Carcinoma Of Upper Urinary Tract Research Articles

Effects of Variant Histology on the Oncologic Outcomes of Patients With Upper Urinary Tract Carcinoma After Radical Nephroureterectomy: A Propensity Score-Matched Analysis.

To determine the prognostic effect of upper tract urothelial carcinoma (UTUC) with variant histology (VH) after radical nephroureterectomy (RNU). The data of 1173 patients who received RNU for UTUC without neoadjuvant chemotherapy in 11 institutions between 2002 and 2016 were retrospectively reviewed. A matched propensity score analysis was performed. Clinicopathologic variables, recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were compared between patients with pure UTUC and patients with UTUC and VH. Univariate and multivariate Cox proportional regression models were used to determine the independent variables associated with oncologic outcomes. UTUC with VH was observed in 93 patients (7.9%). After propensity score matching, UTUC with VH showed no difference in clinicopathologic features compared to pure UTUC; however, it was associated with shorter RFS, CSS, and OS (log rank, P= .011, P= .002, P= .006, respectively). Additionally, the multivariate analysis revealed that VH was independently associated with a poor RFS [hazard ratio (HR)= 1.92; 95% confidence interval (CI), 1.27-2.89; P= .002], CSS (HR= 4.47; 95% CI, 1.99-10.1; P=.001), and OS (HR= 3.00; 95% CI, 1.55-5.78; P= .001). However, the Kaplan-Meier method revealed that differences in RFS, CSS, and OS were not significant in patients who received adjuvant chemotherapy (log rank, P= .562, P= .060, P= .153, respectively). UTUC with VH was independently associated with poor oncologic outcomes in patients with UTUC after RNU. Although patients with UTUC and VH had a poor prognosis compared to patients with pure UTUC, adjuvant chemotherapy would be helpful in improving the survival rates of these patients.

Phenotypic Analysis of Tumor Tissue-Infiltrating Lymphocytes in Tumor Microenvironment of Bladder Cancer and Upper Urinary Tract Carcinoma.

There are no previous reports directly evaluating immunologic conditions in tumor microenvironment including both bladder cancer (BCa) and upper urinary tract carcinoma (UTUC). In this study, we aimed to clarify the difference of immunity status and its clinical significance depending on the tumor site in urothelial carcinoma. Tumor tissue-infiltrating lymphocytes were extracted from 70 urothelial cancer patients who underwent surgical resection (52 cases of BCa and 18 cases of UTUC). The immunologic classification was established by unsupervised clustering analysis according to the expression ratio of 9 extracellular surface markers measured by flow cytometry, and we examined the relationship between immunologic classification and clinical importance such as pathologic status and prognosis (progression-free survival and cancer-specific survival). The immunologic condition was classified into 2 groups. Group 1 (n= 41) comprised the CD4 T-cell-dominant group and group 2 (n=29) the immunologically activated group. This immunologic classification was significantly correlated with tumor grade (P= .020) but not tumor location in multivariate analysis. In invasive BCa patients (n= 33), progression-free survival and cancer-specific survival of group 2 were significantly worse than those of group 1 (P= .021 and P=.022, respectively), while there was no significant difference between groups 1 and 2 in patients with invasive UTUC (n= 17). Although there was no difference in the local immunologic condition of urothelial carcinoma between BCa and UTUC, its significance as a prognostic predictor might vary depending on tumor site.

