Mediation analysis for TNF-α as a mediator between multiple metal exposure and kidney function.

The association between metal mixtures and kidney function has been reported. However, reports on the mechanism of metal toxicity were limited. Oxidative stress was reported as a possible cause. This study aimed to determine the association between of kidney function and metals, such as arsenic (As), cadmium (Cd), cobalt (Co), copper (Cu), lead (Pb), selenium (Se), and zinc (Zn), and to explore the possible mediating role of tumor necrosis factor alpha (TNF-α) between metal toxicity and kidney function. In this study, we recruited 421 adults from a health examination. The concentration of blood metals was analyzed using inductively coupled plasma mass spectrometry. We used linear regression models to assess the association between metals and TNF-α. Then, mediation analysis was applied to investigate the relationship between metal exposure, TNF-α, and kidney function. In univariate linear regression, blood As, Cd, Co, Cu, Pb, and Zn levels significantly increased TNF-α and decreased kidney function. Higher blood As and Pb levels significantly increased TNF-α in multivariable linear regressions after adjusting for covariates. We found that blood levels of As (coefficients = -0.021, p = 0.011), Pb (coefficients = -0.060, p < 0.001), and Zn (coefficients = -0.230, p < 0.001) showed a significant negative association with eGFR in the multiple-metal model. Furthermore, mediation analysis showed that TNF-α mediated 41.7 %, 38.8 %, and 20.8 % of blood Cd, As and Pb, respectively. Among the essential elements, TNF-α mediated 24.5 %, 21.5 % and 19.9 % in the effects of blood Co, Cu, and Zn on kidney function, respectively. TNF-α, acting as a mediator, accounted for 20.1 % of the contribution between the WQS score of metal mixtures and the eGFR (p < 0.001). This study suggested that TNF-α may be a persuasive pathway mediating the association between metals and kidney function. Inflammation and kidney injury could be the underlying mechanisms of metal exposure. However, there is still a need to clarify the biochemical mechanism in follow-up studies.

Functional variants of the pentraxin 3 gene are associated with the metastasis and progression of prostate cancer.

Age, ethnic background and genetic components have been identified as the established risks for prostate cancer (PCa). Pentraxin 3 (PTX3), originally identified as a pattern-recognition molecule for defence against infectious agents, has multiple functions in tissue repair and in the regulation of cancer-associated inflammation. In this study, we sought to investigate the impact of PTX3 gene variants on the development of PCa. Genotypes of four common single-nucleotide polymorphisms (SNPs) of PTX3 gene, including rs1840680, rs2305619, rs3816527 and rs2120243, were profiled among 705 PCa patients and 705 ethnicity-matched controls. In this study, we found that patients who carry at least one minor allele (C) of rs3816527 (AC and CC) tended to develop advanced forms of diseases (clinical large T stage, OR, 1.593, p = 0.032; pathologically-confirmed nodal spread, OR, 1.987, p = 0.011; metastatic tumour, OR, 3.896, p = 0.032) as compared with those homologous for the major allele (AA). Further stratification analysis showed that such association of rs3816527 with lymphatic and distal metastasis of PCa was accentuated in the younger age group (≤65 at diagnosis) but not seen in the older age group (>65 at diagnosis), suggesting an age-specific effect of PTX3 variants. Prediction of PTX3 protein structure implied that polymorphism may alter the quaternary organization and oligomerization of PTX3 protein. Moreover, our gene silencing experiments and survey of public datasets revealed that elevation of PTX3 levels in PCa was required for cell migration and associated with tumour metastasis. Our results highlight an association of PTX3 rs3816527 with the progression of PCa.

Robotic partial nephrectomy for renal tumor: The pentafecta outcomes of a single surgeon experience.

