Objective To optimize the extraction process of Xuetong capsules and establish its quality control method. Methods The extraction process was optimized by orthogonal experiment using ethanol reflux method to investigate the effects of different factors on diphenylstilbene, aloin and extraction yield. The content of 5 anthraquinone compounds in Xuetong capsule was determined by HPLC. Results The optimal extraction process was to add 10 times ethanol, with an ethanol concentration of 70%, and extract 3 times, each time for 1 h; 5 components had a good linear relationship with peak area within a certain concentration range, r>0.999 7; The range of sample recovery rate was 93.66%-96.85%, RSD range of 1.48%-1.66%. The content determination results of the 5 components in three batches of Xuetong capsules were （0.632-0.641）, （0.660-0.681）, （1.968-1.991）, （2.547-2.580）, and （1.076-1.101） mg/g. Conclusion The method was accurate, reproducible, and highly feasible, which could be references for producing and improving the quality control standards of Xuetong capsules.

Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.

Objective:To investigate the efficacy of different treatment modes for locoregional recurrence after nephrectomy in patients with renal cell carcinoma.Methods:A total of 106 patients with locoregional recurrence after nephrectomy without distant metastasis (77 males and 29 females) admitted to Sun Yat-sen University Cancer Center from October 2001 to July 2020 were retrospectively analyzed. The median age was 51 (40, 60) years old. Radical nephrectomy was performed in 90 patients with primary tumor and partial nephrectomy was performed in 16 patients. Pathological diagnosis showed that 54 cases were clear cell carcinoma and 52 cases were non-clear cell carcinoma. 53 cases were in stage T 1-2 and 53 cases in stage T 3-4. The median diameter of recurrent lesions was 3.2 (2.0, 6.3) cm, and the median number was 2 (1, 4). The recurrence sites were divided into renal fossa recurrence (33 cases), renal fossa±retroperitoneal lymph node recurrence (38 cases), and intra-abdominal spread (35 cases). The median duration from primary surgery to local recurrence was 14.8 (7.3, 35.8) months. Two treatment groups were identified as systemic therapy alone (Group A) and local therapy with or without systemic therapy (Group B). The Kaplan-Meier method was used to compare the progression free survival (PFS) and overall survival (OS) between Group A and Group B. The Cox model was used to perform univariate and multivariate analysis. Results:Of all the 106 patients, 33 patients were in Group A and 73 patients were in Group B. In Group A, 29 patients (87.9%) received targeted therapy, and 4 patients (12.1%) received targeted therapy combined with immunotherapy. In Group B, 34 patients (46.6%) received surgery or ablation and 39 patients (53.4%) received SBRT, of which 62 patients (84.9%) received concurrent systemic therapy. Among them, 58 patients (93.5%) received targeted therapy, and 4 patients (6.5%) received targeted therapy combined with immunotherapy. The median follow-up period was 29.0 (15.4, 45.9) months, 64 patients progressed on tumor including 28 patients died. The median PFS and OS were 15.6 (7.1, 35.2) months and 66.9 (37.8, not reached) months. The median PFS of Group A and Group B were 7.6(5.0, 17.2)months and 22.2(9.6, 63.9)months respectively ( P=0.001), median OS of Group A and Group B were 45.7 (23.4, 62.8)months and 71.0(50.6, not reached)months respectively, and the 2-year OS were 70.6% and 85.5% in Group A and Group B respectively ( P=0.023). The univariate analysis showed local therapy with or without systemic therapy was significantly reduced 56% risk of tumor progression ( HR=0.44, P=0.003) and reduced 60% risk of death ( HR=0.40, P=0.028). The multivariate analysis showed that the OS was associated with ECOG score( HR=10.20, 95% CI 4.13-25.30, P<0.001)and local therapy( HR=0.23, 95% CI 0.09-0.58, P=0.002). Conclusion:Compared with systemic therapy alone, local therapy with or without systemic therapy can effectively improve the PFS and OS of patients with locoregional recurrence after nephrectomy.

Radical prostatectomy(RP)was commonly used in localized prostate cancer. For patients with adverse pathological features (APF) after RP, it was controversial about choosing adjuvant radiotherapy or salvage radiotherapy (SRT). Recent studies have found that early salvage radiotherapy(ESRT) had both the same cancer control and reduced overtreatment compared to adjuvant radiotherapy. Nomogram and Gene Classifier(GC) could predict the risk of recurrence after RP and contribute to choose adjuvant radiotherapy or ESRT. PSMA PET/CT was more sensitive to detect distant metastasis after biochemical recurrence, which was helpful to decide whether to implement SRT.