P122 - Association of HLA-A, -B and -DRB1 genes with endemic nephropathy and urothelial carcinoma of upper urinary tract in Croatia

P122 - Association of HLA-A, -B and -DRB1 genes with endemic nephropathy and urothelial carcinoma of upper urinary tract in Croatia

Clinico-pathological profile of patients with upper tract TCC: a single centre experience

Background: Urothelial carcinomas are rare tumors and this rarity have made these tumors greatly significant. Urothelial Carcinoma of Upper Urinary Tract (UC-UUT) are still rarer and occur in elderly population. Much of the literature concerning urothelial neoplasms has focused on the urinary bladder, which is understandable given that the majority of these tumors occur in the bladder. Most common UC-UUT are the renal pelvic tumors followed by distal ureteric tumors. There is paucity of literature of UC-UUT in the Indian context hence this study assumes importance.Methods: 16 cases of UC-UUT were included in the study. A complete preoperative evaluation was done. Radical Nephroureterectomy (RNU) with bladder cuff excision was undertaken and histopathology of resected specimen was noted. Adjuvant therapy was given wherever necessary. A systematic follow-up was done, and recurrences were noted and treated. Data was then analyzed.Results: Male to female ratio was 3:1. Most patients presented with hematuria. Most lesions were left sided. Renal pelvis was the most affected site.73% tumors were of high grade and 47% were in pT3 stage. There was a single case of systemic metastasis in present study.15 out of 16 cases underwent radical nephroureterectomy with bladder cuff excision. In follow up, recurrence free survival was 66.67% and cancer free survival was 86.6% after surgery.Conclusions: Upper urinary tract urothelial tumor is a rare disease In Indian context, majority of patients presented late and were having high stage and grade at the time of diagnosis. Invasive disease was more common. Radical nephroureterectomy in still the gold standard treatment. Conservative treatment should be considered in specific cases. Recurrences in bladder are common and should be treated early.

Prognostic value of circulating microRNAs in upper tract urinary carcinoma.

The identification of upper tract urinary carcinoma (UTUC) prognostic biomarkers is urgently needed to predict tumour progression. This study aimed to identify serum microRNAs (miRNAs) that may be useful as minimally invasive predictive biomarkers of tumour progression and survival in UTUC patients. To this end, 33 UTUC patients who underwent radical nephroureterectomy at the Hospital Clinic of Barcelona were prospectively included. Expression of 800 miRNAs was evaluated in serum samples from these patients using nCounter® miRNA Expression Assays. The study was divided into an initial discovery phase (n=12) and a validation phase (n=21). Cox regression analysis was used for survival analysis. The median follow-up (range) of the series was 42 months (9-100 months). In the discovery phase, 38 differentially expressed miRNAs were identified between progressing and non-progressing UTUC patients (p<0.05). Validation of these 38 miRNAs in an independent set of UTUC patients confirmed the differential expression in 18 of them (p<0.05). Cox Regression analysis showed miR-151b and pathological stage as significant prognostic factors for tumour progression (HR=0.33, p<0.001 and HR=2.62, p=0.006, respectively) and cancer specific survival (HR=0.25, p<0.001 and HR=3.98, p=0.003, respectively). Survival curves revealed that miR-151b is able to discriminate between two groups of UTUC patients with a highly significant different probability of tumour progression (p=0.006) and cancer specific survival (p=0.034). Although the data needs to be externally validated, miRNA analysis in serum appears to be a valuable prognostic tool in UTUC patients. Particularly, differential expression of miR-151b in serum may serve as a minimally invasive prognostic tool in UTUC.

Small cell carcinoma of upper urinary tract

Introduction: Small cell carcinoma (SCC) of upper urinary tract is not common and often associated with poor prognosis. We aimed to analyze the prognostic factors based on the pooled cases published in the literature. Patients and Methods: In addition to 10 cases treated at our hospital since 1990, 52 additional published cases with SCC of renal pelvis and ureter were enrolled into this study. We investigated the following risk factors associated with clinical outcome: age at diagnosis, gender, tumor location, histology, tumor stage, and treatment modality using univariate log-rank test and multivariate Cox analyses. Results: A total of 62 cases were enrolled into the study, including ten added by us. There were 30 cases from renal pelvis, 26 from the ureter, and 6 both sites. The mean age is 65.8 ± 13.0 years, and the median survival is 12 months. Patients with SCC of renal pelvis were significantly younger than did those of the ureter (P = 0.004), as well as higher stage (P = 0.043). Univariate analysis showed that both tumor stage and the presence of radiotherapy were significant predictors of disease-specific overall survival (P = 0.015 and 0.029, respectively), as well as the overall survival (P = 0.035 and 0.036, respectively). Cox's multivariate analysis showed tumor stage is an independent prognostic factor for disease-specific overall survival (hazard ratio, 2.11; 95% confidence interval, 1.08–4.13; P = 0.029). Conclusions: In the current study, tumor stage is significantly associated with disease-specific overall survival. This finding warns us the importance of early diagnosis of SCC.

