Search

Background/Aim: The expression of matrix metalloproteinase 9 (MMP9) is elevated in various renal diseases, including renal cell carcinoma. However, the role of MMP9 genotype in this context remains unclear. This study aimed to investigate the association between MMP9 promoter rs3918242 genotypes and the risk of renal cell carcinoma. Materials and Methods: The MMP9 rs3918242 genotypes of 118 patients with renal cell carcinoma and 590 healthy subjects were determined using the polymerase chain reaction-restriction fragment length polymorphism method. Results: The results indicated that individuals carrying the CT or TT genotype of MMP9 rs3918242 did not exhibit an increased risk of renal cell carcinoma compared to wild-type CC carriers (odds ratio=1.20 and 2.68, 95% confidence interval=0.75-1.92 and 0.89-8.03; p=0.5270 and 0.1420, respectively). However, individuals with the CT and TT genotypes had a higher prevalence of renal cell carcinoma than those with the CC genotype when they also had hypertension (p=0.0010), diabetes (p=0.0010), or a family history of cancer (p<0.00001). No correlation was observed between MMP9 rs3918242 genotypic distribution and age (60 years or younger vs. older than 60 years) or sex (both p>0.05). Additionally, no correlation was found between MMP9 rs3918242 genotype and the risk of renal cell carcinoma in individuals with smoking or alcohol consumption habits. Conclusion: Carrying the T allele for MMP9 rs3918242 may predict a higher risk of renal cell carcinoma among individuals diagnosed with hypertension, diabetes, or with a family history of cancer. [ABSTRACT FROM AUTHOR]

Background: There are limited real-world data to guide the sequencing of targeted therapies in patients with metastatic renal cell carcinoma (mRCC). The objective of this study was to characterize real-world treatment patterns (primarily second line [2L]) after prior vascular endothelial growth factor (VEGF) targeted therapy in an unselected mRCC population from Taiwan between 2013 and 2017. Treatment-related adverse events (TRAEs) and their management were also evaluated (NCT03633579). Methods: This retrospective cohort study included patients who had received prior VEGF-targeted therapy and were treated at the National Taiwan University Hospital or the Taipei Veterans General Hospital between June 2013 and December 2017. Outcomes were characterized using descriptive statistics. Results: Overall, 27 patients were included: 22 (81.5%) male; mean standard deviation (SD) age, 63.1 (11.1) years; 18 (66.7%) initiated targeted therapy during the year immediately following mRCC diagnosis. All patients received sunitinib as their first-line (1L) targeted therapy, with a median (range) treatment duration of 10 (1.8-65.8) months. The most common reason for discontinuing 1L sunitinib was disease progression (88.9% of patients). Everolimus was the most common 2L targeted therapy, in 23 patients (85.2%); 4 patients (14.8%) received 2L axitinib. Median (range) duration of 2L therapy was 4.0 (0.1-30.5) months for everolimus and 4.2 (0.5-9.2) months for axitinib. Ten TRAEs were reported among seven patients receiving 2L everolimus: hypertension (n = 5), hand-foot syndrome (n = 2), hyperglycemia (n = 1), renal failure (n = 1), and interstitial pneumonitis (n = 1). The majority (80%) of TRAEs were managed in the outpatient setting. No TRAEs were reported in the axitinib group. Conclusion: Real-world management of patients with mRCC in Taiwan broadly aligned with clinical guidelines and national reimbursement policy at the time of the study. These findings may be a useful reference for assessing the implications of evolving mRCC management approaches in Taiwan. [ABSTRACT FROM AUTHOR]

Background: Renal cell carcinoma (RCC) is the most common neoplasm in kidneys, and surgical resection remains the mainstay treatment. Few studies have investigated how the postoperative pain changes over time and what has affected its trajectory. This study aimed to characterize the variations in postoperative pain over time and investigate associated factors after RCC surgery. Methods: This retrospective study was conducted in a single medical center in Taiwan, where maximal pain scores in a numeric rating scale were recorded daily in the first five postoperative days (PODs) after RCC surgery. Latent curve models were developed, using two latent variables, intercept and slope, which represented the baseline pain and rate of pain resolution. These models explain the variations in postoperative pain scores over time. A predictive model for postoperative pain trajectories was also constructed. Results: There were 861 patients with 3850 pain observations included in the analysis. Latent curve analysis identified that female patients and those with advanced cancer (stage III and IV) tended to have increased baseline pain scores (p = 0.028 and 0.012, respectively). Furthermore, patients over 60 years, without PCA use (both p < 0.001), and with more surgical blood loss (p = 0.001) tended to have slower pain resolution. The final predictive model fit the collected data acceptably (RMSEA = 0.06, CFI = 0.95). Conclusion: Latent curve analysis identified influential factors of acute pain trajectories after RCC surgery. This study may also help elucidate the complex relationships between the variations in pain intensity over time and their determinants, and guide personalized pain management after surgery for RCC. [ABSTRACT FROM AUTHOR]

