MAOB expression correlates with a favourable prognosis in prostate cancer, and its genetic variants are associated with the metastasis of the disease.

Monoamine oxidase B (MAOB), a neurotransmitter-degrading enzyme, was reported to reveal conflicting roles in various cancers. However, the functional role of MAOB and impacts of its genetic variants on prostate cancer (PCa) is unknown. Herein, we genotyped four loci of MAOB single-nucleotide polymorphisms (SNPs), including rs1799836 (A/G), rs3027452 (G/A), rs6651806 (A/C) and rs6324 (G/A) in 702 PCa Taiwanese patients. We discovered that PCa patients carrying the MAOB rs6324 A-allele exhibited an increased risk of having a high initial prostate-specific antigen (iPSA) level (>10 ng/mL). Additionally, patients with the rs3027452 A-allele had a higher risk of developing distal metastasis, particularly in the subpopulation with high iPSA levels. In a subpopulation without postoperative biochemical recurrence, patients carrying the rs1799836 G-allele had a higher risk of developing lymph node metastasis and recurrence compared to those carrying the A-allele. Furthermore, genotype screening in PCa cell lines revealed that cells carrying the rs1799836 G-allele expressed lower MAOB levels than those carrying the A-allele. Functionally, overexpression and knockdown of MAOB in PCa cells respectively suppressed and enhanced cell motility and proliferation. In clinical observations, correlations of lower MAOB expression levels with higher Gleason scores, advanced clinical T stages, tumour metastasis, and poorer prognosis in PCa patients were noted. Our findings suggest that MAOB may act as a suppressor of PCa progression, and the rs3027452 and rs1799836 genetic variants of MAOB are linked to PCa metastasis within the Taiwanese population.

Outcome benefits of upfront cytoreductive nephrectomy for patients with metastatic renal cell carcinoma: An analysis of the TriNetX database.

BACKGROUND: The role of upfront cytoreductive nephrectomy remains debatable in the present era of tyrosine kinase inhibitors and immune checkpoint inhibitors. Here, we aimed to evaluate the outcomes of metastatic renal cell carcinoma patients treated with upfront CN and modern systemic therapies. METHODS: Using the TriNetX network database, we identified patients, in the period from 2008 to 2022, who were diagnosed with metastatic renal cell carcinoma, receiving first-line systemic therapies with tyrosine kinase inhibitors or immune checkpoint inhibitors. Their overall survivals were evaluated using the Kaplan-Meier method as well as multivariable regressions. RESULTS: We identified 11,094 patients with metastatic renal cell carcinoma. Of them, 2,914 (43%) patients in the tyrosine kinase inhibitor cohort (n = 6,779), and 1,884 (43.7%) in the immune checkpoint inhibitors cohort (n = 4315) underwent upfront cytoreductive nephrectomy. Those receiving upfront cytoreductive nephrectomy showed survival advantages with either tyrosine kinase inhibitor (Hazard ratio 0.722, 95% Confidence interval 0.67-0.73, p<0.001) or immune checkpoint inhibitors (Hazard ratio 65.1, 95% Confidence interval 0.59-0.71, p<0.001). In multivariable analysis, upfront cytoreductive nephrectomy was a factor for improved OS in both cohorts: tyrosine kinase inhibitors (Hazard ratio 0.623, 95% Confidence interval 0.56-0.694, p<0.001) and immune checkpoint inhibitors cohort (Hazard ratio 0.688, 95% Confidence interval 0.607-0.779, p<0.001). CONCLUSIONS: Upfront cytoreductive nephrectomy was associated with an improved overall survival for patients with metastatic renal cell carcinoma receiving either first-line tyrosine kinase inhibitors or immune checkpoint inhibitors. Our results support a clinical role of upfront cytoreductive nephrectomy in the modern era.

Nephroscope-assisted single trocar peritoneal dialysis catheter insertion improves catheter survival compared with laparoscopic technique: Ten-year experience of a single-center.

