Kaiwei Yang

Prognostic and predictive value of epigenetic biomarkers and clinical factors in upper tract urothelial carcinoma.

AIM We conducted this study to identify gene promoter methylation status and clinical predictors for upper tract urothelial carcinoma (UTUC) patients. MATERIALS & METHODS Using methylation-sensitive PCR, we examined ten genes promoter methylation status in 687 UTUC patients. RESULTS A methylated promoter of three genes to predict higher tumor stage (T3 and T4), five genes to predict higher tumor grade (G3) and one gene to predict pN+ were certified in this study. Nine factors were significantly associated with poor cancer-specific survival. Six factors were considered as predictors to develop bladder recurrence after surgery. CONCLUSION Methylation occurs commonly in UTUCs, may affect carcinogenic mechanisms, and is a well predictive factor for cancer-specific survival and bladder recurrence in UTUCs.

A Novel and Simple Modification for Management of Distal Ureter During Laparoscopic Nephroureterectomy Without Patient Repositioning: A Bulldog Clamp Technique and Description of Modified Port Placement

BACKGROUND AND PURPOSE To describe a novel and pure laparoscopic approach using a custom-made bulldog clamp with modified port placement for management of distal ureter during laparoscopic nephroureterectomy. PATIENTS AND METHODS Between October 2013 and December 2014, 31 patients found to have upper tract urothelial carcinoma were treated using this technique. After finishing a standard laparoscopic transperitoneal nephrectomy in a 45° to 60° recumbent position, an additional 12-mm trocar was inserted at the lower abdomen to allow the surgeon to continue dissecting the ureter caudally toward the bladder wall without repositioning the patient. The intramural ureter was separated from the surrounding detrusor muscle and down to the bladder mucosa, until a tent-shaped bladder cuff and intramural ureter could be formed by retraction in the superior and lateral directions. Then, a custom-made laparoscopic bulldog clamp was placed at the bottom of the tent-shaped structure to prevent urine spillage, and the bladder was closed by two-layer running closure using a barbed suture. RESULTS All surgeries were completed uneventfully. The mean operative time and estimated blood loss were 146.6 minutes and 47.3 mL, respectively. The median duration of the postoperative hospital stay was 6 days. No complications were noted. There were no positive margins in any specimen. No patients experienced stone formation or local or bladder recurrence during the 10.5-month follow-up period. CONCLUSIONS Our novel technique fully replicates the open excision technique and conforms to the strictest oncologic principles while avoiding patient repositioning and the use of staplers (EndoGIA or Hemolock) to prevent stone formation.

Prognostic Value of Inflammatory and Nutritional Scores in Renal Cell Carcinoma After Nephrectomy.

Micro‐Abstract Various biomarkers that reflect the nutrition and inflammation status have been associated with survival for renal cell carcinoma (RCC) patients. In the present study, we compared the prognostic significance of inflammatory and nutritional scores, including the prognostic nutritional index (PNI), neutrophil‐to‐lymphocyte ratio, platelet‐to‐lymphocyte ratio, and lymphocyte‐to‐monocyte ratio, in patients with RCC undergoing nephrectomy and found PNI might be a better prognostic factor than are other factors for both overall survival and progression‐free survival. Introduction: We compared the prognostic significance of inflammatory and nutritional scores, including the prognostic nutritional index (PNI), neutrophil‐to‐lymphocyte ratio, platelet‐to‐lymphocyte ratio, and lymphocyte‐to‐monocyte ratio in patients with renal cell carcinoma (RCC) undergoing nephrectomy. Patients and Methods: We retrospectively analyzed the data from 1360 patients with RCC undergoing nephrectomy from 2001 to 2010. The PNI was calculated as the serum albumin level (g/L) + 5 × lymphocyte count (109/L). The receiver operating characteristic (ROC) curve analysis was used to determine the cutoff values. The areas under the ROC curve (AUCs) were calculated to compare the predictive ability of the indexes. Univariate and multivariate analyses were used to identify the prognostic factors for overall survival (OS) and progression‐free survival (PFS). Results: The median follow‐up period after surgery was 67 months (range, 2‐108 months). The PNI had the largest AUC for both OS and PFS. On univariate analysis, each index was associated with OS and PFS. On multivariate analysis, PNI, rather than other inflammatory and nutritional scores, remained as a risk factor for OS (hazard ratio [HR], 1.645; 95% confidence interval [CI], 1.153‐2.348; 2P = .006) and PFS (HR, 1.705; 95% CI, 1.266‐2.296; 2P < .001). Conclusion: The preoperative PNI might be a good prognostic factor for both OS and PFS in RCC patients undergoing nephrectomy.

Detection of urothelial carcinoma, upper tract urothelial carcinoma, bladder carcinoma, and urothelial carcinoma with gross hematuria using selected urine-DNA methylation biomarkers: A prospective, single-center study