Objective:To investigate the prognosis after salvage radiotherapy with or without hormone therapy for prostate cancer.Methods:From May 2014 to December 2020, 248 patients undergoing salvage radiotherapy due to prostate-specific antigen (PSA)persistence or biochemical progression after radical prostatectomy at Sun Yat-sen University Cancer Center (n=157) and West China Hospital, Sichuan University (n=91) were analyzed. Median age was 66 (45-78) years old. Median PSA was 23.50 (0.18-845.00) ng/ml. The number of PSA persistence and biochemical progression were 143 (59%) and 105 (42%). The number of pT 2, pT 3a, pT 3b, pT 4, and unknown T stage was 99, 49, 78, 15 and 7 cases.The number of N 0, N 1 and unknown N stage was 153, 44 and 51 cases. 165 cases had positive surgical margin. Gleason score of 6, 7, 8, >8 score and unknown was in 12, 104, 34, 90 and 8 patients. Early and late salvage radiotherapy was performed in 117 and 131 patients, and 70 patients (28%) were CRPC. Hormone therapy was used combined with radiotherapy in 182 patients (73%). PSA decline after radiotherapy was compared with Chi-squre test. Kaplan-Meier method and log-rank test were used to compare progression free-survival (PFS)after radiotherapy. Univariate and multivariate analyses of PFS were performed using Cox proportional hazards model. Early salvage radiotherapy was defined as PSA≤0.5 ng/ml before radiotherapy, and late salvage radiotherapy was defined as PSA>0.5ng/ml. Results:PSA response (PSA decline ≥50%) rate was 94% (233/248), and 82% (203/248) patients had PSA decline ≥ 90%. Twelve (5%) patients had rising PSA after completing radiotherapy, but only 4 (2%) had real progression. The median PFS was 69 months (95% CI 68-70), and 3-year and 5-year PFS rate were 80% and 67%. PFS of PSA persistence and biochemical progression were similar ( HR =0.71, 95% CI 0.37-1.37, P=0.311). Compared with late salvage radiotherapy, early salvage radiotherapy had better PFS [69 (95% CI 68-70) vs. 59 (95% CI 44-74) months, P<0.001]. Compared with hormone sensitive, castration-resistant was associated with worse PFS (5-year PFS rate 74% vs. 51%, P<0.001). In multivariate analysis, Gleason score>8, castration-resistant and late salvage radiotherapy were unfavorable prognostic factors. Conclusions:In patients receiving salvage radiotherapy with or without hormone therapy for PSA persistence and biochemical progression after radical prostatectomy, high PSA level before radiotherapy and castration resistant is associated with poor prognosis.

Objective:To compare the pathological results and complications of limited and extended pelvic lymph node dissection among high-risk prostate cancer patients, and to explore the risk factors that affect the rate of lymph node metastasis in high-risk prostate cancer patients.Methods:The data of 800 high-risk prostate cancer patients who underwent radical prostatectomy and pelvic lymph node dissection from January 2016 to December 2020 in three affiliated hospital of Sun Yat-sen University were analyzed retrospectively. According to the scope of pelvic lymph node dissection, they were divided into limited pelvic lymph node dissection (LPLND) group and extended pelvic lymph node dissection (EPLND) group. There were 172 patients underwent LPLND, and 628 patients underwent EPLND.The age of the patients in the LPLND group was 67 (62, 72) years old, diagnosed PSA 20.7 (10.9, 54.8) ng/ml. The biopsy Gleason score 6 in 22 cases, 7 in 59 cases, 8 in 56 cases and 9-10 in 35 cases.The clinical T stage: T 1 in 29 cases, T 2 in 102 cases, T 3 in 37 cases, T 4 in 4 cases; N 0 in 160 cases and N 1 in 12 cases. 50 patients received neoadjuvant hormonal therapy. The age of patients in the EPLND group was 67 (63, 72) years old, diagnosed PSA was 23.9 (14.0, 46.8) ng/ml. Biopsy Gleason Score 6 in 51 cases, 7 in 194 cases, 8 in 218 cases and 9-10 in 165 cases. Clinical T stage: T 1 in 114 cases, T 2 in 341 cases, T 3 in 144 cases, T 4 in 29 cases; N 0 in 526 cases and N 1 in 102 cases.158 patients received neoadjuvant hormonal therapy. There were no significant differences in the age, PSA, puncture Gleason score, clinical T stage, and whether or not to receive neoadjuvant hormonal therapy between the two groups of patients ( P>0.05). The difference in clinical N staging was statistically significant ( P=0.002). The number of postoperative lymph nodes, positive pelvic lymph nodes and postoperative complications and other related clinical and pathological data of the two groups were analyzed. Multivariate logistic regression was used to analyze the risk factors of patients with positive lymph nodes. Results:The median number of lymph nodes harvested [13(8, 19)vs. 6(4, 13), P<0.001] and the rate of positive lymph node cases[31.2%(196/628) vs. 10.5%(18/172), P<0.001] in the EPLND group was significantly higher than those in the LPLND group. Preoperative PSA, clinical N staging, Gleason score, and way of lymph node dissection were independent risk factors for postoperative positive pelvic lymph node in high-risk prostate cancer patients. Compared with the LPLND group, the ELPND group had a higher postoperative complication rate [19.9%(125/628) vs. 11.0%(11/172), P=0.007]. Conclusions:Compared with the LPLND, EPLND in high-risk prostate cancer patients can harvest more lymph nodes and increase the detection rate of positive lymph nodes. The complications of EPLND were higher than those of LPLND. Preoperative PSA, clinical N stage, Gleason score, and the way of lymph node dissection are independent risk factors for positive pelvic lymph node dissection.

