Adrenocortical Carcinoma with Vena Cava Involvement

Abstract

Adrenal cancer may involve the inferior vena cava by direct infiltration or with a tumoral thrombus inside the lumen. In the context of a multidisciplinary therapeutic effort, a correct surgical procedure is critical to achieve a chance of long-term survival. This chapter will discuss different important technical details which help to prevent tumor spillage and thrombus dislodgment, while allowing vascular control without hemodynamic derangement.

Adrenocortical carcinoma (ACC) shows a significant propensity to invade vascular structures. Although vascular involvement may reveal itself in the form of direct infiltration of a vein, it more often consists of tumor growth inside the vascular lumen (15–25% of cases), forming a neoplastic thrombus [1]. Regardless of the presentation, venous involvement is a marker of aggressiveness which may bring into question the surgical indication.

10.1 The Guidelines

The guidelines issued in 2018 by the European Society of Endocrinology in collaboration with the European Network for the Study of Adrenal Tumors [2, 3] do not consider the presence of a tumor thrombus as a contraindication for surgery. They state: “We recommend that individualized treatment decisions are made in cases of tumors with extension into large vessels based on multidisciplinary surgical team. Such tumors should not be regarded “unresectable” until reviewed in an expert center”. A main condition must, however, be respected: surgery must be performed by surgeons with special expertise in adrenal surgery for primary malignancy.

The ESMO-EURACAN guidelines issued in 2020 state: “In order to obtain an R0 resection of a locally advanced ACC, it may be necessary to resect (parts of) adjacent organs such as the wall of the vena cava, liver, spleen, colon, pancreas and/or stomach. Complete en bloc resection of the tumoral mass, including periadrenal fat and adjacent organs if necessary, is mandatory to avoid tumor rupture or spillage that portends an adverse outcome” [4].

10.2 The Multidisciplinary Team

It is general opinion that patients with ACC benefit from a multidisciplinary management by a team of experts from the beginning. For surgical planning, the extension of the thrombus and the foreseeable technical solution determine the strategy and suggest the composition of the surgical team, which may include a vascular and/or a cardiac surgeon. Proven expertise in both adrenal and oncologic surgery, including major liver procedures, is needed in view of the specific anatomy, the malignant character of the disease and the potential need for multiorgan en bloc resection. This guarantees the best oncologic standard and the lowest risk of complications. The anesthesiologic team should be involved from the preliminary discussion of the surgical strategy. Dedicated anesthetists are required, with the experience and skills needed to face any complication arising from major splanchnic, vascular and cardiac procedures. Intraoperatively, an expert in transesophageal ultrasonography is required to monitor the stability of the endoluminal thrombus during surgery and to guarantee hemodynamic monitoring if the inferior vena cava (IVC) is clamped above the suprahepatic veins.

10.3 The Cancer and the Patient

Clinical signs of vena cava obstruction are rare, as is neoplastic pulmonary embolism; the flow in the IVC, albeit reduced, persists even if imaging suggests venous thrombosis, which is reported in about 5% of cases [3]. Imaging is characteristic: the neoplastic thrombus appears as an endoluminal growth with contrast medium enhancement at computed tomography (CT); it may fill and dilate the vessel lumen (Fig. 10.1). Its extension is graded as follows: Level I, the thrombus reaches the adrenal or renal vein (left side); Level II, the IVC is occupied up to the level of the hepatic veins; Level III, the thrombus reaches the suprahepatic IVC; Level IV, the right cardiac chamber is occupied by the tumor thrombus. Direct infiltration of the IVC should be suspected whenever the margins of the lesion and the vena cava are not clearly detectable. IVC involvement is typically observed in the presence of large (≥10 cm) and right-sided adrenal masses, as the length of the left renal vein has a protective role [5]. Retrograde non-neoplastic thrombosis is a common finding; it can involve the left renal vein up to the confluence of the gonadal vein.

Fig. 10.1

Coronal (a) and sagittal (b) venous-phase computed tomography (CT) scan show a right adrenocortical carcinoma (ACC) with neoplastic thrombus in the inferior vena cava (IVC) extending to the right cardiac chamber (b). Axial 3D gradient-echo (GRE) fat-suppressed T1w after contrast administration (c) and coronal T2w (d) magnetic resonance imaging (MRI) sequences show an enlarged left renal vein and IVC (asterisk) due to the presence of inhomogeneous neoplastic tissue in its lumen originating from a left ACC. Note the intrinsically better resolution of contrast-enhanced MRI compared to CT

10.4 Technical Aspects

In surgical planning, two phases must be considered: the treatment of the tumor and the management of the vascular invasion.

Difficulties arise from the size and soft consistency of the tumor, the activation of collateral circulation, and the need to perform an en bloc resection of the involved tissues and organs. The literature does not support preoperative embolization to reduce bleeding [6]; some authors advocate early ligature of the adrenal artery to favor the collapse of the collateral circulation [7].

