Robot-assisted partial nephrectomy: Can retroperitoneal approach suit for renal tumors of all locations?-A large retrospective cohort study.

BACKGROUND: This study aimed to explore the appropriate location of renal tumors for retroperitoneal approach. MATERIALS AND METHODS: We retrospectively analyzed 1040 patients with renal tumor who were treated at our institution from Janurary 2015 to June 2020 and had underwent retroperitoneal robotic assisted-laparoscopic partial nephrectomy (rRAPN). Clinical features and postoperative outcomes were evaluated. RESULTS: Patients with incomplete data were excluded, and we included 896 patients in total. The median tumor size was 3.0 (range: 0.8-10.0) cm. The median RENAL Nephrometry Score was 7 (range: 4-11), and the median PADUA Nephrometry Score was 8 (range: 6-14). The median surgical time was 120 min, and the median warm ischemia time was 18 min. The median estimated blood loss was 50 ml. The follow-up time was 20.2 (range: 12-69) months. The mean change of eGFR 1 year after operation was 14.6% ± 19.0% compared with preoperative estimated glomerular filtration rate (eGFR). When compared the tumor at different locations, as superior or inferior pole, anterior of posterior face of kidney, there were no significant differences of intra- and post-operative outcomes such as surgical time, warm ischemia time, estimated blood loss, removal time of drainage tube and catheter, postoperative feeding time and hospital stay, and changes of eGFR one year after surgery. We also compared tumors at special locations as endophytic or exophytic, anterior of posterior hilus of kidney, there were no significant differences in surgical time, warm ischemia time, estimated blood loss and changes of eGFR. There was no significant difference in intraoperative features and postoperative outcomes when tumor larger than 4 cm was located at different positions of kidney. Though the surgical time was longer when BMI ≥ 28 (132.6 min vs. 122.5 min, p = 0.004), no significant differences were observed in warm ischemia time, estimated blood loss, changes in eGFR. Twenty-seven patients (3.0%) had tumor progression, including 8 (0.9%) recurrence, 19 (2.1%) metastasis, and 9 (1.0%) death. CONCLUSION: Retroperitoneal approach for RAPN has confirmed acceptable intra- and postoperative outcomes and suits for renal tumors of all different locations. Large tumor size and obesity are not contraindications for rRAPN.

Si-Wu-Tang ameliorates bile duct ligation-induced liver fibrosis via modulating immune environment.

Si-Wu-Tang (SWT), a traditional Chinese medicine formula firstly recorded from the Tang dynasty, has been reported to alleviate gynecological and liver diseases. We preliminarily demonstrated that SWT could improve liver fibrosis via modulating intestinal microbiota, but little was known about the mechanisms linking its therapeutic effects to the reshaped immune microenvironment within fibrotic livers. Thus, we established a bile duct ligation (BDL)-induced liver fibrosis murine model to evaluate the hepatoprotective effects and potential mechanisms of SWT. The high-performance liquid chromatography, RNA sequencing and other molecular biological techniques were also performed in our study. Our data demonstrated that SWT significantly improved BDL-induced liver fibrosis and inflammatory responses by inhibiting the expression of genes associated with extracellular matrix synthesis and degradation. Combined with the analysis of immune cell infiltration and gene set enrichment analysis (GSEA), we found that SWT remarkably repaired the unbalanced immune microenvironment by modulating the biological functions of different immune cells, especially for macrophages, neutrophils and CD8+ T cells. In addition, SWT significantly inhibited the activation of M2-like macrophages to reduce the release of profibrotic-cytokines and prevented the activation of neutrophils to suppress neutrophil extracellular trap formation. SWT also efficiently promoted the apoptosis of activated hepatic stellate cells via Fas/FasL signaling pathway, which might be mediated by CD8+ tissue-resident memory T cells. In conclusion, our research not only unraveled the intricate mechanisms underlying the hepatoprotective activities of SWT against liver fibrosis but also provided a novel therapeutic strategy for the treatment of liver fibrosis and its relative complications.

