Establishment and validation of a nomogram to select patients with metastatic sarcomatoid renal cell carcinoma suitable for cytoreductive radical nephrectomy.

Introduction: Metastatic renal cell carcinoma (mRCC) with sarcomatoid features has a poor prognosis. Cytoreductive radical nephrectomy (CRN) can improve prognosis, but patient selection is unclear. This study aimed to develop a prediction model for selecting patients suitable for CRN. Materials and methods: Patients with a diagnosis of mRCC with sarcomatoid features in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015 were retrospectively reviewed. CRN benefit was defined as a survival time longer than the median overall survival (OS) in patients who did not receive CRN. A prediction nomogram was established and validated using the SEER cohort (training and internal validation) and an external validation cohort. Results: Of 900 patients with sarcomatoid mRCC, 608 (67.6%) underwent CRN. OS was longer in the CRN group than in the non-CRN group (8 vs. 6 months, hazard ratio (HR) = 0.767, p = 0.0085). In the matched CRN group, 124 (57.7%) patients survived >6 months after the surgery and were considered to benefit from CRN. Age, T-stage, systematic therapy, metastatic site, and lymph nodes were identified as independent factors influencing OS after CRN, which were included in the prediction nomogram. The monogram performed well on the training set (area under the receiver operating characteristic (AUC) curve = 0.766, 95% confidence interval (CI): 0.687-0.845), internal validation set (AUC = 0.796, 95% CI: 0.684-0.908), and external validation set (AUC = 0.911, 95% CI: 0.831-0.991). Conclusions: A nomogram was constructed and validated with good accuracy for selecting patients with sarcomatoid mRCC suitable for CRN.

[Clinical characteristics and prognostic factors of distant metastatic penile cancer].

OBJECTIVE: To investigate the clinical features of distant metastatic penile cancer (DMPC) and the factors influencing its prognosis. METHODS: We searched the Surveillance, Epidemiology and End Results Database for cases of DMPC diagnosed between 2004 and 2019, analyzed their clinical characteristics and the cancer-specific survival (CSS) rates relating to different factors using the Kaplan-Meier method and the differences among the variables by log-rank test. We determined the variables independently associated with CSS by Cox regression analysis. RESULTS: According to the inclusion criteria, 108 cases of DMPC were identified. The patients were mainly married White people, with a median CSS of 9 months, and 1-, 2- and 3-year CSS rates of 36.4%, 17.8% and 13.5%, respectively. Pairwise comparison showed no statistically significant differences in the median overall CSS among the patients in the surgery, chemotherapy and surgery + chemotherapy groups (8 mo vs 9 mo vs 13 mo, P > 0.05). Race was an independent factor affecting the prognosis of CSS. CONCLUSION: Distant metastatic penile cancer is a rare malignancy with poor prognosis, for which there have been no existing ideal treatment options.

Development and validation of a prognostic model incorporating tumor thrombus grading for nonmetastatic clear cell renal cell carcinoma with tumor thrombus: A multicohort study.

There is significant variability with respect to the prognosis of nonmetastatic clear cell renal cell carcinoma (ccRCC) patients with venous tumor thrombus (VTT). By applying multiregion whole-exome sequencing on normal-tumor-thrombus-metastasis quadruples from 33 ccRCC patients, we showed that metastases were mainly seeded by VTT (81.8%) rather than primary tumors (PTs). A total of 706 nonmetastatic ccRCC patients with VTT from three independent cohorts were included in this study. C-index analysis revealed that pathological grading of VTT outperformed other indicators in risk assessment (OS: 0.663 versus 0.501-0.610, 0.667 versus 0.544-0.651, and 0.719 versus 0.511-0.700 for Training, China-Validation, and Poland-Validation cohorts, respectively). We constructed a risk predicting model, TT-GPS score, based on four independent variables: VTT height, VTT grading, perinephric fat invasion, and sarcomatoid differentiation in PT. The TT-GPS score displayed better discriminatory ability (OS, c-index: 0.706-0.840, AUC: 0.788-0.874; DFS, c-index: 0.691-0.717, AUC: 0.771-0.789) than previously reported models in risk assessment. In conclusion, we identified for the first-time pathological grading of VTT as an unheeded prognostic factor. By incorporating VTT grading, the TT-GPS score is a promising prognostic tool in predicting the survival of nonmetastatic ccRCC patients with VTT.

