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.

[Analysis of the results of occupational health examination of radiation workers in Shaanxi Province].

Objective: To analyze the results of occupational health examinations of radiation workers in Shaanxi Province, and to provide basis and reference for effectively conduct occupational health monitoring. Methods: From April 2016 to January 2022, a questionnaire survey was conducted to collect the basic information on occupational health examinations of qualified radiation workers in Shaanxi Province from 2016 to 2021. Based on the abnormal rate of occupational health among radiation workers, 1018 people were randomly selected using a cluster stratified sampling method to analyze the occupational health examination results of different positions, types of work, gender, length of service, and exposure doses. Results: The chromosomal aberration rates of peripheral blood lymphocytes among radiation workers in Shaanxi Province from 2016 to 2021 were 0.26% (10/3876), 0.77% (27/3512), 0.16% (16/10153), 0.09% (13/14769), 0.10% (13/13399), and 0.12% (20/16671), respectively. The abnormal rates of thyroid ultrasound examination were 32.33% (150/464), 24.46% (649/2653), 55.24% (786/1423), 32.89% (888/2700), 35.69% (1475/4133), and 42.51% (1993/4688), respectively. There was a statistically significant difference in the abnormal rates among different years (P<0.05). The abnormal rate of renal function examination in male radiation workers was higher than that in females (P<0.05). Compared with non medical users, the abnormal rates of renal function, thyroid function, and blood routine examination in medical radiation workers were higher (P<0.05), and the abnormal rates of renal function, thyroid function, and blood routine examination in medical applications were higher than those in radiation diagnosis, nuclear medicine, and radiation therapy (P<0.05). The abnormal rates of electrocardiogram, chest X-ray, blood pressure, thyroid function, and blood routine increased with the length of service (P<0.05). The abnormal rates of blood pressure, liver function, kidney function, thyroid function, and blood routine examination increased with the exposure dose (P<0.05) . Conclusion: The occupational health status of radiation workers is not optimistic. Occupational health monitoring should be strengthened, especially interventional radiation diagnosis occupational health examination, as well as changes in the indicators of sensitive organs such as eye lens and thyroid, so as to ensure the health of radiation workers.

[Synchronous primary bilateral macronodular adrenal hyperplasia with renal cell carcinoma: a case series of three patients].

Three cases of synchronous primary bilateral macronodular adrenal hyperplasia(PBMAH) and renal cell carcinoma (RCC) in the Department of Urology of Peking Union Medical College Hospital were retrospectively reviewed. The clinical features, imaging features, treatment methods and pathological features of these patients were analyzed. It was found that the genetic relationship between synchronous PBMAH and RCC needs further research. And RCC is easy to be misdiagnosed. We should pay high attention to imaging features to find out whether there are lesions in bilateral kidneys when we deal with bilateral adrenal lesions. Laparoscopic approach is recommended for PBMAH and RCC. Total or partial nephrectomy should be performed according the tumor size and location of the renal mass. Patients with PBMAH should be closely followed up after bilateral adrenalectomy to avoid delay in diagnosis or treatment of RCC.

[Comparison of early postoperative effects between anterior bladder and posterior bladder approaches in robotic assisted laparoscopic radical prostatectomy].

Objective: To examine the effect of robotic assisted laparoscopic radical prostatectomy with different approaches on early postoperative effects. Methods: Totally 44 patients (average age of 65.9 years, range: 46 to 81 years) underwent robotic assisted laparoscopic radical prostatectomy by a single operator at Department of Urology, Peking Union Medical Collage Hospital from March 2018 to March 2020 were retrospectively analyzed. The mean age was 65.9 years (range: 46 to 81 years), including 24 cases in the anterior bladder approach group (anterior approach group) and 20 cases in the posterior bladder approach group (posterior approach group). The preoperative clinical data, perioperative related data and postoperative urinary control recovery were compared between the two groups by t test, χ2 test or Fisher exact test. Results: In terms of clinical data, there was no difference in age, prostate volume, preoperative prostate specific antigen and Gleason score(all P>0.05). There was no significant difference in operation time ((184±43) minutes vs. (193±42) minutes, t=-0.599, P=0.55), bleeding volume ((218±88) ml vs. (225±115) ml, t=-0.244, P=0.81), postoperative stage (T2/T3: 15/9 vs. 12/8, χ²=0.029, P=0.87) and positive rate of cutting edge (29.2% (7/24) vs. 30.0% (6/20), χ²=0.004, P=0.95). In terms of postoperative urinary control, patient rates who achieved urinary control immediately after extubation was significantly higher for the posterior approach group than the anterior approach group (30.0% (6/20) vs. 4.2% (1/24), P=0.04). There was no significant difference between two groups for those who achieved urinary control 3 months after operation (6 cases vs. 11 cases, P=0.06), 6 months after operation (20 cases vs. 19 cases, P=0.36) and those who achieved urinary control 12 months after operation (23 cases vs. 19 cases, P=1). Conclusion: For robotic assisted laparoscopic radical prostatectomy, the posterior approach does not prolong the operation time, does not increase the amount of bleeding, and improves the short-term postoperative urinary control.

