EXPERIENCE WITH RETROPERITONEAL LAPAROSCOPIC ADRENALECTOMY FOR PHEOCHROMOCYTOMA

0022-5347/01/1656-1871/0 THE JOURNAL OF UROLOGY® Copyright © 2001 by AMERICAN UROLOGICAL ASSOCIATION, INC.®

Vol. 165, 1871–1874, June 2001 Printed in U.S.A.

EXPERIENCE WITH RETROPERITONEAL LAPAROSCOPIC ADRENALECTOMY FOR PHEOCHROMOCYTOMA LAURENT SALOMON, REDOUANE RABII, MICHEL SOULIE, PATRICK MOULY, ANDRAS HOZNEK, ANTONY CICCO, FABIEN SAINT, WALID ALAME, PATRICK ANTIPHON, DOMINIQUE CHOPIN, PIERRE PLANTE AND CLEMENT-CLAUDE ABBOU From the Department of Urology, Henri Mondor Hospital, Cre´teil and Department of Urology, Rangueil Hospital, Toulouse, France

ABSTRACT

Purpose: Although laparoscopic adrenalectomy has become the preferred surgical treatment of benign adrenal masses, for pheochromocytoma it is limited by concerns over hypertensive events related to early access to the adrenal vein. We report our experience with retroperitoneal laparoscopic adrenalectomy for pheochromocytoma. Materials and Methods: From January 1995 to December 1999, 21 retroperitoneal laparoscopic adrenalectomies (left 12 and right 9) were performed for symptomatic pheochromocytoma in 11 men and 9 women 17 to 68 years old (mean age 46). To our knowledge pheochromocytoma was always diagnosed by increased urinary catecholamine, computerized tomography, magnetic resonance imaging and 131iodine iobenguane scintigraphy. Results: There were no conversions to open surgery. The operating time ranged from 100 to 150 minutes (mean 116). Mean blood loss was 140 ml. (minimum 550), and none of the patients required transfusion. Hemorrhage due to adrenal vein injury occurred in 1 patient and was controlled intraoperatively. Average postoperative hospital stay was 3.4 days (range 1 to 12). The mean diameter of the excised masses was 38 mm. (range 15 to 70). Postoperative complications occurred in 4 cases, including hematoma in 1, trocar wound infections in 2 and eventration in 1 after 1 year. With a mean followup of 21.6 months (range 6 to 46), all patients had normal urinary catecholamine levels and 18 had normal blood pressure without treatment. Conclusions: Retroperitoneal laparoscopic adrenalectomy can be safely performed for small (less than 5 cm. diameter) pheochromocytoma. Retroperitoneal laparoscopy is a direct approach that allows the surgeon to control the adrenal vein first, thereby avoiding hypertensive events. KEY WORDS: adrenal gland neoplasms, pheochromocytoma, adrenalectomy, laparoscopy

The adrenal gland is located deep in the retroperitoneum beneath the diaphragm. Open surgery based on the anterior transabdominal, posterior and flank approaches is difficult and demanding, and is associated with complications and lengthy convalescence.1 Since the first report on laparoscopic adrenalectomy by Gagner et al,2 laparoscopy has become the preferred technique for surgical treatment of adrenal tumors.3–7 However, there are still doubts over the use of the laparoscopic approach for pheochromocytoma. During surgery for pheochromocytoma, there is a risk of hypertensive events due to excessive catecholamine secretion. These hypertensive events are thought to be more severe or frequent with the laparoscopic approach than with traditional surgery, although some authors have reported good results.8 –16 Laparoscopic adrenalectomy can be performed either transperitoneally or retroperitoneally.8 –11 Most laparoscopic adrenalectomies for pheochromocytoma have been performed with a transperitoneal approach.11–16 At our 2 institutions we have used the same retroperitoneal approach, which in our opinion is more suitable for initial control of the adrenal vein, and report our experience with it for pheochromocytoma. METHODS

From January 1995 to December 1999, 115 adrenalectomies were performed at our 2 centers with a retroperitoneal laparoscopic approach. There were 11 men and 9 women age 17 to 68 years (mean 46) who underwent 21 adrenalectomies Accepted for publication December 1, 2000.