Ferulic acid ameliorates acetaminophen-induced acute liver injury by promoting AMPK-mediated protective autophagy.

Acetaminophen (APAP), one of the most widely used antipyretics and analgesics, principally results in acute liver injury (ALI) in developed countries when taken overdose. Ferulic acid (FA) is a natural polyphenol compound existing in many plants that has free radical scavenging, anti-inflammatory, and liver-protective properties. However, the effect and underlying mechanism of FA in treating APAP-induced ALI have not been fully elucidated. Herein, we established a mouse model of APAP-induced ALI and used APAP-stimulated MPHs for biochemical assessment of molecular parameters. After constructing networks and obtaining predicted targets from public databases, we further verified the putative pathways using immune-blotting assays both in vivo and in vitro. The reign of liver necrosis, serum levels of ALT and AST, and oxidative stress in livers significantly elevated after APAP treatment, which were almost recovered back to normal levels by FA administration. In addition, FA significantly upregulated the APAP-induced downregulation of hepatic specific markers, including HNF4a, Foxa2, and ALB. Then, the results of functional enrichment indicated the possible signaling pathways of FA against APAP challenge, mainly including AMPK, autophagy, apoptosis, and other metabolic process. Furthermore, FA markedly reversed the APAP-induced decline of mitochondria membrane potential, increased ratio of BAX/BCL2 and CASPASE 3 expression, and promoted autophagy flux of hepatocytes by upregulating AMPK phosphorylation, which were abrogated by a specific AMPK inhibitor, compound C. Overall, the hepatoprotective effect of FA on APAP-induced ALI might be associated with anti-oxidant and anti-apoptosis, which were at least partly attributed to AMPK-mediated protective autophagy.

A systematic review and meta-analysis of clinicopathologic factors linked to oncologic outcomes for renal cell carcinoma with tumor thrombus treated by radical nephrectomy with thrombectomy.

BACKGROUND: There remain discrepancies over the factors that influence oncologic outcomes after radical nephrectomy with thrombectomy (RNTE). To assess significant predictors of oncologic outcomes after RNTE from a systematic review and meta-analysis. METHODS: A comprehensive search of PubMed, Embase, Cochrane Library and Web of Science was performed to identify eligible studies. The endpoints included cancer-specific survival (CSS), overall survival (OS), and recurrence-free survival (RFS). A formal meta-analysis was performed for studies containing non-metastatic and metastatic tumors. Additionally, a sensitivity analysis including the subgroup of studies containing non-metastatic tumors only was conducted. Cumulative analyses of hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were conducted. RESULTS: Overall, 35 retrospective studies of low to moderate risk of bias including 11,929 patients were included. The results indicated that large tumor size, high Fuhrman grade, tumor necrosis, positive lymph node, and metastasis at surgery were adverse significant predictors for both CSS and OS. Also, IVC tumor thrombus, sarcomatoid differentiation, perinephretic fat invasion, and adrenal gland invasion were associated with poor CSS. In the subset of non-metastatic patients, the significant predictors were clinical symptom, thrombus level, Fuhrman grade and adrenal gland invasion for CSS; thrombus consistency, Fuhrman grade and tumor necrosis for OS; tumor size, Fuhrman grade and perinephretic fat invasion for RFS. CONCLUSIONS: A meta-analysis of available data identified significant prognostic factors of CSS, OS and RFS that should be systematically evaluated to propose a risk-adapted approach to postoperative patient counseling, risk stratification, and therapy selection.

Laparoscopic vs robot-assisted partial nephrectomy for renal tumours of >4 cm: a propensity score-based analysis.

