Impact of liminality and rituals on professional identity formation in physician training.

PURPOSE: The transition from medical student to practicing physician affects the complex processes of professional identity formation and professionalism, which have a lasting effect on the physician's career development. This study explored two different transitional processes of medical students in Taiwan, the associated rituals during this transitional period (the 'liminal phase') and their effect on the formation of professional identity. METHOD: Using snowball sampling, we recruited 13 medical students from two training systems: six from the traditional postgraduate year programme and seven from the accelerated postgraduate year (A-PGY) programme. Semi-structured interviews were thematically analysed to identify significant themes that encapsulated trainees' experiences. A consistent and mutually confirmed discussion ensured the identification of robust recurring themes. RESULTS: A comparative analysis of the two training modalities provided critical insights into the relative impact of the training dynamics. The A-PGY cohort, subjected to an altered 'incorporation' ritual, encountered an influx of unexpected symbolic social power, complicating their transformation within the liminal phase. Without a defined internship like in the PGY system, A-PGY trainees exhibited confusion and inconsistencies in professional identity formation marked by conflicting internal and external perceptions. This ambiguity affected their clinical training, social integration and overall development of professionalism. The absence of a structured, sequential liminal phase increased conflict and diminished motivation, culminating in an incomplete self-crafting journey for A-PGY trainees. CONCLUSIONS: This study highlights the impact of the well-sequenced implementation of rituals in liminality on professional identity formation. A good transition training programme for medical students should compass sequential rituals in the liminal phase, including clear starting and ending points, supervision by seniors, guided reflection and plenty of opportunities for observation and imitation in context. Optimal training and pivotal elements in a medical training system warrant delicate design and further research when developing and changing the structure of the training programme.

Prostate health index density aids the diagnosis of prostate cancer detected using magnetic resonance imaging targeted prostate biopsy in Taiwanese multicenter study.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) followed by MRI-targeted prostate biopsy is the current standard for diagnosing prostate cancer (PCa). However, studies evaluating the value of biomarkers, including prostate health index (PHI) and its derivatives using this method are limited. We aimed to investigate the efficacy of PHI density (PHID) in guiding MRI-targeted prostate biopsies to identify clinically significant PCas (csPCa). METHODS: The multicenter prospectively registered prostate biopsy database from three medical centers in Taiwan included patients with PHI and MRI-targeted and/or systematic prostate biopsies. We assessed the required values of prostate-specific antigen (PSA), prostate volume, PHI, PHID, and Prostate Imaging Reporting & Data System (PI-RADS) score using multivariable analyses, receiver operating characteristic curve analysis, and decision curve analyses (DCA). csPCa was defined as the International Society of Urological Pathology Gleason group ≥2 PCa, with an emphasis on reducing unwarranted biopsies. RESULTS: The study cohort comprised 420 individuals. Diagnoses of PCa and csPCa were confirmed in 62.4% and 47.9% of the participants, respectively. The csPCa diagnosis rates were increased with increasing PI-RADS scores (20.5%, 44.2%, and 73.1% for scores 3, 4, and 5, respectively). Independent predictors for csPCa detection included PHI, prostate volume, and PI-RADS scores of 4 and 5 in multivariable analyses. The area under the curve (AUC) for csPCa of PHID (0.815) or PHI (0.788) was superior to that of PSA density (0.746) and PSA (0.635) in the entire cohort, and the superiority of PHID (0.758) was observed in PI-RADS 3 lesions. DCA revealed that PHID achieved the best net clinical benefit in PI-RADS 3-5 and 4/5 cases. Among PI-RADS 3 lesions, cutoff values of PHID 0.70 and 0.43 could eliminate 51.8% and 30.4% of omitted biopsies, respectively. CONCLUSION: PHI-derived biomarkers, including PHID, performed better than other PSA-derived biomarkers in diagnosing PCa in MRI-detected lesions.

α-α Coupling-Dominated PPy Film with a Well-Conjugated Structure for Superlong Cycle Life Supercapacitors.