BACKGROUND: An ideal technique for peritoneal dialysis (PD) catheter insertion should provide a long-term functioning catheter until permanent renal replacement therapy becomes available. We developed a technique using the nephroscope-assisted single-trocar approach in 2011. In this study, we report the outcomes, learning curve analysis and cost-effectiveness analysisof the nephroscopic approach compared with the traditional laparoscopic approach. METHOD: Between January 2005 and December 2020, we retrospectively reviewed 511 patients who received PD catheter insertions using the laparoscopic or nephroscopic approach. We compared the baseline characteristics of the patients, surgical outcomes, and complications of the two groups. We further analyzed the nephroscopic group to determine the cost-effectiveness analysis, learning curve and the complication frequency between the learning and mastery periods of the nephroscopic approach. RESULTS: A total of 208 patients underwent laparoscopic PD catheter insertion, whereas 303 patients received nephroscopic surgery. The median catheter survival in the nephroscopic group is significantly longer (43.1 vs. 60.5 months, p = 0.019). The incidence of peritonitis (29.3% vs.20.8%, p = 0.035) and exit site infection (12.5% vs. 6.6%, p = 0.019) were significantly lower in the nephroscopic group. The cost-effectiveness analysis showed a medical expense reduction of 16000 USD annually by using the nephroscopic technique. There was no difference in the frequency of surgical complications between the learning and mastery phases when examining the learning curve analysis for the nephroscopic technique. CONCLUSIONS: Compared with the traditional laparoscopic approach, the nephroscopic technique effectively prolonged catheter survival and reduces health care cost by reducing infectious complications. The low complication rate during the learning phase of surgery makes the procedure safe for patients and surgeons.

Real world treatment sequences and outcomes for metastatic renal cell carcinoma.

OBJECTIVES: The treatment landscape for metastatic renal cell carcinoma changed a lot in the last few years. This study aimed to assess the treatment sequences and outcomes for metastatic renal cell carcinoma in a real-world setting. MATERIALS AND METHODS: We enrolled patients with metastatic renal cell carcinomawho received first-line systemic treatment with tyrosin kinase inhibitors monotherapy, ipilimumab plus nivolumab, or pembrolizumab plus axitinibbetween January2009 and May 2023 on the database of TriNetX network. Overall survival, time on treatment and time to next treatment were evaluated using Kaplan-Meiermethod. RESULTS: Totally, 4183 received tyrosine kinase inhibitor monotherapy, 1555 received ipilimumab plus nivolumab, and 559 received axitinib plus pembrolizumab. Median time on treatment was 2.5 months for the tyrosine kinase inhibitor monotherapy cohort, 5.4 months for the ipilimumab plus nivolumab cohort, and 8.3 months for the pembrolizumab plus axitinib cohort. Median time to next treatment was 16.6 months for both the tyrosine kinase inhibitor monotherapy and ipilimumab plus nivolumab cohorts, and 22.1 months for the pembrolizumab plus axitinib cohort. Median overall survival was 42.2 months for the tyrosine kinase inhibitor monotherapy cohort, 39.7monthsfor the ipilimumab plus nivolumab cohort, and not reached for the pembrolizumab plus axitinib cohort. In comparison with the tyrosine kinase inhibitor monotherapy cohort, patients in the pembrolizumab plus axitinib cohort showed survival benefit (log-rank p = 0.0168) in overall survival, but not the case in the ipilimumab plus nivolumab cohort. CONCLUSION: There was a trend toward using first-line immuno-oncology based therapy for patients with metastatic renal cell carcinoma in a real-world practice. Axitinib plus pembrolizumuab cohort had survival benefits over tyrosine kinase inhibitor and ipilimumab plus nivolumab cohorts, while patients in the ipilimumab plus nivolumab cohort had more distant metastases and comorbidities.

The impacts of MACC1 gene polymorphisms on urothelial cell carcinoma susceptibility and clinicopathologic characteristics in Taiwan.

Urothelial cell carcinoma (UCC) is a common malignancy of the urinary tract in Taiwan. Metastasis-Associated in Colon Cancer 1 (MACC1), a newly identified oncogene and regulator of the HGF/Met signaling pathway, has been shown to play a critical role in the development and progression of several types of cancer. Our study aims to investigate the impact of MACC1 gene polymorphisms on the clinicopathological features of patients with UCC. In this study, we included a total of 719 patients with UCC and 719 healthy controls. The genotyping of five MACC1 gene polymorphisms (rs1990172, rs975263, rs3095007, rs4721888, and rs3735615) was performed using real-time PCR with TaqMan assays. Our findings indicate that urothelial cancer patients with MACC1 rs3095007 A allele had a decreased risk of >T2 stage [Odds ratio (OR)=0.619, 95% CI=0.394-0.971, p=0.036] and lymph node invasion (OR=0.448, 95% CI=0.201-0.998, p=0.044). Additionally, these individuals were associated with longer relapse-free survival (p=0.007) and overall survival (p=0.028). In conclusion, our findings demonstrate that urothelial cancer patients with MACC1 (rs3095007) CA and AA genotypes have a lower risk of advanced T stage and lymph node metastasis. Additionally, these genotypes were associated with longer relapse-free survival and overall survival, highlighting the potential of these biomarkers as predictors of UCC prognosis.

