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Hau-Chern Jan,1,2 Kuan-Yu Wu,1 Ta-Yao Tai,1 Han-Yu Weng,1 Wen-Horng Yang,1,3 Chien-Hui Ou,1,3 Che-Yuan Hu1,4 1Department of Urology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 704, Taiwan; 2Division of Urology, Department of Surgery, National Cheng Kung University Hospital Dou-Liou Branch, Yunlin, 640, Taiwan; 3Department of Urology, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan; 4Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, 701, TaiwanCorrespondence: Che-Yuan Hu; Chien-Hui Ou, Department of Urology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, No. 138, Sheng-Li Road, Tainan, 70403, Taiwan, Tel +886-6-235-3535, Fax +886-6-238-3678, Email greatoldhu@gmail.com; donou1969@yahoo.com.twPurpose: Lymphovascular invasion (LVI) and systemic immune-inflammation index (SII) both have been proved to correlate with oncologic outcomes in upper tract urothelial carcinoma (UTUC). We hypothesize that integrating SII with LVI may be an aid for risk-stratification of prognosis. This study aimed to evaluate the prognostic significance of combined SII and LVI in patients with localized UTUC.Patients and Methods: A retrospective analysis of clinicopathological data of 554 UTUC patients who underwent radical nephroureterectomy (RNU) was conducted. The SII was calculated using the equation (preoperative serum neutrophil&ast;platelet/lymphocyte). Use of Kaplan–Meier analyses and Cox proportional hazards models were to evaluate associations of combining SII and LVI with overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS). Furthermore, receiver operating characteristic (ROC) analysis was applied to estimate predictive ability of combining SII and LVI for oncological outcomes.Results: Positive LVI was significantly associated with advanced stage, high grade, necrosis, lymph node metastasis, and high-level SII. Positive LVI and high-level SII co-existence was significantly associated with unfavorable OS, CSS, and PFS in Kaplan-Meier analyses (all p < 0.001) and was an independent indicator of OS, CSS, and PFS (HR [95% CI]: 3.918 [2.168– 7.078], 5.623 [2.679– 11.801], 3.377 [2.138– 5.334]), respectively) in multivariate analyses. Furthermore, adding LVI and SII to a model that included standard pathologic predictors exhibited a better ability to predict survival in ROC analysis.Conclusion: The integration of SII and LVI was demonstrated to be a potential factor of poor outcomes in patients with localized UTUC. Notably, the combined use of LVI and SII can be a feasible and complementary factor to TNM staging in the prognostic assessment of UTUC patients in clinical practice. The validity of combination of the two markers would be considered in future prospective studies to evaluate its usefulness in staging and application of post-operative chemo or immunotherapy.Keywords: upper tract urothelial carcinoma, lymphovascular invasion, systemic immune-inflammation index, survival

Background The benefit of adjuvant chemotherapy was investigated for patients with T3 upper urinary tract urothelial carcinoma (UTUC) who underwent radical nephroureterectomy. Methods This is a multicenter retrospective observational study of 482 patients with pathological T3 N0 and Nx UTUC who underwent radical nephroureterectomy with and without adjuvant chemotherapy. The median overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS) of patients who received adjuvant chemotherapy were analyzed to determine predictors of patient prognosis. Results Of the 482 patients, 140 (29.0%) received adjuvant chemotherapy. Adjuvant chemotherapy showed a benefit only for the median DFS rate (58% vs 49%; p = 0.04). Multivariate analyses revealed that adjuvant chemotherapy improved median DFS (HR 0.537; CI 0.35–0.83; p = 0.005). Surgical margin also significantly influenced median OS (HR 4.038; p

Background This study aims to analyze the fertility preservation decision-making and the sperm retrieval rate (SRR) in older adolescents (age 15-19 years) with non-mosaic Klinefelter syndrome (KS) and azoospermia in a male reproductive clinic, and to determine the accumulated SRR in older adolescents by literature review. Methods Older adolescents with non-mosaic KS and azoospermia referred for hypogonadism and fertility concerns were enrolled. Reproductive counseling and fertility preservation options were offered to patients/parents. The acceptability and the reasons affecting the reproductive decision-making were analyzed. Patients/parents who agreed on fertility preservation received microdissection testicular sperm extraction (mTESE) and cryopreservation. A comprehensive literature review regarding the SRRs in older adolescents with KS was conducted. Results A total of eight older adolescents were enrolled. After fertility preservation counseling, three patients/parents (37.5%) agreed to receive mTESE, and spermatozoa were successfully retrieved in two. "Lack of interest" and "inconsistent sperm retrieval result" were the main reasons for refusal. A total of 89 older adolescents from nine articles, and ours were collected for SRR analysis. Most of the reports had a limited number of cases, and none of them described the acceptance rate of sperm retrieval in adolescents. Forty-three out of 89 older adolescents (48.3%) had successful sperm retrieval, and there was no significant difference in the SRR between the mTESE and conventional TESE. Conclusion Successful testicular sperm retrieval in older adolescents with KS is not superior to those reported in adults. Adolescents and their parents should undergo a detailed reproductive consultation process and shared decision-making discussion before considering testicular sperm retrieval.

