Predicting Clinically Significant Prostate Cancer Using Urine Metabolomics via Liquid Chromatography Mass Spectrometry.

PURPOSE: Biomarkers predicting clinically significant prostate cancer (sPC) before biopsy are currently lacking. This study aimed to develop a non-invasive urine test to predict sPC in at-risk men using urinary metabolomic profiles. MATERIALS AND METHODS: Urine samples from 934 at-risk subjects and 268 treatment-naïve PC patients were subjected to liquid chromatography/mass spectrophotometry (LC-MS)-based metabolomics profiling using both C18 and hydrophilic interaction liquid chromatography (HILIC) column analyses. Four models were constructed (training cohort [n=647]) and validated (validation cohort [n=344]) for different purposes. Model I differentiates PC from benign cases. Models II, III, and a Gleason score model (model GS) predict sPC that is defined as National Comprehensive Cancer Network (NCCN)-categorized favorable-intermediate risk group or higher (Model II), unfavorable-intermediate risk group or higher (Model III), and GS ≥7 PC (model GS), respectively. The metabolomic panels and predicting models were constructed using logistic regression and Akaike information criterion. RESULTS: The best metabolomic panels from the HILIC column include 25, 27, 28 and 26 metabolites in Models I, II, III, and GS, respectively, with area under the curve (AUC) values ranging between 0.82 and 0.91 in the training cohort and between 0.77 and 0.86 in the validation cohort. The combination of the metabolomic panels and five baseline clinical factors that include serum prostate-specific antigen, age, family history of PC, previously negative biopsy, and abnormal digital rectal examination results significantly increased AUCs (range 0.88-0.91). At 90% sensitivity (validation cohort), 33%, 34%, 41%, and 36% of unnecessary biopsies were avoided in Models I, II, III, and GS, respectively. The above results were successfully validated using LC-MS with the C18 column. CONCLUSIONS: Urinary metabolomic profiles with baseline clinical factors may accurately predict sPC in men with elevated risk before biopsy.

Clinical effects of traditional Chinese herbal medicine management in patients with COVID-19 sequelae: A hospital-based retrospective cohort study in Taiwan.

Introduction: An estimated 43% of COVID-19 patients showed sequelae, including fatigue, neurocognitive impairment, respiratory symptoms, and smell or taste disorders. These sequelae significantly affect an individual's health, work capacity, healthcare systems, and socioeconomic aspects. Traditional Chinese herbal medicine (TCHM) management showed clinical benefits in treating patients with COVID-19 sequelae. This study aimed to analyze the effects of personalized TCHM management in patients with COVID-19 sequelae. Methods: After the COVID-19 outbreak in Taiwan, we recorded Chronic Obstructive Pulmonary Disease Assessment Tool (CAT), Chalder Fatigue Questionnaire (CFQ-11), and Brief Symptom Rating Scale (BSRS-5) to assess post-COVID respiratory, fatigue, and emotional distress symptoms, respectively. In this study, we retrospectively reviewed the medical records between July 2022 and March 2023. We analyzed the effects of TCHM administration after 14- and 28-days of treatment. Results: 47 patients were included in this study. The results demonstrated that personalized TCHM treatment significantly improved the CAT, CFQ-11, and BSRS-5 scores after 14 and 28 days. TCHM alleviated physical and psychological fatigue. In logistic regression analysis, there was no statistically significant differences in the severity of the baseline symptoms and TCHM administration effects concerning the duration since the initial confirmation of COVID-19, sex, age, or dietary preference (non-vegetarian or vegetarian). Conclusions: Our study suggested that personalized TCHM treatment notably reduced fatigue, respiratory and emotional distress symptoms after 14- and 28-days of treatment in patients with COVID-19 sequelae. We propose that TCHM should be considered as an effective intervention for patients with COVID-19 sequelae.

Prediction of clinically significant prostate cancer through urine metabolomic signatures: A large-scale validated study.

