1.Tumor microenvironment heterogeneity and its regulatory mechanisms in renal cell carcinoma:the latest advances
Yu YANG ; Ruijian LIU ; Lulin MA
Journal of Modern Urology 2026;31(2):187-192
Renal cell carcinoma is one of the most common malignant tumors of the urinary system.Its pronounced heterogeneity plays a crucial role in disease progression, treatment responses, and clinical outcomes.This review focuses on the heterogeneity of the tumor microenvironment in renal cell carcinoma, summarizing the key cellular interactions, the evolution of immunosuppressive states, and the reciprocal regulation between tumor and stromal components.The paper further discusses the clinical impacts of heterogeneity on immuno-targeted combination therapy, along with the application of emerging technologies, such as single-cell sequencing and spatial transcriptomics, so as to provide theoretical insights and practical guidance for the precision therapy for renal cell carcinoma.
2.Research advances in robot-assisted partial nephrectomy for anterior and posterior lip tumors of the kidney:focusing on postoperative complications
Yuanhao PEI ; Lulin MA ; Shuilong ZHAI ; Yimin WANG ; Zhang LIANG
Journal of Modern Urology 2026;31(4):376-381
Renal hilar tumors pose significant surgical challenges due to their proximity to major renal vessels and the collecting system. In robot-assisted partial nephrectomy, although both anterior and posterior lip tumors are considered renal hilar tumors, their operative difficulty and complication profiles differ markedly owing to distinct anatomical relationships and vascular adjacency. Anterior lip tumors, often involving tributaries of the renal vein, carry a relatively higher risk of intraoperative and postoperative bleeding. In contrast, posterior lip tumors, closer to the renal artery, are more likely to prolong warm ischemia time, thereby increasing the risk of postoperative renal impairment. Regarding urine leakage, although anterior lip tumors are theoretically closer to the collecting system and may pose a slightly elevated risk, precision reconstruction strategies—such as lip reconstruction based on sinus space anatomy—can effectively mitigate this risk. However, the specific difference in urine leakage risk between anterior and posterior lip tumors warrants further investigation. Both anterior and posterior lip tumors of the kidney can achieve low positive surgical margin rates in experienced centers. Complication risks are affected by multiple factors, including tumor anatomical complexity, warm ischemia time, and surgeon experience. Notably, R.E.N.A.L. score>8 is associated with significantly increased complication risks. Preoperative meticulous imaging evaluation, selection of an appropriate surgical approach based on tumor location, controlled warm ischemia time, and application of delicate suturing and reconstruction techniques are essential strategies to reduce complications.
3.Influencing factors and prognosis of postoperative complications in elderly(≥75 years)patients with renal cell carcinoma after laparoscopic surgery
Zhiying WU ; Min QIU ; Dameng PAN ; Xiaojun TIAN ; Lei ZHAO ; Hongxian ZHANG ; Shudong ZHANG ; Lulin MA
Journal of Modern Urology 2026;31(6):503-509
Objective To analyze the postoperative complications and survival outcomes of elderly patients with renal cell carcinoma undergoing laparoscopic surgery, and to identify the influencing factors, so as to provide reference for improving the safety of laparoscopic surgery in such patients. Methods A retrospective analysis was conducted on the clinical, surgical, and pathological data of 153 patients aged ≥75 years who underwent laparoscopic nephrectomy for renal cell carcinoma at our hospital during 2012 and 2025.Logistic regression analyses were performed to identify factors influencing postoperative complications, and a nomogram was constructed and validated to predict the complications.Kaplan-Meier method was used to draw the survival curve, and the effects of different surgical approaches on the prognosis and the survival difference in the age subgroups (75-<80 years, ≥80 years) were analyzed.Cox regression analyses were conducted to determine factors affecting survival outcomes. Results Among the 153 patients, 15 developed postoperative complications, including 5 severe cases. Multivariate logistic regression identified Charlson Comorbidity Index (CCI) ≥3 and prolonged operation time as independent risk factors for postoperative complications (P<0.05).The C-index of the logistic regression model constructed based on these factors (age, CCI≥3 and operation time) was 0.77 (95%CI:0.64-0.90), with an average absolute error of 1.6%.Subgroup analysis revealed superior overall survival in patients aged 75-<80 years undergoing partial nephrectomy compared to radical nephrectomy (P=0.005 6).No statistically significant difference in overall survival was observed among patients ≥80 years who received different surgical approaches (P=0.062).Multivariate Cox regression analysis identified preoperative low albumin levels, preoperative renal insufficiency, tumor diameter>4 cm, and pathological stage as independent risk factors for overall survival (P<0.05). Conclusion Laparoscopic surgery is safe and effective for elderly patients with renal cell carcinoma, with survival outcomes correlated to nutritional status, renal function, tumor size and pathological staging.Patients aged ≥80 years still derive surgical benefit, and no survival differences exist between different surgical approaches in this age group.
