Tai-Lung Cha

Histopathological assessment of inflammation and expression of inflammatory markers in patients with ketamine-induced cystitis

The aim of the current study was to evaluate the histopathological features of inflammation and the expression levels of inflammatory markers in tissue samples from patients with ketamine-induced cystitis. Bladder biopsy samples for histological analysis were obtained from 23 patients (18 men and 5 women) with a self-reported history of ketamine use and who were treated for cystitis at the Tri-Service General Hospital of Taipei, Taiwan. Immunohistochemical staining for cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), matrix metallopeptidase-9 (MMP-9), mammalian target of rapamycin (mTOR), and phosphorylated 40S ribosomal protein S6 (Phos-S6) was performed. The results revealed urothelial atypia in all patients, and intravascular eosinophil accumulation in 22 patients. Histopathological features included denuded urothelial mucosa, ulceration, collagen deposition, smooth muscle degeneration and vessel proliferation. Tissue samples were immunopositive for all of the inflammation markers, including the urothelium, vessel walls, and smooth muscle. COX-2 staining revealed a significant difference between the inflammatory levels in the urothelium and smooth muscle, and iNOS staining differed significantly between inflammatory levels in smooth muscle (p=0.029). A positive correlation was observed between the percentage of Phos-S6-positive cells and the levels of inflammation in the urothelium. These results add to the descriptive literature on the histopathological aspects of ketamine-induced cystitis, emphasizing the inflammatory nature and a possible role for proteins such as COX-2, iNOS and Phos-S6 in the degree of inflammation.

The Association between Dietary Patterns and Semen Quality in a General Asian Population of 7282 Males

Objective To explore the associations between different dietary patterns and semen quality in a general Asian male population. Methods Cross-sectional study. Healthy Taiwanese men aged 18 years or older who participated in a standard medical screening program from 2008-2013 run by a private firm were included in this study. Semen parameters including sperm concentration (SC), total sperm motility (TSM), progressive motility (PRM) and normal sperm morphology (NSM) were recorded. A dietary questionnaire was used to categorize the participants into 5 groups: “Healthy diet”, “Western diet”, “High-carbohydrate diet”, “High sweet snacks & sugar-sweetened drinks” and “High-sodium diet”. Results A total of 7282 men completed the questionnaire regarding dietary pattern, and examination of anthropometric indexes was performed and laboratory data were obtained. A high intake of a “Western diet” resulted in statistically linear declines of SC and NSM (P < 0.001 and P < 0.001). Similarly, a greater intake of “High sweet snacks & sugar-sweetened drinks” was associated with a lower SC (P = 0.001). Increased intake of a “High-carbohydrate diet” was related to higher prevalences of abnormal TSM and PRM (P = 0.012 and P = 0.025). Similarly, a greater intake of a “High-sodium diet” was correlated with an elevated prevalence of abnormal NSM (P = 0.035). Conclusions This study showed that a greater intake of a “Western diet” is associated with poorer SC and NSM, a “High sweet snacks and sugar-sweetened drinks” intake is correlated with a lower SC, and high-carbohydrate food is related to elevated prevalences of abnormal TSM and PRM.

Exploration of the association between obesity and semen quality in a 7630 male population.

This study aimed to explore the association between body mass index (BMI), other anthropometric indexes and semen quality in a general male population in Taiwan. In this cross-sectional cohort study, the study cohort consisted of 7941 healthy male individuals aged 18 years or older who participated in a standard medical screening program run by a private firm from January 2008 to May 2013. Semen parameters including sperm concentration (SC), total sperm motility (TSM), progressive motility (PRM), and normal sperm morphology (NSM) were recorded. Anthropometric indexes including BMI, waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and body fat percentage were measured. A total of 7630 men were enrolled for the final analysis, of whom 68.5% had a normal weight distribution and 31.4% were overweight or obese. Total sperm motility, progressive motility, normal sperm morphology and sperm concentration showed a statistically linear decline with increasing age (p < 0.001, p < 0.001, p < 0.001 and p = 0.004). Sperm concentration showed a significantly negatively linear association with BMI (p = 0.005), and normal sperm morphology showed an inverse association with BMI and waist-to-height ratio (p < 0.001 and p = 0.004). The prevalence of abnormal total sperm motility, progressive motility, normal sperm morphology and sperm concentration increased with increasing age (p = 0.011, p < 0.001, p < 0.001 and p = 0.002). Lower normal sperm morphology and sperm concentration were associated with increasing body adiposity (p<0.05). No relationship between obesity and sperm motility was identified.

Artificial neural network for predicting pathological stage of clinically localized prostate cancer in a Taiwanese population.