INTRODUCTION Hematuria is the most common symptom of urothelial carcinomas (UC) but is often idiopathic. Cystoscopy is expensive which involves considerable patient discomfort, and conventional urine cytology for noninvasive UC detection and disease monitoring suffers from poor sensitivity. We aim to evaluate the performance of genes selected from a previous study in detecting UC, especially among patients with gross hematuria, as well as upper tract urothelial carcinoma (UTUC) and bladder carcinoma separately, in voided urine samples. METHODS Using methylation-specific polymerase chain reaction, we examined the promoter methylation status of 10 genes in voided urine samples among 473 patients at our institution, including 217 UC patients and 256 control subjects. RESULTS The final combination of VIM, CDH1, SALL3, TMEFF2, RASSF1A, BRCA1, GDF15, and ABCC6 identified UC with a sensitivity of 0.83 and a specificity of 0.60. Additionally, a panel of selected genes (CDH1, HSPA2, RASSF1A, TMEFF2, VIM, and GDF15) identified UTUC with a sensitivity of 0.82 and a specificity of 0.68, while a panel of selected genes (VIM, RASSF1A, GDF15, and TMEFF2) identified bladder carcinoma with a sensitivity of 0.82 and a specificity of 0.53. Remarkably, a different panel (CDH1, SALL3, THBS1, TMEFF2, VIM, and GDF15) identified UC in patients with gross hematuria with 0.89 sensitivity and 0.74 specificity, and sensitivity (0.91) and specificity (0.92) could be achieved when cytology was included. CONCLUSIONS The selected urine-DNA methylation biomarkers are reliable, noninvasive, and cost-effective diagnostic tools for bladder carcinoma and UTUC, especially among patients with gross hematuria.

Prognostic significance of the combination of preoperative hemoglobin and albumin levels and lymphocyte and platelet counts (HALP) in patients with renal cell carcinoma after nephrectomy

BackgroundTo evaluate the prognostic significance of the novel index combining preoperative hemoglobin and albumin levels and lymphocyte and platelet counts (HALP) in renal cell carcinoma (RCC) patients.MethodsWe enrolled 1360 patients who underwent nephrectomy in our institution from 2001 to 2010. The cutoff values for HALP, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio were defined by using X-tile software. Survival was analyzed by the Kaplan–Meier method, with differences analyzed by the log-rank test. Multivariate Cox proportional-hazards model was used to evaluate the prognostic significance of HALP for RCC.ResultsLow HALP was significantly associated with worse clinicopathologic features. Kaplan-Meier and log-rank tests revealed that HALP was strongly correlated with cancer specific survival (P < 0.001) and Cox multivariate analysis demonstrated that preoperative HALP was independent prognostic factor for cancer specific survival (HR = 1.838, 95%CI:1.260–2.681, P = 0.002). On predicting prognosis by nomogram, the risk model including TNM stage, Fuhrman grade and HALP score was more accurate than only use of TNM staging.ConclusionsHALP was closely associated with clinicopathologic features and was an independent prognostic factor of cancer-specific survival for RCC patients undergoing nephrectomy. A nomogram based on HALP could accurately predict prognosis of RCC.

Prognostic role of chromogranin A in castration-resistant prostate cancer: A meta-analysis

We aimed to investigate the prognostic value of chromogranin A (CgA) in castration-resistant prostate cancer (CRPC). We conducted a systematic literature search of PubMed, Web of Science, and EMBASE for citations published prior to September 2017 that described CgA and CRPC and performed a standard meta-analysis on survival outcomes. Our meta-analysis included eight eligible studies with 686 patients. The results were as follows: progression-free survival (PFS) was associated with CgA level (hazard ratio [HR] = 2.47, 95% confidence interval [CI]: 1.47–4.14, P = 0.0006); PFS was relative to CgA change (HR = 9.22, 95% CI: 3.03–28.05, P < 0.0001); and overall survival (OS) was relative to CgA level (HR = 1.47, 95% CI: 1.15–1.87, P = 0.002). When we divided the patients into two groups according to therapy status, the result for OS relative to CgA level was an HR of 1.26 (95% CI: 1.09–1.45, P = 0.001) in the first-line hormonal therapy group, and an HR of 2.33 (95% CI: 1.40–3.89, P = 0.001) in the second-line hormonal therapy or chemotherapy group. This meta-analysis indicated that a high CgA level had a negative influence on OS and PFS in CRPC patients. In addition, CRPC patients with a rising CgA had a shorter PFS. Further studies are needed to verify the prognostic value of CgA in CRPC.

A Novel Predictor of Survival with Renal Cell Carcinoma After Nephrectomy

PURPOSE To validate plasma fibrinogen and serum cholesterol levels as prognostic factors for patients with renal cell carcinoma (RCC) and to explore the prognostic value of their combination. PATIENTS AND METHODS Medical data for 1360 RCC patients after nephrectomy were collected. X-tile software was used to determine the cutoff values. The association between clinicopathological factors and fibrinogen and cholesterol levels was determined, and factors predicting survival were examined by multivariate analysis. RESULTS The median follow-up was 67 months (interquartile range 36-74 months). On univariate and multivariate analysis, both preoperative plasma fibrinogen and serum cholesterol were independent prognostic factors of cancer-specific survival (CSS) and progression-free survival (PFS). By combining the two factors, we developed a novel index, fibrinogen-cholesterol (FC) score and found it to have better prognostic accuracy than the two factors alone. FC was an independent prognostic factor for both CSS (FC score = 1: hazard ratio [HR] = 3.207, 95% confidence interval [CI] = 1.775-5.793; FC score = 2: HR = 5.516, 95% CI = 2.891-10.527) and PFS (FC score = 1: HR = 2.178, 95% CI = 1.545-3.071; FC score = 2: HR = 3.709, 95% CI = 2.355-5.840). CONCLUSION Both preoperative plasma fibrinogen and serum cholesterol levels are independent prognostic factors for CSS and PFS in RCC patients after nephrectomy. A novel indicator, FC score, could be considered a novel preoperative prognostic index in RCC.