Intracaval Tumors

Tumor thrombus extending from the renal vein into the vena cava has been reported to occur in 4% to 10% of patients with renal cell carcinoma.5 The extent of tumor thrombus involving the inferior vena cava can vary from involvement of the renal vein only to extension into the right atrium, which occurs in some of these patients. The majority of patients with vena caval tumors have right-sided renal primaries because of the short right renal vein. In the absence of metastatic disease, numerous centers have demonstrated long-term cancer-specific survival rates comparable to early-stage renal cell carcinoma following complete surgical excision.
Improvements in surgical technique have allowed the surgeon to safely perform a radical nephrectomy and vena cavotomy. Several centers have documented reduced morbidity and mortality associated with these procedures. We have removed tumor from both renal veins, lumbar veins, hepatic veins, the right atrium, and the right ventricle. Technical difficulties and complications (excessive bleeding, coagulopathy, and postoperative renal failure) can accompany these procedures, especially with extensive intra- or suprahepatic caval neoplastic extension.
DIAGNOSIS
Today, the majority of patients presenting with a renal mass and intracaval tumor extension are diagnosed with computerized tomography (CT). In the past, patients presenting with advanced disease had clinical signs and symptoms related to vena caval occlusion including bilateral lower extremity edema, a recently enlarging varicocele, or dilated abdominal wall veins. Patients may also present with proteinuria, hepatic dysfunction with hepatomegaly, or pulmonary embolus.
Patients should have a thorough evaluation for metastatic disease because, if present, we do not typically recommend proceeding with surgery. Further radiologic imaging typically includes CT of the chest and abdomen and a bone scan if applicable. The renal vein and vena cava can be noninvasively imaged using magnetic resonance imaging (MRI). The MRI can usually define the superior limit of the caval thrombus unless the distal thrombus is mobile, thus limiting its accuracy. The MRI is also effective when total caval occlusion is present. Vena cavography can be used to define a caval tumor; however, its invasive nature, its false-positive and -negative results, and a decreased ability to define the superior extent of the tumor limit its use. To fully delineate the extent of a large caval tumor, the combination of MRI and intraoperative transesophageal sonography provides the best results.8 All patients should have a complete medical evaluation and be deemed candidates to withstand an extensive surgery.
INDICATIONS
The primary indication for nephrectomy and vena cavotomy is a renal mass with intracaval tumor extension in the absence of metastatic disease. The patient should also be medically able to tolerate an extensive surgical procedure.
ALTERNATIVE THERAPY
To date, complete surgical excision of tumor is the only curative treatment. Expectant therapy or systemic protocols may be applicable if the patient is a candidate.
SURGICAL TECHNIQUE
In addition to a general anesthetic, a thoracic epidural can be utilized and is often effective with postoperative pain management with most flank incisions. For the majority of tumors, standard intraoperative monitoring includes central venous pressure, arterial pressure tracings, electrocardiography, and urinary output. Additional monitoring is used for extensive vena cava tumors, including a Swan–Ganz catheter, esophageal and rectal temperature probes, oxygen and carbon dioxide measurements, and transesophageal sonography. A hypothermic blanket is used to maintain body temperature. Elastic stockings and sequential compression devices are placed to prevent lower extremity venous stasis. An intravenous cephalosporin is generally sufficient as prophylactic antibiotic coverage.
The patient’s body habitus and extent of both the primary and intracaval tumor direct the surgical approach. For renal tumors with neoplasm extending minimally into the inferior vena cava, a supra-11th-rib or standard thoracoabdominal approach with rib excision is ideal, especially in obese patients. For left-sided tumors and more extensive caval tumors, an anterior incision will provide good exposure. We have used a thoracoabdominal incision extending from the tip of the scapula across the costal margin to the midline halfway between the umbilicus and the xyphoid process for right-sided tumors with intrahepatic and supradiaphragmatic intracaval tumor extension. In this approach, the patient should be positioned with the right shoulder rotated toward the contralateral side; the hips remain in the supine position, and the table is slightly extended. Although this incision provides both intra-abdominal and intrathoracic exposure, the infradiaphragmatic dissection is easier for the urologist while cannulating the aortic arch for cardiopulmonary bypass is more difficult.
We typically use a median sternotomy extending into either a midline abdominal or a chevron incision when the intracaval neoplasm extends into or beyond the liver and cardiopulmonary bypass is considered (Fig. 8-1).2 The chevron incision is useful in patients with a wide abdominal girth. Although these extensive incisions provide excellent exposure, allowing for additional operations to be performed, we recommend limiting the procedure to nephrectomy and caval thrombectomy.
The operation is commenced by utilizing the entire incision including the median sternotomy, as this approach gives the best exposure. The abdomen is inspected for metastatic disease, and if discovered, the procedure is usually stopped, as cancer-specific survival has not been demonstrated to be improved in the long term. In the absence of overt metastasis, the renal tumor is approached first. For a right renal tumor, the right colon is mobilized along the line of Toldt and retracted medially to gain access to the retroperitoneum. For significant tumors via a midline approach, incision of the root of the mesentery up to the ligament of Trietz with placement of the bowel into an intestinal bag retracted onto the chest provides additional exposure. We use the OmniTract retractor (Minnesota Scientific Inc.), as it provides excellent superficial and deep exposure of the surgical field. The kidney and Gerota’s fascia are mobilized, first by a posterolateral approach developing the plane between the quadratus/psoas muscles and Gerota’s fascia. After the kidney has been mobilized posteriorly, the renal artery is ligated early to keep blood loss to a minimum. Anteriorly, the mesocolon is then reflected medially from the anterior surface of Gerota’s fascia until the vena cava is visualized. A Kocher maneuver provides additional medial exposure near the vena cava. Superiorly, dissection above the adrenal is undertaken with Ligaclips, and the adrenal vein is ligated. Inferiorly, the kidney is mobilized along with ligation of the gonadal vein and ureter. Mobilization of the primary tumor is complete when the kidney remains attached to the vena cava by the renal vein.
A left-sided renal tumor with caval thrombus requires dissection on both sides of the abdomen to access both the vena cava and the left kidney. A midline incision usually provides sufficient exposure. The descending colon is reflected medially by incising the line of Toldt. In a dissection similar to that for a right-sided tumor, the kidney and Gerota’s fascia is mobilized until only the left renal vein remains. The ascending colon is then mobilized medially by incising the line of Toldt, and the duodenum is reflected by the Kocher maneuver. Once adequate exposure to the vena cava is obtained, the remainder of the procedure is similar to that for a right-sided renal primary tumor.
The extent of the intracaval tumor dictates the length the vena caval needs to be isolated. Dissection should proceed directly on the vena cava with care taken to prevent potential dislodgment of caval tumor. If the intracaval tumor extends slightly beyond the ostium of the renal vein into the vena cava, a Statinsky vascular clamp can be placed on the caval sidewall beyond the tumor. This segment of caval wall can be excised with the nephrectomy specimen en bloc, and the cava can be oversewn with a 4-0 polypropylene on a cardiovascular needle.
With a more extensive infrahepatic intracaval tumor, control of the vena cava must be obtained above and below the extent of the caval tumor thrombus. During mobilization of the vena cava, one or more posterior lumbar veins may require ligation to prevent unexpected bleeding. Inferiorly, a Rummel tourniquet (umbilical tape passed through a 16-Fr red rubber catheter) is placed loosely below the tumor thrombus and both renal veins. For a right-sided tumor, a Rummel tourniquet is placed loosely around a segment of the left renal vein to secure control of this vessel. Additional exposure to the vena cava can be gained superiorly by dividing the posterior attachments of the liver and rotating the liver medially. Depending on the superior extent of the caval tumor, variable venous branches draining the caudate lobe of the liver may need to be ligated and divided (Fig. 8-2). If these veins are short, they can be controlled using suture ligatures placed into the liver parenchyma. Cardiopulmonary bypass can be obviated when vascular control using a vascular clamp or Rummel tourniquet can be gained above the superior extent of the tumor. Division of the diaphragm may aid in gaining vascular control above the superior extent of the tumor thrombus.
After adequate mobilization of the vena cava superior and inferior to the tumor thrombus with ligation of any lumbar veins, all vascular clamps or Rummel tourniquets are secured. A narrow elliptical incision circumscribing the ostium of the involved renal vein is made. If the tumor is inseparable from the caval endothelium superior to the renal veins, the involved cava is excised. The renal primary and caval tumor is removed en toto under direct vision. On occasion, we have used a dental mirror to inspect the hepatic veins or the flexible cystoscope to inspect the cava to ensure complete removal of tumor. If additional verification is necessary, transesophageal echography can be used to evaluate the superior extent of the cava, or direct intraoperative sonography can be used to evaluate the extent of the cava.8
To close the vena cava, a 4-0 or 5-0 cardiovascular polypropylene suture is used. Before the cavotomy closure is completed, the inferior tourniquet is released to allow trapped air to escape through the cavotomy site. If excision of the cava decreases the vascular diameter by more than 50%, reconstruction of the vena cava is recommended to prevent caval thrombosis (Fig. 8-3). We prefer to reconstruct the vena cava using pericardium because it is less thrombogenic, although prosthetic grafts can be employed.3 Venous drainage of the right kidney must always be preserved to prevent venous infarction. In some instances, the cava has been oversewn to prevent subsequent embolism if the thrombus below the renal veins is adherent to the caval endothelium.
Cardiopulmonary Bypass, Hypothermia, and Temporary Cardiac Arrest
Cardiopulmonary bypass, hypothermia, and temporary cardiac arrest greatly facilitate the resection of a suprahepatic caval thrombus.4 It is best to dissect as much of the kidney and the vena cava as possible before cardiac bypass. Following isolation of the renal tumor, the pericardium is opened and retracted with stay sutures. Typically, the right atrial appendage is cannulated with a 32-Fr venous cannula, and the aorta is cannulated with a 22-Fr Bardic cannula. Heparin is then administered to maintain an activated clotting time greater than 450 seconds. The patient is placed on bypass with flow rates maintained between 2.5 and 3.5 liters/min. A core temperature of 18° to 20°C is attained within 30 minutes while an 8° to 10°C gradient is maintained between the perfusion and the patient’s core temperature. When a rectal temperature of 20°C is reached, the aorta is cross-clamped, and 500 cc of cardioplegic solution is administered. Once cardiac arrest is achieved, bypass is terminated, and the patient is temporarily exsanguinated into an oxygen reservoir. The patient’s brain is protected by placing ice bags around the head. At this point there is no anesthesia, ventilation, or circulation. To reduce the incidence of complications, circulatory arrest time is best limited to 45 minutes.
An elliptical incision is made around the ostium of the renal vein and carried superiorly along the length of the vena cava. The incision can extend into the right atrium or ventricle, depending on the superior extent of the thrombus. Cardiopulmonary bypass and deep hypothermic circulatory arrest permit the thrombus to be removed in a bloodless field and the interior of the vena cava and heart to be inspected under direct vision (Fig. 8-4). It is not uncommon to find some degree of adherence of the tumor to the endothelium. In this case, the tumor thrombus can be “endarterectomized” from the interior of the vena cava or atrium. Reconstruction of the vena cava is as previously described.
Following closure of the vena cavotomy, cardiopulmonary bypass is begun. The patient is slowly warmed using a 10°C gradient between the bypass machine and a warming blanket. Mannitol (12.5 g) is given along with 1 g of CaCl2 when core temperature reaches 25°C. Electrical defibrillation is necessary if the heart does not resume spontaneous beating. Following resumption of cardiac activity, blood is returned to the patient from the oxygen reservoir. Following the rewarming process, which can take up to 1 hour, heparin is neutralized with protamine. The patient is returned to the cardiac ICU intubated.
OUTCOMES
Complications

