Chandy Ellimoottil, MD
Marcus L. Quek, MD, FACS
BASICS
DESCRIPTION
• Patients with renal cell carcinoma (RCC) are at risk for developing intravenous tumor thrombus (IVTT) with tumor extending into the renal vein (RV) and inferior vena cava (IVC).
• RCC is the most common malignancy to extend into IVC.
• Tumor growth follows the path of least resistance into the venous system extending into the RV and IVC (and into the right atrium) or it can invade into the vein wall.
• Multiple staging systems exist for RCC with venous extension. 3 common staging systems include:
– TNM
pT3a—RV extension
pT3b—IVC below diaphragm
pT3c—IVC above diaphragm
– Anatomic (Hinman system)
Level I—RV/infrahepatic IVC
Level II—Intrahepatic IVC
Level III—Supradiaphragmatic IVC/right atrium
• Anatomic (Neves/Novick system)
– Level 0—RV
– Level I—IVC <2 cm above RV
– Level II—IVC >2 cm above RV and below hepatic veins
– Level III—IVC above hepatic veins and below diaphragm
– Level IV—IVC above diaphragm
EPIDEMIOLOGY
Incidence
There are approximately 63,920 cases of RCC diagnosed each year; about 10% have IVTT.
Prevalence (1)
• RCC with IVTT is seen in 4–15% of cases.
– In 50% of these cases, IVTT only extends to the RV.
– IVTT extends into the right atrium in 1% of cases.
• Among patients that have IVTT, 29–55% will have concomitant metastatic disease.
RISK FACTORS
Risk factors for RCC with IVTT are the same for RCC and include smoking, obesity, hypertension, family history.
Genetics
No known genetic factors exist that predict IVTT.
PATHOPHYSIOLOGY
• RCC with IVTT can occur with all histologic subtypes including clear cell, papillary, and chromophobe
• RCC can occur sporadically or in a hereditary form (although there is no known genetic predisposition to IVTT)
• IVTT can cause occlusion of the IVC, which can cause lower-extremity edema, varicocele in males
• IVTT can also cause a pulmonary embolism
• Acute caval obstruction may rarely lead to disseminated intravascular coagulation, though more commonly IVTT may cause chronic venous obstruction leading to the development of collateral venous drainage
ASSOCIATED CONDITIONS
• Pulmonary embolus
• Bilateral lower-extremity edema
• Lower-extremity DVT
• Varicocele
• Caput medusa
GENERAL PREVENTION
Modification of above risk factors for RCC
DIAGNOSIS
HISTORY
• Presentation of patients with RCC with IVTT is similar to RCC without tumor thrombus, but those with tumor thrombus are more likely to be symptomatic
• Up to 95% of patients with intracaval extension present with symptoms it is an incidental finding in 23%
• Symptoms include:
– Hematuria (35%)
– Flank/abdominal pain (17%)
– Constitutional symptoms including fatigue, weight loss, or paraneoplastic syndrome (9%)
– Flank/abdominal mass (2%)
PHYSICAL EXAM
• Physical exam findings can include:
– Bilateral lower-extremity edema
– Varicocele (right side)
– Dilated superficial abdominal wall veins
– Caput medusa
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Basic lab work is necessary for preoperative workup including
– Liver function tests
– Complete blood count
– Basic metabolic panel
– Urinalysis
Imaging
• Chest imaging (preferably CT) and bone scan should be ordered as part of staging workup
• Assessment of IVTT cephalad extension should be performed 7–14 days before surgery because it can affect the surgical approach and the need for bypass procedures
• Ultrasonography and standard CT can be used to detect the presence of IVTT, but may not be sufficient for surgical planning
• MRI (T1-weighted images) is the gold standard imaging technique used to assess the cephalad extent of the IVTT, the degree of occlusion, and its relationship to liver, diaphragm, and atrium
• Multidetector CT (MDCT) can also be used in patients who are not candidates for MRI
