Toripalimab plus axitinib versus sunitinib as first-line treatment for advanced renal cell carcinoma: RENOTORCH, a randomized, open-label, phase III study.

BACKGROUND: Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC. PATIENTS AND METHODS: Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety. RESULTS: A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab-axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab-axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab-axitinib group and 58.6% of patients in the sunitinib group. CONCLUSION: In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile TRIAL REGISTRATION: ClinicalTrials.gov NCT04394975.

[Effects of normal mitochondrial transplantation on proliferation, apoptosis and stemness of triple-negative breast cancer cells].

Objectives: To observe the mitochondrial morphology of normal and triple-negative breast cancer cells, extract mitochondria from normal cells, and investigate the effects of mitochondrial transplantation on proliferation, apoptosis, and stemness of triple-negative breast cancer cells. Methods: The morphology of mitochondria was observed by transmission electron microscope. Mitochondria were extracted by mitochondrial extraction kit, mitochondrial protein was identified by western blot, and mitochondrial activity was detected by mitochondrial membrane potential detection kit. MitoTracker Green or MitoTracker Deep Red fluorescent probes were used to label the mitochondria of living cells, and the degree of mitochondria entering LTT cells was observed by confocal laser microscopy at 12, 24, and 96 hours. The effects of mitochondrial transplantation on proliferation, apoptosis, and stemness of breast cancer cells were examined by CCK8, colony formation assay, flow cytometry, and sphere formation assay after 24 hours of mitochondrial transplantation. Results: The mitochondria of normal cells were rod-shaped or elongated, while the mitochondria of triple-negative breast cancer cells were swollen and vacuolated. Western blot results showed that cytochrome c oxidase subunit I (MT-CO1) protein encoded by mitochondria was present in the isolated mitochondria. The content of heat shock protein 60 (HSP60) was higher in mitochondria than that in cytoplasm. The result of the multi-mode microplate reader showed that the content of mitochondrial J-aggregates/monomer was 1.67±0.06, which was significantly higher than 0.35±0.04 of the control group (P＜0.001). Exogenous mitochondria were observed in LTT cells at 12, 24, and 96 hours after mitochondrial transplantation. The results of the CCK8 experiment showed that OD450 of LTT cells was 0.27±0.13 after 48 hours transplantation, which was lower than 0.62±0.36 of the control group (P=0.023). The OD450 of MDA-MB-468 cells was 0.30±0.03, which was lower than 0.65±0.10 of the control group (P=0.004). After 120 hours of mitochondrial transplantation, OD450 in both groups was still significantly lower than that in the control group (P＜0.01). The number of clones formed by mitochondrial transplantation of LTT cells was 21.33±7.31, which was lower than 35.22±13.59 of the control group (P=0.016). Flow cytometry showed that the early apoptosis rate of LTT cells was (30.07±2.15)% after 24 hours of mitochondrial transplantation, which was higher than 2.07±1.58 of the control group (P＜0.001). The proportion of early apoptosis in MDA-MB-468 cells was 24.47%±5.22%, which was higher than (7.83±2.06)% in the control group (P=0.007). In addition, the number of mitochondria transplanted LTT cells into the cell sphere was 46.25±5.40, which was significantly lower than 62.58±6.43 of the control group (P＜0.001). Conclusion: Normal mitochondria can enter triple-negative breast cancer cells by co-culture, inhibit the proliferation and stemness of triple-negative breast cancer cells, and promote the apoptosis of triple-negative breast cancer cells.

[Recommendations of diagnosis and treatment of Takayasu's arteritis in China].

Takayasu's arteritis (TAK) mainly involves the aorta and its major branches, which is characterized as a chronic, progressive and inflammatory disease. China belongs to one of the regions with a high prevalence of TAK referring to its global distribution. However, it is insufficient for the spread and update of standardized diagnosis and treatment of TAK. Based on the evidence and guidelines from China and other countries, Chinese Rheumatology Association developed the standardized diagnosis and treatment of TAK in China. The purpose is to standardize the methods for diagnosis of TAK, assessment of disease activity and disease severity, strategies of internal treatment and timing of surgical intervention, and further leading to protect the function of important organs and improve the disease prognosis.

[Relationship between recovery of urinary continence after laparoscopic radical prostatectomy and preoperative/postoperative membranous urethral length].

OBJECTIVE: To evaluate the relationship between recovery of urinary continence after laparoscopic radical prostatectomy (LRP) and preoperative/postoperative membranous urethral length (MUL) on magnetic resonance imaging. METHODS: We retrospectively analyzed 69 patients with pathologic confirmed prostate carcinoma who underwent laparoscopic radical prostatectomy. Preoperative MUL was defined as the distance from the apex of prostate to the level of the urethra at penile bulb on the coronal image. Postoperative MUL was defined as the distance from the bladder neck to the level of the urethra at the penile bulb on the coronal image. MUL-retained rate was defined as the percentage of postoperative MUL to preoperative MUL. All patients received extraperitoneal LRP. Patients reported freedom from using safety pad (0 pad/d) were defined as urinary continence. Multivariate Logistic regression analyses were used to identify independent predictors of early continence recovery after LRP. Kaplan-Meier analyses and log-rank test were used to compare time to continence recovery between the groups. RESULTS: For all the 69 patients, the average age was (71.4±8.6) years. The prostate specific antigen before biopsy was (23.40±30.31) µg/L, and the mean preoperative prostatic volume by magnetic resonance imaging was (39.48±22.73) mL. The mean preoperative MUL was (13.0±3.3) mm, the mean postoperative MUL was (12.3±3.4) mm, and the mean MUL-retained rate was 93.9%±6.2%. The continence rate for all the patients after LRP was 57.9% and 97.1% in three months and one year, respectively. The patients achieving early continence recovery had significant smaller prostatic volume (P=0.028), longer preoperative MUL and postoperative MUL (P < 0.001). Multivariate Logistic regression analyses revealed postoperative MUL (P < 0.001) were predictors of continence recovery after LRP. Kaplan-Meier analyses and Log-rank test revealed that preoperative MUL (≥14 mm vs. < 14 mm, P < 0.001) and postoperative MUL (≥13 mm vs. < 13 mm, P < 0.001), MUL-retained rate (< 94% vs. ≥94%, P < 0.001) were all significantly associated with continence recovery. CONCLUSION: Post-operative MUL was independently predictors of early continence recovery after LRP. Preoperative MUL, postoperative MUL and MUL retained rate were significantly associated with recovery of urinary continence.

