**Abstract**

Pheochromocytomas are tumors composed of chromaffin cells that can produce, secrete and metabolise catecholamines. The surgical excision procedure of these tumors may present the risk of significant variations in blood pressure, as well as the chance of cardiovascular complications in the perioperative period. During surgery, patients may be at risk for cardiovascular events such as major variations in blood pressure, pulmonary edema, stroke, myocardial infraction and a long period of intubation. The surgical approach to pheochromocytomas must always be preceded by accurate imaging evaluation, endocrine screening and identification of associated genetic mutations. In addition, the surgical technique of choice consists in using minimally invasive surgical methods, with a transabdominal or retroperitoneal approach.

**Keywords:** pheochromocytomas, adrenalectomy, laparoscopic surgery, epinephrine, transabdominal approach

### **1. Introduction**

Pheochromocytomas are rare tumors composed of chromaffin tissue that can secrete catecholamines in excess (epinephrine, norepinephrine, and dopamine) and their metabolites (metanephrine, normetanephrine, and 3-methoxytyramine). Pheochromocytomas can develop from the chromaffin cells inside the adrenal gland. Moreover, about 80–85% of these neuroendocrine tumors are localized inside the adrenal gland as pheochromocytomas and 15–20% can be extra-adrenal tumors that are named paragangliomas [1–4].

The USA has a pheochromocytoma's annual incidence of 500–1,600 cases per year with equality between genders and a peak incidence in the forth decade of life. The association with hypertension is well known; in the case of patients with hypertension, it is encountered with an incidence of 0.1–0.6% [5]. The classical mode of presentation of a pheochromocytomas case consists of headaches, diaphoresis, flushing and paroxistic hypertension [6].

The latest studies indicate a genetic cause for pheochromocytomas in about 40% of cases, from specific genetic syndromes or de novo mutation [7]. After the biochemical phenotype established, the genetic screening completed, and the imaging investigations performed, the patient has two surgery approaches: through minimally invasive surgical methods or through classical open surgery technique. The surgical method and grade of adrenalectomy can be decided depending on different factors: germline genetic test results, tumor size, body mass index, surgeon experience, and risk of malignancy [1].

The classic surgical methods approaching the adrenal pathology can be transabdominal, transthoracic and retroperitoneal. These include large incisions and extensive plans dissections to offer a reasonable control of vascular pedicles' maneuvers treatment. Usually, this is the critical point for surgical resection due to the difficulty of reaching the vascular branches and the rule of vein first, artery second (preventing releasing the catecholamine into the bloodstream). Postoperative morbidity can be influenced by the type of surgical approach to the adrenal gland. The development of minimally invasive surgery (MIS) techniques has ensured great changes for most surgical procedures. Adrenalectomy is an excellent example of this. This type of pathology fully benefits from the advantages of laparoscopy.

The first laparoscopic adrenalectomy was performed in 1991 by Dr. Lamar Snow, and in 1992 Dr. Joseph Petelin published the first description of the operation. The first laparoscopic adrenalectomy was performed on January 17th, 1992, by a Japanese surgical team led by Go H at Niigata University School of Medicine, Japan [16]. A significant moment in the evolution of laparoscopic adrenal surgery is the publication of the lateral transperitoneal procedure by Michel Gagner in 1992. This later became the most widely used laparoscopic adrenalectomy procedure. Similar to open procedures, the video-assisted approach recognizes three variants, depending on the patient's position and the access: first: anterior approach (transperitoneal), second: lateral approach (transperitoneal or retroperitoneal), and the third one is the posterior approach (retroperitoneal). Soon after it, the laparoscopic adrenalectomy became the second gold standard therapy (after cholecystectomy) in the field of surgery.

The accuracy of new imaging techniques for locating preoperative tumors is necessary because surgical exploration in the blind manner is unlikely to identify any unlocated tumor.

#### **2. Preoperative management**

The surgical approach of pheochromocytomas can include significant variations in blood pressure values and cardiovascular events such as arrhythmias and tachycardia can appear in the perioperative patient period.

Intraoperatively, patients undergoing surgical resection can have arrhythmias, sustained hypertension or hypotension and also postoperative myocardial infarction, stroke, pulmonary edema, and prolonged intubation.