Collecting Duct Carcinoma of the Kidney: A Single-Center Retrospective Study of 23 Cases.

Objective: To explore the clinical, imaging, pathologic features, treatment, and prognostic outcomes in 23 cases of collecting duct carcinoma (CDC) from a single center. Methods: The clinical and imaging findings, pathological features, treatment methods, and outcomes of the 23 patients with CDC confirmed by microscopic examination between 2003 and 2020 at our institution were retrospectively reviewed. Descriptive statistics of demographic and clinical variables were applied. Kaplan-Meier method was used to analyze survival data and log-rank test statistic survival differences between groups. Cox regression analysis was employed to identify variables independently related to overall survival (OS). Results: A total of 23 patients with CDC were identified. The mean age was 50.8 years. Stage III or IV tumors were diagnosed in 82.6% of the patients at diagnosis. The average size of the tumor was 6.58 cm, and the left kidney was more involved than the right. The median OS was 12 months. The OS rates at 1 and 2 years were 43.5% and 26.1%, respectively. Twenty patients underwent nephrectomy, 3 underwent nephroureterectomy, and 9 (39.1%) patients received subsequent therapeutic interventions following surgery. Distant metastasis and no symptoms at initial diagnosis proved to be an independent factor of unfavorable survival in Cox regression analysis. Conclusions: CDC is a rare and highly aggressive malignant renal tumor, and most patients present at an advanced stage at initial diagnosis. More than half of the patients died within 1 year after surgery. Distant metastasis and no clinical symptoms at initial diagnosis were independent risk prognostic factors for patients with CDC.

[Keratoacanthoma of the penis: A case report and literature review].

OBJECTIVE: To explore the clinical characteristics and treatment options of keratoacanthoma (KA) of the penis. METHODS: We report the diagnosis and treatment of a case of penile keratoacanthoma in our hospital and review the literature. RESULTS: The patient was admitted due to the discovery of a "new lesion on the glans for 4 months," diagnosed with a penile tumor, underwent tumor resection surgery, with histopathological examination revealing squamous epithelial hyperplasia, thickening, and excessive keratinization. The postoperative pathological diagnosis was penile keratoacanthoma. There was no recurrence or metastasis during follow-up. CONCLUSION: KA is a relatively rare benign tumor with potential malignant transformation, and close follow-up is necessary postoperatively.

Exosomal AP000439.2 from clear cell renal cell carcinoma induces M2 macrophage polarization to promote tumor progression through activation of STAT3.

BACKGROUND: Tumorigenic phenotype of M2 tumor-associated macrophages promote tumor progression in response to exosomes cues imposed by tumor cells. However, the effect and underlying mechanisms of clear cell renal cell carcinoma (ccRCC)-derived exosomes (ccRCC-exo) on instructing macrophages phenotype remains unclear. METHODS: Macrophages were cocultured with ccRCC-exo and then evaluate the polarization of macrophages and migration of ccRCC cells. The effect and mechanism of lncRNA AP000439.2 overexpressed or deleted exosomes on macrophages M2 polarization were examined. Xenograft tumor mice model was used for in vivo validation. RESULTS: The ccRCC-exo significantly activated macrophages to M2 phenotype presented by increased expression of transforming growth factor-beta (TGF-ß) and interleukin 10 (IL-10) at mRNA and protein levels, and these M2 macrophages in turn facilitating the migration of ccRCC cells. LncRNA AP000439.2 was highly enriched in the ccRCC-exo. Overexpression of exosomal AP000439.2 promoted M2 macrophage polarization whereas AP000439.2-deficient exosome had the opposite effects. Nuclear-localized AP000439.2 directly interacted with signal transducer and activator of transcription 3 (STAT3) proteins and phosphorylated STAT3 in macrophages. RNA-Seq results showed overexpression of AP000439.2 activated NF-κB signaling pathway. Silencing of STAT3 suppressed overexpression of AP000439.2-induced up-regulation of TGF-ß and IL-10 expression, and p65 phosphorylation. AP000439.2-deleted exosome inhibited tumor growth in vivo. CONCLUSION: Exosomes from ccRCC deliver AP000439.2 to promote M2 macrophage polarization via STAT3, thus enhancing ccRCC progression, indicating exosomal AP000439.2 might be a novel therapeutic target in ccRCC. Video Abstract.

