Recurrent Renal Tumor Thrombus in Inferior Vena Cava After Surgery: Surgical Management and Clinicopathological Features from a Large Chinese Center


 Background: To summarize the surgical technique and clinicopathological features of recurrent renal tumor thrombus in inferior vena cava (IVC) after surgery.Methods: We retrospectively analyzed the clinicopathological data of nine patients with recurrent renal tumor thrombus in IVC after surgery, who were admitted to Peking University Third Hospital between November 2015 and March 2021. Results: Among the nine patients, six patients (66.7%) developed recurrent tumor thrombus in the IVC after radical nephrectomy; two cases (22.2%) were recurrent tumor thrombus in the IVC after partial nephrectomy. One patient (11.1%) underwent partial nephrectomy first and radical nephrectomy for the second time. The recurrence of tumor thrombus in the IVC occurred after the operation. All the nine patients underwent open surgery for IVC thrombectomy. Eight patients (88.9 %) were operated smoothly. Among these eight patients, six patients (75%) underwent IVC segmental resection, and two patients (25%) underwent IVC thrombectomy. Another patient underwent IVC tumor thrombus exclusion. Median operative time was 380 (IQR: 338.5–540.5) min. Median estimated intraoperative blood loss was 1200 (IQR: 600–2250) ml. According to the modified Clavien classification system, one patient had grade I complications, three patients had grade II complications, and one patient had grade IVa complications. During a 20-months (range, 2-58 months) follow-up, tumor-specific death occurred in three patients and distant metastasis occurred in six patients.Conclusions: The operation of recurrent renal tumor thrombus in IVC after surgery is difficult. For patients with high-risk renal cell carcinoma, more close follow-up should be conducted after operation.

According to the nature of tumor thrombus and the degree of vascular wall invasion, IVC surgery was divided into simple IVC thrombectomy, distal IVC transection (retaining the contralateral renal vein back into the IVC), and segmental IVC resection. After cutting the IVC wall during the operation, if the tumor thrombus was lled and completely blocked the IVC, considering the invasion of the IVC wall, a segmental resection of the inferior vena cava was required. For right primary renal tumors with recurrent tumor thrombus in the IVC, 4 − 0 Prolene suture can be used for continuous suture of the left renal vein, the distal end and the proximal end of the IVC during the operation, and the blood can be re uxed only by the branches of the left renal vein. For left primary renal tumor with recurrent tumor thrombus in the IVC, the blood re ux channel from the right renal vein to the distal end of the IVC can be retained, and the proximal end of the inferior vena cava can be sutured. If intraoperative adrenal invasion or metastasis is found, adrenalectomy is needed. Renal hilar lymph node dissection is required during the operation if renal hilar lymph node enlargement is found, The pathological types of renal cell carcinoma, WHO / ISUP nuclear grading, and whether renal hilar lymph node metastasis were analyzed according to postoperative pathology. The preoperative serum creatinine and 1 week after operation were counted to re ect the changes of renal function before and after operation. The modi ed Clavien classi cation system was used to evaluate the postoperative complications(16), among which grades ≥ three were de ned as severe complications (17).
The rst follow-up was conducted within one month after the operation, focusing on postoperative complications. Then the patients were followed up every 3-6 months, every 6-12 months after 2 years, and every year after 5 years. Patients with residual tumor or postoperative recurrence or distant metastasis were treated with tyrosine kinase inhibitors.