[Clinicopathological features and prognostic analysis of papillary renal cell carcinoma].

OBJECTIVE: To investigate the clinicopathological features and prognostic characteristics of papillary renal cell carcinoma (pRCC). METHODS: The clinical data of 114 patients with pRCC, including 91 males and 23 females, admitted to the Department of Urology, Peking University Third Hospital from May 2012 to May 2021 were retrospectively analyzed. All the cases were operated patients with clear pathological diagnosis and complete follow-up data. The log-rank test was used to analyze the relationship between the patients' clinicopathological characteristics and survival time, the Kaplan-Meier method to draw survival curves, and the Cox regression model for univariate and multifactorial analysis. RESULTS: The mean age of the 114 patients was (57.3±12.6) years. The tumors were located in the left kidney in 49 cases and in the right kidney in 65 cases. In the study, 48 radical nephrectomies and 66 partial nephrectomies were performed, 42 cases were type 1 and 72 cases were type 2, and the mean maximum tumor diameter was (5.5±3.6) cm. pT1a stage 52 cases, pT1b stage 22 cases, pT2 stage 4 cases, pT3 stage 33 cases, and pT4 stage 3 cases were staged. According to the World Health Organization / International Society of Urological Pathology (WHO/ISUP), there were 13 cases of gradeⅠ, 44 cases of grade Ⅱ, 51 cases of grade Ⅲ, and 6 cases of grade Ⅳ. And 34 of the 114 patients had vascular cancer embolism, 30 cases had lymph node metastasis, and 3 cases had adrenal metastasis. The median follow-up time after surgery was 22 months, and the 3-year progression-free survival rate was 95.6%. The patients with type 1 and type 2 pRCC showed statistically significant differences in age (P=0.046), body mass index (P=0.008), surgical approach (P=0.001), maximum tumor diameter (P < 0.001), vascular cancer embolism (P < 0.001), lymph node metastasis (P < 0.001), pT stage (P < 0.001), and nuclear grade (P < 0.001). The 3-year progression-free survival rates for type 1 and type 2 pRCC were 100% and 69.4%, respectively, with type 1 having a significantly better prognosis than with type 2 (P=0.003). Univariate analysis of the patients with type 2 pRCC showed that pT stage (P < 0.001), vascular cancer embolism (P < 0.001) and lymph node metastasis (P < 0.001) were strongly associated with their prognosis. Multifactorial analysis showed that vascular cancer embolism was an independent prognostic factor for progression-free survival in type 2 pRCC (P=0.001). Univariate analysis of the pRCC patients undergoing radical nephrectomy showed that pT stage (P=0.006), vascular cancer embolism (P=0.001), and lymph node metastasis (P=0.008) were significant factors affecting their prognosis, and further multifactorial analysis showed that only vascular cancer embolism was an indepen-dent prognostic factor for their progression-free survival (P=0.006). CONCLUSION: Type 2 pRCC has more morbidity, more lymph node metastases, more advanced pT stage, and higher pathologic grading than type 1 pRCC. The presence of vascular cancer embolism is an independent prognostic factor in patients with type 2 pRCC and pRCC undergoing radical nephrectomy.

[Treatment and prognosis of multiple primary malignant neoplasms complicated with renal cell carcinoma].

OBJECTIVE: To investigate the treatment and prognosis of multiple primary malignant neoplasms (MPMN) complicated with renal cell carcinoma (RCC), and to make risk stratification. METHODS: A retrospective study of 27 cases of MPMN with RCC in two centers, including the different tumors of MPMN, specific treatment methods, and the interval between primary cancers. At the same time, the survival conditions, including recurrence, metastasis and survival, were followed up for statistical analysis. The interval between the two kinds of primary cancer within 6 months was simultaneous MPMNs, and more than 6 months was metachronous MPMNs. For simple risk stratification of cases, as long as one of the MPMNs had a stage Ⅲ or higher malignancy, which was defined as high risk. RESULTS: Among the 27 patients, 20 were male and 7 were female, with age at the time of diagnosis was 42-82 years, with an average age of (61.3±11.7) years. The age at the diagnosis of renal cancer was 43-87 years, with an average age of (66.0±11.3) years. There were 21 cases with duplex primary malignant neoplasms, 4 cases with triple primary malignant neoplasms, and 2 cases with quadruple primary malignant neoplasms. The interval between first cancer and second cancer was 0-360 months, with a median of 18 months. There were 17 cases of metachronous multiple primary malignant neoplasms and 10 cases of simultaneous multiple primary malignant neoplasms. The most common system of MPMN with comorbid RCC involved urologic system, digestive system and respiratory system. The most common locations of MPMN with comorbid RCC were bladder cancer, lung cancer and colon cancer. Follow-up time calcu- lated from the last cancer was 2-156 months, with a median of 32 months. And 14 cases survived and 13 cases died, with 11 cases being tumor related. Tumor stage was the risk factor of prognosis. Any kind of tumor stage in stage Ⅲ or above had a relatively poor prognosis. CONCLUSION: MPMN complicated with RCC is relatively rare. Standard treatment should be used for each cancer type during the treatment process. The prognosis mainly depends on the highest stage of each tumor. Simple risk stratification shows that the prognosis of the high-risk group is worse. This simple stratification method may be helpful to predict the prognosis.