Loss of Stromal Antigen 2 (STAG2) Expression in Upper Urinary Tract Carcinoma: Differential Prognostic Effect According to the Ki-67 Proliferating Index.

Inactivating mutation and consequent expression loss of stromal antigen 2 (STAG2, also known as SA2), a component of the cohesion complex, is one of the most common genetic aberrations in urothelial carcinoma. However, the clinicopathologic or prognostic significance of STAG2 alterations in upper tract urothelial carcinoma (UTUC) is largely unknown. This study immunohistochemically examined the expression of STAG2 in 171 patients with UTUC. The correlations of STAG2 loss with clinicopathologic features and patients' prognoses were examined. Loss of STAG2 expression was observed in 28 cases (16%). Loss of STAG2 was significantly correlated with histological low grade, papillary architecture, noninvasive tumors, absence of concomitant carcinoma in situ, and lower Ki-67 expression. Loss of STAG2 alone was not significantly associated with patients' prognoses in either the uni- or multivariate analysis. However, STAG2 loss was significantly associated with worse clinical outcome in UTUC with high Ki-67 proliferation indexes, but not in UTUC with low Ki-67 expression. Loss of STAG2 was generally associated with less aggressive features in UTUC. However, the STAG2 loss was an ominous sign in the subpopulation with higher Ki-67 proliferation indexes. Examining both STAG2 and Ki-67 status may be useful for identifying aggressive clinical behavior of UTUC.

Conservative treatment of upper urinary tract carcinoma: Long-term results.

We sought to assess the long-term results of conservative treatment for upper urinary tract carcinoma (UUTC) with regard to tumour recurrence and preservation of renal unit. From October 1987 to January 2014, 65 patients (median age 68 years) were diagnosed with UUTC and underwent endoscopic and open surgical techniques. Thirteen patients had bilateral disease and one had a single kidney. The primary approach was endoscopic in 37 reno-ureteral units (20 percutaneous resections, 17 ureteroscopies ). Open surgery was performed in 19 cases. A total of 20 patients received mitomycin C. Superficial stage pTa or T1 was noted in 37 patients, infiltrating stage pT2 and pT3 in seven and inverted papilloma in one. The stage of the tumour was impossible to classify in 20. With a median followup of 75.12 months (interquartile range [IQR] 144.71-17.41), the kidney preservation, recurrence, specific survival, and global survival rates were 78.5% (51/65), 40.0% (26/65), 92.3% (60/65), and 69.2% (45/65), respectively. From the patients who had recurrence, 15 were salvaged with radical nephroureterectomy (RNU). The bladder tumour recurrence rate after the surgery was 30.76% (20/65). At the end of the followup, five patients had died of UUTC progression and 16 from other causes. Postoperative complications included one case of fistula, one case of stricture, and one case of nephrectomy due to bleeding. In selected cases, conservative management is a safe and feasible alternative to RNU, with the advantage of renal unit preservation.

Impact of tumor architecture on disease recurrence and cancer-specific mortality of upper tract urothelial carcinoma treated with radical nephroureterectomy.

