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.

[Clinical features of immune checkpoint inhibitor-related myositis in patients with urological cancer].

OBJECTIVE: Immune checkpoint inhibitors (ICI) have significantly improved the treatment efficacy of a variety of malignant tumors. However, patients may experience a series of special side effects during treatments with ICI. Immune-related myositis after ICI treatment is characterized by autoimmune rheumatic and musculoskeletal damage, which is relatively rare. To analyze the clinical characteristics and outcomes of ICI-associated myositis in urological tumors, we summarized the clinical manifestations, electrophysiological and pathological characteristics, treatments and outcomes in 8 patients. METHODS: The clinical data of the 8 patients with immune-related myositis after ICI treatment for urological tumors treated in the Department of Urology, Peking University First Hospital from March 2018 to March 2022 were retrospectively analyzed for demographic characteristics, drug regimen, clinical symptoms, laboratory indices, electromyography examination, pathological manifestations and outcomes. RESULTS: The eight patients included 2 females and 6 males with a median age of 68 years, all treated with ICI for urological neoplasms, including 2 upper tract urothelial carcinoma (UTUC), 3 renal cell carcinoma (RCC), and 3 bladder cancer (BCa). The median time between the first ICI treatment and the detection of immune-related myositis was 39.5 days, and the median duration of treatment was 2 sessions. The main symptoms were muscle pain and weakness, 5 cases with ptosis, 3 cases with secondary rhabdomyolysis, 5 cases with myocarditis, 1 case with myasthenia gravis, and 1 case with enterocolitis. Among them, patients with immune-related myocarditis had a shorter interval from the first anti-programmed cell death protein-1 (PD-1) therapy to the onset of immune-related myositis (P=0.042) compared with patients without myocarditis. The 8 patients had significant elevation of transaminases and muscle enzyme profile indexes, and 5 patients showed positive auto-antibodies. 3 patients had perfected muscle biopsies and showed typical skeletal muscle inflammatory myopathy-like pathological changes with CD3+, CD4+, CD8+, CD20+ lymphocytes and CD68+ macrophage infiltration. After the diagnosis of immune-related myositis, all the 8 patients immediately discontinued ICI therapy and improved after intravenous administration of methylprednisolone alone or in combination with gamma-globulin. CONCLUSION: Immune-related myositis after ICI treatment is an immune-related adverse reactions (irAEs) with unique clinical and pathological features, commonly combined with cardiovascular adverse reactions. Immediate discontinuation of ICI and initiation of glucocorticoid therapy may improve the patient's condition in a timely manner.

[Clinical efficacy of docetaxel combined with carboplatin in patients with metastatic castration-resistant prostate cancer].

OBJECTIVE: To observe the early efficacy and toxicity of docetaxel combined with carboplatin in patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: From May 2017 to July 2019, fifteen patients with mCRPC treated in Peking University First Hospital were collected. The median age was 70 years (43-77 years), and the pathological types were all adenocarcinoma, which was confirmed as distant metastasis by imaging examination. They were given the chemotherapy of docetaxel combined with carboplatin. The specific method was as follows: each cycle was 28 days. Androgen deprivation therapy was administered routinely throughout the treatment period. Blood routine, liver and kidney function, blood clotting function and prostate-specific antigen (PSA) tests were performed before each cycle. Docetaxel was administered intravenously on the first day of each cycle at a dose of 75 mg/m2, and carboplatin was administered intravenously on the second day at the dose calculated by Calvert formula. The main outcome measures including PSA decline range, pain remission rate and occurrence of adverse reactions were observed and analyzed. RESULTS: Among the 15 patients, 12 had completed at least 4 cycles of chemotherapy and had short-term efficacy evaluation. PSA decline range > 50% was observed in 8 patients (66.7%). Among the 9 patients with bone pain, remarkable pain relief was observed in 4 patients (44.4%). Among the 4 patients with measurable metastatic lesions, 2 achieved partial response, 1 was evaluated as stable disease, and 1 was evaluated as progressive disease. The main adverse reactions of chemotherapy included bone marrow suppression, gastrointestinal reactions, fatigue and neurological disorders, and most of them were within the tolerable range. CONCLUSION: This report is a case series study of docetaxel combined with carboplatin in the treatment of mCRPC reported in China and the conclusions are representative. The chemotherapy of docetaxel combined with carboplatin has positive short-term efficacy and high safety in patients with mCRPC, which is worthy of further promotion and exploration in clinical practice.