OBJECTIVES: To compare perioperative data, functional and oncological outcomes between laparoscopic partial nephrectomy (LPN) and robot-assisted partial nephrectomy (RAPN) for renal tumours of >4 cm. PATIENTS AND METHODS: We retrospectively reviewed patients who underwent either LPN or RAPN between 2008 and 2015. To adjust for potential baseline confounders, propensity score matching (1:1) was performed. Perioperative data, functional and oncological outcomes were reviewed. Disease-free survival, cancer-specific survival and overall survival were analysed using Kaplan-Meier survival curves with log-rank tests. RESULTS: In all, 197 patients underwent LPN and 96 underwent RAPN during the study period. After matching, there was no significant difference between the groups for baseline characteristics. Within the matched cohort, the LPN group was associated with significantly higher estimated blood loss (150 vs 100 mL; P < 0.001), longer renal artery clamp time (25 vs 20 min; P < 0.001), longer postoperative hospital stay (7 vs 5 days; P < 0.001), and lower rate of Margin, Ischaemia, and Complications (MIC) achievement (30.2% vs 46.9%; P = 0.018). The postoperative percentage of estimated glomerular filtration rate decline was higher in the LPN group (11.3% vs 5.5%; P = 0.018). Complication and surgical conversion outcomes were similar between LPN and RAPN. There was no significant difference in oncological outcomes between the groups. CONCLUSIONS: For patients with renal tumours of >4 cm, RAPN is more favourable than LPN in terms of perioperative outcomes (i.e. estimated blood loss, renal artery clamp time and postoperative hospital stay) and early renal functional preservation.

Phosphatase and tensin homolog (PTEN) expression on oncologic outcome in renal cell carcinoma: A systematic review and meta-analysis.

The phosphatase and tensin homolog (PTEN) gene is suggested to be a dormant tumor suppressor. However, the prognostic value of the loss of PTEN expression in renal cell carcinoma (RCC) remains controversial. Therefore, we conducted a meta-analysis to evaluate the association of PTEN expression with the clinicopathological presentations and outcomes of patients with RCC through immunohistochemistry staining analysis. We systematically searched for relevant studies in PubMed, Web of Science, and Embase until March 2016. Data regarding clinical stage, pathological type, Fuhrman grade, overall survival (OS), progression-free survival (PFS), and disease-specific survival (DSS) was analyzed in the present study. In total, there were 12 studies with 2,368 patients included in this meta-analysis. The low PTEN expression in RCC was significantly associated with unfavorable DSS (HR = 1.568, 95% CI 1.015-2.242) in a random-effects model but not with OS (HR = 1.046, 95% CI 0.93-1.176) and PFS (HR = 1.244, 95% CI 0.907-1.704). Other results indicated that PTEN expression was not correlated with clinical stage, pathological type, and Fuhrman grade. This meta-analysis suggests that PTEN expression is of limited value in predicting the prognosis of patients with RCC for OS and PFS via immunohistochemistry staining analysis; and that for DSS, low PTEN expression is significantly associated with an unfavorable outcome.

LncRNAs act as prognostic and diagnostic biomarkers in renal cell carcinoma: a systematic review and meta-analysis.

We conducted a systematic review and meta-analysis to investigate the clinical values, including clinicopathology, prognosis, and diagnosis of different long non-coding RNAs (lncRNAs) in renal cell carcinoma (RCC). A total of 14 eligible studies, including 10 on clinicopathological features, 11 on prognosis, and 3 on diagnosis were identified. Results revealed that metastasis-associated lung adenocarcinoma transcript 1(MALAT1) expression was associated with tumor stage (odds ratio [OR], 3.46; 95% confidence interval [CI], 1.63-7.36; p=0.001). The high expression of MALAT1 could be considered a biomarker of the early detection of lymph node metastasis and predictor of poor survival in RCC patients, who likely manifested short overall survival (OS; hazard ratio [HR], 2.97; 95% CI, 1.68-5.28; p<0.001). For diagnostic value, the pooled result showed that lncRNA maintained a sensitivity of 0.89 and specificity of 0.91 in RCC diagnosis, The area under the curve of 0.94 (95% CI, 0.92-0.96) for lncRNA in RCC diagnosis also indicated a significant advantage over other biomarkers. Our systematic review and meta-analysis demonstrated that lncRNAs could be considered biomarkers to detect lymph node metastasis and distant metastasis in early stages. LncRNAs could function as potential prognostic markers in RCC. LncRNAs could also display high accuracy for RCC diagnosis.