Functional variants of the chitinase 3-like 1 gene are associated with clinicopathologic outcomes and progression of prostate cancer.

Chitinase 3-like 1 (CHI3L1 or YKL40) is a secreted glycoprotein highly expressed in advanced stages of several cancer types, including prostate cancer (PCa). Impacts of genetic variants of CHI3L1 on PCa development have not yet been investigated. The most common well-studied genetic variations are single-nucleotide polymorphisms (SNPs). Therefore, the objective of this study was to explore associations of CHI3L1 SNPs with both the susceptibility to PCa and its clinicopathological development. Three promoter SNPs, rs6691378 (-1371, G>A), rs10399805 (-247, G>A) and rs4950928 (-131, C>G), and one non-synonymous SNP, rs880633 (+2950, T>C), were analysed using a TaqMan allelic discrimination assay for genotyping in a cohort of 701 PCa patients and 701 healthy controls. Results indicated that there were no significant associations of PCa susceptibility with these four CHI3L1 SNPs. However, among elderly PCa patients (aged >65 years), it was observed that polymorphic variants (GA + AA) of CHI3L1 rs6691378 and 10399805 were significantly linked to reduced risks of several clinicopathological characteristics, including a high Gleason grade, advanced pathologic T stage and tumour cell invasion. Moreover, analyses of The Cancer Genome Atlas database revealed that CHI3L1 expression levels were elevated in PCa tissues compared with normal tissues. Interestingly, higher CHI3L1 expression levels were found to be associated with longer progression-free survival rates in PCa patients. Our findings indicated that levels of CHI3L1 may influence the progression of PCa, and the rs6691378 and 10399805 SNP genetic variants of CHI3L1 are linked to the clinicopathological development of PCa within a Taiwanese population.

Genetic variants of dipeptidyl peptidase IV are linked to the clinicopathologic development of prostate cancer.

CD26/dipeptidyl peptidase IV (DPP4) is a multifunctional cell-surface glycoprotein widely found in many cell types, and a soluble form is present in body fluids. There is longstanding evidence indicating a tumour-promoting or -suppressive role of DPP4 in different cancer types. However, studies focusing on the impacts of genetic variants of DPP4 on cancers are very rare. Herein, we conducted a case-control study to evaluate whether single-nucleotide polymorphisms (SNPs) of DPP4 were associated with the risk or clinicopathologic development of prostate cancer (PCa). We genotyped four loci of DPP4 SNPs, including rs7608798 (A/G), rs3788979 (C/T), rs2268889 (T/C) and rs6741949 (G/C), using a TaqMan allelic discrimination assay in 704 PCa patients and 704 healthy controls. Our results showed that PCa patients with the DPP4 rs7608798 AG+GG genotype or rs2268889 TC+CC genotype had a higher risk of developing an advanced clinical primary tumour (cT) stage (adjusted odds ratio (AOR): 1.680, 95% confidence interval (CI): 1.062-2.659, p = 0.025; AOR: 1.693, 95% CI: 1.092-2.624, p = 0.018). Additionally, in The Cancer Genome Atlas (TCGA) database, we observed that lower DPP4 expression levels were correlated with higher Gleason scores, advanced cT and pathological stages, tumour metastasis, and shorter progression-free survival rates in PCa patients. Furthermore, overexpression of DPP4 suppressed migration/invasion of metastatic PC3 PCa cells. Our findings suggest that DPP4 levels may affect the progression of PCa, and the DPP4 rs7608798 and rs2268889 SNPs are associated with the clinicopathologic development of PCa in a Taiwanese population.

WWOX Polymorphisms as Predictors of the Biochemical Recurrence of Localized Prostate Cancer after Radical Prostatectomy.