4.Review of the Expanded Clinical Trial System in the United States, Japan and Canada and its Enlightenment for China
Meiying MA ; Xiaopei ZHAO ; Lulin LI
Chinese Medical Ethics 2025;38(1):78-88
The expanded clinical trial system is designed to provide clinical trial drugs for patients suffering from serious or life-threatening diseases for which there is no effective treatment, essentially seeking a balance between the accessibility of drugs to patients and the soundness of the development of the pharmaceutical industry, as well as between the risk of expanding the use of clinical trial drugs and the need to safeguard the rights and interests of patients’ lives and health. Article 23 of China's Drug Administration Law provides only a principled description of the applicable standards and operating procedures for this system, with no implementing regulations, making it difficult for the system to function effectively in practice. The United States, Japan, and Canada have made detailed provisions on the conditions of application, applicants, review subjects and contents, and safeguards of the system through laws, regulations, and guidelines. Based on China's legislative environment and regulatory reality, and considering that the system is still in the initial stage in China, it is recommended that appropriate reference be made to the beneficial experience of foreign countries and that regulations and normative documents be promulgated as soon as possible to clarify the types of expanded clinical trials, applicants, review subjects etc., and to determine the responsibilities of all the parties involved, to promote the standardization of China’s expanded clinical trial system, to promote the availability of medicines to patients, and to effectively safeguard the rights and interests of patients’ lives and health, and the soundness and safety of the development of the pharmaceutical industry.
5.Robot-assisted laparoscopic inferior vena cava segmental resection for renal tumor with tumor thrombus invading the vascular wall
Shuai LIU ; Zhuo LIU ; Yunhe GUAN ; Guoliang WANG ; Xiaojun TIAN ; Hongxian ZHANG ; Lei LIU ; Lulin MA ; Shudong ZHANG
Journal of Peking University(Health Sciences) 2025;57(4):796-802
Objective:To evaluate the safety and oncological outcomes of robot-assisted laparoscopic inferior vena cava(IVC)segmental resection in renal tumor with IVC tumor thrombus(IVCTT).Methods:Clinical data from renal tumor patients undergoing robot-assisted laparoscopic IVC segmental resection at Peking University Third Hospital from Jan.2021 to Feb.2025 were retrospectively analyzed.Data collection included baseline demographics,tumor characteristics,perioperative parameters,and follow-up outcomes.Surgical records and pathological reports were retrieved from the electronic medical record system.Continuous variables were presented as median(P25,P75),and categorical variables as frequency(percentage).Results:Forty-four patients were enrolled.The cohort comprised 31 malesand 13 females,with a median age of 62(55,68)years.Right-sided tumors were observed in 39 cases and left-sided in 5 cases.Median tumor diameter was 8.1(6.1,10.1)cm.Mayo classifications included grade Ⅱ(n=37),Ⅲ(n=6),and Ⅳ(n=1).Neoadjuvant therapy was administered to 23 patients.Seventeen patients were complicated by IVC bland thrombus.Median operative time was 224.0(167.3,303.8)min,with intraoperative blood loss of 500.0(300.0,850.0)mL.Transfusion was administered to 19 patients,with a median blood transfusion of 800.0(400.0,1 200.0)mL.Postoperative complica-tions occurred in 25 cases(56.8%),classified as Clavien-Dindo grade Ⅰ(n=8)and grade Ⅱ(n=17).Procedure-specific complications included deep vein thrombosis(n=6),transfusion-requiring ane-mia(n=5),lower extremity edema(n=2),and pulmonary embolism(n=2),with no procedure-related mortality.Median postoperative serum creatinine was 116.0(86.5,157.5)μmnol/L.Pathological examination identified clear cell renal cell carcinoma as the predominant subtype,observed in 34 cases(77.3%).Pathological staging revealed T3b(n=12),T3c(n=29),and T4(n=3)disease,with nodal involvement(N1)in 8 cases and distant metastasis(M1)in 17.At a median follow-up of 10 months(range:1-49 months),cancer-specific mortality occurred in 3 patients,while 1 succumbed to other causes.Disease progression included pulmonary metastasis(n=5),hepatic metastasis(n=4),and local recurrence(n=4).Adjuvant therapy regimens comprised targeted-immunotherapy combina-tions(n=9)and targeted monotherapy(n=18).Conclusion:Robot-assisted laparoscopic I VC seg-mental resection achieves precise thrombus removal with confirmed short-term efficacy in renal tumor with IVCTT,though vigilance against vascular complications remains critical.