Upper tract urinary carcinoma (UTUC) is a relatively uncommon but aggressive disease. Recent publications have assessed the prognostic significance of tumor architecture in UTUC, but there is still controversy regarding the significance and importance of tumor architecture on disease recurrence. We retrospectively reviewed the medical records of 101 patients with clinical UTUC who had undergone surgery. Univariate and multivariate analyses were conducted to identify factors associated with disease recurrence and cancer-specific mortality. As our single center study and the limited sample size may influence the clinical significance, we further quantitatively combined the results with those of existing published literature through a meta-analysis compiled from searching several databases. At a median follow-up of 41.3 months, 25 patients experienced disease recurrence. Spearman's correlation analysis showed that tumor architecture was found to be positively correlated with the tumor location and the histological grade. Kaplan-Meier curves showed that patients with sessile tumor architecture had significantly poor recurrence free survival (RFS) and cancer specific survival (CSS). Furthermore, multivariate analysis suggested that tumor architecture was independent prognostic factors for RFS (Hazard ratio, HR = 2.648) and CSS (HR = 2.072) in UTUC patients. A meta-analysis of investigating tumor architecture and its effects on UTUC prognosis was conducted. After searching PubMed, Medline, Embase, Cochrane Library and Scopus databases, 17 articles met the eligibility criteria for this analysis. The eligible studies included a total of 14,368 patients and combined results showed that sessile tumor architecture was associated with both disease recurrence with a pooled HR estimate of 1.454 and cancer-specific mortality with a pooled HR estimate of 1.416. Tumor architecture is an independent predictor for disease recurrence after radical nephroureterectomy for UTUC. Therefore, closer surveillance is necessary, especially in patients with sessile tumor architecture.

New technologies for upper tract urothelial carcinoma management.

Image enhancement techniques and optical diagnostic tools have emerged in the quest to improve diagnostics and treatment in patients with upper urinary tract carcinoma (UTUC). The aim of the present report is to describe their mechanisms of action and to assess the current evidence on applicability and utility in UTUC. Image enhancement techniques including narrow band imaging, Image1 S, and photodynamic diagnosis aim at better visualization of malignant urothelium and especially flat tumours or carcinoma in situ which are often difficult to see with white light endoscopy. Conducted studies in the upper tract are scarce but first results show that tumour detection seems to be better for narrow band imaging and photodynamic diagnosis-guided inspection.Optical diagnostic tools as confocal laser endomicroscopy and optical coherence tomography aim at providing real time optical biopsies giving pathologic information. A pilot study of optical coherence tomography proved its feasibility to visualize, grade and stage low and high-grade UTUC. Better visualization of suspect lesions and optical diagnostic techniques providing real time optical biopsies aim to facilitate in higher diagnostic precision and optimal individualized treatment of our patients with UTUC. As the disease is rare, studies are scarce but indispensable for future implication of these techniques.

Prognostic Role of Neutrophil-to-lymphocyte Ratio-based Markers During Pre- and Postadjuvant Chemotherapy in Patients With Advanced Urothelial Carcinoma of Upper Urinary Tract.

The aim of the present study was to assess the prognostic significance of neutrophil-to-lymphocyte ratio (NLR)-based markers before and after adjuvant chemotherapy (ACH) in patients with urothelial carcinoma of the upper urinary tract (UTUC) undergoing radical nephroureterectomy (RNU) and ACH. The data from 112 patients with advanced UTUC who had undergone first-line ACH after RNU from 1994 to 2012 were reviewed. After excluding 22 patients, the clinicopathologic data for 90 patients were analyzed, in particular, the NLR and derived NLR (dNLR) preoperatively and before and after ACH. Cancer-specific survival (CSS) and overall survival (OS) outcomes were measured using Kaplan-Meier analysis. To identify the predictors for the oncologic outcomes, a multivariate Cox regression model was used. Patients with a higher preoperative NLR, pre-ACH dNLR, and post-ACH dNLR had poorer CSS and OS than their counterparts with lower values. After adjustment of various clinicopathologic factors, age at surgery (≥ 65 years; hazard ratio [HR], 3.13) and higher post-ACH dNLR (HR, 3.06) remained significant predictors for CSS. Similarly, age (≥ 65 years; HR, 2.90) and elevated post-ACH dNLR (≥ 2.3; HR, 2.89) were also identified as predictors of OS on multivariate analysis. A higher post-ACH dNLR was independently predictive of poor CSS and OS in patients with advanced UTUC receiving systemic ACH after RNU. From the obtained data, we propose that the NLR-based marker could be a readily available and valuable biomarker for predicting oncologic outcomes after chemotherapy.

