Renal cell carcinoma (RCC) remains one of the most life-threatening malignancies in urology, despite advances in treatment methods following changes in the medical environment [1]. A distinguishing feature of RCC is that the tumor thrombus extends through the vein into the bloodstream [2]. In approximately 4%-15% of individuals with RCC, tumor cells invade the renal vein or inferior vena cava (IVC), resulting in a tumor thrombus [3-9]. RCC with venous tumor thrombosis (VTT) in the vena cava is categorized into several stages according to the thrombus level (Fig. 1) [10].

Figure 1. Tumor thrombus level based on the Mayo classification.

At level III, the thrombus reaches the IVC above the hepatic vein, but not above the atrium, and at level IV, the thrombus extends above the diaphragmatic IVC or right atrium. For level III and IV tumor thrombi, removal from the vena cava is very challenging because of the need for high-level vena cava clamping and extensive tissue dissection [11,12]. However, combining radical nephrectomy with tumor thrombectomy is an oncologically relevant approach that can achieve long-term survival, even in the presence of distant metastases [13]. This clinical review aimed to introduce tips for surgical techniques concerning tumor thrombectomy in the vena cava to aid the surgical treatment of RCC with VTT.

1) Minimal invasive surgery

In recent years, the use of minimally invasive surgery for RCC with VTT has increased, with some studies showing favorable results [14,15]. However, robotic or laparoscopic surgery is limited to level I and II tumor thrombosis. Therefore, there is insufficient evidence to predict the outcomes and safety of minimally invasive surgery when applied to level III and IV tumor thrombosis.

2) Anticoagulation and preoperative renal artery embolization

Although a recent study showed the potential benefit of preventing venous thromboembolism, there is little evidence to support the use of anticoagulants in patients with RCC with VTT before surgery [16]. Renal artery embolization before surgery may facilitate surgery by inducing renal angioinfarction to reduce kidney volume and bleeding; however, there are concerns about its safety. Some studies have suggested that this procedure can reduce surgical duration and blood loss [17-20], but it can also cause various immunological problems when tissue infarction occurs. Postinfarction syndrome may lead to fever, chills, flank pain, hematuria, hypertension, and hyponatremia, which can delay surgery and be harmful to patients with RCC [21-23]. One study showed no significant differences in perioperative mortality and 5-year cancer-related survival between the groups with and without prior renal artery embolization [24]. Therefore, preoperative renal artery embolization is not recommended due to the lack of evidence supporting its benefits and potential risks it may pose.

3) Transesophageal echocardiography and cardiopulmonary bypass

In cases of level III and IV VTT, the upper margin of the thrombus must be identified to enable clamping from the upper side of the thrombus. Therefore, simultaneous monitoring of the tumor thrombus is required, particularly to detect the occurrence of embolism. Additionally, cardiac function monitoring is necessary when the IVC is clamped because the cardiac preload will be rapidly reduced, and cardiac function may deteriorate severely [25,26]. Therefore, transesophageal echocardiography (TEE) should be available for intraoperative use. A cardiopulmonary bypass (CPB) may be necessary in some cases. CPB should be considered when the tumor thrombus penetrates the cardiac chamber and clamping is impossible due to the inability to milk the intracardiac chamber thrombus caudally. Hypothermia, in which the body temperature is lowered to ≤30ºC, may be used to reduce ischemic sequelae when CPB is performed. However, hypothermia can cause coagulopathy and bleeding, which can increase the perioperative mortality rate [27-32].

1) Renal vessel management

When exposure to the surgical field is achieved, ligation of the renal artery is the first step. Inducing infarction by blocking the renal artery preoperatively causes postinfarction syndrome, which is not beneficial for the patient. However, ligation of the renal artery during surgery reduces blood flow and decreases the amount of perioperative bleeding around the kidney [33]. It is convenient to perform renal artery ligation and division in advance during the dissection of tissue. This is because it is difficult to manipulate the renal artery during IVC dissection and thrombectomy. In right-sided RCC, ligation of the renal artery is easier to perform between the aorta and the IVC than around the renal hilum. This procedure reduces the manipulation required to isolate the renal artery from the renal hilum tissue. In the renal vein, if the thrombus is floating and not attached to the IVC wall, caution is required, as the thrombus may cause embolism toward the cephalic direction when the origin stalk is divided while the vein is ligated and resected.

