Neoadjuvant stereotactic ablative body radiotherapy combined with surgical treatment for renal cell carcinoma and inferior vena cava tumor thrombus: a prospective pilot study.

BACKGROUND: Surgical treatment for renal cell carcinoma (RCC) and inferior vena cava (IVC) tumor thrombus (TT) is difficult, and the postoperative complication rate is high. This study aimed to explore the safety and oncologic outcomes of neoadjuvant stereotactic ablative body radiotherapy (SABR) combined with surgical treatment for RCC and IVC-TT. METHODS: Patients with RCC and IVC-TTs were enrolled in this study. All patients received neoadjuvant SABR focused on the IVC at a dose of 30 Gy in 5 fractions, followed by 2 ~ 4 weeks of rest. Then, radical nephrectomy and IVC tumor thrombectomy were performed for each patient. Adverse effects, perioperative outcomes, and long-term prognoses were recorded. RESULTS: From June 2018 to January 2019, 8 patients were enrolled-4 with Mayo grade II TT and 4 with Mayo grade III TT. Four (50%) patients had complicated IVC wall invasion according to CT/MRI. All patients received neoadjuvant SABR as planned. Short-term local control was observed in all 8 patients. Only Grade 1-2 adverse events were reported. In total, 3 (37.5%) laparoscopic surgeries and 5 (62.5%) open surgeries were performed. The median operation time was 359 (IQR: 279-446) min, with a median intraoperative bleeding volume of 750 (IQR: 275-2175) ml. The median postoperative hospital stay was 7 (5-10) days. With a 26-month (range: 5-41) follow-up period, the estimated mean overall survival was 30.67 ± 5.38 months. CONCLUSIONS: This is the first preoperative radiotherapy study in Asia that focused on patients with TT. This study revealed the considerable safety of neoadjuvant SABR for RCC with IVC-TT. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trials Registry on 2018-03-08 (ChiCTR1800015118). For more information, please see the direct link ( https://www.chictr.org.cn/showproj.html?proj=25747 ).

Prognostic Significance of Grade Discrepancy Between Primary Tumor and Venous Thrombus in Nonmetastatic Clear-cell Renal Cell Carcinoma: Analysis of the REMEMBER Registry and Implications for Adjuvant Therapy.

BACKGROUND: Further stratification of the risk of recurrence of clear-cell renal cell carcinoma (ccRCC) with venous tumor thrombus (VTT) will facilitate selection of candidates for adjuvant therapy. OBJECTIVE: To assess the impact of tumor grade discrepancy (GD) between the primary tumor (PT) and VTT in nonmetastatic ccRCC on disease-free survival (DFS), overall survival (OS), and cancer-specific survival (CSS). DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective analysis of a multi-institutional nationwide data set for patients with pT3N0M0 ccRCC who underwent radical nephrectomy and thrombectomy. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS: Pathology slides were centrally reviewed. GD, a bidirectional variable (upgrading or downgrading), was numerically defined as the VTT grade minus the PT grade. Multivariable models were built to predict DFS, OS, and CSS. RESULTS AND LIMITATIONS: We analyzed data for 604 patients with median follow-up of 42 mo (excluding events). Tumor GD between VTT and PT was observed for 47% (285/604) of the patients and was an independent risk factor with incremental value in predicting the outcomes of interest (all p < 0.05). Incorporation of tumor GD significantly improved the performance of the ECOG-ACRIN 2805 (ASSURE) model. A GD-based model (PT grade, GD, pT stage, PT sarcomatoid features, fat invasion, and VTT consistency) had a c index of 0.72 for DFS. The hazard ratios were 8.0 for GD = +2 (p < 0.001), 1.9 for GD = +1 (p < 0.001), 0.57 for GD = -1 (p = 0.001), and 0.22 for GD = -2 (p = 0.003) versus GD = 0 as the reference. According to model-converted risk scores, DFS, OS, and CSS significantly differed between subgroups with low, intermediate, and high risk (all p < 0.001). CONCLUSIONS: Routine reporting of VTT upgrading or downgrading in relation to the PT and use of our GD-based nomograms can facilitate more informed treatment decisions by tailoring strategies to an individual patient's risk of progression. PATIENT SUMMARY: We developed a tool to improve patient counseling and guide decision-making on other therapies in addition to surgery for patients with the clear-cell type of kidney cancer and tumor invasion of a vein.

The Application of CT Radiomics in the Diagnosis of Vein Wall Invasion in Patients With Renal Cell Carcinoma Combined With Tumor Thrombus.