Open surgery is standard [1]. When surgery can be completed via an abdominal approach (the edge of the thrombus remains below the diaphragmatic plane), a bilateral subcostal incision is preferred, with median extension to the xiphoid if needed. When the edge of the thrombus reaches the pericardium, the indication for a wider approach must be discussed. Median sternotomy is mandatory when the thrombus reaches the right atrium, but this is not the rule in any other case: the IVC can be controlled within the pericardium through the diaphragm.

The first phase of the procedure pursues the mobilization of the adrenal gland. Care must be taken to avoid mobilization/fragmentation of the thrombus during the different phases of the procedure, such as liver mobilization and dissection of the suprahepatic veins, maneuvers along the IVC and, above all, positioning of the vascular clamp above the edge of the thrombus. This phase must be always monitored by intraoperative transesophageal ultrasound which may identify unstable or floating thrombus and thus suggest safety maneuvers such as an early clamping of the vein. In any case, the risk of thrombus fragmentation seems to be low and intraoperative neoplastic pulmonary embolism is uncommon [1, 4]. The ipsilateral kidney should be preserved if not infiltrated.

The liver is often enlarged and congested, and pushed toward the diaphragm by the tumor. The advice is not to pursue the dissection plane between the liver and adrenal but to resect the liver in order to optimize radicality. The exact extension of IVC involvement can be verified only after complete dissection of its anterior surface, which is approached with the “liver transplantation technique” [8]. However, differing from liver surgery, any maneuver can be more difficult than usual, in particular if the IVC is dilated and filled by the tumor, and the small accessory veins are particularly short. Nonetheless, the IVC must be completely dissected well above the edge of the thrombus, if necessary above the three hepatic veins, to facilitate positioning of the clamp and allow thrombectomy of the hepatic veins if required. The vascular dissection above the liver is generally easy as the vena cava at this level is rarely infiltrated. In the case of fusion of the lateral or posterior surface of the IVC with the tumor, an anterior approach to the IVC with a subsequent right hepatectomy has been proposed [9, 10]. This technique does not exclude the need to dissect at least the anterior aspect of the IVC; furthermore, such a major liver resection increases the risk of operative morbidity and is not justified from the oncological point of view, considering that microscopic liver involvement occurs in 40% of cases [10]. In our opinion, this approach must be strictly reserved for selected patients. Once dissected free from the kidney, liver and posterior muscular plane en bloc with the perirenal capsule, the adrenal mass remains attached to the IVC, which is dissected free, mobilized and taped above and below the involved tract. Attention must be focused on the accurate control of the lumbar veins, which are hypertrophic if a collateral circulation has been activated.

The “vascular” phase requires an accurate strategy, according to the type and extension of vascular involvement reported by preoperative cross-sectional imaging.

In cases of parietal infiltration, the strategy is dictated by its extension. A lateral vascular clamp, after complete posterior mobilization, allows for preservation of caval flow, for a marginal vein resection and for an easy reconstruction, by direct suture or with patch interposition, of limited infiltrations around or near the adrenal vein confluence. In the event of major infiltration of the IVC, its prosthetic replacement is preferable for oncologic reasons.

When a thrombus is present, the strategy varies according to its cranial extension. Thrombectomy is an “at risk of bleeding” maneuver and the anesthesiologic team should be ready for intraoperative blood transfusion. The use of intraoperative blood recovery is debated but, considering fragmentation of the neoplastic thrombus as a systematic occurrence, it should be reserved for very particular cases.

Correct clamp positioning is critical. If the ostia of the renal veins are spared, clamp positioning above their confluence allows for a retrograde flow which preserves the renal parenchyma. When facing a left-sided cancer, the caudal vascular clamp should be positioned below the left renal vein in an oblique position, so as to preserve the retrograde venous flow of the right kidney. If this is not possible or if the thrombus involves the right renal vein, after arterial exclusion of the right kidney, complete clearing of the ostium of the renal veins may be accomplished from inside the IVC, clamped below the right renal vein. In this case, the IVC reconstruction will begin at the lower edge of the cavotomy and the clamp is promptly repositioned above the renal veins allowing reperfusion of the kidney. Thrombectomy of the IVC and ostium of the left renal vein allows the positioning of a clamp at the renal vein confluence and subsequent thrombectomy of the renal vein. As an alternative, if prosthetic renal vein replacement is considered excessive, it is possible to resect the left renal vein provided that the gonadal vein, generally enlarged, can remain in situ, allowing for renal flow diversion toward the iliac vein. Furthermore, if the vena cava is infiltrated in proximity to the renal confluence, the renal veins can be resected and anastomosed to the prosthetic vena cava replacement (Fig. 10.2).