6.Clinicopathological features and survival analysis of TFE3-rearranged renal cell carcinoma with venous tumor thrombus
Zhanyi ZHANG ; Min LU ; Yuehao SUN ; Jinghan DONG ; Xiaofei HOU ; Chunlei XIAO ; Guoliang WANG ; Xiaojun TIAN ; Lulin MA ; Hongxian ZHANG ; Shudong ZHANG
Journal of Peking University(Health Sciences) 2025;57(4):650-661
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.
7.Experience summary of robot-assisted laparoscopic transplant nephrectomy
Qiming ZHANG ; Zebo CHEN ; Yu TIAN ; Dameng PAN ; Lei LIU ; Hongxian ZHANG ; Lei ZHAO ; Shudong ZHANG ; Lulin MA ; Xiaofei HOU
Journal of Peking University(Health Sciences) 2025;57(4):666-669
Objective:To review and summarize the experience of robot-assisted laparoscopic trans-plant nephrectomy,share the surgical steps and technical key points,and provide a reference for clinical practice.Methods:A retrospective analysis was conducted on the perioperative data of 5 patients who underwent robot-assisted laparoscopic donor nephrectomy at Peking University Third Hospital from August 2023 to December 2024.The surgical steps and key points were summarized.The continuous variables were described by medians(ranges).Results:A total of 5 patients were included in the analysis,of whom 2 were male and 3 were female.The median age of the patients was 37(31-68)years.The me-dian time from kidney transplantation to donor nephrectomy was 10(3-22)years.The indications for donor nephrectomy included recurrent hematuria,abdominal pain,malignant tumor of the transplanted kidney,and recurrent infection with hydronephrosis of the transplanted kidney.The excised transplanted kidneys from all the 5 patients had a single renal artery and a single renal vein.The median operation time was 212(145-351)min,the median blood loss was 300(20-500)mL,and the median post-operative hospital stay was 7(4-25)days.Only 1 patient experienced intraoperative complications,who experienced an external iliac artery injury during the operation and underwent suture repair.No pa-tient died during the perioperative period.Postoperative pathological results showed that 3 patients had end-stage non-functional kidneys,1 patient had BK virus-associated urothelial carcinoma,and 1 patient had chronic pyelonephritis with renal parenchymal atrophy.Conclusion:Robot-assisted laparoscopic transplant nephrectomy as a new surgical approach is feasible and safe.Compared with traditional open transplant nephrectomy,its advantage lies in the ability to directly observe and prioritize the management of the renal pedicle of the transplanted kidney,while completely freeing and removing the transplanted kidney outside the renal capsule.With the continuous accumulation of experience,this surgical technique is expected to become a powerful alternative to traditional open transplant nephrectomy.
8.Cost-effectiveness analysis of four urine tests in the diagnosis of upper tract urothelial carcinoma
Zaili SUN ; Peng HONG ; Xin LI ; Huiying HE ; Lulin MA ; Shudong ZHANG ; Hongxian ZHANG
International Journal of Surgery 2025;52(10):679-685
Objective:To compare the efficacy and clinical practicality of fluorescence in situ hybridization (FISH), thinprep cytology test (TCT), urine nuclear matrix protein 22 (NMP22) and urine cytology test in the diagnosis of upper tract urothelial carcinoma (UTUC). Methods:A retrospective analysis was conducted on the clinical data of 62 patients who underwent surgical treatment (biopsy or partial urothelial resection) for suspected UTUC in the Department of Urology, Peking University Third Hospital from January 2021 to December 2023, and received paraffin pathological diagnosis. Taking the pathological examination results as the diagnostic criteria, the sensitivity, specificity, Youden index, positive predictive value and negative predictive value of the four detection methods in the diagnosis of UTUC were calculated, and the cost-effectiveness analysis was performed. Combine the four detection methods in pairs, calculate the sensitivity, specificity and Youden index after the combination, and conduct a cost-effectiveness analysis. The comparison of sensitivity, specificity and Youden index of the four detection methods was conducted using Chi-test or Fisher exact probability method. The comparison between groups after pairwise combinations was also conducted using Chi-test or Fisher exact probability method. The receiver operating characteristic (ROC) curve was plotted and the area under the curve (AUC) was calculated.Results:The sensitivity (81.1%, 77.4%) and Youden index (0.700, 0.774) of FISH group and TCT group were significantly higher than those of NMP22 group and urine cytology group (39.6%, 43.4%; 0.174, 0.434), and the differences were statistically significant ( P<0.008 3). There were no statistically significant in the specificity (88.9%, 100.0%, 77.8%, 100.0%), positive predictive value (97.7%, 100.0%, 91.3%, 100.0%) and negative predictive value (44.4%, 42.9%, 17.9%, 23.1%) of the four groups ( P>0.008 3). The cost-effectiveness of the FISH group (3 256.4) was significantly higher than that of the TCT group (409.4), the NMP22 group (398.2) and the urine cytology group (627.9). After being combined in pairs, the net sensitivity of NMP22+ urine cytology (45.3%) was significantly lower than that of FISH+ TCT(88.7%), TCT+ NMP22(81.1%), FISH+ NMP22(86.8%), FISH + urine cytology (84.9%), TCT+ urine cytology (86.8%), and the difference was statistically significant ( P<0.008 3). The net specificities of the above combinations were 77.8%, 88.9%, 77.8%, 88.9%, 100.0%, respectively, and the differences were not statistically significant ( P>0.008 3). The cost-effectiveness was 1 008.0, 3 393.5, 632.8, 3 345.0, 3 513.5, and 737.3, respectively. Conclusions:In the diagnosis of UTUC, TCT has the highest diagnostic efficacy and relatively low cost, and is recommended for widespread promotion and application in clinical practice. If the patients economic conditions permit, it is recommended to combine TCT with urine cytology.