for symptomatic pheochromocytoma. One patient had bilateral hereditary pheochromocytoma and multiple endocrine neoplasia syndrome. All patients had hypertension preoperatively. Pheochromocytoma was always diagnosed on the basis of increased urinary catecholamine, including vanillylmandelic acid, metanephrine and normetanephrine, and 131iodine iobenguane scintigraphy. Computerized tomography and nuclear magnetic resonance imaging, including bright “light bulb” image on T2 weighted study, showed pheochromocytoma on the right side in 9 cases and on the left side in 12. Mean body weight was 68.5 kg. (range 53 to 90) and mean height was 166.6 cm. (range 153 to 183). Anesthesia. All patients were treated 2 to 10 days preoperatively with antihypertensive medications, including ␣ and ␤-blocker, and calcium channel blocker (labetalol and nifedipine), to stabilize blood pressure and heart rate. Central venous and arterial catheters for continuous arterial blood pressure monitoring were used. Patients were ventilated with a mixture of air, oxygen and isoflurane. The end-tidal carbon dioxide level was adjusted by varying the tidal volume and respiratory frequency. Hypertensive events were treated with calcium channel blocker (nicardipine) and ␤ blocker (atenolol) infusion. Technique. The technique has been previously described in detail for both sides.9 The patient was placed in the flank position without overextension. An incision was made in the triangle between the 12th rib and latissimus dorsi muscle on the posterior axillary line, and a tunnel was created through the external oblique muscle so that an index finger intro-

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FIG. 1. Position of different trocars. A, 12 mm. trocar for suction irritating device or bipolar coagulator forceps. B, 5 mm. trocar for rotating tip coagulating scissors. C, 10 mm. trocar for laparoscope. D and E, 5 mm. trocar for simple grasping of forceps by assistant. AAL, anterior axillary line. PAL, posterior axillary line.

duced through the first incision was able to push the peritoneum forward. There were 2, 5 mm. trocars inserted for the left and right hand of the assistant on the anterior axillary line, and 2 trocars (12 and 5 mm.) were inserted for the right and left hand of the surgeon on the posterior axillary line. A fifth trocar (10 mm.) was inserted for the lens on the mid axillary line (fig. 1). After creating retroperitoneal access and completing the working space with insufflation and dissection of the retroperitoneal elements, Gerota’s fascia was incised. The renal pedicle was identified, often by arterial pulses. Before mobilizing the adrenal gland, the adrenal vein was first identified, controlled and clipped (fig. 2, A). To the right side, the vena cava then the renal pedicle were identified, allowing dissection to be continued upwards until the adrenal vein was located, clipped and cut (fig. 2, B). To the left side, dissection of the renal pedicle, especially the renal vein, allowed us to distinguish the adrenal vein between the renal vein and renal artery, which was clipped and cut (fig. 2, C). At this stage, the adrenal gland was generally well identified. It was then reclined into a caudal position, freed of upper diaphragmatic attachments, and separated from the upper pole of the kidney and peritoneum with electrocautery. The entire surgical specimen was extracted without morcellation in an Endo Catch* endoscopic bag through the 12 mm. opening. A suction drain was inserted for 24 hours, and the puncture site was closed with 2-zero polyglycolic acid sutures. RESULTS

There were no conversions to open surgery. The operating time, that is time between the first incision to closure of the trocar sites, ranged from 100 to 150 minutes (mean 116). Mean blood loss was 140 ml. (minimum 550), and none of the patients required transfusion. Hemorrhage due to adrenal vein injury occurred in 1 patient and was controlled intraoperatively. No paroxysmal hypertensive crisis was observed. Transitory hypertension, which was systolic pressure superior to 160 mm. Hg, was observed during the procedure in all patients with manipulation of the tumor and in 2 during insufflation and in 1 during intubation. It was easily controlled with small doses of nicardipine. Transitory hypotension, which was systolic pressure inferior to 100 mm. Hg, was observed in 2 patients during exsufflation and in 1 during *U. S. Surgical, Norwalk, Connecticut.

FIG. 2. Control of adrenal vein. A, before mobilizing adrenal gland, adrenal vein was first identified, controlled and clipped. B, right side with vena cava then renal pedicle identified, allowing dissection to be continued upwards until adrenal vein was located, clipped and cut. C, left side with dissection of renal pedicle, especially renal vein, to distinguish adrenal vein between renal vein and renal artery, which was clipped and cut.

positioning in flank position. No arrhythmia or tachycardia were observed. All patients were allowed oral food intake on postoperative day 1, and all were ambulatory 1 or 2 days after surgery. Postoperative parenteral analgesia consisted of an average dose of 5 mg. profacetamol and 36 mg. (range 0 to 80) morphine sulfate equivalent during postoperative day 1, and 1,600 mg. acetaminophen and 120 mg. propoxyphene, 4 tablets daily from postoperative day 2. Analgesics were discontinued after a mean of 2 days (range 1 to 5) according to patient requirements. Average postoperative hospital stay was 3.4 days (range 1 to 12). Pathological examination showed benign pheochromocytoma in every case. The mean diameter of the excised masses was 38 mm. (range 15 to 70). Postoperative complications occurred in 4 (19%) cases, including a minor, spontaneously resolving retroperitoneal bleeding hematoma in 1, wound infections resolving with antibiotics in 2, and a defect parietal incision for trocar (specimen removal site) in 1, 1 year after the procedure, which required surgical repair. This last complication involved an overweight patient (85 kg. and 165 cm.). Mean followup was 21.6 months (range 6 to 46). All patients had normal urinary catecholamine levels, and all but 2 had normal blood pressure without drug therapy.