Background: We developed an artificial neural network (ANN) model to predict prostate cancer pathological staging in patients prior to when they received radical prostatectomy as this is more effective than logistic regression (LR), or combined use of age, prostate‐specific antigen (PSA), body mass index (BMI), digital rectal examination (DRE), trans‐rectal ultrasound (TRUS), biopsy Gleason sum, and primary biopsy Gleason grade. Methods: Our study evaluated 299 patients undergoing retro‐pubic radical prostatectomy or robotic‐assisted laparoscopic radical prostatectomy surgical procedures with pelvic lymph node dissection. The results were intended to predict the pathological stage of prostate cancer (T2 or T3) after radical surgery. The predictive ability of ANN was compared with LR and validation of the 2007 Partin Tables was estimated by the areas under the receiving operating characteristic curve (AUCs). Results: Of the 299 patients we evaluated, 109 (36.45%) displayed prostate cancer with extra‐capsular extension (ECE), and 190 (63.55%) displayed organ‐confined disease (OCD). LR analysis showed that only PSA and BMI were statistically significant predictors of prostate cancer with capsule invasion. Overall, ANN outperformed LR significantly (0.795 ± 0.023 versus 0.746 ± 0.025, p = 0.016). Validation using the current Partin Tables for the participants of our study was assessed, and the predictive capacity of AUC for OCD was 0.695. Conclusion: ANN was superior to LR at predicting OCD in prostate cancer. Compared with the validation of current Partin Tables for the Taiwanese population, the ANN model resulted in larger AUCs and more accurate prediction of the pathologic stage of prostate cancer.

Novel Cancer Therapeutics with Allosteric Modulation of The Mitochondrial C-Raf/DAPK Complex by Raf Inhibitor Combination Therapy

Mitochondria are the powerhouses of cells. Mitochondrial C-Raf is a potential cancer therapeutic target, as it regulates mitochondrial function and is localized to the mitochondria by its N-terminal domain. However, Raf inhibitor monotherapy can induce S338 phosphorylation of C-Raf (pC-Raf(S338)) and impede therapy. This study identified the interaction of C-Raf with S308 phosphorylated DAPK (pDAPK(S308)), which together became colocalized in the mitochondria to facilitate mitochondrial remodeling. Combined use of the Raf inhibitors sorafenib and GW5074 had synergistic anticancer effects in vitro and in vivo, but targeted mitochondrial function, rather than the canonical Raf signaling pathway. C-Raf depletion in knockout MEF(C-Raf-/-) or siRNA knockdown ACHN renal cancer cells abrogated the cytotoxicity of combination therapy. Crystal structure simulation showed that GW5074 bound to C-Raf and induced a C-Raf conformational change that enhanced sorafenib-binding affinity. In the presence of pDAPK(S308), this drug-target interaction compromised the mitochondrial targeting effect of the N-terminal domain of C-Raf, which induced two-hit damages to cancer cells. First, combination therapy facilitated pC-Raf(S338) and pDAPK(S308) translocation from mitochondria to cytoplasm, leading to mitochondrial dysfunction and reactive oxygen species (ROS) generation. Second, ROS facilitated PP2A-mediated dephosphorylation of pDAPK(S308) to DAPK. PP2A then dissociated from the C-Raf-DAPK complex and induced profound cancer cell death. Increased pDAPK(S308) modification was also observed in renal cancer tissues, which correlated with poor disease-free survival and poor overall survival in renal cancer patients. Besides mediating the anticancer effect, pDAPK(S308) may serve as a predictive biomarker for Raf inhibitors combination therapy, suggesting an ideal preclinical model that is worthy of clinical translation.

Does radical cystectomy outperform other bladder preservative treatments in elderly patients with advanced bladder cancer

Background To assess the impacts of age, performance status, and clinical stage on advanced urothelial carcinoma of the bladder (UCB) in patients treated with different treatment modalities. Methods This retrospective study included 160 patients who underwent radical cystectomy (RC) with/without neoadjuvant or adjuvant chemoradiotherapy, palliative chemotherapy/radiotherapy/chemoradiotherapy (CRT), and transurethral resection of bladder tumor (TURBT) monotherapy for advanced UCB in one institution from 2000 to 2010. Kaplan–Meier analysis was used to calculate the survival distributions of overall survival (OS). The quality of life of the patients was also analyzed. Results The median age of the patients was 74.0 years, and the mean survival interval was 31.5 months. The 2‐year OS was significantly different among the three modalities [RC > TURBT monotherapy, odds ratio (OR): 1.86, 95% CI: 1.17–2.96, p = 0.009; CRT > TURBT monotherapy, OR: 1.65, 95% CI: 1.06–2.57, p = 0.026]. There were no significant differences in the 5‐ and 10‐year OS rates between the three treatment modalities. Those younger than 76 years receiving RC had a significantly better 2‐year OS than those undergoing CRT and TURBT monotherapy (RC > TURBT monotherapy, OR: 2.38; 95% CI: 1.30–4.33, p = 0.005). The number and duration of re‐hospitalizations were highest in the CRT group and lowest in the TURBT group. Conclusion The short‐ and long‐term OS rates of the three modalities were similar in those older than 76 years. Therefore, patients younger than age 76 years are likely to have a better outcome undergoing radical cystectomy for advanced UCB.

An Unexpected Clinical Feature of Zinner's Syndrome – A Case Report

We present a case of a healthy 43-year-old man who experienced right lower abdominal mass with gastrointestinal upset for 6 months. A series of imaging studies revealed a large lobulated cyst in the right pelvis and retroperitoneum. Because of the persistent symptom, surgical intervention was performed to remove the cystic lesion. The final pathology report demonstrated a large seminal vesicle cyst with agenesis of kidney. It is compatible with the diagnosis of Zinners syndrome. However, right lower abdominal mass is a rare manifestation of this syndrome. This case reminds us a unique differential diagnosis of a right lower abdominal mass.

Dedifferentiated liposarcoma of the left kidney: A rare case report

a Division of Urology, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan Department of Surgery, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan c Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan d Department of Nutritional Science, Fu Jen Catholic University, New Taipei, Taiwan e Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan