Objective:To evaluate risk factors for local recurrence and prognosis in patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy combined with lymph node dissection (LND).Methods:The data of 237 patients who were diagnosed with UTUC in Peking University First Hospital and received radical nephroureterectomy combined with LND during January 2010 and March 2022 were retrospectively reviewed. Clinicopathologic characteristics and oncological outcomes were compared according to lymph node metastasis. There were 122 males and 115 females. The tumors of 122 cases were located on the left, while 115 cases were on the right. The tumors of 102 cases were in the renal pelvic, 124 cases in the ureter and 11 cases in both sites. The mean age was (65.52±10.14) years old. The overall survival (OS), cancer-specific survival (CSS), local recurrence-free survival (LRFS) of all patients were valued using Kaplan-Meier method, and the survival curves with statistical significance between two groups were analyzed by log-rank test. Univariate and multivariate Cox proportional hazards regressions were performed to identify the independent risk factors for CSS and LRFS.Results:There were 122 males and 115 females. According to the lymph node metastasis, the patients were divided into lymph node negative group ( n=180, 75.9%) and lymph node positive group ( n=57, 24.1%). Lymph node positive group had a higher percentage in renal tumor [57.9%(33/57) vs. 38.1% (69/180)], stage T 3-4 [84.2%(48/57) vs. 32.8%(59/180)], G 3 [91.2%(52/57) vs. 55.6%(100/180)], glandular differentiation [17.5%(10/57) vs. 4.4%(8/180)], sarcomatoid differentiation [22.8%(13/57) vs. 9.4%(17/180)], necrosis [47.4%(27/57) vs. 16.1%(29/180)], lymphovascular invasion [40.4%(23/57) vs. 12.2%(22/180)] and the number of lymph node dissection [ 4(1, 10) vs. 2(1, 5)]. There were significant differences between the two groups ( P<0.05). Of 237 patients, 42 lost of follow up. The median follow-up time was 46(22, 79) months. Among the 195 patients, 52 patients died, and 42 died due to the tumor. Of all patients, 58(29.7%) had local recurrence, 34 had local recurrence alone, and 24 had concurrent distant metastasis. The 5-year OS and CSS were 67.4% and 71.3%, respectively. The 5-year OS and CSS were 70.5% and 75.1% respectively in the lymph node negative group, 57.5% and 59.4% respectively in the lymph node positive group ( P < 0.05). The 3-year LRFS was 68.0% for all the patients. The 3-year LRFS was 75.6% in the lymph node negative group and 44.5% in the lymph node positive group ( P<0.05). Multivariate analysis showed that tumor stage T 3-4( HR =3.924, 95% CI 2.045-7.529, P<0.001) and G 3( HR=2.871, 95% CI 1.193-6.909, P =0.019) were independent risk factors for LRFS. Multivariate analysis showed that age ≥70 years ( HR = 3.578, 95% CI 1.917-6.678, P<0.001) and pathological stage T 3-4 ( HR =2.366, 95% CI 1.278-4.381, P =0.006) were independent risk factors for CSS. Multivariate analysis showed that age ≥70 years ( HR = 3.874, 95% CI 2.190-6.853, P<0.001) and pathological stage T 3-4 ( HR = 2.757, 95% CI 1.565-4.857, P<0.001) were independent risk factors for OS. Conclusions:Patients with high T stage, high grade, as well as glandular differentiation, sarcomatoid differentiation, necrosis, lymphovascular invasion are more likely to have positive lymph node detection. Age ≥70 years and stage T 3-4 were independent risk factors for CSS and OS. Stage T 3-4 and G 3were independent risk factors for LRFS.

Objective:To evaluate the safety and effectiveness of Kangduo endoscopic surgical robot system for partial nephrectomy.Methods:Consecutive patients with stage T 1 renal tumor meeting the inclusion criteria from the Department of Urology, Peking University First Hospital from December 2020 to February 2021 were prospectively enrolled. All patients underwent partial nephrectomy with the Kangduo endoscopic surgical robot system after signing the informed consent. Clinical data including preoperative, perioperative and postoperative pathology and follow-up were collected. Results:Among the 26 patients, there were 16 males and 10 females, with a median age of 53(33-74) years, and a median body mass index of 25.99(20.90-32.91) kg/m 2. There were 12 cases of left kidney tumor and 14 cases of right kidney tumor. The median tumor diameter was 2.2(1.0-3.5) cm. The median time of warm ischemia was 17.7(7.1-29.2) minutes, and all of them were less than 30 minutes. The median docking time was 4.7(2.3-9.9) minutes, and the median time of robotic arm operation was 65.0 (37.0-155.0) minutes. The median National Aeronautics and Space Administration Task Load Index (NASA-TLX) score was 5.3 (2.0-28.0), and no instrument-related adverse events occurred intraoperatively. The median postoperative hospital stay was 4 (4-5) days. All tumor margins were negative on pathologic reports. No Clavien Ⅱ stage operative complications occurred in all patients during perioperative period and 1 month after the surgery. Conclusions:The partial nephrectomy using the kangduo endoscopic surgical robot system were completed successfully, and no instrument-related adverse events and complications occurred, showing that this surgical system used for partial nephrectomy is safe and effective.

Objective:To evaluate the feasibility and prognostic features of surgical resection of locally recurrent renal cell carcinoma patients after initial radical or partial nephrectomy.Methods:The data of the patients treated for postoperative locally recurrent renal cell carcinoma from Jan 2005 to Dec 2019 in the Department of Urology, Peking University First Hospital, were analyzed retrospectively. Postoperative locally recurrent of renal cell carcinoma is defined as disease recurring in the remnant kidney, renal fossa, adjacent abdomen, ipsilateral adrenal or retroperitoneal lymph nodes. Secondary surgery includes radical nephrectomy, partial nephrectomy, recurrent mass resection or radiofrequency ablation. The adjuvant therapy and prognostic information after secondary surgery were obtained and analyzed. Ninety-five patients were included in the study, with the median age of 56 years old (14-82 years old). The overall median recurrent interval was 25 months (2-164 months) and the median recurrent interval for radical and partial nephrectomy patients were 30 months and 25 months, with no significant difference. As for the secondary surgery, 63 patients underwent open surgery, 22 patients with laparoscopic surgery and 10 patients with radiofrequency ablation therapy.Result:The median operation time of secondary surgery was 148 minutes (35-330 minutes) and median intraoperative blood loss of 150 ml (20-3 000 ml). There were 8 cases of stage Ⅰ or stage Ⅱ postoperative complication, including wound infection and anemia. A stage Ⅲ complication of postoperative hematuria occured. The patient underwent renal artery embolization to control the hematuria. Eight patients suffered local recurrence and 10 patients experienced distant metastasis after the secondary surgery. During the follow-up, 6 patients died. The overall 3-year, 5-year disease free survival rate was 85.8% and 53.3%, respectively. The median survival time of patients with remnant kidney, renal fossa, and adjacent abdomen recurrence was 78 months, while 49 months for patients with ipsilateral adrenal and retroperitoneal lymph nodes recurrence ( P=0.141). Conclusions:With sufficient evaluation and preparation, the resection of the recurrent mass could be feasible and safe. With completion resection and negative surgery margin, patients could obtain relative long-term survival.

Objectives:To summarize the experience of treatment of 23 cases of urachal carcinoma in order to improve the diagnosis and treatment of urachal carcinoma.Methods:Clinical data of a total of 23 patients with urachal carcinoma from January 2014 to August 2019, including 19 males and 4 females, with a median age of 53 years (34 to 84 years) were retrospectively analyzed. The most common symptom was painless gross hematuria (20/23, 87.0%). All patients underwent CT examination before operation. Three of them had calcification (13.0%), and the median maximum diameter was 3.5 cm (2.0-7.0 cm). Preoperative cystoscopy revealed 23 cases of anterior or parietal mass of the bladder. Partial cystectomy and urachectomy were performed in 17 cases, partial cystectomy plus urachectomy (including umbilectomy) were performed in 5 cases, and total cystectomy were performed in 1 case. Eleven patients (47.8%) underwent pelvic lymph node dissection. Twenty-one cases (91.3%) had Sheldon stage Ⅲ or above tumors.Results:There were 21 cases of urachal adenocarcinoma and 2 cases of transitional cell carcinoma with adenoid differentiation. Five patients underwent adjuvant therapy (21.7%), including 1 patient of 5-fluorouracil (5-fu)+ cisplatin, two patients of gemcitabine+ cisplatin, and one patient of gemcitabine+ cisplatin+ vascular endothelial inhibitor. One case underwent local pelvic radiotherapy alone. No recurrence or metastasis occurred during the follow-up period. All patients were followed up for 38 months (2 to 68 months). A total of 3 patients developed distant metastasis and died during follow-up. The death occurred at 15 months, 40 months, and 49 months after surgery, all of which were caused by tumor metastasis. Two other patients had recurrence at 9 and 13 months after surgery, respectively, and they were followed up for 55 and 25 months after recurrence. Survival analysis showed that the 2-year cancer-specific survival rate was 94.1%, and the 5-year cancer-specific survival rate was 74.9%.Conclusions:Early diagnosis of urachal cancer is difficult. Emphasizing the examination of the urachus during physical examination may help early detection. Surgery-based comprehensive treatment can achieve good tumor control for localized umbilical carcinoma. The accurate pathological staging through pelvic lymph node dissection and the early postoperative adjuvant therapy may improve the prognosis of the patients.

Objective: To study the clinical characteristics, image findings, therapeutic method and prognosis of metanephric adenoma. Method: The clinical characteristic, image findings, operation methods and prognosis of 16 metanephric adenoma patients treated at Department of Urology, Peking University First Hospital from January 2004 to March 2016 were analyzed retrospectively. Results: There were 6 male and 10 female patients in the study. The mean age of patients was 33.7 years (ranging from 14 to 83 years). Two patients came to the hospital because of fever, while other 14 patients had no symptoms and found renal tumor by medical examination. One case was found polythemia vera and another 1 case showed mild anemia. Serum creatine of all the cases were in normal range. The tumor of 11 cases were at left side and 5 cases were at right. All patients took urinary tract ultrasound. Fifteen patients took CT examination. Among them, 14 cases were solid mass and 1 case was cystosolid.CT value was (41±4) HU. CT scan showed that the tumor was slight enhanced and CT value increased to (77±9) HU. Six patients took MRI examination. The MRI showed high or low signal of T1WI or T2WI scans.Tumor size was (4.7±3.9)cm (ranging from 1.7 to 17.5 cm). All 16 patients took operation and 11 of them took laparoscopic surgery while the other 5 cases took open surgery. Eleven cases took partial nephrectomy, 4 cases took nephrectomy and 1 case took nephroureterectomy. The surgical procedures were all successful and no complications occured during perioperative period. All cases were all confirmed metanephric adenoma by postoperative pathology and surgery cut edge were all negative. Immunohistochemical study showed that the positive rate of Vimentin, CD57, AE1/AE3, WT1, CK7 and AMACR respectively were 16/16, 15/16, 12/16, 10/16, 3/16 and 2/16. The median follow-up time of 16 cases was 44 months (ranging from 8 to 125 months) and none had recurrence or metastasis.One case died 125 months after surgery because of advanced age(83 years old). Conclusions Metanephric adenoma is difficult to be diagnosed relying on clinical characteristics and image features. Pathology can help confirm the diagnosis. Partial nephrectomy is the first choice for operation and can achieve good prognosis. But it still needs a regular follow-up.

Objective: To assess the diagnostic rate, safety and clinical application of percutaneous renal masses biopsy for advanced renal cell carcinoma patients.Methods: In this retrospective study, we collected the data of renal masses from the patients who underwent renal masses biopsy under ultrasound from April 2001 to December 2014 in Peking University First Hospital.A total of 75 patients who were undiagnosed or diagnosed with advanced renal cell carcinoma by the imageological method were enrolled in this study.The patient and lesion characteristics such as tumor size, pathology of tumor, histologic subtype, pathological grade, biopsied location and biopsied cores were recorded and analyzed.Results: Among all the 75 patients, biopsy was diagnostic in 64 cases (85.3%) and non-diagnostic in 11 cases (14.7%).Of the 64 diagnostic biopsies, 60 were malignant, including 37 (61.7%) renal cell carcinoma (RCC), 13 (21.7%) urothelial carcinoma and 10 (16.7%) other malignant masses.Of all the RCC subjects, 24 suffered from clear cell RCC, 5 papillary RCC, 3 collecting duct carcinomas, 1 unclassified RCC and 4 unknown subtypes.The 11 non-diagnostic biopsied samplings included inflammatory, blood and extrarenal tissue and normal renal tissue.The proportion of collecting duct carcinoma in RCC was 10.8% and the proportion of squamous carcinoma in urothelial carcinoma was 23.1%, which were both higher than the previous research findings.For the male and female groups, non-diagnostic yields were 6.5% and 30.4%, respectively (P=0.022).Of all the 75 patients, 13 renal cell carcinoma patients underwent the surgical treatment and got the results of postoperative pathology.Comparing preoperative biopsy pathological diagnosis with postoperative pathological diagnosis, we found the diagnostic correct rates for benign and malignant lesions, pathological subtype and pathological grade were 100%, 81.8% and 60%, respectively.Mild macroscopic hematuria occurred in 1 case after RMB and there were no serious complications in all the cases.Conclusion: Percutaneous renal masses biopsy under ultrasound with a high diagnostic rate which can define the histologic subtype of renal cell carcinoma.With targeted therapy, more and more patients whose evaluation suggests local advanced disease or metastatic tumors adopt renal tumor biopsy to define the histologic subtype, which could avoid unnecessary surgical treatment.