Background/aim: Renal cell carcinoma (RCC) presents a formidable clinical challenge due to its aggressive behavior and limited therapeutic options. Matrix metalloproteinase-8 (MMP-8) has recently emerged as a potential biomarker and therapeutic target for various cancers. However, the genetic involvement of MMP-8 in RCC has remained largely obscure. This study aimed to elucidate the role of MMP-8 genotypes in RCC susceptibility., Materials and Methods: The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was employed to scrutinize the genotypes of MMP-8 C-799T (rs11225395), Val436Ala (rs34009635), and Lys460Thr (rs35866072) among 118 RCC patients and 590 controls. Furthermore, potential associations between MMP-8 genotypes and age, sex, smoking, alcohol consumption, hypertension, diabetes, and family history status in relation to RCC risk were assessed., Results: No significant disparities in the distribution of MMP-8 rs11225395, rs34009635, and rs35866072 genotypes were observed between the RCC case and control cohorts (p>0.05). Individuals with CT and TT genotypes at MMP-8 rs11225395 exhibited 0.86- and 0.80-fold RCC risks, respectively (OR=0.57-1.31 and 0.42-1.55, p=0.5585 and 0.6228, respectively). Intriguingly, hypertensive individuals carrying the MMP-8 rs11225395 CT or TT genotype demonstrated an elevated risk for RCC compared to those with wild-type CC genotype (p=0.0440). No interactions of MMP-8 genotypes with age, sex, smoking, alcohol consumption, or diabetes status were evident (all p>0.05). No significant association was discerned for MMP-8 rs34009635 or rs35866072 genotypes., Conclusion: MMP-8 genotypes appear to have a modest influence on individual susceptibility to RCC. Hypertensive patients with the CT or TT MMP-8 rs11225395 genotype may have an elevated risk of RCC., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Elevated Renal cell carcinoma (RCC) risk has been associated with the use of several antihypertensive medications but has not yet been elucidated in the populations prescribed alpha-1 blockers that are commonly used in the treatment of hypertension and lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS-BPH). The aim of the present study was to investigate the association between alpha-1 blocker use and the risk of developing RCC using a nationwide population-based database in Taiwan. Patients who were treated with alpha-1 blockers for at least 28 days were identified through the Taiwan National Health Insurance Research Database from 2000 to 2010. The unexposed participants were matched with the exposed cases according to age, sex, and index year at a ratio of 3:1. Cox proportional hazards regression, stratified by sex and comorbidities and adjusted for age, was performed to estimate hazard ratios (HRs) for the risk of subsequent RCC. Among 2,232,092 subjects, patients who received alpha-1 blocker treatment had a higher risk of RCC than the unexposed group. Taking into account hypertension and BPH, the adjusted HR was significantly higher in male alpha-1 blocker users who had no BPH and either the presence (HR: 1.63, 95% confidence interval [CI] = 1.22–2.18) or absence (HR: 2.31, 95% CI = 1.40–3.81) of hypertension than in men not receiving these drugs. Taken together, male alpha-1 blocker users who had no comorbidity of BPH exhibited an increased risk for developing RCC independent of hypertension. Further study is warranted to elucidate the underlying mechanisms of this association. [ABSTRACT FROM AUTHOR]