PURPOSE: Currently, there are no accurate markers for predicting potentially lethal prostate cancer (PC) before biopsy. This study aimed to develop urine tests to predict clinically significant PC (sPC) in men at risk. METHODS: Urine samples from 928 men, namely, 660 PC patients and 268 benign subjects, were analyzed by gas chromatography/quadrupole time-of-flight mass spectrophotometry (GC/Q-TOF MS) metabolomic profiling to construct four predictive models. Model I discriminated between PC and benign cases. Models II, III, and GS, respectively, predicted sPC in those classified as having favorable intermediate risk or higher, unfavorable intermediate risk or higher (according to the National Comprehensive Cancer Network risk groupings), and a Gleason sum (GS) of ≥ 7. Multivariable logistic regression was used to evaluate the area under the receiver operating characteristic curves (AUC). RESULTS: In Models I, II, III, and GS, the best AUCs (0.94, 0.85, 0.82, and 0.80, respectively; training cohort, N = 603) involved 26, 24, 26, and 22 metabolites, respectively. The addition of five clinical risk factors (serum prostate-specific antigen, patient age, previous negative biopsy, digital rectal examination, and family history) significantly improved the AUCs of the models (0.95, 0.92, 0.92, and 0.87, respectively). At 90% sensitivity, 48%, 47%, 50%, and 36% of unnecessary biopsies could be avoided. These models were successfully validated against an independent validation cohort (N = 325). Decision curve analysis showed a significant clinical net benefit with each combined model at low threshold probabilities. Models II and III were more robust and clinically relevant than Model GS. CONCLUSION: This urine test, which combines urine metabolic markers and clinical factors, may be used to predict sPC and thereby inform the necessity of biopsy in men with an elevated PC risk.

Endoscopic management of upper tract urothelial cancer in a highly endemic area: A Taiwan nationwide collaborative study.

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.

Impact of pathological response on oncological outcomes in patients with upper tract urothelial cancer receiving neo-adjuvant chemotherapy.

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.

Folic Acid Ameliorates Renal Injury in Experimental Obstructive Nephropathy: Role of Glycine N-Methyltransferase.

Folic acid exerts both anti-inflammatory and antifibrotic effects. Glycine N-methyltransferase (GNMT), the major folic acid-binding protein in the liver, is a crucial enzyme that regulates the cellular methylation process by maintaining S-adenosylmethionine levels. However, as yet neither the therapeutic effects of folic acid in renal fibrosis nor whether GNMT is involved in these folic acid-associated mechanisms has been investigated. First, the expression of GNMT was examined in human kidneys with or without obstructive nephropathy. Later, wild-type and GNMT knockout (GNMT-/-) mice were subjected to unilateral ureteral obstruction (UUO) and then treated with either folic acid or vehicle for 14 days. Renal tubular injury, inflammation, fibrosis, and autophagy were evaluated by histological analysis and Western blotting. We observed increased expression of GNMT in humans with obstructive nephropathy. Furthermore, UUO significantly increased the expression of GNMT in mice; in addition, it caused renal injury as well as the development of both hydronephrosis and tubular injury. These were all alleviated by folic acid treatment. In contrast, GNMT-/- mice exhibited exacerbated UUO-induced renal injury, but the protective effect of folic acid was not observed in GNMT-/- mice. We propose a novel role for folic acid in the treatment of renal fibrosis, which indicates that GNMT may be a therapeutic target.

Preoperative hydronephrosis is an independent protective factor of renal function decline after nephroureterectomy for upper tract urothelial carcinoma.

Objectives: To 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 methods: This 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. Results: 404 (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<0.001). Pre-NU hydronephrosis was associated with a lower post-NU CKD progression rate (33.1% versus 50.7%, p< 0.001) and was an independent protective factor for RF decline after covariate adjustment (OR=0.46, p<0.001). Patients with pre-NU hydronephrosis had a higher preserved eligibility rate for either adjuvant cisplatin-based chemotherapy (OR=3.09, 95%CI 1.95-4.69) or immune-oncology therapy (OR=2.31, 95%CI 1.23-4.34). Conclusion: Pre-NU hydronephrosis is an independent protective predictor for post-NU RF decline, CKD progression, and eligibility for adjuvant therapy. With cautious selection for those unfavorably prognostic, non-metastatic UTUC patients with preoperative hydronephrosis, adjuvant rather than neoadjuvant therapy could be considered due to higher chance of preserving eligibility.