Current position of diagnostics and surgical treatment for upper tract urothelial carcinoma.

The applicability of urinary biomarkers and optical diagnostics in upper urinary tract carcinoma (UUT-UC) are increasingly debated. To receive insight in the opinion of the urological community involved in this field, a survey was sent out to identify the most promising techniques and understand the need for new diagnostics. Primary objective of this study was to provide an overview of current diagnostics in upper urinary tract urothelial carcinoma. Secondary objectives of this study was to assess the need for additional diagnostic techniques in the current diagnostic work-up for UUT-UC and to assess knowledge of novel techniques. An electronic survey was distributed to all participants of the upper urinary tract tumor registration study by the Clinical Research Office of the Endourological Society. Additionally, based on publications, experts in the field were contacted. Analysis was performed on the results overviewed by the survey monkey website. In total 81 of the 112 invited individuals responded resulting in a response rate of 72.3%. Most urologists involved in the treatment of upper urinary tract tumors follow the guidelines in their diagnostic work-up of patients suspected for UUT-UC. 61.4% of all responders consider current available diagnostic methods insufficient to select patient candidates for conservative renal sparing surgery. According to the responders, digital endoscopes for retrograde intrarenal surgery (RIRS) including narrow-band imaging (NBI) are best known and most likely to be beneficial compared to all evaluated diagnostic tools currently available. Urologists consider current diagnostic techniques for upper urinary tract tumors insufficient for optimal patient selection for conservative renal sparing surgery. Among the new techniques, NBI and digital RIRS are best known and considered to be beneficial in the diagnostic work-up.

Sulfotransferase-1A1-dependent bioactivation of aristolochic acid I and N-hydroxyaristolactam I in human cells.

Aristolochic acids (AA) are implicated in the development of chronic renal disease and upper urinary tract carcinoma in humans. Using in vitro approaches, we demonstrated that N-hydroxyaristolactams, metabolites derived from partial nitroreduction of AA, require sulfotransferase (SULT)-catalyzed conjugation with a sulfonyl group to form aristolactam-DNA adducts. Following up on this observation, bioactivation of AA-I and N-hydroxyaristolactam I (AL-I-NOH) was studied in human kidney (HK-2) and skin fibroblast (GM00637) cell lines. Pentachlorophenol, a known SULT inhibitor, significantly reduced cell death and aristolactam-DNA adduct levels in HK-2 cells following exposure to AA-I and AL-I-NOH, suggesting a role for Phase II metabolism in AA activation. A gene knockdown, siRNA approach was employed to establish the involvement of selected SULTs and nitroreductases in AA-I bioactivation. Silencing of SULT1A1 and PAPSS2 led to a significant decrease in aristolactam-DNA levels in both cell lines following exposure to AA-I, indicating the critical role for sulfonation in the activation of AA-I in vivo Since HK-2 cells proved relatively resistant to knockdown with siRNAs, gene silencing of xanthine oxidoreductase, cytochrome P450 oxidoreductase and NADPH:quinone oxidoreductase was conducted in GM00637 cells, showing a significant increase, decrease and no effect on aristolactam-DNA levels, respectively. In GM00637 cells exposed to AL-I-NOH, suppressing the SULT pathway led to a significant decrease in aristolactam-DNA formation, mirroring data obtained for AA-I. We conclude from these studies that SULT1A1 is involved in the bioactivation of AA-I through the sulfonation of AL-I-NOH, contributing significantly to the toxicities of AA observed in vivo.