[Seasonal variations influenced the semen quality of the sperm donor in Beijing area].

OBJECTIVE: To investigate the change trends of sperm quality with seasonal variations among the volunteers of sperm donors in Beijing area, as well as the relationship between two parameters. METHODS: Semen data from the volunteers of sperm donors in Human Sperm Bank of Peking University Third Hospital were collected using a retrospective study method. The subjects were divided into 4 seasonal groups based on the lunar solar terms and the time of sperm donation. The data were assessed to find whether there were differences in semen parameters among different seasonal groups, and to analyze the change trends and the influence of seasonal factors on semen parameters. RESULTS: A total of 21 174 semen parameter data were analyzed. Firstly, to analyze all data as a whole, in spring, summer, autumn and winter groups, sperm concentration was (106.04±59.67)×106/mL, (97.61±47.41)×106/mL, (100.18±47.17)×106/mL, (100.59±38.68)×106/mL, respectively, and the spring group was significantly higher than the other 3 seasonal groups (P < 0.001); proportion of progressive motility sperm (PR) was 56.49%±12.76%, 58.02%±13.65%, 58.05%±12.36%, and 57.66%±12.61%, respectively, spring group was lower than the other three seasonal groups, and summer group was better among the latter (P < 0.001). There was no difference in normal rate of sperm morphology among the four seasonal groups. The qualified rate of sperm donors in the winter group was higher than that in the other three seasons groups (P < 0.01), while the qualified rate in the summer group was lower than that in the other three seasons groups. In addition, the semen parameters of the volunteers during the screening period and the official sperm donation period were analyzed respectively, which revealed that sperm concentration of spring group was higher than that of summer and winter groups, and PR was lower than that of summer and autumn groups. On account of the semen parameters of official sperm donation period, multiple linear regression analysis found that season was the main factor affecting sperm concentration, the average sperm concentration in spring group was about 6×106/mL higher than in winter group, but PR was 2.9% lower in spring group compared with autumn group (all P < 0.05). CONCLUSION: Season was the influencing factor of semen quality of sperm donors in Beijing area. We recommend spring and winter may be the preferred seasons for sperm donation.

[Intervention effects of drugs on GSH and SOD enzyme activity of rats kidney acutely poisoned by nickel carbonyl].

Objective: To evaluate the intervention effect of various drugs on glutathione (GSH) and superoxide dismutase (SOD) enzyme activity of rats kidney with acute nickel carbonyl poisoning. Methods: In January 2019, The 250 SPF male SD rats were randomly divided into normal control group (n=10) , poisoned group (n=40) and treatment groups (n=200) according to the random number table method. And the treatment groups were divided into methylprednisolone group (20 mg/kg) , DDC group (100 mg/kg) , sodium selenite group (10 µmol/kg) , Shenfu huiyang decoction group (0.25 ml) and methylprednisolone combined with DDC group (100 mg/kg) , with 40 mice in each group. Except for the normal control group, rats in the other groups were exposed to nickel carbonyl for 30 min, at 4 h and 30 h after exposure, the rats in each treatment group were intraperitoneally injected with corresponding drugs, and kidney tissues were collected 3 d and 7 d after administration, with 10 mice in each group. The activities of GSH and SOD in kidney were measured by enzyme-linked immunosorbent assay, and using electron microscopy observe ultrastructure changes. Results: Compared to the control group, the activities of GSH and SOD enzyme of poisoned group were significantly decreased at 3 d or 7 d after 4 h or 30 h exposure, and the difference was statistically significant (P=0.000, 0.031, 0.001, 0.033) , the epithelial nuclei of proximal convoluted tubules were pyknosis and lysosome hyperplasia in the cytoplasm. And compared to poisoned group, the activities of GSH and SOD enzyme of methylprednisolone+DDC group were significantly increased at treatment with 7 d after 4 h exposure, the difference was statistically significant (P=0.022, 0.000) , and the activities of GSH and SOD enzyme of methylprednisolone and enzyme of methylprednisolone+DDC group were significantly higher at 7 days than at 3 days, the difference was statistically significant (P=0.020, 0.017, 0.018, 0.033) . The results of electron microscopy showed that the cell nuclei and cytoplasmic organelles of proximal convolute tubule were almost restored to normal tissue level of both methylprednisolone group and methylprednisolone+DDC group. Conclusion: The methylprednisolone and methylprednisolone+DDC have obvious repair effect on renal enzyme activity level of rats with acute nickel carbonyl poisoning, and the treatment effect is better for a long time of medication.

[Prognostic value of preoperative platelet parameters in locally advanced renal cell carcinoma].