[One-stage surgery in patients with both cardiac and non-cardiac diseases].

OBJECTIVE: To investigate the possibility and feasibility of one-stage cardiac and non-cardiac surgery. METHODS: From July 1999 to August 2018, one hundred and eleven patients suffering from cardiac and non-cardiac diseases were treated by one-stage cardiac and non-cardiac operation in Department of Cardiac Surgery and Thoracic Surgery, General Surgery, Urinary Surgery, and Gynecology, Peking University First Hospital. There were 83 males (74.8%) and 28 females (25.2%), aged 41 to 84 years [mean age: (64.64±8.97) years]. The components of the cardiac disease included coronary heart disease, valvular heart disease, cardiac tumors, chronic constrictive pericarditis and congenital heart disease. The components of the non-cardiac diseases included lung benign and malignant diseases, thymoma and thymic cyst, breast cancer, chest wall giant hemangioma, digestive tract benign and malignant diseases, urinary system carcinoma and gynecological diseases. RESULTS: Two patients died after operations in hospital; thus, the hospital mortality rate was 1.8%. One patient died of multiple organ failure on the 153th days after emergency coronary artery bypass grafting (CABG) combined with radical resection of bladder cancer. The other of pericardium stripping with lung cancer operation died of the multiple organ failure on the tenth day after surgery. The remaining 109 patients recovered and were discharged. There were 13 cases of complications during the days in hospital. The total operative morbidity was 11.7%: postoperative hemorrhage in 2 cases (1.8%), pulmonary infection and hypoxemia in 3 cases (2.7%), hemorrhage of upper digestive tract in 1 case (0.9%), incisional infection in 3 cases (2.7%), subphrenic abscess in 1 case (0.9%), and postoperative acute renal failure and hemofiltration in 3 case (2.7%). Of the 109 patients discharged, 108 patients were followed up. All the patients survived for 6 months, and 21 patients died due to tumor recurrence or metastasis within 1 to 5 years of follow-up, but no cardiogenic death. During the follow-up period, 1 patient developed cardiac dysfunction, 1 patient underwent percutaneous coronary intervention (PCI), 1 patient had cerebral hemorrhage due to excessive postoperative anticoagulation, and 1 patient suffered from incisional hernia. CONCLUSION: One-stage surgeries in patients suffering from both cardiac and non-cardiac benign or malignant diseases are safe and possible with satisfactory short-term and long-term survival.

[A clinical analysis of 14 cases of prostatic stromal tumor of uncertain malignant potential].

OBJECTIVE: To investigate the clinical and pathologic characteristics, diagnosis, treatment, prognosis and survival of prostatic stromal tumor of uncertain malignant potential. METHODS: Overall 14 patients with prostatic stromal tumor of uncertain malignant potential were treated from October 2008 to April 2020, the patient age ranged from 27 to 78 years (mean 54 years). The disease duration was 1 to 180 months (mean duration of 46 months). The clinical manifestations mainly included urinary obstructive symptoms and urethral irritating symptoms. The tumors were located in the peripheral zone or the transition zone. Digital rectum examination indicated prostatic tumor. Serum prostatic specific antigen level was always normal or elevated. Transrectal ultrasonography and magnetic resonance imaging indicated prostatic tumor. Magnetic resonance imaging in showed large, round, well-defined masses, which were diffusely heterogeneous signal on T2 weighted imaging. Following the administration of intravenous contrast medium, the lesion had diffuse and heterogeneous enhancement. RESULTS: In the study, 3 cases underwent prostate biopsy, 2 cases underwent transurethral resection of the prostate, 9 cases underwent radical excision or transurethral resection of the prostate with definite diagnosis of pathologic features. Under the light microscope, the interstitial cells of stromal tumor of uncertain malignant potential were overgrowth and fusiform cells showed some degree of pleomorphism, nuclei with few mitotic figures, and necrosis was not often seen. Immunohistochemical staining showed that prostate specific antigen was negative, while vimentin was positive in the tumor tissue, CD34, progesterone receptor and smooth muscle actin were positive in the majority, and Ki67 positive index was 1%-20% (mean 6%). Twelve cases were followed-up, and the time of survival varied from 10 to 96 months (mean 65 months), two cases were lost to the follow-up, one case died of disease at the end of 10 months, nine cases were free of disease recurrence after surgery, two cases underwent more transurethral resection of the prostate due to local recurrence. CONCLUSION: STUMP is a very rare tumor of the specialized prostatic stroma with an unpredictable clinical behavior. The clinical manifestations, transrectal ultrasonography and magnetic resonance imaging are valuable for the diagnosis of prostatic stromal tumor of uncertain malignant potential. Its definite diagnosis depends on pathological examination. Up to now, early surgery and combined therapy are effective treatments for prostatic stromal tumor of uncertain malignant potential.