OBJECTIVE: The objective of this study was to explore the application of radiomics combined with machine learning to establish different models to assist in the diagnosis of venous wall invasion in patients with renal cell carcinoma and venous tumor thrombus and to evaluate the diagnostic efficacy. MATERIALS AND METHODS: We retrospectively reviewed the data of 169 patients in Peking University Third Hospital from March 2015 to January 21, who was diagnosed as renal mass with venous invasion. According to the intraoperative findings, 111 patients were classified to the venous wall invasion group and 58 cases in the non-invasion group. ITK-snap was used for tumor segmentation and PyRadiomics 3.0.1 package was used for feature extraction. A total of 1598 features could be extracted from each CT image. The patients were divided into training set and testing set by time. The elastic-net regression with 4-fold cross-validation was used as a dimension-reduction method. After feature selection, a support vector machines (SVM) model, a logistic regression (LR) model, and an extra trees (ET) model were established. Then the sensitivity, specificity, accuracy, and the area under the curve (AUC) were calculated to evaluate the diagnostic performance of each model on the testing set. RESULTS: Patients before September 2019 were divided into the training set, of which 88 patients were in the invasion group and 42 patients were in the non-invasion group. The others were in the testing set, of which 32 patients were in the invasion group and 16 patients were in the non-invasion group. A total of 34 radiomics features were obtained by the elastic-net regression. The SVM model had an AUC value of 0.641 (95% CI, 0.463-0.769), a sensitivity of 1.000, and a specificity of 0.062. The LR model had an AUC value of 0.769 (95% CI, 0.620-0.877), a sensitivity of 0.913, and a specificity of 0.312. The ET model had an AUC value of 0.853 (95% CI, 0.734-0.948), a sensitivity of 0.783, and a specificity of 0.812. Among the 3 models, the ET model had the best diagnostic effect, with a good balance of sensitivity and specificity. And the higher the tumor thrombus grade, the better the diagnostic efficacy of the ET model. In inferior vena cava tumor thrombus, the sensitivity, specificity, accuracy, and AUC of ET model can be improved to 0.889, 0.800, 0.857, 0.878 (95% CI, 0.745-1.000). CONCLUSION: Machine learning combined with radiomics method can effectively identify whether venous wall was invaded by tumor thrombus and has high diagnostic efficacy with an AUC of 0.853 (95% CI, 0.734-0.948).

Construction of the prognostic model in non-metastatic renal cancer patients with venous tumor thrombus.

Background: Venous system invasion is a prominent characteristic of local progression in renal cancer and treatment-naïve renal cancer patients with venous tumor thrombus (VTT) gained short natural course and poor prognosis. This study aimed to investigate the efficacy of the surgery and prognostic factors in non-metastatic renal cancer patients with VTT and to construct a nomogram prognostic model. Methods: Clinical data of 114 non-metastatic renal cancer patients with VTT who underwent surgical treatment from January 2011 to September 2022 were retrospectively analyzed. In order to find independent risk factors of prognosis, survival analysis was performed via univariate and multivariate Cox regression models and Kaplan-Meier method. Nomogram prognostic model was established to calculate patients' risk scores. Receiver operating characteristic curve and decision curve analysis were conducted to evaluate the efficacy of the prognostic model. Results: A total of 114 patients were included in this study and there were 48, 12, 25, 23, and 6 cases of grade 0-IV VTT. No perioperative death occurred. The 3-year probabilities of overall survival (OS) and 5-year probabilities of OS were 67% and 43.8%, respectively. Multivariate Cox regression analysis revealed that kidney tumor diameter, preoperative lactate dehydrogenase (LDH), and preoperative neutrophils were independent risk factors. Nomogram was constructed to predict prognosis in renal cancer patients with VTT based on above indicators and Mayo VTT grading. The area under the ROC curve of 1-, 2-, 3-, and 5-year OS of the patients were 0.82, 0.67, 0.57, and 0.55 respectively. Conclusions: Surgical treatment enables renal cancer patients with VTT to gain a better prognosis. Kidney tumor diameter, preoperative LDH, and preoperative neutrophils were independent risk factors. The nomogram perfects the Mayo grading, and provides a reliable reference for evaluation of prognosis of renal cancer patients with VTT.

Inferior Vena Cava Thrombus Associated With Renal Cell Carcinoma With an Atypical Radiological Presentation: A Case Report.

Renal cell carcinoma (RCC) is characterized by the development of kidney masses, which can lead to various long-term complications. Among the extrarenal manifestations associated with RCC, the formation of a thrombus within the inferior vena cava (IVC) is particularly prevalent due to the substantial tumor burden imposed by the kidneys. In this report, we present an exceptional case involving an 80-year-old male patient who presented with an intravascular thrombus within the inferior vena cava (IVC), which originated from RCC. The diagnosis of RCC was conclusively established through core needle biopsy and subsequent tumor marker staining. Remarkably, despite the confirmation of RCC within the IVC thrombus through biopsy and tumor marker analysis, radiological assessments failed to reveal any discernible renal cell masses within the kidneys. The patient subsequently received treatment for RCC with a combination regimen of cabozantinib and nivolumab, which resulted in a noteworthy improvement in his clinical condition. The presentation of RCC in this report is notably atypical, given that the biopsy of the thrombus yielded definitive evidence of RCC while radiological investigations did not yield any indications of renal masses or a tumor burden within the kidneys that would typically be associated with RCC.

[Risk factors for massive hemorrhage after radical nephrectomy and removal of venous tumor thrombus].

OBJECTIVE: To investigate and analyze the risk factors of massive hemorrhage in patients with renal cell carcinoma and venous tumor thrombus undergoing radical nephrectomy and removal of venous tumor thrombus. METHODS: From January 2014 to June 2020, 241 patients with renal cancer and tumor thrombus in a single center of urology at Peking University Third Hospital were retrospectively analyzed. All patients underwent radical nephrectomy and removal of venous tumor thrombus. The relevant preoperative indicators, intraoperative conditions, and postoperative data were statistically analyzed by using statistical software of SPSS 18.0. The main end point of the study was intraoperative bleeding volume greater than 2 000 mL. Logistic regression analysis was used to determine the relevant influencing factors. First, single factor Logistic regression was used for preliminary screening of influencing factors, and variables with single factor Logistic regression analysis P < 0.05 were included in multivariate Logistic regression. In all statistical analyses, P < 0.05 is considered statistically significant. RESULTS: Among the 241 patients included, there were 60 cases of massive hemorrhage, 48 males and 12 females, with a median age of 62 years. The number of non-massive hemorrhage was 181. There were 136 males and 45 females, with a median age of 59 years. Univariate analysis showed that the clinical symptoms (both systemic and local symptoms, OR 2.794, 95%CI 1.087-7.181, P=0.033), surgical approach (open surgery, OR 9.365, 95%CI 4.447-19.72, P < 0.001), Mayo grade (Mayo 3-4, OR 5.257, 95%CI 2.806-10.886, P < 0.001), American Society of Anesthesiologists (ASA) score (ASA level 3, OR 2.842, 95%CI 1.338-6.036, P=0.007), preoperative hemoglobin (OR 0.978, 95%CI 0.965-0.991, P=0.001), preoperative platelet count (OR 0.996, 95%CI 0.992-1.000, P=0.037), maximum tumor thrombus width (OR 1.061, 95%CI 1.033-1.091, P < 0.001), Complicated with bland thrombus (OR 4.493, 95%CI 2.264-8.915, P < 0.001), adrenalectomy (OR 3.101, 95%CI 1.614-5.958, P=0.001), segmental resection of the inferior vena cava (OR 2.857, 95%CI 1.395-5.852, P=0.004). There was a statistically significant difference in these aspects(P < 0.05). Multivariate Logistic regression analysis showed that there was a statistically significant difference in surgical approach (open surgery, OR 6.730, 95%CI 2.947-15.368;P < 0.001), Mayo grade (Mayo 3-4, OR 2.294, 95%CI 1.064-4.948, P=0.034), Complicated with bland thrombus (OR 3.236, 95%CI 1.492-7.020, P=0.003). CONCLUSION: Combining the results of univariate and multivariate Logistic regression analysis, the surgical approach, Mayo grade, and tumor thrombus combined with conventional thrombus were associated risk factors for massive hemorrhage during surgery for renal cell carcinoma with tumor thrombus. Patients who undergo open surgery, high Mayo grade, and tumor thrombus combined with conventional thrombus are at a relatively higher risk of massive hemorrhage.

Breaking down tumor thrombus: Current strategies for medical management.

Tumor thrombus, the intravascular extension of tumor into adjacent blood vessels, is frequently encountered in patients with renal cell carcinoma and hepatocellular carcinoma, and often involves the abdominal vasculature including the renal vein, portal vein, and the inferior vena cava. While a bland thrombus is composed of platelets and fibrin, in contrast, a tumor thrombus refers to an organized collection of tumor cells. Though oftentimes detected incidentally on imaging, tumor thrombus may have significant clinical implications and can be challenging to differentiate from bland thrombus. Additionally, the optimal management of tumor thrombus, including the use of anticoagulation, remains poorly described. This review summarizes common causes of tumor thrombus, as well as its impact on staging, prognosis, and treatment.