Robot-assisted laparoscopic resection of a huge pelvic tumor: A case report.

The traditional open surgery, for the treatment of huge tumor in the narrow space of pelvic cavity and in close proximity to pelvic organs and neurovascular structures, is very difficult and challenging. We report a case of huge neurilemmoma operated using the robot-assisted laparoscopy. We used interventional pre-operation embolization to control blood supply of tumor because MRI showed the tumor had a sufficient blood supply.

Prevalence and characterization of somatic mutations in Chinese aldosterone-producing adenoma patients.

Recently somatic mutations of KCNJ5, ATP1A1, ATP2B3, and CACNA1D have been identified in patients with aldosterone-producing adenoma (APA). The present study sequenced the DNA in the tissues and blood samples from Chinese patients with APA for KCNJ5, ATP1A1, ATP2B3, and CACNA1D gene mutations.Among the 114 patients, 86 (75.4%) were identified with KCNJ5 somatic mutations, including 3 previously reported (G151R, L168R, T158A) and 2 other unreported mutations. One patient presented with both a point mutation (E147) and an insertion mutation, whereas another had a 36-base duplication, G153_G164dup. No mutation of ATP1A1 and ATP2B3 in the known hotspots was identified and only 1 male patient was detected with a novel CACNA1D mutation, V748I. Unlike other studies, male and female patients had similar KCNJ5 mutation rates (76.9% vs 74.2%). Mutation carriers were younger and had lower preoperative potassium level, whereas male (but not female) mutation carriers had higher preoperative plasma aldosterone concentration and preoperative blood pressures. Mutation carriers also had higher LV mass index (LVMI) than nonmutation carriers. After surgery, LVMI improved significantly in the KCNJ5 mutation group but not in the nonmutation group. The mRNA expression of KCNJ5, CYP11B2, and ATP2B3 was higher in the KCNJ5-mutated APA tissues. Functional characterization of the 2 novel KCNJ5 mutations showed that they were associated with decreased proliferation, membrane depolarization, elevated secretion of aldosterone, and increased expression of CYP11B1 and CYP11B2.In conclusion, Chinese APA patients appear to have a high frequency of somatic KCNJ5 mutation. Mutation prevalence rates are similar among men and women and 2 novel mutations are identified. KCNJ5-mutated patients benefit more from surgical resection of APA than nonmutated patients.

Hypoxia-induced overexpression of stanniocalcin-1 is associated with the metastasis of early stage clear cell renal cell carcinoma.