[Clinicopathologic features and prognostic analyses of locally recurrent renal cell carcinoma patients after initial surgery].

OBJECTIVE: To evaluate the clinicopathologic features and potential prognostic predictors of locally recurrent renal cell carcinoma patients after initial surgery. METHODS: Authors retrospectively analyzed data extracted from 81 patients who were treated for postoperative locally recurrence of renal cell carcinoma from January 2006 to June 2016 in the Department of Urology, Peking University First Hospital. Postoperative locally recurrence of renal cell carcinoma was defined as disease recurring in the remnant kidney, renal fossa, adjacent abdomen, ipsilateral adrenal and retroperitoneal lymph nodes. RESULTS: In the study, 81 patients were finally included, of whom 43 were initially treated in our hospital and 38 were initially treat in other centers. Partial nephrectomy (PN) was performed for 38 cases (26 in our hospital and 12 in other hospitals) as initial treatment and radical nephrectomy (RN) was conducted for the remnant 43 cases (17 in our hospital and 26 in other hospitals). Overall median recurrence time was 26 months (range: 3-164 months), in which 26 months (range: 3-55 months) for PN cases and 30 months (range: 4-164 months) for RN cases (P=0.009). Sixty-nine patients had single site recurrence, including remnant kidney (n=29), renal fossa (n=20), abdomen (n=4), ipsilateral lymph nodes (n=5), ipsilateral adrenal (n=11), while 12 patients had multiple sites recurrence. Seventy-eight patients were managed by complete surgical resection, while three patients were managed by radiofrequency ablation. Postoperative pathological diagnoses included clear cell carcinoma (n=72), papillary renal cell carcinoma (n=8, 7 cases with type 1, 1 case with type 2) and Xp11 translocation/TFE3 gene fusion renal cell carcinoma (n=1). Complete pathologic information of the initial surgery could be extracted from 43 patients who were initially treated in our hospital. Seventeen patients with initial radical nephrectomy were staged as T1a (n=4), T1b (n=2), T2a (n=1), T3a (n=8), and T3b (n=2). Twenty-six patients with initial partial nephrectomy were staged as T1a (n=18), T1b (n=7), and T3a (n=1). For PN cohort, the patients with T1a stage disease had longer median recurrence time than those with beyond T1a stage disease, and the difference was significant (29 months vs. 18 months, P=0.041). At the end of the follow-up, 58 patients were alive, 4 died and 19 lost the follow-up. Overall, 3-year and 5-year disease free survival rates were 81.9%, and 53.6%, respectively. CONCLUSION: The present research reported a large-scale single central experience of locally recurrent renal cell carcinoma. The recurrence time of the PN group is shorter than that of the RN group. For patients after PN surgery, median recurrence time is longer for patients with T1a stage tumor when compared with those with stage beyond T1a. Patients can obtain relative long-term survival after complete secondary surgery resection.

[Evaluating inferior vena cava wall invasion in renal cell carcinoma tumor thrombus with MRI].