Venous tumor thrombus consistency: is it a prognostic factor of survival for patients with renal cell carcinoma?

OBJECTIVES: To evaluate whether venous tumor thrombus (VTT) consistency is a risk factor for the patient's prognosis with renal cell carcinoma (RCC). MATERIALS AND METHODS: A total of 190 RCC patients with VTT, who were treated at Department of Urology, Chinese PLA General Hospital, were retrospectively analyzed in this study. The baseline clinical characteristics, postoperative outcomes, and pathological findings were analyzed. Tumor thrombus was classified as solid and friable based on their respective characteristics. Survival curves were estimated using the Kaplan-Meier survival curve analysis, and univariable and multivariable cox proportional hazard regression models were used. RESULTS: Among the total 190 patients included in this study, 145 (76.3%) patients had solid VTT, and 45 (23.7%) patients had friable VTT in their renal veins and inferior vena cava (IVC). There were no significant differences in the age, gender, BMI, symptoms, complex diseases, tumor side, tumor size, TNM stage, Mayo stage, tumor grade, sarcomatous differentiation, pelvic invasion, and sinus fat invasion of patients. Solid VTT consistency was more likely to have a capsule as compared to those with friable VTT (P = 0.007). Kaplan-Meier survival curve analysis demonstrated no statistically significant differences in the overall survival (OS) (P = 0.973) and progression-free survival (PFS) (P = 0.667) of patients. Moreover, VTT consistency was not associated with OS (P = 0.706) of PFS (P = 0.504) in multivariate cox regression analysis. CONCLUSIONS: RCC VTT consistency was not a prognostic risk factor for predicting the OS and PFS of patients.

Development and validation of a prognostic model incorporating tumor thrombus grading for nonmetastatic clear cell renal cell carcinoma with tumor thrombus: A multicohort study.

There is significant variability with respect to the prognosis of nonmetastatic clear cell renal cell carcinoma (ccRCC) patients with venous tumor thrombus (VTT). By applying multiregion whole-exome sequencing on normal-tumor-thrombus-metastasis quadruples from 33 ccRCC patients, we showed that metastases were mainly seeded by VTT (81.8%) rather than primary tumors (PTs). A total of 706 nonmetastatic ccRCC patients with VTT from three independent cohorts were included in this study. C-index analysis revealed that pathological grading of VTT outperformed other indicators in risk assessment (OS: 0.663 versus 0.501-0.610, 0.667 versus 0.544-0.651, and 0.719 versus 0.511-0.700 for Training, China-Validation, and Poland-Validation cohorts, respectively). We constructed a risk predicting model, TT-GPS score, based on four independent variables: VTT height, VTT grading, perinephric fat invasion, and sarcomatoid differentiation in PT. The TT-GPS score displayed better discriminatory ability (OS, c-index: 0.706-0.840, AUC: 0.788-0.874; DFS, c-index: 0.691-0.717, AUC: 0.771-0.789) than previously reported models in risk assessment. In conclusion, we identified for the first-time pathological grading of VTT as an unheeded prognostic factor. By incorporating VTT grading, the TT-GPS score is a promising prognostic tool in predicting the survival of nonmetastatic ccRCC patients with VTT.

Based on disulfidptosis, revealing the prognostic and immunological characteristics of renal cell carcinoma with tumor thrombus of vena cava and identifying potential therapeutic target AJAP1.

BACKGROUND: Patients with clear cell renal cell carcinoma (ccRCC) with venous tumor thrombus have a poor prognosis, high surgical risk, and lack of targeted therapeutic agents. METHODS: Genes with consistent differential expression trends in tumor tissues and VTT groups were first screened, and then differential genes associated with disulfidptosis were found by correlation analysis. Subsequently, identifying ccRCC subtypes and constructing risk models to compare the differences in prognosis and the tumor microenvironment in different subgroups. Finally, constructing a nomogram to predict the prognosis of ccRCC and validate key gene expression levels in cells and tissues. RESULTS: We screened 35 differential genes related to disulfidptosis and identified 4 ccRCC subtypes. Risk models were constructed based on the 13 genes, and the high-risk group had a higher abundance of immune cell infiltration, tumor mutational load, and microsatellite instability scores, predicting high sensitivity to immunotherapy. The 1-year AUC = 0.869 for predicting OS by nomogram has a high application value. The expression level of the key gene AJAP1 was low in both tumor cell lines and cancer tissues. CONCLUSIONS: Our study not only constructed an accurate prognostic nomogram for ccRCC patients but also identified an AJAP1 biomarker as a potential biomarker for the disease.