MiR-212-5p inhibits the malignant behavior of clear cell renal cell carcinoma cells by targeting TBX15.

OBJECTIVE: To investigate the role of microRNA-212-5p (miR-212-5p) in clear cell renal cell carcinoma (ccRCC) and to explore the potential underlying mechanisms. MATERIALS AND METHODS: 32 pairs of ccRCC clinical samples were collected. Renal ccRCC cells (786-O) and embryonic kidney cells (293T) were cultured in vitro. The ability of cell proliferation was detected by 3-(4,5)-dimethylthiazol(-z-y1)-3,5-diphenyl tetrazolium bromide (MTT) assay. Transwell migration assay was used to detect the abilities of cell invasion and migration. The relative protein and mRNA expressions of miR-212-5p were detected by Western blot and quantitative Real-time polymerase chain reaction (qRT-PCR) analysis, respectively. Furthermore, bioinformatics online sites and luciferase reporter gene assay were performed to predict and verify the potential targets of miR-212-5p, respectively. RESULTS: The expression level of miR-212-5p in ccRCC tissues and cell lines was significantly inhibited. Bioinformatics online sites and luciferase reporter gene assay confirmed that T-box transcription factor TBX15 (TBX15) was the potential target gene of miR-212-5p. In vitro experiments demonstrated that the proliferation, cell cycle, cell invasion and migration of ccRCC cells were obviously restricted after up-regulation of miR-212-5p. However, the above functional effects were significantly abolished in ccRCC cells after co-transfection with miR-212-5p mimics and LV-TBX15. CONCLUSIONS: MiR-212-5p acted as a tumor suppressor gene in ccRCC. Through targeting TBX15, miR-212-5p significantly inhibited the malignant behavior of ccRCC cells. Our findings revealed that miR-212-5p/TBX15 axis might be a potential therapeutic target for the treatment of ccRCC.

[Comprehensive treatment of adrenal cortical carcinoma].

OBJECTIVE: To investigate the clinical and functional imaging examination and pathological features of adrenocortical carcinoma (ACC), in order to improve the diagnosis and treatment of ACC. METHODS: The clinical data of 93 patients with ACC were analyzed retrospectively. Their diagnosis, surgical treatment and follow-up of mitotane medcine therapy were madeaccording to clinical manifestations, adrenal endocrine function determination, imaging examination characteristics and histopathological results. RESULTS: Among the 93 patients, the age ranged from 11 to 76 years, with a median age of 48 years. The ratio of male to female was 1:1.2. Twenty-four hours urinary free cortisol (UFC) elevated in 86 cases, adrenocorticotropic hormone (ACTH) decreased in 88 cases, blood F rhythm disappeared in 82 cases, and 31 cases of aldosterone increased. Thirty-six cases of sexual hormone increased. Neuron specific enolase (NSE) increased in 27 cases. Insulin-like growth factor-1 (IGF-1) increased in 26 cases. Seventy-six cases of high-dose dexamethasone suppression test (HDDST) and low-dose dexamethasone supression test (LDDST) were not suppressed separately. There were 62 cases of hypertension, and typical Cushing manifestations in 81 cases. Blood glucose elevated in 54 cases. Hypokalemia was in 21 cases and androgen secretion increased in 36 cases. The maximum diameter of the tumor was 3-17 cm, with 6 cases of adrenal central vein, renal vein and inferior vena cava tumor thrombus. The recurrence time was 1.2-5.0 years after operation. Metastasis and recurrence were in 56 cases during the follow-up, lung metastasis in 13 cases, liver metastasis in 17 cases, retroperitoneal lymph node metastasis in 9 cases, lumbar metastasis in 7 cases, ovarian metastasis in 3 cases, abdominal wall and incision implantation in 4 cases. Fifteen cases with distant metastasis. Seventy-seven patients were treated with radical adrenalectomy, and the other patients were treated with renal and adrenal resection on the same side of the kidney. There were 5 cases of adrenal tumor with vena cava tumor thrombus in the removal of the tumor, and the other for the partial resection of the vena cava in 3 cases. Regarding the clinical stage, stage I was in 39 cases, stage II in 28 cases, stage III in 16 cases and stage IV in 10 cases. The patients were followed up for 8-69 months, and 43 patients survived more than 5 years. CONCLUSION: Function imaging combined with clinical features and endocrine hormone levels have important roles in ACC early diagnosis. Radical excision is the only effective treatment. Adjuvant or adjuvant mitotane drug therapy can brused for the treatment of recurrence and metastasis ACC patients,. ACC is a tumor with high malignancy and poor prognosis.

