Cuijian Zhang

The correlation between size of renal cell carcinoma and its histopathological characteristics: a single center study of 1867 renal cell carcinoma cases

Study Type – Prognosis (case series)

The nucleosome binding protein NSBP1 is highly expressed in human bladder cancer and promotes the proliferation and invasion of bladder cancer cells.

NSBP1 is a recently identified member of the HMGN protein family which binds to nucleosomes and regulates gene transcription through chromatin remodeling. In this study, we aimed to investigate the potential role of NSBP1 in human bladder cancer. We examined NSBP1 expression in 114 surgically removed bladder cancer specimens as well as 11 human bladder cell lines by immunohistochemistry and Western blot analysis, and found that NSBP1 level was correlated with the increased tumor grade and pathologic stage, and lymph node metastasis. RNAi-mediated knockdown of NSBP1 in EJ cells, a bladder cancer cell line that overexpressed NSBP1, resulted in moderate decrease of cell viability, moderate blockage of cell cycle at G2/M phase, and decreased cyclin B1 expression, but had no effects on apoptosis. Moreover, NSBP1 knockdown led to reduced activity of MMP-9 but not MMP-2. Taken together, these results suggest that NSBP1 promotes the viability of bladder cancer cells through increased cell proliferation but not decreased apoptosis, and increases the invasion ability of metastatic bladder cancer cells through the upregulation of MMP-9 activity. Our findings not only provide a molecular understanding of the role of NSBP1 in bladder cancer, but also suggest NSBP1 RNAi as a novel therapeutic approach for bladder cancer.

Different Hereditary Contribution of the CFH Gene Between Polypoidal Choroidal Vasculopathy and Age-Related Macular Degeneration in Chinese Han People

PURPOSE To investigate whether 11 variants in complement factor H gene contributed differently in patients with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) of Chinese descent. METHODS We performed a case-control study in a group of Chinese patients with nAMD (n = 344) or PCV (n = 368) and contrasted the results against an independent control group comprising 511 mild cataract patients without any evidence of age-related maculopathy. Association analysis of allele and genotype frequencies was performed for 11 haplotype-tagging single-nucleotide polymorphisms (SNPs) at the CFH locus (rs1061170, rs1329428, rs1410996, rs2284664, rs375396, rs529825, rs551397, rs7540032, rs800292, rs2274700, and rs1065489). Multinomial logistic regression analyses were performed to estimate and compare the effect of these 11 CFH polymorphisms on AMD and PCV, using the wild-type genotype as reference. Differences in the observed genotypic distributions between cases and controls were tested by using χ(2) tests, with age and sex adjusted for using logistic regression. RESULTS CFH rs1065489 was not significantly associated with the nAMD phenotype in Chinese collections either on univariate or multivariate analysis (P > 0.05 for all comparisons). The other 10 SNPs of CFH were significantly associated with the nAMD phenotype. As for PCV, all 11 SNP markers were significantly associated with risk of PCV before or after correction for age and sex differences. Eight of the 11 SNP markers showed significant evidence of heterogeneity between AMD and PCV (P < 0.05 for all comparisons). CONCLUSIONS Our data suggest that the genetic architecture at the CFH locus is complex with some markers showing significant skewing of the genotypes toward nAMD or PCV in Asians. This further supports the clinical observation that nAMD and PCV could have distinct pathogenesis mechanisms, which will require larger studies to accurately dissect.

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.

The Significance of Metastasectomy in Patients with Metastatic Renal Cell Carcinoma in the Era of Targeted Therapy

Objective. To investigate the efficacy of surgery in the treatment of metastatic renal cell carcinoma (mRCC) and to identify prognostic factors. Methods. A single center retrospective study of 96 patients with mRCC from December 2004 to August 2013. Results. The median follow-up time was 45 months. Thirty-one (32.3%) of the patients received complete resection of metastatic sites, 11 (11.5%) of the patients underwent incomplete resection of metastatic sites, and 54 (56.3%) of the patients received no surgery. In the univariate Kaplan-Meier analysis, the median overall survival times of the three groups were 52 months, 16 months, and 22 months, respectively (p < 0.001). The difference in the overall survival time was statistically significant between complete resection and no surgery groups (HR = 0.43, p = 0.009), while there was no significant difference between the incomplete metastasectomy and no surgery groups (HR = 1.80, p = 0.102). According to the multivariate Cox regression analysis, complete metastasectomy (HR = 0.49, p = 0.033), T stage > 3 (HR = 1.88, p = 0.015), disease free interval <12 months (HR = 2.34, p = 0.003), and multiorgan involvement (HR = 2.00, p = 0.011) were significant prognostic factors. Conclusion. In the era of targeted therapy, complete metastasectomy can improve overall survival. Complete metastasectomy, T stage > 3, disease free interval <12 months, and multiorgan involvement are independent prognostic factors.