The present study aimed to evaluate the influence of pre-treatment neutrophil-to-lymphocyte ratio (NLR) on bladder recurrence in patients with impaired renal function following radical nephrouretectomy (RNU) to treat pure upper tract urothelial carcinoma (UTUC). Retrospective data of 362 patients with pure UTUC who underwent RNU between 2008 and 2019 were analyzed. Kaplan-Meier analyses were performed to evaluate the association of preoperative NLR and estimation of the glomerular filtration rate (eGFR) with intravesical recurrence-free survival (IVRF). Furthermore, multivariate analyses were conducted to determine independent factors for predicting IVRF. In the retrospective cohort study of 362 patients, 103 patients (28%) had intravesical recurrence in a median follow-up of 50.1 months; among those, 85 (83%) developed bladder recurrence within two years after RNU. The Kaplan-Meier analysis indicated that patients exhibiting lower eGFR and higher NLR showed significantly poor IVRF rates (P=0.044). The simultaneous presence of eGFR45 and NLR3.8 was an independent factor for the shorter IVRF time in multivariate analysis with Cox's proportional hazards model. Most intravesical recurrences occurred within two years after RNU, particularly in pre-existing poor eGFR patients with preoperative high NLR. Moreover, pre-existing moderate to severe CKD synchronous with pre-operative NLR3.8 was demonstrated as an independent factor for subsequent bladder recurrence in patients with pure UTUC following RNU. Therefore, such high-risk patients ought to be provided with close bladder monitoring during the follow-up.

To maximize the chance of maintaining peritoneal dialysis (PD) after retroperitoneoscopic nephroureterectomy without interruption in PD-dependent patients who were suspected as having upper tract urothelial carcinoma (UTUC). During 2005–2018 at our hospital, 10 PD-dependent patients who were suspected as having UTUC underwent hand-assisted retroperitoneoscopic nephroureterectomy (HARN) and bladder cuff resection by a single surgeon. The medical record and post-operative outcomes were retrospectively analyzed. Our surgical tips aiming at staying on PD including keeping adequate but relatively lower insufflation pressure during the operation, reducing the negative pressure of the drain tube post-operatively and initiating PD at a low volume with gradual titration, were also presented in the article. A total of ten patients were enrolled in our study. The first five patients failed to resume PD and need interim hemodialysis due to various reasons. After some technique modifications, all the following five patients have PD reinstitution immediately after the operation without increasing the incidence of post-operative complications. Staying on PD wound be beneficial for those ESRD patients who underwent retroperitoneoscopic nephroureterectomy due to UTUC, mainly to avoid hemodynamic interference and possible complications related to hemodialysis during the peri-operative period. However, it remains challenging for surgeons. We concluded the key points to minimize peritoneal violation. By adherence to our tips, retroperitoneoscopic nephroureterectomy should be strongly considered in PD patients with suspicious UTUC if feasible.

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.

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.

Tumor multifocality and location are prognostic factors for upper tract urothelial carcinoma (UTUC). However, confounding effects can appear when these two factors are analyzed together. Therefore, we aimed to investigate the impact of tumor distribution on the outcomes of multifocal UTUC after radical nephroureterectomy. From the 2780 UTUC patients in the Taiwan UTUC Collaboration Group, 685 UTUC cases with multifocal tumors (defined as more than one tumor lesion in unilateral upper urinary tract) were retrospectively included and divided into three groups: multiple renal pelvic tumors, multiple ureteral tumors, and synchronous renal pelvic and ureteral tumors included 164, 152, and 369 patients, respectively. We found the prevalence of carcinoma in situ was the highest in the synchronous group. In multivariate survival analyses, tumor distribution showed no difference in cancer-specific and disease-free survival, but there was a significant difference in bladder recurrence-free survival. The synchronous group had the highest bladder recurrence rate. In summary, tumor distribution did not influence the cancer-specific outcomes of multifocal UTUC, but synchronous lesions led to a higher rate of bladder recurrence than multiple renal pelvic tumors. We believe that the distribution of tumors reflects the degree of malignant involvement within the urinary tract, but has little significance for survival or disease progression.

We sought to examine the effect of tumor location on the prognosis of patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). This retrospective study came from the Taiwan UTUC Collaboration Group, which consisted of 2658 patients at 15 institutions in Taiwan from 1988 to 2019. Patients with kidney-sparing management, both renal pelvic and ureteral tumors, as well as patients lacking complete data were excluded, the remaining 1436 patients were divided into two groups: renal pelvic tumor (RPT) and ureteral tumor (UT), with 842 and 594 patients, respectively. RPT was associated with more aggressive pathological features, including higher pathological T stage (p &lt, 0.001) and the presence of lymphovascular invasion (p = 0.002), whereas patients with UT often had synchronous bladder tumor (p &lt, 0.001), and were more likely to bear multiple lesions (p = 0.001). Our multivariate analysis revealed that UT was a worse prognostic factor compared with RPT (overall survival: HR 1.408, 95% CI 1.121&ndash, 1.767, p = 0.003, cancer-specific survival: HR 1.562, 95% CI 1.169&ndash, 2.085, p = 0.003, disease-free survival: HR 1.363, 95% CI 1.095&ndash, 1.697, p = 0.006, bladder-recurrence-free survival: HR 1.411, 95% CI 1.141&ndash, 1.747, p = 0.002, respectively). Based on our findings, UT appeared to be more malignant and had a worse prognosis than RPT.

Background Intracranial atherosclerosis (ICAS) is a common etiology of ischemic stroke in Chinese patients, probably leading to regional hypoperfusion in the brain. The purpose of this prospective study was to investigate the association between ICAS and poststroke depression in Chinese patients with ischemic stroke. Methods During the study period, a total of 569 patients aged between 40 and 80 years with acute ischemic stroke were consecutively admitted and screened. Patients with a National Institutes of Health Stroke Scale (NIHSS) total score of 15 or higher, with severe cognitive impairment, or with a history of depression before stroke were excluded. Two hundred seven patients with ischemic stroke were consecutively recruited in the study. Depressive symptoms were assessed in the acute stage and 3 months after stroke. Poststroke depression was defined as a score of 8 or higher in the 24-item Hamilton Depression Rating Scale. The evaluation of the magnetic resonance imaging scans focused on infarctions, white matter lesions, brain atrophy, and ICAS. Results In the acute stage of stroke, logistic regression revealed that female sex, NIHSS score at admission, prestroke insomnia, and ICAS were significant predictors of poststroke depression. At 3 months after stroke, prestroke insomnia, the Mini-Mental State Examination score and ICAS were significant predictors of poststroke depression. Conclusions ICAS may be a significant independent predictor of poststroke depression in Chinese patients with ischemic stroke.

Background: Anxiety is prevalent after a stroke. The pathophysiological mechanisms underlying the development of poststroke anxiety (PSA) remain unclear. The aim of this study was to investigate the clinical and neuroimaging risk factors for development of PSA and examine the effects of PSA on activities of daily living (ADL) and quality of life (QOL) in Chinese patients with ischemic stroke.Methods: Two hundred nineteen patients with acute ischemic stroke were recruited to the study. A series of comprehensive assessments, including Hamilton Anxiety Rating Scale (HARS), Hamilton Depression Rating Scale (HDRS), Lawton ADL Scale, and the Stroke-Specific Quality of Life (SSQOL) Scale, were conducted in the acute stage and 3 months after stroke. Magnetic resonance imaging assessment focused on evaluation of infarctions, white matter lesions, and brain atrophy.Results: In the acute stage and 3 months after stroke, 34 (16%) and 33 (15%) patients had PSA, respectively. Multiple logistic regression analysis indicated that HDRS (OR = 1.269, 95% CI = 1.182–1.364, P < 0.001) and acute infarcts in cerebral hemispheric white matter (CHWM; OR = 2.902, 95% CI = 1.052–8.007, P = 0.040) were significant correlates of PSA in the acute stage of stroke. Three months after stroke, these correlates remained significant predictors, along with male sex. Multiple linear regressions showed that age, NIHSS, HARS, and HDRS in the acute stage were significant predictors for both ADL and SSQOL at 3 months after stroke.Conclusion: Depressive symptoms are the major correlates of PSA while more severe PSA is associated with poorer ADL and health-related QOL. Acute lesions involving CHWM may correlate with PSA in ischemic stroke patients with mild-to-moderate neurologic deficits, supporting a lesion-location hypothesis in PSA.