As the electrode of a supercapacitor, polypyrrole (PPy) inevitably suffers from structural rupture during repeated doping/dedoping processes and releases low practical capacitance due to the large amount of aggregation or cross-linking in PPy chains. The coupling mode (α-α, α-ß, or ß-ß coupling) of pyrroles is critical to the conjugated structure, the conductivity, and cycling stability of PPy. Here, we prepared an α-α coupling-dominated PPy film via simple frozen interfacial polymerization. The PPy film with a nanostructure exposes more electrochemical active sites for the electrode, which can enhance the practical capacitance. The high proportion of the α-α coupling mode results in a high degree of large π-conjugation and a planar structure that can effectively improve the reversible ion transport efficiency and promote uniform stress distribution during the charge and discharge process. The assembled symmetric water-based supercapacitor delivers a high specific capacitance of 267.1 F g-1 at 1 A g-1 and 266.7 F g-1 at 5 A g-1 and exhibits an outstanding cycling performance of above 200 F g-1 even after 60,000 cycles.

Prognostic factors of intravesical recurrence after radical nephroureterectomy for upper tract urothelial carcinoma.

PURPOSE: To evaluate predictive factors of increasing intravesical recurrence (IVR) rate in patients with upper tract urothelial carcinoma (UTUC) after receiving radical nephroureterectomy (RNUx) with bladder cuff excision (BCE). MATERIALS AND METHODS: A total of 2114 patients were included from the updated data of the Taiwan UTUC Collaboration Group. It was divided into two groups: IVR-free and IVR after RNUx, with 1527 and 587 patients, respectively. To determine the factors affecting IVR, TNM stage, the usage of pre-operative ureteroscopy, and pathological outcomes were evaluated. The Kaplan-Meier estimator was used to estimate the rates of prognostic outcomes in overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and bladder recurrence-free survival (BRFS), and the survival curves were compared using the stratified log-rank test. RESULTS: Based on our research, ureter tumor, female, smoking history, age (< 70 years old), multifocal tumor, history of bladder cancer were determined to increase the risk of IVR after univariate analysis. The multivariable analysis revealed that female (BRFS for male: HR 0.566, 95% CI 0.469-0.681, p < 0.001), ureter tumor (BRFS: HR 1.359, 95% CI 1.133-1.631, p = 0.001), multifocal (BRFS: HR 1.200, 95% CI 1.001-1.439, p = 0.049), history of bladder cancer (BRFS: HR 1.480, 95% CI 1.118-1.959, p = 0.006) were the prognostic factors for IVR. Patients who ever received ureterorenoscopy (URS) did not increase the risk of IVR. CONCLUSION: Patients with ureter tumor and previous bladder UC history are important factors to increase the risk of IVR after RNUx. Pre-operative URS manipulation is not associated with higher risk of IVR and diagnostic URS is feasible especially for insufficient information of image study. More frequent surveillance regimen may be needed for these patients.

Active Surveillance for Taiwanese Men with Localized Prostate Cancer: Intermediate-Term Outcomes and Predictive Factors.

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 <50%: HR 1.41, 95% CI 0.91-2.18; ≥50%: HR 1.97, 95% CI 1.1453-3.40) compared with that of <15%. A Gleason grade group (GGG) of 3 tumor also predicted conversion (HR 2.69, 95% CI 1.06-6.79; GGG 3 vs 1). One patient developed metastasis, but none died of PC during the study period (2,141 person-years). CONCLUSIONS: AS is a viable option for Taiwanese men with non-high-risk PC, in terms of reclassification and conversion. High PSAD predicted reclassification, whereas high PSAD, MPCPC, and GGG predicted conversion.

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.

NKG2A and circulating extracellular vesicles are key regulators of natural killer cell activity in prostate cancer after prostatectomy.

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.

Proliferative ability of circulating tumor cells is a prognostic factor in Early-Stage lung adenocarcinoma.

INTRODUCTION: Circulating tumor cells (CTCs) and their proliferative ability in lung adenocarcinoma (LUAD) were not well-investigated. We developed a protocol combining an efficient viable CTC isolation and in-vitro cultivation for the CTC enumeration and proliferation to evaluate their clinical significance. METHOD: The peripheral blood of 124 treatment-naïve LUAD patients were processed by a CTC isolation microfluidics, DS platform, followed by in-vitro cultivation. LUAD-specific CTCs were defined by immunostaining of DAPI+/CD45-/(TTF1/CK7)+ and were enumerated upon isolation and after 7-day cultivation. The CTC proliferative ability was evaluated by both the cultured number and the culture index, a ratio of cultured CTC number to the initial CTC number in 2 mL of blood. RESULT: All but two LUAD patients (98.4%) were detected with at least one CTC per 2 mL of blood. Initial CTC numbers did not correlate with metastasis (75 ± 126 for non-metastatic, 87 ± 113 for metastatic groups; P = 0.203). In contrast, both the cultured CTC number (mean: 28, 104, and 185 in stage 0/I, II/III, and IV; P < 0.001), and the culture index (mean: 1.1, 1.7 and 9.3 in stage 0/I, II/III, and IV; P = 0.043) were significantly correlated with the stages. Overall survival analysis within the non-metastatic group (N = 53) showed poor prognosis for patients with elevated cultured counts (cutoff ≥ 30; P = 0.027). CONCLUSION: We implemented a CTC assay in clinical LUAD patients with a high detection rate and cultivation capability. Cultured CTC count and proliferative ability, rather than the crude CTC numbers, highly associated with cancer prognosis.

