Renal Cell Carcinoma Tumor Thrombus Research Articles

Systematic review and meta-analysis of preoperative imaging prediction of renal cell carcinoma tumour thrombus inferior vena cava wall invasion

To summarise published evidence assessing the preoperative diagnostic performance of identifying inferior vena cava (IVC) wall invasion in patients with renal cell carcinoma (RCC). A systematic approach was used to identify studies that assessed IVC wall invasion with non-invasive imaging preoperatively. Search limits included English language and human study participants. A meta-analysis was conducted using random effects models to compare radiographic vascular size parameters and the association of IVC wall invasion. A total of 15 studies were identified, which included computed tomography (CT), magnetic resonance imaging (MRI), positron-emission tomography (PET), and ultrasound assessment. In the majority of cases, CT and MRI was utilised with high accuracy in predicting IVC wall invasion. A meta-analysis of commonly reported radiographic vascular size parameters found that IVC wall invasion was associated with greater IVC maximum anteroposterior (AP) diameter (mean difference [MD]=6.58 mm, 95% confidence interval [CI]: 2.84-10.33, p=0.0006) and IVC maximum AP diameter at the level of the renal vein ostium (MD=5.69 mm, 95% CI: 4.35-7.03, p<0.0001). Renal vein maximum AP dimension was not associated with IVC wall invasion (MD=2.56 mm, 95% CI: -0.46-5.58, p=0.10). Multi-technique work-up, specifically CT and MRI and reporting of vascular radiographic parameters, of RCC patients with IVC tumour thrombus may be useful in predicting IVC wall invasion, thereby allowing appropriate surgical planning and patient education.

Characterization of tumor thrombus in renal cell carcinoma with prostate specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT).

Venous tumor thrombus (TT) occurs as part of the natural history of renal cell carcinoma (RCC) local progression in a small minority of cases. MRI is currently the most accurate imaging modality for determining TT extent. PSMA PET/CT may improve RCC staging and IVC TT characterization. The objective of this study was to investigate the role of PSMA PET/CT in defining superior extent of TT in RCC and TT IVC tributary vessel spread, with comparative accuracy vs. MRI, to assess suitability for resection and inform preoperative surgical planning. Patients who underwent PSMA PET/CT for assessment of renal malignancy with TT from 2015 to 2020 at 3 tertiary hospitals in Brisbane, Australia, were retrospectively identified. TT extent was classified using Mayo Clinic levels and compared according to imaging modality. Fourteen patients were included, all of which were clear cell RCC. Ten patients also underwent MRI, 6 of which were concordant in extent according to MRI and PSMA PET. Discordant extent occurred in 4 patients, of which 2 patients had non-PSMA avid thrombus (Mayo level 0 and level 3 on MRI). Further discordance was seen in a patient with adrenal vein and lumbar vein TT only seen on MRI and PSMA PET/CT, respectively. Finally, discordant extent was seen in another patient with Mayo level 4 TT without lumbar vein involvement on MRI vs. level 3 on PSMA PET/CT with lumbar vein involvement. PSMA PET/CT can provide additional information about TT extent in RCC which may not be seen on MRI. Additional information from PSMA PET/CT in this setting may assist surgical planning, in addition to detection of metastatic disease.

A rare case of renal cell carcinoma with hematogenous extension into the right atrium discovered incidentally on echocardiogram

While hematogenous spread of renal cell carcinoma (RCC) is common, isolated extension into the renal vein and inferior vena cava (IVC) is rare and extension to the right atrium is even less likely. In the case, a 62-year-old Hispanic female was admitted for a suspected inferior myocardial infarction, and her echocardiogram revealed a right atrial mass consistent with the appearance of an atrial myxoma. Following cardiac catheterization, a histopathological examination of the mass revealed a clear cell tumor consistent with metastatic clear cell RCC. Following a CABG with excision of the atrial mas, the CT demonstrated a 5 cm right lower pole renal mass with hilar involvement, as well as filling defects in the IVC extending into the right renal vein; these findings were consistent with RCC tumor thrombus extension into the renal vein, IVC, and right atrium. The radical nephrectomy necessary for tumor removal could not be performed at this hospital, so the patient was discharged to a higher level of care. The incidence rate for RCC with extension into the right atrium is quite low, but clinicians should understand the lethality of RCC warrants immediate clinical investigation upon diagnosis. The increased utilization of sophisticated imaging modalities will likely continue to increase the rate of incidental discovery of such neoplasms, and physicians should keep RCC on the differential when a right atrial mass is discovered incidentally on echocardiogram.