The downregulation of WW domain-containing oxidoreductase (WWOX), a tumor suppressor gene, is associated with the tumorigenesis and poor prognosis of various cancers. In this study, we investigated the associations between the polymorphisms of WWOX, clinicopathologic features of prostate cancer (PCa), and risk of postoperative biochemical recurrence (BCR). We evaluated the effects of five single-nucleotide polymorphisms (SNPs) of WWOX on the clinicopathologic features of 578 patients with PCa. The risk of postoperative BCR was 2.053-fold higher in patients carrying at least one "A" allele in WWOX rs12918952 than in those with homozygous G/G. Furthermore, patients with at least one polymorphic "T" allele in WWOX rs11545028 had an elevated (1.504-fold) risk of PCa with seminal vesicle invasion. In patients with postoperative BCR, the risks of an advanced Gleason grade and clinical metastasis were 3.317- and 5.259-fold higher in patients carrying at least one "G" allele in WWOX rs3764340 than in other patients. Our findings indicate the WWOX SNPs are significantly associated with highly aggressive pathologic features of PCa and an elevated risk of post-RP biochemical recurrence.

Prostate­specific antigen density and preoperative MRI findings as predictors of biochemical recurrence in high­risk and very high­risk prostate cancer.

Patients with high-risk prostate cancer after prostatectomy have a particularly high chance of being diagnosed with biochemical recurrence (BCR). Patients with BCR have a greater risk of disease progression and mortality. The present retrospective observational study aimed to clarify the risk factors for the BCR of prostate cancer after radical prostatectomy in patients with high-risk and very high-risk prostate cancer. Patients diagnosed with prostate cancer who received radical prostatectomy in a single center from January 2009 to June 2020 were included in the study. Data from medical records were reviewed and the patients were followed up for ≥6 years. The primary outcome was BCR within 1 year after surgery. A total of 307 patients were included, with 187 in the high-risk group and 120 in the very high-risk group as classified by the National Comprehensive Cancer Network (NCCN) guidelines. Patients in the very high-risk group had a lower BCR-free survival rate compared with those in the high-risk group, with a high risk of BCR even if their PSA levels were initially undetectable after prostatectomy, and a high risk of postoperatively detectable PSA. In patients with undetectable PSA after prostatectomy, BCR was associated with the initial PSA density, imaging stage (T3aN0M0 and T3bN0M0), and pathologic stage (any N1). Postoperatively detectable PSA was associated with pathologic stage (T3bN0M0 and any N1) In conclusion, preoperative MRI imaging stage and PSA density are predictors for short-term BCR after prostatectomy. NCCN-defined high-risk patients with a high initial PSA density, imaging stage (T3aN0M0 and T3bN0M0), and pathologic stage (any N1) had a higher risk of BCR when compared with other patients with undetectable PSA, while those with pathologic stage (T3bN0M0 or any N1) displayed a higher risk of postoperatively detectable PSA. These findings may help urologists to identify patients for whom active therapeutic protocols are necessary.

Geriatric nutritional risk index as a prognostic marker for patients with upper tract urothelial carcinoma receiving radical nephroureterectomy.

To investigate the prognostic value of the geriatric nutritional risk index (GNRI) in patients with upper tract urothelial cell carcinoma (UTUC) receiving radical nephroureterectomy (RNU). Between January 2001 and December 2015, we enrolled 488 patients with UTUC underwent RNU in Taichung Veterans General Hospital. GNRI before radical surgery was calculated based on serum albumin level and body mass index. The malnutritional status was defined as GNRI < 92.0. Using Kaplan-Meier analyses and Cox proportional hazards models to analyze the risk factors on disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS). 386 patients were categorized as normal nutritional status (GNRI ≥ 92) and 102 patients as malnutritional status (GNRI < 92). We used the receiver operating characteristic (ROC) curve for determined the association between GNRI and OS, with area under the curve (AUC) being 0.69. The 5-year survival rate of DFS, CSS and OS were 48.6%, 80.5% and 80.5% in the normal nutritional group and 28.0%, 53.2% and 40% in the malnutritional group. Using the multivariate analysis, malnutritional status was found as an independent risk factor for OS (hazard ratio [HR] = 3.94, 95% confidence interval [CI] 2.70-5.74), together with age (HR = 1.04, 95% CI 1.02-1.06), surgical margin positive (HR = 1.78, 95% CI 1.13-2.82), pathological T3 (HR = 2.54, 95% CI 1.53-4.21), pathological T4 (HR = 6.75, 95% CI 3.17-14.37) and lymphovascular invasion (HR = 1.81, 95% CI 1.16-2.81). We also found GNRI index as independent risk factor in DFS (HR = 1.90, 95% CI 1.42-2.54) and CSS (HR = 5.42, 95% CI 3.24-9.06). Preoperative malnutritional status with low GNRI is an independent marker in predicting DFS, CSS and OS in UTUC patients underwent RNU.