OBJECTIVE: To explore the prognostic value of preoperative platelet parameters in locally advanced renal cell carcinoma for the risk stratification of such patients. METHODS: Clinical data of patients with locally advanced renal cell carcinoma in the Third Hospital of Peking University from January 2015 to December 2017 were collected. The patients were divided into progression group and progression-free group according to follow-up data, and preoperative platelet parameters and clinical data between the two groups were compared. The optimal cut-off value of platelet parameters was determined by receiver operating characteristic curve (ROC) and analyzed by Kaplan-Meier survival curve. Cox proportional hazards model was used to analyze the independent risk factors of PFS. Time dependent ROC curve, net reclassification index (NRI), and integrated discrimination improvement (IDI) were used to evaluate the improvement of SSIGN model by incorporating platelet parameters. RESULTS: Of the 215 patients, 192 (89.3%) were followed up for a median of 36 months. Sixty-four patients (29.8%) had disease progression during the follow-up, and the median PFS was 46 months. In progression group, the platelet count (PLT) was higher [(250.72 ± 88.59)×109/L vs. (227.27 ± 66.94)×109/L, P=0.042] and the platelet distribution width (PDW) was lower [(12.01 ± 2.27)% vs. (13.31 ± 2.74)%, P = 0.001] than that of progression-free groups. 285×109 /L and 12.65% as the best cut-off values of PLT and PDW, the median PFS of PLT≤285×109 /L group was significantly longer than that of PLT>285×109 /L group (53 months vs. 41 months, P=0.033), and the median PFS of PDW>12.65% group was also significantly longer than that of PDW≤12.65% group (56 months vs. 41 months, P < 0.001). Multivariate analysis showed that preoperative PDW (HR=0.735, P < 0.001), nuclear grade Ⅲ to Ⅳ (HR=2.425, P=0.001) and sarcomatoid differentiation (HR=3.101, P=0.008) were independent risk factors for PFS. The area under the curve of PDW combined with SSIGN model was larger than that with the original SSIGN model [0.748 (95%CI: 0.662－0.833) vs. 0.678 (95%CI: 0.583－0.773), P=0.193], NRI was 0.262 (P=0.04), and IDI was 0.085 (P=0.01), indicating that the predictive ability of PDW combined with SSIGN model was improved. CONCLUSION: Preoperative high PLT and low PDW are associated with adverse prognosis of locally advanced renal cell carcinoma, and PDW is an independent risk factor. Therefore, preoperative PDW could serve as biomarker for risk stratification of locally advanced renal cell carcinoma.

[Clinical analysis of testicular rhabdomyosarcoma].

Testicular rhabdomyosarcoma is relatively rare in testicular tumors, but the age of patient is relatively young and the degree of malignancy is high. Therefore, this article introduces 4 cases of testicular rhabdomyosarcoma who were admitted to Peking University Third Hospital from May 1994 to February 2019, and reviews the literature to improve the diagnosis and treatment of this disease. The average age of the 4 patients was 17.5 years (14-21 years), the average hospital stay was 22.0 d (17-31 d), and the average body mass index was 19.6 kg/m2 (14.7-25.8 kg/m2). All the patients underwent routine preoperative blood and urine routine, biochemical tests, as well as serum tumor markers. Preoperative examinations also included chest radiograph, electrocardiogram, ultrasound of the scrotum and groin, and abdominal enhanced CT. Lung CT or other examinations were performed if necessary. The median serum human chorionic gonadotropin (HCG) of the 4 patients was 0.20 IU/L (0.06-0.86 IU/L) (all normal), and the median serum alpha-fetoprotein (AFP) was 1.03 g/L (0.65-1.66 g/L) (all normal). The average maximum diameter of the tumor was 10.0 cm (4.5-15.0 cm). Testicular rhabdomyosarcoma was mainly diagnosed by pathology. The main treatment was radical orchiectomy combined with retroperitoneal lymph node dissection, with or without postoperative adjuvant chemotherapy. The clinical manifestations of the patients with testicular rhabdomyosarcoma had no specific characteristics, but most patients were young at onset with mainly painless masses in the testicles, which were already large when they were found. Patients with testicular rhabdomyosarcoma have a poor prognosis, most of whom recur within two years. Because of the small number of cases of testicular rhabdomyosarcoma, there is no standard treatment currently. It is recommended that patients with testicular rhabdomyosarcoma undergo radical testicular resection combined with retroperitoneal lymph node dissection. Retroperitoneal lymph node metastasis is an important prognostic factor, and patients with postoperative adjuvant chemotherapy can still survive for a longer time. If local recurrence or limited metastasis is found after operation, local resection and salvage radiotherapy are feasible.

[Clinical and pathological features of renal cell carcinoma with urinary tract tumor thrombus: 6 cases report and literature review].

OBJECTIVE: To investigate the clinical characteristics, diagnosis and treatment of renal cell carcinoma with urinary tract tumor thrombus. METHODS: From January 1, 2015 to December 31, 2019, patients with renal cell carcinoma complicated with urinary tract tumor thrombus who were hospitalized in the Peking University Third Hospital and Beijing Friendship Hospital, Capital Medical University were retrospectively analyzed. Meanwhile, we reviewed the literature, and the reported patients of renal cell carcinoma with urinary tract tumor thrombus were also included in our study. The basic information, clinical manifestations, treatment, pathological characteristics and follow-ups of all the patients were analyzed. RESULTS: In our study, 6 patients from the two hospitals and 16 patients from previous literature reports were included. There were 13 males and 9 females with an average age of 54.7 years (22-79 years). Fifteen patients had renal cell carcinoma on the left side, 6 on the right side, and 1 on the unknown side. Gross hematuria was the most common chief complaint, including 18 patients. One patient complained of weight loss, 1 patient complained of microscopic hematuria, and 1 patient was found by ultrasound examination. Tumor thrombus was classified as grade Ⅰ in 9 cases (the tumor embolus protruded into the renal pelvis, but did not reach the ureteropelvic junction), grade Ⅱ in 10 cases (the tumor embolus protruded into the ureter, but not into the bladder), and grade Ⅲ in 3 cases (the tumor embolus passed through the ureter and protruded into the bladder). Only 11 patients were diagnosed with renal cell carcinoma before operation. Radical nephrectomy was performed in 9 cases and nephroureterectomy in 12 cases. In pathological diagnosis, there were 15 cases of clear cell renal cell carcinoma, 1 case of papillary renal cell carcinoma, 1 case of chromophobe cell carcinoma, 1 case of mixed cell renal cell carcinoma, 4 cases of renal cell carcinoma with undetermined classification. Eleven patients were followed up for 3-31 months, and 3 patients had lung metastasis within 6 months. CONCLUSION: Renal cell carcinoma with urinary tract tumor thrombus is rare in clinic. It needs to be differentiated from renal pelvis carcinoma in diagnosis. The treatment principle can refer to general renal carcinoma. For locally advanced cases, complete resection is the best treatment, and its oncological prognosis needs more long-term and large-scale follow-up observation.