PURPOSE: This study investigated the oncological and functional surgical outcomes for patients with renal tumor who underwent robot-assisted partial nephrectomy (PN) by a single surgeon in Taiwan from 2006 to 2019. METHODS: This retrospective study assessed patients who underwent robot-assisted PN for renal tumor. Patient data were analyzed for age, sex, body mass index, operative time and total ischemic time, surgical margin (positive/negative), and surgical complications. To evaluate functional and oncological outcomes, achievement of trifecta, and pentafecta criteria was used. Trifecta criteria were defined as a negative surgical margin, no postoperative complications, warm ischemia time <25 min. Pentafecta criteria were the trifecta criteria, >90% preservation of estimated glomerular filtration rate (eGFR) preservation, and no stage progression of chronic kidney disease at 1-year follow-up. RESULTS: Of 101 patients who received robot-assisted PN, the most common type of renal tumor was clear cell renal cell carcinoma (RCC) (38%), followed by angiomyolipoma (26%). Patient characteristics were mean age 54.59 ± 13.8 years; mean RENAL Nephrometry score 6.63 ± 2.16; mean operative time 102.34 ± 50.06 min; and warm ischemia time 20.01 ± 14.12 min. The mean eGFR was 104.43 ± 31.73 mL/min/1.73 m2 preoperatively and 89.39 ± 32.3 mL/min/1.73 m2 postoperatively. Pathologic evaluation showed malignant tumors in 57 patients, among whom achievement of trifecta criteria occurred for 39 (68.42%) and pentafecta criteria for 18 (31.57%). Operation time was the only predictor for pentafecta achievement. CONCLUSION: Robotic PN is a safe and effective approach for patients with renal tumor that can preserve most renal function and achieve oncological control. Pentafecta criteria can be used to more clearly define the surgical outcome of RAPN.

Robot-assisted radical prostatectomy using hugo RAS system: The pioneer experience in Taiwan and Northeast Asia.

BACKGROUND: Among the novel robotic platforms, the Hugo RAS system is the second most studied platform, next to the da Vinci system, and we aim to address our experiences in radical prostatectomy (RP) with the Hugo RAS system. METHODS: We recorded our first 12 cases of prostate cancer undergoing RP with the Hugo RAS system. The median console time was 145 min and median hospital stay was 7 days. Hedge' g was applied to search for the cut-off case in four parameters in surgeries. RESULTS: Pre-console preparation was significantly improved after the first seven cases, and the console time was remarkably shortened after the first two cases. The intraoperative pause for trouble shooting was remarkably shortened after the first three cases. CONCLUSIONS: We found that RP with the Hugo RAS system was feasible, and the learning curve was short as surgeons may benefit from the previous experience with the da Vinci system.

Impact of tissue inhibitor of metalloproteinases-3 genetic variants on clinicopathological characteristics of urothelial cell carcinoma.

To investigate the distribution of single nucleotide polymorphism (SNP) of tissue inhibitor of metalloproteinases-3 (TIMP-3) in patients with/without urothelial cell carcinoma (UCC), three loci of TIMP-3 SNPs (rs9862 C/T, rs9619311 T/C, rs11547635 C/T) were genotyped via TaqMan allelic discrimination for 424 UCC patients and 848 non-UCC participants. Furthermore, the TIMP-3 mRNA expression and its correlation with clinical characters of urothelial bladder carcinoma was analyzed using The Cancer Genome Atlas database (TCGA). The distribution of all 3 studied SNPs of TIMP-3 was insignificantly different between the UCC and non-UCC groups. However, significantly lower tumor T status was found in TIMP-3 SNP rs9862 CT + TT variant than the wild type (OR: 0.515, 95% CI: 0.289-0.917, P = 0.023). Moreover, the muscle invasive tumor type was significantly correlated to the TIMP-3 SNP rs9619311 TC + CC variant in the non-smoker subgroup (OR: 2.149, 95% CI: 1.143-4.039, P = 0.016). With the TIMP-3 expression data provided in TCGA, significantly higher TIMP-3 mRNA expression was observed in UCC with high tumor stage (P < 0.0001), high tumor T status (P < 0.0001) and high lymph node status (P = 0.0005). In conclusions, TIMP-3 SNP rs9862 variant is associated with lower tumor T status of UCC while TIMP-3 SNP rs9619311 variant is correlated to muscle invasive UCC development in non-smoker.

Incidental Prostate Cancer from Prostate with Benign Biopsies: A Predictive and Survival Analysis from Cohort Study.

Purpose: This cohort was to evaluate incidental prostate cancer (iPCa) from men with preoperative benign biopsies and demonstrate their outcomes under different managements. Patients and Methods: Between 2015 and 2017, we analyzed the risk factors having iPCa from surgical specimens from men provided with benign preoperative biopsies of their prostates. Furthermore, we compared the survival outcomes according to the different managements after iPCa was diagnosed. Receiver operating characteristic (ROC) curve was utilized to find the best thresholds. Univariable and multivariable nested logit regression were performed to estimate the effect size of different independent variables. Odds ratio (OR) was expressed with 95% confidence interval, and the alpha level was 5%. Results: In 295 men we enrolled, there were 57 (19%) men having iPCa from surgical specimens. In univariable logit regression, we found significant variables of age, PSA, prostatic volume, PSA velocity ≥ 0.75 ng/mL/year for 3 years, taking 5α reductase inhibitors, abnormal digital rectal examination, cores of biopsy and surgical methods. In multivariable model, PSA was the strongest variable predicting iPCa (OR 3.81 [2.04-7.07]; Wald: 17.75; p < 0.001). In ROC curve, the best threshold was 9.025 ng/mL (area under curve: 0.95; sensitivity: 0.947; specificity: 0.866). In Kaplan-Meier curve of 27.89-month follow-up, robot-assisted simple prostatectomy (RASP) can provide similar PSA progression-free period as robot-assisted radical prostatectomy (RARP) following transurethral surgeries in organ-confined cancer (Log rank test, p = 0.293), and both of them were better than external-beam radiation therapy (RT) following transurethral surgeries (Log rank test, p < 0.001). Conclusion: PSA was the strongest variable to predict iPCa out of prostate with preoperative benign biopsies. RASP was parallel to RARP following transurethral surgeries in organ-confined cancer in the short term.

Radium-223 for metastatic, castration-resistant prostate cancer: A retrospective chart review study of real-world use in a tertiary hospital in Taiwan.

BACKGROUND: Radium-223 is an alpha-emitting, bone-targeting radiopharmaceutical that confers a survival benefit in patients with confirmed bone-metastatic, castration-resistant prostate cancer with no visceral metastases. We studied real-world use of radium-223 in eligible patients from a tertiary hospital. METHODS: We retrospectively collected clinical data of patients treated with radium-223 in Tungs' Taichung MetroHarbor Hospital by chart review. Data included biochemical parameters, pain scores, other prostate cancer treatments received and adverse events (AEs). RESULTS: Of 36 patients included in the study, 12 patients received radium-223 as first-line therapy, 11 as second-line treatment and 13 as third-line treatment. Prostate-specific antigen significantly increased from baseline in patients who received radium-223 as third-line treatment and in patients who received radium-223 post-chemotherapy. Pain scores significantly decreased when radium-223 was given as second-line and as third-line treatment. In the patients who were naive to novel anti-hormone (NAH) therapy and chemotherapy, mean alkaline phosphatase level significantly decreased from baseline. The most common AE was anemia, found in 16.7% of patients. CONCLUSION: Radium-223 had early biochemical benefits, while in the later stages of the disease, it reduced bone pain in this real-world cohort of chemotherapy-naive, NAH-naive patients, and patients with prior therapy, from a tertiary institution in Taiwan.

Validation of robotic-assisted ureteroplasty with buccal mucosa graft for stricture at the proximal and middle ureters: the first comparative study.

Although ureteroplasty with buccal mucosa graft for long-segmental ureteral stenosis has been developed long ago, evidence was still restricted to case series in published literature. This study aims to validate ureteroplasty with buccal mucosa graft (BMG) in long-segment stricture at the proximal and middle ureters under designed comparative methods. From April 2015 to January 2019, we performed robotic-assisted ureteroplasty with BMG with a two-phase design and compared ureteroplasty and BMG (phase 2 surgery) with endoscopic stenting (phase 1 surgery). Paired data of effective renal plasma flow (ERPF), glomerular filtration rate (GFR), hydronephrosis grade, and physical and psychological domains of the World Health Organization Quality of Life (WHOQOL)-BREF were compared. A total of 29 patients were enrolled, and only three (10%) patients had hydronephrosis resolution after treatment with endoscopic stenting (p = 0.250 to baseline). Compared to endoscopic ureteral stent, Hedges' g of ureteroplasty with BMG was 0.56 (95% CI 0.43-0.69), 0.63 (95% CI 0.46-0.80), 0.80 (95% CI 0.56-1.04), and 1.06 (95% CI 0.69-1.43) in EGFR, GFR, physical domain of WHOQOL-BREF, and psychological domain of WHOQOL-BREF, respectively (All significance; p < 0.001). After 12-month follow-ups, no recurrence of stricture was reported. In conclusion, Robotic-assisted ureteroplasty with BMG onlay is efficient in reconstruction of long-segment stricture of the proximal and middle ureters.