Pure Retroperitoneal Laparoscopic Peritoneum Incision Technique in Right Nephrectomy and Inferior Vena Cava Tumor Thrombectomy: A Novel Surgical Technique and Long-Term Outcomes from a Large Chinese Center.

Purpose: To explore the safety and effectiveness of the Pure Retroperitoneal Laparoscopic Peritoneum Incision Technique (PREP-IT) in laparoscopic radical nephrectomy (LRN) and inferior vena cave (IVC) tumor thrombectomy for right renal-cell carcinoma (RCC) with level Mayo I to III venous tumor thrombus (VTT). Patients and Methods: From May 2015 to September 2020, 92 patients with right RCC and Mayo I to III VTT were retrospectively reviewed, including 57 patients who underwent retroperitoneal LRN and IVC thrombectomy using PREP-IT, and 35 patients who underwent open surgery. PREP-IT refers to dissecting the retroperitoneum and temporarily placing the right kidney into the abdominal cavity to enlarge the retroperitoneal workspace for a safer and faster IVC operation. Results: Compared with the open surgery group, the PREP-IT group had a larger tumor diameter, while a larger proportion of Mayo I tumor thrombus and smaller maximum tumor thrombus width. Two patients (3.5%) in the PREP-IT group had a history of abdominal surgery. No conversion to open surgery or standard laparoscopic surgery occurred in PREP-IT group. Laparoscopic surgery with PREP-IT was characterized by shorter operative time, less surgical blood loss, shorter postoperative hospital stay, and lower postoperative complication rate. With a 33-month (ranges: 2-86) follow-up time period, the estimated mean overall survival time was 57.2 ± 5.3 and 58.1 ± 71.5 months in the PREP-IT group and open surgery group, respectively. Log-rank test indicated no significant difference between the two groups in terms of overall survival and cancer-specific survival. Conclusions: The PREP-IT is relatively safe and feasible for retroperitoneal LRN with right renal tumor and IVC tumor thrombus, allowing for a large workspace and wide exposure for IVC operations.

Integrative analysis of transcriptomic landscape and urinary signature reveals prognostic biomarkers for clear cell renal cell carcinoma.

Background: Clear cell renal cell carcinoma (ccRCC) patients with venous tumor thrombus (VTT) have poor prognosis. We aimed to reveal features of ccRCC with VTT and develop a urine-based prognostic classifier to predict ccRCC prognosis through integrative analyses of transcriptomic landscape and urinary signature. Methods: RNA sequencing was performed in five patients with ccRCC thrombus-tumor-normal tissue triples, while mass spectrometry was performed for urine samples from 12 ccRCC and 11 healthy controls. A urine-based classifier consisting of three proteins was developed to predict patients' survival and validated in an independent cohort. Results: Transcriptomic analysis identified 856 invasion-associated differentially expressed genes (DEGs). Furthermore, proteomic analysis showed 133 differentially expressed proteins (DEPs). Integration of transcriptomic landscape and urinary signature reveals 6 urinary detectable proteins (VSIG4, C3, GAL3ST1, TGFBI, AKR1C3, P4HB) displaying abundance changes consistent with corresponding genes in transcriptomic profiling. According to TCGA database, VSIG4, TGFBI, and P4HB were significantly overexpressed in patients with shorter survival and might be independent prognostic factors for ccRCC (all p<0.05). A prognostic classifier consisting of the three DEPs highly associated with survival performed satisfactorily in predicting overall survival (HR=2.0, p<0.01) and disease-free survival (HR=1.6, p<0.001) of ccRCC patients. The ELISA analysis of urine samples from an independent cohort confirmed the satisfied predictive power of the classifier for pathological grade (AUC=0.795, p<0.001) and stage (AUC=0.894, p<0.001). Conclusion: Based on integrative analyses of transcriptomic landscape and urinary signature, the urine-based prognostic classifier consisting of VSIG4, TGFBI, and P4HB has satisfied predictive power of ccRCC prognosis and may facilitate ccRCC molecular subtyping and treatment.

[Application of Intraoperative Transesophageal Echocardiography in the Treatment of Renal Cell Carcinoma with Inferior Vena Cava Tumor Thrombus].

