Objective:To review the clinicopathological features of TFE3-rearranged renal cell carcino-ma(TFE3-RCC)with venous tumor thrombus(VT)(TFE3-VT),to explore treatment strategies and to prognostic characteristics,and to provide diagnostic and therapeutic references for TFE3-VT patients.Methods:Patients who underwent surgery at Department of Urology,Peking University Third Hospital from January 2013 to January 2024 were enrolled,including three cohorts:Pathologically confirmed TFE3-VT patients,TFE3-RCC patients without VT(TFE3-non-VT),and non-TFE3-rearranged renal cell carcinoma patients with VT(non-TFE3-VT).Clinical history,imaging data,pathological data,and follow-up records were collected.Primary and secondary endpoints were progression-free survival(PFS)and overall survival(OS),respectively.(1)Baseline characteristics were compared between the TFE3-VT and TFE3-non-VT patients.Normally distributed continuous variables were expressed as mean±SD and compared using Student's t-test;non-normally distributed variables were expressed as M(P25,P75)and analyzed with Mann-Whitney U test;categorical variables were described as frequency and percentage[n(％)]and compared by x2 test or Fisher's exact test.(2)Clinical history,radiological presenta-tions,surgical data,and histopathological features of the TFE3-VT patients were comprehensively charac-terized.(3)Survival analysis was performed for the TFE3-VT patients.Follow-up data of the TFE3-VT patients were described in detail,and their survival outcomes were compared with the TFE3-non-VT and non-TFE3-VT patients.When compared with the TFE3-non-VT counterparts,Kaplan-Meier method was used to generate PFS and OS curves among:(1)the TFE3-RCC patients across clinical stages Ⅰ-Ⅳ;(2)TFE3-VT versus TFE3-non-VT cohorts;(3)stage Ⅲ subgroups of the TFE3-VT and TFE3-non-VT patients.Intergroup survival differences were statistically evaluated using Log-rank tests.For comparisons with the non-TFE3-VT patients,a 1∶1 propensity score matching(PSM)was implemented to balance baseline characteristics between the two cohorts.Post-matching Kaplan-Meier curves were generated to compare PFS and OS between the matched groups,with Log-rank tests employed to determine statistical significance of survival disparities.All statistical analyses were conducted with R software(v 4.2.3),and two-tailed P＜0.05 was considered statistically significant.Results:The study included 45 TFE3-RCC patients:13 TFE3-VT and 32 TFE3-non-VT cases.Additionally,523 non-TFE3-VT patients were enrolled.Among the 13 TFE3-VT patients,9 were female(69.2％)and 4 male(30.8％),with a mean age of(37.9±14.4)years,mean BMI of(22.2±3.5)kg/m2,median age-adjusted Charlson comorbidity index(aCCI)of 1.0(0.0,1.0),and preoperative creatinine level of(75.3±15.9)μmol/L;tumors were located in the left kidney in 7 patients(53.8％)and right kidney in 6(46.2％);preoperative distant metastasis(M1 stage)was present in 6 patients(46.2％),while 7(53.8％)showed no metastasis;VT distribution by Mayo level comprised 7 cases(53.8％)at level 0,1 case each at levels Ⅰ and Ⅳ(7.7％respectively),and 2 cases each at levels Ⅱ and Ⅲ(15.4％respectively);surgical approaches comprised open surgery(n=2,15.4％),laparoscopic surgery(n=6,46.1％),and robot-assisted laparoscopic surgery(n=5,38.5％);mean operative time was(273±79)min,and intraoperative blood loss was(722±570)mL;mean maximum tumor diameter was(10.8±2.4)cm.All the 13 patients underwent TFE3 protein immunohistochemistry(IHC)staining,with 7 confirmed by fluorescence in situ hybridization(FISH).Tumor recurrence or metastasis occurred in 11 patients(84.6％),and 9(69.2％)patients died during follow-up.Median PFS was 4 months(1 year PFS rate:31％),and median OS was 13 months(1 year OS rate:54％).Survival analysis of 45 TFE3-RCC pa-tients revealed statistically significant differences in PFS and OS across all the clinical stages(P＜0.001).The TFE3-VT patients exhibited significantly worse PFS and OS than the TFE3-non-VT patients(P＜0.001),with persistent significance in stage Ⅲ subgroup analysis(P＜0.05).After PSM,TFE3-VT pa-tients showed significantly inferior PFS compared with non-TFE3-VT(P=0.01),though no significant difference was shown between the OS curves(P=0.11).Conclusion:TFE3-VT predominantly occurs in young females with frequent preoperative metastases.Strongly-positive staining of TFE3 protein in IHC stai-ning and red-green split signals in FISH tests are reliable diagnostic markers.TFE3-VT patients exhibit in-ferior survival compared with TFE3-non-VT patients and earlier progression than non-TFE3-VT patients.