Objective:To evaluate the preliminary clinical efficacy and safety of stereotactic body radiation therapy (SBRT) in combination with targeted therapy for metastatic renal cell carcinoma (mRCC).Methods:Clinical data of 58 patients with mRCC who were treated with SBRT in combination with targeted therapy in Sun Yat-sen University Cancer Center from June 2013 to December 2018 were retrospectively analyzed. Among them, 79.3% patients were classified as intermediate or high risk according to International Metastatic Renal Cell Carcinoma Database Consortium Criteria. The median biologically equivalent dose (BED) was 147 Gy (67 to 238 Gy).Results:Overall, 32, 13, 7, 5 and 1 patients received SBRT for 1, 2, 3, 4 and 6 metastatic sites (105 lesions) and 71.4% of them were bone lesions. Targeted therapy was continued during SBRT. With a median follow-up of 9.4 months (range 2.7 to 40.1 months), 18 patients died. The 1-year local control rate was 97.4%. The 1-year progression-free survival was 50.3%. The 1-and 2-year overall survival was 72% and 53%. Approximately 85% patients experienced pain relief after SBRT. Patients who achieved complete or partial response after SBRT obtained better overall survival than those with stable disease or disease progression (1-year overall survival: 83% vs. 48%, P=0.021). In the whole cohort, 6 cases developed Grade Ⅲ adverse events, 4 of which were Grade Ⅲ myelosuppression, 1 case of Grade Ⅲ neuropathy and 1 case of radiation-induced skin injury. Conclusion:Preliminary study reveals that combined use of targeted therapy and SBRT is an efficacious and safe treatment of advanced mRCC.

Objective:To evaluate the efficacy and safety of Tyrosine Kinase Inhibitors (TKIs) combined with stereotactic body radiation therapy(SBRT) in the treatment of renal cell carcinoma (RCC) patients with bone metastasis.Methods:The clinical data of 80 RCC patients with bone metastasis in Sun Yat-sen University Cancer Center from April 2010 to April 2020 were analyzed retrospectively. Among them, 64 patients were medium or high risk according to the International Metastatic Renal Cell Carcinoma Database Consortium(IMDC) score. Twenty-four patients received TKI therapy alone(Group A), and the other 56 cases received TKIs combined with SBRT to bone metastastic lesions (Group B).Results:The median follow-up period was 20.7 months (4.8-115.6 months), 70 patients received second or third-line targeted drug therapy, and 4 patients in group A and 15 patients in group B received TKI plus immunotherapy. Fifty-four patients had symptoms of bone pain before radiotherapy, 46 patients were satisfied with the analgesic effect after SBRT treatment. Twelve patients got complete response (CR) after bone lesions, and 32 patients achieved partial response (PR). Forty patients died of disease progression during follow-up. The median OS was: 20.7 months vs not reached(Group A vs. Group B), and the 2-y OS and 5-y OS were 50% vs. 62%, and 19% vs. 56%, respectively ( P=0.006). There were only 2 patients (3.6%) had grade 3 SBRT related adverse events. Conclusions:SBRT combined with TKIs improved the quality of life and prolonged the overall survival of RCC patients with bone metastasis.