MiR-1299 functions as a tumor suppressor to inhibit the proliferation and metastasis of prostate cancer by targeting NEK2.

OBJECTIVE: The aim of this study was to investigate the inhibitory role of microRNA-1299 (miR-1299) in prostate cancer, and to explore the possible underlying mechanism. PATIENTS AND METHODS: The expression of miR-1299 in 35 PCa tissues and para-carcinoma tissues, as well as PCa cell lines (PC-3) and prostatic epithelial cell line (RWPE-1), was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Then, we explored the possible targets of miR-1299 by searching online databases. NIMA-related kinase 2 (NEK2) was identified as a direct target gene of miR-1299. Subsequently, qRT-PCR, Western blot (WB), and luciferase reporter gene assay were used to further verify the correlation between miR-1299 and NEK2. To better characterize the role of miR-1299 and NEK2 in PCa, we conducted functional experiments (MTT, flow cytometry, scratch-wound, and transwell assay) by transfecting PC-3 cells with miR-1299 mimics and si-NEK2 in different groups. RESULTS: The expression level of miR-1299 in PCa tissues was significantly lower than that of para-carcinoma tissues. Meanwhile, the expression of miR-1299 in PC-3 cells was also significantly downregulated when compared with RWPE-1 cells. Subsequent qRT-PCR, WB, and luciferase reporter gene assay verified that miR-1299 transcriptionally repressed NEK2 by interacting with the essential binding sequence in 3'-UTR. Also, functional experiments demonstrated that decreased expression of NEK2 resulting from miR-1299 up-regulation could remarkably inhibit the proliferation, invasion, and migration of PCa cells. CONCLUSIONS: Our study indicated that miR-1299 was a novel suppressor in PCa through its negative regulation of NEK2. Moreover, our findings revealed that miR-1299/NEK2 axis might be a potential therapeutic target for the treatment of PCa.

[Diagnosis and treatment of adrenal ganglioneuroma: a report of 80 cases].

Objective: To review and discuss the experience of diagnosis and treatment of adrenal ganglioneuroma. Methods: Clinical data of 80 cases of adrenal ganglioneuroma undergoing surgery during January 1982 to May 2017 at Peking Union Medical College Hospital were retrospectively analyzed. There were 36 male and 44 female patients. Age ranged from 8 to 69 years old (mean 37.7 years old). The tumor diameter were 1.5 to 18.0 cm (mean 4.3 cm). There were 61 cases of adrenal ganglioneuroma diagnosed by imaging examination. All patients underwent adrenalectomy. Results: All procedures were performed successfully without serious complication. Including 15 open surgery and 64 retroperitoneal laparoscopic surgery. One laparoscopic case conversion to open surgery. The pathological diagnosis was adrenal ganglioneuroma. Fifteen cases were mixed with other tumor components. No recurrence or metastasis was observed during the follow-up of 2 months to 35 years. Conclusions: The diagnostic techniques for adrenal ganglioneuroma are helpful to judge the tumor property before operation. The laparoscopic surgery has become the current method for resecting tumors. It shows advantages of small trauma and speedy recovery. The relationship between tumor and surrounding tissues should be understand clearly before operation. Full preparation must be made before operation if adrenal ganglioneuroma mixed with other tumor components.

[The study of renal safety in elderly patients with benign prostatic hyperplasia treated with α receptor blockers].