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4 (19)

– 1 Transfusion (10)

– – 12 (52.1) 1 Fever (20) 1 Hematoma (7.6) –

3.4 (1–12) (1.5–7) 3.8 140 (0–150) 116 (100–140) 21 Present series

Retroperitoneal

(4–19) 4 6 3 3.8 (1.7–7.5) – 20 90 243 (125–360) 8 10 Bonjer et al4 Mo¨bius et al15

Retroperitoneal Transperitoneal

5.3 6.7 (3.5–10) 5.7 (1–8)

8.4 7.2 4.4 (3.7–5) 4.9 (3–7)

– – – – 1 (7.6) 1 Vena caval injury (7.1) – 1 Renal vein injury (10) – (2–7) – 4

(2–7) 1–7 – 4.1

203 (80–360) 10–120 – 342 – 130 (0–300) 127 (65–330) 124 (45–225) 380 (220–540) 182 115 (90–120) 150 (90–240) 7 7 23 5 13 14 Fernandez-Cruz et al18 Walz et al10 Gagner et al16 Miccoli et al12 Chigot et al5 Janetschek et al11

Transperitoneal Retroperitoneal Transperitoneal Transperitoneal Transperitoneal Transperitoneal

Days Hospital Stay (range) Tumor Cm. (range) Ml. Blood Loss (range) Mins. Operating Time (range) References

Surgical Approach No. Pts.

Worldwide experience with laparoscopic adrenalectomy for pheochromocytoma

No. Conversion (%)

No. Complications (%)

DISCUSSION

Several studies have shown that morbidity with laparoscopic adrenalectomy is lower than that with open surgery.3, 4, 6, 8, 9, 11 However, surgery for pheochromocytoma differs from that for other adrenal tumors with the risk of hypertensive events intraoperatively.8, 11, 15 Laparoscopic procedures were thought to be contraindicated for pheochromocytoma because carbon dioxide pneumoperitoneum and increased intra-abdominal pressure could induce hemodynamic changes and catecholamine release, which might be aggravated in patients with pheochromocytoma.17 Indeed, carbon dioxide can produce hypercapnia and respiratory acidosis, with a high risk of hypertension during laparoscopic adrenalectomy for pheochromocytoma.15, 18 The use of helium gas was proposed for laparoscopic treatment of pheochromocytoma because it was well tolerated and avoided respiratory acidosis and hypercapnia.15, 18 However, Fernandez-Cruz et al clearly showed that laparoscopy for pheochromocytoma was associated with a smaller increase in serum catecholamine than with open surgery.18 They demonstrated that hypertensive events were mainly triggered by direct manipulation of the adrenal gland and that ligation of it was required before manipulating the tumor. Joris et al confirmed that pneumoperitoneum and adrenal gland manipulation was responsible for significant hypertension.17 Recently, Sprung et al demonstrated that intraoperative hemodynamic values during laparoscopic adrenalectomy for pheochromocytoma were comparable to those for traditional open surgery.19 The number of hypertensive episodes and highest intraoperative blood pressure were equivalent and with the laparoscopic procedure, intraoperative hypotension was less severe. Morbidity with the laparoscopic approach may be reduced by anesthetic management of hypertension and initial ligation of the adrenal vein.4, 18 Preoperative ␣ and ␤-blockade and, more recently, the use of calcium channel blockers and minimal manipulation of the adrenal gland have emerged as being essential to prevent hypertensive events.2, 20 Transperitoneal and retroperitoneal laparoscopic procedures have been described.4, 9, 10, 16, 20, 21 The transperitoneal approach is most commonly used because it creates a large working space, permits exploration of the entire abdominal cavity and can be used to treat bilateral pheochromocytoma during the same session.4, 14 –16, 21 Recently, Janetschek et al reported laparoscopic tumorectomy of 2 bilateral pheochromocytomas, measuring less than 3 cm. in diameter, in which the normal adrenal gland was spared.14 However, although the right adrenal gland is readily accessible, exposure of the left adrenal gland can be difficult because it requires mobilization of the spleen and splenic flexure of the colon, or ligation of the pancreatic tail.8 Nevertheless, ligation of the adrenal vein is easier on the left than the right side. Indeed, Janetschek et al reported an increased risk of intraoperative hemorrhage due to damage to the vena cava.11 The retroperitoneal approach requires less dissection and retraction of structures surrounding the adrenal gland.22 Reported disadvantages of retroperitoneal adrenalectomy are the limited space for maneuvering the endoscopic instruments, inadequacy of landmarks, difficulty with initial ligation of the adrenal vein and the impossibility of exploring the abdominal cavity. Previous reports have also suggested that carbon dioxide absorption is higher during retroperitoneal laparoscopy than transperitoneal laparoscopy.4, 14 However, Ng et al demonstrated that retroperitoneoscopic renal and adrenal surgery was not associated with increased carbon dioxide absorption compared with transperitoneal laparoscopy.23 Retroperitoneal laparoscopy also produces a small increase in intra-abdominal pressure.24 With retroperitoneal laparoscopy, there is little stimulation of the peritoneum and,