2) Dissection of the retrohepatic IVC and central diaphragm tendon

Before performing a cavotomy, preparation for clamping the contralateral renal vein and infrarenal and suprahepatic IVC is necessary. In the case of infrarenal IVC, the flow is restricted due to the proximal thrombus, and the collateral veins, including the lumbar veins, often become relatively larger than normal [34]. Therefore, ligation of these veins must be performed prior to cavotomy. In retrohepatic IVC, short hepatic veins can be torn during vena caval thrombectomy or blood can be introduced into the cavotomy site; therefore, all identified veins should be ligated and divided. A piggybacked liver mobilization must be completed to ensure circumferential IVC control and facilitate subsequent sequential clamping [35,36].

Even if a thrombus is located above the diaphragm, a method to perform thrombectomy without performing sternotomy or CPB has also been introduced [37-39]. For this procedure, it is necessary to first completely isolate the IVC from the central tendon of the diaphragm. If the IVC is separated from the surrounding tissue, it can be pulled down toward the patient’s leg until the lower margin of the atrium is visible (Fig. 2). A pericardiotomy can be performed to widen the exposed area of the atrium, if necessary. Care should be taken as the coronary sinus may be invaded if the clamp is raised excessively [40]. When the supradiaphragmatic IVC is completely exposed, the tumor thrombus must be carefully pulled downward to a position where it can be clamped [41]. This milking-down process should be performed carefully while touching the thrombus with the thumb and forefinger and monitored with intraoperative TEE to ensure that the free-floating thrombus does not cause embolization (Fig. 3). At this time, if a round-shaped DeBakey or Satinsky vascular clamp is used for the supradiaphragmatic IVC, a higher level of clamping is possible than a linear-shaped vascular clamp, while reducing the risk of fragmentation of the thrombus tip.

Figure 2. Exposure of the supradiaphragmatic inferior vena cava within the thoracic cage through dissection of the central tendon and inferior vena cava.

Figure 3. Gentle traction of the tumor thrombus in the inferior vena cava using a finger, while being cautious to prevent embolism.

3) The Pringle maneuver

The hepatic veins exhibit many variations at the point where the middle, right, and left hepatic veins join the IVC [42]. In many cases, the liver parenchyma must be dissected to clamp the hepatic veins separately at the level just before their junction with the IVC. Therefore, performing the Pringle maneuver to reduce blood flow from the hepatic veins to the IVC during cavotomy is easier than clamping the hepatic veins [43,44]. After clamping the hepatic pedicle for the Pringle maneuver, the surface of the liver is gently squeezed to remove any remaining blood inside the liver. If IVC clamping is performed after squeezing the liver, blood loss inside the liver flowing out during cavotomy can be reduced, and the volume of the liver also decreases; thus, a good view can be secured during thrombectomy [45]. If the Pringle maneuver is performed for more than 20 minutes, reperfusion is required for 5 minutes [46]. However, if sequential clamping is performed, vena cava thrombectomy at the level of the hepatic vein can be completed within 20 minutes, even with meticulous inspection and removal of the thrombus from the IVC intima.

