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Purpose: To investigate the effect of androgen deprivation therapy (ADT) on health-related quality of life (HRQOL) in Asian men with all stages of prostate cancer. Materials and Methods: READT (real-life evaluation of the effect of ADT in prostate cancer patients in Asia) was a multicenter, prospective observational study involving six sites across four Asian populations. We enrolled eligible prostate cancer patients, who opted for ADT alone or in combination without prior neoadjuvant or adjuvant ADT within 12 months. The EuroQoL- 5 dimensions, 5 level scale (EQ-5D-5L) utility index scores and visual analog scale (VAS) were evaluated at baseline, month 6 and month 12. Results: A total of 504 patients were recruited into READT between September 2016 and May 2020 with 52.9% diagnosed with metastatic prostate cancer. The EQ-5D-5L was evaluable in 442/504 (87.7%) of patients. Overall baseline EQ-5D-5L utility index score was 0.924 (interquartile range [IQR] 0.876–1.000). We observed a statistically significant difference in baseline EQ-5D-5L utility index score among different populations with a median EQ-5D-5L utility index score of 1 for Taiwan & Hong Kong, 0.897 for China and 0.838 for Malaysia. Similar trend was observed throughout multiple treatment timepoints. Stage IV prostate cancer were significantly associated with a lower baseline EQ-5D-5L utility index score compared to stage I–III prostate cancer, producing a median disutility value of -0.080. Participants had a high median VAS (80, IQR 70–90), indicating good overall health on average during ADT initiation. Conclusions: The study highlights the differences in health state utility index scores among various Asian prostate cancer patients receiving ADT at real-world setting. Our findings will be informative and useful in cost-effectiveness evaluation and policy decision making.

Purpose: We reviewed the clinical experience of using the ureteral tumor stent (Bard®, angiomed UROSOFT) in the National Taiwan University Hospital. We focused on the efficacy and durability of the ureteral tumor stent. Materials and Methods: We collected the patient data from April 2013 to 2014. A total of 94 patients with 157 ureteral units which received ureteral tumor stent in the National Taiwan University Hospital were enrolled. We analyzed the effectiveness according to the hydronephrosis grading. The durability was counted if it did not match any of the failure criteria including the following: 1. Hydronephrosis upgrade, 2. Serum creatinine elevated over 150% of baseline, 3. Ipsilateral percutaneous nephrostomy insertion or failure to remove it after antegrade insertion, and 4. Replacement due to clinically significant symptoms. Results: In general, 65% hydronephrosis downgrade, 25% remained stationary without severe hydronephrosis, while only 10% deteriorated or remain severe hydronephrosis. The median durability was 6.8 months. The bacteriuria and size of the ureteral tumor stent were the significant factors about the durability in single variant analysis. Conclusion: The ureteral tumor stent would improve the obstructive uropathy and persist functional for an average period over half a year.

Extracellular vesicles (EVs) are an important regulatory factor for natural killer cell activity (NKA) in the tumor microenvironment. The relationship between circulating EVs in the peripheral blood and natural killer (NK) cells in prostate cancer (PCa) is unclear. This study aimed at investigating the key regulators in the interaction between circulating EVs and NK cells in PCa patients before and after tumor removal. NK‐cell characteristics were prospectively assessed in 79 patients treated with robot‐assisted laparoscopic radical prostatectomy preoperatively and postoperatively. Compared with healthy donors, the existence of prostate tumors increased the number of circulating EVs and altered ligand expression of EVs. Circulating EVs extracted from cancer patients significantly decreased NKA of NK cells compared with those extracted from healthy donors. Upon treatment with an inhibiting antibody or small interfering RNA, natural killer cell protein group 2A (NKG2A) was identified as the main NKA regulator in cancer patients for accepting the signal from circulating EVs. After surgery, NKA was increased and NKG2A expression on NK cells was significantly reduced. The expression of ligands for natural killer cell protein group 2D (NKG2D) on EVs and the level of circulation EVs both significantly increased. With the decrease in NKG2A levels on NK cells and the increase in total NKG2D ligands on circulating EVs, which was increased postoperatively, both NKG2A on NK cells and NKG2D ligands on circulating exosomes are main regulators of NKA restoration after prostatectomy.

Background: Endoscopic management of upper tract urothelial cancer (UTUC) is an important treatment option for low risk UTUC. Although Taiwan is an endemic area for UTUC, endoscopic treatment outcomes in Taiwan are frequently under- reported. Methods: This study retrospectively reviewed the treatment outcomes of endoscopic management for clinically localized UTUC. Patients with biopsy or washing cytology confirmed UTUC who underwent endoscopic or percutaneous management with a curative intent were retrospectively reviewed for eligibility of analysis. Those cases without pre-intervention confirmed UTUC, and metastatic or nodal disease at diagnosis were excluded. Results: In total, 307 patients who underwent endoscopic management were reviewed and 279 cases were eligible for final analysis. With a median follow-up of 44.3 months (inter-quartile range (IQR): 23.4–76.4 months), 117 cases (46.4%) were endoscopic cured after median one session (range:1–8; IQR:1–2) of endoscopic treatment. Those endoscopic cured UTUC was associated with more small-sized tumor, more low-grade biopsied-histology, less concomitant bladder UC and less pre-operative hydronephrosis.In addition, 201(79.7%) cases among 252 cases with confirmed oncological outcome were free of UTUC at the end of follow-up and only 43 (17%) patients had a UTUC related mortality. Salvage RNU offered a better tumor free survival rate (92% vs. 77.5%) than those without salvage RNU in those UTUC refractory to endoscopic management. In multivariable analyses, pre-operative hydronephrosis was the independent risk factor for OS. Multiplicity and concomitant bladder UC were independent risk factors for DFS. Conclusions: We confirmed the consistent safety and efficacy of endoscopic management of clinical localized UTUC in a highly UTUC endemic area like Taiwan. Early salvage RNU is mandatory in those UTUC refractory to endoscopic management in prevention of UTUC related death.

Abstract Background In critically ill patients, measured creatinine clearance (CrCl) is the most reliable method to evaluate glomerular filtration rate in routine clinical practice and may vary subsequently on a day-to-day basis. We developed and externally validated models to predict CrCl one day ahead and compared them with a reference reflecting current clinical practice. Methods A gradient boosting method (GBM) machine-learning algorithm was used to develop the models on data from 2825 patients from the EPaNIC multicenter randomized controlled trial database. We externally validated the models on 9576 patients from the University Hospitals Leuven, included in the M@tric database. Three models were developed: a “Core” model based on demographic, admission diagnosis, and daily laboratory results; a “Core + BGA” model adding blood gas analysis results; and a “Core + BGA + Monitoring” model also including high-resolution monitoring data. Model performance was evaluated against the actual CrCl by mean absolute error (MAE) and root-mean-square error (RMSE). Results All three developed models showed smaller prediction errors than the reference. Assuming the same CrCl of the day of prediction showed 20.6 (95% CI 20.3–20.9) ml/min MAE and 40.1 (95% CI 37.9–42.3) ml/min RMSE in the external validation cohort, while the developed model having the smallest RMSE (the Core + BGA + Monitoring model) had 18.1 (95% CI 17.9–18.3) ml/min MAE and 28.9 (95% CI 28–29.7) ml/min RMSE. Conclusions Prediction models based on routinely collected clinical data in the ICU were able to accurately predict next-day CrCl. These models could be useful for hydrophilic drug dosage adjustment or stratification of patients at risk. Trial registration. Not applicable.

