Peking University Third Hospital Score: A Comprehensive System to Predict Intra-Operative Blood Loss in Radical Nephrectomy and Thrombectomy
Radical nephrectomy and thrombectomy is the standard surgical procedure for the treatment of renal cell carcinoma (RCC) with tumor thrombus (TT). However, the estimation of intra-operative blood loss has traditionally relied on the surgeon’s experience, which can lead to significant variability and potential complications. This study introduces the Peking University Third Hospital score (PKUTH score), a structured and quantitative scoring system designed to predict intra-operative blood loss volume in radical nephrectomy and thrombectomy.
The study retrospectively analyzed the clinical data of 153 cases of renal mass with renal vein (RV) or inferior vena cava (IVC) tumor thrombus admitted to the Department of Urology, Peking University Third Hospital from January 2015 to May 2018. The total amount of blood loss during the operation was calculated as the amount of blood sucked out by the aspirator plus the amount of blood in the blood-soaked gauze. Univariate linear analysis was used to identify risk factors for intra-operative blood loss, and significant factors were included in subsequent multivariable linear regression analysis.
The final multivariable model identified three significant factors associated with intra-operative blood loss: open operative approach, Neves classification IV, and IVC resection. The PKUTH score, ranging from 0 to 3, was calculated based on the number of these risk factors. The study found a significant increase in blood loss with higher PKUTH scores. The estimated median blood loss for PKUTH scores 0 to 3 was 280 mL, 1250 mL, 2000 mL, and 5000 mL, respectively. Additionally, higher PKUTH scores were associated with an increased chance of post-operative complications. A tendency, though not statistically significant, was observed in overall survival differences between PKUTH risk scores 0 versus 1 to 3.
The PKUTH score provides a reproducible and quantitative method to predict intra-operative blood loss, which can aid in better pre-operative planning and resource allocation. The study’s findings highlight the importance of considering surgical approach, tumor thrombus classification, and the need for IVC resection in predicting blood loss during radical nephrectomy and thrombectomy.
Introduction
In locally advanced renal cell carcinoma (RCC), 4% to 10% of patients have tumor thrombus (TT) involving the renal vein (RV) or inferior vena cava (IVC). Radical nephrectomy and thrombectomy is the standard surgical procedure for the treatment of RCC with IVC TT and can effectively improve the prognosis, with a 5-year tumor-specific survival rate of 40% to 65%. However, this procedure is one of the most difficult and complicated urological operations due to its high injury rate and significant intra-operative blood loss. If the TT extends to the IVC, the classical surgical procedure requires cutting the IVC vessel wall after temporary occlusion to remove the TT, followed by closure with non-absorbable sutures. Even in experienced hands, large blood loss remains a significant problem.
Effective pre-operative preparation, including blood preparation, is essential for such confined operations. However, factors such as fewer blood donors, excessive consumption of blood in other emergencies, and special blood types can lead to insufficient pre-operative blood preparation, potentially delaying the surgery. Therefore, a predictive model is needed to estimate intra-operative blood loss based on pre-operative clinical data, which will be helpful for clinical blood preparation before the operation.
Methods
The study was conducted in accordance with the Declaration of Helsinki and approved by the Peking University Third Hospital Medical Science Research Ethics Committee. Informed consent was obtained from all patients prior to their enrollment. The clinical data of 153 cases of renal mass with RV or IVC TT admitted to the Department of Urology, Peking University Third Hospital from January 2015 to May 2018 were retrospectively analyzed. Patients without surgical treatment, with recurrence of tumor thrombectomy, nephroblastoma, urothelial carcinoma, or other pathological types were excluded, leaving 123 cases with follow-up for analysis.
The total amount of blood loss during the operation was calculated as the amount of blood sucked out by the aspirator plus the amount of blood in the blood-soaked gauze. The method of weighing was used to calculate the amount of bleeding in the blood-soaked gauze. The study population was divided into ten groups according to the total intra-operative blood loss volume, with 400 mL as a classification increment.