Evaluating inferior vena cava wall invasion in renal cell carcinoma tumor thrombus with MRI

To evaluate the diagnostic performance of MRI for the assessment of inferior vena cava (IVC) wall invasion by IVC thrombus in patients with renal cell carcinoma (RCC). We retrospectively collected patients who underwent radical nephrectomy and thrombectomy for RCC between 2010 and 2018 at Peking University First Hospital. All the patients underwent imaging on a 1.5 Tesla or 3.0 Tesla MRI scanner. Fifty-six patients met the inclusion criteria. Preoperative imaging was reviewed by two radiologists blinded to details of the patient's surgical procedure and histopathology. Two radiologists measured the maximum anterior-posterior diameter and coronal diameters of the IVC and renal vein, and the craniocaudal extent of tumor thrombus, and evaluated the MRI features of IVC thrombus, including occlusion of the IVC lumen, the margin of the tumor thrombus (smooth vs. irregular), contact of the IVC thrombus and IVC wall, and altered signal of the IVC wall. Univariable and multivariable associations of clinical and radiographic features with IVC wall invasion were evaluated by Logistic regression. Of the 56 patients [male: 43, female: 13, mean age: (55.64±0.43) years], 17 (30.36%) were detected with IVC wall invasion, and most were clear cell carcinoma. Tumor thrombus with IVC wall invasion showed an increase in length of IVC thrombus [(7.91±3.59) cm vs. (5.94±3.57) cm, P=0.049], and more features of complete occlusion of the IVC lumen (P=0.002), irregular margin of the IVC thrombs (P=0.005), contact of the IVC thrombus and IVC wall (P=0.001), and altered signal of the low-intensity vessel wall (P<0.001), with a sensitivity of 94.12% and a specificity of 79.49%. The present study indicates that MRI could be a means of evaluating RCC with IVC wall invasion, and the combination of tumor thrombus length and subjective impression of IVC wall invasion achieved a high sensitivity and specificity for diagnosis.

Renal cell carcinoma with thrombus extending to the hepatic veins or right atrium: operative strategies based on 41 consecutive patients.

The natural history of renal cell carcinoma (RCC) with tumour thrombus extending at or above the hepatic veins is dismal. Different surgical approaches have been described including cardiopulmonary bypass (CPB) with deep hypothermic circulatory arrest. We here report our experience in terms of surgical techniques and outcomes on 41 consecutive patients presenting an RCC extending to the hepatic veins or the right atrium. A surgical decision-making algorithm is discussed. Retrospective review of 41 patients operated for RCC extending in the retrohepatic vena cava (extent level III-IV) between 2000 and 2015. Patients were operated by a dedicated urology/cardiac surgery team. The mean age was 62.6 ± 10.4 years; 39% were female. Surgery was emergent in 7.3% of patients, 2.4% of patients had preoperative dialysis, 4.9% required a redo sternotomy and 19.5% had coronary artery disease. Tumour thrombus extended above the diaphragm in 23 patients (level IV) and to the level of hepatic veins (level III) in 18 patients. CPB was used in 38 patients. Arterial cannulation was in the aorta or femoral artery in 14 patients during the initial experience. In the current era, the axillary artery and the innominate artery were used in 12 patients each. Mean CPB, cross-clamp and circulatory arrest times were, respectively, 96.5 ± 42.9, 21.1 ± 16.4 and 10.2 ± 8.2 min (mean temperature of 25.7 ± 4.9°C). Hepatic exclusion without the use of CPB was performed to excise the thrombus in 3 patients. A right nephrectomy was performed in 25 patients, a left in 15 patients and a bilateral nephrectomy in 1 patient. Five patients had a partial inferior vena cava (IVC) resection, with 4 patients requiring a patch reconstruction of the IVC. Three patients had an infrarenal IVC ligation. One patient suffered a cerebrovascular accident in the postoperative period. One in-hospital death occurred (in-hospital mortality 2.4%). The mean follow-up was 1.9 ± 2.0 years. Twenty-three patients died during follow-up; 21 were disease-related. Three-year survival rate was 37.1%. High-level RCC tumour thrombus is a rare clinical entity, the treatment of which is complex and requires dedicated operative teams. The operative technique should be tailored according to the level of extension and the extent of vena cava obstruction/occlusion of the tumour thrombus. Contemporary operative techniques may be conducted with excellent results. Mid-term survival is limited, supporting the necessity to pursue research efforts towards establishing effective adjunct therapies.