Diffusive Ki67 and vimentin are associated with worse recurrence-free survival of upper tract urothelial carcinoma: A retrospective cohort study from bench to bedside.

OBJECTIVES: This study aimed to determine the prognostic values of Ki67 and vimentin in upper tract urothelial carcinoma (UTUC) after extirpative surgery. METHODS AND MATERIALS: Between 2014 and 2019, patients diagnosed with UTUC and receiving radical nephroureterectomy were included retrospectively. Nuclear MIB-1 clones and cytoplasmic VIM 3B4 clones were used to assess Ki67 and vimentin levels, respectively. A unified reading protocol was applied, and the expression level was read by a single pathologist. Receiver operating characteristic curves were utilized to determine the best threshold for Ki67 and vimentin regarding recurrence, and this level was set as the diffusive level. The outcome of recurrence-free survival (RFS) was analyzed via a Cox regression model with univariable and multivariable approaches. Survival outcomes were analyzed via Kaplan-Meier (KM) curves. RESULTS: A total of 247 patients were included, and the mean follow-up was 29.90 ± 6.80 months. Diffusive thresholds were 17.5% for both Ki67 and vimentin. Under multivariable Cox regression, diffusive Ki67 (hazard ratio: 4.20 [2.39-7.37], P < 0.001) and diffusive vimentin (hazard ratio: 5.34 [3.10-9.22], P < 0.001) were significant prognostic indicators of worse RFS. Diffusive Ki67 was accompanied by diffusive vimentin (chi square with Yates' correction, P = 0.015), and vice versa. In the KM curve, there was no difference between diffusive Ki67/nondiffusive vimentin and nondiffusive Ki67/diffusive vimentin (log-rank test, P = 0.073). Significant differences (log-rank test, P < 0.001) were seen in different combinations of diffusive Ki67/vimentin (Mean RFS: 19.76 [18.56-20.96] months), only one diffusive in Ki67 or vimentin (Mean RFS: 22.94 [21.88-24.00] months), and nondiffusive Ki67/vimentin (Mean RFS: 32.96 [32.43-33.50] months). CONCLUSIONS: Diffusive Ki67 and vimentin were related to each other, and they exerted equivalent and synergic effects on predicting worse RFS in UTUC.

Biochemical recurrence of pathological T2+ localized prostate cancer after robotic-assisted radical prostatectomy: A 10-year surveillance.