All patients underwent B-mode ultrasonography, abdominal computed tomography (CT), and/or magnetic resonance imaging (MRI) scan before the operation to assess the renal mass, including the tumor side, location, diameter, and relationship with renal vessels and the collecting system. Chest CT scan and abdominal CT scan were performed for TNM staging of renal tumors. Abdominal MRI scan was used to measure the length of TT and determine whether the TT invaded the vessel wall. Echocardiography was performed to assess cardiac function and the presence of atrial TT. Karnofsky performance score (KPS) was used to classify patients according to their physical condition and surgical risk.
Serum hemoglobin, white blood cell count, neutrophil count, lymphocyte count, platelet count, total protein, albumin, blood urea nitrogen, serum creatinine, and alkaline phosphatase were collected pre-operatively. Serum creatinine was retested one week after surgery. Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and systemic immune-inflammation index (SII) were calculated and included in the analysis. Pre-operative distant metastasis status was confirmed by positron emission CT or chest CT, abdominal CT, cranial MRI, and bone scans. Post-operative immunotherapy or targeted molecular therapies were suggested if distant metastasis existed before surgery.
In laparoscopic radical nephrectomy and thrombectomy, the retroperitoneal space was established by the balloon method. A 13-mm trocar was inserted to establish a carbon dioxide pneumoperitoneum. An 11-mm trocar was placed on the iliac crest of the midaxillary line, and a 5-mm trocar was placed under the costal margin of the anterior axillary line. If necessary, another 5-mm assistant trocar was inserted. In open radical nephrectomy and thrombectomy, right RCC was treated with a chevron incision from the xiphoid process to the axillary midline at 2 cm below the right rib margin, extending about 5 cm below the left rib margin. For left renal tumors, the open incision was symmetrical to the right renal tumors. In level IV TT, the central tendon of the diaphragm could be cut around the IVC, and the TT could be squeezed into the IVC by gently pushing and squeezing, so that the thrombus could be changed into level III. Conventional right atrial thrombectomy required opening the chest to establish cardiopulmonary bypass (CPB) under beating or non-beating conditions.
The modified Clavien grading system was used to evaluate post-operative complications, with complications of grade >III defined as severe complications. The first follow-up was carried out one month after the operation, and then every three months in the first two years, and every six months after two years. Appropriate treatments were provided in cases of local recurrence or distant metastasis. Follow-up information was obtained from phone interviews and outpatient records. The last follow-up was completed in December 2018.
Results
The clinical and radiographic features of the cohort are shown in Table 1. The average surgical blood loss volume was 1372.2 ± 1679.3 mL (range: 10–10,000 mL). Univariate and multivariate associations of pre-operative clinical and radiographic features predicting intra-operative blood loss volume are shown in Tables 2 and 3. Univariate analysis confirmed that clinical N (cN) stage, absolute value of monocytes, pre-operative serum creatinine, alkaline phosphatase, serum urea nitrogen, KPS, operative approach, Neves classification, and IVC resection were significantly associated with intra-operative blood loss.
The final multivariable model included three features that combined to discern intra-operative blood loss volume with the greatest discriminatory ability: open operative approach, Neves classification IV, and IVC resection. The prediction formula of the bleeding volume is: y = 1205.853 × (open approach) + 2097.358 × (Mayo grade IV) + 1134.090 × (IVC wall resection) + 372.202. To ensure the convenience of the model, the weights of the three independent variables (open pathway, Mayo grade IV, IVC wall resection) were assigned as 1, 2, and 1, respectively. Because all patients of Mayo IV grade in this group adopted the open approach, there are only six possibilities divided by the three variables. Because 2 points and 3 points have similar bleeding volume in this classification, they were merged and simplified to the current score. The weights of the three independent variables (open pathway, Mayo grade IV, IVC wall resection) were assigned as 1 point, 1 point, and 1 point, respectively.
The blood loss of different PKUTH risk score cohorts is shown in Figure 3. A significant increase in blood loss was noticed along with higher risk scores. The median blood loss and its interquartile range (IQR) were presented with each score. For a patient with Neves classification 0 to III IVC TT, the surgeon assessed that laparoscopic surgery would be performed without conversion into open surgery. Moreover, there was no adhesion or invasion between the TT and the IVC wall, and segmental resection of the IVC wall was not necessarily required. Such patients would fit the characteristic description of PKUTH risk score 0, with an estimated median blood loss of 280 mL (IQR 100–600 mL). Patients with only one risk factor, such as an open approach only or IVC resection only, would fit the characteristic description of PKUTH risk score 1, with an estimated median blood loss of 1250 mL (IQR 575–2700 mL). Patients with two risk factors, such as an open approach and IVC vascular wall resection only or Mayo IV grade TT and open approach only, would fit the characteristic description of PKUTH risk score 2, with an estimated median blood loss of 2000 mL (IQR 1250–2900 mL). Simultaneous existence of three risk factors would fit the characteristic description of PKUTH risk score 3, with an estimated median blood loss of 5000 mL (IQR 4250–8000 mL). There was no significant difference in bleeding volume in different cases of the same PKUTH risk score.
The modified Clavien grading system was used to evaluate post-operative complications, with complications of grade ≥III defined as severe complications. The higher the PKUTH risk score, the higher the incidence of post-operative complications, as shown in Table 4 (P = 0.004). Although there was no statistical difference in the incidence of serious complications, an upward trend was observed, with higher PKUTH risk scores associated with a higher incidence of serious post-operative complications (P = 0.279).
The median follow-up time was 14.0 months (range: 0–44.0 months). The survival information of all patients was available. At the last follow-up, 32 patients had died, all of cancer-related causes. Overall survival of RCC with venous tumor thrombus (VTT) stratified by PKUTH risk score (0 vs. 1–3) is shown in Figure 4. A non-significant but a tendency of difference was noticed between these two groups (P = 0.098).
Discussion
The study presents the PKUTH score, a structured, reproducible, and quantitative scoring system to predict intra-operative blood loss volume in radical nephrectomy and thrombectomy. The final multivariable model included three features: open operative approach, Neves classification IV, and IVC resection, which were the only factors associated with intra-operative blood loss. A significant increase in blood loss was noticed along with higher risk scores.
Open radical nephrectomy and thrombectomy are traditional and effective treatments for RCC with RV or IVC TT. With the popularization of laparoscopic and robotic techniques in urology, laparoscopic or robotic-assisted thrombectomy has been carried out in some centers. Complete laparoscopic surgery can be used for Neves classification II or less. Laparoscopic surgery is minimally invasive and has the same therapeutic effect as open surgery. Laparoscopic surgery has several advantages: small trauma reduces bleeding caused by open incision; good visual field exposure helps directly separate and cut off the renal artery, reducing the blood supply of tumors; and intra-operative pneumoperitoneum can reduce collateral blood vessel bleeding. However, laparoscopic thrombectomy requires high professional skills, especially vascular suture skills. In contrast, for high-level TT, open approaches are often used with greater complexity, and the open approach itself is traumatic, which may result in increased intra-operative bleeding.
Neves classification IV is another factor contributing to increased intra-operative bleeding. Neves classification IV refers to the TT extension to the IVC above the diaphragm or to the atrium. Surgery requires a larger scope of vascular control, extracorporeal circulation assistance, and multi-disciplinary collaboration to complete. Generally, open radical nephrectomy and IVC thrombectomy are the standard surgical methods for the treatment of Neves IV TT. In this center, the technique of excision of the diaphragm without thoracotomy can be used to remove the thrombus above the diaphragm. The diaphragm is opened longitudinally, and the atrial TT is squeezed into the IVC by finger compression, and the upward-shifting access is blocked. The IVC is blocked by blocking-tape at the proximal end of the TT, or the thrombus can also be removed by balloon urethral catheter. This method can effectively simplify the procedure, reduce the amount of bleeding, and reduce the complications caused by CPB. However, if the TT grows into the right atrium and exceeds 2 cm or longer, CPB is needed.
IVC resection is also a factor contributing to increased intra-operative bleeding. The objective of surgical treatment for RCC with TT is to completely remove all tumor loads. If the TT invades the IVC wall, the involved vena cava wall should be removed thoroughly, so that the surgical margin can be negative, improving the survival rate of the patients after the operation. In contrast-enhanced CT, the invasion of the IVC wall can be characterized by the irregular contour of the IVC. Pre-operative color Doppler ultrasonography and contrast-enhanced magnetic resonance angiography can further assess the involvement of IVC. Contrast-enhanced magnetic resonance angiography showed that the wall of IVC was invaded: the wall of IVC was rough and not smooth, which could be characterized as “burr sign”; the diameter of IVC was enlarged; and the “edema zone” wall of IVC was visible. In this study, the so-called IVC vessel wall resection includes resection of the invaded part of the IVC vessel wall and segmental resection of the IVC. Whether the resection of the blood vessel wall is necessary can be preliminarily judged by some imaging examination before the operation. However, its limitation is that pre-operative imaging cannot absolutely predict the need for vascular wall resection.
In this study, tumor size is not a factor affecting the amount of bleeding. In previous studies, we found that compared with the diameter of primary renal cancer tumor, the height of TT had a greater impact on the amount of bleeding.
To reduce intra-operative blood loss effectively, our experience is as follows: (1) Before the treatment of TT, cutting off the renal artery can effectively reduce the blood supply of renal tumors and reduce bleeding when the kidney is free along the perirenal fascia. In addition, renal artery occlusion can also reduce the size of the kidney and tumors to a certain extent, reducing the difficulty of surgery. (2) Full exposure of IVC is necessary. Only after cutting off the lumbar vein and other branches of IVC can the related vessels be blocked. Otherwise, incision of the IVC wall will cause massive bleeding and blurred vision. (3) Hemorrhage during IVC wall incision is mostly caused by incomplete vascular occlusion. The most common is incomplete IVC occlusion below the RV. We used the vascular occlusion band to complete the occlusion. If incomplete occlusion is found, the vascular occlusion band can be pulled up and Hem-o-lok can be clamped after tightening. (4) To shorten the incision of IVC as far as possible on the premise of ensuring the complete removal of thrombus. The needle spacing should be uniform (about 2 mm). The blood loss of different PKUTH risk score cohorts shows a significant increase in blood loss along with higher risk scores. Overall survival of RCC with TT stratified by PKUTH risk score (0 vs. 1–3) shows a non-significant but a tendency of difference between these two groups (P = 0.098). Though a tendency of survival difference was noticed between high/low risk score groups, the limited sample size and relatively short follow-up resulted in a non-significant P value. As blood loss was reported as an independent prognostic factor in RCC with TT, the exact role of our risk score in prognostic stratification needs further confirming.
Our study has some limitations. This study is a retrospective analysis. Intra-operative blood loss is determined by many complex factors, such as the clinical experience of the surgeon, the application of hemostatic devices, and the factors of the tumor itself. The experience of the surgeon has a great influence on the amount of intra-operative blood loss. In addition, with the rich experience of the surgeon, the learning curve may reduce the amount of intra-operative bleeding. To reduce the bias caused by these aspects, we selected three doctors with similar seniority in our center. These surgeons have similar surgical experience. In the study population, we chose patients with a shorter time span to minimize the impact of the learning curve on intra-operative blood loss volume. The choice of hemostatic devices is also an important factor affecting intra-operative bleeding. In this group, we choose bipolar electrocoagulation for hemostasis through laparoscopy and ligasure for hemostasis in open surgery. The use of these hemostatic devices can reduce the amount of bleeding during the operation to a certain extent.
In conclusion, we found that open operative approach, Neves classification IV, and IVC resection were independently associated with intra-operative blood loss of nephrectomy and thrombectomy. The PKUTH score containing these factors correlated with blood loss significantly. It may help urologists prepare such a challenging surgery in a more quantitative way, though external validation is warranted before generalization of this score system.
doi.org/10.1097/CM9.0000000000000799
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