Mucinous Tubular and Spindle Cell Carcinoma of the Kidney: A Study of Clinical, Imaging Features and Treatment Outcomes.

Purpose: To describe the clinical, imaging, pathological features and oncologic outcomes of mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney. Patients and Methods: Twenty-two cases of MTSCC were pathologically identified between January 2004 and April 2021 at our institution. The clinical and imaging findings, pathological features, treatment methods and outcomes of the patients were reviewed. Results: These cases included 17 women and 5 men, with a median age at diagnosis of 52.5 years. On contrast-enhanced CT, MTSCC was less enhanced than the adjacent renal parenchyma. Tumor attenuation values were 33.3 ± 6.8HU, 44.0 ± 9.1HU, 54.4 ± 13.9HU and 67.1 ± 11.8HU in the non-contrast, corticomedullary, nephrographic and excretory phases of CT, respectively. Contrast-enhanced ultrasonography and MRI also showed hypovascular features of the masses. On MRI, the tumors were isointense on T1-weighted images and slightly hypo- or hyperintense on T2-weighted images. Diffusion-weighted imaging revealed a low apparent diffusion coefficient of the tumor. The patients were managed with laparoscopic partial nephrectomy (n=5), radical nephrectomy (n=16), or robotic-assisted laparoscopic partial nephrectomy (n=1). The median follow-up time was 59.5 months. All the patients were free of local recurrence or distant metastasis. Conclusions: MTSCC is generally indolent and has favorable outcomes. The imaging features of MTSCC are generally hypovascular, which is significantly different from clear cell renal cell carcinoma. However, it is still difficult to distinguish MTSCC from other hypovascular renal tumors preoperatively because their imaging features overlap. Further studies are essential to fully characterize the features of this rare RCC variant.

Incidence, Clinical Characteristics, and Survival of Collecting Duct Carcinoma of the Kidney: A Population-Based Study.

OBJECTIVE: To investigate the exact age-adjusted incidence (AAI), clinical characteristics, and survival data of collecting duct carcinoma of the kidney (CDCK) recorded in the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute. METHODS: Patients with CDCK confirmed by microscopic examination from 2004 to 2018 were selected from the SEER database. AAI rates were calculated using SEER*Stat software (version 8.3.9). The Kaplan-Meier method was used to evaluate cancer-specific survival (CSS) rates according to tumor size, tumor stage, and treatment methods, and differences among these variables were assessed by the log-rank test. Cox regression analysis was employed to identify variables independently related to CSS. RESULTS: A total of 286 patients with CDCK were identified from the database. The majority of the patients were white (69.2%), male (67.5%), and married (60.5%), and the median age was 59 years. Most patients with CDCK (74.4%) presented with stages III or IV disease. The diameter of most (59.4%) tumors was less than 7 cm, and the tumors were more commonly found on the left than on the right (55.2% vs. 44.8%). The incidence of CDCK decreased over time. The median CSS time was 17 months. In terms of the treatment modalities used, 83.9% of the patients underwent surgery; 32.9% underwent chemotherapy, and 13.6% underwent radiotherapy. The CSS rates at 1, 2, and 5 years were 57.3%, 43.2%, and 30.7%, respectively. In patients with stage IV CDCK treated with surgery alone, chemotherapy alone, and surgery plus chemotherapy, the median survival time was 5 months, 9 months, and 14 months, respectively (P =0.024). Multivariate Cox regression analysis showed surgery, chemotherapy, stage, regional lymph node metastasis, and distant metastasis were independent prognostic factors for patients with CDCK. CONCLUSIONS: CDCK is an uncommon malignant renal carcinoma, and its incidence is decreasing based on the analysis of current data. CDCK is a high stage, regional lymph-nodes positive, and metastatic disease. Compared with surgery alone or chemotherapy alone, patients with stage IV could gain survival benefit from surgery combined with chemotherapy.