Background: Since 2012, several immune checkpoint inhibitors have been approved by the Taiwan FDA for various types of cancer treatment. However, none of them are covered by Taiwan National Health Insurance due to the fact that they are expensive, and there is a lack of clinical evidence as to their effectiveness. Objectives: This study was aimed toward an exploration of clinical experiences with use of immune checkpoint inhibitors, including indications, prescription types, drug effectiveness, adverse drug event types, and incidence, all of which shall serve as references for future clinical drug use. Methods: This is a retrospective study focusing on three immune checkpoint inhibitors (ipilimumab, nivolumab, and pembrolizumab), which are available for cancer treatment in Taiwan. We collected data from medical records for the period from January 1st, 2015 to January 12th, 2017 at National Cheng Kung University Hospital (NCKUH), a medical center in southern Taiwan, and recorded these cases until May 31st, 2017. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method, and adverse drug reaction odds ratios were analyzed using a chi-square analysis. Results: The 50 patients under consideration in this study had used any one of the immune checkpoint inhibitors in NCKUH. Non-small cell lung cancer (n = 24, 48%) accounted for the highest percentage, followed by hepatocellular carcinoma (n = 4, 8%). The median OS was not reached, and the PFS for all immunotherapies was 4.9 months. The median OS period and PFS for non-small cell lung cancer (NSCLC) patients were 13 and 4.9 months, respectively, which were similar to those in many clinical trials. For NSCLC patients, the OS and PFS were only 0.63 and 1.37 months for squamous cell type NSCLC, and for patients who were PD-L1 negative, the OS and PFS were only 11.53 and 2.6 months, respectively. The most common adverse events in this study included fatigue (42%), rashes (22%), nausea (20%), and fever (20%), while one patient developed severe deep venous thrombosis and tissue inflammation, which was not confirmed in previous clinical trials. Conclusions: The histological subtype, the intensity of the PD-L1 expression, and the timing of treatment affected the NSCLC therapeutic results. It is recommended that clinical tests be conducted in order to enhance therapeutic effectiveness. It is expected that more testing, observation-based studies, and research results will validate their efficacy and the tolerance levels of patients. [ABSTRACT FROM AUTHOR]

Background/purpose: To compare the clinical outcomes of Taiwanese patients with ovarian clear cell carcinomas (CCCs) and serous carcinomas (SCs).Methods: We retrieved the clinical records of women with epithelial ovarian cancer (Stage I-IV) who received primary surgeries between 2000 and 2013. Cancer-specific survival (CSS), progression-free survival, and survival after recurrence (SAR) of CCC and SC patients were retrospectively compared. Multivariate analysis was used to identify the independent predictors of survival.Results: Of 891 women diagnosed with epithelial ovarian cancer, 169 CCCs and 351 high-grade SCs were analyzed. The 5-year CSS rates of CCC patients were significantly lower than those of SC for both Stage III (22.3% vs. 47.3%, p = 0.001) and Stage IV (0% vs. 24.4%, p = 0.001) disease. In the absence of gross residual malignancies, the 5-year CSS rate was better for CCC (82.3%) than SC (75.2%, p = 0.010). The 5-year SAR rate was significantly lower for CCC than SC (14.3% vs. 24.4%, p = 0.002). Old age and residual malignancies were independent prognostic factors for CSS in the entire cohort of CCC patients. In the subgroup of Stage I CCC, positive cytology was identified as the only adverse prognostic factor for CSS.Conclusion: The clinical outcomes of CCC are generally poorer than SC. Complete cytoreduction to no gross residual disease should be ideally achieved in CCC patients. A greater understanding of the molecular pathogenesis of CCC may lead to tailored therapies, ultimately optimizing outcomes. [ABSTRACT FROM AUTHOR]

Antcin-H, a natural triterpene, is purified from a famous anticancer medicinal mushroom, Antrodia cinnamomea, in Taiwan. This study showed that antcin-H inhibited the growth of human renal carcinoma 786-0 cells; the IC50 value (for 48 h) was 170 μM. Besides, the migration and invasion of 786-0 cells were suppressed by antcin-H under noncytotoxic concentrations (<100 μM); these events were accompanied by inhibition of FAK and Src kinase activities, decrease of paxillin phosphorylation, impairment of lamellipodium formation, and upregulation of TIMPs and downregulation of MMPs, especially MMP-7 expression. Luciferase reporter assay showed that antcin-H repressed the MMP-7 promoter activity, in parallel to inhibiting c-Fos/AP-1 and C/EBP-β transactivation abilities. Moreover, antcin-H suppressed the activity of ERK1/2 and decreased the binding ability of C/EBP-β and c-Fos on the upstream/enhancer region of MMP-7 promoter. Overall, this study demonstrated that the anti-invasive effect of antcin-H in human renal carcinoma 786-0 cells might be at least in part by abrogating focal adhesion complex and lamellipodium formation through inhibiting the Src/FAK-paxillin signaling pathways and decreasing MMP-7 expression through suppressing the ERK1/2-AP-1/c-Fos and C/EBP-β signaling axis. Our findings provide the evidence that antcin-H may be an active component existing in A. cinnamomea with anticancer effect. [ABSTRACT FROM AUTHOR]