Cardiovascular risk of gonadotropin-releasing hormone antagonist versus agonist in men with prostate cancer: an observational study in Taiwan.

BACKGROUND: The impact of gonadotropin-releasing hormone (GnRH) antagonist and agonist (GnRHa) treatment on cardiovascular disease (CVD) risk in prostate cancer (PCa) remains inconclusive due to conflicting findings. We compared the effects of GnRH antagonist and GnRHa treatments on CVD risk in patients with PCa and pre-existing CVD, in a Taiwan population-based database. METHODS: We assessed the risk of major adverse CV events (MACE: ischemic heart disease [IHD], stroke, congestive heart failure [CHF] or all cause deaths) and composite CV events (IHD, stroke, CHF or CV deaths) occurring ≥90 days after androgen deprivation therapy (ADT) initiation in patients with PCa after 90 days of treatment with either GnRH antagonist (degarelix; n = 499) or GnRHa (goserelin, leuprolide, triptorelin; n = 15,127). Patients identified with pre-existing CVD had received cardiac therapy for IHD, reported a stroke or CHF within a year before ADT initiation. Adjusted hazard ratios (aHR) and 95% confidence interval (CI) were obtained for MACE and composite CV events risk after adjusting for age, baseline status of diabetes, hypertension and treatments received. RESULTS: All GnRH antagonist-treated patients showed lower risk of composite CV events than the GnRHa-treated patients. The lower composite CV events risk associated with GnRH antagonist was also observed in patients with metastasis at diagnosis (aHR 0.16; 95% CI, 0.04-0.38; p = 0.013) and those receiving ADT for more than six months (aHR 0.30; 95% CI, 0.16-0.54; p < 0.0001). In patients with pre-existing CVD, the MACE risk was 33% lower (aHR 0.67; 95% CI, 0.46-0.96; p = 0.0299) and composite CV events risk was 84% lower (aHR 0.16; 95% CI, 0.05-0.50; p = 0.0017) in GnRH antagonist-treated than the GnRHa-treated patients. CONCLUSIONS: In patients with PCa and pre-existing CVD, GnRH antagonist use was associated with lower risks for composite CV events and MACE compared with GnRHa.

Clinical Implications of Nadir Serum Prostate-Specific Antigen Levels After Transurethral Enucleation of the Prostate.

Objective: Prostate-specific antigen levels after transurethral enucleation of the prostate may serve as indicators of residual cancer foci. The objective of this study was to investigate the association between the post-transurethral enucleation of the prostate nadir prostate-specific antigen level and prostate cancer. Materials and Methods: We retrospectively reviewed the data of 428 men who underwent transurethral enucleation of the prostate between March 2015 and April 2021. Based on the following exclusion criteria, we excluded 106 men from our analysis: men with metastatic prostate cancer, incomplete transurethral enucleation of the prostate, and missing prostate-specific antigen or prostate size data. Three hundred and twenty-two patients were finally enrolled in our study. These patients were classified into four groups according to the surgical pathology: benign, transition zone (cancer only in the adenoma or transition zone), peripheral zone, and transition and peripheral zones. The optimal cutoff post-transurethral enucleation of the prostate nadir prostate-specific antigen level that predicted residual prostate cancer was determined using receiver operating characteristic curve analysis. Results: In total, 71 (22.0%) men exhibited prostate cancer (median follow-up, 38.0 months). The benign and combined cancer groups showed similar adenoma removal rates (103.0% and 106.7%, respectively). The median nadir prostate-specific antigen levels after transurethral enucleation of the prostate were 0.76, 0.63, 1.79, and 1.70 ng/ml in the benign, transition zone, peripheral zone, and transition and peripheral zone groups, respectively (p < 0.001), with no difference between the benign and transition zone groups (p = 0.458); this suggested that complete transurethral enucleation of the prostate removed all cancer nests in the adenoma in the transition zone group. Receiver operating characteristic curve analysis showed that nadir prostate-specific antigen ≧1.7 ng/ml predicted residual cancer (area under the curve: 0.787) or cancer with a Gleason score of ≧7 (area under the curve: 0.816) in the remaining prostate. Limitations include the retrospective design and the perioperative peripheral zone biopsy rate. Conclusions: The post-transurethral enucleation of the prostate nadir prostate-specific antigen ≧1.7 ng/ml after complete transurethral enucleation of the prostate can predict significant residual cancer. Prostate cancer patients with low post-transurethral enucleation of the prostate prostate-specific antigen levels can be conservatively managed.