Identification of Immune-Related Cells and Genes in Tumor Microenvironment of Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is one of the most common tumors in the urinary system. Progression in immunotherapy has provided novel options for the ccRCC treatment. However, the understanding of the ccRCC microenvironment and the potential therapeutic targets in the microenvironment is still unclear. Here, we analyzed the gene expression profile of ccRCC tumors from the Cancer Genome Atlas (TCGA) and calculated the abundance ratios of immune cells for each sample. Then, seven types of immune cells were found to be correlated to overall survival, and 3863 immune-related genes were identified by analyzing differentially expressed genes. We also found that the function of immune-related genes was mainly focused on ligand-receptor binding and signaling pathway transductions. Additionally, we identified 13 hub genes by analyzing the protein-protein interaction network, and seven of them are related to overall survival. Our study not only expands the understanding of fundamental biological features of microenvironment but also provides potential therapeutic targets.

Nobiletin inhibits viability of human renal carcinoma cells via the JAK2/STAT3 and PI3K/Akt pathway.

Nobiletin, a flavonoid found chiefly in oranges and lemons, has exhibited potential anti-proliferative and pro-apoptotic activities in various types of cancers. However, the inhibitory effect and mechanisms of nobiletin on renal cancer cells are unclear.  CCK8 and plate clone formation assay were used to determine the effect of nobiletin on the proliferation of renal cancer cells, while scratch healing test was used to assay its effect on migration ability. The effect of nobiletin on the invasion of renal cancer cells was determined using Trans well chamber assay. Flow cytometry was used to determine the effect of nobiletin on apoptosis of renal cancer cells, while Western blotting assay was used to determine its effect on the expressions of JAK2/STAT3 and PI3K/Akt pathway proteins, and apoptosis-related proteins. Nobiletin inhibited the proliferation of renal carcinoma cells in a time- and dose-dependent manner. It inhibited the migration and invasion of renal cancer cells, and promoted their apoptosis. Western blot results showed that nobiletin inhibited the phosphorylations of JAK2, STAT3, PI3K, and Akt, and promoted the expressions of apoptosis-related proteins. Nobiletin inhibits the proliferation, invasion and migration of renal cell carcinoma by inhibiting JAK2/STAT3 and PI3K/Akt pathways, and promotes their apoptosis. These findings provide a new experimental basis for the application of nobiletin in the treatment of renal cancer.

Crosstalk between long non-coding RNAs and Wnt/ß-catenin signalling in cancer.

Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts in the human genome which perform crucial functions in diverse biological processes. The abnormal expression of some lncRNAs has been found in tumorigenesis, development and therapy resistance of cancers. They may act as oncogenes or tumour suppressors and can be used as diagnostic or prognostic markers, prompting their therapeutic potentials in cancer treatments. Studies have indicated that many lncRNAs are involved in the regulation of several signal pathways, including Wnt/ß-catenin signalling pathway, which has been reported to play a significant role in regulating embryogenesis, cell proliferation and controlling tumour biology. Emerging evidences have suggested that lncRNAs can interact with several components of the Wnt/ß-catenin signalling pathway to regulate the expression of Wnt target genes in cancer. Moreover, the expression of lncRNAs can also be influenced by the pathway. Nevertheless, Wnt/ß-catenin signalling pathway-related lncRNAs and their interactions in cancer are not systematically analysed before. Considering these, this review emphasized the associations between lncRNAs and Wnt/ß-catenin signalling pathway in cancer initiation, progression and their therapeutic influence. We also provided an overview on characteristics of lncRNAs and Wnt/ß-catenin signalling pathway and discussed their functions in tumour biology. Finally, targeting lncRNAs or/and molecules associated with the Wnt/ß-catenin signalling pathway may be a feasible therapeutic method in the future.