[Influence of deep invasive tumor thrombus on the surgical treatment and prognosis of patients with non-metastatic renal cell carcinoma complicated with venous tumor thrombus].

OBJECTIVE: To evaluate the impact of deep invasive tumor thrombus on the surgical complexity and prognosis of patients with renal cell carcinoma complicated with inferior vena cava tumor thrombus. METHODS: We retrospectively reviewed the clinical data of 94 patients with non-metastatic renal cell carcinoma complicated with inferior vena cava tumor thrombus, who underwent surgical treatment in Peking University Third Hospital from January 2017 to June 2020. The patient's general condition, clinicopathological characteristics, surgery and survival information were collected. The patients were divided into two groups based on the intra-operative findings of tumor thrombus adhesion to the venous wall, of which 64 cases were in the deep invasive tumor thrombus (DITT) group and 30 cases were in the non-invasive tumor thrombus (NITT) group. Chi-square, t test and Mann-Whitney U test were used for categorical and continuous variables respectively. Kaplan-Meier plots and multivariable Cox regressions were performed to evaluate the influence of DITT on the prognosis of the patients with renal cell carcinoma with inferior vena cava tumor thrombus. RESULTS: DITT significantly increase the difficulty of surgery for the patients with renal cell carcinoma with venous tumor thrombus, which was mainly reflected in the longer operation time (362.5 vs. 307.5 min, P=0.010), more surgical bleeding (1 200 vs. 450 mL, P=0.006), more surgical blood transfusion (800 vs. 0 mL, P=0.021), more plasma transfusion (200 vs. 0 mL, P=0.001), a higher proportion of open surgery (70.3% vs. 36.7%, P=0.002), a longer post-operative hospital stay (9.5 vs. 8 days, P=0.036), and a higher proportion of post-operative complications (46.9% vs. 13.8%, P=0.002). DITT was associated with worse overall survival of the patients with renal cell carcinoma with inferior vena cava tumor thrombus (P=0.022). Even in the multivariate analysis, DITT was still a poor prognostic factor for the overall survival of these patients [HR: 4.635 (1.017-21.116), P=0.047]. CONCLUSION: For patients with non-metastatic renal cell carcinoma with inferior vena cava tumor thrombus, DITT will significantly increase the difficulty of surgery, and may lead to poor prognosis.

[Risk factors of renal sinus invasion in clinical T1 renal cell carcinoma patients undergoing nephrectomy].

OBJECTIVE: To summarize the clinicoradiological characteristics of clinical T1 renal cell carcinoma patients and to investigate the risk factors of renal sinus invasion in cT1 renal cell carcinoma patients undergoing nephrectomy. METHODS: A retrospective study was conducted in cT1 renal cell carcinoma patients from January 2016 to August 2019 in Department of Urology, Peking University Third Hospital, who underwent partial or radical nephrectomy by analyzing clinicopathological and radiological data. The influencing factors of renal sinus invasion for cT1 renal cell carcinoma were determined by χ2 test, Mann-Whitney U test and Logistic regression analysis. RESULTS: A total of 507 patients were enrolled, including 354 males (69.8%) and 153 females (30.2%). The median age was 59 years and the median body mass index (BMI) was 25.5 kg/m2. Eighteen patients (3.6%) had gross hematuria preoperatively. The median tumor diameter was 3.5 cm. Three hundred twenty-two patients (63.5%) were staged clinical T1a and 165 cases (36.5%) were staged clinical T1b. The median R.E.N.A.L. score was 8. Three hundred fifty-nine patients (70.8%) had regular tumor border and 148 (29.2%) irregular. All the patients underwent surgical treatment, including 186 (36.7%) partial nephrectomy and 321 (63.3%) radical nephrectomy. Postoperative pathology showed seventy-five patients (14.8%) had renal sinus invasion, including 18 in cT1a (5.6%) and 57 in cT1b (30.8%). Univariate analysis showed that age (P=0.020), R.E.N.A.L. score (R value, E value, N value, P < 0.001) and tumor border (P < 0.001) were associated risk factors for cT1 renal cell carcinoma with renal sinus invasion. On multivariate binary Logistic analysis, R.E.N.A.L. score (P≤0.020) and irregular tumor border (P=0.001) were independent risk factors. CONCLUSION: For cT1 renal cell carcinoma patients undergoing nephrectomy, about 15% had renal sinus invasion postoperatively. High R.E.N.A.L. score and irre-gular tumor border help predicting cT1 renal cell carcinoma renal sinus invasion.