Intraoperative complications include excessive bleeding and coagulopathy. Coagulopathy is more common with prolonged cardiopulmonary bypass and cardiac arrest times. Intraoperatively, red blood cells, platelets, fresh frozen plasma, and calcium chloride are routinely administered. Furosemide and/or mannitol is given if urine output remains low. Transient hypotension can occur when the vena cava is clamped. This can be managed with volume expansion and is less of a problem if venous collaterals have developed with a completely occluded vena cava. Embolization of a segment of tumor thrombus can be a potentially lethal intraoperative complication, and extreme care should be taken when handling the vena cava to prevent such an occurrence.
Postoperatively, several complications can occur because of the magnitude of the surgical procedure or the use of cardiopulmonary bypass. Potential complications include caval thrombosis, deep venous thrombosis, pulmonary embolus, postoperative bleeding, or coagulopathy. Patients may also develop hepatic dysfunction, renal failure, sepsis, or myocardial infarction. Although the mortality rate associated with this procedure is tolerable, most patients who die of complications within the first postoperative month succumb to multisystem organ failure.
Results
The 5-year survival rates in most reported large series vary from 14% to 68% following complete surgical removal of the renal tumor and caval extension.1,6,7 Differences in reported survival may reflect several factors, including local extension of the primary tumor, presence of lymphatic or visceral metastases, level of caval tumor extension, or invasion into the vascular wall. lt is generally agreed that patients with metastatic disease and significant perinephric fat involvement tend to have a poor prognosis. The majority of patients eventually dying of their disease succumb to metastases, which suggests that occult metastatic disease is frequently present at the time of surgery.6 We believe that patients with good performance status who have tumors confined to the renal capsule and are without evidence of metastatic disease are ideal candidates for this surgery and have improved long-term survival.

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Pheochromocytoma

Pheochromocytomas are tumors that arise from chromaffin cells of the adrenal medulla. When such tumors arise at an extra-adrenal site, they are called paragangliomas, which can be located from the neck to the base of the pelvis (Fig. 4-1). These tumors have an incidence of one to two per 100,000 adults and represent a curable cause of hypertension in 0.1% to 1% of hypertensive patients.1,2 The malignancy rate is thought to be between 10% and 20%, though paragangliomas have a higher reported rate of malignancy, with over 50% reported malignant in some series.3,4 Pheochromocytomas may be familial in 10% of cases and are associated with a variety of other conditions including the syndromeof multiple endocrine neoplasia (MEN) type II-A,II-B, von Hippel–Lindau disease, and von Reckling-hausen’s disease.

The diagnosis and medical and surgical management of this condition have been evolving continuously since the first surgical resections of these lesions by C. H. Mayo in the United States and Roux in Europe.5,6 The nature of the biochemical pathways and the diagnostic urinary studies for catecholamines and their metabolites were established by Crout et al. in the early 1960s.7 The development of computed tomography in the 1970s provided an accurate, noninvasive method of imaging the adrenal glands and localizing these tumors,8 as has the later development of magnetic resonance imaging. Throughout the 1980s new medications and surgical techniques were developed to control intraoperative hemodynamics, which allowed a variety of surgical approaches including laparoscopy to be utilized for resection of these lesions.
DIAGNOSIS
Symptoms

Pheochromocytomas are rarely asymptomatic, though the symptoms may be varied and frequently mimic those of other conditions. Paroxysmal symp-toms (headache, diaphoresis, pallor, palpitations, andapprehension) are present in over 50% of patients. Hy-pertension, present in more than 90% of patients,may be paroxysmal in 25% to 50%. Other symptomsinclude nausea, trembling, weakness, epigastric pain, and syncope.
Biochemical
Pheochromocytoma or paraganglioma can be confirmed by demonstration of elevated urinary catecholamine levels (>100 µg total catecholamines per 24 hours overall, with epinephrine >20 µg and norepinephrine >80 µg, per 24 hours, respectively) or catecholamine degradation products such as metanephrines (>1.3 mg per 24 hours) and vanillymandelic acid (>6.5 mg per 24 hours); a value of >9.0 mg/24 hours determines over 90% of patients with pheochromocytomas.1 Total catecholamines, such as epinephrine, norepinephrine, and dopamine, can also be measured in the blood. Although urinary catecholamines have a higher specificity than plasma catecholamines, either may give misleadingresults because of other medical conditions (acute alco-holism, hypothyroidism, or volume depletion) or in-terfering medications. A combined free plasma norepinephrine and epinephrine level in excess of 950 pg/ml has a diagnostic sensitivity of 94% and a specificity of 97%. The radioenzymatic assay is sensitive to the circumstances in which the blood was collected, and this should be carefully controlled by having the patient in a fasting state and supine for at least 30 minutes before blood sampling through a large-bore needle placed at least 20 minutes beforehand to avoid a spurious catecholamine elevation caused by pain or apprehension. Baseline plasma norepinephrine and epinephrine levels of more than 2,000 pg/ml (norepinephrine >2,000pg/ml, epinephrine >200 pg/ml) indicate a pheochromocytoma. Failure of these levels to decline to less than 500 pg/ml after oral clonidine is also indicative of tumor.
Stimulation or provocation tests of patients suspected of this diagnosis can be extremely hazardous and are not recommended. Despite the reliance on diagnostic measurements of urinary catecholamines and their degradation products, newer agents have been tried to delineate borderline patients. Plasma catecholamines are measured after administration of clonidine or pentolinium tartrate. Patients with pheochromocytoma experience no significant decrease in circulating catecholamines with either agent, as opposed to normal patients, who do.
Imaging Techniques
A variety of imaging techniques are available for the detection of pheochromocytoma. Several decades ago, angiography and venography were the imaging techniques of choice. However, along with a low sensitivity, these modalities carried a significant morbidity and a risk of provoking a hypertensive crisis if the possibility of pheochromocytoma had not been considered.
The most frequent initial diagnostic modality currently is the abdominal CT scan, which, as a result of its widespread usage, has led to a significant increase in the diagnosis of asymptomatic adrenal lesions. This test has an accuracy rate for diagnosis of pheochromocytomas of over 90% and can be performed in patients who have not previously undergone a blockade, although unenhanced CT has been recommended as the initial localizing study to avoid even the small risk of precipitating a hypertensive crisis during the intravenous injection of contrast medium.9 Computed tomography has largely replaced nephrotomography, ultrasonography, selective angiography, and venography with venous sampling. However, CT does not differentiate among adrenal lesions and benign and malignant disease.
Magnetic resonance imaging (MRI) appears to be as accurate as CT in identifying adrenal lesions and also has a characteristically bright, light bulb image on T2-weighted study (Fig. 4-2). It is also very useful in the detection of recurrent local tumors in patients with metal clips and may have indications in pregnant patients. Sagittal and coronal imaging can give excellent definition of the surrounding anatomic and vascular relationships.
An alternative in the search for residual or multiple pheochromocytoma is the meta-iodobenzylguanidine scan (131I-MIBG). This compound is taken up by adrenergic granules and adrenal medulla cells and causesvirtually no pharmacologic effects. Because MIBG is concentrated in catecholamine storage vesicles, it is quite specific for pheochromocytoma rather than just an adrenal mass: MIBG scans have a 78.4% sensitivity in primary sporadic lesions, 92.4% in malignant lesions, and 94.3% in familial cases, giving an overall 87.4% sensitivity with 99% specificity. Although it provides no anatomic detail, this test is extremely useful when CT and MRI findings are confusing (Fig. 4-3).