Long non-coding RNA H19 regulates E2F1 expression by competitively sponging endogenous miR-29a-3p in clear cell renal cell carcinoma.

BACKGROUND: Numerous recent studies indicate that the long non-coding RNAs (lncRNAs) are frequently abnormal expressed and take critical roles in many cancers. Renal cell carcinoma is the secondary malignant tumors in the urinary system and has high mortality and morbidity. Around 80% of RCCs is clear cell renal cell carcinoma (ccRCC) and is characterized by high metastasis and relapse rate. However, the clinical significances of lncRNAs in ccRCC are still unknown. METHODS: The human cancer lncRNA PCR array (Yingbio) was performed to detect the differentially expressed lncRNAs in human ccRCC samples. Real-time PCR (RT-PCR), dual-luciferase assay, RNA binding protein immunoprecipitation (RIP) assay, transwell assay, CCK-8 assay, and western blot were performed to explore the molecular mechanism of lncRNAs in ccRCC cell migration and invasion. RESULTS: In this study, lncRNA-H19 was high expressed and negatively correlated with miR-29a-3p in ccRCC. By bioinformatics software, dual-luciferase reporter and RIP assays, we verified that miR-29a-3p was identified as a direct target of lncRNA-H19. RT-PCR and western blot demonstrated that down-regulated lncRNA-H19 could affect the expression of miR-29a-3p targeting E2F1 with competitively binding miR-29a-3p. Furthermore, transwell assays indicated that lncRNA-H19 knockdown inhibited cells migration and invasion, but this effect was attenuated by co-transfection of lncRNA-H19 siRNA and miR-29a-3p inhibitor. Over expression of E2F1 could rescue lncRNA-H19 siRNA induced suppression on cell migration and invasion in ccRCC cells. CONCLUSIONS: These results show a possible competing endogenous RNAs regulatory network involving lncRNA-H19 regulates E2F1 expression by competitively sponging endogenous miR-29a-3p in ccRCC. This mechanism may contribute to a better understanding of ccRCC pathogenesis, and lncRNA-H19 may be further considered as a potential therapeutic target for ccRCC intervention.

MiRNA-21 has effects to protect kidney injury induced by sepsis.

To investigate the miRNA-21 over-expression in the acute kidney injury induced by sepsis, we developed a sepsis induced in vitro model by lip polysaccharide (LPS) and in vovo model by cecal ligation and puncture (CLP) surgery. LPS or CLP surgery induced kidney cell apoptosis increasing. However, the kidney injury indexes of miRNA groups which were transfected with miRNA-21 were significantly suppressed. In further study, the relative proteins expressions were evaluated to explain the miRNA-21 mechanism to improve sepsis induced kidney cell apoptosis. The results were shown that miRNA-21 over-expression had effects to protect kidney cell apoptosis induced by sepsis via PTEN/PI3K/AKT signaling pathway.

Impact of vascular endothelial growth factor gene-gene and gene-smoking interaction and haplotype combination on bladder cancer risk in Chinese population.

AIMS: To investigate the association of single nucleotide polymorphisms (SNPs) within vascular endothelial growth factor (VEGF) gene polymorphisms, additional gene- gene and gene- smoking interactions with bladder cancer risk. RESULTS: Bladder cancer risk was significantly higher in carriers of the rs699947- A allele within VEGF gene than those with rs699947- CC genotype (CA+ AA versus CC), adjusted OR (95%CI) = 1.70 (1.16-2.31), and higher in carriers of the rs833052- A allele of within VEGF gene than those with rs833052- CC genotype (CA+ AA versus CC), adjusted OR (95%CI) = 1.65 (1.23-2.12). GMDR analysis indicated a potential interaction between rs2010963 and smoking on bladder cancer risk. Current smokers with rs2010963- GC+CC genotype within VEGF gene have the highest bladder cancer risk, compared to never smokers with rs2010963- GG genotype within VEGF gene, OR (95%CI) = 3.25 (1.71-4.83). Haplotype containing the rs2010963- C and rs833052- A alleles were associated with a statistically increased bladder cancer risk, OR (95%CI) = 2.21 (1.12-3.42). MATERIALS AND METHODS: Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among SNPs and smoking. Logistic regression was performed to investigate association of 6 SNPs within VEGF gene, additional gene- gene and gene- smoking interaction with bladder cancer risk. CONCLUSIONS: We found that the A allele of rs699947 and the A allele of rs833052 within VEGF gene, interaction between rs2010963 and smoking, haplotype containing the rs2010963- C and rs833052- A alleles were all associated with increased bladder cancer risk.

