Evolving Surgical Management for Patients with Pheochromocytoma

Quan-Yang Duh

Department of Surgery University of California–San Francisco Surgical Service, Veterans Affairs Medical Center San Francisco, California 94121

Address correspondence and requests for reprints to: Quan-Yang Duh, M.D., Department of Surgery, University of California—San Francisco, Surgical Service, Veterans Affairs Medical Center, San Francisco, California 94121.


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In this issue of JCEM, Plouin et al. (1) report their experience of 165 operations for pheochromocytoma on 147 patients. They found the perioperative complications (2.4% death, 23.6% morbidity) to be associated strongly with reoperations and with the severity of disease as reflected by the patients’ preoperative systolic blood pressure and metanephrine excretion. This is one of the largest series published on the results of surgical treatment for pheochromocytoma from a single institution. The authors are acknowledged experts in the field, and we can learn much from their experience that was carefully analyzed and distilled for us in this paper.

To draw appropriate conclusions from this paper, we must interpret their results within a historical context. Medical and surgical treatment of pheochromocytoma has evolved continuously, so that this series that spans 22 yr from 1975 to 1997, although excellent for analysis of long-term surgical results, may not reflect what is currently achievable for short-term perioperative complications. In this editorial, I review the major advances that have lowered the mortality and morbidity of operations for patients with pheochromocytoma over the past decades and attempt to show that the recent advances in localizing studies and the switch to laparoscopic surgery have significantly benefited these patients.

Surgeons and physicians have always treated patients with pheochromocytomas with extreme caution, and for good reasons. From the time pheochromocytoma was first successfully resected in 1926 until the early 1950s, the operative mortality was at least 26% (2). Many other patients with unrecognized pheochromocytomas died from crisis, usually precipitated by other procedures, childbirth, stress, or trauma. Patients with pheochromocytomas die because of the hypertension caused by excess catecholamines, as well as hypotension and cardiovascular collapse after tumor removal and sudden withdrawal of the excess catecholamines.

This changed in 1956 when Priestley and colleagues (3) from the Mayo Clinic reported a series of 51 patients from whom 61 pheochromocytomas were removed without mortality. This remarkable result was possible mainly because of their routine use of {alpha}-adrenergic blocker phentolamine to treat hypertension and norepinephrine to treat hypotension (3). Subsequently, the role of hypovolemia was also recognized and preoperative volume expansion was advocated to prevent shock after pheochromocytoma resection (4). Excess catecholamine causes vasoconstriction that leads to hypertension and also hypovolemia. The sudden withdrawal of catecholamine when the pheochromocytoma is resected leads to vasodilatation, which in the presence of hypovolemia leads to hypotension and shock.

These two major advances in preoperative care, {alpha}-adrenergic blockade and volume expansion, in addition to other advances in intraoperative and postoperative anesthetic care, reduced the operative mortality rate for resection of pheochromocytoma to less than 5% in most published series since the 1970s (reviewed in Ref. 1). Death mainly occurs in patients who are inadequately prepared because pheochromocytoma was not anticipated before the operation, or in patients who have pheochromocytoma crisis that leads to multisystem organ failure.

Despite the lowering mortality rate, open operations for pheochromocytoma continued to cause much morbidity. One of the main reasons was the need, both real and perceived, for extensive exploratory laparotomy in most patients undergoing resection for pheochromocytoma. Abdominal exploration was required in some patients because the tumor could not be located by older preoperative radiographic studies. In addition, extensive abdominal exploration was also advocated because pheochromocytomas, the so-called 10% tumor, may be bilateral, multiple, extra-adrenal, or malignant. The classical operative approach, thus, was a long anterior midline incision or bilateral subcostal incision. This approach enables the surgeon to explore, by sight and palpation, both adrenal glands, the adjacent organs, along the aorta down to the bifurcation for the organ of Zuckerkandl, and the bladder. Thoracoabdominal incision, which was even more morbid, was mainly used to expose and resect very large or invasive pheochromocytomas. Some surgeons preferred a flank incision, as is for a nephrectomy, and others used the posterior retroperitoneal approach. (The surgical techniques are reviewed in Ref. 5 .) The main disadvantage of the latter two approaches was the inability to explore the rest of the abdomen for additional tumors that may be present. However, their advantages were also due to the more limited incision and exploration. All these open surgical approaches were associated with significant perioperative and postoperative complications, including bleeding, pain, respiratory and cardiac compromises, ileus, injury to adjacent organs, and incisional hernias.

Accurate preoperative localization of pheochromocytoma became available in the 1970s and 1980s and lead to the next major improvement in surgical morbidity. Ultrasonography and computed tomography were used to preoperatively identify pheochromocytoma(s) in the adrenal gland and elsewhere. Magnetic resonance imaging (MRI) and metaiodobenzylguanidine (MIBG) scanning provide even more specific localization for pheochromocytomas. Pheochromocytomas are characteristically bright on a T2-weighted MRI scan. The MIBG scan surveys the whole body, so it is used to identify extra-adrenal pheochromocytomas and metastases. MIBG is especially useful for those patients at risk for multiple or extra-adrenal tumors, such as the young patients, patients with a family history of pheochromocytomas, those with multiple endocrine neoplasia type 2, von Hippel-Lindau, neurofibromatosis, and other syndromes known to be associated with pheochromocytomas.