Heart failure risk can be influenced by high levels of metanephrines and normetanephrines associated with large tumor size and a longer duration of surgery due to technically difficult surgical excision [8].

Preoperative alpha-blockers ensure a significant decrease in the risk of major hypertensive crises intraoperatively. Patients with pheochromocytoma are systematically examined preoperatively by the cardiologist and anesthesiologist, and the latter will be provided at the time of surgery with all necessary material and drug support (invasive monitoring of BP, central venous catheter, sufficient doses of sodium nitroprusside, etc.) [9].

However, experienced medical specialists (surgeons and endocrinologists) agree that preoperative optimisation must include a seated blood preasure of 120–130/80 mmHg, a standing systolic blood pressure over 90 mmHg, a seated heart rate between 60–70 bpm and a heart rate 70–80 bpm in standing position. In addition, is important to encourage patients to supplement their water intake along with a high sodium diet before surgery [8, 10].

**49**

*Surgical Approach in Pheochromocytoma DOI: http://dx.doi.org/10.5772/intechopen.96066*

tension less frequently than alpha blockers.

thus blocking the catecholamine synthesis pathway.

logical disorders, and intestinal transit disorders.

imbalance and the treatment of possible anemia.

cardiac output and possible arrhythmias [14–16].

**3. Surgical intervention approach**

unopposed alpha vasoconstriction [12].

surgical procedure [13].

blockers, beta-blockers and calcium channel blockers [11].

Regarding specific drugs utilized in the preoperative period, Phenoxybenzamine is a non-selective alpha receptor blocker that has been associated with better perioperative hemodynamics parameters, compared with other medication [9].

However, due to the slower onset than selective alpha-blockers such as doxazosin or prazosin it is preferably to be used for 10–14 days instead of 4–7 days. In addition, alpha adrenergic blockers side effects can consists of orthostatic hypotension with secondary tachycardia, palpitation, nasal congestion and headache. In terms of pharmacological actions, alpha adrenergic blockers control volume expansion, minimize the frequency of hypertensive peaks during surgery and control blood pressure values [11, 12].

Furthermore, calcium channel blockers represents a proper variant as a primary drug choice or as an alternative medication. In addition, they can counterbalance coronary vasospasm caused by catecholamines and may induce orthostatic hypo-

Methyrosine is a pharmacological blocking agent of the enzyme tyrosine hydroxylase that inhibits the conversion of tyrosine to dihydroxyphenylalanine,

This drug can be used in patients who do not tolerate treatment with alpha blockers or is reserved for cases of hypertension refractory to the use of alpha-

Possible unpleasant side effects of this medication include drowsiness, neuro-

In addition, the main medical management approaches are: the expansion of intravascular volume with a saline solution together with the control of hypertension or other cardiovascular events, the correction of metabolic and electrolyte

Beta-adrenergic receptor blockade with propranolol is used in the treatment of catecholamine induced tachycardia after at least three to four days of alpha blockade administration; beta blockers usage is contraindicated until the alpha-adrenergic receptor blockade is done, in order to prevent severe hypertensive crisis caused by

Appropriate and smooth venous access and arterial catheters for continuous blood pressure monitoring must be placed before surgery. Communication between the anesthesiologist and surgeon is essential to ensure safe results. Ideally, the anesthesia team should be prepared to use intravenous vasoactive drugs to manage hemodynamic variations and has to remain vigilant throughout the entire medical-

More than that, the timing of surgical dissection should be coordinated with the anesthesiologist's maneuvers even from the time of pneumoperitoneum inflation – new recordings of blood pressure (BP) of the patient should be registered every minute, according to the gas amount already introduced (until the value of 12 mmHg); if the BP is too high, a lower intraperitoneal pressure should be taken into consideration during the all-time of the procedure. Another example of surgeon-anesthesiologist cooperation can be the proper time of dissection around the gland – touching the gland (with catecholamine release and rapid increase of BP). The surgeon requires rapid measures from the anesthesiologist to control the

Surgery is the curative therapy for either benign or malignant pheochromocytoma. Morbidity in adrenalectomy operations is about 40% and can be associated

#### *Surgical Approach in Pheochromocytoma DOI: http://dx.doi.org/10.5772/intechopen.96066*

*Pheochromocytoma, Paraganglioma and Neuroblastoma*

tages of laparoscopy.

the field of surgery.

any unlocated tumor.