Abstract Purpose To investigate the survival outcomes of metastatic castration-resistant prostate cancer (mCRPC) patients receiving first-line novel androgen receptor axis-targeted therapies (ARATs) and prognostic factors for patient survival. Methods This retrospective study obtained data from 202 patients who started abiraterone acetate or enzalutamide as first-line therapy for mCRPC between 2016 and 2021 from a single academic center. The primary endpoint was overall survival (OS) defined as the interval from the start of ARAT to death, loss to follow-up, or the end of the study period. The secondary endpoints were PSA decline, PSA nadir, and time to nadir (TTN) after ARATs. Kaplan–Meier survival analyses were applied for depicting OS. Cox proportional hazards model with inversed probability of treatment weighing-adjustment was used to validate the effect of patient, disease, and treatment response factors on OS. Results Among 202 patients, 164 patients were treated with first-line ARATs alone and 38 patients received second-line chemotherapy. The median OS was not reached in patients with first-line ARATs alone and was 38.8 months in those with subsequent chemotherapy after failure from ARATs. OS was not different between the use of abiraterone and enzalutamide, though enzalutamide showed a higher rate of PSA decline ≧ 90% (56% versus 40%, p = 0.021) and longer TTN (5.5 versus 4.7 months, p = 0.019). Multivariable analysis showed that PSA nadir > 2 ng/mL [hazard ratio (HR) 7.04, p

Darolutamide, a second-generation androgen receptor inhibitor (SGARI), has been shown to increase metastasis-free survival and overall survival among men with non-metastatic castration-resistant prostate cancer (nmCRPC). Its unique chemical structure potentially provides efficacy and safety advantages over the SGARIs apalutamide and enzalutamide, which are also indicated for nmCRPC. Despite a lack of direct comparisons, the SGARIs appear to have similar efficacy, safety, and quality of life (QoL) results. Indirect evidence suggests that darolutamide is preferred for its good adverse event profile, an attribute valued by physicians, patients, and their caregivers for maintaining QoL. Darolutamide and others in its class are costly; access may be a challenge for many patients and may lead to modifications to guideline-recommended regimens.

Abstract To compare clinical outcomes between the use of robotic-assisted laparoscopic radical prostatectomy (RP) and radiotherapy (RT) with long-term androgen deprivation therapy (ADT) in locally advanced prostate cancer (PC), 315 patients with locally advanced PC (clinical T-stage 3/4) were considered for analysis retrospectively. Propensity score-matching at a 1:1 ratio was performed. The median follow-up period was 59.2 months (IQR 39.8–87.4). There were 117 (37.1%) patients in the RP group and 198 (62.9%) patients in the RT group. RT patients were older and had higher PSA at diagnosis, higher Gleason score grade group and more advanced T-stage (all p

ObjectivesTo evaluate the predictive role of pre-nephroureterectomy (NU) hydronephrosis on post-NU renal function (RF) change and preserved eligibility rate for adjuvant therapy in patients with upper tract urothelial carcinoma (UTUC).Patients and methodsThis retrospective study collected data of 1018 patients from the Taiwan UTUC Collaboration Group registry of 26 institutions. The patients were divided into two groups based on the absence or presence of pre-NU hydronephrosis. Estimated glomerular filtration rate (eGFR) was calculated pre- and post-NU respectively. The one month post-NU RF change, chronic kidney disease (CKD) progression, and the preserved eligibility rate for adjuvant therapy were compared for each CKD stage.Results404 (39.2%) patients without and 614 (60.8%) patients with pre-NU hydronephrosis were enrolled. The median post-NU change in the eGFR was significantly lower in the hydronephrosis group (-3.84 versus -12.88, p

PurposeThis study aimed to evaluate the oncological outcome of delayed surgical wait time from the diagnosis of upper tract urothelial carcinoma (UTUC) to radical nephroureterectomy (RNU).MethodsIn this multicenter retrospective study, medical records were collected between 1988 and 2021 from 18 participating Taiwanese hospitals under the Taiwan UTUC Collaboration Group. Patients were dichotomized into the early (≤90 days) and late (>90 days) surgical wait-time groups. Overall survival, disease-free survival, and bladder recurrence-free survival were calculated using the Kaplan–Meier method and multivariate Cox regression analysis. Multivariate analysis was performed using stepwise linear regression.ResultsOf the 1251 patients, 1181 (94.4%) were classifed into the early surgical wait-time group and 70 (5.6%) into the late surgical wait-time group. The median surgical wait time was 21 days, and the median follow-up was 59.5 months. Our study showed delay-time more than 90 days appeared to be associated with worse overall survival (hazard ratio [HR] 1.974, 95% confidence interval [CI] 1.166−3.343, p = 0.011), and disease-free survival (HR 1.997, 95% CI 1.137−3.507, p = 0.016). This remained as an independent prognostic factor after other confounding factors were adjusted. Age, ECOG performance status, Charlson Comorbidity Index (CCI), surgical margin, tumor location and adjuvant systemic therapy were independent prognostic factors for overall survival. Tumor location and adjuvant systemic therapy were also independent prognostic factors for disease-free survival.ConclusionsFor patients with UTUC undergoing RNU, the surgical wait time should be minimized to less than 90 days. Prolonged delay times may be associated with poor overall and disease-free survival.

PurposeTaiwan has a high incidence of upper tract urothelial carcinoma (UTUC). This study aimed to compare the surgical outcomes following transperitoneal hand-assisted laparoscopic nephroureterectomy (TP-HALNU) and transperitoneal pure laparoscopic nephroureterectomy (TP-LNU) from the Taiwan nationwide UTUC collaboration database using different parameters, including surgical volumes.Materials and methodsThe nationwide UTUC collaboration database includes 14 hospitals in Taiwan from the Taiwan Cancer Registry. We retrospectively reviewed the records of 622 patients who underwent laparoscopic nephroureterectomy between July 1988 and September 2020. In total, 322 patients who received TP-LNU or TP-HALNU were included in the final analysis. Clinical and pathological data and oncological outcomes were compared.ResultsOf the 322 patients, 181 and 141 received TP-LNU and TP-HALNU, respectively. There were no differences in clinical and histopathological data between the two groups. No differences were observed in perioperative and postoperative complications. There were no significant differences in oncological outcomes between the two surgical approaches. In the multivariate analysis, the cohort showed that age ≥70 years, positive pathological lymph node metastasis, tumors located in the upper ureter, and male sex were predictive factors associated with an increased risk of adverse oncological outcomes. A surgical volume of ≥20 cases showed a trend toward favorable outcomes on cancer-specific survival [hazard ratio (HR) 0.154, p = 0.052] and marginal benefit for overall survival (HR 0.326, p = 0.019) in the multivariate analysis.ConclusionAlthough different approaches to transperitoneal laparoscopic nephroureterectomy showed no significant differences in surgical outcomes, age, sex, lymph node metastasis, and tumor in the upper ureter in the following period were predictive factors for oncological outcomes. Higher surgical volume did not impact disease-free survival and bladder recurrence-free survival but was associated with improved overall survival and cancer-specific survival. Exploration of unknown influencing factors is warranted.