Complete Cycles of Radium-223 Improve Overall Survival in Patients With Metastatic Castration-resistant Prostate Cancer: A Retrospective Study.

BACKGROUND/AIM: The aim of this study was to investigate whether complete cycles of Radium-223 (Ra-223) improved survival in patients with metastatic castration resistant prostate cancer (mCRPC). PATIENTS AND METHODS: We retrospectively analyzed mCRPC patients treated with Ra-223 at Taichung Veterans General hospital. Patient and disease characteristics, laboratory results, number of bone metastases, mCRPC treatment sequence, Ra-223 treatment cycles and survival outcomes were collected. Overall survival and progression-free survival (PFS) were analyzed with Kaplan-Meier analysis. Uni- and multivariate analysis was used to identify clinical-radiologic factors that influence outcomes. RESULTS: From October 2016 to December 2020, 42 patients with mCRPC were enrolled. Twenty-three patients received <4 cycles of Ra-223 for mCRPC and 19 patients received 5-6 cycles. The median PSA progression free survival was 2.07 months in the <4 cycles group, compared to 3.93 months in the 5-6 cycles group (log rank p=0.006). The median overall survival was 3.93 months in the <4 cycles group, compared to 28.5 months in the 5-6 cycles group (log rank p<0.001). In the multivariate model, the course number of Ra-223 and pre-treatment alkaline phosphatase (ALP) levels were independent risk factors for overall survival. CONCLUSION: Patients who complete 5-6 cycles of Ra-223 had significantly better overall survival than those who didn't. Patients with a lower pre-treatment ALP were more likely to benefit from Ra-223 treatment.

Hospice Care Improves Patients' Self-Decision Making and Reduces Aggressiveness of End-of-Life Care for Advanced Cancer Patients.

The aim of the current study is to evaluate the different degrees of hospice care in improving patients' autonomy in decision-making and reducing aggressiveness of cancer care in terminal-stage cancer patients, especially in reducing polypharmacy and excessive life-sustaining treatments. This was a retrospective cross-sectional study conducted in a single medical center in Taiwan. Patients with advanced cancer who died in 2010-2019 were included and classified into three subgroups: hospice ward admission, hospice shared care, and no hospice care involvement. In total, 8719 patients were enrolled, and 2097 (24.05%) admitted to hospice ward; 2107 (24.17%) received hospice shared care, and 4515 (51.78%) had no hospice care. Those admitted to hospice ward had significantly higher rates of having completed do-not-resuscitate order (100%, p < 0.001) and signed the do-not-resuscitate order by themselves (48.83%, p < 0.001), and they had lower aggressiveness of cancer care (2.2, p < 0.001) within the 28 days before death. Hospice ward admission, hospice shared care, and age > 79 years were negatively associated with aggressiveness of cancer care. In conclusion, our study showed that patients with end-of-life hospice care related to higher patient autonomy in decision-making and less excessively aggressive cancer care; the influence of care was more overt in patients approaching death. Further clinical efforts should be made to clarify the patient and the families' satisfaction and perceptions of quality after hospice care involvement.

The prognostic impact of lymph node dissection for clinically node-negative upper urinary tract urothelial carcinoma in patients who are treated with radical nephroureterectomy.