**2. Preoperative management**

sodium nitroprusside, etc.) [9].

cardia can appear in the perioperative patient period.

due to technically difficult surgical excision [8].

with a high sodium diet before surgery [8, 10].

tion, stroke, pulmonary edema, and prolonged intubation.

The classic surgical methods approaching the adrenal pathology can be transabdominal, transthoracic and retroperitoneal. These include large incisions and extensive plans dissections to offer a reasonable control of vascular pedicles' maneuvers treatment. Usually, this is the critical point for surgical resection due to the difficulty of reaching the vascular branches and the rule of vein first, artery second (preventing releasing the catecholamine into the bloodstream). Postoperative morbidity can be influenced by the type of surgical approach to the adrenal gland. The development of minimally invasive surgery (MIS) techniques has ensured great changes for most surgical procedures. Adrenalectomy is an excellent example of this. This type of pathology fully benefits from the advan-

The first laparoscopic adrenalectomy was performed in 1991 by Dr. Lamar Snow, and in 1992 Dr. Joseph Petelin published the first description of the operation. The first laparoscopic adrenalectomy was performed on January 17th, 1992, by a Japanese surgical team led by Go H at Niigata University School of Medicine, Japan [16]. A significant moment in the evolution of laparoscopic adrenal surgery is the publication of the lateral transperitoneal procedure by Michel Gagner in 1992. This later became the most widely used laparoscopic adrenalectomy procedure. Similar to open procedures, the video-assisted approach recognizes three variants, depending on the patient's position and the access: first: anterior approach (transperitoneal), second: lateral approach (transperitoneal or retroperitoneal), and the third one is the posterior approach (retroperitoneal). Soon after it, the laparoscopic adrenalectomy became the second gold standard therapy (after cholecystectomy) in

The accuracy of new imaging techniques for locating preoperative tumors is necessary because surgical exploration in the blind manner is unlikely to identify

The surgical approach of pheochromocytomas can include significant variations in blood pressure values and cardiovascular events such as arrhythmias and tachy-

Intraoperatively, patients undergoing surgical resection can have arrhythmias, sustained hypertension or hypotension and also postoperative myocardial infarc-

Heart failure risk can be influenced by high levels of metanephrines and normetanephrines associated with large tumor size and a longer duration of surgery

Preoperative alpha-blockers ensure a significant decrease in the risk of major hypertensive crises intraoperatively. Patients with pheochromocytoma are systematically examined preoperatively by the cardiologist and anesthesiologist, and the latter will be provided at the time of surgery with all necessary material and drug support (invasive monitoring of BP, central venous catheter, sufficient doses of

However, experienced medical specialists (surgeons and endocrinologists) agree that preoperative optimisation must include a seated blood preasure of 120–130/80 mmHg, a standing systolic blood pressure over 90 mmHg, a seated heart rate between 60–70 bpm and a heart rate 70–80 bpm in standing position. In addition, is important to encourage patients to supplement their water intake along

**48**

Regarding specific drugs utilized in the preoperative period, Phenoxybenzamine is a non-selective alpha receptor blocker that has been associated with better perioperative hemodynamics parameters, compared with other medication [9].

However, due to the slower onset than selective alpha-blockers such as doxazosin or prazosin it is preferably to be used for 10–14 days instead of 4–7 days. In addition, alpha adrenergic blockers side effects can consists of orthostatic hypotension with secondary tachycardia, palpitation, nasal congestion and headache. In terms of pharmacological actions, alpha adrenergic blockers control volume expansion, minimize the frequency of hypertensive peaks during surgery and control blood pressure values [11, 12].

Furthermore, calcium channel blockers represents a proper variant as a primary drug choice or as an alternative medication. In addition, they can counterbalance coronary vasospasm caused by catecholamines and may induce orthostatic hypotension less frequently than alpha blockers.

Methyrosine is a pharmacological blocking agent of the enzyme tyrosine hydroxylase that inhibits the conversion of tyrosine to dihydroxyphenylalanine, thus blocking the catecholamine synthesis pathway.