PurposeWe aimed to evaluate the impact of preoperative local symptoms on prognosis after radical nephroureterectomy in patients with upper tract urothelial carcinoma (UTUC).MethodsThis retrospective study consisted of 2,662 UTUC patients treated at 15 institutions in Taiwan from 1988 to 2019. Clinicopathological data were retrospectively collected for analysis by the Taiwan UTUC Collaboration Group. The Kaplan-Meier method was used to calculate overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and bladder recurrence-free survival (BRFS). The prognostic value of preoperative local symptoms in OS, CSS, DFS, and BRFS was investigated using Cox proportional hazards models.ResultsThe median follow-up was 36.6 months. Among 2,662 patients, 2,130 (80.0%) presented with hematuria and 398 (15.0%) had symptomatic hydronephrosis at diagnosis. Hematuria was associated with less symptomatic hydronephrosis (p

The ARC predictor is a prediction model for augmented renal clearance (ARC) on the next intensive care unit (ICU) day that showed good performance in a general ICU setting. In this study, we performed a retrospective external validation of the ARC predictor in critically ill coronavirus disease 19 (COVID-19) patients admitted to the ICU of the University Hospitals Leuven from February 2020 to January 2021. All patient-days that had serum creatinine levels available and measured creatinine clearance on the next ICU day were enrolled. The performance of the ARC predictor was evaluated using discrimination, calibration, and decision curves. A total of 120 patients (1064 patient-days) were included, and ARC was found in 57 (47.5%) patients, corresponding to 246 (23.1%) patient-days. The ARC predictor demonstrated good discrimination and calibration (AUROC of 0.86, calibration slope of 1.18, and calibration-in-the-large of 0.14) and a wide clinical-usefulness range. At the default classification threshold of 20% in the original study, the sensitivity and specificity were 72% and 81%, respectively. The ARC predictor is able to accurately predict ARC in critically ill COVID-19 patients. These results support the potential of the ARC predictor to optimize renally cleared drug dosages in this specific ICU population. Investigation of dosing regimen improvement was not included in this study and remains a challenge for future studies.

Purpose: In advanced or high-grade prostate cancer (PCa), prostate-specific antigen (PSA) is usually elevated, however, some patients may present with low initial PSA (iPSA) levels. The objective of this study was to evaluate whether different iPSA levels were associated with dissimilar clinical outcomes among men with high-grade PCa and advanced disease after robot-assisted laparoscopic radical prostatectomy (RaLRP). Methods: This study enrolled 69 PCa patients with initial Gleason score ≥8 and pathologic T-stage ≥3a from April 2012 to December 2018. Patients were stratified into 3 groups based on iPSA levels at diagnosis:

BackgroundThe advantage of adjuvant chemotherapy for upper urinary tract urothelial cancer (UTUC) has been reported, whereas its impact on upper tract cancer with variant histology remains unclear. We aimed to answer the abovementioned question with our real-world data.Design, Setting, and ParticipantsPatients who underwent radical nephroureterectomy (RNU) and were confirmed to have variant UTUC were retrospectively evaluated for eligibility of analysis. In the Taiwan UTUC Collaboration database, we identified 245 patients with variant UTUC among 3,109 patients with UTUC who underwent RNU after excluding patients with missing clinicopathological information.InterventionThose patients with variant UTUC were grouped based on their history of receiving adjuvant chemotherapy or not.Outcome Measurements and Statistical AnalysisPropensity score matching was used to reduce the treatment assignment bias. Multivariable Cox regression model was used for the analysis of overall, cancer-specific, and disease-free survival.Results and LimitationsFor the patients with variant UTUC who underwent adjuvant chemotherapy compared with those without chemotherapy, survival benefit was identified in overall survival in univariate analysis (hazard ratio (HR), 0.527; 95% confidence interval (CI), 0.285–0.973; p = 0.041). In addition, in multivariate analysis, patients with adjuvant chemotherapy demonstrated significant survival benefits in cancer-specific survival (OS; HR, 0.454; CI, 0.208–0.988; p = 0.047), and disease-free survival (DFS; HR, 0.324; 95% CI, 0.155–0.677; (p = 0.003). The main limitations of the current study were its retrospective design and limited case number.ConclusionsAdjuvant chemotherapy following RNU significantly improved cancer-related survivals in patients with UTUC with variant histology.

PurposeThis study aimed to compare the oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) without clinical lymph node metastasis (cN0) undergoing lymph node dissection (LND) during radical nephroureterectomy (NU).MethodsFrom the updated data of the Taiwan UTUC Collaboration Group, a total of 2726 UTUC patients were identified. We only include patients with ≥ pT2 stage and enrolled 658 patients. The Kaplan–Meier estimator and Cox proportional hazards model were used to analyze overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and bladder recurrence-free survival (BRFS) in LND (+) and LND (−) groups.ResultsA total of 658 patients were included and 463 patients without receiving LND and 195 patients receiving LND. From both univariate and multivariate survival analysis, there are no significant difference between LND (+) and LND (-) group in survival rate. In LND (+) group, 18.5% patients have pathological LN metastasis. After analyzing pN+ subgroup, it revealed worse CSS (p = 0.010) and DFS (p < 0.001) compared with pN0 patients.ConclusionsWe found no significant survival benefit related to LND in cN0 stage, ≥ pT2 stage UTUC, irrespective of the number of LNs removed, although pN+ affected cancer prognosis. However, from the result of pN (+) subgroup of LND (+) cohort analysis, it may be reasonable to not perform LND in patients with cT2N0 stage due to low positive predictive value of pN (+). In addition, performing LND may be considered for ureter cancer, which tends to cause lymphatic and hematogenous tumor spreading. Further large prospective studies are needed to validate our findings.

Abstract Background Hyperglycemia is associated with series of process leading to oncogenesis. Evidence has shown that diabetes mellitus (DM) seems to be associated with poor prognosis in patients with bladder cancer. However, evidence on the effect of glycemic control on the outcomes of bladder cancer is still limited. In the current study, we aimed to investigate the effect of DM and glycemic control on the prognosis of bladder cancer. Methods We conducted a retrospective chart review of a prospective database from January 2012 to December 2017. Patients with newly diagnosed non-muscle invasive bladder cancer (NMIBC) were included. They were classified into the DM and non-DM groups. Prognosis including recurrence rate, progression rate, recurrence-free survival (RFS), and progression-free survival was compared between the two groups. Subgroup analysis of the DM subgroup, in which patients were classified by HbA1C level, was conducted to investigate the effect of glycemic control. Results A total of 287 patients were included in our study, with 61 patients in the DM group and 226 patients in the non-DM group. No statistically significant difference was found in the prognosis between the DM and non-DM groups. Subgroup analysis revealed higher recurrence rate (P = 0.037) and worse RFS (log-rank P = 0.019) in patients with HbA1C ≥ 7. Conclusions DM is not a risk factor for recurrence and progression in patients with NMIBC. However, poor glycemic control is associated with poor prognosis in patients with both DM and NMIBC. Further prospective studies are needed to confirm current results.