Surgical outcome predictor analysis following hand-assisted or pure laparoscopic transperitoneal nephroureterectomy using the Taiwan upper urinary tract urothelial carcinoma database.

Purpose: Taiwan 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 methods: The 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. Results: Of 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. Conclusion: Although 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.

The Value of Preoperative Local Symptoms in Prognosis of Upper Tract Urothelial Carcinoma After Radical Nephroureterectomy: A Retrospective, Multicenter Cohort Study.

Purpose: We aimed to evaluate the impact of preoperative local symptoms on prognosis after radical nephroureterectomy in patients with upper tract urothelial carcinoma (UTUC). Methods: This 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. Results: The 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 <0.001), more dialysis status (p = 0.027), renal pelvic tumors (p <0.001), and early pathological tumor stage (p = 0.001). Symptomatic hydronephrosis was associated with female patients (p <0.001), less dialysis status (p = 0.001), less bladder cancer history (p <0.001), ureteral tumors (p <0.001), open surgery (p = 0.006), advanced pathological tumor stage (p <0.001), and postoperative chemotherapy (p = 0.029). Kaplan-Meier analysis showed that patients with hematuria or without symptomatic hydronephrosis had significantly higher rates of OS, CSS, and DFS (all p <0.001). Multivariate analysis confirmed that presence of hematuria was independently associated with better OS (HR 0.789, 95% CI 0.661-0.942) and CSS (HR 0.772, 95% CI 0.607-0.980), while symptomatic hydronephrosis was a significant prognostic factor for poorer OS (HR 1.387, 95% CI 1.142-1.683), CSS (HR 1.587, 95% CI 1.229-2.050), and DFS (HR 1.378, 95% CI 1.122-1.693). Conclusions: Preoperative local symptoms were significantly associated with oncological outcomes, whereas symptomatic hydronephrosis and hematuria had opposite prognostic effects. Preoperative symptoms may provide additional information on risk stratification and perioperative treatment selection for patients with UTUC.

Is Lymph Node Dissection Necessary During Radical Nephroureterectomy for Clinically Node-Negative Upper Tract Urothelial Carcinoma? A Multi-Institutional Study.

Purpose: This 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). Methods: From 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. Results: A 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. Conclusions: We 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.

Impact of Adjuvant Chemotherapy on Variant Histology of Upper Tract Urothelial Carcinoma: A Propensity Score-Matched Cohort Analysis.

Background: The 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 Participants: Patients 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. Intervention: Those patients with variant UTUC were grouped based on their history of receiving adjuvant chemotherapy or not. Outcome Measurements and Statistical Analysis: Propensity 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 Limitations: For 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. Conclusions: Adjuvant chemotherapy following RNU significantly improved cancer-related survivals in patients with UTUC with variant histology.

Clinical Efficacy of Adjuvant Chemotherapy in Advanced Upper Tract Urothelial Carcinoma (pT3-T4): Real-World Data from the Taiwan Upper Tract Urothelial Carcinoma Collaboration Group.

The clinical efficacy of adjuvant chemotherapy in upper tract urothelial carcinoma (UTUC) is unclear. We aimed to assess the therapeutic outcomes of adjuvant chemotherapy in patients with advanced UTUC (pT3-T4) after radical nephroureterectomy (RNU). We retrospectively reviewed the data of 2108 patients from the Taiwan UTUC Collaboration Group between 1988 and 2018. Comprehensive clinical features, pathological characteristics, and survival outcomes were recorded. Univariate and multivariate Cox proportional hazards models were used to evaluate overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS). Of the 533 patients with advanced UTUC included, 161 (30.2%) received adjuvant chemotherapy. In the multivariate analysis, adjuvant chemotherapy was significantly associated with a reduced risk of overall death (hazard ratio (HR), 0.599; 95% confidence interval (CI), 0.419-0.857; p = 0.005), cancer-specific mortality (HR, 0.598; 95% CI, 0.391-0.914; p = 0.018), and cancer recurrence (HR, 0.456; 95% CI, 0.310-0.673; p < 0.001). The Kaplan-Meier survival analysis revealed that patients receiving adjuvant chemotherapy had significantly better five-year OS (64% vs. 50%, p = 0.002), CSS (70% vs. 62%, p = 0.043), and DFS (60% vs. 48%, p = 0.002) rates compared to those who did not receive adjuvant chemotherapy. In conclusion, adjuvant chemotherapy after RNU had significant therapeutic benefits on OS, CSS, and DFS in advanced UTUC.