This drug can be used in patients who do not tolerate treatment with alpha blockers or is reserved for cases of hypertension refractory to the use of alphablockers, beta-blockers and calcium channel blockers [11].

Possible unpleasant side effects of this medication include drowsiness, neurological disorders, and intestinal transit disorders.

In addition, the main medical management approaches are: the expansion of intravascular volume with a saline solution together with the control of hypertension or other cardiovascular events, the correction of metabolic and electrolyte imbalance and the treatment of possible anemia.

Beta-adrenergic receptor blockade with propranolol is used in the treatment of catecholamine induced tachycardia after at least three to four days of alpha blockade administration; beta blockers usage is contraindicated until the alpha-adrenergic receptor blockade is done, in order to prevent severe hypertensive crisis caused by unopposed alpha vasoconstriction [12].

Appropriate and smooth venous access and arterial catheters for continuous blood pressure monitoring must be placed before surgery. Communication between the anesthesiologist and surgeon is essential to ensure safe results. Ideally, the anesthesia team should be prepared to use intravenous vasoactive drugs to manage hemodynamic variations and has to remain vigilant throughout the entire medicalsurgical procedure [13].

More than that, the timing of surgical dissection should be coordinated with the anesthesiologist's maneuvers even from the time of pneumoperitoneum inflation – new recordings of blood pressure (BP) of the patient should be registered every minute, according to the gas amount already introduced (until the value of 12 mmHg); if the BP is too high, a lower intraperitoneal pressure should be taken into consideration during the all-time of the procedure. Another example of surgeon-anesthesiologist cooperation can be the proper time of dissection around the gland – touching the gland (with catecholamine release and rapid increase of BP). The surgeon requires rapid measures from the anesthesiologist to control the cardiac output and possible arrhythmias [14–16].

#### **3. Surgical intervention approach**

Surgery is the curative therapy for either benign or malignant pheochromocytoma. Morbidity in adrenalectomy operations is about 40% and can be associated with cardiac events such as arrhythmia, myocardial dysfunction, pulmonary embolism and sepsis. Mortality for adrenalectomy has improved in the last decade, with an under 2% rate of death.

Firstly, the main critical point in adrenalectomy in pheochromocytoma is the minimal manipulation of the tumor to avoid seeding the tumor in adjacent tissues and in order to prevent a hypertensive crisis during the operation (it is said that adrenalectomy should be performed by dissecting away the body from the gland, not the gland from the body). Secondly, another crucial step during the surgical procedure is the control of vascular supply together with the complete tumor resection. All of these can be provided by adequate surgical exposure in order to prevent other organs injuries.

Minimally invasive techniques can be done laparoscopically or robotically. The aim of minimally invasive procedures and open surgical approach is the minimal manipulation of the tumor, in order to prevent catecholamine release as mentioned above; if this is not respected, it can result in hemodynamic instability and tumor rupture.

Also, to diminish the risk of releasing large amounts of hormones, it is indicated to early ligature the adrenal vein. This step can be performed through the transabdominal or posterior surgical approaches.

Furthermore, the surgical approach is dependent on surgeon choise, experience and familiarity with the specific techniques. However, some factors may influence the decision of surgical approach: body mass index, tumor size and location, and patient's personal pathological history of abdominal or retroperitoneal surgical procedures [14].

Our paper will focus mainly on the minimally invasive laparoscopic approach, being the surgical procedure of choice for adrenal tumors, due to its advantages of surgical technique.

The laparoscopic approach includes normal anatomy and easy conversion to open surgery if necessary for exceptional cases [15].

Although the retroperitoneal approach can directly access the adrenal gland and would require less effort to dissect and mobilize nearby visceral organs, this technique is not easy for general surgeons due to lack of familiarity with it. In addition, the contraindications for the retroperitoneal surgical approach include tumors bigger than seven to eight cm due to the narrow working space and an increased body mass index with increased retroperitoneal fat. Simultaneously, a tumor lying around the inferior vena cava (on the right side) or close to the aorta (on the left side) can lead to a complex surgical resection by retroperitoneal access [13].

Retrospective studies from literature have shown that robotic and laparoscopic resection of pheochromocytomas are equivalent in terms of operative time, blood loss volumes, intraoperative hemodynamic events, rates of morbidity and mortality, and rates of conversion from minimally invasive approach to open surgery technique [9].

Furthermore, the main advantages of robotic adrenalectomy include: the three dimensional acces, improved wrist mobilization for the surgeon, and a stable camera port. Disadvantages of robotic adrenal surgery include increased cost, insufficient learning curve and lack of tactile feedback.

When invasive malignant pheochromocytoma is suspected or concerned clinically, open approach is the first choice. Open treatment may benefit from a greater risk of tumor rupture, which may lead to pheochromocytoma disease. For patients with confirmed SDHB mutations, that are associated with a higher metastatic disease rate, the open approach is prefered [16].

For patients with pheochromocytoma associated with different syndromes, minimally invasive or open surgical methods can also be used for cortical sparing

**51**

surgeon).

*Surgical Approach in Pheochromocytoma DOI: http://dx.doi.org/10.5772/intechopen.96066*

**4. Laparoscopic technique**

gravity force.

adrenal lodge).

can reduce the risk of Addisonian disease [17].

**4.1 Elements of surgical technique and tactics**

(partial) adrenalectomies. Patients with multiple endocrine tumor 2 (MEN2) or von Hippel–Lindau disease (VHL) syndrome can benefit from cortical-preserving adrenalectomy in order to preserve and to maximize the adrenal function and to avoid chronic glucocorticoids replacement. Furthermore, cortical sparing technique

The operating table must benefit from adequate mobility in order to allow an adequate angulation in order to optimally open the anatomical space from the costal rim to the iliac crest. The operating surgeon and the cameraman are positioned in front of the patient and the assistant on the opposite side. The patient can be placed on the operating table in a lateral decubitus with a 90-degree angle position to ensure the full retraction of the spleen and a partial retraction of the liver by the

At the time of pneumoperitoneum installation, the patient is already lying on his side. The Veress needle will be inserted through the abdominal flank, being warned of the risk of visceral (liver or colon on the right side) or vascular (epigastric pedicle branches) injuries. Classic, there are three subcostal ports that can be positioned on the left and one epigastric port that is localized at the inferior margin of the liver. It is not unusual for the first trocar (corresponding to the left mid-clavicular line) to be inserted just a little bit slower than the other three subcostal trocars in order to offer a comprehensive view of the operative field and to identify the entire trajectory of the left colonic flexure (to facilitate the dissection of the colonic ligament for a lower positioning of the colon and to offer a better view over the left

For the left adrenalectomy, the spleen can be mobilized till the gastric fundus appears in the visual field, this can allow the spleen to retract more medially. This maneuvers can develop the plane between the spleen and the pancreas' tail, up to the left adrenal gland. The first maneuver is the incision made at the later splenic peritoneum. Further dissection is performed in a relatively avascular plane that is located close to the retropancreatic and anterior to the adrenal and renal capsule. Through this conjunctive structure's transparency, the adrenal tissue specific aspect

Sometimes, it is mandatory to cut the conjunctive tissue between the left colonic flexure (at its highest point) to the abdominal wall and to re-positioning the colon down below the level of the inferior pole of the spleen. After that, a broad view of this area is noticed. More than that, an easy discovery of the kidney superior left pole is possible, and this should be the start to identify (especially on obese patients) the groove between the left kidney and the pancreas – the normal localization of the left adrenal gland. For a pheochromocytoma dissection, the surgical gestures should be delicate, precise, and firm – a proper instrument of dissection should be used (sealing-cutting device, ultrasound device – electrocautery hook is to be avoided by the beginners and is a time-consuming device for an experienced

The essential vascular anatomical elements that will be treated in left adrenalectomy are the central vascular pedicle and the upper vascular pedicle. The left central vein (LCV) goes into the left renal vein, most commonly into the common trunk with the lower-left diaphragmatic vein (LLDV), from which it should be disected before injuring or clipping. The sectioning of this common

is easily distinguished as having a specific yellowish color.

(partial) adrenalectomies. Patients with multiple endocrine tumor 2 (MEN2) or von Hippel–Lindau disease (VHL) syndrome can benefit from cortical-preserving adrenalectomy in order to preserve and to maximize the adrenal function and to avoid chronic glucocorticoids replacement. Furthermore, cortical sparing technique can reduce the risk of Addisonian disease [17].