Abstract Anoctamins were originally identified as a family of calcium‐activated chloride channels, but recently their roles in the development of different types of malignancies were suggested. Here, we evaluated the associations between 211 common single‐nucleotide polymorphisms in 10 anoctamin genes with biochemical recurrence (BCR) after radical prostatectomy (RP) for localized prostate cancer. Four SNPs (ANO4 rs585335, ANO5 rs4622263, ANO7 rs62187431, and ANO10 rs118005571) remained significantly associated with BCR after multiple test correction (P

Abstract Background The optimal adjuvant treatment for stage III endometrial cancer in the era of modern radiotherapy remains undefined. We investigated the benefit of adjuvant radiotherapy for women who underwent optimal resection for stage III endometrial cancer in the era of modern radiotherapy. Methods We retrospectively reviewed patients with endometrial cancer who were treated between 2010 and 2018. Adjuvant treatment included radiotherapy by modern radiotherapy techniques (intensity-modulated or volumetric modulated arc radiotherapy), chemotherapy, or both. Recurrence-free survival (RFS) and overall survival (OS) were calculated using the Kaplan-Meier method and analyzed via multivariate Cox proportional hazards models. Results One hundred sixty-one patients were initially included (52, 9, and 100 with stages IIIA, IIIB, and IIIC cancer, respectively); 154 patients (96%) received adjuvant therapy. Such adjuvant treatment was associated with improved RFS (p = 0.014) and OS (p = 0.044) over surgery alone. Adjuvant radiotherapy by modern radiotherapy techniques led to low incidence of acute (25%) and chronic (7%) grade ≥ 2 gastrointestinal toxicity. On univariate analysis, non-endometrioid histology and grade 3 status were associated with higher risks of tumor recurrence and death, whereas adjuvant radiotherapy alone or in combination chemotherapy reduced their risks. On multivariate analysis, non-endometrioid histology was associated with increased recurrence (hazard ratio [HR], 2.95; p = 0.009), whereas adjuvant radiotherapy alone or with chemotherapy was associated with lower recurrence (HR, 0.62; p = 0.042). Patients > 60 years of age (p = 0.038) as well as those with endometrioid histology (p = 0.045), lymphovascular space invasion (p = 0.031), and ≥ 2 positive lymph nodes (p = 0.044) benefited most from adjuvant radiotherapy. Conclusions Modern adjuvant radiotherapy (intensity-modulated or volumetric modulated arc radiotherapy) alone or with chemotherapy should be considered for women with optimally resected stage III endometrial cancer. Trial registration ClinicalTrials.gov, NCT04251676 . Registered 24 January 2020. Retrospectively registered.

Epigenetic effects of environmental pollutants may be related to carcinogenesis. This study aimed to explore the association between the global DNA methylation marker: 5-methyl-2-deoxycytidine (5mdC) and renal cell carcinoma (RCC), and further investigated whether plasma folate and vitamin B12 levels and 5mdC modified the association between blood cadmium concentrations and RCC. We recruited 174 RCC patients and 673 non-RCC controls. Blood cadmium concentrations, plasma folate and vitamin B12 levels were measured. The amount of 5mdC in the DNA sample was expressed as percentages of the total cytosine content. An increase of 5mdC (%) and plasma folate and vitamin B12 levels were associated with decreasing odds ratio (OR) of RCC. Although plasma folate levels were not directly associated with 5mdC (%), a combined effect was observed with the odds of low plasma folate levels and low 5mdC (%) were greater among RCC patients compared to controls (OR (95% confidence interval, CI) = 11.86 (5.27–26.65)). Additionally, we observed that the odds of low plasma folate and high blood cadmium levels were greater among RCC patients than in controls (OR (95% CI): 8.15 (1.39–7.13)). This study provides suggestive evidence that plasma folate levels may modify the associations between 5mdC (%) or blood cadmium concentrations and RCC.

PurposeThis study aimed to compare the oncological outcomes and surgical complications of patients with upper tract urothelial carcinoma (UTUC) treated with different minimally invasive techniques for nephroureterectomy.MethodsFrom the updated data of the Taiwan UTUC Collaboration Group, a total of 3,333 UTUC patients were identified. After excluding ineligible cases, we retrospectively included 1,340 patients from 15 institutions who received hand-assisted laparoscopic nephroureterectomy (HALNU), laparoscopic nephroureterectomy (LNU) or robotic nephroureterectomy (RNU) between 2001 and 2021. Kaplan-Meier estimator and Cox proportional hazards model were used to analyze the survival outcomes, and binary logistic regression model was selected to compare the risks of postoperative complications of different surgical approaches.ResultsAmong the enrolled patients, 741, 458 and 141 patients received HALNU, LNU and RNU, respectively. Compared with RNU (41.1%) and LNU (32.5%), the rate of lymph node dissection in HALNU was the lowest (17.4%). In both Kaplan-Meier and univariate analysis, the type of surgery was significantly associated with overall and cancer-specific survival. The statistical significance of surgical methods on survival outcomes remained in multivariate analysis, where patients undergoing HALNU appeared to have the worst overall (p = 0.007) and cancer-specific (p = 0.047) survival rates among the three groups. In all analyses, the surgical approach was not related to bladder recurrence. In addition, HALNU was significantly associated with longer hospital stay (p = 0.002), and had the highest risk of major Clavien-Dindo complications (p = 0.011), paralytic ileus (p = 0.012), and postoperative end-stage renal disease (p

Ferroptosis is a type of iron-dependent cell death pertaining to an excess of lipid peroxidation. It has been suggested that sorafenib—an anti-angiogenic medication for hepatocellular carcinoma (HCC)—induces ferroptosis, but the underlying mechanism for this remains largely unknown. We employed siRNA-mediated gene silencing to investigate the role of Src homology region 2 domain-containing phosphatase-1 (SHP-1), following sorafenib treatment, in cystine/glutamate-antiporter-system-Xc−-regulated cystine uptake. Co-immunoprecipitation was also performed to examine the interactions between MCL1, beclin 1 (BECN1), and solute carrier family 7 member 11 (SLC7A11), which functions as the catalytic subunit of system Xc−. The results of this study showed that sorafenib enhanced the activity of SHP-1, dephosphorylated STAT3, downregulated the expression of MCL1 and, consequently, reduced the association between MCL1 and BECN1. In contrast, increased binding between BECN1 and SLC7A11 was observed following sorafenib treatment. The elevated interaction between BECN1 and SLC7A11 inhibited the activity of system Xc−, whereas BECN1 silencing restored cystine intake and protected cells from ferroptosis. Notably, ectopic expression of MCL1 uncoupled BECN1 from SLC7A11 and rescued cell viability by attenuating lipid peroxidation. The results revealed that ferroptosis could be induced in HCC via SHP-1/STAT3-mediated downregulation of MCL1 and subsequent inhibition of SLC7A11 by increased BECN1 binding.

Sketch-based data streaming algorithms are used in many network traffic monitoring applications to obtain accurate estimates of traffic flow statistics. However, the current implementation of sketch-based methods in network monitoring is too application-specific. Their flexibility is limited as the hardware implementation of sketch data structure in the network device depends on the measurement tasks. The sketch counters only summarize flow statistics that are relevant to a specific measurement task and cannot be reused for different measurement tasks. In this paper, we propose FlexSketchMon, a system designed to provide the flexibility of using various sketch-based algorithms for traffic monitoring and measurement tasks. FlexSketchMon leverages on a novel data plane architecture that collects traffic flow statistics and provides arbitrary flow aggregations to the monitoring applications. The data plane design comprises a flow counter table and a flow key table for storing flow-level data. FlexSketchMon is implemented on the NetFPGA-SUME platform and is capable of processing network traffic at line rate in a worst-case scenario corresponding to a 64-byte minimum Ethernet frame size. The update of the flow counter table, which is the critical path in the proposed system, can achieve a throughput of 96 Gbps. The simulation results based on a real-world network traffic traces for three monitoring applications-estimation, superspreader detection, and heavy hitter detection-are presented to demonstrate the performance of FlexSketchMon. The results show that FlexSketchMon yields comparable and better measurement accuracy compared to previous approaches.