BACKGROUND: To evaluate the prognostic impact of lymph node dissection (LND) in patients who underwent radical nephroureterectomy (RNU) with bladder cuff excision (BCE) for clinically node-negative (cN0) upper urinary tract urothelial carcinoma (UTUC). METHODS: We retrospectively enrolled 520 patients with cN0 UTUC in a single tertiary referral center from 2000 to 2015. The patients were divided into three groups: patients with and without pathologically proved lymph node metastasis (pN1-3 and pN0, respectively) and patients without LND (pNx). We analyzed associations between overall survival (OS)/ disease-free survival (DFS)/ cancer-specific survival (CSS) and clinical characteristics. RESULTS: The patients were divided into three groups (pN1-3, pN0 and pNx with 20, 303, and 197 patients, respectively). OS/DFS/CSS in the pN1-3 group were significantly worse (all p<0.001) compared with the pN0 group. However, there were no significant differences between the pNx and pN0 groups. In the multivariate analyses, CSS was only affected by age [(hazard ratio (HR) = 1.03, p = 0.008]), positive surgical margin (HR = 3.38, p<0.001) and pathological T3-4 stages (HR = 4.07, p<0.001). In the subgroup analyses for patients with LND, locally advanced disease (pT3 and pT4) had significantly more metastases [T3-4: 13.91% (16/115) vs. T0-2: 1.92% (4/208), p<0.001]. CONCLUSIONS: In the pN0 group, LND for cN0 UTUC did not show therapeutic benefits in terms of DFS, CSS, and OS. However, LND with RNU allowed optimal tumor staging, through patients still had a poor prognosis. Clinically occult LN metastases were found in 6.2% of our patients.

Significant predictors of contralateral upper tract recurrence after radical nephroureterectomy for upper tract urothelial carcinoma.

OBJECTIVES: To investigate the significant predictors of contralateral upper tract recurrence after radical nephroureterectomy for upper tract urothelial carcinoma. METHODS: Between January 2001 and December 2015, 548 patients with upper tract urothelial carcinoma who underwent radical nephroureterectomy in a single institution were included in this retrospective cohort study. Several clinicopathological characteristics and outcomes were explored. The crucial end-point was the diagnosis of contralateral upper tract recurrence after radical nephroureterectomy. RESULTS: Of the 548 patients, the median age was 68 years (range 24-93 years), and the median follow-up time after radical nephroureterectomy was 41 months (range 8-191 months). Contralateral upper tract recurrence occurred in 28 patients (5.1%). The median time period between radical nephroureterectomy and contralateral upper tract recurrence was 15.4 months (range 3.4-52.4 months). In the multivariate analysis, preoperative estimated glomerular filtration rate <30 mL/min/1.73 m2 (hazard ratio 3.08, P = 0.003) and tumor multifocality (hazard ratio 2.16, P = 0.043) were independent risk factors. CONCLUSION: Preoperative estimated glomerular filtration rate <30 and tumor multifocality are significant predictors of contralateral upper tract recurrence after radical nephroureterectomy for upper tract urothelial carcinoma.

Impact of Clinicopathological Characteristics and Tissue Inhibitor of Metalloproteinase-3 Polymorphism Rs9619311 on Biochemical Recurrence in Taiwanese Patients with Prostate Cancer.

The tissue inhibitors of metalloproteinases-3 (TIMP3) are not only endogenous regulators of matrix metalloproteinases (MMPs), but also induce apoptosis and inhibit endothelial cell migration and angiogenesis. The focus of this study was to investigate the relationship between TIMP3 genetic polymorphisms and biochemical recurrence and clinicopathological features of prostate cancer. The TIMP3 rs9619311, rs9862, and rs11547635 genetic polymorphisms were analyzed by real-time polymerase chain reaction to determine their genotypic distributions in 579 patients with prostate cancer. This study found that individuals with the TIMP3 rs9619311 TC or TC + CC genotypes have a significantly higher risk of biochemical recurrence of prostate cancer (p = 0.036 and 0.033, respectively). Moreover, in the multivariate analysis, our results showed that pathologic Gleason grade, pathologic T stage, seminal vesicle invasion, lymphovascular invasion, and TIMP3 rs9619311 were associated with increased odds of biochemical recurrence. Patients with a PSA concentration under 7 ng/mL that were found to have the TIMP3 rs9619311 genetic polymorphism were associated with Gleason total score upgrade (p = 0.012) and grade group upgrade (p = 0.023). Compared with the CC homozygous, the TIMP3 rs9862 CT + TT polymorphic variant was found to be associated with clinically advanced tumor stage (p = 0.030) and Gleason total score upgrade (p = 0.002) in prostate cancer patients. In conclusion, the results of our study demonstrated that the TIMP3 rs9619311 genetic polymorphism was significantly associated with susceptibility to biochemical recurrence of prostate cancer. TIMP3 genetic polymorphisms, especially rs9619311, can serve as key predictors of biochemical recurrence and disease prognosis of prostate cancer.