Background: The association of renal cancer with viral hepatitis infection remains unclear. Using an insurance data set, this population-based case-control study evaluated the association of renal cancer with chronic hepatitis virus infection in an endemic area of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection.Methods: We enrolled 17,747 patients with renal cancer during the period from 2000 to 2011 from the National Health Insurance Research Database of Taiwan. The control group comprised 35,494 randomly selected people without renal cancer matched by age and gender to the patients in the study group. ORs were calculated to assess the association of chronic hepatitis virus infection with renal cancer by using logistic regression analysis.Results: Renal cancer was associated with HBV and HCV infection (OR 1.38, 95% CI 1.24-1.54; OR 1.24, 95% CI 1.07-1.44, respectively). An analysis stratified by gender and age revealed that young male HBV carriers had a higher risk of renal cancer compared with men without viral hepatitis (age <55 years: OR 1.94, 95% CI 1.57-2.39; 55≤ age <64 years: OR 1.40, 95% CI 1.05-1.86). Male HCV-infected patients aged <55 years (OR 1.90, 95% CI 1.11-3.26) and female HCV carriers aged between 55 and 64 years (OR 1.59, 95% CI 1.00-2.53) had a significantly higher risk of renal cancer compared with their counterparts.Conclusions: Renal cancer is significantly associated with chronic hepatitis infection, particularly in younger HBV-infected men. [ABSTRACT FROM AUTHOR]

Background/aim: To survey the safety and efficacy of percutaneous cryoablation for renal tumors under local anesthesia and pain control by using the -40°C lethal isotherm of the ice ball to cover the tumor margin as well as the coaxial cryoablation technique., Patients and Methods: All procedures were performed between February 2014 and November 2021 with computed tomography (CT) guidance. All tumors were ablated by following the aforementioned plan, according to which tumor margins were covered by the -40°C lethal isotherm. Hydrodissection and coaxial cryoablation were performed in some cases to avoid organ injury and massive bleeding. 2% xylocaine was used for local anesthesia and 50 mg of pethidine (meperidine) was injected intramuscularly for pain control and sedation. The complications were evaluated and the Kaplan-Meier method was used to estimate local recurrence-free survival (LRFS)., Results: Sixty-five tumors [49 renal cell carcinomas (RCC) and 16 angiomyolipomas] were ablated in 55 patients (median Charlson Comorbidity Index=5.0). Local recurrence occurred in three of the 49 RCC cases. Two received a second cryoablation. LRFS at three and five years were both 91%. LRFS at three and five years reached 100% in tumors <3 cm. A large tumor (≥3 cm) was observed in the recurrence group. Hemorrhage was the most common complication (76.9%). Two patients who needed blood transfusion did not receive coaxial cryoablation. Three (4.6%) major complications (Clavien-Dindo grade ≥3) occurred., Conclusion: By using -40°C as the pre-plan tumor coverage, with the aid of coaxial cryoablation and multiplanar reconstruction method, CT-guided percutaneous renal cryoablation under local anesthesia is a safe and effective procedure in patients with many comorbidities., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Abstract: Background: Xp11.2 translocation renal cell carcinoma (RCC), a recently recognized distinct subtype of RCC, is characterized by various translocations, all involving the TFE3 transcription factor gene. These rare cancers occur predominantly in children and young adults and comprise about one-third of pediatric RCCs. In the present study, we review the clinical course of Xp11.2 translocation renal cell carcinoma in our institution. Methods: We identified eight cases with Xp11.2 translocation RCC between 2007 and 2010 from the pathological archives of the Taipei Veterans General Hospital. We retrospectively analyzed the patients’ characteristics, clinical manifestations, and specific pathological features for definitive diagnosis, surgical and systemic treatment and clinical outcome of these rare cancers. Results: Patients were aged 20 years to 49 years (mean age 28 years) with female predominance (6 females, 2 males). One patient presented with asymptomatic renal mass detected incidentally during abdominal sonography. Four patients complained of flank or abdominal pain, and the other three complained of gross hematuria at initial presentation. The mean tumor size was 9.2cm (range, 4cm–17cm). Seven patients underwent radical nephrectomy for the primary tumor, while one presented with multiple metastases. All cases were confirmed by TFE3 immunohistochemistry, a sensitive and specific marker of tumors with TFE3 gene fusion, which showed positive nuclear staining. Three patients presented initially with metastatic diseases, and another three patients progressed to lung, liver and bone metastases at eight, seven and nine months postoperatively. Conclusion: Although RT-PCR and DNA sequencing are the final diagnoses of the molecular identity of Xp11.2 translocation RCC, experienced pathologists could confirm the histologic diagnosis based on the distinctive morphologic features with positive TFE3 immunochemical nuclear stain. Surgical resection is the only treatment. The role of systemic therapy for local recurrence and metastasis remains to be determined. [Copyright &y& Elsevier]