Objective: Atypical small acinar proliferation (ASAP) and high-grade prostatic intraepithelial neoplasia (HGPIN) are two pathological findings occasionally noted in prostate biopsies. Previous Western studies reported that they were associated with prostate cancer. However, none Taiwanese series report the subsequent cancer detection in ASAP and HGPIN patients. This study aimed to examine the results of repeated biopsies in the patients with ASAP and HGPIN. Materials and Methods: A total of 220 consecutive patients with ASAP and/or HGPIN at our institute between January 1990 and December 2010 were enrolled. Patient demographics and clinical information were extracted from the electronic database of our institute. Prostate biopsies were performed through transrectal ultrasound guidance. The patients who had concurrent prostate cancer (n = 51) and no repeated prostate biopsies (n = 103) were excluded from the study. Patients with biopsy pathologies reporting low-grade prostatic intraepithelial neoplasia (n = 2) were also excluded. The remaining 64 patients were available for the final analysis. Results: Nearly, 38, 24, and 2 patients were initially diagnosed as ASAP, HGPIN, and ASAP along with HGPIN, respectively. After 10 years of follow-up, 36.8% patients in ASAP group developed prostate cancer, while 16.7% in HGPIN group and 100% in ASAP + HGPIN group. Median time to developing prostate cancer were 20 months in ASAP group, 31 months in HGPIN group, and 48 months in ASAP + HGPIN group. There was no significant difference of prostate cancer development between ASAP and HGPIN group (P = 0.291). Only older age, classified by 65 years, was significantly associated with a higher detection rate of prostate cancer. Conclusion: Patients with the initial diagnosis of ASAP or PIN has a high risk of developing prostate cancer. Therefore, those patients should be well announced and followed regularly.

Objectives: Some studies have shown that in patients with upper tract urothelial carcinoma (UTUC) who have undergone hand-assisted laparoscopic nephroureterectomy (HALNU), the narrow working space and inevitable manipulation that occurs during the retroperitoneal approach (RP-HALNU) enhances tumor cell seeding in the bladder mucosa. This study was an attempt to investigate the differences in intravesical recurrence between transperitoneal HALNU (TP-HALNU) and RP-HALNU. Patients and Methods: From 1999 to 2011, a total of 197 patients with UTUC were enrolled. After excluding those with a previous history of bladder cancer, 170 patients were analyzed. Sixty-five of these underwent RP-HALNU, and 105 of these underwent TP-HALNU. The median follow-up periods were 39.2 and 46.2 months. Tumor location was divided into three groups: In the renal pelvis, in the ureter, and in both the renal pelvis and ureter. Results: There was no significant difference in the intravesical recurrence rate in relation to the different surgical approaches (P = 0.10), but tumor location in both the renal pelvis and ureter significantly increased the risk (hazard ratio [HR] = 3.11, P = 0.01). In addition, advanced T stage (HR = 9.63, P < 0.01) was the only significant risk factor related to death. Conclusions: In patients with UTUC, tumor location in both the renal pelvis and ureter determined higher susceptibility to intravesical recurrence. However, different surgical approaches to HALNU were not a significant risk factor for intravesical recurrence.

Neuregulins (NRGs) activate receptor tyrosine kinases of the ErbB family, and play essential roles in the proliferation, survival, and differentiation of normal and malignant tissue cells. We hypothesized that genetic variants of NRG signalling pathway genes may influence treatment outcomes in prostate cancer. To test this hypothesis, we performed a comprehensive analysis to evaluate the associations of 459 single-nucleotide polymorphisms in 19 NRG pathway genes with cancer-specific survival (CSS), overall survival (OS), and progression-free survival (PFS) in 630 patients with prostate cancer receiving androgen-deprivation therapy (ADT). After multivariate Cox regression and multiple testing correction, we found that NRG1 rs144160282 C > T is significantly associated with worsening CSS, OS, and PFS during ADT. Further analysis showed that low expression of NRG1 is closely related to prostate cancer, as indicated by a high Gleason score, an advanced stage, and a shorter PFS rate. Meta-analysis of 16 gene expression datasets of 1,081 prostate cancer samples and 294 adjacent normal samples indicate lower NRG1 expression in the former compared with the latter (p < 0.001). These results suggest that NRG1 rs144160282 might be a prognostic predictor of the efficacy of ADT. Further studies are required to confirm the significance of NRG1 as a biomarker and therapeutic target for prostate cancer.

Current non-invasive approaches for detection of urothelial cancers are suboptimal. We developed a test to detect urothelial neoplasms using DNA recovered from cells shed into urine. UroSEEK incorporates massive parallel sequencing assays for mutations in 11 genes and copy number changes on 39 chromosome arms. In 570 patients at risk for bladder cancer (BC), UroSEEK was positive in 83% of those who developed BC. Combined with cytology, UroSEEK detected 95% of patients who developed BC. Of 56 patients with upper tract urothelial cancer, 75% tested positive by UroSEEK, including 79% of those with non-invasive tumors. UroSEEK detected genetic abnormalities in 68% of urines obtained from BC patients under surveillance who demonstrated clinical evidence of recurrence. The advantages of UroSEEK over cytology were evident in low-grade BCs; UroSEEK detected 67% of cases whereas cytology detected none. These results establish the foundation for a new non-invasive approach for detection of urothelial cancer.

In Taiwanese patients, carcinoma of the penis is an uncommon disease. We retrospectively reviewed potential prognostic factors in Taiwanese patients with invasive-penile squamous cell carcinoma (SCC). From 1997 to 2009, 52 patients were enrolled. The median patient age at diagnosis was 66.5 years and the peak incident occurred during the 6th and 7th decades of life. Thirteen patients (25%) died of penile cancer, with a mean follow-up time of 45 months (interquartile range: 15–64 months). The 5-year cumulative cancer-specific survival rate was 81%, with 100% for those with Stage I, 90% for those with Stage II, 60% for those with Stage III, and 14% for those with Stage IV. Eleven variables, including grade, tumor, node, metastasis (TNM) stage, involvement of corpus spongiosum or corpora cavernosa, lymphovascular or perineural invasion, lymphadenectomy, and palpable lymph node, with p

Cigarette smoking, exposure to secondhand smoke, and arsenic exposure are well known risk factors for developing urothelial carcinoma (UC). We investigated the combined effects of cigarette smoking, exposure to secondhand smoke, and the presence of urinary total arsenic on the risk of developing UC. Methods: We conducted a hospital-based, case–control study involving 261 UC patients and 672 cancer-free control individuals between September 2002 and May 2009. Results: Individuals who had smoked 100 cigarettes in their lifetime (ever smokers) and had a high urinary total arsenic level, had increased risks of developing UC (3.20-fold and 6.45-fold greater), respectively, compared to individuals who were never smokers and had a low urinary total arsenic level. Individuals who had high urinary total arsenic levels and had been exposed to secondhand smoke, and individuals with high urinary arsenic levels who had not been exposed to secondhand smoke, had increased chances (2.71-fold and 5.00-fold greater, respectively) of developing UC, compared to individuals who were not exposed to secondhand smoke and had low urinary total arsenic levels. Ever smokers who had been exposed to secondhand smoke and had a high urinary total arsenic level had the greatest increased risk for developing UC (10.82-fold greater). Conclusion: Individuals in a Taiwanese population who smoked cigarettes, were exposed to secondhand smoke, and a high urinary total arsenic level, had a significant risk for developing UC.