OBJECTIVE: To evaluate the diagnostic performance of MRI for the assessment of inferior vena cava (IVC) wall invasion by IVC thrombus in patients with renal cell carcinoma (RCC). METHODS: We retrospectively collected patients who underwent radical nephrectomy and thrombectomy for RCC between 2010 and 2018 at Peking University First Hospital. All the patients underwent imaging on a 1.5 Tesla or 3.0 Tesla MRI scanner. Fifty-six patients met the inclusion criteria. Preoperative imaging was reviewed by two radiologists blinded to details of the patient's surgical procedure and histopathology. Two radiologists measured the maximum anterior-posterior diameter and coronal diameters of the IVC and renal vein, and the craniocaudal extent of tumor thrombus, and evaluated the MRI features of IVC thrombus, including occlusion of the IVC lumen, the margin of the tumor thrombus (smooth vs. irregular), contact of the IVC thrombus and IVC wall, and altered signal of the IVC wall. Univariable and multivariable associations of clinical and radiographic features with IVC wall invasion were evaluated by Logistic regression. RESULTS: Of the 56 patients [male: 43, female: 13, mean age: (55.64±0.43) years], 17 (30.36%) were detected with IVC wall invasion, and most were clear cell carcinoma. Tumor thrombus with IVC wall invasion showed an increase in length of IVC thrombus [(7.91±3.59) cm vs. (5.94±3.57) cm, P=0.049], and more features of complete occlusion of the IVC lumen (P=0.002), irregular margin of the IVC thrombs (P=0.005), contact of the IVC thrombus and IVC wall (P=0.001), and altered signal of the low-intensity vessel wall (P<0.001), with a sensitivity of 94.12% and a specificity of 79.49%. CONCLUSION: The present study indicates that MRI could be a means of evaluating RCC with IVC wall invasion, and the combination of tumor thrombus length and subjective impression of IVC wall invasion achieved a high sensitivity and specificity for diagnosis.

[The clinical focus and prospect of medical treatments in genitourinary tract tumors].

In recent years, the field of medical treatment of genitourinary tract tumors has made rapid progress. Precision medicine has provided important role in selecting the potential patients. Immunotherapy is a new choice for metastatic disease. The combination therapy has also brought the light for better tumor control. This article briefly introduces these progresses and provides new conception and research directions for treatment of genitourinary tract tumors.

[Clinical features analysis of metanephric adenoma: a series of 16 cases].

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.

[Clinical features and prognosis of rare subtypes of renal cell carcinoma].

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.

[The impact to operation safety of preoperative renal artery embolization for management of diameter≥10 cm renal cell carcinoma].

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 χ(2) 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%, χ(2)=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%, χ(2)=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.

[Percutaneous biopsy of the renal masses under ultrasound: a single-center 14 years experience].

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.

[Clinical and pathological characteristics of prostate cancer patients younger than 55 years old].

Objective: Prostate cancer is commonly diagnosed among old men while younger men are rarely diagnosed with prostate cancer. In this study we identify clinical and pathological features of 154 patients with prostate cancer younger than 55 years old and to assist intreatment decisions. Methods: The medical records of 154 prostate cancer patients younger than 55 years old in Peking University First Hospital from Feb 1953 to Jun 2016 were reviewed, retrospectively. Data was collected including symptoms, digital rectal examination (DRE), prostate-specific antigen (PSA), Gleason score, tumor stage, treatment strategies. Results: The mean age was 50.9±4.5, and 25.3% patients were between 40-50 years. Fifty-six (36.4%) patients initially presented with lower urinary tract symptoms. A solid mass could be found by digital rectal examination in 48(31.2%) patients. All patients were diagnosed by pathology of biopsy or surgery. The median Gleason score was 8. Gleason 2-6, 3+ 4, 4+ 3, 8, 9-10 were 15 cases(9.7%), 28 cases(18.2%), 21 cases(13.6%), 15 cases(9.7%), 51 cases(33.1%), respectively. Based on 2009 AJCC TNM Classification criteria the distribution of tumor stage was T1, T2, T3, and T4 in 2(1.3%), 54 (35.1%), 60 (39.0%), and 37 (24.0%) patients. Forty patients (25.9%) were found with bone metastasis and four (2.5%) suffered from visceral metastasis. Fifty-three(34.4%)underwent hormonal therapy and 79(51.3%) underwent radical prostatectomy. Conclusion: Younger prostate caner patients usually presented with LUTS symptoms and were featured for higher tumor stage and aggressiveness. More optimal and personalized risk-based therapy options are required.