Background: The von Hippel-Lindau (VHL) tumor suppressor gene located on chromosome 3p25-26 is implicated in VHL disease. Two informative single nucleotide polymorphisms are at positions 19 and 1149 on the nucleotide sequence from Gene Bank NM_000551. In this study we examined the allele frequencies at these two loci in the Taiwanese population and compared the results to those from European ethnic populations.Methods: The allele frequency was examined in 616 healthy individuals including 301 university students and 315 neonates. Both A/G polymorphisms were investigated using restriction fragment length polymorphism analysis created by restriction enzymes, BsaJ I and Acc I.Results: Among these subjects, the allele frequencies at 19 SNP and 1149 SNP for variant G were 0.130 and 0.133, respectively. And these results were significant differences from those of the Caucasian populations. In addition, 90% of the tested subjects had identical genotypes at these two loci suggesting the existence of nonrandom association of alleles.Conclusion: We found that the G allele frequency at these two loci in the Taiwanese population is much lower than that in people from Western countries. This phenomenon may be attributed to ethnic effects. [ABSTRACT FROM AUTHOR]

Background: Renal oncocytoma has been reported mostly in the Western literature, and only a few cases have been reported in Eastern populations. In the present study, we review the clinical course of renal oncocytoma in our institution. Methods: We obtained the files of 13 cases of renal oncocytoma between 1988 and 2006 from the pathological archives of Taipei Veterans General Hospital. We retrospectively analyzed the patients’ characteristics, clinical manifestations, surgical technique and clinical outcome. Results: The study population comprised 10 men and 3 women, and the mean age at diagnosis was 59.6 years (range, 37–75 years). Twelve patients (92%) were asymptomatic at presentation and were incidentally diagnosed to have renal tumor by sonography (9 patients), computed tomography (1 patient) or magnetic resonance imaging (2 patients), and 1 presented with hematuria. The clinical impression of oncocytoma was made preoperatively in only 3 patients by imaging studies, and most of the patients (76.9%) were diagnosed with renal cell carcinoma before surgery. Ten were treated with radical nephrectomy, 2 with partial nephrectomy, and 1 received excisional biopsy. All patients had unilateral solitary renal tumor; the right kidney was involved in 7 cases (54%) and the left in 6 (46%). Mean tumor size was 5.3 cm (range, 2.7–8.5 cm). Three patients were lost to follow-up in our series, and there was no recurrence or death (100% disease-specific survival) in the remaining 10 patients (77%) who were followed-up for a mean duration of 53.2 months (range, 10–117 months). Conclusion: Renal oncocytoma has a benign clinical course with excellent long-term outcomes. Currently, nephron-sparing surgery is the mainstay of treatment, especially in patients with small tumors. However, accurate preoperative diagnosis based only on imaging studies is difficult, and radical nephrectomy was performed for most of the patients in our series. [J Chin Med Assoc 2008;71(5):254–258] [Copyright &y& Elsevier]

Introduction: Although many studies have reported that upper urinary tract stones in patients with nonfunctioning kidneys are associated with malignancy, the incidence and frequency of the tumor cell type remain unclear. Therefore, we aimed to investigate the percentage of malignancies present in patients with nonfunctional kidneys who underwent nephrectomy. Materials and Methods: From July 1995 to December 2005, we reviewed a total of 47 patients who underwent nephrectomy to treat a nonfunctional kidney due to urolithiasis with clinical symptoms such as complicated chronic infection. Pathology revealed malignancies in 24 patients. Relationships between clinical presentations and malignancy were analyzed. Results: Malignancy was diagnosed in 24 patients after nephrectomy. Image studies revealed possible malignancy in only 7 patients before surgery. A high incidence (17/24) of transitional cell carcinoma was noted. The remaining malignancies included 5 renal cell carcinomas, 1 squamous cell carcinoma and 1 epidermoid carcinoma. There were 5 deaths during the follow-up interval. Conclusions: There is a high incidence of malignancy associated with nonfunctional kidney caused by stone disease. We suggest careful examination of the pathological specimens from nephrectomy for nonfunctional kidney regardless of clinical manifestations. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Partial nephrectomy has been considered an effective and efficient method in the treatment of localized renal cell carcinoma. Herein, we retrospectively review our experience with partial nephrectomy in the treatment of localized renal cell carcinoma and compared it with patients who received radical nephrectomy. Methods: From 1982 to 2005, 35 patients who received partial nephrectomy for localized renal cell carcinoma were enrolled in this study. Ten patients were female (28.6%). The median age was 70 years (range, 42–82 years). Sixteen (45.7%) patients had pathologic T1a tumors; 17 (48.6%) patients had pathologic T1b tumors and 2 (5.7%) patients had pathologic T2 tumor (7 cm). In the meantime, 128 patients who had T1N0M0 renal cell carcinoma and who received radical nephrectomy were assigned to a control group. Thirty-nine patients (30.5%) were female in this group. The median age was 62 years (range, 30–83 years). The tumor characteristics, location, surgical techniques and patient survival were subsequently compared. Results: The median tumor size in the partial nephrectomy group was 3.9 cm (range, 1.5–7.0 cm), and it was 4.5 cm (range, 1–6.5 cm) in radical nephrectomy group. The tumor size was smaller in the partial nephrectomy group (p = 0.003). The median follow-up period was 4.38 years (range, 0.05–17.99 years) in the partial nephrectomy group and 5.66 years (range, 0.01–22.25 years) in the radical nephrectomy group. There was no local recurrence or distant metastasis in the partial nephrectomy group. The 5-year overall survival was 85.0% compared with 91.4% in the radical nephrectomy group (p = 0.126). The 5-year disease-specific survival in the partial nephrectomy group was 100%. The postoperative serum creatinine level increased to > 2.0 mg/dL in 5 (14.3%) patients in the partial nephrectomy group, but no patient needed hemodialysis during follow-up. Conclusion: From our review, partial nephrectomy is safe and provides excellent disease control in the treatment of localized renal cell carcinoma in selected patients. Renal function preservation was observed in the partial nephrectomy group, while the operated kidney showed functioning in the follow-up nuclear medicine survey. [Copyright &y& Elsevier]