BACKGROUND: pT2+ prostate cancer (PCa), a term first used in 2004, refers to organ-confined PCa characterized by a positive surgical margin (PSM) without extracapsular extension. Patients with a PSM are vulnerable to biochemical recurrence (BCR) following radical prostatectomy (RP); however, whether adjuvant radiotherapy (aRT) is imperative to PSM after RP remains controversial. This study had the longest follow-up on pT2+ PCa after robotic-assisted RP since 2004. Moreover, we discussed our viewpoints on pT2+ PCa based on real-world experiences. AIM: To conclude a 10-year surveillance on pT2+ PCa and compare our results with those of the published literature. METHODS: Forty-eight patients who underwent robotic-assisted RP between 2008 and 2011 were enrolled. Two serial tests of prostate specific antigen (PSA) ≥ 0.2 ng/mL were defined as BCR. Various designed factors were analyzed using statistical tools for BCR risk. SAS 9.4 was applied and significance was defined as P < 0.05. Univariate, multivariate, linear regression, and receiver operating characteristic (ROC) curve analyses were performed for statistical analyses. RESULTS: With a median follow-up period of 9 years, 25 (52%) patients had BCR (BCR group), and the remaining 23 (48%) patients did not (non-BCR group). The median time for BCR test was 4 years from the first postoperative PSA nadir. Preoperative PSA was significantly different between the BCR and non-BCR groups (P < 0.001), and ROC curve analysis of preoperative PSA suggested a cut-off value of 19.09 ng/mL (sensitivity, 0.600; specificity: 0.739). The linear regression analysis showed no correlation between time to BCR and preoperative PSA (Pearson's correlation, 0.13; adjusted R 2 = 0.026). CONCLUSION: Robotic-assisted RP in pT2+ PCa of worse conditions can provide better BCR-free survival. A surgical technique limiting the PSM in favorable situations is warranted to lower the pT2+ PCa BCR rate. Preoperative PSA cut-off value of 19.09 ng/mL is a predictive factor for BCR. Based on our experiences and review of the literature, we do not recommend routine aRT for pT2+ PCa.

Robotic Incisional Hernia Repair After Robotic-assisted Radical Prostatectomy (RARP): A 3-port Approach.

BACKGROUND/AIM: Incisional hernia is a complication that occurs occasionally, and surgical intervention is required to prevent more severe sequela. While there are several options for management, robotic-assisted incisional repair has not been well discussed yet. We herein report a case series of 10 patients who underwent robotic-assisted incisional hernia repair (RIHR) after robotic-assisted radical prostatectomy (RARP). The aim of the study was to examine the feasibility of incisional hernia repair with da Vinci® robotics. PATIENTS AND METHODS: We recruited patients from a group of 2,000 consecutive patients who underwent RARP from December, 2005 to June, 2020 by a single surgeon. Patient characteristics included age, body mass index (BMI), PSA level, pathology Gleason score, and pathology TNM staging. The variants regarding the patients' incisional hernia included incisional hernia occurrence time after RARP, defect size, operation time, console time, blood loss, and follow-up time after the herniation occurrence. Furthermore, we established a defect size of 3x2 cm2 as the cutoff value for using mesh reinforcement or not. RESULTS: The mean defect area was 27.7 cm2, and the average operative time was 114.8 min, with a mean console time of 87 min. Blood loss was 32.5 ml, and the hospital stay for all patients was 3 days without complications. The mean follow-up period was 29.5 months, with no recurrence. CONCLUSION: RIHR is a feasible surgical method that is not inferior to the traditional open or laparoscopic repair. Furthermore, RIHR can possibly lessen the burden of both the surgeon and patient.

Building a Nomogram for Prediction of Prostate Cancer in Patients With Preoperatively Suspected Prostate Cancer.

BACKGROUND/AIM: Expanded indications for patients with preoperatively suspected prostate cancer (PC) undergoing theranostic robotic-assisted laparoscopic radical prostatectomy (T-RARP) are reported. We aimed to build a nomogram of T-RARP to predict final pathologically proven PC. This study reviewed data of 153 patients that underwent T-RARP for suspected PC performed by the same surgeon. PATIENTS AND METHODS: Patients' preoperative demographic and clinical characteristics included age, prostate-specific antigen (PSA) level, PSA density (PSAD), history of acute urinary retention (AUR), abnormal digital rectal examination (DRE) of the prostate, and Prostate Imaging Reporting and Data System (PI-RADS) classification at 3-T multiparametric magnetic resonance imaging (MRI). Logistic regression with backward elimination was used to select potential risk factors. RESULTS: Based on Harrell's guidelines, we chose seven variables for our final model: Age, DRE corresponding with MRI, AUR, PSAD, prostate-specific antigen velocity (PSAV), PI-RADS, and biopsy pathology. A nomogram for prediction of adenocarcinoma was developed. The original C-index for the nomogram was 0.80 (95% confidence interval=0.74-0.89). The cut-off of the nomogram score for predicting PC was 50 (sensitivity=55.4%; specificity=91.9%). The receiver operating characteristic curve of the model analysis showed an area under the curve of 0.801. CONCLUSION: A nomogram was produced using age, DRE-corresponding MRI, AUR, PSAD, PSAV, PI-RADS, and biopsy pathology. A preoperative nomogram prediction of prostate adenocarcinoma can help the patient and his family understand the possibility of PC and assist them in their decision-making.