[Preoperative prognostic factors and preoperative risk stratification of upper tract urothelial carcinoma].

OBJECTIVE: To identify the preoperative prognostic factors of upper tract urothelial carcinoma (UTUC) and construct preoperative risk stratification system. METHODS: A retrospective study including 686 patients who were diagnosed with UTUC and received radical nephroureterectomy or partial ureterectomy in Peking University First Hospital during 2003 and 2013. RESULTS: Of the 686 UTUC patients, 303 (44.2%) were male and 383 (55.8%) female. The postoperative pathological examination showed that 203 (29.6%) had high tumor stages (T3, T4), 300 (43.7%) had high tumor grades (G3) and 54 (7.9%) had lymph nodes metastasis (N1). After multivariate analysis, renal pelvic tumor, large tumor, estimated glomerular filtration rate (eGFR)≥30 mL/min, and male were associated with high tumor stage. Ureteral tumor, large tumor, and non-smoking history were associated with high tumor grade. Renal pelvis tumor, large tumor, and preoperative anemia were associated with positive N status. During the follow-up, 208 (30.3%) died for cancer and 210 (30.6%) developed intravesical recurrence. Multivariate analysis showed: large tumor (P=0.001), concomitant ipsilateral hydronephrosis (P=0.041), and preoperative anemia (P=0.001) were independently associated cancer-specific mortality after surgery, while ureteral tumor (P=0.04), multiple tumor (P=0.005), and high preoperative creatinine (P=0.036) were independent risk factors for intravesical recurrence. CONCLUSION: Of the preoperative clinical parameters of UTUC patients, the large tumor, concomitant ipsilateral hydronephrosis, and preoperative anemia were independently associated with cancer-specific mortality after surgery. Ureteral tumor, multiple tumor, and high preoperative creatinine were independently associated with intravesical recurrence after surgery.

[Prognostic factors of patients with T3N0M0 renal cell carcinoma: a single-center retrospective study of 182 patients].

OBJECTIVE: To evaluate the impacts of clinical, pathological, and laboratory factors on oncological outcomes of patients with T3N0M0 renal cell carcinoma. METHODS: The clinical data, laboratory exam results, and follow-up outcomes of 182 patients with T3N0M0 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 percentage 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 factors significantly associated with cancer-specific survival of T3N0M0 renal cell carcinoma patients; higher Fuhrman grade and anemia were independent risk factors significantly associated with tumor recurrence of T3N0M0 renal cell carcinoma patients.

[Impact of different surgical methods of radical cystectomy on the perioperative complications in patients over 75 years].

OBJECTIVE: To analyze the impact of different surgical methods on perioperative complication rate after radical cystectomy in patients over 75 years of age. METHODS: A retrospective study reviewed 1 432 patients who received radical cystectomy from January 2003 to January 2015. A total of 239 patients were ≥75 years (median age: 78 years), of whom, 74 patients (31.0%) suffered one or more perioperative complications. According to the different operation methods, patients could be divided into ileal conduit group and cutaneous ureterostomy group. The ileal conduit group included laparoscopic and open radical cystectomy with ileal conduit. The cutaneous ureterostomy group included transperitoneal laparoscopic, transperitoneal and extraperitoneal open radical cystectomy with cutaneous ureterostomy. RESULTS: Perioperative complications were significantly associated with the patient's age (P=0.012), American Society of Anesthesiologists (ASA) score (P=0.001), node staging (P=0.043), and different surgical methods. Perioperative complications caused a prolonged hospital stay and delayed recovery (34 d vs. 21 d, P=0.002). For different surgical methods, the perioperative complication rate of ileal conduit was higher than cutaneous ureterostomy (P=0.013). However, there were no significant differences between transperitoneal laparoscopic and open radical cystectomy with ileal conduit in perioperative complication rate (P=0.836). The perioperative complication rate was statistically significant among transperitoneal laparoscopic, transperitoneal and extraperitoneal open radical cystectomy with cutaneous ureterostomy (P=0.022). On multivariate analysis, age (hazard ratio=4.856, 95% CI: 1.465-16.103, P=0.010), ASA score (P=0.008), and different surgical methods (P=0.016) were significantly associated with the perioperative complication rate. CONCLUSION: The perioperative complication rate after radical cystectomy in elderly patients was associated with the patients' age, ASA score, and different surgical methods. Patients who received extraperitoneal open radical cystectomy with cutaneous ureterostomy suffered fewer perioperative complications, which was an appropriate choice for elderly patients.