Objective:To review the clinicopathological features of TFE3-rearranged renal cell carcino-ma(TFE3-RCC)with venous tumor thrombus(VT)(TFE3-VT),to explore treatment strategies and to prognostic characteristics,and to provide diagnostic and therapeutic references for TFE3-VT patients.Methods:Patients who underwent surgery at Department of Urology,Peking University Third Hospital from January 2013 to January 2024 were enrolled,including three cohorts:Pathologically confirmed TFE3-VT patients,TFE3-RCC patients without VT(TFE3-non-VT),and non-TFE3-rearranged renal cell carcinoma patients with VT(non-TFE3-VT).Clinical history,imaging data,pathological data,and follow-up records were collected.Primary and secondary endpoints were progression-free survival(PFS)and overall survival(OS),respectively.(1)Baseline characteristics were compared between the TFE3-VT and TFE3-non-VT patients.Normally distributed continuous variables were expressed as mean±SD and compared using Student's t-test;non-normally distributed variables were expressed as M(P25,P75)and analyzed with Mann-Whitney U test;categorical variables were described as frequency and percentage[n(％)]and compared by x2 test or Fisher's exact test.(2)Clinical history,radiological presenta-tions,surgical data,and histopathological features of the TFE3-VT patients were comprehensively charac-terized.(3)Survival analysis was performed for the TFE3-VT patients.Follow-up data of the TFE3-VT patients were described in detail,and their survival outcomes were compared with the TFE3-non-VT and non-TFE3-VT patients.When compared with the TFE3-non-VT counterparts,Kaplan-Meier method was used to generate PFS and OS curves among:(1)the TFE3-RCC patients across clinical stages Ⅰ-Ⅳ;(2)TFE3-VT versus TFE3-non-VT cohorts;(3)stage Ⅲ subgroups of the TFE3-VT and TFE3-non-VT patients.Intergroup survival differences were statistically evaluated using Log-rank tests.For comparisons with the non-TFE3-VT patients,a 1∶1 propensity score matching(PSM)was implemented to balance baseline characteristics between the two cohorts.Post-matching Kaplan-Meier curves were generated to compare PFS and OS between the matched groups,with Log-rank tests employed to determine statistical significance of survival disparities.All statistical analyses were conducted with R software(v 4.2.3),and two-tailed P＜0.05 was considered statistically significant.Results:The study included 45 TFE3-RCC patients:13 TFE3-VT and 32 TFE3-non-VT cases.Additionally,523 non-TFE3-VT patients were enrolled.Among the 13 TFE3-VT patients,9 were female(69.2％)and 4 male(30.8％),with a mean age of(37.9±14.4)years,mean BMI of(22.2±3.5)kg/m2,median age-adjusted Charlson comorbidity index(aCCI)of 1.0(0.0,1.0),and preoperative creatinine level of(75.3±15.9)μmol/L;tumors were located in the left kidney in 7 patients(53.8％)and right kidney in 6(46.2％);preoperative distant metastasis(M1 stage)was present in 6 patients(46.2％),while 7(53.8％)showed no metastasis;VT distribution by Mayo level comprised 7 cases(53.8％)at level 0,1 case each at levels Ⅰ and Ⅳ(7.7％respectively),and 2 cases each at levels Ⅱ and Ⅲ(15.4％respectively);surgical approaches comprised open surgery(n=2,15.4％),laparoscopic surgery(n=6,46.1％),and robot-assisted laparoscopic surgery(n=5,38.5％);mean operative time was(273±79)min,and intraoperative blood loss was(722±570)mL;mean maximum tumor diameter was(10.8±2.4)cm.All the 13 patients underwent TFE3 protein immunohistochemistry(IHC)staining,with 7 confirmed by fluorescence in situ hybridization(FISH).Tumor recurrence or metastasis occurred in 11 patients(84.6％),and 9(69.2％)patients died during follow-up.Median PFS was 4 months(1 year PFS rate:31％),and median OS was 13 months(1 year OS rate:54％).Survival analysis of 45 TFE3-RCC pa-tients revealed statistically significant differences in PFS and OS across all the clinical stages(P＜0.001).The TFE3-VT patients exhibited significantly worse PFS and OS than the TFE3-non-VT patients(P＜0.001),with persistent significance in stage Ⅲ subgroup analysis(P＜0.05).After PSM,TFE3-VT pa-tients showed significantly inferior PFS compared with non-TFE3-VT(P=0.01),though no significant difference was shown between the OS curves(P=0.11).Conclusion:TFE3-VT predominantly occurs in young females with frequent preoperative metastases.Strongly-positive staining of TFE3 protein in IHC stai-ning and red-green split signals in FISH tests are reliable diagnostic markers.TFE3-VT patients exhibit in-ferior survival compared with TFE3-non-VT patients and earlier progression than non-TFE3-VT patients.