LMNB1, a potential marker for early prostate cancer progression.

Although prostate cancer (PC) is the most common cancer among men in the Western world, there are no good biomarkers that can reliably differentiate between potentially aggressive and indolent PC. This leads to overtreatment, even for patients who can be managed conservatively. Previous studies have suggested that nuclear lamin proteins-especially lamin B1 (LMNB1)-play important roles in PC progression. However, the results of these studies are inconsistent. Here, we transfected the LMNB1 gene into the telomerase reverse transcriptase-immortalized benign prostatic epithelial cell line, EP156T to generate a LMNB1-overexpressing EP156T (LMN-EP156T) cell line with increased cellular proliferation. However, LMN-EP156T cells could neither form colonies in soft agar, nor establish subcutaneous growth or metastasis in the xenograft NOD/SCID mouse model. In addition, immunohistochemical staining of LMNB1 in PC specimens from 143 patients showed a statistically significant trend of stronger LMNB1 staining with higher Gleason scores. A univariate analysis of the clinicopathological parameters of 85 patients with PC who underwent radical prostatectomy revealed that pathological stage, resection margin, and extracapsular extension were significant predictors for biochemical recurrence (BCR). However, LMNB1 staining showed only a non-significant trend of association with BCR (high vs. low staining: hazard ratio (HR), 1.83; 95% confidence interval (CI), 0.98-3.41; P = 0.059). In multivariate analysis, only pathological stage was a significant independent predictor of BCR (pT3 vs. pT2: HR, 2.29; 95% CI, 1.18-4.43; P = 0.014). In summary, LMNB1 may play a role in the early steps of PC progression, and additional molecular alterations may be needed to confer full malignancy potential to initiated cells.

Propensity score matching analysis comparing radical prostatectomy and radiotherapy with androgen deprivation therapy in locally advanced prostate cancer.

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 < 0.001). After propensity score-matching, there were 68 patients in each group. Among locally advanced PC patients, treatment with RP had a higher risk of biochemical recurrence compared to the RT group. In multivariate Cox regression analysis, treatment with RT plus ADT significantly decreased the risk of biochemical failure (HR 0.162, p < 0.001), but there was no significant difference in local recurrence, distant metastasis and overall survival (p = 0.470, p = 0.268 and p = 0.509, respectively). This information supported a clinical benefit in BCR control for patients undergoing RT plus long-term ADT compared to RP.

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.

Protective Effects of Curcumin-Regulated Intestinal Epithelial Autophagy on Inflammatory Bowel Disease in Mice.

Objective: This study was aimed at exploring the ameliorating effect of curcumin (Cur) on inflammatory bowel disease (IBD) in mice induced by 3% dextran sodium sulfate (DSS) by regulating intestinal epithelial cell autophagy. Methods: 45 BALB/c mice were randomly divided into three groups: control group, DSS group, and Cur group, with 15 mice in each group. Expect for the control group, 3% DSS was freely drunk by the mice for 7 days to induce acute IBD, and the Cur group was given Cur gavage treatment. Hematoxylin-Eosin (HE) staining was performed to observe the pathological changes of mice colon tissue. The formation of autophagosomes in intestinal epithelial cells was detected by transmission electron microscopy (TEM). The protein expressions of LC3-II/LC3-I, p62, and Beclin1 were detected by Western blot. Results: Compared with that of the control group, body weight of mice in DSS group was significantly reduced, stool was not formed or presented with loose stools, there was occult blood or blood in the stool, hair color lost luster, disease activity index (DAI) score was significantly increased, and colonic mucosal epithelial cells showed colitis; LC3-II/LC3-I and Beclin1 expression were significantly decreased (P < 0.05), p62 was significantly increased, and autophagy was not obvious. In addition, compared with that of the DSS group, the diet of mice in the Cur group was improved, the decline of body weight was slowed down, the hair glossiness was restored, the blood in the stool gradually decreased or occulted, the DAI score was decreased, the colon tissue was significantly improved, the expressions of LC3-II/LC3-I and Beclin1 were significantly increased (P < 0.05), and the p62 was significantly decreased. Conclusions: The effect of Cur on IBD mice was related to the regulation of the expression of autophagy pathway proteins LC3-II/LC3-I, Beclin1, and p62 in intestinal epithelial cells.