Impact of Gene Polymorphisms in GAS5 on Urothelial Cell Carcinoma Development and Clinical Characteristics.

Urothelial cell carcinoma (UCC) is the commonest malignant tumor of the urinary tract and the second most common kidney cancer malignancy. Growth arrest-specific 5 (GAS5), a long noncoding RNA, is encoded by the GAS5 gene and plays a critical role in cellular growth arrest and apoptosis. In the current study, two single nucleotide polymorphisms (SNPs) in the GAS5 gene, rs145204276 and rs55829688, were selected to investigate correlations between these single SNPs and susceptibility to UCC. A total of 430 UCC cases and 860 ethnically matched healthy controls were included. SNP rs145204276 and SNP rs55829688 were determined using a TaqMan genotyping assay. Logistic regression models demonstrated that female patients with UCC carrying the rs145204276 GAS5 Ins/Del or Del/Del genotype had a 3.037-fold higher risk of larger tumor status (95% confidence interval 1.259-7.324) than did rs145204276 wild type (Ins/Ins) carriers (p = 0.011). The Cancer Genome Atlas validation cohort analysis demonstrated that the expression of GAS5 in female patients with bladder urothelial carcinoma (BLCA) with larger tumor size was much lower than that in patients with a smaller tumor size (p = 0.041). Kaplan-Meier curve analysis and the log-rank test revealed that female patients with BLCA and lower GAS5 expression had poorer overall survival than those with higher GAS5 expression. In conclusion, genetic variations in GAS5 rs145204276 may serve as a critical predictor of the clinical status of female patients with UCC.

Simultaneous upper and lower urinary tract invasive Lymphoepithelioma-like carcinoma with programmed death-ligand 1 full expression on combined positive score.

Lymphoepithelioma-like carcinoma, named after nasopharyngeal lymphoepithelioma and rarely seen at genitourinary malignancy, accounts for 1%-2% along the upper and lower urinary tract. For its rarity, no published guideline can be adhered to. Roles of surgery and chemotherapy are solid, and rich Programmed Death-Ligand 1 characteristics may furthermore light on the possible immunotherapy. This female case had it at both upper and lower urinary tract simultaneously. No involved regional lymph nodes and no distant metastasis were investigated. No adjuvant chemotherapy was given after robotics-assisted left nephroureterectomy and bladder cuff excision with partial cystectomy, and no recurrence was observed.

Early Dutasteride Monotherapy in Patients With Elevated Serum Prostate-Specific Antigen Levels Following Robot-Assisted Radical Prostatectomy.

Background: To evaluate the efficacy of early dutasteride administration in patients with a detectable prostate-specific antigen (PSA) levels after robot-assisted radical prostatectomy (RARP). Methods: We retrospectively analyzed RARP patients whose pathological stage is T2a to T3b without lymph node or distant metastasis from 2007 to 2017. All patients received a daily dose of 0.5 mg of dutasteride when post-RARP PSA levels were increasing but had not achieved biochemical recurrence. PSA levels were monitored every 3 months after dutasteride administration. None of the patients received radiotherapy (RT) or androgen-deprivation therapy (ADT) before taking dutasteride. All follow-ups were begun from RARP to January 2019 or to the date of RT/ADT. Results: Thirty-five patients were included in this analysis. The median followed up was 53.6 months. Twenty-two patients (62.9%) showed a PSA response in which the PSA decreased more than 10% at the first follow-up after dutasteride administration. The Pathological stage > T2 (p = 0.012) and positive surgical margin (p = 0.046) were prognostic factors for a PSA response. Twenty-three out of 35 included patients (65.7%) did not require further RT/ADT. The significant risk factor was the PSA level (p = 0.011) at the beginning of dutasteride treatment. The cut-off value of the PSA level to avoid further RT/ADT was 0.195 ng/ml. Conclusions: Early dutasteride administration showed a significant decline in the PSA levels of patients with pathology stage >T2 and positive surgical margin in our retrospective hypothesis-generating study. If dutasteride was provided before the PSA value increased to 0.195 ng/ml after RARP, it would reduce the probability of acquirement of RT/ADT.