BACKGROUND: Although metastasis of clear cell renal cell carcinoma (ccRCC) is predominantly observed in late stage tumors, early stage metastasis of ccRCC can also be found with indefinite molecular mechanism, leading to inappropriate clinical decisions and poor prognosis. Stanniocalcin-1 (STC1) is a glycoprotein hormone involved in calcium/phosphate homeostasis, which regulates various cellular processes in normal development and tumorigenesis. This study aimed to investigate the role and mechanism of regulation of STC1 in the metastasis of early stage ccRCC. METHODS: STC1 mRNA and protein expression was determined in ccRCC surgical specimens, RCC cell lines, and human kidney tubule epithelial cell line HKC by real-time polymerase chain reaction (RT-PCR) and western blotting. Immunohistochemistry staining (IHC) and immunofluorescence were also used to examine the expression and localization of STC1 in ccRCC tissues and cancer cells. Knockdown and overexpression studies were conducted in vitro in RCC cell lines using small interfering RNAs (siRNA) and lentiviral-mediated gene delivery to evaluate the role of STC1 in cell proliferation, anchorage-dependent and independent growth, cell cycle control, and migration and invasion. RESULTS: STC1 mRNA and protein expression were significantly up-regulated in tumors when compared with non-tumor tissues, with the greatest increase in expression observed in metastatic tissues. Clinicopathological analysis revealed that STC1 mRNA expression was associated with Fuhrman tumor grade (P = 0.008) and overall Tumor Node Metastasis (TNM) staging (P = 0.018). STC1 expression was elevated in T1 stage metastatic tumors when compared with localized tumors, and was positively correlated with average tumor diameter. Silencing of STC1 expression by Caki-1 and A498 resulted in the inhibition of cell proliferation, migration, and invasion, meanwhile down-regulation of STC1 impaired epithelial-mesenchymal transition (EMT) of ccRCC cell lines. Overexpression of STC1 in Caki-2 enhanced cell growth and proliferation but not migration and invasion. Further investigation identified hypoxia and HIF-1α as candidate regulators of STC1 expression. CONCLUSIONS: Our findings demonstrate a role for STC1 in metastasis of early stage ccRCC and suggest that STC1 may be a biomarker of potential value both for the prognosis of this disease and for guiding clinical decisions regarding surgical strategies and adjuvant treatment.

Elevated S100A6 (Calcyclin) enhances tumorigenesis and suppresses CXCL14-induced apoptosis in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is often resistant to existing therapy. We found elevated S100A6 levels in ccRCC tissues, associated with higher grade pathological features and clinical stages in ccRCC patients. Knockdown of S100A6 inhibited cell proliferation in vitro and tumor growth in vivo. Gene expression profiling suggests a novel function of S100A6 in suppressing apoptosis, as well as a relationship between S100A6 and CXCL14, a pro-inflammatory chemokine. We suggest that the S100A6/CXCL14 signaling pathway is a potential therapeutic target in ccRCC.

High-level S100A6 promotes metastasis and predicts the outcome of T1-T2 stage in clear cell renal cell carcinoma.

S100A6 (calcyclin), functions in cell cycle progression and differentiation, has been reported to promote the tumorigenesis and malignancy of many types of cancers. Clear cell renal cell carcinoma (ccRCC) is the most common subtype of RCC, lacking both promising prognostic markers and effective therapeutic targets. In our previous study, we have found the elevated S100A6 in the ccRCC tumor tissues, and the differentially expressed genes determined by microarray analysis were found to be strongly related to tumor metastasis after S100A6 knockdown and overexpression in the ccRCC cell line 786-O. The mRNA expression of S100A6 detected by RT-PCR in 6 cell lines and 174 tumor tissues, including 58 metastatic ccRCC and 116 clinicopathological features paired non-metastatic ccRCC (1:2), indicated S100A6 was elevated in the metastatic cells and tumor tissues. The protein expression was consistent with mRNA expression. The biological function of S100A6 in promoting metastasis was determined through overexpression and knockdown of S100A6 in the ccRCC cell lines 786-O, caki-1, and ACHN. In the scratch wound migration assay as well as migration and invasion assays, S100A6 knockdown significantly suppressed the migratory and invasive abilities of tumor cells, whereas overexpression enhanced the malignancy. Further research with the follow-up data of 129 ccRCC patients were analyzed by the Cox regression and survival analysis. The expression of S100A6 was up-regulated in metastatic ccRCC cells. In the metastatic tumor tissues, the expression of S100A6 was also higher than in the non-metastatic tissues. High S100A6 expression might be crucial to promote metastasis in ccRCC by enhancing the ability of tumor cells migration and invasion. In addition, the quantitative mRNA expression of S100A6 in the tumor tissues was an independent risk factor and might be used as a prognostic marker for the metastatic risk of the localized T1-T2 stage ccRCC.