Objective:To investigate the treatment efficacy of adjuvant anti-VEGF/VEGFR targeted therapy in patients with non-metastatic (cM 0) non-clear cell renal cell carcinoma and tumor thrombus (nccRCC-VTT). Methods:This retrospective study enrolled 26 patients who underwent radical nephrectomy combined with inferior vena cava tumor thrombectomy at Peking University Third Hospital from January 2014 to July 2021. Patients were divided into adjuvant therapy group (10 cases) and control group (16 cases)based on the use of postoperative targeted therapy. The distribution of baseline clinical characteristics in the adjuvant therapy group and the control group were as follows: gender (6 males and 4 females in the adjuvant therapy group, 12 males and 4 females in the control group, P=0.66), age (56.2±18.5 years old in the adjuvant therapy group; 54.6±14.5 years old in the control group; P=0.80), BMI(24.0±3.5 in the adjuvant therapy group; 24.3±3.3 in the control group; P=0.80), presence of clinical symptoms (8 cases in the adjuvant therapy group; 15 cases in the control group; P=0.54), tumor laterality(6 cases on the left and 4 cases on the right in the adjuvant therapy group; 6 cases on the left and 10 cases on the right in the control group; P=0.42), location of tumor thrombus (2 cases with renal vein tumor thrombus and 8 cases with inferior vena cava tumor thrombus in the adjuvant therapy group; 2 cases with renal vein tumor thrombus and 14 cases with inferior vena cava tumor thrombus in the control group; P=0.67), ASA classification (2 cases in ASA class 1 and 8 cases in ASA class 2 in the adjuvant therapy group; 2 cases in ASA class 1 and 14 cases in ASA class 2 in the control group; P=0.63), surgical approach (7 minimally invasive surgeries and 3 open surgeries in the adjuvant therapy group; 9 minimally invasive surgeries and 7 open surgeries in the control group; P=0.68), conversion to open surgery (2 cases in the adjuvant therapy group; 2 cases in the control group; P=0.63), operation time [287.5(222.2, 456.0) minutes in the adjuvant therapy group; 344.0(287.8, 482.5) minutes in the control group; P=0.34), blood loss [400.0(250.0, 600.0)ml in the adjuvant therapy group; 575.0(175.0, 800.0)ml in the control group; P=0.63), Clavien-Dindo classification of postoperative complications (8 cases with no postoperative complications, 2 cases with level 1-2 complications, and 0 cases with level ≥3 complications in the adjuvant therapy group; 10 cases with no postoperative complications, 4 cases with level 1-2 complications, and 2 cases with level ≥3 complications in the control group; P=0.68), postoperative hospital stay (8.5 [5.5, 11.5] days in the adjuvant therapy group; 7.5 [6.0, 13.0] days in the control group; P=1.00), maximum tumor diameter[ (9.2±2.7)cm in the adjuvant therapy group; (8.9±3.3)cm in the control group; P=0.81], sarcomatoid differentiation (0 cases in the adjuvant therapy group; 1 case in the control group; P=1.00), perinephric fat invasion (2 cases in the adjuvant therapy group; 7 cases in the control group; P=0.40), tumor necrosis (6 cases in the adjuvant therapy group; 5 cases in the control group; P=0.23), pathological subtype (1 case of PRCC type 1, 6 cases of PRCC type 2, and 3 cases of TFE3 rearrangement RCC in the adjuvant therapy group; 2 cases of PRCC type 1, 10 cases of PRCC type 2, and 1 case each of oncocytic PRCC, TFE3 rearrangement RCC, FH-deficient RCC, and unclassified RCC in the control group; P=0.72), WHO/ISUP nuclear grade (10 cases of grades 3-4 in the adjuvant therapy group; 4 cases of grades 1-2 and 12 cases of grades 3-4 in the control group; P=0.14), invasion of tumor thrombus into the vessel wall (5 cases in the adjuvant therapy group; 5 cases in the control group; P=0.43), T stage (1 case of T 3a, 3 cases of T 3b, 5 cases of T 3c, and 1 case of T 4 in the adjuvant therapy group; 1 case of T 3a, 4 cases of T 3b, 10 cases of T 3c, and 1 case of T 4 in the control group; P=1.00), and positive lymph nodes metastasis(3 cases in the adjuvant therapy group; 0 cases in the control group; P<0.05). The recommended doses for sunitinib, axitinib, and pazopanib are 50mg qd, 5mg q12h, and 800mg qd, respectively. The primary endpoint of this study was disease-free survival (DFS), and the