The impact of receptor of advanced glycation end-products polymorphisms on prostate cancer progression and clinicopathological characteristics.

The receptor for advanced glycation end products (RAGE) overexpression was suggested to be associated with prostate cancer development and poor prognosis. In this study, we focused on the correlations between the clinicopathological characteristics and susceptibility of prostate cancer and RAGE single-nucleotide polymorphisms (SNPs). In 579 prostate cancer patients, the RAGE SNPs rs1800625, rs1800624, rs2070600 and rs184003 in patients with or without grade group upgrade were analysed with real-time polymerase chain reaction. The results demonstrated that the prostate cancer patients who carried the RAGE SNPs rs2070600 'GA' genotypic variants were significantly associated with lower risk to develop grade group upgrade. Moreover, patients with the RAGE rs1800625 'TC + CC' genotypic variants were associated with higher risk of perineural invasion. In 343 prostate cancer patients who carried the RAGE rs1800625 'TC + CC' genotype without grade group upgrade were correlated with higher risk of biochemical recurrence and perineural invasion. In the analysis of TCGA database, significant differences of the RAGE mRNA level were found between the normal controls and prostate cancer patients (p < 0.0001), and the pathologic stage N1 and N0 patients (p = 0.0027). The prostate cancer patients with high RAGE expression were associated with lower overall survival rate (p = 0.025). In conclusion, our results have revealed that the RAGE SNPs rs2070600 and rs1800625 were associated with the grade group upgrade of prostate cancer and clinical status. The RAGE polymorphisms may provide as a pivotal predictor to evaluate prostate cancer disease progression and prognosis.

Docetaxel Rechallenge Improves Survival in Patients With Metastatic Castration-resistant Prostate Cancer: A Retrospective Study.

BACKGROUND/AIM: Docetaxel has been widely used in metastatic Castration-resistant Prostate Cancer (mCRPC) patients for decades. The purpose of the study was to evaluate the efficacy of docetaxel rechallenge in patients with mCRPC. PATIENTS AND METHODS: We retrospectively compared patients who had received either first-line docetaxel and rechallenge after Androgen Receptor-axis Targeted therapies (ARAT), to those without rechallenge docetaxel. Multivariate cox-regression analysis was used to evaluate survival. RESULTS: Out of the 204 patients with mCRPC enrolled in the study, 24 patients received docetaxel rechallenge and 180 did not. The median overall survival was 50.11 months in the rechallenge group, as compared to 26.36 months in the non-rechallenge group (p of log rank=0.044). In the multivariate model, doxetaxel rechallenge was an independent risk factor for overall survival [hazard ratio (HR)=0.59, 95% confidence interval (CI)=0.32-0.99], together with the performance status score 2 (HR=2.46, 95%CI=1.32-4.58), hormone-sensitive state duration (HR=0.99, 95%CI=0.99-0.999), liver (HR=1.90, 95%CI=1.04-3.47) and brain metastases (HR=2.23, 95%CI=1.26-5.46). The advantage of rechallenge was addressed in the androgen receptor-axis-targeted (ARAT) non-responsive patients (HR=0.36, 95%CI=0.17-0.78). Adverse events were at 29.17% with Grade 3/4 neutropenia and at 20.83% with Grade 1/2 neutropenia in the docetaxel rechallenge group. CONCLUSION: The docetaxel rechallenge improved survival in patients with mCRPC failure of first-line docetaxel and subsequent abiraterone acetate or enzalutamide. Independent predictive factors for overall survival included i) the performance status, ii) hormone-sensitive state duration, iii) liver and iv) brain metastases. Patients non-responsive to ARATs will benefit from docetaxel rechallenge with regards to overall survival.

Associations between LncRNA MALAT1 Polymorphisms and Lymph Node Metastasis in Prostate Cancer.

