Keywords

12.1 The Guidelines

According to the 2020 European Society for Medical Oncology guidelines [1], 2019 Associazione Italiana di Oncologia Medica guidelines [2] and 2014 Endocrine Society guidelines [3], surgical excision is the first line treatment for pheochromocytomas (PHEOs).

12.2 Indication for Surgery

Preoperative diagnosis of malignant PHEO in patients without metastatic disease or clear evidence of locoregional invasion is challenging, even though it does not impact the therapeutic strategy. Surgical excision is recommended in all PHEOs due to the catecholamine-related risks.

Regardless of the type of approach and preoperative diagnosis, proper resection must involve complete excision of the neoplasm without spillage of the mass. It is important to minimize manipulation to reduce hypertensive spikes [4].

The main outcome of complete surgical resection (R0) is to cure or increase overall survival.

Surgical debulking aims to control catecholamine-related symptoms and prevent potentially fatal hemodynamic events. Ellis et al. showed that patients with disease located in the abdomen had longer-lasting relief from hypertensive symptoms after debulking. Unfortunately, most patients experienced biochemical recurrence within a year, and 5 years after surgery only 30% of patients had not relapsed. Debulking procedures with evidence of residual disease at the end of surgery resulted in poor and short-lasting biochemical control; upon these bases the authors suggested that a debulking operation should be undertaken only if complete removal of the tumor is anticipated on the basis of preoperative imaging [5].

12.3 Surgical Strategies and Techniques

The surgical strategy for malignant PHEO does not differ from benign disease and must respect the “no touch” or the “as minimal manipulation as possible” principles to avoid hemodynamic instability resulting from catecholamine release. This strategy also prevents tumor effraction and seeding [6, 7].

The surgical approach depends on the surgeon’s choice and experience; it can be influenced by patient or tumor characteristics: mass size and location, body mass index (BMI), previous history of abdominal surgery, good control of hypertensive symptoms before surgery.

Minimally invasive surgery can be performed with a transabdominal or a retroperitoneal approach. Most general surgeons prefer the transabdominal route due to the more familiar anatomy and easier conversion to open surgery; the advantage of the retroperitoneal approach is the direct access to the adrenal gland without mobilization of other abdominal organs.

A comparison between transabdominal and retroperitoneal approach showed that in cases treated with the retroperitoneal approach the operative time is shorter, blood loss is lower, and postoperative hospital stay is reduced.

Contraindications to the retroperitoneal approach are tumors larger than 7–8 cm because of the poor working space that can be created in the retroperitoneum, and patients with high BMI because of the large amount of retroperitoneal fat [7].

Laparoscopic adrenalectomy is less invasive as it reduces postoperative pain and allows faster recovery with earlier discharge; it is the first-choice approach when malignancy is unlikely: small tumors with no evidence of local invasiveness or distant metastasis [4].

In malignant PHEOs or in those with a high suspicion of malignancy, the minimally invasive approach is controversial because of the risk of lesion rupture and neoplastic contamination of the peritoneal cavity. In these cases, a complete resection respecting the integrity of the adrenal gland has a critical value. In fact, tumor effraction may result in dissemination of neoplastic cells with pheochromocytomatosis, most often observed at the surgical site or in the surgical wounds including the trocar entry points [8, 9]. A further limitation for minimally invasive surgery is represented by the larger dimensions and higher frequency of infiltration of the tumor capsule and surrounding tissues of malignant PHEOs [6]. Despite this, laparoscopic resection of malignant PHEO proved safe and effective in high-volume centers. In fact, for this disease routine regional adrenalectomy and lymphadenectomy are not required to achieve surgical radicality.

The “vein first” technique was long considered the first step of this surgery. However, this may be difficult to achieve and does not seem to prevent the release of catecholamines. In fact, the venous drainage of the adrenal gland is not carried out only by the main adrenal vein: other “minor” adrenal veins carry blood to the renal capsule, the inferior phrenic veins and even into some tributary veins of the portal system. Some authors have investigated the safety of late adrenal vein ligation and they found that this technique is not associated with increased morbidity or increased frequency of hemodynamic instability during surgery, provided that the procedure is conducted limiting improper manipulation of the gland, which is the main cause of dangerous fluctuations in blood pressure during the procedure [10,11,12,13,14].

The presence of many newly formed vessels reduces the effectiveness of adrenal vein ligation in reducing episodes of hemodynamic instability, the frequency of which depends mostly on the intraoperative manipulation of the mass [2].

Ochi et al. demonstrated that the pre-emptive ligation of the adrenal arteries reduces the amount of catecholamines released from the tumor in the later stages of surgery [12]. Supporters of the retroperitoneal approach also support and disseminate the message of the “artery first” procedure [15].

Otsuka’s group reported the case of a patient with a large malignant PHEO with liver invasion. Preoperative computed tomography showed that the tumor received arteries from the celiac tripod and right renal artery. The surgical strategy involved an initial laparoscopic retroperitoneal time during which all the tributary vessels of the tumor found in this space were transected and a second open time that allowed the excision of the mass en bloc with the posterior segments of the liver [16].

12.4 Case Report

In the Supplementary material of this chapter a video is provided concerning the case of a locally advanced adrenal PHEO with multiple nodal metastases. In this case a robot approach was chosen, using indocyanine green dye to detect retroperitoneal lymphatic routes.