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hence, it should have a weaker sympathic response and less catecholamine release. In our experience the space created with digital dissection is large enough to insert the 4 or 5 trocars. After the trocars were inserted with digital guidance, the working space was completed with insufflation and dissection. Balloon dissection that provided good working space but no control of retroperitoneal dissection was unnecessary. Contrary to the transperitoneal approach in which the working space already exists, a sufficient working space must be created for the retroperitoneal approach.9 We consider retroperitoneal laparoscopy a better approach to initial ligation of the adrenal vein. Our technique is reproducible and standardized in this regard. We were always able to ligate the adrenal vein before proceeding with the technique. On the right side the vena cava is the first and the renal pedicle is the second landmark. The adrenal vein is found above the renal pedicle. On the left side the adrenal vein is found between the renal vein and renal artery. Thus, the adrenal vein can be controlled, clipped and cut before manipulating the pheochromocytoma. In our series all pheochromocytomas had been diagnosed before laparoscopy. However, initial ligation of the adrenal vein before manipulation of it is particularly valuable when the nature of the adrenal tumor is first unknown. It is noteworthy that, after initial experience with transperitoneal laparoscopic adrenalectomy, Bonjer et al adopted the retroperitoneal approach.22 Although Bonjer4 and Walz10 et al did not first ligate the adrenal vein, no increase in the risk of intraoperative hypertensive events was observed. The development of methods for accurate, reliable and noninvasive preoperative localization of pheochromocytoma, such as 131iodine iobenguane scintigraphy, computerized tomography and magnetic resonance imaging, avoids exploration of the abdominal cavity and allows a direct approach to the pheochromocytoma.4, 10, 12 In our series the pheochromocytomas were entirely removed, and with a mean followup of 21.6 months, all patients had normal urinary catecholamine levels and all but 2 had normal blood pressure without drug therapy. When the retroperitoneal approach to adrenalectomy is compared with the transperitoneal approach, published series suggest that retroperitoneoscopy is more rapid, with mean operating times from 90 to 124 and 115 to 243 minutes, respectively (see table). Bonjer et al did not give specific operating times for pheochromocytoma.4 The morbidity rate is similar in the different series. However, these results must be interpreted with care, given the limited number of retroperitoneoscopic series, but they can be explained by the direct access to the retroperitoneum.

2. 3.

4. 5. 6. 7.

8. 9. 10.

11. 12.

13. 14. 15. 16. 17. 18. 19.

CONCLUSIONS

Retroperitoneal laparoscopic adrenalectomy is feasible and can be safely performed for pheochromocytoma when the tumor diameter does not exceed 5 cm. There are 2 reasons for this size limit, including the low risk of malignancy, and difficult or even impossible initial ligation of the adrenal vein when a large tumor phagocytoses the adrenal vein. Retroperitoneal laparoscopy offers a direct approach and permits the adrenal vein to be ligated initially, thereby avoiding hypertensive events. REFERENCES

1. Vaughan, E. D. and Blumenfeld, J. D.: The adrenals. In: Campbell’s Urology, 7th ed. Edited by P. C. Walsh, A. B. Retik, E. D.

20. 21. 22. 23. 24.

