal had longer operative times than the open procedure, yet less blood loss and shorter hospital stays overall. Laparoscopic adrenalectomy is comparable to the open approach, and should be considered preferentially in patients

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with tumors less than 6 cm. For larger or extraadrenal pheochromocytomas an open approach is favored. Given that the laparoscopic assisted approach was similar to the open approach for operating time and length of stay, we recommend an open procedure if it is unlikely that the entire procedure can be done fully laparoscopically. When performed by an experienced team of surgeon, endocrinologist, and anesthesiologist, the inherent risk of managing pheochromocytomas is not increased by the laparoscopic approach. Overall, surgical management should be individualized to better serve patients with this uncommon disease.

Acknowledgments Supported by a grant from the Goldberg Family Charitable Trust of Northwestern Memorial Hospital and by the generous support of Julia Saccente and Barry Levine.

References [1] Wilbourn R. Early surgical history of phaeochromocytoma. Br J Surg 1987;74:594 – 6. [2] Goldstein RE, O’Neill JA, Holcomb GW, et al. Clinical experience over 48 years with pheochromocytoma. Ann Surg 1999;229:755– 66. [3] Foster RS HJ, Spivak H, Smith CD. Open adrenalectomy. Anatomic basis of tumor surgery. St. Louis: Quality Medical, 1999, p 784 – 808. [4] Duncan JL, Fuhrman GM, Bolton JS, et al. Laparoscopic adrenalectomy is superior to an open approach to treat primary hyperaldosteronism. Am Surg 2000;66:932–56. [5] Prinz RA. A comparison of laparoscopic and open adrenalectomies. Arch Surg 1995;130:489 –94. [6] Gagner M, Lacroix A, Bolte E. Laparoscopic adrenalectomy in Cushing’s syndrome and pheochromocytoma. N Engl J Med 1992;327: 1033. [7] Sardi A, McKinnon W. Laparoscopic adrenalectomy for primary aldosteronism. JAMA 1993;269:989 –90. [8] Gagner M, Breton G, Pharand D, Pomp A. Is laparoscopic adrenalectomy indicated for pheochromocytomas? Surgery 1996;120(6):76 – 80. [9] Janetschek G, Neumann HP. Laparoscopic surgery for pheochromocytoma. Urol Clin North Am 2001;28:97–105. [10] Mann C, Millat B, Boccara G, et al. Tolerance of laparoscopy for resection of phaeochromocytoma. Br J Anaesth 1996;77:795–7. [11] Fernandez-Cruz L, Saenz A, Taura P, et al. Pheochromocytoma: laparoscopic approach with CO2 and helium pneumoperitoneum. Endosc Surg Allied Technol 1994;2:300 – 4. [12] Fernandez-Cruz L, Taura P, Saenz A, et al. Laparoscopic approach to pheochromocytoma: hemodynamic changes and catecholamine secretion. World J Surg 1996;20:762– 8. [13] Ishikawa T, Sowa M, Nagayama M, et al. Laparoscopic adrenalectomy: comparison with the conventional approach. Surg Laparosc Endosc 1997;7:275– 80. [14] Korman JE, Ho T, Hiatt JR, Phillips EH. Comparison of laparoscopic and open adrenalectomy. Am Surg 1997;63:908 –12. [15] Winfield HN, Hamilton BD, Bravo EL, Novick AC. Laparoscopic adrenalectomy: the preferred choice? A comparison to open adrenalectomy. J Urol 1998;160:325–9.

Discussion Maria Allo (San Jose, CA): The authors present a retrospective review of 17 patients over five years undergoing operative management of pheochromocytoma. Patients were analyzed in three cohorts. Those undergoing open procedures, those having a laparoscopically assisted procedure and those undergoing laparoscopy—purely laparoscopic operations. The conclusion—their conclusions are reasonable and are similar to those reported in similar series. My main critique of this paper has to do with the fact that the series is not randomized and that consequently the groups compared are not really comparable. The times—my first question is, the times for laparoscopic assisted cases were significantly longer than for open or laparoscopic operations. Can you please define the term laparoscopic assisted were these and any case conversions of operations that were originally designated to be laparoscopic. And along those same lines, it’s been my experience that positioning a patient for laparoscopic adrenalectomy puts them in a very awkward position for opening. Among the laparoscopically assisted cases, how many required repositioning and possibly also re-prepping in order to facilitate open exposure? The other question has to do with blood loss. The standard open approach has historically been transabdominal and it’s been my experience that as these tumors get to be larger, particularly on the right side, there intimacy with vascular structures becomes such that the actual dissection is a lot more treacherous and a lot more interesting and particularly on the right, as I mention, where vena cava is sometimes encircled by the tumor and obviously this would potentially be a source of more blood loss. Do you feel that the increase in blood loss in your open cases was as much related to the difference in that population, for example, your open tumors were largely 6 cm or more as opposed to the laparoscopic ones as opposed to something intrinsically related to the procedure? And my last question is sort of—the standard open approach as always been transabdominal, but if you can justify laparoscopic removal of the smaller tumors, could you also justify approaching them open from a posterior approach? In open cases where I go posteriorly and don’t cut any muscle, maybe take the 12th rib, the operative times are significantly shorter, about 45 minutes, blood loss is fairly minimal and patients go home the next day. David Bentrem: First a comment, this was not a randomized series. We’d love to be able to see the volume to be able to randomize. The Vanderbilt Series was one of the largest and they had a 100 pheochromocytomas, but it took them 50 years to accrue that. Nevertheless, times are longer for the laparoscopic assisted. They all had been planned, but it did take us a while to do the full laparoscopic set up, break that down and then to do an open incision to remove the tumor. Blood loss being the function of the tumor

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