4) Sequential clamping

Sequential clamping is a method of dividing the thrombectomy into two stages by clamping the IVC twice: first suprahepatically and then midretrohepatically (Fig. 4). This method offers several advantages over one-time clamping. First, it can reduce the time during which blood pressure is lowered. In infrahepatic IVC clamping, blood flow through the hepatic vein is maintained to some extent, and the degree of blood pressure drop is less than that during suprahepatic IVC clamping, which blocks the flow of the hepatic vein. Minimizing the time spent on the first upper-level thrombectomy and quickly restoring hepatic vein flow by changing from a suprahepatic IVC clamp to a retrohepatic IVC clamp reduces the duration of low blood pressure. CPB should be performed if complications are expected because of a significant decrease in blood pressure during test clamping performed prior to cavotomy [47]. However, since there is no consensus on the acceptable blood pressure reduction during test clamping, it is important to minimize the time spent on blood pressure reduction that occurs during IVC clamping as much as possible. It also has the advantage of reducing the duration of blocking hepatic flow in the Pringle maneuver. The Pringle maneuver, which is performed to block hepatic flow, causes ischemic damage to the liver in a time-dependent manner. However, to investigate closely whether a remnant tumor is attached to the IVC intima, the time required for the Pringle maneuver must be increased. If a hepatic vein-level IVC thrombectomy is completed in the first clamping among the sequential clamps, the Pringle maneuver can be terminated. Subsequently, the second sequential clamping for vena caval thrombectomy can be performed on the remaining thrombus. The actual sequence of the procedure is as follows: first, the suprahepatic IVC is clamped, followed by the midretrohepatic IVC. Subsequently, vena caval thrombectomy is performed as quickly as possible in the clamped area, and the IVC is closed. Next, because a part of the tumor may have been trapped below the lower clamp site, the clamp is repositioned slightly higher than the previous retrohepatic IVC clamp, and the suprahepatic IVC clamp and Pringle maneuver are released to restore the flow of the hepatic vein. Finally, the infrarenal IVC and opposite renal vein are clamped, and thrombectomy is performed for any remaining thrombus.

Figure 4. Sequential clamping of the inferior vena cava to minimize hemodynamic instability time.

5) Spiral cavotomy and closure

When performing a cavotomy, it is best to perform it spirally, especially near the renal vein, and include the renal vein in the spiral cavotomy. This allows a thorough examination of any residual tumor thrombus that may remain at the ostium of the renal vein. If the narrowing is >50% during the closure of cavotomy site with a running suture, a patch angioplasty should be performed to prevent complications due to IVC narrowing [48,49]. However, if a spiral cavotomy is performed, the degree of primary closure narrowing can be reduced. Although spiral cavotomy makes it difficult to simultaneously perform a wide-range thrombectomy, sequential clamping can be performed to examine the interior of the IVC in detail. When closing the cavotomy site after thrombectomy, a running suture could be performed using 4-0 prolene. While releasing the clamp, it is advisable to adopt the Trendelenburg position immediately before releasing it to minimize the risk of air embolism because air can enter the IVC [50]. If tumor invasion occurs in the IVC, the risk of local recurrence is high [51]. In such cases, the IVC wall must be resected and reconstructed; however, recent studies have shown that IVC interruption does not increase the risk of postoperative complications [52]. If the IVC is interrupted, postoperative anticoagulants should be administered [53].

There are a few studies on surgery for level III or IV tumor thrombi without CPB, but the rates of perioperative complications and mortality are not high compared with those of CPB [43,54]. Complications include an embolism of tumor thrombus during IVC manipulation or clamping and massive blood loss. Since an individual surgeon’s experience is very important in reducing complications and mortality, it is generally recommended to perform surgery at high-volume centers because complication rates tend to increase with the level of thrombus [51,53]. In terms of oncological outcomes, at 5 years, cancer-specific survival for patients following radical nephrectomy and tumor thrombectomy ranges between 30% and 70% [4,55-57].

Performing vena cava thrombectomy for level III and IV RCC with VTT is challenging. However, this can be accomplished without intraoperative complications if appropriate thrombectomy techniques are used. High-level thrombectomy can also be performed without CPB by milking down the thrombus through the central diaphragmatic tendon dissection. Sequential IVC clamping and the Pringle maneuver can reduce the low blood pressure time and minimize the blood loss, allowing for a more detailed thrombectomy. Spiral cavotomy can help maintain smoothen venous flow. The oncological prognoses of patients can be improved using the aforementioned technical tips.

Jun Gyo Gwon, Youngjin Han, and Seung-Kee Min have been the editorial board members of the VSI since 2019. They were not involved in the review process. Otherwise, no potential conflict of interest relevant to this article was reported.

Jun Gyo Gwon, Youngjin Han, and Seung-Kee Min have been the editorial board members of the VSI since 2019. They were not involved in the review process. Otherwise, no potential conflict of interest relevant to this article was reported.

Concept and design: SKM. Analysis and interpretation: SKM. Writing the article: JGG, YH, YPC. Critical revision of the article: JS. Final approval of the article: all authors. Statistical analysis: none. Obtained funding: none. Overall responsibility: SKM.