INDICATIONS FOR SURGERY
Indications for surgery are an adrenal mass or extra-adrenal mass that meets the biochemical criteria for a pheochromocytoma. Additional indications include a positive MIBG scan or MRI with borderline biochemical criteria.
ALTERNATIVE THERAPY
There is no acceptable alternative therapy to the management of pheochromocytoma except surgery. Alternative approaches to the adrenal would include laparoscopic surgery, though with the high perioperative risks associated with this procedure, open surgery is by far the preferred route. In pregnant patients, oral blocking agents may be utilized until the fetus has matured, and cesarean section and tumor excision can be safely performed as one procedure, avoiding the potential stress of vaginal delivery.
SURGICAL TECHNIQUE
Preoperative Management

The localization of a pheochromocytoma is essential in planning definitive therapy and is influenced by whether it is sporadic (80% solitary adrenal lesion) or familial (50% bilateral) and whether it occurs in children or in adults. Multiple or extra-adrenal lesions occur in 10% of cases in adults and up to 30% in children. Localization techniques usually involve one or more of the imaging techniques listed above.
Adequate preoperative pharmacologic blockade provides a smoother and safer procedure for the surgeon, patient, and anesthesiologist. Phenoxybenzamine hydrochloride is an a-adrenergic blocker with both postsynaptic (a1) and presynaptic (a2) blocking capabilities. An initial divided dose of 30 to 60 mg orally is commenced. The dose is increased by 10 to 20 mg per day until the blood pressure has stabilized (maximum 100 mg/day). Recently, newer blocking agents have become available that are more selective and avoid some of the associated side effects. Patients are usually adequately blocked when they complain of postural hypotension and nasal stuffiness.
b-Blockers protect against arrhythmias, control tachyphylaxis from a-blockers and permit a decrease in the amount of a-blocker necessary to control blood pressure. These agents should be used only after a-blockade has been established because, alone, they may precipitate a rise in total peripheral vascular resistance through unopposed a-adrenergic activity, and used only when cardiac arrhythmias are expected.
a-Methylparatyrosine has been utilized in addition to phenoxybenzamine and/or propranolol. This agent decreases the rate of catecholamine synthesis and is particularly useful in patients who are resistant to a-blockers or have multiple paragangliomas.
Preoperative preparation also requires intravenous fluid replacement to ensure adequate hydration because many patients will have a depleted intravascular volume. Unless active fluid expansion is planned, the pharmacologic blockade should be of at least 2 weeks’ duration in order to allow the patient’s own homeostatic mechanisms to compensate for the recently expanded intravascular space. Crystalloids and in some cases blood transfusions may be required to accommodate the expanded intravascular volume produced by blockade, and an extra fluid load of 1 to 2 liters should be administered the night before surgery.
Anesthesia
The primary focus of anesthetic management of a pheochromocytoma patient is hemodynamic control. Close monitoring of the blood pressure, EKG, urinary output, and central venous pressure is essential in all phases of the procedure. An arterial line and Swan–Ganz catheter are frequently utilized. Sodium pentobarbital is usually used for induction, and virtually all inhalational agents have been administered for maintenance of anesthesia; these are usually combined with the neuromuscular blocking agents succinylcholine, d-tubocurarine, or pancuronium. The two inhalational agents of choice appear to be enflurane and isoflurane, with the latter decreasing myocardial contractility but being more resistant to metabolism and consequently less toxic. Either agent can also be combined with phentolamine or nitroprusside to control hypertension. Intraoperative arrhythmias can be controlled with either lidocaine or propranolol, although they frequently resolve following blood pressure normalization. Following interruption of the venous drainage of a pheochromocytoma, profound hypotension may ensue, and the surgeon should inform the anesthesiologist before performing this maneuver. Volume replacement is the treatment of choice, which may be augmented by the addition of vasopressors (Levophed) if necessary until the situation stabilizes.
Surgical Approach
There are numerous approaches to the adrenal gland, and the appropriate choice of access is governed by the size, multiplicity, and site of the lesion and the underlying pathology. In situations where a paraganglioma is a possibility, a midline abdominal incision allows a full assessment of the abdomen, retroperitoneum, and pelvis. The one essential is a detailed knowledge of the surgical anatomy of the adrenal glands (Fig. 4-4 and Fig. 4-5). Other factors such as the body habitus of the patient and the preference and experience of the surgeon must also be considered. Therefore, in view of all these variables, it is apparent that each case should be approached individually, with account taken of the various preferred guidelines for individual diseases.
The left adrenal gland is supplied by multiple small arteries superiorly originating from the inferior phrenic artery. Medially, multiple arteries arise directly from the aorta. Inferiorly, a constant artery arises either directly from the aorta just above the left renal artery or from the proximal renal artery itself. The venous drainage of the left gland is mainly through the inferior adrenal vein, which drains into the superior aspect of the left renal vein, usually just lateral to the aorta. There are virtually no blood vessels entering or draining the lateral aspect of the left adrenal under normal circumstances. Gerota’s fascia can be dissected anteriorly off the posterior aspect of the pancreas and the splenic vein and artery. If an anterior approach is used, the splenorenal ligaments must be divided, and the colon reflected medially, before Gerota’s fascia can be dissected, following which the spleen and pancreas can be elevated superiorly to expose the underlying anterior surface of the adrenal gland. A virtually avascular plane also exists posteriorly between Gerota’s fascia and the paraspinous muscles such that the gland can be mobilized from the surrounding structures before its blood supply.
The right adrenal gland is supplied superiorly by branches of the inferior phrenic artery that are often obscured by the overlying liver and inferior vena cava. Medially, small direct branches from the aorta course beneath the vena cava, and inferiorly a fairly constant branch of the proximal renal artery enters the gland. The venous drainage is again mainly through one vessel, which is short and enters directly into the vena cava just below the hepatic veins. Securing this vein is perhaps the most challenging aspect of adrenal surgery, as it is nearly always higher and shorter than expected, and adjacent vascular and fascial structures may have to be divided beforehand. In cases involving a large right-sided tumor, following reflection of the colon and duodenum it is not unusual to have to divide the caudate lobe veins entering directly into the vena cava in order to gain adequate exposure anteriorly. Once again, there are relatively avascular planes anteriorly, posteriorly, and laterally. Care should be exercised when freeing the inferior aspect of the gland, which can have vascular attachment to the upper pole of the kidney.
Small well-localized adrenal lesions may be approached by either a posterior, modified posterior, or flank approach. Larger lesions including pheochromocytomas, both single and multiple, may be approached by either an abdominal or thoracoabdominal incision. These latter two options are dealt with below, and the other approaches are described elsewhere in this section.
Thoracoabdominal and Transabdominal Approaches
The thoracoabdominal eighth, ninth, or tenth intercostal approach is the incision preferentially utilized for large right-sided pheochromocytomas.10 This approach offers the advantage of excellent adrenal exposure and an opportunity to palpate the thoracic sympathetic chain in the case of a rare associated paraganglioma metastasis. The peritoneal cavity may be widely opened for laparotomy, and in cases in which the contralateral gland must be explored, the incision is extended, though closure may be tedious. There is usually less requirement for this incision, with its extrapulmonary morbidity, when dealing with left-sided lesions. There is generally less vascularity to deal with, especially on the superior, lateral, and posterior aspects of the tumor, and the pancreas and spleen can be mobilized away from the lesion with ease.
The patient is placed in a semioblique position on a bean bag that is rolled to elevate the relevant flank and hemithorax. For this description the lesion is assumed to be right-sided, but the approach is similar for left-sided lesions. The right arm is then draped across the chest over a Mayo stand with careful padding and positioning to avoid a stretch or pressure injury. The left axilla is protected with a pad. The pelvis should lie almost parallel, with the contralateral knee flexed 90 degrees and lying under the straight ipsilateral leg, with padding between the two gFigure 4-6). The table is then hyperextended, and the patient is fixed in position with adhesive tape. The incision is made in the eighth, ninth, or tenth intercostal space at the angle of the rib and extended across the costal margin to curve inferiorly to the midpoint of the opposite rectus muscle. Once the latisimus dorsi, posterior inferior serratus, and the external oblique have been divided, the internal oblique is divided on the upper border of the rib itself, which need not be resected; the costvertebral ligament is divided, allowing the rib to swing down after division of the intercostal muscles. The pleura is then carefully entered, and the lung protected by a padded retractor. The diaphragm with overlying pleura will then be visualized and should be divided at the periphery about 2 cm from the chest wall in a circumferential pattern from anterior to posterior to allow for later reconstruction and to avoid damage to the phrenic nerve.
Heavy scissors are used to divide the costochondral junction, the peritoneum is opened, and the underlying liver can then be retracted upward. Because this incision is usually employed in large pheochromocytomas, the right triangular and coronary ligaments are divided, thus mobilizing the right lobe of the liver, which can be further retracted upward, providing excellent exposure of the suprarenal vena cava and the adjoining right adrenal vein. A fixed retractor (either Omnitract or Bookwalter) is preferred for this procedure. With the liver well protected and retracted into the chest, the posterior peritoneum lateral to the right colon is incised, and the incision is carried up along the vena cava to the level of the retracted liver edge (at the level of the hepatic veins) (Fig. 4-7). The right colon and duodenum are mobilized medially, and the kidney is gently retracted downward to bring the adrenal into view. The attachment of the kidney to the adrenal should be preserved until the gland has been completely mobilized, as this facilitates exposure and prevents direct manipulation of the tumor. At this point care must be exercised to avoid trauma to the small veins draining directly into the vena cava from the caudate lobe. If necessary, these veins may be divided between Adson clamps and sutured below the clamps with 5-0 Proline. At this point, full retraction is instituted to expose the entire operative field.
In pheochromocytomas, it is essential that the blood supply be isolated as soon as possible, with the adrenal vein ligated with either silver clips or 2-0 silk sutures. In cases where the vein lies far superior, extensive dissection and division of the arterial supply medially and inferiorly may be necessary to allow safe and satisfactory exposure of the vein. When there are large tumors extending medially below the vena cava, mobilization of the vena cava with division of the relevant lumbar veins, if necessary, facilitates exposure and ligation of the medial vessels between vascular clips. The vena cava can be retracted by passing vascular tapes below it to provide the necessary medial traction. If the tumor is confined to the adrenal gland, the remaining lateral and inferior attachments of the gland are mobilized and divided to complete the adrenalectomy.
An alternative approach to large pheochromocytomas is the anterior transperitoneal approach. This approach also allows early vascular control and provides the opportunity for a thorough laparotomy. The optimal approach involves a bilateral subcostal or chevron incision. A midline incision is used only when an extra-adrenal pheochromocytoma is suspected in either the pelvis or retroperitoneum. This approach is particularly suitable for left-sided large pheochromocytomas.
A number of approaches are available to expose the left adrenal gland. Exploration through the lesser sac or the avascular plane in the transverse mesocolon is ideal for small tumors. However, for large tumors, following laparotomy, the posterior peritoneum lateral to the left colon is incised, and the incision is extended to include the lienorenal ligament. Splenic injury is a risk during this maneuver. Once again, a fixed ring retractor is optimal in this procedure. The initial dissection involves exposure of the left adrenal vein, which is easier to approach on this side and is ligated at its entry into the renal vein with 2-0 silk ligatures. The anterior and posterior adrenal planes are then developed, and the spleen and pancreas are gently retracted superiorly. The left colon and duodenum are reflected medially. Leaving the distal ligature long permits the ligated adrenal vein to be utilized to provide retraction to facilitate ligation of the inferior adrenal artery (Fig. 4-8). The gland is then mobilized with gentle blunt dissection on its lateral and posterior margins. Downward traction on the kidney facilitates exposure of the superior vascular ligaments, which may be tied with 3-0 silk or ligated with vascular clips. Lateral traction is then employed to expose the medial arteries and lymphatic vessels, which are ligated. Finally, the remaining inferior attachments are divided, and the adrenal gland is removed (Fig. 4-9, Fig. 4-10 and Fig.4-11).
The adrenal fossa is carefully inspected for bleeding and, after electrocautery, packed while the surrounding viscera are carefully examined. Persistent oozing may be controlled with Surgicel or Gelfoam. The incisions are closed in a standard fashion, with no drainage utilized. Nasogastric suction may be employed for 48 hours to minimize postoperative distention.
Postoperative Care and Specific Complications
In the recovery room, vital signs and mental status are closely monitored. Patients with a flank, posterior, or thoracoabdominal incision should have a chest radiograph to rule out a pneumothorax or document proper positioning of a chest tube. Pain control is a major contributing factor to reduce atelectasis and promote early ambulation. Intensive care monitoring for the initial 24-hour period is prudent following removal of a pheochromocytoma.
OUTCOMES
Complications