V42 Conservative treatment of the upper urinary tract carcinoma

V42 Conservative treatment of the upper urinary tract carcinoma

806 Chronological changes of clinical outcome after radical nephroureterectomy in patients with localized upper urinary tract carcinoma treated in the last two decades: Are we succeeding?

806 Chronological changes of clinical outcome after radical nephroureterectomy in patients with localized upper urinary tract carcinoma treated in the last two decades: Are we succeeding?

Is Overexpression of Ki-67 a Prognostic Biomarker of Upper Tract Urinary Carcinoma? A Retrospective Cohort Study and Meta-Analysis

Background: Upper tract urinary carcinoma (UTUC) is a relatively uncommon but aggressive disease. The Ki-67 antigen is a classic marker of cellular proliferation, but there is still controversy regarding the significance and importance of Ki-67 in tumor progression. Methods: In this study, we first detected Ki-67 expression in UTUC patients by immunohistochemistry (IHC). Subsequently, we quantitatively combined the results with those from the published literature in a meta-analysis after searching several databases. Results: IHC results demonstrated that patients with muscle-invasive tumors (T2-T4) had higher Ki-67 expression than those with non-muscle-invasive tumors (Tis-T1), suggesting that high Ki-67 expression may be associated with the aggressive form of UTUC. Kaplan-Meier curves showed that patients with high Ki-67 expression had significantly poorer cancer-specific survival (CSS) and disease-free survival (DFS). Furthermore, multivariate analysis suggested that Ki-67 expression was an independent prognostic factor for CSS (hazard ratio, HR=3.196) and DFS (HR=3.517) in UTUC patients. Then, a meta-analysis of the published literature investigating Ki-67 expression and its effects on UTUC prognosis was conducted. After searching the PubMed, Medline, Embase, Cochrane Library and Scopus databases, 12 articles met the eligibility criteria for this analysis. The eligible studies included a total of 1740 patients with a mean number of 82 patients per study (range, 38-475). The combined results showed that increased Ki-67 levels were associated with poor survival and disease progression, with a pooled HR estimate of 2.081 and 2.791, respectively. In subgroup analysis, the pooled HR was statistically significant for cancer-specific survival (HR=2.276), metastasis-free survival (HR=3.008) and disease-free survival (HR=6.336). Conclusions: In conclusion, high Ki-67 expression was associated with poor survival in patients with UTUC, as well as a high risk of disease progression, although these findings need to be interpreted with caution. Large-scale, adequately designed, prospective trials are needed to further confirm the value of Ki-67 in prognosis of UTUC patients.

Necdin Overexpression Predicts Poor Prognosis in Patients with Urothelial Carcinomas of the Upper Urinary Tract and Urinary Bladder

Background and Aims: Oncogenesis is a multistep process, resulting from the accumulations of multiple mutations. Of these mutations, self-sufficiency in growth signals, i.e., disruption of cell growth regulation, is the first episode. Nonetheless, the genes associated with cell growth dysregulation have seldom been systematically evaluated in either urothelial carcinomas of upper urinary tract (UTUC) or urothelial carcinomas of urinary baldder (UBUC). By data mining a published transcriptomic dataset of UBUCs (GSE31684), we identified the NDN gene as one of the most significant of those associated with the regulation of cell growth and found this gene is associated with advanced tumor status and metastatic disease (GO:0001558). Accordingly, we analyzed NDN transcript and protein expression with their clinicopathological significance.Materials and Methods: We used real time RT-PCR to detect NDN transcript levels in 27 UTUCs and 27 UBUCs, respectively. Immunohistochemical study was performed to determine NDN protein (a.k.a. Necdin) expression evaluated by H-score method in 340 UTUCs and 295 UBUCs. NDN expression was further correlated with clinicopathological features and disease-specific survival (DSS) and metastasis-free survival (MeFS).Results: NDN transcriptional level was significantly higher in UCs of both sites with stepwise more advanced pT statuses. Through immunohistochemistry, we found NDN protein expression was significantly associated with adverse clinicopathological parameters, e.g., advanced pT status, nodal metastasis, high grade histological patterns, and frequent mitotses (all P<0.05). In univariate analysis, NDN overexpression not only predicted worse DSS and MeFS in both the UTUC and UBUC groups, it also served as an independent prognostic factor for DSS and MeFS in multivariate analysis (all P<0.05).Conclusions: NDN may play an important role in tumor progression in UC and could serve as a prognostic biomarker and a potential novel therapeutic target in UC.