secondary endpoint was overall survival (OS). Statistical analyses were performed using R v4.2.2. Confounding factors were adjusted using propensity score weighting. Results:The median follow-up time for DFS was 29 months in the adjuvant therapy group and not reached in the control group, while median follow-up time for OS was 28 and 26 months, respectively. In the univariate Cox regression analysis, there were no statistically significant difference in the impact of all baseline characteristics and exposure factors on DFS and OS between the two groups. In survival analysis, there were no significant difference between DFS and OS curves of patients in the adjuvant therapy group and the control group (DFS, P=0.62; OS, P=0.74). The median DFS of patients in the adjuvant therapy group and the control group were 17 and 19 months, respectively, while the median OS was 43 and 27 months. After adjusting for confounding factors, the median DFS of patients in the adjuvant therapy group and the control group were 26 and 12 months, respectively, and the median OS remained 43 and 27 months, with no significant difference (DFS, P=0.81; OS, P=0.40). Conclusion:There is currently a lack of definitive evidence for survival benefit from adjuvant anti-VEGF/VEGFR targeted therapy in patients with cM0 nccRCC-VTT after surgery.

This article introduces the contents of the latest edition Risk of Bias in Non-randomized Studies-of Exposure (ROBINS-E) published in June 2022 [ROBINS-E (2022)], and gives some examples about its usage. ROBINS-E is a tool for assessing the risk of bias in non-randomized studies-of exposure. Compared with ROBINS-E (2019), ROBINS-E (2022) adds more bias for observational studies, covers a more comprehensive range of bias, and adds the assessment of the external authenticity of the study. ROBINS-E (2022) adds a preliminary evaluation process to improve the efficiency of evaluation. In addition, ROBINS-E (2022) visualizes and instrumentalizes the use of signal problems in the form of path graph, making it more convenient to use. ROBINS-E (2022), although more consideration has been given to the issue of co-exposure, still does not address the problem of effect modification in co-exposure, and there is still room to expand the applicable research.

Objective:To explore new methods to assist the diagnosis of glucose transporter type 1 deficiency syndrome (GLUT1-DS).Methods:Sixteen children with epilepsy and/or movement disorder carrying the SLC2A1 mutation who admitted to Department of Pediatrics, the First Medical Center, Chinese People′s Liberation Army General Hospital and Department of Nutrition, Shanghai Deji Hospital from October 2019 to October 2020 were retrospectively analyzed.GLUT1-DS was diagnosed based on clinical phenotype, glucose level in CSF and/or genetic testing results.Forty-four healthy children who underwent physical examination in the First Medical Center, Chinese People′s Liberation Army General Hospital during the same period were selected as healthy control group.Glucose transporter 1 (GLUT1) level on the membrane surface of peripheral red blood cells and erythrocyte glucose uptake rate were measured by flow cytometry and glucose oxidase method, respectively.Their differences between groups were compared by the rank sum test.The receiver operating cha-racteristic (ROC) curve was plotted to assess their diagnostic value. Results:Sixteen children were diagnosed as GLUT1-DS.GLUT1 levels of 16 children with GLUT1-DS were significantly lower than those of healthy control group [17.96% (13.43%, 22.12%) vs.27.93% (24.76%, 34.30%), Z=5.249, P<0.001]. Area under curve (AUC) was 0.946, and weighted Kappa was 0.791 ( P<0.001). The erythrocyte glucose uptake was measured in 12 children with GLUT1-DS, which was significantly lower than that of healthy control group [23.14% (14.80%, 26.45%) vs.27.40% (24.61%, 32.82%), Z=2.366, P=0.018]. AUC and weighted Kappa were 0.724 and 0.344, respectively ( P<0.001), showing a poor consistency. Conclusions:GLUT1 level on the surface of human erythrocyte membrane measured by flow cytometry may be a new method to assist the diagnosis of GLUT1-DS.The erythrocyte glucose uptake rate test requires stricter experimental conditions and needs further investigation.