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.

A modified suture technique for transperitoneal laparoscopic dismembered pyeloplasty of pelviureteric junction obstruction.

OBJECTIVE To describe a modified suture technique for transperitoneal laparoscopic dismembered pyeloplasty (TPLDP) that can be consistently replicated. METHODS Between June 2010 and April 2014, 21 men and 7 women with primary pelviureteric junction obstruction underwent our modified TPLDP suture technique performed by the same surgeon. In our method, the dismembering should be performed after performing half of anastomosis to achieve the maintenance of correct orientation and the prevention of torsion of anastomosis. We defined the success criteria as complete clinical resolution of flank pain for the patients with flank pain and complete radiologic resolution for the asymptomatic patients. RESULTS The mean overall operative time for our technique was 137.3 minutes. The mean operative time for procedures on the left side was longer than on the right side (P = .02). The mean suture time was 37.2 minutes. The mean estimated blood loss was 29.4 mL, and the crossing vessel was found in 7 of 28 patients (25.0%). No open conversion was required. The mean follow-up time was 21.0 months. Only 1 patient still had frequent and intolerable flank pain after surgery whose treatment was unsuccessful. The rest of the patients got complete clinical or radiologic resolution. The success rate was 27 of 28 (96.4%). CONCLUSION Our modified TPLDP suture technique is feasible and seems to be safe and to allow high success rate for the treatment of pelviureteric junction obstruction. Sizable sample and further analysis about technique will be completed in the future.

Retrospective Analysis of the Efficacy and Safety of Sorafenib in Chinese Patients With Metastatic Renal Cell Carcinoma and Prognostic Factors Related to Overall Survival.

AbstractSorafenib has been recommended as first- or second-line treatment for metastatic renal cell carcinoma (mRCC) by several guidelines. The objective of this study is to evaluate the efficacy of sorafenib monotherapy in Chinese patients with mRCC and determine the prognostic clinicopathologic factors associated with survival in these patients.This is a single-arm retrospective study conducted in 2 tertiary medical centers; 140 mRCC patients were enrolled between January 2007 and June 2014. Sorafenib was administered at a dose of 400 mg twice daily, and continued until disease progression, at which point the dose was increased to 600 or 800 mg twice daily, or the onset of an intolerable adverse drug event (ADE) that required dose reduction or temporary suspension of treatment.The primary endpoint was overall survival (OS), and the secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety.The median follow-up time was 32 months. The median OS and PFS were 24 months (range, 3–88 months) and 16 months (range, 0–88 months), respectively. Patients with clear cell carcinoma had a greater OS (P = 0.001) whereas sarcomatoid differentiation (P = 0.045) and disease progression (P = 0.010) negatively impacted OS; time from kidney surgery or biopsy to initiation of sorafenib treatment was associated with PFS (P = 0.027). Efficacy analysis revealed that 3 (2.1%) patients achieved complete responses, 28 (20.0%) patients experienced partial responses, 88 (62.9%) patients had stable disease, and 21 (15.0%) patients developed progressive disease. Moreover, the ORR was 22.1%, and the DCR was 85.0%. Most ADEs were classified as grades 1 or 2 with only 14 (10.0%) patients experiencing a severe ADE (grade 3).Sorafenib monotherapy can achieve promising OS and PFS for Chinese patients with mRCC, especially in those with clear cell carcinoma, with manageable adverse events.

Squamous Cell Carcinoma of the Enlarged Prostatic Utricle in an Adult

A 39-year-old man with gross terminal hematuria and urethral discharge for 5 months was found to have a partial cystic and partial solid mass above the normal site of prostate, which was confirmed by magnetic resonance imaging (MRI) and transrectal ultrasonagraphy. A radical resection of the tumor was performed, and classical squamous cell carcinoma was confirmed by pathologic assay.

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.