Specific complications seen during both the intra- and postoperative period include profound hemodynamic instability, which requires precise monitoring and adequate preoperative preparation. Postoperatively, large boluses of intravenous fluids with pressor support may be necessary to maintain stability. Vasospasm sufficient to reduce enteral blood flow may be encountered and should be considered along with possible neurologic complications in inadequately blocked or unrecognized cases.
When dealing with large lesions, the surgeon needs to bear in mind that the renal vascular anatomy may be distorted and out of position, putting it at risk of inadvertent injury. Significant hemorrhage secondary to vena caval or renal vein lacerations may occur and require repair with 4-0 or 5-0 Proline once adequate control has been established. Left-sided lesions may be associated with pancreatic or splenic injuries resulting in postoperative bleeding and hypotension (which may be attributed to metabolic causes) or a fistula. In cases where such an injury has occurred, placement of a drain may be prudent.
Results
The Lahey Clinic reported a 0% mortality in 62 patients treated for pheochromocytoma and a 25% postoperative morbidity rate in the 41 patients whose records were available.11 However, overall, convalescence of patients undergoing adrenal surgery is reasonably benign.

Primary Aldosteronism

EPIDEMIOLOGY
Primary aldosteronism was first described by Jerome Conn in 1955.3 The clinical characteristics and manifestations, frequently referred to as Conn’s syndrome, include hypertension, hypokalemia, hypernatremia, and alkalosis with increased urinary potassium excretion and decreased urinary sodium. Many patients with aldosteronism exhibit certain forms of diabetes.1
The most common cause of primary aldosteronism is a solitary aldosterone-secreting adrenal adenoma. However, there are a large group of patients who will exhibit primary aldosteronism as a result of bilateral focal or nodular adrenal hyperplasia. In addition, a few patients have been reported with aldosteronism as a manifestation of adrenocortical carcinoma; the syndrome may be exaggerated in these rare instances. In children, aldo-steronoma is rare, with most cases secondary to adrenocortical hyperplasia.
PATHOPHYSIOLOGY
The electrolyte and acid–base disorders of aldosteronism are readily understood as a consequence of excessive production of aldosterone. However, the exact mechanism of the hypertension, generally indistinguishable from essential hypertension, is not easily explained. On the other hand, hypertension in the presence of hypokalemia (serum potassium less than 3.5 mEq/liter), alkalosis (serum bicarbonate more than 30 mEq/liter), and hyperkaluria (urinary excretion of more than 30 mEq/24 hr) is most certainly caused by aldosteronism. The diagnosis can be confirmed by measurement of plasma aldosterone levels, remembering that there will be a diurnal variation and postural responses. A more reliable method of establishing elevated aldosterone levels is the measurement of 24-hour urinary excretion values (normal range 5 to 19 µg/24 hr).10
DIAGNOSIS
Laboratory