Fig. 10.2

Polytetrafluoroethylene (PTFE) graft replacement of the inferior vena cava. The left renal vein was anastomosed to the prosthetic graft

Rapid clamp repositioning has also a crucial role when the cranial clamp is placed above the suprahepatic veins: after clearing at least the cranial part of the thrombus and, if indicated, the ostium of the hepatic veins, the suture of the caval wall starts from the upper edge of the cavotomy and, as soon as it passes the suprahepatic veins caudally, the clamp is repositioned below them, allowing restoration of splanchnic flow. In fact, if exclusion of the IVC flow is generally well tolerated, its association with the sudden drop of splanchnic flow must be discussed during the multidisciplinary planning meeting to implement any required compensatory measures. At this point hemodynamic monitoring by transesophageal ultrasound plays a critical role for the anesthetist, in regulating volume needs and amino support. If hemodynamic failure develops (some minutes of compensation are needed) a venovenous bypass may be required. This must be prepared in advance: arranging the venous accesses during the preliminary phases of the operation allows for rapid activation of the bypass when required. Some authors advocate the “milking” maneuver (i.e., manual dislodgment of the edge of the thrombus downward) with the aim of directly applying the clamp below the suprahepatic veins or accelerating clamp repositioning [7, 10]. This maneuver may expose to thrombus fragmentation and dislodgment in the suprahepatic veins if incorrectly performed.

Management of level III and IV thrombus is more complex. Circulatory arrest is needed if the cardiac cavities must be approached and an aortopulmonary bypass must be activated. Atriotomy makes it possible to clear the cardiac chamber as well as the highest portion of the IVC and to easily control the hepatic vein confluence from above (Fig. 10.3), facilitating clamp positioning below the hepatic veins. The advantage of operating in a blood-free field without time-related constraints is counterbalanced by the heparinization and consequent derangement of coagulation, in particular if a hypothermic strategy is implemented. In these cases, a meticulous hemostasis must be pursued on all dissection planes before pump activation. A limited extension of the thrombus inside the right atrium may be controlled by a clamp inserted tangentially just above the thrombus, thus avoiding cardiac arrest; in any case, in these conditions collaboration with the cardiac surgeon is mandatory.

Fig. 10.3

View of the suprahepatic inferior vena cava through a right atriotomy, after removal of the atrial edge of the neoplastic thrombus. The caval thrombus is still in place

Cavotomy is regulated by the thrombus extension. Generally, it is possible to spare the IVC itself; sometimes a small resection of the vein’s wall including the confluence of an apparently infiltrated right adrenal vein must be performed. In the presence of massive IVC infiltration there are no alternatives to its resection.

Reconstruction is the final phase of the procedure, as restoration of caval flow must always be pursued. Even though IVC ligation may be tolerated, especially after sacrifice of the right kidney, it has a major impact on quality of life; for this reason, it must be considered an extreme option. Under the protection of extracorporeal circulation or after splanchnic flow restoration, the reconstruction—or its completion—must be done paying special attention to its technical quality, without time constraints. Direct reconstruction of the IVC is generally possible without stenosis, especially if the vein was dilated by the intraluminal thrombus, but stenoses up to 50% of the lumen are tolerated (Fig. 10.4). The positioning of prosthetic patches or IVC replacement should be chosen according to the different clinical presentations. Bovine pericardium is generally preferred for prosthetic patches; the same material can be used for replacement of the vena cava, especially in the case of major discrepancies between the diameter of the two stumps, as an alternative to the widely used polytetrafluoroethylene (PTFE) graft or human homograft (Fig. 10.5).

Fig. 10.4

Direct reconstruction of the inferior vena cava after its resection. A stenosis <50% is appreciable. The postoperative course was uneventful

Fig. 10.5

Homograft replacement of the inferior vena cava

10.5 Results

Operative mortality ranges between 4% and 13% and is linked to hemorrhagic complications [1, 5], which represent the only cause of death in some experiences [2]. Long-term survival may be obtained after radical surgery. In the collective review by Chiche, 35% of patients survived at least 24 months [1]; in a subgroup analysis including only locally advanced ACC patients with complete (R0) resection, Laan et al. [11] reported similar survival at 24 months between patients with vena cava tumor thrombus and non-vena cava involvement, but at 36 months survival was better for the group with non-vena cava involvement (65% vs. 29%).

10.6 Final Considerations

Complete resection of the tumor remains the standard of care for adrenal cancer. The presence of IVC involvement is a further complication for the surgical procedure, but a technical solution is generally possible. The multidisciplinary evaluation, under the direction of the oncologist, has the role of defining the right indication, considering both the risk of surgery and the poor prognosis. A further evaluation of the medical regimen in the pre/postoperative setting, probably based on mutation pattern and gene expression, will be able to further select the patients for this complex surgery.