Objective: To investigate the renal safety in patients with benign prostatic hyperplasia treated with tamsulosin hydrochloride. Methods: A retrospective analysis of 10 cases of patients, who had renal dysfunction after treatment with long-term tamsulosin hydrochloride. Results: The average duration of oral medicine was 2 to 24 months with an average of 7.2 months. The serum creatinine after discontinuation of tamsulosin hydrochloride decreased from 132.5 µmol/L (100-208 µmol/L, normal 59-104 µmol/L) to 95.7 µmol/L (73-122 µmol/L, normal: 59-104 µmol/L) (F=10.385, P=0.000). Conclusion: Preliminary results show that taking tamsulosin hydrochloride might lead to renal damage in old patients with benign prostatic hyperplasia. Safety is the premise, and the right medicine should be chosen for different side effects in order to protect the safety of patient.

[Surgery treatment of ectopic adrenocorticotrophic hormone syndrome].

OBJECTIVE: To investigation the diagnosis and treatment of ectopic adrenocorticotrophic hormone (ACTH) syndrome. METHODS: The clinical characters of 57 cases of ecotopic ACTH syndrome from Jan. 1996 to Dec. 2016 were collected and analyzed. The 57 cases included 32 males and 25 females. The age ranged from 11 to 68 years (average 32 years). ACTH levels significantly increased from 16.5 to 365.6 pmol/L, with average 77.6 pmol/L (normal range <10.1 pmol/L). The pituitary MRI did not found lesions. The CT showed that their bilateral adrenal glands diffused small nodular changes or nodular hyperplasia. The 57 cases were divided into 3 groups according to different treatment options. In the study, 25 ectopic ACTH syndrome cases (44%) were group A, without identified source of ectopic hormone, were treated with bilateral or unilateral adrenalectomy due to the severity of the disease and difficulty of operation. Group B was composed of 16 cases (28%) diagnosed as ectopic ACTH syndrome by finding ectopic ACTH tumors and surgical resection. Group C included 16 cases (28%) with nonsurgical therapy. Different treatment results and prognosis were analyzed. RESULTS: In the study, 40 cases of the 57 had been followed up for 6 months to 10 years. In group A, of the 25 cases with bilateral or unilateral adrenalectomy, 4 died of diabetes and severe pulmonary infection, 18 survived, and 3 were lost to the follow-up, and the survival rate was 81% (18/22). In group B, of the 16 cases with radical tumor resection, 5 died of tumor recurrence 0.5-6.0 years after operation, 3 survived, and 8 were lost to the follow-up, and the survival rate was 37.5% (3/8). In group C, of the 16 non-operation patients, 4 with radiotherapy and chemotherapy died of metastases, diabetes or pulmonary infection, 6 with chemotherapy died of pulmonary infection within 1 year and the others were lost to the follow-up, and the survival rate was 0. CONCLUSION: Ectopic ACTH syndrome is difficult to treat. Adrenalectomy is effective for the management of ectopic ACTH syndrome, especially for those patients with severe Cushing's syndrome, but the primary tumor can not be located.

[Recent progress in MRI-ultrasound fusion for guidance of targeted prostate biopsy].

Prostate cancer is currently diagnosed by prostate biopsy performed by the transrectal ultrasound-guided technique. However, overdetection of clinical insignificant tumours and missed detection of clinical significant tumours have become problematic. MRI of the prostate, particularly if performed with multiparametric imaging, is capable of detecting clinical significant prostate cancer, which has brought the opportunity to use those images as targets for needle biopsy. Three methods of fusing MRI for targeted biopsy have been recently described: MRI-ultrasound fusion, MRI-MRI fusion ('in-bore' biopsy) and cognitive fusion. Fusion of MRI with ultrasound allows urologists to progress from blind, systematic biopsies to biopsies, which are mapped, targeted and tracked. In the future, MRI-ultrasound fusion for lesion targeting is likely to result in fewer and more accurate prostate biopsies than the present use of systematic biopsies with ultrasound guidance alone.

Renal epithelioid angiomyolipoma without obvious local progress in 10 years: a case report and literature review.

Epithelioid angiomyolipoma (eAMLoma) is an uncommon renal mesenchymal tumor with malignant potential. It is composed of tumor cells arranged in an epithelioid manner. Differential diagnosis from renal cell carcinoma is often challenging because of its epithelioid morphology. Herein is reported a case of eAMLoma, involving a 49-year-old man with eAMLoma. The patient had undergone radical nephrectomy via retroperitoneal laparoscope successfully. He had an uneventful postoperative recovery. The tumor was positive for Desmin, Hmb45, and Sma. We recommend surgical treatment and a follow-up regimen similar to that for renal carcinoma. There was no recurrence and metastases after 1-year follow-up.