Previous studies investigated the impacts of a partial nephrectomy (PN) or radical nephrectomy (RN) on cardiovascular events and death. However, the association between the type of nephrectomy (PN vs. RN) and cardiovascular disease is still equivocal. This retrospective cohort study aimed to compare the risk of coronary heart disease (CHD) between patients who underwent a PN and those who underwent an RN. We used data from the Taiwan Longitudinal Health Insurance Database 2005. In total, 60 patients who underwent a PN and 545 patients who underwent an RN were included. Each patient was tracked for 1-, 2-, 3-, and 5-year periods to identify those who were subsequently diagnosed with CHD. Cox proportional hazard regression analyses were used to calculate hazard ratios (HRs) for CHD during 1-, 2-, 3-, and 5-year follow-up periods between these two cohorts. For the 1-year follow-up period, the adjusted HR was 0.39 (95% CI: 0.05~2.90, p = 0.355) for patients who underwent a PN compared to those who underwent an RN. Additionally, the adjusted HRs of CHD in patients who underwent a PN for 2-, 3- and 5-year follow-up periods were 1.40 (95% CI: 0.62~3.16, p = 0.417), 1.09 (95% CI: 0.52~2.31, p = 0.814), and 1.02 (95% CI: 0.48~2.18, p = 0.961), respectively, compared to those who underwent an RN. We concluded that there was no significant difference in the risk of CHD between patients who underwent a PN and those who underwent an RN.

To evaluate the long-term oncological outcomes of hand-assisted retroperitoneoscopic radical nephrectomy (HARRN) for treating clinically localized renal cell carcinoma. Methods: We retrospectively collected and analyzed the data and clinical outcomes of 46 patients who underwent HARRN and 50 patients who underwent conventional open radical nephrectomy (ORN) at our institution for clinical localized renal cell carcinoma (RCC). Results: The median follow-up period of the HARRN group was 56.5 months (range: 14.6–78.7 months); for the ORN group, the median follow-up period was 110.8 months (range: 15.5–123 months). Patient age, sex, body mass index, pathologic parameters, and classification based on the guidelines of the American Society of Anesthesiologists were not significantly different between the two groups. The HARRN group had a significantly longer operative time (218 minutes vs. 178 minutes, p = 0.003) and less blood loss (203 mL vs. 670 mL, p

The purpose of this study was to compare prostate cancer detection rates and pathology results, using the Gleason grading system, of 12-core systemic random transrectal ultrasound- guided prostate biopsy (SB) and 3-core finger-guided prostate nodule biopsy (FGNB). Methods: Between January 2002 and December 2006, 148 patients with digitally palpable prostate nodules received SB and additional FGNB. The prostate cancer detection rates and Gleason scores of positive cancer specimens were compared between SB and combination biopsy (SB + FGNB). The patients' characteristics, including age, prostate specific antigen (PSA), percentage of free PSA and prostate volume were also recorded. Results: With simple SB, FGNB, and combination biopsy, the prostate cancer detection rates were 39.9%, 37.9%, and 44.6%, respectively. Of the 66 patients with prostate cancer, the Gleason sum was underestimated in three patients with simple SB only and in one patient with FGNB only. The false-negative rates for SB and FGNB were 10.6% and 15.2%, respectively. Conclusion: In patients with a palpable prostate nodule, combination biopsy with systemic and nodule biopsy could avoid some misdiagnoses of prostate cancer and provide more accurate information for pathology grading.

Dermatomyositis associated with genitourinary malignancies is not uncommon. However, only a few cases associated with ureteral stricture have been reported, and ureteral rupture is even rarer. A 56-year-old woman with dermatomyositis who had been treated with prednisolone, cyclophosphamide, and azathioprine for 2 months presented with fever, hematuria, and abdominal pain for 2 days. Radiographic imaging revealed bilateral ureteral spontaneous rupture and intraperitoneal urinoma formation. Urine cytology and endourologic examinations showed no evidence of genitourinary malignancy. Ureteral urine leakage was managed successfully by drainage through percutaneous catheter and bilateral double-J ureteral stenting. The stents were removed 9 months later. Follow-up intravenous urography 12 months after ureteral stent placement showed good renal function with left mild hydronephrosis and hydroureter above the previous rupture site. Bilateral ureters were patent and there was no evidence of contrast medium extravasation from either ureter. Diuretic renal scanning also showed bilateral nonmechanical obstruction with left-side mild hydronephrosis without urine extravasation. Dermatomyositis can be complicated with spontaneous ureteral rupture. Conservative management with urinary diversion and stenting is feasible. [J Formos Med Assoc 2007;106(3):251-254]

Angiomyolipoma (AML) is a common benign renal tumor composed of thick-walled blood vessels, smooth muscle, and adipose tissue, but the malignant epithelioid variant is extremely rare. A 78-year-old woman presented with fever and left flank pain for 3 days. Computed tomography showed a heterogeneously enhanced mass without fat density in the left kidney. Radical nephrectomy was performed and pathology showed malignant epithelioid AML with regional lymph node metastases. The tumor cells were positive for human melanosome-associated protein (HMB-45) on immunohistochemical staining. The patient died of disseminated metastases (lungs and bones) 5 months postoperatively. Epithelioid AML is a potentially aggressive tumor. The prognosis is poor in metastatic disease. HMB-45 immunoreactivity is a useful marker to make diagnosis. [J Formos Med Assoc 2007;106(2 Suppl):S51-S54]

Abstract Background Nephroureterectomy with bladder cuff excision is the standard treatment for high-risk upper urinary tract urothelial carcinoma (UTUC). The role of minimally invasive surgery in treating locally advanced UTUC remains controversial. This study aimed to compare the outcomes of open, laparoscopic, and robotic surgeries for managing locally advanced UTUC. Methods We retrospectively reviewed 705 patients with locally advanced UTUC from multiple institutions throughout Taiwan. Perioperative outcomes and oncological outcomes, such as cancer-specific survival, overall survival, disease-free survival and bladder-free survival, were compared between the open, laparoscopic and robotic groups. Results The minimally invasive group had better overall and cancer-specific survival (CSS) rates. The 2-year CSS rates of the open, laparoscopic and robotic groups were 71%, 83%, and 77% respectively (p

Abstract Patients with end stage renal disease (ESRD) are at high risk of developing upper tract urothelial carcinoma (UTUC). Due to high recurrence rate of UTUC in contralateral kidney and ureter, and high risk of complications related to surgery and anesthesia, whether it’s necessary to remove both kineys and ureters at one time remains in debate. We utilized Taiwanese UTUC Registry Database to valuate the difference of oncological outcomes and perioperative complications between patients with ESRD with unilateral and bilateral UTUC receiving surgical resection. Patients with ESRD and UTUC were divided into three groups, unilateral UTUC, previous history of unilateral UTUC with metachronous contralateral UTUC, and concurrent bilatetral UTUC. Oncological outcomes, perioperative complications, and length of hospital stays were investiaged. We found that there is no diffence of oncological outcomes including overall survival, cancer specific survival, disease free survival and bladder recurrence free survival between these three groups. Complication rate and length of hospital stay are similar. Adverse oncological features such as advanced tumor stage, lymph node involvement, lymphovascular invasion, and positive surgical margin would negatively affect oncological outcomes.