Intracellular lipid in clear cell renal cell carcinoma tumor thrombus and metastases detected by chemical shift (in and opposed phase) MRI: radiologic-pathologic correlation.

Clear cell renal cell carcinoma (RRC) characteristically contain intracellular lipid which is also detectable in tumor thrombus and metastases. To assess the incidence of intracellular lipid in clear cell RCC metastases and tumor thrombus using chemical shift MRI. With REB approval, 33 consecutive patients with clear cell RCC and tumor thrombus/metastatic disease underwent magnetic resonance imaging (MRI) over a 10-year period. Diagnosis was established by histopathology for tumor thrombi (n = 25) and metastases (n = 15) or growth for metastases (n = 14). Two blinded radiologists independently assessed for a signal intensity (SI) drop at chemical shift MRI (indicative of intracellular lipid) and a third radiologist established consensus. Chemical shift SI (CS-SI) index ([SItumorIP - SItumorOP]/SITumorIP x 100) was calculated. Inter-observer agreement was assessed using intra-class correlation (ICC) and tests of association were performed using the Chi-square test and Spearman correlation. Using CS-MRI, intracellular lipid was detected in 36.4% of clear cell RCC, with moderate agreement, (ICC = 0.5). Intracellular lipid was detected in 20% of tumor thrombi and 20% of metastases with strong agreement (ICC = 0.73). Intracellular lipid within tumor thrombi/metastases was not associated with lipid within the primary tumor (P = 0.09). There was a correlation in CS-SI index between primary tumor and thrombi/metastases when lipid was detected in both lesions (r = 0.91, P = 0.005); however, there was no correlation when lipid was not detected in both lesions (r = -0.09, P = 0.72). The presence of intracellular lipid in tumor thrombus and metastases from clear cell RCC is uncommon and, is not necessarily associated with lipid within the primary tumor at chemical shift MRI.

Clinical management of renal cell carcinoma with venous tumor thrombus.

Venous invasion is common in advanced renal cell carcinoma (RCC) due to the unique biology of this cancer. The presence of a tumor thrombus often makes clinical management challenging. In this review, we detail specific preoperative, perioperative, and surgical strategies involving the care of the complex kidney cancer patient with venous tumor involvement. We performed a comprehensive review of selected peer-reviewed publications regarding RCC tumor thrombus biology, medical and surgical management techniques, and immediate and long-term outcomes. The perioperative management may require special imaging techniques, preoperative testing, very recent imaging, and consultation with other surgical services. There are various approaches to these patients as the clinical presentation, stage of disease, primary tumor size, level of thrombus, degree of venous occlusion, presence of bland thrombus, and primary tumor laterality influence management. Select patients with metastatic disease can do well with cytoreductive nephrectomy and thrombectomy. Those with localized disease have a high risk of recurrence; however, some patients can exhibit durable survival with surgery alone. The evolving surgical and medical treatments are discussed. Even when these surgeries are performed in high volume centers, significant perioperative complications are common and greater complications are seen with higher thrombus extent. If surgery is attempted, it is important for urologic oncologists to follow strict attention to specific surgical principles. These general principles include complete vascular control, avoidance of thrombus embolization, close hemodynamic monitoring, and institutional resources for caval resection/replacement and venous bypass if necessary.

Intrahepatic extension of renal cell carcinoma tumor thrombus causing Budd-Chiari syndrome

Intrahepatic extension of renal cell carcinoma tumor thrombus causing Budd-Chiari syndrome

Does left side renal cell carcinoma (RCC) with renal vein/vena cava thrombus predict worse prognosis than equivalent right side RCC tumor thrombus?

To determine whether renal cell carcinoma (RCC) thrombi that reach the vena cava from the left kidney are associated with a greater risk of RCC death than equivalent thrombi from the right kidney. Two hundred and fifty-nine patients treated with radical nephrectomy (1970-2006) for unilateral, sporadic RCC with level 1-4 RCC tumor thrombus were identified. Clinicopathologic features between patients with right-sided (N = 183) and left-sided (N = 76) thrombus were compared utilizing Wilcoxon rank sum and Fisher's exact tests. Associations with RCC-specific death using hazard ratios (HR) and 95 % confidence intervals (CIs) from Cox proportional hazards models were evaluated. Left-sided RCC patients with thrombus are less likely to be clear cell subtype (85 % vs. 93 %; p = 0.013) and more likely to have nodal involvement (28 % vs. 16 %; p = 0.018) compared to right side RCC patients with thrombus. Overall, there is little evidence that the risk of RCC death is higher for left versus right-sided RCC thrombus (HR = 1.11; 95 % CI 0.81-1.53; p = 0.52). However, among those patients with a thrombus that has reached the vena cava (level III/IV), we observe evidence after multivariate adjustment that the risk of RCC death is higher for left versus right side patients (HR = 2.02; 95 % CI 0.91-4.47; p = 0.08). Left side RCC with tumor thrombus is not associated with worse prognosis than right-sided tumors (all tumor thrombi levels). Our data suggest that among RCC patients with advanced tumor thrombi (level III/IV), a left side thrombus may be associated with worse prognosis compared to a right side thrombus.

Intrahepatic extension of renal cell carcinoma tumor thrombus causing Budd-Chiari syndrome

A 66-year-old woman presented with a 10-day history of progressive shortness of breath, epigastric pain and 10-pound weight loss. Physical examination revealed a palpable mass involving the right upper quadrant. Computed tomography (CT) of the abdomen demonstrated a 6.8 × 8.8 × 7.5 cm right renal mass with tumour thrombus extending into the inferior vena cava and right atrium (Fig 1). In addition, the tumour extended retrograde into the right hepatic vein, associated with abnormal attenuation in the right lobe of the liver on the CT scan of the abdomen (Fig 2). This obstruction caused Budd-Chiari syndrome, associated with abnormal liver function tests and ascites. Alanine transferase, aspartate trasnferrase, alkaline phosphatase and gamma-glutamyl transpeptidase levels were 946, 1047, 396 and 203 U/L, respectively. The bilirubin level was 76 umol/L and the international normalized ratio was 1.5. Fig. 1. A: Coronal computed tomography image of thorax/abdomen/pelvis with intravenous contrast demonstrating a large tumour thrombus extending into the right hepatic vein (double arrows) and just below the right atrium (single arrow). B: Sagittal view showing ... Fig. 2. A: Axial computed tomography image of tumour thrombus extending into the right hepatic vein. Arterial phase scan demonstrates enhancement of the tumour in the inferior vena cava and of the tumour extension into the right hepatic vein (red arrow). B: Portal ... The patient underwent right radical nephrectomy, cardiopulmonary bypass and caval thrombectomy with right hepatic venotomy. Notably, the thrombus slid out of the hepatic vein without evidence of hepatic attachment or infiltration (Fig. 3). Fig. 3. Tumour thrombus with extension into the right hepatic vein (blue arrow) and associated bland thrombus (red arrow). The thrombus slid out of the vein without evidence of hepatic attachment or infiltration. Final pathology revealed Fuhrman 3 clear cell renal cell carcinoma with negative margins (T3cN0M0). She was re-imaged with thoracic and abdominal CT scanning and is free of disease 4 months postoperatively. Liver function tests have also normalized.