Long non-coding RNA ATB promotes growth and epithelial-mesenchymal transition and predicts poor prognosis in human prostate carcinoma.

Long non-coding RNAs (lncRNAs) have been identified to be critical mediators in various tumors associated with cancer progression. Long non-coding RNA activated by TGF-ß (lncRNA-ATB) is a stimulator of epithelial-mesenchymal transition (EMT) and serves as a novel prognostic biomarker for hepatocellular carcinoma. However, the biological role and clinical significance of lncRNA-ATB in human prostate cancer have yet to be fully elucidated. The present study was designed to explore the expression of lncRNA-ATB in human prostate cancer patients and the role of lncRNA-ATB in prostate cancer cells. We showed that lncRNA-ATB expression was significantly upregulated in tumor tissues in patients with prostate cancer in comparison with adjacent non-tumor tissues. Further analysis indicted that high lncRNA-ATB expression may be an independent prognostic factor for biochemical recurrence (BCR)-free survival in prostate cancer patients. Overexpression of lncRNA-ATB promoted, and knockdown of lncRNA-ATB inhibited the growth of prostate cancer cells via regulations of cell cycle regulatory protein expression levels. In addition, lncRNA-ATB stimulated epithelial-mesenchymal transition (EMT) associated with ZEB1 and ZNF217 expression levels via ERK and PI3K/AKT signaling pathways. These results indicated that lncRNA-ATB may be considered as a new predictor in the clinical prognosis of patients with prostate cancer. Overexpression of lncRNA-ATB exerts mitogenic and EMT effects of prostate cancer via activation of ERK and PI3K/AKT signaling pathways.

Fast track surgery vs. conventional management in the perioperative care of retroperitoneal laparoscopic adrenalectomy.

OBJECTIVE: It has been demonstrated that fast track (FT) surgery can accelerate the recovery of the patients in limited urologic procedures, but there are no reports regarding FT surgery within retroperitoneal laparoscopic adrenalectomy (RLA). This study aims at evaluating the impact of FT surgery on recovery after RLA. METHODS: One hundred patients in our centre are randomly assigned to FT group and conventional group. The patients who have undergone RLA receive either conventional care or an FT recovery program. Surgical outcome, complications, gastrointestinal function, visual analogue scale (VAS) general state and VAS pain scores are compared between the two groups. In addition, white blood cell count, serum interleukin-6 and C-reactive protein levels are measured. Patients are discharged home when they meet discharge criteria. RESULTS: Compared with the conventional group, the time of first flatus (18.97±8.45 vs. 37.66±17.17 h), initiation of normal diet (18.76±4.94 vs. 53.15±15.99 h), the time of first ambulation (19.64±6.23 vs. 51.89±18.19 h), length of post-operation hospital stay (2.35±0.87 vs. 5.23±1.62 d), duration of drainage (18.19±5.19 vs. 68.10±18.06 h) and catheter (17.19±4.49 vs. 60.83±25.53 h) are markedly shorter in FT group (P<0.01). Post-operative coughing pain scores at 2 h (1.00±0.61 vs. 1.42±1.18), 12 h (0.96±0.78 vs. 2.00±1.40), 24 h (1.10±0.97 vs. 4.22±1.53) and resting pain scores at 12 h (0.64±0.56 vs. 1.44±0.91), 24 h (0.66±0.63 vs. 1.22±0.86) are consistently lower in the FT group. The level of CRP, IL-6 at 2 h and 24 h post-operation are lower than that of control group, and white blood cell count is lower than conventional group at 24 h after surgery (P<0.01). FT patients have a overall higher level of post-operative VAS general state than conventional groups (P<0.01). Age, sex, tumor size and side, BMI, ASA score, operation time, blood loss and complications are similar in both groups. CONCLUSIONS: FT surgery within RLA shortens the length of post-operative hospital stay without increasing the postoperative complication, lowers patients' VAS pain scores, and reduces inflammatory response intensity and improves the general state. Therefore, FT can be applied feasibly and safely in RLA.