The routine laboratory determinations noted above are fundamental to the diagnosis of primary aldosteronism. Measurement of plasma and urinary aldosterone can generally be accomplished in hospital and commercial laboratories. Adrenal venous sampling for measurement of plasma adosterone is almost always accurate in determining elevated levels of aldosterone as well as aiding in the localization of solitary adenomas.
The postural stimulation test (PST) may be used not only to confirm the diagnosis of primary aldosteronism but also to distinguish between aldosterone-producing adenoma and idiopathic hyperplasia as the cause of the syndrome. Serum aldosterone and cortisol levels are measured after overnight recumbency, patients are ambulated for 4 hours, and the tests are then repeated. Patients with adenoma exhibit elevated base levels of aldosterone that will either fall or increase minimally after upright activity, whereas the high base level of aldosterone in patients with hyperplasia will generally rise signficantly, more than 30%. Demonstration of a reduced or unchanged cortisol after ambulation confirms the validity of the test, reflecting the usual morning fall in ACTH.
Further diagnostic confirmation of primary aldosteronism may be gained through measurement of plasma renin.4 Renin production is suppressed, usually below normal levels, in aldosteronism as compared with renin levels in normal subjects or those with hypertension of other causes. This is the consequence of the homeostatic mechanism by which blood volume and hence blood pressure is maintained under normal circumstances. Figure 3-1 graphically depicts this mechanism in which a decreased blood volume or flow to the kidney stimulates the stretch receptor mechanism, invoking increased production of renin. Renin then acts on angiotensin I to convert it to angiotensin II, which in turn stimulates adrenocortical production of aldosterone. This generates increased excretion of urinary potassium with conservation of sodium, leading to fluid retention, which, in turn, increases the blood volume. Clearly, the presence of increased aldosterone will lead to some degree of hypervolemia, which will result in decreased production of renin.
Aldosteronoma may also be differentiated from idiopathic hyperplasia by serum assay for 18-hydroxycorticosterone (18-OHB). Young and Klee10 observed that patients with adenoma usually have 18-OHB levels more than 100 ng/dl after overnight recumbency, whereas patients with hyperplasia have values less than 100 ng/dl. It has been reported that 18-OHB assay accuracy is increased by intravenous saline infusion, and it has also been observed that the ratio of 18-OHB to cortisol is greater than 3 in patients with aldosteronoma but not in patients with hyperplasia.
The diagnosis of primary aldosteronism may be confirmed or excluded using the fluorocortisone (0.1 mg q6h for 4 days) suppression test. Similarly, familial hyperaldosteronism type 1 may be diagnosed or excluded by use of the dexamethasone (0.5 mg q6h for 4 days) suppression test, although identification of the hybrid gene in peripheral blood DNA may also be diagnostic.
Localization Techniques
A variety of imaging techniques may be employed for localization of aldosterone-producing adenomas or adrenal hyperplasia, though actual adrenal enlargement with patients with focal micronodular hyperplasia is uncommon. Large adrenal tumors greater than 3.0 cm in diameter may be visualized on a plain film of the abdomen or by intravenous pyelography. However, it is extremely unusual for aldosterone tumors of the benign type to present as a large mass. In contrast, the rare malignancy may achieve significant size.
In years past, retroperitoneal carbon dioxide insufflation studies were employed for visualization of the adrenals. This invasive technique is no longer necessary because both CT scanning and magnetic resonance imaging are extremely effective in identifying hyperplastic adrenals or aldosterone-producing adenomas as small as 6 or 7 mm.6 The anatomic relationship of the adrenal glands to the kidneys or other viscera as delineated by CT or MRI is illustrated in Fig. 3-2.
Adrenal venography is not recommended as a routine procedure. The retrograde injection of contrast material into the adrenal may produce an infarction on occasion. If such injury is incurred by the normal adrenal, removal of the contralateral adrenal with an aldosteronoma could result in adrenal insufficiency. However, adrenal venography may be accomplished on some occasions, particularly if adrenal vein hormone sampling is desired.
Adrenal scintigraphy is one of the most useful noninvasive studies in functional evaluation and anatomic localization of aldosteronomas.5 Adrenocortical scanning is performed with the radionuclide 131I-6-b-iodomethyl-19-norcholesterol (NP-59). All antihypertensive medications should be discontinued for 1 week, allowing normal dietary sodium intake with the addition of dexamethasone treatment for 3 to 7 days. Oral iodide is given to block tracer uptake by the thyroid, and imaging is performed 2 to 5 days after administration of NP-59. Prompt unilateral adrenal uptake and activity are evidence of aldosteronoma, whereas bilateral uptake is evidence of adrenal hyperplasia. The test has about a 75% accuracy.
INDICATIONS FOR SURGERY
It is imperative that the cause of primary aldosteronism be established because the etiology will determine treatment and management.7 Patients with adrenal carcinoma most certainly should have adrenalectomy, preferably by open surgery and usually through the transabdominal approach. Patients with idiopathic hyperplasia as a cause of aldosteronism are best managed medically because surgical removal of the adrenals rarely will result in control of hypertension. Medical management consists of administration of spironolactone, diuretics such as hydrochlorothiazide, and antihypertensive medications if necessary.
Removal of a discrete aldosteronoma will result in cure of hypertension and conversion of biochemical abnormalities in 80% to 90% of patients. Accordingly, adrenalectomy or partial adrenalectomy is the procedure of choice in patients with an aldosterone-producing adenoma. Because bilateral and ectopic aldosteronomas are essentially unheard of, the unilateral removal of the adenoma or the adrenal is preferred.
ALTERNATIVE THERAPY
It must be stated that aldosterone-producing adenomas of the adrenal are essentially ideal for laparoscopic management.2 This technique is amply described in Chapter 132. Laparoscopic adrenalectomy will become the procedure of choice for the single adenoma producing aldosteronism, but there will be instances in which open surgery is desirable.9
SURGICAL TECHNIQUE
General endotracheal anesthesia is required. Position of the patient demands control of the airway, and forceful ventilation at times during the procedure is necessary for identifying and protecting the diaphragm and pleura and in closing any pleural rents that may be incurred during the exposure. There are no special anesthetic requirements, such as nitroprusside, as with pheochromocytoma.
The preferred approach to the involved adrenal in cases of primary aldosteronism secondary to adenoma is posterior (Fig. 3-3). Incision may be the classical hockey stick, as described by Hugh Hampton Young, or a rib incision may be utilized. Personal preference is for an oblique incision over the 11th rib, resecting the rib as far medially as possible but preserving the periosteum, which affords excellent substance for closure. An alternative is the supracostal incision of Turner-Warwick, cutting the rib at its posterior angle to allow for inferior deflection. The supracostal incision avoids the infracostal vessels and nerves. Personal preference is for rib resection (Fig. 3-4).
Entry into the pleural cavity can be avoided by carefully reflecting the pleura upward. This is best accomplished by beginning the dissection laterally at the extreme lateral margin of the incision. By blunt and sharp dissection, the pleura and most of the diaphragmatic muscle fibers can be swept medially and superiorly, literally moving the pleural cavity away from the diaphragm to give access to the retroperitoneal space. By using this technique and proceeding from lateral to medial, it is usually possible to avoid entry into the pleural cavity.
Once the retroperitoneal space has been entered, Gerota’s fascia can be identified. This should be opened as far superiorly as possible. The perinephric fat is readily identified, having slightly different texture than the surrounding retroperitoneal fat deposits. The peri-nephric fat is dissected medially and superiorally to expose the upper pole of the kidney, which is then freed of surrounding fat. A padded Deaver rectractor is then introduced over the upper pole of the kidney, which is retracted inferiorly. This maneuver will almost always bring the ipsilateral adrenal into view in the operative field.
The adipose tissue surrounding the adrenal is delicately teased away from the adrenal gland. No significant vasculature is encountered in this dissection, but small bleeders may be controlled by electrocautary. The adrenal is thoroughly exposed before an attempt is made to gain access to the vessels.
The blood supply of the adrenals is variable from side to side and from patient to patient. It is relatively independent of renal circulation (Fig. 3-5). The arterial supply to each adrenal consists of a multitude of small branches derived from the renal artery, the aorta, the inferior phrenic, and occasionally from the splenic artery on the left. The venous return is much more constant than the arterial supply, the right adrenal vein arising from the hilum of the gland medially and emptying directly into the vena cava, whereas on the left, the main adrenal vein joins the inferior phrenic to empty into the left renal vein. Control of the vasculature is generally achieved with small metal surgical clips as the dissection proceeds.
Injury to contiguous structures must be avoided. On the right, the adrenal is in close proximity to the liver superiorly and anteriorly, the vena cava medially, and the kidney inferiorly. Great care should be taken to identify the vena cava because the gland is in intimate contact. On the left, the adrenal is somewhat closer to the renal pedicle, and care must be taken in exposing the inferior surface of the gland to prevent damage to the renal artery and vein. The posterior aspect of the stomach and the tail of the pancreas are in close approximation to the left adrenal anteriorly.
Once the gland has been isolated, it is removed from the wound, and the bed is inspected for bleeding, which is controlled by cautery in most instances. Occasionally it is useful to employ a square of Gelfoam or Oxycel in the bed of the adrenal. Surgical drains are unnecessary in virtually all cases. When retraction is discontinued, the kidney will ascend into its normal position, virtually obliterating the space from which the adrenal gland was removed.
Gerota’s fascia is closed using multiple running and interrupted sutures of absorbable materials, usually catgut or polyglycolic acid (PGA). Closure of the rib bed consists of approximating the two portions of the periosteum with either absorbable or nonabsorbable suture material, usually 2-0 catgut, taking care to avoid injury to the infracostal neurovascular bundle.
There is scanty musculature overlying the rib, but this may be closed with interrupted absorbable sutures. Subcutaneous tissue is approximated with running or interrupted plain catgut, and skin may be closed with metal clips or, preferably, with interrupted vertical mattress sutures of 3-0 silk.
With the imaging studies available, aldosterone tumors will almost always have been localized preoperatively. Rarely, it may be necessary to accomplish bilateral adrenal exploration before making a decision about adrenalectomy. If this is the case, simultaneous and identical exposures of the adrenal area may be achieved. The Finochietto thoracic retractor may be utilized with the blades reversed to compress the paraspinialis musculature in the fashion shown in Fig. 3-6.
OUTCOMES AND COMPLICATIONS
Entry into the pleura occurs with great frequency simply because of the deep inferior reflection in many patients. Indeed, such entry into the pleural cavity cannot be regarded as a complication but rather as the anatomic consequence in most instances. Opening into the pleura can be managed near the conclusion of the case. A soft rubber catheter of about 18 F caliber with multiple openings cut near its tip is introduced into the pleural cavity. The pleura with diaphragm is then closed with running sutures incorporating the catheter. The anesthesiologist is requested to fully expand the lungs for a period of about 30 seconds while suction is applied to the catheter, which is then quickly withdrawn, and the suture is tied securely while the lung is inflated. A postoperative chest x-ray obtained in the recovery room will assure that there is no residual pneumothorax.
Intraoperative bleeding is virtually never a problem. On the left, the aorta is readily identified by palpation of its pulsation, which permits avoiding any injury in dissection. A bit more caution must be employed on the right because the vena cava is not as readily identified. If the vena cava is opened during the process, it is best closed with running suture of atraumatic 3-0 vascular silk.
Variations in blood pressure during surgery are rarely encountered. Whereas the patient with pheochromocytoma may experience wide fluctuations in blood pressure, the hypertensive patient with aldosteronism does not exhibit this same lability. As a consequence, preventive measures such as administration of blood volume expanders or whole blood are rarely necessary.
Postoperative infection is also a rarity in surgery for aldosteronoma. Although the patient with Cushing’s disease may suffer immune suppression and a tendency to infection, this is not the case in primary aldosteronism. Ordinarily, prophylactic postoperative antibiotic therapy is not employed, but an elderly person with poor ventilation and potential pulmonary compromise may justify utilization of anticipatory antibiotic therapy.
Early ambulation is optimal. To facilitate patient mobility, a Marcaine block of the intercostal nerves attendant to the resected rib and the ribs above and below the line of incision may be useful.
A simple dry dressing is applied in the operating room but may be removed the day after surgery. Discharge can be effected on the second postoperative day in some cases.
The most significant complication of surgery of aldosteronism is the persistence of hypertension. This is common in patients with idiopathic adrenal hyperplasia but uncommon in patients who have a solitary adenoma as the etiology of aldosteronism.8
If a normal adrenal gland is present contralaterally, there should be no problem with adrenal insufficiency. However, in congenital absence of the opposite adrenal, supplemental corticosteroids and mineralocorticoids will be necessary.