Purpose: Active surveillance (AS) is one of the management options for patients with low-risk and select intermediate-risk prostate cancer (PC). However, factors predicting disease reclassification and conversion to active treatment from a large population of pure Asian cohorts regarding AS are less evaluated. This study investigated the intermediate-term outcomes of patients with localized PC undergoing AS. Materials and Methods: This cohort study enrolled consecutive men with localized non-high-risk PC diagnosed in Taiwan between June 2012 and Jan 2023. The study endpoints were disease reclassification (either pathological or radiographic progression) and conversion to active treatment. The factors predicting endpoints were evaluated using the Cox proportional hazards model. Results: A total of 405 patients (median age: 67.2 years) were consecutively enrolled and followed up with a median of 64.6 months. Based on the National Comprehensive Cancer Network (NCCN) risk grouping, 70 (17.3%), 164 (40.5%), 140 (34.6%), and 31 (7.7%) patients were classified as very low-risk, low-risk, favorable-intermediate risk, and unfavorable intermediate-risk PC, respectively. The 5-year reclassification rates were 24.8%, 27.0%, 18.6%, and 25.3%, respectively. The 5-year conversion rates were 20.4%, 28.8%, 43.6%, and 37.8%, respectively. A prostate-specific antigen density (PSAD) of ≥0.15 ng/mL2 predicted reclassification (hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.17–2.88) and conversion (HR 1.56, 95% CI 1.05–2.31). A maximal percentage of cancer in positive cores (MPCPC) of ≥15% predicted conversion (15% to

Abstract In order to improve the driving ability of the explosion wave simulation equipment, reduce the erosion effect of condensed explosives on the explosion wave simulation equipment, improve the safety of the test process, and make better use of the meteorological detonation driving method, it is necessary to optimize the source of the shock wave load in the driving section. Based on the finite volume method of FLACS, a methane detonation driving model corresponding to the test is established to explore the feasibility of using methane as an explosion source to test the structure against explosion shock wave. A methane detonation drive test was carried out to verify the accuracy of the numerical model. Finally, an engineering model for attenuation of shock wave overpressure peak value in pipeline is established by dimensional analysis, and the model coefficient is determined by numerical simulation and test data. The results show that the blast pressure is the highest when the methane volume ratio reaches 9.5 vol% in the methane-air mixture. Simply increasing oxygen content has little effect on the peak overpressure and positive pressure duration of shock wave. In the pure oxygen environment, the detonation effect can be achieved when the volume ratio of methane to oxygen is 1:2, and the incident pressure of the shock wave is proportional to the volume of the gas cloud. When the gas cloud volume is constant, a reasonable selection of methane-oxygen mixture ratio can achieve a better detonation effect, which can effectively increase the peak overpressure of the shock wave in the test section. The research results can provide technical reference for the development of new explosion wave simulation equipment.

Background: This study aimed to investigate the influence of immunonutritional factors on treatment-related toxicities and survival outcomes in patients with cervical cancer undergoing definitive radiochemotherapy. Methods: Patients with cervical cancer who received curative radiochemotherapy between 2016 and 2021 were retrospectively investigated. Pretreatment prognostic nutritional index (PNI), neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) were measured. Survival outcomes, acute and late toxicities were evaluated. Results: Among the 138 patients, those with larger tumor diameters had significantly lower pre-treatment PNI (p = 0.005). Pre-treatment immunonutritional factors were predictive of clinical survival, whereas post-treatment factors did not correlate with prognosis. Patients with low pre-treatment PNI (2.4) had shorter progression-free survival (PFS, HR: 1.86, p = 0.045 for PNI; HR: 3.15, p = 0.002 for NLR) and overall survival (OS, HR: 1.80, p = 0.048 for PNI; HR: 3.83, p = 0.015 for NLR). High pre-treatment NLR was associated with an increased risk of acute diarrhea (p = 0.049) and late severe toxicities (p = 0.046). Combined analysis revealed that pre-treatment good nutritional status and low systemic inflammation were linked to longer PFS (p = 0.007) and OS (p = 0.002), and poor nutritional status and substantial systemic inflammation were associated with higher rates of late severe toxicities (p = 0.036), with higher prognostic value in advanced stage patients. Conclusion: Pretreatment immunonutritional measures serve as quantitative biomarkers for predicting survivals and treatment toxicities in patients with cervical cancer treated with definitive radiochemotherapy.

Purpose:. According to the National Comprehensive Cancer Network guidelines, segmental ureterectomy (SU) of upper tract urothelial carcinoma (UTUC) is a considerable option for selected mid- and distal ureteral urothelial carcinoma (UC). As a UTUC endemic area, Taiwan lacks treatment outcome analysis of SU. Materials and methods:. This study retrospectively reviewed the treatment outcomes of SU for clinically localized UTUCs. Patients with biopsy or washing cytology-confirmed UTUCs who underwent open, laparoscopic, or robot-assisted management with curative intent were retrospectively reviewed for the eligibility of analysis. Cox regression was applied for univariable and multivariable analyses. Results:. A total of 161 patients who underwent SU were reviewed and analyzed. The median follow-up period was 44.5 (interquartile range, 21.6–84.9) months. After SU, 56/161 (34.8%) patients were free of UTUCs after the follow-up, 25/161 (15.5%) patients had local recurrence, and 35/161 (21.7%) had lymph node or distant metastasis. Surgical margin involvement was a risk factor associated with worse cancer-specific survival. Higher bladder recurrence and local recurrence rates were observed with concurrent bladder UC. Lymphovascular invasion and previous radical nephroureterectomy (RNU) for UC were related to higher local recurrence rates. Patients with pathological T3/T4 stage and end-stage renal disease tended to have higher metastasis rates. For the management of local recurrence, 19 patients received salvage RNU and 25 patients had adjuvant chemotherapy. However, 26/161 (16.1%) patients died of UTUCs and 2/161 (1.2%) patients died of surgery-related complications. Conclusion:. SU provides acceptable oncological outcomes if the surgeons select candidates carefully. SU is not recommended if the patient has T3 or higher stage or comorbidity of end-stage renal disease. Concurrent bladder UC is a risk factor for worse bladder recurrence-free survival and local recurrence-free survival. Lymphovascular invasion and previous RNU for UC were related to higher local recurrence rates. After SU, periodic follow-up is mandatory because the local recurrence rate is higher than radical surgery.