Objective: To investigate the mechanisms of nuclear export signal of androgen receptor (NESAR) in the regulation of androgen receptor (AR) protein expression and stability in prostate cancer.Methods: The green fluorescent protein fusion protein expression vectors pEGFP-AR(1-918aa), pEGFP-NESAR (743-817aa), pEGFP-NAR (1-665aa) and pEGFP-NAR-NESAR, and lysine mutants of NESAR pEGFP-NESAR K776R, pEGFP-NESAR K807R and pEGFP-NESAR K776R/K807R, were transiently transfec-ted into prostate cancer cell line PC3.Fluorescence microscopy, Western blot and immunoprecipitation were used to detect NESAR regulation of androgen receptor stability.Results: Under the fluorescence microscope, NESAR-containing fusion proteins were cytoplasmic localization, and their fluorescence intensities were much weaker than those without NESAR.The expression levels of NESAR-containing fusion proteins were significantly lower than those without NESAR.The half-lives of GFP-NESAR and GFP-NAR-NESAR were less than 6 h, while the expression of GFP and GFP-NAR was relatively stable and the half-life was more than 24 h in the presence of cycloheximide.The expression levels of GFP-NESAR were significantly increased by proteasome inhibitor MG132 treatment in a dose-dependent manner;in contrast, MG132 did not show any significant effect on the protein levels of GFP.When new protein synthesis was blocked, MG132 could also prevent the degradation of GFP-NESAR in the transfected cells in the presence of cycloheximide, while it had no significant effect on GFP protein stability in the parallel experiment.GFP immunoprecipitation showed that the ubiquitination level of GFP-NESAR fusion protein was significantly higher than that of the GFP control.The mutations of lysine sites K776 and K807 in NESAR significantly reduced the level of ubiquitination, and showed increased protein stability, indicating that they were the key amino acid residues of NESAR ubiquitination.Conclusion: NESAR was unstable and decreased the stability of its fusion proteins.NESAR was the target of polyubiquitination and mediated the degradation of its fusion proteins through the ubiquitin-proteasome pathway in prostate cancer cells.Our research provides a new way to regulate the level and/or activity of AR proteins, thus helping us understand the molecular mechanisms of AR degradation and strict control of AR in the progression to castration-resistance.

Objective: To study the impact to operation safety of preoperative renal artery embolization for management of ≥10 cm renal cell carcinoma. Methods: The clinical data of 239 cases with ≥10 cm renal cell carcinoma which all had underwent operation in Department of Urology, Peking University First Hospital from January 2002 to December 2014 were retrospectively analyzed. Fifty-three patients underwent preoperative renal artery embolization (therapeutic group) and 186 patients did not (control group). The effect of embolization on operative time, transfusion requirements, hospitalization, ICU stay and perioperative complications were analyzed by comparing the two groups using rank sum test and χ² test or Fisher exact test. Results: Comparing the therapeutic group and control group, there was significant difference in tumor location (on the left or right). The mean age, sex, mean primary tumor size, and TNM stage were similar in both groups. Comparing the therapeutic group and control group, there were more open surgeries in therapeutic group (96.2% vs. 82.3%, χ²=6.438, P=0.013). There were no significant differences in mean operative time (238 (525) minutes vs. 208 (583) minutes, Z=-2.182, P=0.062). The mean blood transfusion (700 (1 900) ml vs. 925 (8 800) ml, Z=-1.064, P=0.006) had significant difference. The therapeutic group had a longer mean hospitalization (21 (50) days vs. 15 (79) days, Z=-4.322, P=0.000) and higher rate of intensive care unit stay (54.7% vs. 34.4%, χ²=6.103, P=0.027). There was no significant difference in perioperative complications between two groups (0 vs.3.2%, P=0.408). Conclusion Preoperative renal artery embolization in ≥10 cm renal cell carcinoma patients undergoing operation provides benefit in increasing operation safety and reducing perioperative death.