Background . Renal oncocytoma has been repeatedly reported in Western countries, but only a few cases have been reported in Eastern countries. This study aims to review the clinical course of renal oncocytoma in an Eastern country such as Taiwan. Materials and Methods . Sixteen cases of renal oncocytoma seen between 1987 and 2002 at Chang Gung Memorial Hospital, Taipei, Taiwan, were studied. Results . Preoperatively, all patients were diagnosed to have renal cell carcinoma, following various radiologic studies. Perioperatively, frozen sections of three patients indicated renal oncocytoma in two and renal cell carcinoma in one. Renal oncocytoma has marked similarities to renal cell carcinoma, according to various radiologic, cytologic, and pathological investigations, so an accurate diagnosis is difficult to achieve, either preoperatively or perioperatively. Therefore, rather than being treated with partial nephrectomy, all patients were treated aggressively with unilateral radical nephrectomy. Postoperatively, all 16 patients were followed up, from 12 to 189 months, with a mean of 58.7 months. Notably, all patients survived with no evidence of tumor recurrence. Conclusions . The experience in Taiwan is generally that renal oncocytoma behaves benignly, as reported in other areas. The excellent prognosis associated with this tumor appears to indicate that partial nephrectomy may suffice for removing the tumor, while sparing other unaffected renal parenchyma. [ABSTRACT FROM AUTHOR]

High total urinary arsenic concentrations and low estimated glomerular filtration rate (eGFR) increase the risk of renal cell carcinoma (RCC). This study aimed to determine whether other metals or metalloids can affect RCC. A total of 401 patients with RCC and 774 age- and sex-matched controls were recruited between November 2006 and December 2012 in Taiwan. Surgical resection or image-guided biopsy of renal tumors was performed to pathologically verify RCC. High-performance liquid chromatography linked to a hydride generator and atomic absorption spectrometer were used to measure the urinary arsenic species concentrations. Inductively coupled plasma mass spectrometry was used to determine plasma selenium and red blood cell cadmium and lead concentration. Plasma selenium levels were inversely related to RCC, whereas red blood cell cadmium levels were directly related to RCC. The odds ratio (OR) and 95% confidence interval (CI) were 0.14 (95% CI, 0.10-0.20) and 1.33 (95% CI, 1.03-1.72), respectively. A low plasma selenium level tended to interact with high total urinary arsenic levels or with high red blood cell cadmium concentration to increase the OR of RCC. In particular, low eGFR multiplicatively interacted with high red blood cell cadmium concentration to increase the OR of RCC (P interaction =0.003). This study was the first to find a significant multiplicative interaction between eGFR and the red blood cell cadmium levels on the increased OR of RCC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