Impact of prostatic anterior fat pads with lymph node staging in prostate cancer.

Background: Several reports have revealed the presence of lymph nodes in the prostatic anterior fat pad (PAFP). To date, no study has described the characteristics of Taiwanese patients harboring PAFP lymph nodes with metastatic prostate cancer involvement. Method: Between December 2006 and May 2015, a total of 849 consecutive patients underwent robot-assisted laparoscopic radical prostatectomy with PAFP dissection. Pathological examination of the dissected PAFP was conducted to assess the presence of lymphoid tissue and prostate cancer involvement. Results: Of the 849 patients, 76 (9.0%) had 1-3 PAFP lymph nodes. Moreover, 11 (1.3%) of the 76 patients had positive lymph node metastases of prostate cancer in the PAFP; 5 (0.6%) of the 11 patients, who had negative pelvic lymph node involvement, were upstaged because of positive metastases in PAFP lymph nodes. Among the 76 patients having PAFP lymph nodes, metastatic lymph nodes were associated with the clinical T stage, preoperative Gleason score, pathological T stage, and pathological N stage (p < 0.001). Patients with pathological seminal vesicle invasion and a higher surgical Gleason score also exhibited PAFP lymph node metastases (p < 0.005). Conclusion: Our data show that 9.0% of patients had PAFP lymph nodes and that 1.3% had prostate cancer metastases. Additionally, 0.6% of patients were upstaged because of positive metastases in PAFP lymph nodes. Because of the pathological analysis of the PAFP, a few patients were upstaged. Thus, routine pathological analysis of the PAFP should only be conducted for those with higher preoperative prostate-specific antigen, higher Gleason score, and advanced T stage observations.

Activation of Lysophosphatidic Acid Receptor 3 Inhibits Megakaryopoiesis in Human Hematopoietic Stem Cells and Zebrafish.

Lysophosphatidic acid (LPA) is a membrane-derived lysophospholipid that exists in the plasma and platelets. It exerts its functions through activation of various LPA receptors (LPARs), which belong to the family of G protein-coupled receptors. Activation of LPARs has important roles in stem cell differentiation. However, how LPA affects human hematopoietic stem cell (HSC) differentiation remains elusive. In our previous studies, we have suggested that LPA receptor 2 (LPA2) and LPA receptor 3 (LPA3) play opposing roles and may act as a molecular switch during megakaryocytic differentiation in K562 cells. In this study, human CD34+ HSCs and zebrafish are adopted to investigate the roles of LPA3 during megakaryopoiesis/thrombopoiesis in vitro and in vivo. Our results show that LPAR3 mRNA expression level is decreased upon induction by thrombopoietin and stem cell factor in human HSCs. Using pharmacological activators and shRNA knockdown experiments, we demonstrate that activation of LPA3 inhibits megakaryopoiesis in human HSCs. In addition, pharmacological activation of LPA3 suppressed thrombopoiesis in zebrafish. Furthermore, blockage of LPA3 translation by morpholino increased the number of CD41-GFP+ cells in Tg(CD41:eGFP) zebrafish. Moreover, the mRNA expression level of zCD41 increased significantly in LPA3-knockout zebrafish. These results clarify the negative role of LPA3 during megakaryopoiesis and provide important information for potential treatments of related diseases, such as megakaryopenia.

Prophylactic Robotic-assisted Laparoscopic Radical Prostatectomy for Preoperative Suspicion of Prostate Cancer: Experience with 55 Cases.