[Relationship between prostate apex depth and early recovery of urinary continence after laparoscopic radical prostatectomy].

OBJECTIVE: To evaluate the relationship between recovery of urinary continence after laparoscopic radical prostatectomy (LRP) and preoperative prostate apex depth (PAD) on magnetic resonance imaging (MRI). METHODS: We retrospectively analyzed 184 patients with pathologic confirmed prostate carcinoma who underwent LRP in Department of Urology, Peking University Third Hospital. All the patients received MRI examination before surgery. Membranous urethral length (MUL) was defined as the distance from the apex of prostate to the level of the urethra at penile bulb on the coronal image. PAD was defined as the distance from the apex of prostate to the suprapubic ridge line on sagittal MRI. PAD ratio (PADR) was defined as PAD/pubic height. All the patients received extraperitoneal LRP. The patients' reporting freedom from using safety pad (0 pad/d) were defined as urinary continence. Univariate and multivariate regression analyses were used to identify independent predictors of early continence recovery after LRP. Kaplan-Meier analyses and log-rank test were used to compare time to continence recovery between the groups. RESULTS: For all the 184 patients, the average age was (69.0±7.7) years, the ave-rage mass index(BMI) was (25.07±3.29) kg/m2, and the pre-biopsy PSA was (16.80±21.99) g/L. For all the patients who underwent MRI preoperatively, the mean PV was (39.35±25.25) mL and the mean MUL was (14.0±3.7) mm. The mean PAD was (24.52±4.97) mm and the mean PADR was 0.70±0.14. The continence rate for all the patients after LRP was 62.0% and 96.2% in three months and one year. The patients achieving early continence recovery had significant smaller PV (P=0.049), longer MUL (P < 0.001) and higher PADR (P=0.005). Multivariate analysis revealed MUL (P < 0.001) and PADR (P=0.032) were predictors of continence recovery after LRP. Kaplan-Meier analyses and Log-rank test revealed that MUL (≥14 mm vs. < 14 mm, P < 0.001) and PADR (≥0.70 vs. < 0.70, P < 0.001), PV(< 50 mL vs. ≥50 mL, P=0.001) were all significantly associated with continence recovery. CONCLUSION: MUL and PADR are independent predictors of early continence recovery after LRP. MUL, PADR and PV are significantly associated with recovery of urinary continence.

[Primary application of Gerota's fascia suspension device in retroperitoneal laparoscopic partial nephrectom].

OBJECTIVE: To evaluate the value of Gerota's fascia suspension device in retroperitoneal laparoscopic partial nephrectomy, and to share the operation experience. METHODS: From October 2018 to December 2020, 6 cases of tumor located in the ventral side of the kidney were selected, including 3 males and 3 females, with 3 cases on the right side and 3 cases on the left side, aged 38-60 years, with an average of 52 years. The body mass index (BMI) was 18.3-30.2 kg/m2, with an average of 22.9 kg/m2. One patient with diabetes mellitus, three patients with renal cysts, and two patients underwent cholecystectomy before. All the patients were found by physical examinations. The course of disease was 7 days to 20 years, with a median time of 1 month. The tumor was in the ventral side of the kidney, 2 cases located in the upper pole, 1 case in the lower pole and 3 cases near the renal hilum. The tumor size was 1.2-7.8 cm, with an average of 4.5 cm. The R.E.N.A.L score was 7 in 1 case, 8 in 3 cases and 9 in 2 cases. After the preoperative examination completed, retroperitoneal laparoscopic partial nephrectomy (Gerota's fascia suspension device) was performed. RESULTS: All the operations were successfully completed. The operation time ranged from 139 to 193 min, with an average of 172 min. The renal artery occlusion time was 7-43 min, with an average of 19 min, only one case was more than 30 min. The blood loss ranged from 10 to 500 mL, with an average of 128 mL. The postoperative hospital stay ranged from 4 to 13 days, with an average of 6.5 days. Postoperative pathology revealed 4 cases of renal angiomyolipoma and 2 cases of renal clear cell carcinoma. The patients were followed up for 2-27 months, with an average of 17 months, without recurrence. CONCLUSION: In the operation of retroperitoneal laparoscopic partial nephrectomy, Gerota's fascia suspension device is beneficial to expose the ventral surgical field, and it is convenient for the surgeon to operate with both hands. This technique is an effective method to deal with the ventral renal tumor, which is worthy of promotion.

[Strategy of reoperation for pheochromocytoma and paraganglioma].