Cigarette Smoke Containing Acrolein Contributes to Cisplatin Resistance in Human Bladder Cancers through the Regulation of HER2 Pathway or FGFR3 Pathway.

Cisplatin-based chemotherapy is the first-line therapy for bladder cancer. However, cisplatin resistance has been associated with the recurrence of bladder cancer. Previous studies have shown that activation of FGFR and HER2 signaling are involved in bladder cancer cell proliferation and drug resistance. Smoking is the most common etiologic risk factor for bladder cancer, and there is emerging evidence that smoking is associated with cisplatin resistance. However, the underlying mechanism remains elusive. Acrolein, a highly reactive aldehyde, is abundant in tobacco smoke, cooking fumes, and automobile exhaust fumes. Our previous studies have shown that acrolein contributes to bladder carcinogenesis through the induction of DNA damage and inhibition of DNA repair. In this study, we found that acrolein induced cisplatin resistance and tumor progression in both non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC) cell lines RT4 and T24, respectively. Activation of HER2 and FGFR3 signaling contributes to acrolein-induced cisplatin resistance in RT4 and T24 cells, respectively. Furthermore, trastuzumab, an anti-HER2 antibody, and PD173074, an FGFR inhibitor, reversed cisplatin resistance in RT4 and T24 cells, respectively. Using a xenograft mouse model with acrolein-induced cisplatin-resistant T24 clones, we found that cisplatin combined with PD173074 significantly reduced tumor size compared with cisplatin alone. These results indicate that differential molecular alterations behind cisplatin resistance in NMIBC and MIBC significantly alter the effectiveness of targeted therapy combined with chemotherapy. This study provides valuable insights into therapeutic strategies for cisplatin-resistant bladder cancer.

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.

Prostate Health Index Density Outperforms Prostate Health Index in Clinically Significant Prostate Cancer Detection.

BACKGROUND: Prostate-specific antigen (PSA) is considered neither sensitive nor specific for prostate cancer (PCa). We aimed to compare total PSA (tPSA), percentage of free PSA (%fPSA), the PSA density (PSAD), Prostate Health Index (PHI), and the PHI density (PHID) to see which one could best predict clinically significant prostate cancer (csPCa): a potentially lethal disease. METHODS: A total of 412 men with PSA of 2-20 ng/mL were prospectively included. Serum biomarkers for PCa was collected before transrectal ultrasound guided prostate biopsy. PHI was calculated by the formula: (p2PSA/fPSA) x √tPSA. PHID was calculated as PHI divided by prostate volume measured by transrectal ultrasound. RESULTS: Of the 412 men, 134 (32.5%) and 94(22.8%) were diagnosed with PCa and csPCa, respectively. We used the area under the receiver operating characteristic curve (AUC) and decision curve analyses (DCA) to compare the performance of PSA related parameters, PHI and PHID in diagnosing csPCa. AUC for tPSA, %fPSA, %p2PSA, PSAD, PHI and PHID were 0.56、0.63、0.76、0.74、0.77 and 0.82 respectively for csPCa detection. In the univariate analysis, the prostate volume, tPSA, %fPSA, %p2PSA, PHI, PSAD, and PHID were all significantly associated with csPCa, and PHID was the most important predictor (OR 1.41, 95% CI 1.15-1.72). Besides, The AUC of PHID was significantly larger than PHI in csPCa diagnosis (p=0.004). At 90% sensitivity, PHID had the highest specificity (54.1%) for csPCa and could reduce the most unnecessary biopsies (43.7%) and miss the fewest csPCa (8.5%) when PHID ≥ 0.67. In addition to AUC, DCA re-confirmed the clinical benefit of PHID over all PSA-related parameters and PHI in csPCa diagnosis. The PHID cut-off value was positively correlated with the csPCa ratio in the PHID risk table, which is useful for evaluating csPCa risk in a clinical setting. CONCLUSION: The PHID is an excellent predictor of csPCa. The PHID risk table may be used in standard clinical practice to pre-select men at the highest risk of harboring csPCa.