Results
Among the nine patients in this group, six cases (66.7%) had clinical symptoms, and all showed local symptoms. Six patients (66.7%) underwent radical nephrectomy for RCC, and recurrent tumor thrombus was found in the IVC during postoperative follow-up. Partial nephrectomy was performed in two patients (22.2%) due to RCC. Tumor recurrence was found in the affected kidney during postoperative follow-up, and renal tumor broke through the renal vein to form tumor thrombus in the IVC. Another patient underwent partial nephrectomy because of RCC. Local recurrence of the affected kidney was found during postoperative review. The second radical nephrectomy was performed for local recurrence. The recurrence of tumor thrombus in the IVC was found during postoperative follow-up. Before the operation of inferior vena cava tumor thrombus in nine patients, no obvious metastatic tumor was found in renal hilum lymph nodes. Four patients (44.4%) considered ipsilateral adrenal metastases before surgery. Four patients (44.4%) found other metastases except for adrenal metastasis. Three patients had pulmonary metastasis and one patient had thoracic spine metastasis combined with pulmonary metastasis. There were ve patients (55.6%) with IVC tumor thrombus combined with bland thrombus (non-neoplastic thrombus). The average length of IVC tumor thrombus was 7.7 cm, and the average width was 2.5 cm. (Table 1) All the nine patients underwent open surgery for IVC thrombectomy. Eight patients (88.9 %) were operated smoothly. Among these eight patients, six patients (75%) underwent IVC segmental resection, and two patients (25%) underwent IVC thrombectomy, namely IVC incision, tumor thrombus removal and vascular suture. Another patient (11.1%) underwent IVC tumor thrombus exclusion, simple palliative nephrectomy and ipsilateral adrenal metastasis resection. Four patients (44.4%) underwent renal hilar lymph node dissection. Adrenalectomy was performed in four cases (44.4%) due to the consideration of ipsilateral adrenal metastasis. Median operative time was 380 (IQR: 338.5-540.5) min. Median estimated intraoperative blood loss was 1200 (IQR: 600-2250) ml. Median intraoperative infusion of suspended red blood cells was 400 (IQR: 0-950) ml, median intraoperative infusion of plasma volume was 0 (IQR: 0-400) ml. (Table 2) The median postoperative hospital stay was 11 (IQR: 9-25) d. The serum creatinine before median operation was 97 (IQR: 84.5-126) µmol/L, serum creatinine at one week after surgery was 111 (IQR: 67.5-133) µmol/L. Eight cases (88.9%) were clear cell renal cell carcinoma, and one case (11.1%) was papillary renal cell carcinoma. No lymph node metastasis was reported in all patients undergoing intraoperative lymph node dissection and three cases of adrenal metastasis were found after adrenalectomy. In this group, ve cases (55.6%) had postoperative complications, including one case (11.1%) with severe complications. One case of grade I complication, manifested as edema of both lower extremities, was improved after conservative observation. Three cases of grade II complications, including one case of postoperative gastroparesis, gradually improved after fasting and rehydration therapy. One case of incomplete intestinal obstruction was improved after fasting rehydration therapy. Anemia accompanied by coagulation dysfunction in 1 case, after infusion of plasma and suspended red blood cells improved.
Grade II complications occurred in three cases (33.3%), including postoperative gastroparesis in one case, gradually improved after fasting rehydration therapy, incomplete intestinal obstruction in one case, improved after fasting rehydration therapy, anemia with coagulation dysfunction in one case, improved after transfusion of plasma and suspended red blood cells. Grade IVa complication was found in one case with renal insu ciency, which was improved by hemodialysis.
During a 20-months (range, 2-58 months) follow-up, tumor-speci c death occurred in three patients and distant metastasis occurred in six patients. TKI drugs or mTOR inhibitors were used after operation. (Table 3) There are few studies on the recurrence of tumor thrombus found in the IVC after partial nephrectomy or radical nephrectomy for renal tumors. Previously, most were case studies. Parker et al evaluated the prognosis of patients with recurrent vena cava tumor thrombus after prior nephrectomy for RCC. They found that surgical resection is complex but feasible, and the survival rate after resection is very low, the median time of recurrence and death was 4 (IQR: 1.7-16) months and 12 (IQR: 6-30.4) months, respectively(10). Rosen et al reported that under the care of experienced robotic surgeons, robotic resection of recurrent RCC with IVC thrombus is a potential treatment(18). Ciancio et al introduced the transplantation-based thrombectomy method, which provided good exposure and vascular control, so as to minimize the incidence of complications and provide a safe treatment option for patients (19). This study retrospectively analyzed the data of nine cases of recurrent renal tumor thrombus in IVC after RCC surgery, which was a relatively large sample size study in the current related studies.
The surgical incision for recurrent tumor thrombus in the IVC after RCC surgery was chosen as an abdominal Chevron incision. If the initial partial nephrectomy or radical nephrectomy is done by an open approach. During the second operation, it is necessary to remove the skin scar from the rst herringbone incision to ensure the good wound healing ability of the wound after this operation. If the rst operation is retroperitoneal laparoscopic approach, the second operation still chooses the abdominal Chevron incision. The rst operation was partial nephrectomy, and the second operation requires to remove the affected kidney. The experience in this group of patients found that the rst operation will cause severe intra-abdominal tissue adhesions, increasing the di culty of surgery.
Surgery for recurrent tumor thrombus in the inferior vena cava is a secondary operation, and intraoperative adhesions increase the di culty of the operation. In areas with severe adhesions, the IVC adheres to the surrounding intestines. When intestinal adhesions are involved, the use of scissors should be used to avoid thermal damage to the intestines, such as ultrasonic scalpel or monopolar electrotome. One patient (Case nine) had severe adhesion between the jejunum and the IVC, which was separated with sharp scissors. The intestinal wall was partially damaged, and 4 − 0 absorbable suture was used to repair the intestinal canal rupture. In another patient (Case eight), the tumor adhered to the diaphragm, psoas major muscle and spleen. During the operation, the invaded psoas major muscle, spleen and diaphragm were excised and repaired with silk suture. One patient in this group (Case ve) was found to be extremely malignant during the operation. The vascular wall of the IVC was stiff, and the tumor thrombus invaded the vascular wall and involved the hepatic vein. The possibility of tearing the IVC wall and hepatic vein wall during operation is great, and tumor thrombus of the IVC should be excluded. Only the left adrenal gland tumor was removed. Our experience shows that surgery for recurrent IVC tumor thrombus is di cult. Clearing the time interval between the initial RCC surgery and the detection of recurrent tumor thrombus in the IVC is of great signi cance for understanding the characteristics of the disease. In this study, we found that the median time interval between the rst and second operation was 20 months (range: 6 to 36) months. This helps to pay attention to the probable time of recurrent tumor thrombus in the IVC during follow-up after initial surgery. Patients at high risk should be followed up more closely. IVC ultrasonography should be used as a routine examination after RCC surgery. In addition, regular urinary CT imaging examination is also necessary. Two of the patients in this group had recurrent tumor thrombus in the IVC after partial nephrectomy. The enlightenment for us is that the initial diagnosis of tumors with a diameter of less than 7 cm (stage T2) (20)should be carefully read, and the differential diagnosis of T3a (renal vein tumor thrombus or renal sinus invasion) should be paid attention to. Patients with recurrence risk should be fully informed of the corresponding risk.
Partial nephrectomy is a treatment for localized RCC, and more reasonable clinical diagnosis should be made before operation. Radical nephrectomy should be performed for T3a RCC to avoid tumor recurrence.
We acknowledge that this study has some limitations. In this retrospective study, no case-control study was conducted between patients with recurrent tumor thrombus in the IVC and patients with traditional RCC and IVC tumor thrombus. The number of patients is limited, although it is a study with a large number of cases reported in the literature at present, multi-center and larger sample size studies can be carried out.

Conclusions
The operation of recurrent renal tumor thrombus in IVC after surgery is di cult. For patients with high-risk renal cell carcinoma, more close follow-up should be conducted after the operation.