Objective To investigate the value of intraoperative transesophageal echocardiography (TEE) in the diagnosis and treatment of renal cell carcinoma with inferior vena cava tumor thrombus. Methods Ten patients of renal cell carcinoma with inferior vena cava tumor thrombus treated in the Second Hospital of Hebei Medical University from January 2017 to January 2021 were selected.TEE was employed to locate the position of the tumor thrombus,determine the occlusion point of the inferior vena cava,count the intraoperative tumor thrombus shedding rate,examine the tumor thrombus resection integrity,and measure blood loss and other indicators,on the basis of which the application value of TEE in the operation of renal cell carcinoma with inferior vena cava tumor thrombus was evaluated. Results All the 10 patients had completed the operations successfully,including 8 patients of open operation and 2 patients of laparoscopic operation.TEE showed tumor thrombi clearly,and all the tumor thrombi were completely removed.There was no tumor thrombus shedding during the operation.The blood loss varied within the range of 300-800 ml,with the mean of (520.0±193.2) ml.The grade III tumor thrombi in 2 patients and the grade I tumor thrombus in 1 patient diagnosed before operation were reduced to grade Ⅱ and upgraded to grade Ⅱ,respectively,by TEE.One patient had no floating tumor thrombus at the end of tumor thrombus before operation,and the blocking position was adjusted in time with the assistance of TEE to avoid the shedding of the floating tumor thrombus. Conclusion TEE can accurately determine and dynamically monitor the location and shape of inferior vena cava tumor thrombus,which provides an important reference and has a significant clinical value in the operation of renal cell carcinoma with inferior vena cava tumor thrombus.

Adjuvant anti-PD-1 antibody for hepatocellular carcinoma with high recurrence risks after hepatectomy.

BACKGROUND AND PURPOSE: The clinical role of postoperative adjuvant therapy in hepatocellular carcinoma (HCC) is still unclear. The purpose of our study was to explore the clinical value of postoperative adjuvant anti-programed cell death 1 antibody (PA-PD-1) on the prognosis of HCC patients with high relapse risks after surgery. PATIENTS AND METHODS: Data of consecutive HCC patients with high recurrence risks treated with liver resection at our center during January 2019 and March 2021 were prospectively collected. Baseline differences were balanced between HCC patients with (PA-PD-1 group) or without PA-PD-1 (non-PD-1 group) after hepatectomy by propensity-score matching (PSM). Between these two groups, we compared overall survival (OS) and recurrence-free survival (RFS). Independent prognostic risk factors for OS and RFS were confirmed by Cox regression analysis, and subgroup analysis was also performed. RESULTS: 47 pairs of patients with or without PD-1 treatment after hepatectomy were matched. After PSM, the 1-year and 2-year RFS was 58.4% and 44.1% in the PA-PD-1 group, and 34.0% and 21.3% in the non-PD-1 group (p = 0.008). The OS at 1 year and 2 years was 91.2% and 91.2% in the PA-PD-1 group, compared with 85.1% and 61.7% in the non-PD-1 group (p = 0.024). Multivariable analyses demonstrated that PA-PD-1 was an independent protective predictor associated with RFS and OS. Through subgroup analysis, we concluded that HCC patients with portal venous tumor thrombus (PVTT) or tumor size ≥ 5 cm significantly benefited from PA-PD-1 therapy in RFS and OS. CONCLUSIONS: Adjuvant anti-PD-1 antibody can effectively improve the survival outcomes of HCC patients with high relapse risks after hepatectomy in this prospective observational study. This finding should be confirmed by results of the ongoing phase 3 randomized controlled trials.

Initial experience in robot-associated radical nephrectomy with inferior vena cava tumor thrombectomy.

Background: Renal cell carcinoma (RCC) is often locally invasive and may extend from the renal vein into the inferior vena cava (IVC) as a venous tumor thrombus (VTT). Radical nephrectomy with IVC tumor thrombectomy (IVC-TT) via an open approach has been shown to carry high morbidity and mortality. Recently, robot-associated radical nephrectomy (RARN) has been developed with the aim of improving the performance and outcomes of surgery for RCC with IVC-VTT. Methods: We here present four patients who had right RCC with IVC-VTT and underwent RARN with IVC-TT in Nagasaki University Hospital. All four patients had level II IVC-TT and underwent RARN with IVC-TT using a da Vinci Xi surgical system. The procedure comprised performing the Kocher maneuver, exposing the right renal artery in the aortocaval region dorsal to the left renal vein, exposing, mobilizing, and clipping the IVC, clamping and incising the IVC, and removing the kidney with the VTT en bloc. Results: The mean tumor size was 83.1 (range, 50.1-115.2) mm and the mean length of the VTT within the IVC 41.6 (range, 25.3-44.3) mm. The mean console time was 290 (range, 287-367) minutes and the mean blood loss was 200 (range, 175-260) mL and no patient required blood transfusion. Conclusions: Our initial experience of the procedure of RARN with IVC-TT for level II IVC-VTT is that it is safe and has acceptable perioperative outcomes and complications.