The DNA repair capacity plays a critical role in maintaining the genomic stability and gatekeeping for individual cancer risk. In this study, we aim at evaluation the role of the Asp 148 Glu (rs1130409) variant at apurinic/apyrimidinic endonuclease (APE) gene in renal cell carcinoma (RCC) risk and the contribution of different genotypes to its transcriptional mRNA levels. In the case-control study, 92 RCC patients and 580 cancer-free patients matched by age and gender were recruited. The apurinic/APE genotyping work was conducted with typical restriction fragment length polymorphism methodology after polymerase chain reaction. At the meanwhile, thirty renal tissue samples with variant genotypes were examined for their apurinic/APE mRNA and protein expressions by real-time quantitative reverse transcription method and Western blotting. The results showed that compared with the wild-type TT genotype, the people with TG and GG genotypes of apurinic/APE Asp 148 Glu had 0.88- and 1.09-fold risk of RCC, respectively. We have also examined the in vivo transcriptional (RNA) and translational (protein) levels with renal tissues of various apurinic/APE Asp 148 Glu genotypes, revealing that the apurinic/APE mRNA and protein were of similar levels among people of TT, TG, or GG genotypes. There was no joint gene-environment effect of apurinic/APE Asp 148 Glu genotype and smoking habit on RCC risk. The evidence indicated that apurinic/APE Asp 148 Glu genotypic variants did not alter its mRNA and protein expression among RCC patients. The genotype of apurinic/APE Asp 148 Glu may not serve as a proper predictive marker for RCC risk in Taiwan., Competing Interests: None

Interleukin-18 (IL-18) is a multi-functional immuno-mediator in the development and progression of many types of infectious and inflammatory diseases. In this study, we evaluated the contribution of IL-18 genotypes to renal cell carcinoma (RCC) in Taiwan via the genotyping of IL-18 -656 (A/C), -607 (A/C), and -137 (G/C). Moreover, we analyzed their interactions with smoking, alcohol drinking, hypertension, and diabetes status. The results showed an association of the AC and CC genotypes of IL-18 −607 with a significant decrease in the risk of RCC compared with the AA genotype (odds ratio (OR) = 0.44 and 0.35, 95% confidence interval (CI) = 0.27–0.72 and 0.18–0.66, p = 0.0008 and 0.0010, respectively). Furthermore, a significantly lower frequency of the C allele at -607 was observed in the RCC group (35.3% vs. 49.8%; OR = 0.53; 95% CI = 0.35–0.71, p = 0.0003). However, IL-18 -656 and -137 did not exhibit a likewise differential distribution of these genotypes between the control and case groups. Stratifying the population according to smoking, alcohol drinking, hypertension, and diabetes status revealed a different distribution of IL-18 -607 genotypes among non-smokers, non-drinkers, and patients without diabetes, but not among smokers, drinkers, or patients with diabetes. These findings suggest that IL-18 -607 genotypes may play a role in the etiology and progression of RCC in Taiwan and may serve as a useful biomarker for early detection. [ABSTRACT FROM AUTHOR]