Objective: To report the experience on the multi-disciplinary management of metastatic renal cell (mRCC) patients in a single center. Methods: Data of 168 mRCC patients treated by multi-disciplinary team (MDT) at Sun Yat-sen University Cancer Center from December 2007 to February 2019 was retrospectively analyzed.Three treatment groups were identified, including 76 patients with 55 males and 21 females, received anti-angiogenic agents alone (Group A), 66 patients with 55 males and 11 males, received anti-angiogenic agents plus local therapy (Group B)and 26 patients, with 19 males and 7 females, received anti-angiogenic agents plus immunotherapy and local therapy (Group C). The Sunitinib, Sorafenib, Axitinib were chosen for the TKI. The Pembrolizumab was used for immunotherapy. The stereotactic body radiation therapy and surgical excision were considered as the local therapy. The study aims to compare the age, gender, IMDC score, pathology, nbephrectomy, adverse events, progression-free survival and overall survival (OS). Results: Of all patients, the median follow-up duration was 23 months (ranging 6-117 cmonths). The PFS was 18.3 months and median OS was 33.5 months. The 2 years and 5 years survival rate was 66% and 35%, respectively. The median OS of Group A, B and C were 29.8 months, 44.6 months and not reached. 2y-OS was 58%, 67% and 89%, while 5y-OS 12%, 46% and 57%.There was no difference in age, gender, IMDC score, pathology, synchronous metastases or nephterectomy between the three groups. The prognostic result in TKI based combination therapy was superior to TKI therapy alone, which the 5y-OS was 51% and 11%, respectively. The prognostic result in group C's moderate-high risk mRCC patients was superior to group A and B. The median OS in TKI+ DC and CIK+ Pembrolizumab was 49.1 months and 53.1 months. On univariate analyses, IMDC score, nephrectomy and treatment group was associated with OS (P<0.05). On multivariate analyses, treatment group, nephrectomy was associated with OS (P<0.05). The risk of death of Group C decreased about 60% [HR 0.39 (0.17, 0.89), P=0.026]. 78 (46.4%) patients on TKI alone and 16 (61.5%) patients treated with TKI plus immunotherapy had Grade 3 or 4 adverse events. 16 (20.3%) patients had Clavien Ⅲ-Ⅳ toxicity after surgical procedures. 6 (5.7%) patients had Grade 3 toxiciy after SBRT. Conclusions Patients treated with combined therapy had better survival than those treated with anti-angiogenic agents alone. MDT approach could bring survival benefit to mRCC patients.

Objective To evaluate the efficacy of patients with stage T2 bladder cancer who underwent combined treatment of bladder-preserving surgery and adjuvant intra-arterial chemotherapy.Methods The survival data of bladder cancer paients from January 2000 to December 2014 with stage T2N0M0 were retrospectively analyzed.Thirty-five patients of cT2N0M0 receive combined treatment of bladder-preserving surgery and adjuvant intra-arterial chemotherapy(group A),and 80 patients of pT2N0M0 underwent radical cystectomy (RC) (group B).The pathological diagnosis of all patients was urothelial carcinoma.In group A,there were 33(94.2％) males and 2 (5.8％) females;20 (57.1％) tumor size less than 3 cm and 15 (42.9％) larger than 3 cm;24 (68.6％) with single tumor and 11 (31.4％) with multiple tumors;11 (31.4％) patients with primary tumors and 24 (68.6％) recurrent tumors.In group B,there were 71 (88.7％) males and 9 (11.3％) females;35 (43.8％) tumor size less than 3 cm and 45(56.2％) larger than 3 cm;44 (55.0％) with single tumors and 36 (45.0％) with multiple tumors;22(27.5％) patients with primary tumors and 58 (72.5％) recurrent tumors.Results Groups A and B consisted of 35 and 80 patients and median follow-up time was 68 (13-157)and 67 (4-198)months,respectively.There was no significantly statistical difference in disease-specific survival (DSS) between the two groups(P =0.888),76.5％ for group A and 60.6％ for group B respectively.In group A,26 (74.3％) patients achieved complete response (CR) to intra-arterial chemotherapy.Additionally,amounts of 21 (60.0％) patients preserve their functional bladder successfully and their median follow-up time was 69 (13-134)months.8 patients receive delayed radical cystectomy when suffered tumor recurrence and none of them had lymph node metastases.Of those pathological stage was presented as stage T2 5 cases,T3 2 cases and T4 1 case.Importantly,the 8 patients who receive delayed RC did not confer worse DSS when compared with those underwent immediate RC in group B (P =0.809).Cox proportional hazards model showed that tumor number and CR to intra-arterial chemotherapy was independent prognostic factor for disease-free survival (HR =0.238,P =0.007) and DSS(HR =0.085,P =0.004) respectively.During the period of intra-arterial chemotherapy,we did not observe hematological toxicity of grade Ⅳ and the hematological toxicity of grade Ⅰ-Ⅲ was 9 (25.7％),6 (17.1％) and 4 (11.4％).Conclusions For patients with T2N0M0,combined treatment of bladder-preserving surgery and adjuvant intra-arterial chemotherapy could be a therapy with long-term survival outcome and safety.The therapy could be offered as alternative treatment option for patients who were unsuitable for receiving RC.