In the clinical practice, we found a particular type of patients whose tumor thrombus is growing against the direction of venous return. We define it as GADVR tumor thrombus(Tumor thrombus growing against the direction of venous return). Veins are blood vessels that carry blood back to the heart. The ventricles draw blood from the atria and large veins during diastole. When inhaling, the pleural cavity's negative pressure increases, and the pressure in the large veins in the thoracic cavity decreases, thereby promoting the return of venous blood(19). Through the role of heart and respiration, for the left kidney, blood flows from the branch of the left renal vein to the left renal vein and then enters the IVC. For the right kidney, blood flows from the right renal vein into the IVC. GADVR tumor thrombus is a characteristic feature of tumor thrombus, a secondary manifestation of rapid tumor growth or high malignancy. The malignant degree of tumors in these patients is often high, and it is easy to cause tumor thrombus to obstruct the IVC. The space in the inferior vena cava is limited, limiting the proliferation and growth of tumors. Therefore, the tumor thrombus extends to the branch vein or contralateral renal vein, showing an abnormal growth pattern against the direction of venous return. For the right RCC and VTT, the GADVR tumor thrombus is manifested as the left renal vein tumor thrombus. For left RCC and VTT, the GADVR tumor thrombus showed left adrenal vein, left gonadal vein (testicular or ovarian vein), and left lumbar ascending vein tumor thrombus. Although GADVR tumor thrombus is a secondary manifestation, the importance of this concept has not been emphasized or reflected in previous studies. We came up with this concept because we found that patients with this type of surgery are more complicated and have a worse prognosis in clinical practice.
In this study, we found that GADVR tumor thrombus incidence was 9.9% in all patients with RCC and VTT. In terms of surgical approach, 76.2 % of patients with GADVR tumor thrombus chose open surgery, while the proportion of patients with non-GADVR tumor thrombus was 52.1 %. With the progress of minimally invasive technology, more and more centers have applied laparoscopic or robotic surgery, and the open approach is still a traditional and effective treatment. Our previous studies have found that the open approach is usually associated with large tumor load, severe adhesion, tumor thrombus invasion of the vascular wall, and full-filled tumor thrombus, which is a manifestation of complex surgery.(20)
This study found that GADVR tumor thrombus had a higher proportion of adhesion to the IVC and IVC segmental resection. In clinical practice, we found that GADVR tumor thrombus is easy to obstruct the IVC. After the tumor thrombus adheres to the IVC, the inferior vena cava space is limited, limiting tumor proliferation and growth. Therefore, the tumor thrombus extends to the branch vein or contralateral renal vein, showing an abnormal growth pattern against the direction of venous return. In previous studies, we found that tumor thrombus combined with bland thrombus was a risk factor for surgical complexity and poor prognosis(15), and bland thrombus was also a manifestation of obstructive tumor thrombus(21). We believe that the obstruction of tumor thrombus caused the slow blood flow, and the platelets and red blood cells in the blood gathered at the distal end of the tumor thrombus, resulting in long-term thrombosis; on the other hand, the obstruction caused the space limitation and formed the tumor thrombus against the direction of venous return. Therefore, it is considered that either tumor thrombus with bland thrombus or GADVR tumor thrombus formation is a secondary manifestation of tumor thrombus obstruction.
GADVR tumor thrombus has more operation time and more surgical blood loss in terms of surgical complexity, which requires clinicians to pay more attention. Before surgery, patients and their families should be fully communicated to inform them of surgical risks and get an understanding of patients. Although the incidence of severe complications was not significantly different from that of non-GADVR tumor thrombus, the overall incidence of postoperative complications was high, and more intensive care was needed after the operation.
In terms of prognosis, GADVR tumor thrombus is an independent risk factor affecting PFS. In this study, it was found that the median survival time of patients with GADVR tumor thrombus was 14.0 months, while that of patients with non-GADVR tumor thrombus was 32.0 months, and the difference was statistically significant. Patients with GADVR tumor thrombus should be followed up more closely after the operation.
We distinguished 21 patients with GADVR tumor thrombus according to the type of vein involved. Before surgery, we confirmed GADVR tumor thrombus's presence by urinary system enhanced CT or inferior vena cava enhanced MRI. Imaging findings usually show thickening of the branch vein with filling defect inside, and enhancement can be seen after the enhanced scan, which can be diagnosed as a branch tumor thrombus. Preoperative imaging is essential to determine the length of branch tumor thrombus to ensure sufficient resection of the involved vein. The operation will be as radical as possible to remove all tumor thrombus branches, along with the branch vein and its internal tumor thrombus, to ensure that the tumor resection clean, reduce the local recurrence rate. If necessary, a frozen pathological examination can be performed on the vein's stump to ensure that the vascular wall margin is negative.
This study has the following limitations: the amount of data included in this study is small, and a larger sample of long-term follow-up studies is needed for further verification. This paper is a single-center study and needs to be further verified by the subsequent inclusion of multi-center studies to ensure broad adaptability.