Background: The molecular mechanism underlying clear cell renal cell carcinoma (ccRCC) metastasis remains unclear. We therefore aimed to elucidate the role of IMPA2 in ccRCC metastatic progression., Methods: Using the Cancer Genome Atlas (TCGA) database and immunohistochemistry (IHC) staining, we investigated differences in IMPA2 mRNA and protein expression, as well as their clinical relevance, in ccRCC. To investigate the function of IMPA2 in ccRCC metastasis, we performed in vitro migration and in vivo lung colony-forming assays. We further explored the effect of microRNA (miR)-25 on IMPA2 expression by performing a luciferase reporter assay., Findings: We show that ccRCC expresses relatively lower transcript levels of IMPA2 than normal kidney tissue. IMPA2 downregulation was greater in high-grade ccRCC than in low-grade ccRCC and was correlated with a poor prognosis in ccRCC patients. Importantly, we demonstrate that IMPA2 expression is inversely associated with the metastatic potential of ccRCC cells. We found that IMPA2 knockdown promotes, but overexpression suppresses, the cellular migration and lung colony-forming abilities of ccRCC cells. By using in silico and luciferase reporter assays, we found that IMPA2 expression is primarily influenced by miR-25 in ccRCC cells. Significantly, the inhibition of miR-25 function restored IMPA2 expression, thereby diminishing the metastatic potential of ccRCC cells., Interpretation: We conclude that miR-25-mediated IMPA2 downregulation constitutes a novel signature for cancer metastasis and poor outcomes in ccRCC. We further postulate that the therapeutic targeting of miR-25 can be useful for preventing the metastatic progression of ccRCC associated with IMPA2 downregulation. FUND: This study was supported by the Ministry of Science and Technology, Taiwan (MOST 107-2314-B-038-094, MOST 106-2314-B-038-069-MY3, MOST 105-2320-B-038-021-MY3 and MOST 107-2320-B-038-056)., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Our recent study found that high urinary total arsenic levels were associated with renal cell carcinoma (RCC). Recent studies demonstrated that low circulating adiponectin was related to RCC. The aim of the present study was to explore the relationship between adiponectin gene (ADIPOQ) polymorphisms and RCC and investigate whether individuals with an ADIPOQ risk genotype, obesity, and high urinary total arsenic levels have a modified odds ratio (OR) of RCC. A total of 389 RCC patients and 389 age- and sex-matched controls were recruited between November 2006 and December 2012 in Taiwan. Image-guided biopsy or surgical resection of renal tumors was performed to pathologically verify RCC. Genomic DNA was used to examine the genotypes of the ADIPOQ rs182052, ADIPOQ rs2241766, ADIPOQ rs1501299, and ADIPOQ rs1063539 SNPs by PCR-RFLP. HPLC-HG-AAS was used to measure the concentrations of urinary arsenic species. Participants with the ADIPOQ rs182052 G/A+A/A genotype had a significantly higher OR of RCC compared with those with the ADIPOQ rs182052 G/G genotype. The OR (95% confidence interval [CI]) was 1.70 (1.23-2.36). The OR of RCC for the combined effect of high urinary total arsenic levels and obesity, which was dose-dependent, in individuals with the ADIPOQ rs182052 G/A+A/A genotype was 9.33 (3.85-22.62). The present study found significant combined effects of obesity and the ADIPOQ rs182052 G/A+A/A genotype on the arsenic-related risk of RCC in a population with low arsenic exposure. Arsenic exposure, obesity, and the ADIPOQ rs182052 polymorphism could be predictors of a higher OR of RCC., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Our previous study showed that high urinary total arsenic levels were associated with higher odds ratio (OR) for renal cell carcinoma (RCC). Single nucleotide polymorphisms (SNPs) of DNA methyltransferases (DNMTs) might influence DNMT enzyme activity associated with tumorigenesis. In this study, we investigated the association of five SNPs from DNMT1 (rs8101626 and rs2228611), DNMT3A (rs34048824 and rs1550117), and DNMT3B (rs1569686) with the risk of clear cell renal cell carcinoma (ccRCC). We also examined the combined effects of DNMT genotypes and urinary arsenic levels on ccRCC risk. We conducted a hospital-based case-control study, which included 293 subjects with ccRCC and 293 age- and gender-matched controls. The urinary arsenic species were determined by a high performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Genotypes were investigated using polymerase chain reaction and restriction fragment length polymorphism analyses. We observed that the DNMT1 rs8101626 G/G genotype was significantly associated with reduced odds ratio (OR) of ccRCC [OR=0.38, 95% confidence interval (CI) 0.14-0.99]. Subjects with concurrent DNMT1 rs8101626 A/A+A/G and DNMT3A rs34048824 T/T+T/C genotypes had significantly higher OR for ccRCC [OR=2.88, 95% CI 1.44-5.77]. Participants with the high-risk genotype of DNMT1 rs8101626 and DNMT3A rs34048824 with concurrently high urinary total arsenic levels had even higher OR of ccRCC in a dose-response manner. This is the first study to evaluate variant DNMT1 rs8101626 and DNMT3A rs34048824 genotypes that modify the arsenic-related ccRCC risk in a geographic area without significant arsenic exposure in Taiwan., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: We assessed the value of TNM staging for predicting outcome of renal cell carcinoma (RCC) in Taiwan. Methods: To analyze 298 RCC patients who were surgically treated at this hospital between 1998 and 2003, tumor staging was performed according to the 2002 American Joint Committee on Cancer (AJCC) TNM classification. The Fuhrman grading system was used for nuclear grading of tumors. The 5-year cancer-specific survival data were analyzed by Kaplan-Meier statistical analysis. Prognostic factors were calculated with Log Rank test and Cox proportional hazards regression method. Results: The mean follow-up period of these patients was 40.6 months. The 5-year cancer-specific survival rates were 85.6%, 69.2%, 50.0% and 26.0% in T1, T2, T3 and T4, respectively. The survival rates were 87.2%, 73.6%, 47.5% and 40.5% in TNM stages 1, II, III and IV, respectively. In tumor grades 1-4, the survival rates were 77.1%, 77.5%, 48.9% and 28.6%, respectively. The survival rates for patients with and without tumor necrosis were 68.3% and 74.6%, respectively. The survival rate was 72.5% for patients with clear cell type, 69.9% for papillary type, 85.9% for chromophobe type and 67.7% for sarcomatoid type. Univariate analysis revealed that tumor grade, TNM stage and tumor stage were statistically significant prognostic factors. Multivariate analysis showed that TNM stage was the most important predictive factor in patient survival. Conclusions: In this population-based study, TNM stage provides the most important prognostic factor of RCC in the population of Taiwan. [ABSTRACT FROM AUTHOR]