BACKGROUND/AIM: Expanded indications are not yet reported for robotic-assisted laparoscopic radical prostatectomy (RARP) performed by experienced surgeons for patients with preoperative suspicion of prostate cancer. We report our experience with 55 cases of prophylactic RARP for preoperative suspicion of prostate cancer, including postoperative pathological characteristics and outcomes. PATIENTS AND METHODS: This retrospective study reviewed data of a subset of 55 consecutive patients among 1,060 patients who underwent RARP for preoperative suspicion of prostate cancer. Pathological characteristics and outcomes of patients with suspected prostate cancer were analyzed and preoperative, intraoperative and postoperative parameters were compared between three groups. Patients were stratified by final pathology reports of RARP specimens: Group I: Prostate cancer, N=22 (40%); group II: abnormal (prostate intraepithelial neoplasia; atypical small acinar proliferation), N=18 (32.7%); and group III: benign (nodular hyperplasia or inflammation), N=15 (27.3%). RESULTS: Mean preoperative prostate-specific antigen (PSA) was 16.04±2.21 ng/ml. Twenty-two patients with adenocarcinoma had pathology stage pT2a/T2b/ T2c/T3a/T3b (6/7/2/6/1 patients, respectively), with positive surgical margins in 18.2% (4/22). Preoperative incidence of PSA velocity >0.75 ng/ml/yr was significantly higher in group I than in groups II and III (81.8% vs. 38.9% vs. 33.3%, p=0.004). Predictive parameters of prostate cancer showed that PSA velocity (>0.75 vs. ≤0.75 ng/ml/yr) had crude odds ratio of 9.0 for group I vs. group III, p=0.005. Posteperatively, statistically significant improvements were found in uroflow rate, post-voiding residual urine and symptom scores (all p<0.0001). CONCLUSION: Prophylactic RARP with bilateral neurovascular bundle preservation performed by experienced surgeons is a safe and viable option for preoperative suspicion of prostate cancer.

Effect of CD44 gene polymorphisms on risk of transitional cell carcinoma of the urinary bladder in Taiwan.

The carcinogenesis of transitional cell carcinoma (TCC) of the urinary bladder involves etiological factors, such as ethnicity, the environment, genetics, and diet. Cluster of differentiation (CD44), a well-known tumor marker, plays a crucial role in regulating tumor cell differentiation and metastasis. This study investigated the effect of CD44 single nucleotide polymorphisms (SNPs) on TCC risk and clinicopathological characteristics. Five SNPs of CD44 were analyzed through real-time polymerase chain reaction in 275 patients with TCC and 275 participants without cancer. In this study, we observed that CD44 rs187115 polymorphism carriers with the genotype of at least one G were associated with TCC risk. Furthermore, TCC patients who carried at least one G allele at CD44 rs187115 had a higher stage risk than did patients carrying the wild-type allele (p < 0.05). In addition, The AATAC or GACGC haplotype among the five CD44 sites was also associated with a reduced risk of TCC. In conclusion, our results suggest that CD44 SNPs influence the risk of TCC. Patients with CD44 rs187115 variant genotypes (AG + GG) exhibited a higher risk of TCC; these patients may possess chemoresistance to developing late-stage TCC compared with those with the wild-type genotype. The CD44 rs187115 SNP may predict poor prognosis in patients with TCC.

Interactions between environmental factors and melatonin receptor type 1A polymorphism in relation to oral cancer susceptibility and clinicopathologic development.

BACKGROUND: The purpose of this study was to explore the combined effect of melatonin receptor type 1A (MTNR1A) gene polymorphisms and exposure to environmental carcinogens on the susceptibility and clinicopathological characteristics of oral cancer. METHODOLOGY AND PRINCIPAL FINDINGS: Three polymorphisms of the MTNR1A gene from 618 patients with oral cancer and 560 non-cancer controls were analyzed by real-time polymerase chain reaction (PCR). The CTA haplotype of the studied MTNR1A polymorphisms (rs2119882, rs13140012, rs6553010) was related to a higher risk of oral cancer. Moreover, MTNR1A gene polymorphisms exhibited synergistic effects of environmental factors (betel quid and tobacco use) on the susceptibility of oral cancer. Finally, oral-cancer patients with betel quid-chewing habit who had T/T allele of MTNR1A rs13140012 were at higher risk for developing an advanced clinical stage and lymph node metastasis. CONCLUSION: These results support gene-environment interactions of MTNR1A polymorphisms with smoking and betel quid-chewing habits possibly altering oral-cancer susceptibility and metastasis.