9.Robot-assisted laparoscopic inferior vena cava segmental resection for renal tumor with tumor thrombus invading the vascular wall
Shuai LIU ; Zhuo LIU ; Yunhe GUAN ; Guoliang WANG ; Xiaojun TIAN ; Hongxian ZHANG ; Lei LIU ; Lulin MA ; Shudong ZHANG
Journal of Peking University(Health Sciences) 2025;57(4):796-802
Objective:To evaluate the safety and oncological outcomes of robot-assisted laparoscopic inferior vena cava(IVC)segmental resection in renal tumor with IVC tumor thrombus(IVCTT).Methods:Clinical data from renal tumor patients undergoing robot-assisted laparoscopic IVC segmental resection at Peking University Third Hospital from Jan.2021 to Feb.2025 were retrospectively analyzed.Data collection included baseline demographics,tumor characteristics,perioperative parameters,and follow-up outcomes.Surgical records and pathological reports were retrieved from the electronic medical record system.Continuous variables were presented as median(P25,P75),and categorical variables as frequency(percentage).Results:Forty-four patients were enrolled.The cohort comprised 31 malesand 13 females,with a median age of 62(55,68)years.Right-sided tumors were observed in 39 cases and left-sided in 5 cases.Median tumor diameter was 8.1(6.1,10.1)cm.Mayo classifications included grade Ⅱ(n=37),Ⅲ(n=6),and Ⅳ(n=1).Neoadjuvant therapy was administered to 23 patients.Seventeen patients were complicated by IVC bland thrombus.Median operative time was 224.0(167.3,303.8)min,with intraoperative blood loss of 500.0(300.0,850.0)mL.Transfusion was administered to 19 patients,with a median blood transfusion of 800.0(400.0,1 200.0)mL.Postoperative complica-tions occurred in 25 cases(56.8%),classified as Clavien-Dindo grade Ⅰ(n=8)and grade Ⅱ(n=17).Procedure-specific complications included deep vein thrombosis(n=6),transfusion-requiring ane-mia(n=5),lower extremity edema(n=2),and pulmonary embolism(n=2),with no procedure-related mortality.Median postoperative serum creatinine was 116.0(86.5,157.5)μmnol/L.Pathological examination identified clear cell renal cell carcinoma as the predominant subtype,observed in 34 cases(77.3%).Pathological staging revealed T3b(n=12),T3c(n=29),and T4(n=3)disease,with nodal involvement(N1)in 8 cases and distant metastasis(M1)in 17.At a median follow-up of 10 months(range:1-49 months),cancer-specific mortality occurred in 3 patients,while 1 succumbed to other causes.Disease progression included pulmonary metastasis(n=5),hepatic metastasis(n=4),and local recurrence(n=4).Adjuvant therapy regimens comprised targeted-immunotherapy combina-tions(n=9)and targeted monotherapy(n=18).Conclusion:Robot-assisted laparoscopic I VC seg-mental resection achieves precise thrombus removal with confirmed short-term efficacy in renal tumor with IVCTT,though vigilance against vascular complications remains critical.
10.Clinicopathological features and survival analysis of TFE3-rearranged renal cell carcinoma with venous tumor thrombus
Zhanyi ZHANG ; Min LU ; Yuehao SUN ; Jinghan DONG ; Xiaofei HOU ; Chunlei XIAO ; Guoliang WANG ; Xiaojun TIAN ; Lulin MA ; Hongxian ZHANG ; Shudong ZHANG
Journal of Peking University(Health Sciences) 2025;57(4):650-661
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.

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