[Impact of different surgical methods of radical cystectomy on the perioperative complications in patients over 75 years].

OBJECTIVE: To analyze the impact of different surgical methods on perioperative complication rate after radical cystectomy in patients over 75 years of age. METHODS: A retrospective study reviewed 1 432 patients who received radical cystectomy from January 2003 to January 2015. A total of 239 patients were ≥75 years (median age: 78 years), of whom, 74 patients (31.0%) suffered one or more perioperative complications. According to the different operation methods, patients could be divided into ileal conduit group and cutaneous ureterostomy group. The ileal conduit group included laparoscopic and open radical cystectomy with ileal conduit. The cutaneous ureterostomy group included transperitoneal laparoscopic, transperitoneal and extraperitoneal open radical cystectomy with cutaneous ureterostomy. RESULTS: Perioperative complications were significantly associated with the patient's age (P=0.012), American Society of Anesthesiologists (ASA) score (P=0.001), node staging (P=0.043), and different surgical methods. Perioperative complications caused a prolonged hospital stay and delayed recovery (34 d vs. 21 d, P=0.002). For different surgical methods, the perioperative complication rate of ileal conduit was higher than cutaneous ureterostomy (P=0.013). However, there were no significant differences between transperitoneal laparoscopic and open radical cystectomy with ileal conduit in perioperative complication rate (P=0.836). The perioperative complication rate was statistically significant among transperitoneal laparoscopic, transperitoneal and extraperitoneal open radical cystectomy with cutaneous ureterostomy (P=0.022). On multivariate analysis, age (hazard ratio=4.856, 95% CI: 1.465-16.103, P=0.010), ASA score (P=0.008), and different surgical methods (P=0.016) were significantly associated with the perioperative complication rate. CONCLUSION: The perioperative complication rate after radical cystectomy in elderly patients was associated with the patients' age, ASA score, and different surgical methods. Patients who received extraperitoneal open radical cystectomy with cutaneous ureterostomy suffered fewer perioperative complications, which was an appropriate choice for elderly patients.

Modulation of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in RAW264.7 cells by irradiation.

Radiation-induced pulmonary injury is a severe complication affecting the quality of life of patients. Although the pathophysiology of the process is not fully understood, we hypothesized that it is potentially related to macrophages and their secretion of matrix metalloproteinase-9 (MMP-9). Macrophages are a type of inflammatory cell that synthesize hundreds of bioactive substances and enzymes. MMP-9 is closely involved in the maintenance of the basilar membrane, and leads to increased extracellular matrix deposition within the lung, which is a characteristic feature of radiation-induced lung fibrosis. We examined the role of ionizing radiation in modulating the production of MMP-9 in a macrophage cell line. RAW264.7 cells were irradiated with various doses of γ-rays, and then MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels were determined at several time points. RT-PCR revealed a marked increase in the levels of MMP-9 mRNA, which peaked at 24 h post-irradiation and had begun to decline by 48 h. By contrast, TIMP-1 mRNA experienced only a slight increase at 24 h post-irradiation, reaching significance at 48 h post-irradiation. Western blot analysis demonstrated an increased expression of MMP-9 protein in the irradiated cells, while TIMP-1 protein levels were not notably changed. Dexamethasone inhibited the increased expression of MMP-9 protein induced by ionizing radiation. These results indicate that MMP-9 expression by RAW264.7 cells, and an imbalance between MMP-9 and TIMP-1, may be involved in radiation-induced lung injury.

Cartorimine, a new cycloheptenone oxide derivative from Carthamus tinctorius.

Cartorimine (1), a new cycloheptenone oxide derivative, was isolated from Carthamus tinctorius, and its structure was established from spectral data interpretation and single-crystal X-ray analysis.