Adrenal Adenoma and Carcinoma

Adrenal tumors present either as a result of their clinical symptoms or as incidental findings during radiologic imaging studies. The nomenclature “adrenal incidentaloma” describes adrenal tumors discovered inadvertently by radiologic imaging in the absence of clinical indication.
The objectives of this chapter are to discuss the various aspects of adrenal incidentaloma and adrenocortical carcinoma with regard to the epidemiology, natural history, investigation, diagnosis, and treatment with particular emphasis on their surgical management. Aldo-steronoma, pheochromocytoma, Cushing’s disease and syndrome, and laparoscopic adrenalectomy have been purposely excluded from this chapter because they are reviewed in detail in Chapter 1, Chapter 3, Chapter 4, and Chapter 132.
EPIDEMIOLOGY AND NATURAL HISTORY
The prevalence of adrenal incidentalomas is estimated to approach 2%,3 similar to the 1.9% figure of autopsy series, considering the increasing and widespread use of various radiologic images such as ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI).1,3,10 The incidence of adrenocortical carcinoma, on the other hand, is extremely rare, with an estimated annual rate of 0.00006% to 0.00017% in the population, i.e., approximately one in a million.4 Because the majority of adrenal carcinomas present late, and approximately half are hormonally active, it is calculated that the chance of detecting an adrenocortical carcinoma is one in 1,700 adrenal incidentalomas. Adrenocortical carcinomas occur in all age groups but are most common in the fifth to seventh decades of life.
The vast majority of adrenal incidentalomas are benign, remain asymptomatic, and have favorable outcome. On the other hand, the opposite is true in adrenocortical carcinoma, which is an aggressive malignant disease with ominous prognosis. The majority present late with local invasion, regional lymph node involvement, or distant metastases (stages III and IV) rather than early, i.e., confined to the adrenal gland (stages I and II). Approximately half of these tumors are hormonally active and release excessive secretions of glucocorticoids, estrogens, androgens, and, rarely, mineralocorticoids.
DIAGNOSIS
Biochemical Evaluation
Incidentally discovered adrenal tumors found by radiologic imaging can exhibit hormonal activity that initially may not be clinically apparent. Subsequent detailed endocrine clinical assessment may reveal, for the first time, clinical features suggestive of hormonal activity.
In these patients, further evaluation with appropriate biochemical testing is indicated according to the clinical suspicion. On the other hand, 15% of adrenal incidentalomas may be totally asymptomatic in a setting of subclinical hormonal activity. Much debate currently exists regarding the recommended biochemical evaluation in this latter group. It is to be emphasized that before embarking on an extensive and exhaustive biochemical evaluation, one must consider the expected detection rate and cost/benefit ratio of such an empirical approach. The overall low prevalence of hormonal activity in these adrenal incidentalomas and the type of hormonal dysfunction likely to be encountered call for a more selective approach. The calculated possibility of uncovering a pheochromocytoma or aldosteronoma is one per 15 adrenal incidentalomas, and for a glucocorticoid-producing adenoma or adrenal carcinoma, it is one per 1,700 to 2,800.9 It therefore seems reasonable to initiate biochemical screening for primary hyperaldosteronism with serum potassium first and for pheochromocytoma with urinary VMA, catecholamines, and metanephrines. Biochemical assessment for glucocorticoid and sex hormones should be reserved for patients with clinical features suggestive of such hormonal dysfunction.
Radiologic Evaluation
Computerized tomography (CT) is the standard radiologic imaging modality for adrenal tumors. It is utilized to delineate the anatomy and characterize the morphology of adrenal tumors. Although CT is reliable in the diagnosis of certain benign adrenal masses such as myelolipoma (Fig. 2-1) and simple cysts, its dependability in accurately differentiating between benign and malignant tumors is limited. Certain CT features suggestive of a malignant process include a tumor >6 cm, inhomogeneity, irregular contours, thickened walls, and calcification, as illustrated in Fig. 2-2.
Magnetic resonance imaging (MRI) is increasingly becoming a valuable radiologic tool in the evaluation of adrenal tumors. The MRI provides better visual clarity and resolution than CT imaging. Furthermore, the utilization of coronal planes in MRI (Fig. 2-3 and Fig. 2-4) offers superior images for understanding anatomy and for assessing vena cava involvement. More recent advances in the MRI technique have revealed encouraging results in distinguishing between benign and malignant adrenal tumors.2,5,6,7 and 8 This is achieved by the manipulation of fat and water MRI signals (chemical shift technique), which allows for the detection of microlipids within the tumor; these are a hallmark for benign adrenal adenomas. A significant subtraction of microlipids from the adrenal mass tissue on MRI as illustrated in Fig. 2-5 implies a benign adrenal adenoma. Conversely, lack of microlipid subtraction from the adrenal tissue, i.e., an area of hyperintensity, correlates with the presence of malignancy (Fig. 2-6). Further clinical experience and future refinements of this technique hold a real potential for MRI to become the imaging modality of choice in the evaluation of adrenal masses.