Techniques for Avoidance of Sternotomy and Cardiopulmonary Bypass During Resection of Extensive Renal Cell Carcinoma with Vena Caval Tumor Thrombus Extension Above the Diaphragm

Renal cell carcinoma (RCC) is a commonly encountered malignancy in urology. Extensive RCC may frequently invade the renal vein and the inferior vena cava (IVC). In advanced cases, this tumor thrombus may grow cephalad up to the level of the right atrium. The mainstay of surgical treatment for such lesions remains resection of all possible tumor burden. Current techniques for resection of supradiaphragmatic RCC tumor thrombus in the IVC incorporate cardiopulmonary bypass (CBP) with deep hypothermic circulatory arrest, especially in cases where the thrombus reaches the right atrium. We report a safe technique using a transabdominal approach to such lesions that allows exposure to the level of the intrapericardial IVC and right atrium permitting safe resection of the tumor thrombus without median sternotomy, CBP, or deep hypothermic circulatory arrest.

Intraoperative Thrombus Embolization During Nephrectomy and Tumor Thrombectomy: Critical Analysis of the University of California-Los Angeles Experience

Vascular invasion commonly occurs in renal cell carcinoma and intraoperative thrombus embolization is a known complication of tumor thrombectomy. We reviewed our experience with this complication to determine frequency, mortality, common factors and management strategies. We retrospectively reviewed a prospective database of cases of open nephrectomy/tumor thrombectomy performed from 1989 to 2008. All cases were reviewed to identify clinicopathological variables, the thrombus extent and intraoperative complications. All cases with events were reviewed to identify preoperative pulmonary embolism, preoperative imaging, thrombus extent, presentation, management and outcome. A total of 282 cases of venous tumor thrombus were identified. Tumor thrombus level was 0 in 133 cases (47.2%), I to II in 85 (30.1%), III in 27 (9.6%) and IV in 29 (10.3%). Thrombus embolization was identified in 5 patients (1.8%). The incidence in level 0 vs I to IV was 0 of 133 cases (0%) vs 5 of 149 (3.4%), which was statistically significant (p = 0.04). Three patients (60%) died of the event. A review of recent series demonstrated a 1.49% incidence with 75% mortality. Intraoperative thrombus embolization is rare but when it occurs, mortality is extremely high. Strict attention to surgical principles is necessary to decrease risk. Extension into the vena cava, preoperative pulmonary embolism and a bland thrombus component may indicate increased risk. Adjunct procedures, such as preoperative filters and endoluminal occlusive balloons, may be justified in patients at high risk. Even with prompt recognition and embolectomy survival is rare.

Challenging Surgery for Retroperitoneal Tumors and Liver Transplant Surgeons

Resection of tumors in the retroperitoneum, surrounding, invading, or growing into the inferior vena cava (IVC), presents challenges to most surgeons. Of the uncommon tumors that present in this way, the most common is renal cell carcinoma (RCC), which has the unique propensity to grow into the lumen of the IVC via the renal vein. Other retroperitoneal tumors, such as adreno-cortical carcinomas and primary sarcomas arising in the retroperitoneum, may invade the IVC and/or other surrounding structures, such as the liver or the diaphragm. The article published in this issue of World Journal of Surgery by Facciuto et al. [1] describes the application of surgical techniques used in liver transplantation for the resection of these tumors. Safe and complete resection of these lesions requires familiarity with mobilization of the liver and the dissection and control of the infrahepatic, intrahepatic, and suprahepatic IVC. Liver transplant surgeons are uniquely placed in possessing the experience and skills required for such exposure and dissection. Other critical facilities and expertise available to these surgeons are the routine availability of intraoperative ultrasound, venovenous bypass, specialist anesthetic assistance with the intraoperative management of patients undergoing this type of surgery, and the ability to resect involved liver segments simultaneously. If resection and replacement of the IVC is also required, liver transplant units will have access to a bank of allogeneic venous grafts from deceased organ donors. The rationale for surgical excision even for locally advanced neoplasms with tumor thrombus in the IVC, shortand long-term outcomes, and the effect of other treatment modalities have been published mostly for RCCs [2, 3]. The remarkably low morbidity and zero mortality achieved by Facciuto and colleagues compares favorably with previously published results in this area. In describing the Mayo Clinic experience during a 30-year period since 1970, Blute et al. [4] reported two intraoperative and two perioperative deaths (14.2%) in 28 patients who had level III (TNM classification: pT3B) RCC tumor thrombus in the IVC. Our own unpublished experience mirrors that of the New York group with no intraoperative or perioperative mortality in the resection of pT3b RCCs in more than 30 patients. All of our cases were initially referred to a specialist urological surgeon and involved multidisciplinary discussion on the management approach. Patients with tumor thrombus extending into the intrahepatic and suprahepatic IVC were selected for surgery to be jointly performed by a urologist and a liver transplant surgeon in the liver transplant unit. An important technical consideration is the gradual obstruction to flow in the IVC from the tumor thrombus, which results in the development of collateral venous circulation in the retroperitoneum. Even after clamping proximal and distal IVC as well as the contralateral renal vein, these venous collaterals cause significant blood loss when the isolated segment of the IVC is opened. One of the key maneuvers in avoiding blood loss from these collateral veins is complete mobilization and retraction of the liver and full exposure of the intrahepatic IVC to the level of the hepatic veins. Placement of the surgeon’s (left) hand posterior to the IVC and pressing it anteriorly is then adequate to minimize blood loss when the IVC is incised for the extraction of the contained tumor thrombus. Collaboration between urologists and liver transplant surgeons has been one of the key developments in the M. Akyol (&) Scottish Liver Transplant Unit, The Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, Scotland, UK e-mail: murat.akyol@ed.ac.uk