The accuracy of these localizing studies (all greater than 90%) made it possible for the surgeon to do a more limited and focused exploration in most patients, with minimal risk of missing a concurrent tumor. The posterior retroperitoneal approach, through the bed of the 12th rib, became a preferred approach by many surgeons for solitary pheochromocytomas smaller than 5–6 cm (6). The larger tumors still required resection by a larger incision through the flank approach or the anterior approach. The focused exploration approach was as successful and had a lower surgical morbidity than the extensive exploration approach. Thus, the advances in preoperative localizing studies of pheochromocytoma made focused exploration possible, lowering the morbidity of surgical resection.

Starting in mid 1990s, combining the acceptance of focused exploration for pheochromocytoma with the recently developed laparoscopic surgical techniques, surgeons began to resect pheochromocytomas, among other adrenal tumors, laparoscopically (7). Several laparoscopic approaches were used successfully, including the lateral or anterior transabdominal approaches and the posterior or lateral retroperitoneal approaches, and they were shown to lower the morbidity compared with open adrenalectomy (8, 9, 10). Although laparoscopic adrenalectomy for pheochromocytoma is more difficult and is associated with more complications than for small adrenal cortical tumors, laparoscopic resection is becoming the standard surgical treatment for pheochromocytoma, except for tumors that are very large or locally invasive (11). We have performed 40 laparoscopic resections of pheochromocytomas in 38 consecutive patients since 1994. All were completed laparoscopically, except for a 15-cm tumor that required a 7-cm incision hand-assisted laparoscopic operation. Extra-adrenal pheochromocytomas have also been resected laparoscopically. Except for those admitted in pheochromocytoma crisis, patients now stay in the hospital only 1–2 days after laparoscopic resection. This current experience is a significant improvement from that before the era of laparoscopic adrenalectomy and was possible because of adequate preoperative preparation, definitive localization studies, and minimally invasive laparoscopic surgical approach.

The perioperative complications that are analyzed and reported by Plouin et al. (1) can be classified into two types, those that are medical or anesthetic related and those that are surgically related. The medical/anesthetic complications may be related to the adequacy of preparation of the patients with adrenergic blockade and vascular volume replenishment, or whether the patients were admitted in pheochro-mocytoma crisis. Surgically related complications, on the other hand, are more likely to be affected by the size and location of the tumor, scarring from prior operations, surgeon experience, the extent of exploration, and the technique of exposure.

Some of the complications reported in the series by Plouin et al. (1) likely have occurred because of the practice of extensive exploration instead of focused exploration. For example, 4 of the 11 splenectomies occurred in patients with a 3-cm, benign right adrenal tumor. Iatrogenic splenic injury is not uncommon in open operations involving the left upper quadrant, such as operations involving the left colon, left kidney, stomach, pancreas, or aorta. It occurs less often in laparoscopic operations of these same organs in the left upper quadrant. Some splenectomies, especially those that occurred in patients who had a right adrenal tumor, would likely have been avoided with the current practice of focused exploration with a laparoscopic adrenalectomy.

The authors found patients undergoing reoperations are five times more likely to suffer complications than those undergoing initial operations. This is not surprising, because of the differences in the type of disease and the anatomy of tumors in these patients. Patients with cancers are more likely to require reoperations, sometimes repeatedly. Patients with multiple tumors are more likely to require reoperations in extra-adrenal locations that may be more challenging to the surgeons. Scarring in previously operated areas is also more likely to cause complications. In contrast to the conclusion by Plouin et al. (1) of conservative nonsurgical treatment in these reoperative cases, we believe these patients should be treated with reoperation, if at all possible, because nonsurgical approaches have not proven to be as effective. Similar to other endocrine tumors, patients with pheochromocytomas suffer more from the endocrine hyperfunction than from local invasion or metastases to vital organs. Thus, debulking of a tumor without complete resection and repeated resection for recurrences are frequently palliative, despite their higher risk of surgical complications.

Surgical management of pheochromocytoma has continued to evolve and improve because of our understanding of the disease, development of new radiological and surgical techniques, and, most importantly, because of the collaboration of endocrinologists, anesthesiologists, pharmacologists, nurses, and surgeons. Most patients with pheochromocytomas can now expect definitive preoperative diagnosis (by urinary metanephrine), accurate preoperative localization of the tumor (by computed tomography, MRI, or MIBG), and appropriate preoperative medical preparation (by {alpha} blockade and volume restoration). Most can also expect less pain, fewer days of hospitalization and disability, and less surgical morbidity from laparoscopic surgery and focused exploration, with a similar high rate of success as in the past. The study by Plouin et al. (1) reminds us just how challenging it is, but also how gratifying it is, to treat patients with pheochromocytoma.

Received February 28, 2001.

Accepted February 28, 2001.


    References
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 Introduction
 References
 

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