• Studies comparing MRI to MDCT for staging IVTT have shown comparable results
• Transesophageal echocardiography can be used intraoperatively for real-time monitoring of thrombus
• Size of tumor thrombus on imaging studies may predict vein wall invasion and need for vein reconstruction
Diagnostic Procedures/Surgery
Biopsy can be performed if urothelial cell carcinoma is suspected or patient is poor surgical candidate
Pathologic Findings
• All subtypes of RCC have been associated with IVTT
• Clear cell is the most common histologic subtype associated with IVTT
DIFFERENTIAL DIAGNOSIS
Other tumors associated (rarely) with IVTT include urothelial cell carcinoma, adrenocortical carcinoma, and angiomyolipoma
TREATMENT
GENERAL MEASURES
• For those with no evidence of distant metastatic disease, surgical resection is the gold standard for RCC with IVTT
• For patients who present with metastatic disease, biopsy may be indicated for consideration of systemic therapy
• For select patients with metastatic disease, cytoreductive nephrectomy with tumor thrombectomy may be considered, although the outcomes in this setting are usually poor
MEDICATION
First Line
• Anticoagulation (preoperatively) should be considered for patients with IVTT to prevent bland thrombus development and propagation below the tumor
• Preoperative tyrosine kinase inhibitors (TKIs)
– Controversial
– May be utilized in the metastatic setting or when tumor felt not to be surgically resectable
– Most common TKIs used preoperatively are sorafenib and sunitinib; may decrease tumor size before surgical resection; may reduce level of IVTT, potentially altering surgical approach
Second Line
N/A
SURGERY/OTHER PROCEDURES
• Surgery is the gold standard for the treatment of RCC with IVTT (2,3,4)
• Accurate assessment of the cephalad extent of the tumor thrombus is critical in determining the surgical approach and need for adjunctive procedures
• While there are some reports of robotic and laparoscopic approaches to RCC with IVTT, the mainstay is open surgery
• Midline, subcostal (chevron), or thoracoabdominal incisions can be used
• Median sternotomy or thoracoabdominal approaches can be used for IVTT above the diaphragm
• For all levels, IVC should be resected if tumor is invading into the wall and reconstruction can be performed with graft (if lumen diameter compromised >50%)
• Resection of retroperitoneal lymph nodes and/or metastasectomy can be performed as needed
• Surgical steps include:
– Expose renal hilum, ligate renal artery
– Expose the RV and IVC
– Isolate venous inflow into IVC
– Cavotomy, tumor extraction
– Caval repair/reconstruction/ligation
• Level I Thrombus Specifics
– Milk the thrombus into the RV and take a side bite of the IVC using a vascular clamp making sure not to occlude IVC flow
– Incise the IVC and remove the thrombus and kidney under direct vision
– Oversew the caval defect
• Level II Thrombus Specifics
– Mobilize the liver and divide minor hepatic veins to expose the intrahepatic IVC
– Place Rummel tourniquets or vascular clamps sequentially on the infrarenal vena cava, contralateral RV, and suprarenal vena cava above the thrombus
– Incise IVC, remove the thrombus and kidney
– Flush-exposed IVC with heparinized saline
– Suture cavotomy; release vascular clamps
• Level III–IV Thrombus Specifics
– A wide variety of surgical approaches have been described
– Clamping of the IVC at the this level can compromise hemodynamic stability
– Cardiopulmonary bypass: Used for IVTT above the diaphragm, maintains continuous arterial/venous blood flow during IVC occlusion
– Deep hypothermic circulatory arrest (DHCA) cools the body and create a bloodless field
– Venovenous bypass can be used for level II–IV tumors. Venovenous bypass allows for continuous venous return to the heart while IVC is clamped.
