Liquid biopsy is a noninvasive analysis of tumor related substances in fluid samples, which overcomes the limitations of traditional histological biopsy, and beneficial for early diagnosis and differentiation, prediction of response to treatment, longitudinal monitoring of disease progression and prediction of prognosis. Renal cell carcinoma is lack of mature serum tumor markers, and the diagnosis and monitoring of the disease still rely on imaging. In recent years, liquid biopsy has become a hotspot in renal cell carcinoma. In this paper, we will review the application and research progress of circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), circulating tumor RNA (ctRNA), exosomes, tumor "education" platelets (TEPs) in renal cell carcinoma.

Objective:To investigate the correlation between preoperative platelet parameters and clinicopathological features of renal cell carcinoma.Methods:The data of 452 patients with renal cell carcinoma treated in the Peking University Third Hospital from January 2015 to December 2016 were retrospectively analyzed, including 308 males and 144 females, and the mean age was 56.5(15-86) years. There were 178 cases, 72 cases, and 42 cases combined with hypertension, diabetes, and coronary heart disease, respectively. Preoperative platelet parameters were the mean PLT of 218.56(72-568)×10 9/L, MPV of 9.65(6.2-20.5)fl, PDW of 14.44(7.9-23.1) fl, and PCT of 20.72%(8%-49%). The data of 253 patients with simple renal cysts were selected as the controls, including 140 males and 113 females, and the mean age was 58(9-84) years. There were 178 cases, 72 cases, and 42 cases combined with hypertension, diabetes, and coronary heart disease, respectively. Preoperative platelet parameters were the mean PLT of 207.08(84-362)×10 9/L, MPV of 9.50(6.9-13.9)fl, PDW of 14.59(8.9-21.6)fl, and PCT of 19.49%(9%-36%). Propensity score matching method was used to balance the baseline differences between the two groups, and the differences of platelet parameters between the two groups were compared. The correlation between different clinicopathological characteristics of renal cell carcinoma and platelet parameters was analyzed. Multivariate logistic regression model was used to explore the risk factors of renal cell carcinoma with lymph node or distant metastasis. Results:After matching the baseline data, PLT( t=1.993, P=0.047) and PCT( t=2.396, P= 0.017) in renal cell carcinoma group were significantly higher than those in controls. Among 452 cases in renal cell carcinoma, there were 395 cases (87.4%) with clear cell renal cell carcinoma and 57 cases (12.6%) with non-clear cell renal cell carcinoma. For pathological stage, there were 325 cases (71.9%) of T 1-T 2 stage and 127 cases (28.1%) of T 3-T 4 stage. In addition, there were 444 cases (98.2%) of N 0 stage, 8 cases (1.8%) of N 1 stage, 428 cases (93.6%) of M 0 stage, and 24 cases (6.4%) of M 1 stage. There were 320 cases of nuclear grade Ⅰ-Ⅱ, 99 cases of nuclear grade Ⅲ-Ⅳ, and 33 cases without nuclear grade. Preoperative high PLT was significantly correlated with T 3-T 4( t=3.409, P=0.001), M 1( t=2.772, P=0.011) and nuclear grade Ⅲ-Ⅳ( t=2.859, P=0.005). Low MPV was significantly correlated with M 1( t=2.981, P=0.003). Low PDW was correlated with T 3-T 4( t=2.567, P=0.011). High PCT was significantly correlated with T 3-T 4( t=2.722, P=0.007) and nuclear grade Ⅲ-Ⅳ( t=3.011, P=0.003). Multivariate logistic regression analysis showed that PLT( OR=1.007, 95% CI 1.002-1.012, P=0.009), clear cell renal cell carcinoma( OR=4.467, 95% CI 1.574-12.679, P=0.005)and nuclear grade Ⅲ-Ⅳ( OR= 5.554, 95% CI 2.399-12.856, P<0.001)were independent risk factors for lymph node or distant metastasis of RCC. Conclusions:PLT and PCT are higher in patients with renal cell carcinoma compared to simple renal cysts. High PLT, PCT, and low MPV, PDW are correlated with the poor clinicopathological characteristics of renal cell carcinoma. Preoperative PLT can be used as an independent risk factor for lymph node or distant metastasis of renal cell carcinoma.