OBJECTIVE: To explore the surgical strategy and experience of reoperation for pheochromocytoma and paraganglioma which is very challenging. METHODS: The clinical data of 7 patients with pheochromocytoma and paraganglioma who underwent reoperation in Department of Urology, Peking University Third Hospital from August 2016 to February 2021 were analyzed retrospectively. There were 4 males and 3 females, with an average age of (44.1±11.5) years (28-60 years), 6 cases on the right side and 1 case on the left side. The causes of the operations included: (1) 2 cases of tumor recurrence after resection; (2) The primary operations failed to completely remove the tumors in 3 cases, because the tumors were large and closely related to blood vessels. (3) Pheochromocytoma and paraganglioma wasn't diagnosed before primary operation, therefore, drug preparation wasn't prepared. Two cases were interrupted by severe blood pressure fluctuations during the primary operations. Imaging evaluation, catecholamine biochemical examination and adequate adrenergic α receptor blockers were administrated in all the cases. The surgical approaches included open transperitoneal surgery in 4 cases, robot-assisted laparoscopy in 1 case and retroperitoneal laparoscopy in 2 cases. The innovative techniques included mobilization of the liver, inferior vena cava transection and anastomosis, and transection of left renal vein. RESULTS: The average tumor size was (8.0±3.2) cm (3.6-13.9 cm). The median interval between the reoperation and the primary operation was 9 months (IQR: 6, 19 months). The median operation time was 407 min (IQR: 114, 430 min) and the median blood loss was 1 500 mL (IQR: 20, 3 800 mL). Operations of 5 cases were performed successfully, and 1 case failed only by exploration during the operation. One case died perioperatively. There were 5 cases of intraoperative blood transfusion, the median transfusion volume of red blood cells was 800 mL (IQR: 0, 2 000 mL). One case experienced postoperative lymphorrhagia, and recovered after conservative treatment. The renal function was normal in 2 cases after resection and anastomosis of inferior vena cava or transection of left renal vein. The average postoperative hospital stay was (7.2±3.3) d (4-13 d). The median follow-up time of 6 patients was 33.5 months (IQR: 4.8, 48.0 months). The case who failed in the reoperation still survived with tumor and there was no recurrence in the rest of the patients. CONCLUSION: The reoperation of pheochromocytoma and paraganglioma, which can not be resected in the primary operation or recurred postoperatively, is difficult with high risk of hemorrhage, and there is a risk of failure and perioperative death. Different surgical approaches and strategies need to be adopted based on the different situation.

[Bilateral papillary renal cell carcinoma following kidney transplantation: A case report].

With the continuous development of kidney transplantation technique, the survival time after kidney transplantation is gradually prolonged. Thus, the malignant tumor has been the important influencing factor on the long-term survival for kidney transplantation patients. Renal cell carcinoma is a relatively common tumor after kidney transplantation. Besides, clear cell renal cell carcinoma and papillary renal cell carcinoma are the relatively common pathological types for renal cell carcinoma following kidney transplantation. However, bilateral renal cell carcinoma following kidney transplantation is comparatively rare. In this article, we presented a case of bilateral papillary renal cell carcinoma, which occurred after kidney transplantation. And the diagnosis and treatment were introduced in detail. The patient was 37 years old, and he underwent kidney transplantation 13 years ago in our hospital, because of kidney failure. After kidney transplantation, he had regular medical check-up every year. In this year, his urological ultrasound results indicated bilateral renal tumors. And then, he received abdominal and pelvic computed tomography, and the result also showed bilateral renal tumors, which were likely to be malignant tumors. After adequate consultation, the patient chose surgical treatment. The patient received long-term immunosuppressive therapy, because of kidney transplantation. Considering this, the surgeon decided to choose a staging surgical treatment, in order to reduce the bad influence of one-stage surgery. Then, the patient first underwent retroperitoneal laparoscopic radical nephrectomy for right renal tumor in our hospital, and he had no complications after operation. The pathological results showed papillary renal cell carcinoma. He was discharged successfully. He underwent retroperitoneal laparoscopic radical nephrectomy for left renal tumor in our hospital one month later, and he had no complications after operation. The pathological results also showed papillary renal cell carcinoma. He was discharged successfully two days after surgery. In the 3-month follow-up, the patient was recovering well. To sum up, the incidence of bilateral renal cell carcinoma following kidney transplantation is relatively rare, and bilateral radical nephrectomy is effective and safe treatment. Above all, it is the patient's condition that determines the choice of staging surgery or simultaneous surgery.

[Effect of birth spacing on the pelvic floor type â and type â ¡ fiber muscle strength of postpartum women with parities of two in different delivery modes].

Objective: To speculate the effect of birth spacing on the pelvic floor type Ⅰ and Ⅱ fiber muscle strength of postpartum women with parities of two in different delivery modes. Methods: Totally 2 361 parturients who were investigated in Xuzhou Central Hospital from June 2016 to December 2020 were included in the questionnaire, clinical examination and pelvic floor surface electromyography assessment. According to the interval years between two parities and the pelvic floor typeⅠ and Ⅱ fiber muscle strength under different modes of delivery, curve fitting function equation was performed using curve regression method. The accuracy of the equation was verified by the receiver operating characteristic curve and the maximum area under the curve, and calculating the relative error rate. Results: A total of 2 357 parturients were included in the study and were divided into 4 groups based on delivery modes, women with both normal vaginal delivery were assigned to group A (589 cases); women with a first vaginal delivery and a second cesarean section were assigned to group B (480 cases); women with both cesarean deliveries were assigned to group C (1 273 cases); women with a first cesarean section and a second vaginal delivery were assigned to group D (15 cases). All of the curve fitting results were quadratic curves, and the appropriate interval years were selected when the muscle strength of type Ⅰ muscle fibers was>35 µV and that of type Ⅱ muscle fibers was>40 µV: 6-8 years in the group A, 5-10 years in the group B, and 1-11 years in the group C. The peak values of the quadratic curve were as follows: 7-8 years in the group A, 7-8 years in the group B, and 6 years in the group C. The maximum area under the curve of the function equations were all>0.6 (all P<0.05), the average relative error rate was 4.909%. Conclusions: The pelvic floor function of postpartum women with parities of two increases firstly and then decreases over time, showing a quadratic curve shape. In order to protect the pelvic floor function, the appropriate interval of birth spacing is 6-8 years.

[Surgical strategy selection and experience summary of prostate cancer with positive single needle biopsy].