Vaughan et al. Philadelphia: W. B. Saunders Co., vol. 3, chapt. 96, pp. 2915–2972, 1998 Gagner, M., Lacroix, A. and Bolte´, E.: Laparoscopic adrenalectomy in Cushing’s syndrome and Pheochromocytoma. N Engl J Med, 327: 1033, 1992 Guazzoni, G., Montorsi, F., Bocciardi, A. et al: Transperitoneal laparoscopic versus open adrenalectomy for benign hyperfunctioning adrenal tumors: a comparative study. J Urol, 153: 1597, 1995 Bonjer, H. J., Van der Harst, E., Steyerberg, E. W. et al: Retroperitoneal adrenalectomy: open or endoscopic? World J Surg, 22: 1246, 1998 Chigot, J. P., Movschin, M., el Bardissi, M. et al: Etude comparative entre la surre´nalectomie laparoscopique et conventionnelle dans les phe´ochromocytomes. Ann Chir, 52: 346, 1998 Winfield, H. N., Hamilton, B. D., Bravo, E. L. et al: Laparoscopic adrenalectomy: the preferred choice? A comparison to open adrenalectomy. J Urol, 160: 325, 1998 Takeda, M., Go, H., Watanabe, R. et al: Retroperitoneal laparoscopic adrenalectomy for functioning adrenal tumors: comparison with conventional transperitoneal laparoscopic adrenalectomy. J Urol, 157: 19, 1997 Gagner, M., Pomp, A., Heniford, B. T. et al: Laparoscopic adrenalectomy: lessons learned from 100 consecutive procedures. Ann Surg, 226: 238, 1997 Gasman, D., Droupy, S., Koutani, A. et al: Laparoscopic adrenalectomy: the retroperitoneal approach. J Urol, 159: 1816, 1998 Walz, M. K., Peitgen, K., Hoermann, R. et al: Posterior retroperitoneoscopy as a new minimally invasive approach for adrenalectomy: results of 30 adrenalectomies in 27 patients. World J Surg, 20: 769, 1996 Janetschek, G., Altarac, S., Finkenstedt, G. et al: Technique and results of laparoscopic adrenalectomy. Eur Urol, 30: 475, 1996 Miccoli, P., Bendinelli, C., Materazzi, G. et al: Traditional versus laparoscopic surgery in the treatment of pheochromocytoma: a preliminary study. J Laparoendosc Adv Surg Tech A, 7: 167, 1997 Chigot, J. P., Menegaux, F., Movschin, M. et al: La surre´nalectomie laparoscopique dans les phe´ochromocytomes. Presse Med, 27: 359, 1998 Janetschek, G., Finkenstedt, G., Gasser, R. et al: Laparoscopic surgery for pheochromocytoma: adrenalectomy, partial resection, excision of paragangliomas. J Urol, 160: 330, 1998 Mo¨bius, E., Nies, C. and Rothmund, M.: Surgical treatment of pheochromocytomas: laparoscopic or conventional? Surg Endosc, 13: 35, 1999 Gagner, M., Breton, G., Pharand, D. et al: Is laparoscopic adrenalectomy indicated for pheochromocytomas? Surgery, 120: 1076, 1996 Joris, J. L., Hamoir, E. E., Hartstein, G. M. et al: Hemodynamic changes and catecholamine release during laparoscopic adrenalectomy for pheochromocytoma. Anesth Analg, 88: 16, 1999 Fernandez-Cruz, L., Taura, P., Saenz, A. et al: Laparoscopic approach to pheochromocytoma: hemodynamic changes and catecholamine secretion. World J Surg, 20: 762, 1996 Sprung, J., O’Hara, J. F., Jr., Gill, I. S. et al: Anesthetic aspects of laparoscopic and open adrenalectomy for pheochromocytoma. Urology, 55: 339, 2000 Lepsien, G., Neufang, T. and Lu¨dtke, F. E.: Laparoscopic resection of pheochromocytoma. Surg Endosc, 8: 906, 1994 Meurisse, M., Joris, J., Hamoir, E. et al: Laparoscopic removal of pheochromocytoma. Why? When? and Who? (reflections on one case report). Surg Endosc, 9: 431, 1995 Bonjer, H. J., Lange, J. F., Kazemier, G. et al: Comparison of three techniques for adrenalectomy. Br J Surg, 84: 679, 1997 Ng, C. S., Gill, I. S., Sung, G. T. et al: Retroperitoneoscopic surgery is not associated with increased carbon dioxide absorption. J Urol, 162: 1268, 1999 Chiu, A. W., Chang, L. S., Birkett, D. H. et al: The impact of pneumoperitoneum, pneumoretroperitoneum and gasless laparoscopy on the systemic and renal hemodynamics. J Am Coll Surg, 181: 397, 1955