Review of Robotic-Assisted Radical Nephrectomy with Inferior Vena Cava Thrombectomy in Renal Cell Carcinoma.

PURPOSE OF REVIEW: Recent advances in minimally invasive technology have compelled surgeons to perform nephrectomy with inferior vena cava thrombectomy using robotic assistance. Here, we aim to review the data comparing open versus robot-assisted nephrectomy with IVC thrombectomy, as well as review operative robotic techniques for nephrectomy with IVC thrombectomy. RECENT FINDINGS: Over the last decade, there have been increasing reports of successful robotic-assisted IVC thrombectomy among skilled robotic surgeons, with case series detailing operative technique, as well as operative and oncologic outcomes for levels I-IV caval thrombus. While there is immense promise in the future of robotic-assisted IVC thrombectomy, further studies with direct comparison to open surgical intervention will be needed to ensure the oncologic principles and outcomes are non-inferior.

Diagnostic performance and prognostic value of preoperative 18F-FDG PET/CT in renal cell carcinoma patients with venous tumor thrombus.

BACKGROUND: To observe the diagnostic efficacy of preoperative fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) upon venous tumor thrombus (VTT) in patients with renal cell carcinoma (RCC), and investigate the prognostic value of imaging parameters integrated with clinicopathological characteristics in patients with VTT after nephrectomy with tumor thrombectomy. METHODS: Patients with newly diagnosed RCC who underwent 18F-FDG PET/CT were reviewed retrospectively. The diagnostic efficacy of 18F-FDG PET/CT in VTT was analyzed. Logistic regression analysis was carried out to identify the clinical variables and PET/CT variables (including maximum standardized uptake value (SUVmax) of primary tumor, VTT SUVmax and primary tumor size) for differentiating early VTT (Mayo 0-II) from advanced VTT (Mayo III-IV). Cox proportional hazard analyses were used to evaluate clinicopathological factors and PET/CT factors (including distant metastasis, primary tumor SUVmax, VTT SUVmax and primary tumor size) for disease-free survival (DFS) in patients with VTT after operation. RESULTS: A total of 174 eligible patients were included in this study, including 114 men (65.5%) and 60 women (34.5%), with a median age of 58 years (range, 16-81 years). The distribution of pathological tumor stage (T stage) was 56 (T1), 17 (T2), 95 (T3), and 6 cases (T4), respectively. According to WHO/ISUP grade, except for 4 cases of chromophobe cell RCC, there were 14 patients (8.0%) of grade 1, 59 patients (33.9%) of grade 2, 74 patients (42.5%) of grade 3 and 23 patients (13.2%) of grade 4. The median maximum diameter of the primary tumor on PET/CT was 7.3 cm (5.0-9.5 cm). The distal metastasis was observed in 46 patients (26.4%). Sixty-one cases (35.1%) were confirmed with VTT by pathology. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 18F-FDG PET/CT imaging were 96.7, 99.1, 98.3, 98.3, and 98.2%, in detecting VTT, respectively, and 70.0, 100.0, 94.9, 100.0, and 94.2%, in evaluating the level of VTT, respectively. Elevated VTT SUVmax (≥5.20) could significantly distinguish the early VTT group and advanced VTT group (P = 0.010). In the prognosis analysis, elevated VTT SUVmax (≥4.30) (P = 0.018, HR 3.123, 95% CI 1.212-8.044) and distant metastasis (P = 0.013, HR 3.344, 95% CI 1.293-8.649) were significantly independent predictors for DFS. CONCLUSION: Preoperative 18F-FDG PET/CT has a high diagnostic efficacy in detecting VTT and evaluating its level in RCC patients. Those patients with elevated VTT SUVmax should be carefully monitored to detect the possibility of disease progression after operation.

Nomograms for Predicting Overall Survival and Cancer-Specific Survival of Patients With Renal Cell Carcinoma and Venous Tumor Thrombus: A Population-Based Study.