Objective: To investigate the clinical features and prognosis of rare subtypes of renal cell carcinoma. Methods: This retrospective study collected the data of 52 rare subtypes of renal cell carcinoma of patients who underwent surgery from January 2002 to December 2014 at Department of Urology, Peking University First Hospital. There were 12 patients with collecting duct carcinoma, 5 patients with Xp11.2 translocation renal cell carcinoma, 5 patients with mucinous tubular and spindle cell carcinoma, 30 patients with unclassified renal cell carcinoma. The study group included 25 male and 27 female patients, with mean age of 52 years. The mean tumour size was (6.5±3.9) cm (range: 1.5 to 21.0 cm). The basic clinical features, gross appearance, Fuhrman nuclear grade, TNM staging and prognosis of rare subtypes of RCC were studied. The OS curves were obtained for rare subtypes of renal cell carcinoma using the Kaplan-Meier method and compared using a Log-rank test. Results: The rate of lymph node and distant metastasis were 34.6% (18/52) and 17.3% (9/52). Malignancies were screened and detected by color Doppler ultrasonography or CT scan, however, no case was diagnosed before operation or aspiration, all cases were confirmed by the pathological examination. The average period of postoperative follow-up process was 65 months, and the mean survival time was (34±23) months. Conclusion The clinical features of rare subtypes of renal cell carcinoma are similar to those of clear cell renal cell carcinoma, while the imaging changes will be helpful for diagnosis before operation.

Objective:To evaluate the impacts of clinical,pathological,and laboratory factors on on-cological outcomes of patients with T3 N0 M0 renal cell carcinoma.Methods:The clinical data,laboratory exam results,and follow-up outcomes of 182 patients with T3 N0 M0 renal cell carcinoma who underwent nephrectomy from 2007 to 2012 in Peking University First Hospital were retrospectively collected.The 5-year cancer-specific survival and 5-year recurrence-free survival of all the patients were calculated using Kaplan-Meier method,and the statistical significance between the survival curves were compared using the Log-rank test.Variables with significant differences in the univariate analysis were subjected to the multivariate analysis by Cox regression model.All the comparisons were conducted using two-tailed test and P <0.05 was considered statistically significant.Results:A total of 182 patients were included in this study.Of all the 182 patients,126 were male (69.23%)and 56 were female (30.77%).The mean age was (56.75 ±12.45)years.The median follow-up time was 48 months (3 -99 months).At the end of the follow-up,50 patients (27.47%)died due to the disease after a median of 29.74 months and 59 patients (32.42%)had tumor recurrence after a median of 22.12 months.The 5-year cancer-specific survival of all patients was 68.30% (95% CI:60.16% -75.84%);the 5-year recurrence-free survival was 60.70% (95% CI:53.16% -68.84%).In the univariate analysis,diabetes mellitus, tumor invasion status,Fuhrman grade,serum album,serum cholestenone,anemia,and neutrophils per-centage were associated with the cancer-specific survival and Fuhrman grade,serum album and anemia were associated with the recurrence-free survival.Variables with significant differences on univariate analysis were included in Cox multivariate regression analysis.Multivariate Logistic regression analysis showed that diabetes mellitus (HR =2.434,95% CI:1.243 -4.769,P =0.010),hypoalbuminemia (HR =2.188,95% CI:1.074 -1.074,P =0.031),and anemia (HR =3.320,95% CI:1.839 -5.991,P <0.001)were independent risk factors significantly associated with cancer-specific survival;and higher Fuhrman grade (HR =2.552,95% CI:1.433 -4.545,P =0.001),anemia (HR =2.535, 95% CI:1.497 -4.293,P =0.001)were independent factors significantly associated with recurrence-free survival.Conclusion:Diabetes mellitus,hypoalbuminemia,and anemia were independent risk fac-tors significantly associated with cancer-specific survival of T3 N0 M0 renal cell carcinoma patients;higher Fuhrman grade and anemia were independent risk factors significantly associated with tumor recurrence of T3 N0 M0 renal cell carcinoma patients.