MAGE-A expression, immune microenvironment, and prognosis in upper urinary tract carcinoma

The melanoma-associated antigen A (MAGE-A) family comprises cancer-testis antigens that represent promising prognostic biomarkers and immunotherapy targets in several cancer types. The aim of this study was to investigate the significance of MAGE-A expression in upper urinary tract urothelial carcinoma in relation to clinicopathological features, lymphocytic infiltration, and clinical outcome. We immunohistochemically examined the expression of MAGE-A in 171 patients with upper urinary tract urothelial carcinoma. High (≥ 50% positive) and low MAGE-A expression levels were observed in 33 (19%) and 49 (29%) cases, respectively. MAGE-A was negative in 89 cases (52%). MAGE-A expression was positively correlated with high histologic grade; concomitant carcinoma in situ; higher Ki-67 proliferation index; and infiltration of CD3-, CD8-, and CD45RO-positive T lymphocytes, but not with CD20-positive B lymphocytes. High MAGE-A expression was significantly associated with shorter metastasis-free survival after nephroureterectomy (log-rank P = .019; multivariate hazard ratio, 1.98; 95% confidence interval, 1.00-3.92). MAGE-A expression in metastatic lymph nodes was highly correlated with its expression in primary lesions. MAGE-A expression was retained in chemotherapy-resistant metachronous metastatic lesions of urothelial carcinoma. MAGE-A may be a promising prognostic biomarker and potential immunotherapeutic target for patients with upper urinary tract urothelial carcinoma.

Differential microRNA expression in aristolochic acid-induced upper urothelial tract cancers ex vivo

Aristolochic acid (AA) is a carcinogenic, mutagenic and nephrotoxic compound commonly isolated from members of the plant family of Aristolochiaceae (such as Aristolochia and Asarum) and used in Chinese herbal medicine. Use of AA and AA-containing plants causes chronic kidney disease (CKD) and upper urinary tract carcinoma (UUC); however, the underlying mechanism remains to be defined. miRNAs regulate a number of biological processes, including cell proliferation, differentiation and metabolism. This study explored differentially expressed miRNAs between AA-induced upper urothelial tract cancer (AAN-UUC) and non-AAN-UUC tissues. Patients with AAN-UUC and non-AAN-UUC (n=20/group) were recruited in the present study. Five tissue samples from each group were used for miRNA microarray profiling and the rest of the tissue samples were subjected to reverse transcription-quantitative polymerase chain reaction analysis including seven selected miRNAs for confirmation. A total of 29 miRNAs were differentially expressed between AAN-UUC and non-AAN-UUC tissues (P<0.05). TargenScan and Gene ontology analyses predicted the functions and targeted genes of these differentially expressed miRNAs, i.e. Akt3, FGFR3, PSEN1, VEGFa and AR. Subsequently, expression of the selected differentially expressed miRNAs (Hsa-miR-4795-5p, Hsa-miR-488, Hsa-miR-4784, Hsa-miR-330, Hsa-miR-3916, Hsa-miR-4274 and Hsa-miR-181c) was validated in another set of tissue samples. A total of 29 miRNAs were identified to be differentially expressed between AAN-UUC and non-AAN-UUC tissues and these miRNA target genes in FGFR3 and Akt pathways, which regulate cell growth and tumor progression, respectively.

Our experience of tissue glue injection in tubeless percutaneous nephrolithotomy

Our experience of tissue glue injection in tubeless percutaneous nephrolithotomy