Fine Needle Aspiration Cytology
When clinical, biochemical, and radiologic evaluation fail to provide sufficient diagnostic information for an appropriate management decision, fine needle aspiration (FNA) cytology may play a role. Difficulty in tissue sampling, preparation, and interpretation can lead to false-negative results and limit its reliability. Potential indications for FNA cytology include atypical adrenal cysts, i.e., with thick, irregular walls or inhomogeneous fluid content, and differentiation between primary and metastatic deposits in individual cases.
Other Evaluation
Recent advances in noninvasive radiologic imaging such as CT and MRI have replaced the need for scintigraphy as well as NP-59 and MIBG, venography, and arteriography. The previously recommended use of venography in the assessment of inferior vena caval involvement has been superseded by the less invasive MRI. In rare circumstances, preoperative arteriography may have a role in delineating the vascular supply of large adrenal masses to aid in planning surgical resection.
INDICATIONS FOR SURGERY
Generally, there are two definitive indications for surgical excision: (a) symptomatic and hormonally active adrenal tumor and (b) adrenal carcinoma.
The dilemma arises in patients with asymptomatic adrenal tumors and unconfirmed diagnosis despite extensive evaluation. These constitute a gray zone into which fall the majority (>80%) of adrenal incidentalomas. Conservative management of these patients by observation and serial imaging poses certain concerns about the possibility of delayed or missed diagnosis of a biologically active lesion. To date, the controversies continue with no clear answers to the primary concern of whether or not a tumor is malignant.
As a result of the available epidemiologic data, the influence of radiologic features, and FNA cytology, certain guidelines are becoming available for management decisions in an attempt to minimize unnecessary surgical excisions without compromising the final outcome.
Surgical resection continues to be the treatment of choice for adrenal masses with features suggestive of malignancy such as large size (>6 cm), inhomogeneity, irregular contours, thickened walls, calcification, regional lymphadenopathy, lack of microlipids on chemical-shift MRI, and suspicious FNA cytology. Conservative management with observation and serial imaging is recommended for small tumors (<3 cm) with benign radiologic features and negative FNA cytology (Fig. 2-7).
In the midst of this spectrum reside the 3- to 6-cm tumors that pose the greatest diagnostic difficulties, especially when their imaging features and FNA cytology are equivocal.
The decision whether to observe or operate should be carefully tailored in each individual case, keeping in mind the possibility of small adrenocortical carcinoma. In patients with a metastatic deposit to the adrenal gland, the decision for surgical excision should be meticulously evaluated, and surgical excision should be limited to patients with solitary metastatic deposits in whom the primary malignancy has been adequately treated.
SURGICAL TECHNIQUE
Surgical Approaches to the Adrenal Gland
Adrenalectomy can be performed through a number of surgical approaches. These include posterior (with and without rib resection); posterior transthoracic; lateral flank (with and without rib resection); anterior transabdominal through subcostal, transverse, Chevron, or midline incisions; thoracoabdominal; and laparoscopic approaches. The choice of surgical approach is influenced by the tumor pathology, size of the adrenal tumor, and patient’s habitus as well as by the surgeon’s preference, familiarity, and experience with the surgical technique. This chapter focuses primarily on the lateral flank approach because the remaining surgical approaches are discussed in detail in the other chapters.
General Considerations
Regardless of the surgical approach, it is of paramount importance for the urologist to fully understand the anatomic position and relation, the blood supply of the adrenal glands, and the difference between the two sides. Each adrenal is a delicate and friable gland located superior to the upper pole of the kidney on the right but in a more superomedial position on the left. They lie adjacent to their respective great vessels, with the right posterolateral to the inferior vena cava and the left adrenal lateral to the aorta (Fig. 2-8 and Fig. 2-9). Other structures in close anatomic proximity include the duodenum on the right and the stomach, spleen, and pancreas on the left (Fig. 2-9). The sympathetic chain and ganglia are also closely located posteromedially to the adrenal glands, particularly on the left side.
The arterial blood supply originates from three sources: the inferior phrenic artery superiorly, the aorta centrally, and the renal artery inferiorly (Fig. 2-8). This rich blood supply enters the adrenal gland in a stellate fashion, primarily superomedially, while the base and the posterior surface of the gland often lack vasculature. Each adrenal has one central vein; the one on the right is short and drains directly into the inferior vena cava, and that on the left is longer and drains into the left renal vein.
The Posterior, Modified Posterior, and Posterior Transthoracic Approaches
The posterior surgical approach is performed through a subcostal incision, though resection of a rib (12th or 11th) is frequently required for better exposure. This approach was favored in the past in bilateral adrenal surgery for diagnostic exploration and total ablative adrenalectomy. However, with better preoperative radiologic diagnosis and localization of adrenal masses and the decline of bilateral surgical adrenalectomy in cancer therapy, the use of this approach has diminished. The posterior approach provides a limited surgical field, and the incidence of pleurotomy increases with rib resection, which may prove challenging and unsuitable for excision of large adrenal masses and in overweight patients. Nonetheless, it provides a relatively direct access to the adrenal gland, is potentially less traumatic, is well tolerated by patients, and causes less postoperative ileus. In our opinion, the posterior approach to adrenalectomy is best reserved for thin patients with small well-localized benign adrenal tumors in anatomically favorably positioned glands.
Modifications of the standard posterior approach have been utilized for excision of larger adrenal masses. Such modifications include an upward extension of the medical end of the standard posterior oblique skin incision, rib resection, and transthoracic accesses. A superior surgical exposure is achieved at the expense of more extensive dissection and the need for chest tubes postoperatively.
Lateral Flank Approach
The lateral flank approach offers better and larger operative exposure for excision of larger tumors in adrenal glands positioned in less favorable anatomic locations. In general, urologists tend to be more familiar with this approach because of its frequent utilization in renal surgery.
Following the administration of general anesthesia with endotracheal intubation, a Foley catheter is used to drain the bladder, and sequential compression devices (SCD) are placed on the legs. The patient is then placed in the lateral position with the flank over the flexion/kidney rest site of the operating table with the patient’s back close to the edge. Both arms are kept extended, with the contralateral one resting on an arm rest with an axillary roll and the ipsilateral arm on a stand adjusted to the appropriate height and angle. A pillow is placed between the legs, keeping the contralateral leg flexed, and the ipsilateral leg is allowed to remain straight. The kidney rest is then raised, and the table is flexed to 30 to 45 degrees (Fig. 2-10). The patient position is then further secured by the use of wide adhesive tape over the hip and shoulder.
Following skin preparation and draping, a flank skin incision is made along the rib extending from sacrospinalis muscle posteriorly to lateral border of the rectus abdominis muscle anteriorly. The incision is deepened through the subcutaneous fat layer, exposing the external oblique muscle anterolaterally and the latissimus dorsi muscle posteriorly, under which lies the internal oblique muscle and inferior part of the serratus posterior muscle. The muscles are incised with diathermy along the line of the incision to expose the rib, thoracodorsal fascia, and the transversus abdominis muscle. Two spring retractors are placed to retract the muscle edges and facilitate the exposure. The periosteum over the rib is incised and elevated using a periosteal elevator or diathermy. The tip of the rib is freed and gently retracted outward with the aid of a Kocher clamp to expose its undersurface. The rib is dissected off its bed along its entire length, starting at the tip. It is then transected at its proximal end with the aid of a guillotine rib resector. The use of diathermy instead of conventional periosteal elevators during rib dissection allows for better control of hemostasis and decreases the chance of accidentally injuring the neurovascular bundle or the pleura. The lumbodorsal fascia and the transversus abdominus muscle are incised, exposing the peritoneum and its preperitoneal fat. The peritoneum is bluntly dissected off the abdominal wall using the index finger in gentle sweeping motions, and the dissection is continued to free the undersurface of the rib bed. Starting anteriorly, the rib bed is carefully incised to complete the access into the flank. Careful attention should be practiced to avoid injury to the neurovascular bundle inferiorly, pleura, and diaphragm superiorly, and a Finochietto self-retaining retractor is then placed.
Once in the flank, the kidney is partially mobilized by blunt dissection of the overlapping peritoneum and colon off Gerota’s fascia. Crossing vessels along the dissection plane are coagulated or ligated to secure hemostasis as the dissection is continued medially toward the renal hilum. The renal vein is visualized laterally and inferiorly to further mobilize the lower pole of the kidney. The superior pole of the kidney and the adrenal gland are purposely kept attached together to aid in the dissection later; this allows the adrenal gland to be brought down by gentle inferior traction of the kidney and thus facilitates the identification of its vessels and surrounding attachments. The vessels and the surrounding attachments of the adrenal are then secured with 3-0 silk ligatures, surgical clips, or electrocautery, resulting in mobilization of the adrenal gland (Fig. 2-11 and Fig. 2-12). It is to be stressed that the adrenal vessels are small, short, and easily traumatized, especially on the right, thus demanding gentle retraction and careful dissection. Finally, unless simultaneous nephrectomy is not indicated, the adrenal gland is dissected off the upper pole of the kidney and removed (Fig. 2-13 and Fig. 2-14).
In the treatment of adrenocortical carcinomas, surgical treatment also necessitates additional en bloc radical nephrectomy. The renal vessels and ureter are therefore identified, ligated with 2-0 silk, and transected. The kidney is removed en bloc with its Gerota’s fascia and attached adrenal gland. Surgical excision of the regional lymph nodes is performed by removing the retroperitoneal tissue surrounding the adjacent great vessels. Drains are not used unless there is some residual bleeding. The flank musculature and fascia including the periosteum of the rib bed are closed in layers using running 0 polyglycolic (Dexon) or polygalactic polymer (Vicryl) sutures. Subcutaneous tissue is closed with interrupted or running fine (3-0) plain catgut sutures, and the skin is closed with standard skin staples.
Anterior Transabdominal and Thoracoabdominal Approaches
For large adrenal tumors, where a posterior or flank approach offers a limited and relatively inadequate exposure, the transabdominal or transthoracic surgical approach is a preferred alternative because of its superior operative exposure. The anterior abdominal approach can be performed through subcostal, transverse, chevron, or midline incisions. The use of these approaches is dictated by the size and pathology of the adrenal tumor as well as patient habitus and operator preference. In general, adrenocortical carcinomas are excised through such approaches to ensure ample exposure, control, and the ability to accurately stage the disease intraoperatively.
Laparoscopic Approach
The demand for minimally invasive alternative surgical therapies and for cost savings in our current health care system has initiated the concept of laparoscopic adrenalectomy. To date, the experience with this approach is limited to a few medical centers with specific interest in laparoscopic surgery. Technical difficulties, limited instrumentation, and the low volume of surgical adrenalectomies have restricted the utilization of this approach. Laparoscopic adrenalectomy is discussed in detail in Chapter 132.
OUTCOMES
Complications