OBJECTIVE: To analyze the clinicopathological characteristics of prostate cancer patients undertaking radical prostatectomy with single positive core biopsy, and to optimize the rational choice of therapeutic strategy. METHODS: In the study, 53 patients with single positive core prostate biopsy and treated by radical prostatectomy from January 2010 to December 2018, were analyzed retrospectively. The mean age was (69.7±6.9) years (54-81 years), the mean prostate specific antigen (PSA) level was (9.70±5.24) µg/L (1.69-25.69 µg/L), and the mean prostate volume was (50.70±28.39) mL (12.41-171.92 mL). Thirty-nine out of 54 (73.6%) patients presented Gleason score with 6, 11 patients (20.8%) had Gleason score of 7 and 3 patients (5.7%) showed Gleason score ≥8. For clinical stages, 6 out of the 53 patients (11.3%) had prostate cancer in cT1, 44 cases (83.0%) had prostate cancer in cT2, and 3 cases (5.7%) in cT3.The patients were divided into subgroups according to age, preoperative PSA level, Gleason score, percentage of tumor in single needle tissue and clinical stage, and the differences of their clinicopathological characteristics were compared. RESULTS: Postoperative Gleason score of 6, 7 and ≥8 were found in 20 cases (37.7%), 21 cases (39.6%) and 10 cases (18.9%) respectively, another 2 cases (3.8%) were pT0 prostate cancer; pathological stages of T0, T2a, T2b, T2c and T3 were found in 2 cases (3.8%), 9 cases (17.0%), 2 cases (3.8%), 29 cases (54.7%) and 11 cases (20.8%) respectively; 11 cases (20.8%) had positive surgical margin, 10 cases (18.9%) had extracapsular invasion of prostate, and 1 case (1.9%) showed seminal vesicle invasion. Forty-two cases (79.2%) had multifocal lesions and 37 cases (69.8%) presented bilateral lesion. Compared with the biopsy Gleason score, the postoperative Gleason score was downgrated in 3 cases (5.7%), unchanged in 28 cases (52.8%), and upgraded in 20 cases (37.7%), of which 2 cases (3.8%) were pT0. Compared with the clinical stage, the postoperative pathological stage decreased in 2 cases (3.8%), unchanged in 10 cases (18.9%), and upgraded in 41 cases (77.4%). According to the postoperative pathology, the patients were divided into two groups: microfocus cancer group (n=8) and non-microfocus cancer group (n=45). The difference between the two groups in the percentage of tumor in the single-needle tissue ≤5% was statistically significant (P=0.014). Other parameter diffe-rences including age, prostate volume, and preoperative prostate special antigen density (PSAD) and Gleason scores were not statistically significant (P>0.05). The method to determine the location of cancer at the apex of prostate according to biopsy results showed 41.4% (12/29) false negative rate and 50.0% (12/24) false positive rate. There was statistically significant difference between the actual cases of lymph node dissection and reserved nerve and the cases of scheme selection in theory according to the postoperative pathology (P < 0.05). CONCLUSION: The proportion of single needle cancer tissue less than or equal to 5% is a predictor of prostate microfocal cancer. 37.7% cases had pathological upgrading and 77.4% cases had pathological staging upgrading. When choosing the operation scheme, such as sexual nerve reserved, lymph node dissection and apex operation skill, it is necessary to comprehensively analyze multiple factors, such as tumor risk classification, prediction factors of nomogram, multi-parameter MRI and intraoperative situation and so on.

[Usefulness of the indocyanine green fluorescence imaging technique in laparoscopic partial nephrectomy].

OBJECTIVE: To detail a novel technique for marking renal tumors with intravenous indocyanine green (ICG) during laparoscopic partial nephrectomy, and to investigate the feasibility and safety of this technique with the use of near-infrared fluorescence imaging. METHODS: Between July 2019 and January 2020, 25 consecutive cases with renal masses underwent intraoperative ICG tumor marking laparoscopic partial nephrectomy, at the department of urology in Peking University Third Hospital by the same surgeon. The key benefits included quick intraoperative identification of the mass with improved visualization and real-time control of resection margins by the ICG Immunofluorescence imaging technique. Clinical data were prospectively collected in our institutional database. Perioperative, pathological, and clinical outcomes of the partial nephrectomy were assessed. Measurement data with normal distribution and count data were respectively described as M(range) and percentage. Among these cases, 16 cases were male and 9 cases female, The median body mass index was 25.4 (20.0-35.4) kg/m2. The average age was 54 (29-77) years. The maximum tumor diameter was 2.75(1.30-5.20) cm. The R.E.N.A.L score was 7.5 (5.0-10.0).The tumor locations were distributed with upper pole (11, 42%), middle (6, 23%), and lower pole (9, 35%).The clinical stages of the tumor were described as follows: T1aN0M0 (23, 88.5%), T1bN0M0(2, 7.7%), T2aN0M0 (1, 3.8%). RESULTS: All the 25 cases were performed 26 times with intraoperative ICG tumor marking laparoscopic partial nephrectomy. There were no allergy, infection and other complications with intravenous indocyanine green. The surgical procedure was successful in all the patients. No conversion and blood transfusion were needed. All the cases of the surgical margin were negative. Overall the operative time was 136 (50-247) min and warm ischemia time was 14 (7-30) min.The estimated blood loss was 50 (10-400) mL and the hospital stay was 5.5 (3.0-31.0) days. One case with perirenal hematoma, one case with urine leak, one with respiratory failure and deep venous thrombosis. All of these cases were cured by the corresponding treatment. The others had no severe complications. There was no tumor recurrence and metastasis during the follow up with 4 to 10 months. CONCLUSION: ICG marking and near-infrared fluorescence imaging technology has now emerged as a safe, feasible and useful tool that may facilitate laparoscopic partial nephrectomy.