Comparison of oncological outcomes for hand-assisted and pure laparoscopic radical nephroureterectomy: results from the Taiwan Upper Tract Urothelial Cancer Collaboration Group.

PURPOSE: Laparoscopic radical nephroureterectomy (LNU) has gradually become the new standard treatment for localized upper tract urothelial cancer (UTUC). With more blunt dissection and tactile sensation, hand-assisted LNU might shorten the operative time compared with the pure laparoscopic approach. However, whether the use of the hand-assisted or the pure laparoscopic approach has an effect on oncological outcomes remains unclear. METHODS: We retrospectively identified 629 patients with non-metastatic UTUC who underwent hand-assisted (n = 515) or pure LNU (n = 114) at 9 hospitals in Taiwan between 2004 and 2019. Overall survival, cancer-specific survival, recurrence-free survival, and bladder recurrence-free survival were compared between these two groups using inverse-probability of treatment weighting (IPTW) derived from the propensity scores for baseline covariate adjustment. RESULTS: The median follow-up period was 32.9 and 28.7 months in the hand-assisted and the pure groups, respectively. IPTW-adjusted Cox proportional hazards models showed that the laparoscopic approach (pure vs. hand-assisted) was not significantly associated with all-cause mortality (HR 0.79, 95% CI 0.49-1.24, p = 0.304), cancer-specific mortality (HR 0.88, 95% CI 0.51-1.51, p = 0.634), or extra-vesical recurrence (HR 0.65, 95% CI 0.41-1.04, p = 0.071). However, the pure laparoscopic approach was significantly associated with lower intra-vescial recurrence (HR 0.64, 95% CI 0.43-0.96, p = 0.029) for patients who underwent LNU. Kaplan-Meier curves also revealed that the pure laparoscopic approach was associated with better bladder recurrence-free survival compared with the hand-assisted laparoscopic approach in both the original cohort and the IPTW-adjusted cohort (log-rank p = 0.042 and 0.027, respectively). CONCLUSIONS: The performance of hand-assisted or pure LNU does not significantly affect the all-cause mortality, cancer-specific mortality, or extra-vesical recurrence for patients with non-metastatic UTUC. However, the hand-assisted laparoscopic approach could increase the risk of intra-vesical recurrence for patients who undergo LNU.

Oncologic impact of delay between diagnosis and radical nephroureterectomy.

Purpose: This 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). Methods: In 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. Results: Of 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. Conclusions: For 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.

Comparing Oncological Outcomes and Surgical Complications of Hand-Assisted, Laparoscopic and Robotic Nephroureterectomy for Upper Tract Urothelial Carcinoma.

PURPOSE: This 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. METHODS: From 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. RESULTS: Among 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 <0.001). CONCLUSIONS: Minimally invasive surgery can be safe and feasible. We proved that compared with the HALNU group, the LNU and RNU groups have better survival rates and fewer surgical complications. It is crucial to uphold strict oncological principles with sophisticated technique to improve outcomes. Further prospective studies are needed to validate our findings.

Endoscopic management versus radical nephroureterectomy for localized upper tract urothelial carcinoma in a high endemic region.