Re-evaluation of renal cell carcinoma tumor thrombus extension by intraoperative transesophageal echocardiography

T RANSESOPHAGEAL ECHOCARDIOGRAPHY (TEE) is well accepted and extensively used by cardiologists, anesthesiologists, and cardiothoracic surgeons perioperatively to monitor cardiac function and great vessel anatomy.’ TEE remains underused in noncardiac surgical procedures, however. This oversight may be due, in part, to inadequate resources or the specialized training and qualifications necessary to perform TEE.* Alternatively, other physicians may be unfamiliar with its diagnostic capabilities. This case report describes a patient whose treatment was dramatically altered by perioperative TEE. He was brought to the operating room with a diagnosis of renal cell carcinoma and his preoperative diagnostic evaluation revealed extension of the tumor thrombus into the inferior vena cava and intrahepatic vessels. There was no tumor thrombus extension visualized above the level of the diaphragm by magnetic resonance imaging (MRI) or transthoracic echocardiography. The patient was brought to the operating room for a planned surgical resection of the tumor and subdiaphragmatic tumor thrombus.

Usefulness of cardiopulmonary bypass in reconstruction of inferior vena cava occupied by renal cell carcinoma tumor thrombus.

Aggressive surgical treatment in renal cell carcinoma is still controversial. The aim of this paper is to assess inferior vena caval (IVC) reconstruction for suprahepatic vena caval renal cell carcinoma (RCC) tumor thrombus. Twelve patients with suprahepatic vena caval thrombus from renal cell carcinoma who underwent surgical repair with cardiopulmonary bypass were evaluated. The vena caval defect was reconstructed by direct suture, patch repair, or graft replacement. Of 12 patients undergoing partial cardiopulmonary bypass, tumor thrombus extended to the junction of the hepatic vein in three patients and to the right atrium in one. Tumor thrombus was removed manually or with balloon catheter. Tumor thrombus in the right atrium was removed during electrical ventricular fibrillation. Repair of the IVC was performed by direct suture of the IVC wall in two patients, patch repair with expanded polytetrafluoroethylene (EPTFE) graft in seven, and graft replacement with an EPTFE graft in three. There were no operative deaths and the only postoperative complication was one patient death from pulmonary emboli. The four patients with nonlocalized disease died within 2 years, but four patients lived for more than 3 years postoperatively. Survival was 37.5% at 3 years and 18.8% at 5 years by the Kaplan-Meier's method. (1) Partial cardiopulmonary bypass is useful for the control of bleeding when tumor thrombus in the IVC extends to the junction of the hepatic vein. (2) Nephrectomy with tumor thrombectomy of the IVC is valuable, and long-term survival is possible in patients without distant metastases or regional lymph node metastases.

Vena cava resection for renal cell carcinoma.

Vena cava resection for renal cell carcinoma.