Current evidence elucidates that long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) could regulate genetic expression and play a crucial role in both the diagnosis and prognosis of prostate cancer. Single-nucleotide polymorphisms (SNPs) of MALAT1 could alter the oncogenesis in various cancers. However, the associations between MALAT1 SNPs and prostate cancer have barely been investigated to date. This study included 579 patients with prostate cancer who received robotic-assisted radical prostatectomy at Taichung Veterans General Hospital from 2012 to 2017. Three SNPs of MALAT1 were analyzed to identify the impacts of SNPs on the clinicopathologic features in Taiwanese prostate cancer. Our results show that patients with a polymorphic G allele at rs619586 had a significantly higher risk of being in an advanced Gleason grade group (AOR: 1.764; 95% CI: 1.011-3.077; p = 0.046). Moreover, individuals with at least one polymorphic A allele at MALAT1 rs1194338 in the PSA >10 ng/mL group were positively associated with node-positive prostate cancer. In conclusion, MALAT1 SNPs are significantly associated with the susceptibility to both advanced Gleason grade and nodal metastasis in prostate cancer. The presence of MALAT1 SNPs rs619586 and rs1194338 seems to enhance oncogenesis in prostate cancer.

Clinical Factors Associated with Asymptomatic Women Having Inconclusive Screening Mammography Results: Experiences from a Single Medical Center in Taiwan.

Screening mammography is used worldwide for the early detection of breast cancer in women experiencing no symptoms. The Breast Imaging Reporting and Database System (BI-RADS) is used to report mammographic findings. However, little is known about the clinical characteristics of Asian women with BI-RADS category 0, and we aimed to explore such characteristics in the context of Taiwan. This retrospective cross-sectional study was conducted using data from a single tertiary medical center. We examined the association of blood test data and estrogen exposure-related medical histories with BI-RADS reports from screening mammography of 4280 women between 1 January 2010 and 31 July 2019. The data of 4280 participants were evaluated, and they were categorized into BI-RADS category 0 (n = 413; 9.6%) and 1-5 (n = 3867; 90.4%) subgroups. In a multivariate analysis, breast surgery history and premenopausal status had a positive relationship with a category 0 status, with respective risk increases of 64% and 34% (p = 0.010 and 0.013). Hormone contraceptive use for ≥5 years was a negative independent predictor of having a category 0 status. In conclusion, breast surgery history and premenopausal status significantly increased the likelihood of individuals having incomplete mammographic findings, even when they were older than 45 years. Identifying related factors before screening mammography is helpful for clinical physicians to arrange more proper and alternative examination and obtain a definite diagnosis.

Association between lymphovascular invasion and oncological outcome in node-negative upper tract urothelial carcinoma with different stage.

OBJECTIVES: To evaluate the prognostic impact of lymphovascular invasion (LVI) on node-negative upper tract urothelial carcinoma (UTUC) in patients treated with radical nephroureterectomy (RNU). MATERIALS AND METHODS: A retrospective study was performed in single tertiary referral center of middle Taiwan between 2001 and 2015. Seven hundred and twenty-eight patients were diagnosed of UTUC and underwent RNU with ipsilateral bladder cuff excision including 303 and 195 patients with N0 and Nx status respectively. LVI status was assessed as a prognostic factor for cancer-specific (CSS) and overall survival (OS) using univariate and multivariate Cox regression analysis. RESULTS: LVI was observed in 82 patients (16.5%). LVI presentation associated with smoking status, advanced tumor stage, high tumor grade, positive surgical margin, and consequence lung/liver/bone metastasis. In the multivariate analysis, LVI was failed to predict CSS, OS, and disease-free survival (DFS) (hazard ratio [HR] [95% confidence interval [CI]: 1.07 [0.55-2.09], 1.05 [0.62-1.79], 1.15 [0.69-1.92], in CSS, OS, DFS, respectively). In the subgroup analysis of pT1-2 disease, the CSS, OS, and DFS were associated with LVI status (HR [95% CI]: 2.29 [0.44-11.84], 3.17 [1.16-8.67], 2.66 [1.04-6.79], in CSS, OS, DFS, respectively). In contrast, there was no difference in pT3 disease. CONCLUSION: In conclusion, LVI status was not associated with survival outcomes of node-negative UTUC in our study. The subgroup analysis showed different prognostic impacts of LVI status in node-negative UTUC with T1-2 and T3 stage. Further evidence to clarify the prognostic effect is needed to make LVI became a practical factor in clinical decision-making.