Our aim was to analyze the clinical and survival differences among patients who underwent the two main treatment modalities, endoscopic ablation and radical nephroureterectomy. This study examined all patients who had undergone endoscopic management and RNU between Jul. 1988 and Mar. 2019 from the Taiwan UTUC registry. The inclusion criteria were low stage UTUC in RNU and all cases in endoscopic managed UTUC with a curative intent. The demographic and clinical characteristics were included for analysis. In total, 84 cases in the endoscopic group and 272 cases in the RNU group were enrolled for final analysis. The median follow-up period were 33.5 and 42.0 months in endoscopic and RNU group, respectively (p = 0.082). Comparison of Kaplan-Meier estimated survival curves between groups, the endoscopic group was associated with similar overall survival (OS), cancer specific survival (CSS), and intravesical recurrence free survival (IVRS) but demonstrated inferior disease free survival (DFS) (p = 0.188 for OS, p = 0.493 for CSS and p < 0.001 for DFS). Endoscopic management of UTUC was as safe as RNU in UTUC endemic region.

Comparative analysis of patients with upper urinary tract urothelial carcinoma in black-foot disease endemic and non-endemic area.

BACKGROUND: A high incidence of upper urinary tract urothelial carcinoma has been reported in the southwestern area of Taiwan, where arsenic water contamination was considered the main cause. However, there is no definite proof to show a correlation between arsenic water contamination and upper urinary tract urothelial carcinoma. To investigate the clinical and epidemiological features of patients with upper urinary tract urothelial carcinoma between arsenic water endemic and non-endemic areas, we analyzed patients in terms of characteristics, stratified overall survival, disease-free survival, and cancer-specific survival. METHODS: The records of a total of 1194 patients diagnosed with upper urinary tract urothelial carcinoma were retrospectively reviewed. Clinical data and current medical status were collected from the medical records. Statistical analyses were performed to determine the clinical variables and stratified survival curves between endemic and non-endemic groups. RESULTS: Female predominance was revealed in both endemic and non-endemic groups (male:female ratio = 1:1.2-1.4). No statistical differences were found in histological types, staging, and tumor size between the two groups. Nonetheless, patients with characteristics of aging and having end-stage renal disease were outnumbered in the non-endemic group, while a higher prevalence of previous bladder tumors and more ureteral tumors were found in the endemic group. Adjusted stratified cumulative survival curves suggested a poorer prognosis in endemic patients, especially in disease-free survival of early stage disease. CONCLUSIONS: A higher mortality rate with more previous bladder cancer history and ureteral tumors was seen in patients with upper urinary tract urothelial carcinoma residing in the arsenic water contamination area. This may be attributed to the long-term carcinogenic effect of arsenic underground water.

Predictive factors of post-laparoscopic inguinal hernia acute and chronic pain: prospective follow-up of 807 patients from a single experienced surgeon.

INTRODUCTION: Convalescence after hernia repair is one of the main focuses for hernia surgeons. We analyzed our prospectively collected data to identify possible predictive factors for post-operative acute and chronic pain. MATERIALS AND METHODS: We prospectively collected the demographic data and peri-operative findings. Post-operative acute pain was evaluated with Visual Analog Pain Scale. The chronic pain (pain persists for > 6 months since operation) was also recorded. RESULTS: From June 2008 to August 2018, there were 807 patients with 1029 sites of inguinal hernia enrolled in our analysis. Pain before operation was associated with the severity of acute pain on OP (operation) day, POD 1 (post-operative day 1), and POD 7 (post-operative day 7). Younger patients had significantly higher post-operative acute pain on OP day, POD 1, and POD 7. The staple mesh fixation method resulted in a higher pain score at OP day and POD 1. The predictive factors for chronic pain were sex (female), young age (< 65 years), having no past history of hypertension, pain before operation, and mesh material. CONCLUSION: A younger age and inguinal pain before operation were the main predictive factors for higher post-operative pain. Younger patients, females, having inguinal pain before surgery, and using heavy weight mesh have a higher risk of chronic pain.

Factors Predicting Oncological Outcomes of Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma in Taiwan.