Background: To provide better prognostic information for patients with renal cell carcinoma (RCC) combined with venous tumor thrombus (VTT). In turn, guide patients' families and doctors to formulate plans for follow-up treatment and follow-up. We developed nomograms to predict cancer-specific survival (CSS) and overall survival (OS). Methods: A total of 2961 cases were included in this study. Through univariate and multivariate Cox proportional hazard regression analysis, independent risk factors affecting CSS and OS were screened out, and then a nomogram was drawn based on the screened variables. Results: Independent risk factors affecting CSS include: tumor size (HR = 1.05), histology (HR = 1.75), grade (HR = 1.94), N staging (HR = 2.06), and M staging (HR = 2.87). The median survival time for CSS was 106 months. Independent risk factors for OS include age (HR = 1.60), tumor size (HR = 1.04), histology (HR = 1.60), grade (HR = 1.68), N staging (HR-1.99), M staging (HR = 2.45). The median survival time for OS is 67 months. Conclusions: The nomogram based on independent risk factors affecting CSS and OS can well predict the prognosis of renal cell carcinoma with venous tumor thrombus.

The Latinx Disparity in Surgery for Kidney Cancer: Data from The South Texas Region.

The South Texas region, with a predominantly Latinx population, has a very high incidence of renal cell carcinoma (RCC), including those with tumor extending into the major blood vessels called venous tumor thrombus (VTT). There is currently no data on outcomes of Latinx patients with VTT as most published studies are from predominantly Caucasian population. Therefore, we performed this study to fill an urgent, unmet need. We reviewed patients who underwent radical nephrectomy with removal of VTT (called tumor thrombectomy) between 2015 and 2020. We collected data on demographics, clinical, pathological characteristics and outcomes of patients. Univariate and multivariate Cox regression analyses were used to evaluate the associations between ethnicity and disease progression or survival. We identified 112 patients, of which 67 (62%) were Latinx, and 41 (38%) were non-Latinx. Approximately 60% of patients had Level II-IV VTT; Latinx presented with a higher level of tumor thrombus (p=0.046). Latinx patients had a higher rate of no insurance (11% vs. 27%, p=0.04) and were more likely to lost to follow-up after surgery (22.4% vs. 13.3%, p=0.23) compared to non-Latinx. Fewer Latinx received systemic therapy (28% vs. 42%; p=0.13). Ninety-day mortality for the entire cohort was 3.8%. The Latinx population in the South Texas region present late, with advanced thrombus level, and do not have access to systemic therapy. Given symptomatic disease, surgical treatment, if feasible, is their only option. Our results highlight disparate treatment patterns which require further investigation and health-care policy changes.

Influence of Deep Invasive Tumor Thrombus on the Surgical Complexity and Prognosis of Patients With Non-Metastatic Renal Cell Carcinoma Combined With Venous Tumor Thrombus.

BACKGROUND: To evaluate the impact of deep invasive tumor thrombus (DITT) on the surgical complexity and prognosis of patients with renal cell carcinoma with venous tumor thrombus. METHODS: We retrospectively reviewed clinical data of 138 patients with non-metastatic renal cell carcinoma combined with venous tumor thrombus, who underwent surgical treatment in Peking University Third Hospital from January 2015 to June 2020. Patients were divided into the DITT group (84 patients) and non-invasive tumor thrombus (NITT) group (54 patients). Chi-square, t-test and Mann-Whitney U test were used for categorical and continuous variables, respectively. Kaplan-Meier plots were performed to evaluate the influence of DITT. Univariable and multivariable Cox regressions were conducted to determine independent prognostic factors and then assembled to make a nomogram to predict the survival. The performance of the nomogram was evaluated by Harrell's consistency index (C-index) and calibration plot. RESULTS: Deep invasive tumor thrombus significantly increased the difficulty of surgery for patients with renal cell carcinoma with venous tumor thrombus, which is mainly reflected in longer operation time (p < 0.001), more surgical bleeding (p  < 0.001), a higher proportion of perioperative blood transfusion (p  = 0.006), a higher proportion of open surgery (p = 0.001), a longer postoperative hospital stay (p = 0.003), and a higher proportion of postoperative complications (p = 0.001). DITT (hazard ratio [HR] = 2.781, p = 0.040) was one of the independent risk factors for worse prognosis. Multivariate analysis showed that sarcoma-like differentiation (p = 0.040), tumor thrombus invasion (p = 0.040), low hemoglobin (p = 0.003), and pathological type (p < 0.001) were independent prognostic factors. The nomogram, combining all these predictors, showed powerful prognostic ability with a C-index of 78.8% (CI: 71.2%-86.4%). The predicted risk closely matches the observed recurrence probability. CONCLUSION: Deep invasive tumor thrombus significantly increased the difficulty of surgeries for patients of renal cell carcinoma with venous tumor thrombus, and may lead to poor prognosis.