Preoperatively, patients with hormonally active adrenal tumors should undergo careful preparation to control their hormonal dysfunction and optimize their fluid and electrolyte status. These are essential prerequisites in pheochromocytoma, aldosteronoma, and Cushing’s syndrome. In pheochromocytoma, a blockers are used to decrease vascular tone and control hypertension while intravenous fluid hydration is used to counteract the potential of vasodilation and vascular collapse on excision of the tumor. In aldosteronoma, hypokalemia is treated with spironolactone and potassium supplements. Such preparation should be instituted for a number of weeks to ensure adequate correction and recovery of the suppressed zona glomerulosa of the contralateral adrenal gland. In glucocorticoid-secreting adrenal tumors, glucocorticoid is given intraoperatively and continued postadrenalectomy because the zona fasciculata of the contralateral adrenal function may be suppressed by negative feedback from the excessive glucocorticoid secreted by the tumor. Careful monitoring during the postoperative period is mandatory to recognize and correct such potential adverse events. It should also be emphasized that healing in patients with Cushing’s syndrome may be slow because of the compromised tissue status from excessive glucocorticoid and associated glucose intolerance and the increased potential risks for wound infection, dehiscence, and the development of postoperative incisional hernia. The use of prophylactic antibiotics, meticulous wound closure, and careful postoperative wound care should decrease the risk for such adverse events. Early ambulation and aggressive pulmonary toilet are encouraged to minimize the development of postoperative respiratory complications as well as venous thrombosis and pulmonary embolism.
Intraoperatively, injury to adjacent structures may result, including a pneumothorax, which can be recognized by the formation of bubbles at the site of pleurotomy. Treatment includes closure of the pleural tear with running 4-0 chromic catgut suture and removal of the air and fluid from the pleural cavity through a soft catheter at time of closure. The use of suction or an underwater seal system during hyperinflation of the lung by the anesthesiologist aids in accomplishing this task. Rarely, a chest tube is required for larger pneumothorax (greater than 10%) or when respiratory compromise results. Careful follow-up with serial chest x-rays is needed to ensure resolution of the pneumothorax.
Other structures at risk for injury during adrenalectomy include the kidney, spleen, liver, and pancreas. A tear of the renal capsule may result from forceful retraction of the kidney during dissection and may be treated with gentle tamponading in minor injuries; larger tears may require repair by suturing. Splenic capsular injuries may also occur as a result of retraction or direct dissection, and the use of pressure tamponade is usually sufficient, though occasionally hemostatic gel packing, splenic repair, cauterization with an argon beam coagulator, or even splenectomy may be indicated. Liver injuries may also occur through the same mechanism and should be handled by hemostatic gel packing or repair. Injuries to the pancreas and subsequent pancreatic inflammation may occur during dissection at the region of the upper pole of the left kidney, leading to the postoperative pancreatitis. Rarely, however, a more substantial injury may result in fulminant pancreatitis and significant pancreatic leak and fistula.
Avulsion of the adrenal vessels, especially the delicate central veins, can lead to significant bleeding. Hemostasis is secured by packing and suture ligation. With all such injuries in which there is a potential of delayed bleeding, the use of postoperative drains is recommended.
Results
Generally, convalescence of patients undergoing adrenal surgery is surprisingly smooth. Careful preoperative preparation of the patient, meticulous intraoperative surgical technique, and proper postoperative care are mandatory for successful outcome and complication-free recovery.
The prognosis of adrenalectomy in benign adrenal disease is most favorable once the tumor is completely excised and recovery is uneventful. Complete cure from the disease process and return to normal function are expected in the majority of patients.
The prognosis of adrenalectomy in malignant disease, however, is variable depending on the stage of the disease and on whether or not complete surgical excision is achieved. The potential for a cure can be achieved only in early-stage adrenocortical carcinoma on complete excision of the disease without tumor spillage or positive surgical margins. The 5-year survival in early (stage I or II) adrenocortical carcinoma is 50%, which drops to 5% to 10% in the advanced (stage III or IV) disease.

Cushing’s Disease and Syndrome

The association of pituitary lesions in patients with hirsutism, proximal muscle weakness, round plethoric faces, increased supraclavicular and infrascapular fat pads, thin skin, and other less frequent signs such as acne, purple abdominal striae, and psychiatric symptoms (Cushing’s syndrome) has been known as Cushing’s disease since the original description relating the illness to pituitary lesions by Cushing in 1912. It was many years later that the syndrome was found to be caused by cortisol excess, and later still it was found that there were multiple etiologies for this excess, including ectopic production of ACTH in adrenal tumors and tumors arising in other organs, including some that may be ectopic sources for corticotropin-releasing factor.
The first planned operation for adrenal tumor was performed in 1914, with removal of a 17-cm adrenal adenoma and subsequent cure of hyperadrenocorticism. Initial attempts at curative pituitary surgery for Cushing’s disease were short lived for lack of the necessary technology, but with modern microsurgical techniques, transsphenoidal pituitary microsurgery has become the treatment of choice. Adrenal surgery for Cushing’s syndrome has in the past varied from partial to total adrenalectomy, depending on the availability of supplemental glucocorticoids.
The etiologies of Cushing’s syndrome are summarized in Table 1-1 and Fig. 1-1. In general, the pathophysiology of these disorders involves the production of excessive ACTH from pituitary adenomas or from ectopic sources, benign adrenal tumors and macronodular and micronodular adrenal hyperplasia, which usually produce excessive glucocorticoids only, whereas many adrenal malignancies also produce excessive androgens and mineralocorticoids. Iatrogenic administration of glucocorticoids is also a common etiology of Cushing’s syndrome.
DIAGNOSIS
The sine qua non for the diagnosis of Cushing’s syndrome is an abnormality of the plasma or urinary cortisol and/or ACTH. Because these studies are extremely variable, sometimes fluctuating daily and frequently negative, a high degree of suspicion usually leads the clinician to evaluate the patient with an overnight dexamethasone suppression test, a metapyrone stimulation test, or corticotropin-releasing factor stimulation. Imaging studies such as CT scanning, adrenal arteriography and venography, MRI (with and without gadolinium), and scintigraphy have also been used with some success. Because of the lack of sensitivity and specificity of these studies, it would also be common to perform repetitive evaluations in many patients.
INDICATIONS FOR SURGERY
Indications for surgery of the adrenal gland in patients with Cushing’s syndrome include adrenal adenoma, adrenal hyperplasia, and adrenal carcinoma. Bilateral adrenalectomy has been suggested for those patients with micronodular adrenal hyperplasia, macronodular hyperplasia, patients with unknown sources of ACTH, and those with incurable pituitary Cushing’s syndrome.3,6
ALTERNATIVE THERAPY
Treatment of the aforementioned causes of Cushing’s disease all require surgical management except for the iatrogenic administration of glucocorticoids.
SURGICAL TECHNIQUE
The posterior approach to the adrenal glands is described here; the other surgical approaches to the adrenals are described in Chapter 2, Chapter 3, Chapter 4 and Chapter 132. The posterior approach to the adrenal gland was first described by Young in 1936. Most authors would reserve this technique for small adrenal adenomas or adrenal hyperplasia, i.e., noncancerous states with small lesions.1,6 It is also the ideal method for bilateral adrenal exploration because the patient does not have to be repositioned. The patient is placed in the prone position under general endotracheal anesthesia. Appropriate padding is used to pad the chest, anterior pelvis, and legs (Fig. 1-2).
Several incisions have been described, and we prefer the hockey-stick incision, which begins just lateral to the midline at the ninth or tenth rib and extends downward and then laterally over the 11th or 12th ribs. Alternatively, an 11th rib incision or supracostal incision is used.4,6 In the supracostal incision, the rib is spared, the intercostal muscles are divided, the pleura is swept away from the rib, and the retroperitoneum is entered (Fig. 1-3). In the other approaches, the latissimus dorsi and sacrospinalis muscles are divided and retracted medially. The incision is extended through the periosteum of the 12th rib, which is resected close to the vertebral body (Fig. 1-4). The deep periosteum is incised, avoiding the neurovascular bundle, while laterally the abdominal muscles are divided and the pleura dissected from the diaphagm, exposing Gerota’s fascia. As an alternative, in the transthoracic approach, the exposed pleura and diaphragm are incised, again exposing Gerota’s fascia. It should be noted that the decision on which rib space to utilize (10, 11, or 12) depends on the position of the adrenal as estimated by the imaging studies, and it would be rare to be too high with the placement of the incision. In bilateral adrenalectomy, a Finochetti retractor can be placed for exposure (Fig. 1-5).
Gerota’s fascia is incised, and the perinephric fat is swept away or incised superiorly, exposing the adrenal. Inferior retraction3,6 of the kidney aids this portion of the dissection (Fig. 1-6). On the left side, the resection of the adrenal proceeds from laterally and superiorly to medially and inferiorly, where the main veins are ligated, the largest draining into the renal vein while the major adrenal artery arises from the main renal artery. On the right, the dissection is similar, but care is taken medially where the short right adrenal vein (and occasional accessory veins) empties into the vena cava. The largest adrenal artery usually arises from the main renal artery.
If the pleura is entered, a temporary “pull-out” Robinson catheter (14 to 18 F) is placed, the pleura sutured, and the musculature approximated. While deep inspiration is maintained by the anesthesiologist, and the catheter is placed in an underwater seal, the catheter is quickly removed after all air bubbling in the water ceases. The remainder of the wound closure is completed, and a dressing applied.
OUTCOMES
Complications
Surgical complications following adrenal surgery for Cushing’s syndrome include not only those that pertain to routine retroperitoneal surgery, e.g., blood loss and infection, but also those complications specific to patients with hormonal imbalances. It should be mentioned that a chest x-ray in the recovery room is essential after any flank surgery in which the patient has been placed in the lateral or prone position, to evaluate the patient’s pulmonary status for atelectasis and/or pneumothorax when the pleura has been violated. The occurrence of adrenocortical insufficiency should be kept uppermost in the clinician’s mind even in the patient who has had a unilateral adrenalectomy. The use of supplemental glucocorticoids and mineralocorticoids is commonplace in these complex patients, whereas those in whom adrenalectomy is not curative need further evaluation, looking for ectopic sites of disease, either benign or malignant. Postoperative wound healing may be impaired, and the infection rate has been described to be between 4% and 21%. Other complications, e.g., thromboembolism, may be related to Cushing’s syndrome or the associated obesity.
Results
The operative mortality for adrenalectomy in patients with Cushing’s syndrome has been reported to be 2% to 6%, and the occurrence of Nelson’s syndrome (the development of invasive pituitary tumors after adrenalectomy) seems minimal. Most patients with pituitary Cushing’s syndrome who have poor results from pituitary surgery are cured with bilateral adrenalectomy, and a successful outcome should occur after adenalectomy in the patient with adrenal hyperplasia or an adrenal adenoma correctly diagnosed.
In the small number of patients with adrenal malignancy, sugery may be curative if the tumor is localized, but metastatic disease responds poorly to the combination of adrenalectomy, radiation, and chemotherapy. It still remains, however, that management of these complicated endocrinologic patients is a continuing challenge for the urologic surgeon.