BACKGROUND: Taiwan is one of the endemic regions where upper tract urothelial carcinoma (UTUC) accounts for approximately a third of all urothelial tumors. Owing to its high prevalence, extensive experience has been accumulated in minimally invasive radical nephroureterectomy (RNU). Although a variety of predictive factors have been explored in numerous studies, most of them were on a single-center or limited institutional basis and data from a domestic cohort are lacking. OBJECTIVE: This study aims to identify significant predicting factors of oncological outcomes, including overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and intravesical recurrence-free survival (IVRFS), following RNU for UTUC in Taiwan. METHODS: A multicenter registry database, Taiwan UTUC Collaboration Group, was utilized to analyze oncological outcomes of 3,333 patients undergoing RNU from 1988 to 2021 among various hospitals in Taiwan. Clinicopathological parameters were recorded according to the principles established by consensus meetings. The Kaplan-Meier estimator was utilized to estimate the survival rates, and the curves were compared using the stratified log-rank test. Univariate and multivariate analyses were performed with the Cox proportional hazard model to explore potential predicting factors. RESULTS: With a median follow-up of 41.8 months in 1,808 patients with complete information, the 5-year IVRFS, DFS, CSS, and OS probabilities were 66%, 72%, 81%, and 70%, respectively. In total, 482 patients experienced intravesical recurrence, 307 died of UTUC, and 583 died of any cause. Gender predominance was female (57%). A total of 1,531 patients (84.7%) had high-grade tumors; preoperative hydronephrosis presented in 1,094 patients (60.5%). Synchronous bladder UC was identified in 292 patients (16.2%). Minimally invasive procedures accounted for 78.8% of all surgeries, including 768 hand-assisted laparoscopic (42.5%) and 494 laparoscopic (27.3%) approaches. Synchronous bladder UC was the dominant adverse predicting factor for all survival outcomes. Other independent predicting factors for OS, CSS, and DFS included age ≧70, presence of preoperative hydronephrosis, positive surgical margin, LVI, pathological T and N staging, and laparoscopic RNU. CONCLUSION: Synchronous UC of the urinary bladder is an independent adverse prognostic factor for survival in UTUC. The presence of preoperative hydronephrosis was also corroborated as a disadvantageous prognostic factor. Our multivariate analysis suggested that laparoscopic RNU might provide better oncological control.

Novel robot-assisted laparoscopic total extra-peritoneal repair with primary fascial closure plus pre-peritonea mesh for large groin defects.

BACKGROUND: Since the introduction of robot-assisted laparoscopic surgery, a variety of conventional laparoscopic procedures have been explored via this approach. In the robotic era, most of the reported robot-assisted laparoscopic hernia repairs were performed with the trans-abdominal pre-peritoneal approach. According to the evidence extrapolated from laparoscopic ventral hernia repair, simultaneous fascial defect closure and mesh repair can significantly decrease the risk of seroma formation and recurrence over those without fascial closure. Therefore, we describe our novel technique of robot-assisted total extra-peritoneal (TEP) repair with primary fascial closure and pre-peritoneal mesh and its preliminary clinical outcomes. METHODS: We retrospectively reviewed our prospectively collected hernia database from October 2017 to July 2019, which included 26 consecutive patients with primary or recurrent groin hernias. Patients' baseline characteristics and perioperative outcomes were compared and analyzed. Perioperative factors included operative time, visual analog scale (VAS) score (0-100), hospital stay, perioperative complications, time to return to normal activity, and the modified Medical Outcome Study (MOS; item 3-12/36 items) score. RESULTS: All procedures were completed successfully without conversion to open or conventional laparoscopic surgery. The patients' age ranged from 28 to 74 years (median 57.5). The mean operative time was 115 minutes (range 95-172 min). There were no major procedure-related complications. Only four cases experienced asymptomatic seromas, which were detected by ultrasonography; and all resolved spontaneously within 6 weeks after the operation. The VAS and modified MOSs revealed quick recovery after robot-assisted endoscopic TEP repair. CONCLUSIONS: Robot-assisted endoscopic TEP repair combined with primary fascial closure and pre-peritoneal mesh is a safe and feasible technique for groin hernia repair.