Purpose:. The purpose of this study is to demonstrate the feasibility and safety of the Senhance robotic system in urologic surgeries. Materials and methods:. Patients were included prospectively from July 2018 to December 2020. The exclusion criteria included severe cardiopulmonary diseases and previous extensive abdominal surgeries. Institutional approval and informed consent were obtained. We used the Clavien-Dindo classification system to evaluate the complications that occurred within 30 days after surgery. Common technical and mechanical events encountered were also recorded. Results:. A total of 173 patients were recruited. The median age was 65 (58–74) years, and the median body mass index was 24.7 (16.5–35.6) kg/m2. Seventeen (9.8%) patients had previously undergone abdominal surgeries. Eighty-three (48%) cases had total extraperitoneal hernioplasty and 32 (18.5%) cases radical prostatectomy, which were the largest 2 surgeries in our study. Sixty-one (35.3%) patients received surgeries due to malignancy. The median docking time was 5 (1–35) minutes. There were 28 (16.2%) cases with grade I complications and 9 (5.2%) cases with grade II complications. Only one case of a grade IIIb complication occurred during radical prostatectomy. No grade IV complications or mortalities were noted. Robotic arm collisions and forces exceeding the limit were the most commonly encountered problems intraoperatively. Conclusion:. In our initial experiences, the Senhance robotic system was feasible in oncologic and nononcologic urologic surgeries and had acceptable outcomes. The haptic feedback system is unique and requires a learning period. This system may serve as an alternative tool for robotic urologic surgeries.

Abstract Ferroptosis, an iron-dependent form of regulated cell death, plays a crucial role in modulating the therapeutic response in non-small cell lung cancer (NSCLC) patients. Studies have identified the signal transducer and activator of transcription 3 (STAT3) and myeloid cell leukemia-1 (MCL1) as potential targets for sorafenib, which exhibits activities in inducing ferroptosis. However, the role of STAT3-MCL1 axis in sorafenib-induced ferroptosis in NSCLC is still unclear. This study provided evidence that ferroptosis is a critical driver of sorafenib-induced cell death in NSCLC, supported by the accumulation of lipid peroxidation products, indicative of oxidative stress-induced cell death. Additionally, both in vitro and in vivo experiments showed that ferroptosis contributed to a significant portion of the anti-cancer effects elicited by sorafenib in NSCLC. The noticeable accumulation of lipid peroxidation products in sorafenib-treated mice underscored the significance of ferroptosis as a contributing factor to the therapeutic response of sorafenib in NSCLC. Furthermore, we identified the involvement of the STAT3/MCL1 axis in sorafenib-induced antitumor activity in NSCLC. Mechanistically, sorafenib inhibited endogenous STAT3 activation and downregulated MCL1 protein expression, consequently unleashing the ferroptosis driver BECN1 from the BECN1-MCL1 complex. Conversely, there is an augmented association of BECN1 with the catalytic subunit of system Xc−, SLC7A11, whose activity to import cystine and alleviate lipid peroxidation is hindered upon its binding with BECN1. Notably, we found that MCL1 upregulation correlated with ferroptosis resistance in NSCLC upon sorafenib treatment. Our findings highlight the importance of sorafenib-triggered ferroptosis in NSCLC and offer a novel strategy to treat advanced NSCLC patients: by downregulating MCL1 and, in turn, predispose NSCLC cells to ferroptosis.

Abstract Background Treatment failure following androgen deprivation therapy (ADT) presents a significant challenge in the management of advanced prostate cancer. Thus, understanding the genetic factors influencing this process could facilitate the development of personalized treatments and innovative therapeutic strategies. The phosphoinositide 3-kinase (PI3K)/AKT signaling pathway plays a pivotal role in controlling cell growth and tumorigenesis. We hypothesized that genetic variants within this pathway may affect the clinical outcomes of patients undergoing ADT for prostate cancer. Methods We genotyped 399 single-nucleotide polymorphisms (SNPs) across 28 core PI3K/AKT pathway genes in a cohort of 630 patients with prostate cancer undergoing ADT. We assessed the potential association of the SNPs with patient survival. Functional analyses of the implicated genes were also performed to evaluate their effects on prostate cancer. Results After multivariate Cox regression analysis and multiple testing correction, GABRB3 rs12591845 exhibited the most significant association with both overall and cancer-specific survivals (P

Abstract Docetaxel‐based chemotherapy has generally been considered as one of the effective treatments for castration‐resistant prostate cancer (PCa). However, clinical treatment with docetaxel often encounters a number of undesirable effects, including drug resistance. Tubulin isoforms have been previously examined for their resistance to docetaxel in many cancers, but their real mechanisms remained unclear. In this study, a series of docetaxel‐resistant PC/DX cell sublines were established by chronically exposing PC3 to progressively increased concentrations of docetaxel. Western blotting results showed significantly higher expression of acetyl‐tubulin, α‐tubulin, β‐tubulin, γ‐tubulin, and βIII‐tubulin in PC/DX25 than in parental PC3 cells. PC/DX25 with greater resistance to docetaxel had higher levels of acetyl‐tubulin and mitotic centromere‐associated kinesin (MCAK) than PC3 cells. This study found that docetaxel induced the expression of acetyl‐tubulin and MCAK in PC3 cells at a dose‐ and time‐dependent manner. Both mRNA and protein levels of histone deacetylase 6 (HDAC6) were significantly decreased in PC/DX25 compared with PC3 cells. PC3 increased the resistance to docetaxel by HDAC6 knockdown and Tubastatin A (HDAC6 inhibitor). Conversely, PC/DX25 reversed the sensitivity to docetaxel by MCAK knockdown. Notably, flow cytometry analysis revealed that MCAK knockdown induced significantly sub G1 fraction in PC/DX cells. Overexpression of polo‐like kinase‐1 increased the cell survival rate and resistance to docetaxel in PC3 cells. Moreover, epidermal growth factor receptor (EGFR) activation induced the upregulation of acetyl‐tubulin in docetaxel‐resistant PCa cells. These findings demonstrated that the EGFR‐mediated upregulated expression of acetyl‐tubulin played an important role in docetaxel‐resistant PCa.

Purpose: The purpose of this study is to evaluate the rates of pathological complete response (ypT0N0/X) and pathological response (ypT1N0/X or less) in patients with upper tract urothelial cancer who were treated with neo-adjuvant chemotherapy and to examine their impact on oncological outcomes. Methods: This study is a multi-institutional retrospective analysis of patients with high-risk upper tract urothelial cancer who underwent neoadjuvant chemotherapy and radical nephroureterectomy between 2002 and 2021. Logistic regression analyses were used to investigate all clinical parameters for response after neoadjuvant chemotherapy. Cox proportional hazard models were performed to assess the effect of the response on the oncological outcomes. Results: A total of 84 patients with UTUC who received neo-adjuvant chemotherapy were identified. Among them, 44 (52.4%) patients received cisplatin-based chemotherapy, and 22 (26.2%) patients had a carboplatin-based regimen. The pathological complete response rate was 11.6% (n = 10), and the pathological response rate was 42.9% (n = 36). Multifocal tumors or tumors larger than 3 cm significantly reduced the odds of pathological response. In the multivariable Cox proportional hazard model, pathological response was independently associated with better overall survival (HR 0.38, p = 0.024), cancer-specific survival (HR 0.24, p = 0.033), and recurrence-free survival (HR 0.17, p = 0.001), but it was not associated with bladder recurrence-free survival (HR 0.84, p = 0.69). Conclusion: Pathological response after neo-adjuvant chemotherapy and radical nephroureterectomy is strongly associated with patient survival and recurrence, and it might be a good surrogate for evaluating the efficacy of neo-adjuvant chemotherapy in the future.