MicroRNA Expression Profiling in Clear Cell Renal Cell Carcinoma: Identification and Functional Validation of Key miRNAs.

OBJECTIVE: This study aims to profile dysregulated microRNA (miRNA) expression in clear cell renal cell carcinoma (ccRCC) and to identify key regulatory miRNAs in ccRCC. METHODS AND RESULTS: miRNA expression profiles in nine pairs of ccRCC tumor samples at three different stages and the adjacent, non-tumorous tissues were investigated using miRNA arrays. Eleven miRNAs were identified to be commonly dysregulated, including three up-regulated (miR-487a, miR-491-3p and miR-452) and eight down-regulated (miR-125b, miR-142-3p, miR-199a-5p, miR-22, miR-299-3p, miR-29a, miR-429, and miR-532-5p) in tumor tissues as compared with adjacent normal tissues. The 11 miRNAs and their predicted target genes were analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and three key miRNAs (miR-199a-5p, miR-22 and miR-429) were identified by microRNA-gene network analysis. Dysregulation of the three key miRNAs were further validated in another cohort of 15 ccRCC samples, and the human kidney carcinoma cell line 786-O, as compared with five normal kidney samples. Further investigation showed that over-expression of miR-199a-5p significantly inhibited the invasion ability of 786-O cells. Luciferase reporter assays indicated that miR-199a-5p regulated expression of TGFBR1 and JunB by directly interacting with their 3' untranslated regions. Transfection of miR-199a-5p successfully suppressed expression of TGFBR1 and JunB in the human embryonic kidney 293T cells, further confirming the direct regulation of miR-199a-5p on these two genes. CONCLUSIONS: This study identified 11 commonly dysregulated miRNAs in ccRCC, three of which (miR-199a-5p, miR-22 and miR-429) may represent key miRNAs involved in the pathogenesis of ccRCC. Further studies suggested that miR-199a-5p plays an important role in inhibition of cell invasion of ccRCC cells by suppressing expression of TGFBR1 and JunB.

A modified adrenal gland-sparing surgery based on retroperitoneal laparoscopic radical nephrectomy.

BACKGROUND: The objective of this study was to modify the adrenal gland-sparing strategy based on retroperitoneal laparoscopic radical nephrectomy by reviewing the anatomic relationship between the kidney and the adrenal gland. METHODS: From June 2010 to October 2012, a total of 68 patients (45 males and 23 females) with localized renal cell carcinoma were treated at our hospital. The study included 35 cases that were right side and 33 cases that were left, and average patient age was 54.06 years. The average tumor size was 4.7 cm. Tumors were classified via the TNM staging system. All patients underwent adrenal gland-sparing surgery based on retroperitoneal laparoscopic radical nephrectomy. RESULTS: For each patient, surgery was successful without conversion to open surgery. The average operative time was 56.65 ± 26.60 min, and the mean blood loss was 70.61 ± 60.96 ml. All patients were discharged from the hospital 3 to 8 days after surgery. During surgery, the adrenal gland was slightly lacerated in three cases and the peritoneum showed perforation in six cases. Only one case recurred during the study follow-up. CONCLUSIONS: Based on retroperitoneal laparoscopy radical nephrectomy, this effective adrenal gland-sparing surgery showed direct exposure of tissue and little interference of the upper pole of the kidney. Elevation of the adrenal gland could help with the complete dissection of the adrenal gland from the kidney. The separation of the kidney was rapid, simple and accurate. The probability of adrenal gland damage was reduced. This strategy is recommended for widespread use in T1-2 renal neoplasms.