Background Fatigue is a common problem in ischemic stroke survivors. The mechanisms of poststroke fatigue are uncertain yet. The effects of it on functional status have rarely been studied. Aims The aim of this study was to investigate the risk factors of poststroke fatigue and its effect on activities of daily living and health-related quality of life in Chinese patients with ischemic stroke. Methods Two hundred and eighteen patients with ischemic stroke formed the study sample. A comprehensive assessment, including the Fatigue Severity Scale, Hamilton Depression Rating Scale, Lawton activities of daily living scale, and the stroke-specific quality of life scale, was conducted three-months after stroke. Magnetic resonance imaging scans focused on the evaluation of infarctions, white matter lesions, and brain atrophy. Results In the whole sample, with Fatigue Severity Scale as the dependent variable in a linear regression model, Hamilton Depression Rating Scale, prestroke fatigue, and the National Institutes of Health Stroke Scale score at admission were significant correlates of Fatigue Severity Scale, accounting for 36% of the variance of it. When subjects with depression (Hamilton Depression Rating Scale ≥ 20 or current usage of antidepressants) were excluded, only Hamilton Depression Rating Scale and prestroke fatigue remained significant correlates of Fatigue Severity Scale, accounting for 33% of the variance of Fatigue Severity Scale. No magnetic resonance imaging variables correlated with Fatigue Severity Scale. In bivariate correlation analyses, Fatigue Severity Scale was significantly correlated with both activities of daily living and stroke-specific quality of life. In linear regression models, Fatigue Severity Scale independently contributed to activities of daily living accounting for 27% of the variance. Fatigue Severity Scale was also a significant contributor to stroke-specific quality of life accounting for 39% of the variance. Conclusion Depressive symptoms and prestroke fatigue are major correlates of poststroke fatigue while more severe post-stroke fatigue is associated with poorer activities of daily living and health-related quality of life.

Objectives The aim of the present study was to explore the magnetic resonance imaging correlates of the performance of instrumental activities of daily living (IADL) in patients with Alzheimer's disease combined with cerebrovascular disease. Methods A total of 66 patients with Alzheimer's disease combined with cerebrovascular disease formed the study sample. Two regression models were constructed to find correlates of IADL. Model 1 only included clinical variables and model 2 included both clinical and magnetic resonance imaging variables. Results In model 1, with IADL as the dependent variable, the Mini-Mental State Examination (MMSE) score, Physical Self-Maintenance Scale score at baseline and age were significant correlates accounting for 40.1% of the variance of IADL at baseline. MMSE score and age were also significant correlates of IADL at 6 months, accounting for 38.1% of the variance of it. In model 2, severity of white matter lesions, MMSE and Physical Self-Maintenance Scale scores at baseline significantly correlated with IADL at baseline, accounting for 52.1% of the variance of the dependent variables; severity of white matter lesions and MMSE significantly correlated with IADL at 6 months, accounting for 41.5% of the variance of the dependent variables. Conclusion In patients with Alzheimer's disease combined with cerebrovascular disease, subcortical ischemic lesions might be significant contributor to the functional status. Geriatr Gerontol Int 2015; 15: 588–593.

The aim of the present study was to explore the magnetic resonance imaging correlates of the performance of instrumental activities of daily living (IADL) in patients with Alzheimer's disease combined with cerebrovascular disease.A total of 66 patients with Alzheimer's disease combined with cerebrovascular disease formed the study sample. Two regression models were constructed to find correlates of IADL. Model 1 only included clinical variables and model 2 included both clinical and magnetic resonance imaging variables.In model 1, with IADL as the dependent variable, the Mini-Mental State Examination (MMSE) score, Physical Self-Maintenance Scale score at baseline and age were significant correlates accounting for 40.1% of the variance of IADL at baseline. MMSE score and age were also significant correlates of IADL at 6 months, accounting for 38.1% of the variance of it. In model 2, severity of white matter lesions, MMSE and Physical Self-Maintenance Scale scores at baseline significantly correlated with IADL at baseline, accounting for 52.1% of the variance of the dependent variables; severity of white matter lesions and MMSE significantly correlated with IADL at 6 months, accounting for 41.5% of the variance of the dependent variables.In patients with Alzheimer's disease combined with cerebrovascular disease, subcortical ischemic lesions might be significant contributor to the functional status.