Objective To investigate the clinicopathological features,diagnosis,treatment and prognosis of a case of large cell neuroendocrine carcinoma (LCNEC) in urinary bladder and ureter.Methods The clinical pathological data of a patient with LCNEC in urinary bladder and ureter was retrospectively analyzed and the related literatures were reviewed.It was a male patient,78 years old,presenting with total painless gross hematuria.The ultrasonography showed nodules on the left lateral wall of bladder.Cystoscopy showed 2 cm cauliflower-like mass on the left lateral wall of bladder,and pathologic biopsy showed bladder urothelial carcinoma.Results Transurethral resection of bladder tumor was performed.The tumor cells were large in size,with vesicular nuclei,prominent nucleoli and nested/trabecular architecture.Immunohistochemical analysis demonstrated that tumor cells were positive for synaptophysin,chromogranin A and CD56.The proliferation index evaluated with Ki-67 was about 80％.The pathology report revealed a large cell neuroendocrine bladder tumor with focal areas of high-grade urothelial carcinoma.After intravesical instillation therapy for 2 months,tumor recurrence was detected by CT.Laparoscopic radical cystectomy and ureteral segmental resection was performed.The pathology report revealed a LCNEC with focal areas of highgrade invasive urothelial carcinoma in the bladder and ureter.CT showed tumor recurrence with liver metastasis 1 month after the operation.The overall survival was 9 months.Conclusions The clinical and imaging findings of LCNEC in bladder and ureter are nonspecific.Diagnosis must depend on the pathological and immunohistochemical staining.The tumor is aggressive with high risk of recurrence and metastasis and has a poor prognosis.It is mainly treated with radical resection combined with chemotherapy.

Objective:To investigate the risk factors of massive intraoperative bleeding in patients with renal cell carcinoma and tumor thrombus.Methods:Data of 177 patients with renal cell carcinoma and tumor thrombus in Peking University Third Hospital from January 2017 to July 2020 were retrospectively analyzed, including 129 males and 48 females. The average age was (59.3±10.6) years. The tumors were located on the left in 66 cases and on the right in 111 cases. The tumor size was less than 7 cm in 52 cases, 7-10 cm in 63 cases and >10 cm in 62 cases. There were 45 cases with tumor thrombus of Mayo grade 0, 101 cases of grade Ⅰ-Ⅱ and 31 cases of grade Ⅲ-Ⅳ. There were 93 cases undergoing laparoscopic surgery and 84 cases undergoing open surgery. Segmental resection of vena cava was performed in 30 cases. Massive intraoperative bleeding was defined as the total of bleeding ≥ 1 500 ml. The difference of clinical data between massive bleeding group and non-massive bleeding group was compared. Logistic multivariate regression was used to analyze the independent risk factors of massive intraoperative bleeding.Result:The median intraoperative bleeding of 177 cases was 600 (200, 1 500) ml. There were 50 cases (28.2%) in massive bleeding group and 127 cases(71.8%) in non-massive bleeding group. Comparing massive bleeding group and non-massive bleeding group, the preoperative ASA scores of 1-2 scores were 38 cases (76.0%) and 114 cases (89.8%) respectively, and the 3 scores were 12 cases (24.0%) and 13 cases (10.2%) respectively ( P=0.029); Hemoglobin was (116.8±23.1) g/L and (127.6±23.6) g/L respectively ( P=0.006); The tumor size less than 7 cm in 10 cases (20.0%) and 42 cases (33.1%), 7-10 cm in 15 cases (30.0%) and 48 cases (37.8%), and >10 cm in 25 cases (50.0%) and 37 cases (29.1%)( P=0.024); Tumor thrombus of Mayo grade 0 were 3 cases (6.0%) and 42 cases (33.1%), grade Ⅰ-Ⅱ were 27 cases (54.0%) and 74 cases (58.3%), grade Ⅲ-Ⅳ were 20 cases (40.0%) and 11 cases (8.6%) respectively ( P<0.01); Open surgery were performed in 42 (84.0%) and 42 (33.1%) cases ( P<0.01); Segmental resection of vena cava was performed in 19 cases (38.0%) and 11 cases (8.7%) respectively ( P<0.01). Multivariate analysis showed that Mayo grade Ⅲ-Ⅳ tumor thrombus ( OR=10.261, P=0.006), tumor size > 10 cm ( OR=3.223, P=0.030), open surgery ( OR=5.454, P<0.01) and segmental resection of vena cava ( OR=4.441, P<0.01) were independent risk factors for massive intraoperative bleeding. The median bleeding of Mayo grade Ⅲ-Ⅳ tumor thrombus, tumor size >10cm, open surgery and segmental resection of vena cava were 2000, 750, 1 450 and 1 650 ml respectively. Conclusions:Renal cell carcinoma with tumor thrombus has a high risk of bleeding. Mayo grade Ⅲ-Ⅳ tumor thrombus, tumor size >10 cm, open surgery and segmental resection of vena cava are independent risk factors for massive intraoperative bleeding.