– Pringle maneuver (clamping of the hepatic pedicle) can be used to avoid hepatic congestion and/or IVC bleeding that may occur when IVC is clamped above the hepatic veins (limit warm hepatic ischemia to 20 min)
– Cephalad IVC control can be obtained by exposing the intrapericardial IVC via pericardiotomy
– Langenbuch maneuver (medial mobilization of liver) to expose retrohepatic IVC
– Transesophageal echocardiography should be used for real-time intraoperative monitoring to identify tumor emboli
– A multidisciplinary approach, including the involvement of cardiac, vascular, hepatic surgeons as well as a specialized anesthesia team, is highly encouraged for these complex tumors
ADDITIONAL TREATMENT
Radiation Therapy
No role, except for palliation
Additional Therapies
• IVC filter can be used to prevent pulmonary embolus, however its use is controversial
– IVTT may become incorporated into IVC filter causing a surgical challenge
– When IVC is chronically occluded, simple ligation of IVC below hepatic veins may be performed
• Preoperative renal artery embolization
– Allows for early venous clamping when renal artery control may be difficult; may cause pain and complications (angioinfarction syndrome)
– Can be used as a palliative procedure
Complementary & Alternative Therapies
None
ONGOING CARE
PROGNOSIS
• Prognostic factors include TNM stage, nuclear grade, presence of necrosis, histologic type (worse for unclassified RCC and collecting duct carcinomas), sarcomatoid features, invasion into adjacent structures (renal sinus, perinephric fat, hepatic veins, collecting system, RV ostium), ECOG performance status, presence of lymph nodes, and distant metastasis
• Prognostic significance of tumor thrombus level remains controversial
• Median survival for nonmetastatic disease: 38–116 mo; 5-yr disease specific survival 40–60% when all gross disease is resected
• Median survival for metastatic disease: 11–20 mo and 5-yr disease specific survival is 4–30%. Patients that present with metastatic disease: 5-yr survival 0–10%.
COMPLICATIONS
• Overall complication rate is 12.5%, however, the complication rates vary greatly with level of tumor thrombus.
• Perioperative death varies from 0.8–10%. There has been a reported rate of mortality up to 40% for level IV IVTT.
• Most common complications are hemorrhage, pulmonary embolism, wound infection, acute renal failure, ileus, and need for additional surgery.
• The incidence of intraoperative tumor thrombus embolization is 1.5% and is associated with 75% mortality rate.
• Cardiopulmonary bypass is a risk factor for stroke (6% of cases) during nephrectomy for RCC with IVTT.
FOLLOW-UP
Patient Monitoring
• Surveillance based on TNM staging
• Surveillance labs include metabolic panel, liver function tests
• Surveillance imaging includes abdominal and thoracic imaging
Patient Resources
• American Cancer Society http://www.cancer.org/acs/groups/cid/documents/webcontent/003107-pdf.pdf
• Kidney Cancer Foundation http://www.kidneycancer.org/
REFERENCES
1. González J. Update on surgical management of renal cell carcinoma with venous extension. Curr Urol Rep. 2012;13(1):8–15.
2. Karnes RJ, Blute ML. Surgery insight: Management of renal cell carcinoma with associated inferior vena cava thrombus. Nat Clin Pract Urol. 2008;5(6):329–339.
3. Lawindy SM, Kurian T, Kim T, et al. Important surgical considerations in the management of renal cell carcinoma (RCC) with inferior vena cava (IVC) tumour thrombus. BJU Int. 2012;110(7):926–939.
4. Pouliot F, Shuch B, Larochelle JC, et al. Contemporary management of renal tumors with venous tumor thrombus. J Urol. 2010;184(3):833–841.
ADDITIONAL READING
None
See Also (Topic, Algorithm, Media)
• Deep Venous Thrombosis and Pulmonary Embolus, Urologic Considerations
• RCC, General
• Renal Cell Carcinoma, Locally Advanced (T3–T4)
• Renal Cell Carcinoma with Tumor Thrombus Image 
• Renal Vein Thrombosis, Adult and Pediatric
CODES
ICD9
• 189.0 Malignant neoplasm of kidney, except pelvis
• 453.2 Other venous embolism and thrombosis of inferior vena cava
• 453.3 Other venous embolism and thrombosis of renal vein
ICD10
• C64.9 Malignant neoplasm of unsp kidney, except renal pelvis
• I82.3 Embolism and thrombosis of renal vein
• I82.220 Acute embolism and thrombosis of inferior vena cava
CLINICAL/SURGICAL PEARLS
Preoperative assessment of cephalad extent of thrombus is critical for surgical planning.