Hui Han

Expression of Bmi-1 is a prognostic marker in bladder cancer.

BackgroundThe molecular mechanisms of the development and progression of bladder cancer are poorly understood. The objective of this study was to analyze the expression of Bmi-1 protein and its clinical significance in human bladder cancer.MethodsWe examined the expression of Bmi-1 mRNA and Bmi-1 protein by RT-PCR and Western blot, respectively in 14 paired bladder cancers and the adjacent normal tissues. The expression of Bmi-1 protein in 137 specimens of bladder cancer and 30 specimens of adjacent normal bladder tissue was determined by immunohistochemistry. Statistical analyses were applied to test the relationship between expression of Bmi-1, and clinicopathologic features and prognosis.ResultsExpression of Bmi-1 mRNA and protein was higher in bladder cancers than in the adjacent normal tissues in 14 paired samples (P < 0.01). By immunohistochemical examination, five of 30 adjacent normal bladder specimens (16.7%) versus 75 of 137 bladder cancers (54.3%) showed Bmi-1 protein expression (P < 0.05). Bmi-1 protein expression was intense in 20.6%, 54.3%, and 78.8% of tumors of histopathological stages G1, G2, and G3, respectively (P < 0.05). Expression of Bmi-1 protein was greater in invasive bladder cancers than in superficial bladder cancers (81.5% versus 32.5%, P < 0.05). In invasive bladder cancers, the expression of Bmi-1 protein in progression-free cancers was similar to that of cancers that have progressed (80.0% versus 82.4%, P > 0.5). In superficial bladder cancers, the expression of Bmi-1 protein in recurrent cases was higher than in recurrence-free cases (62.5% versus 13.7%, P < 0.05). Bmi-1 expression was positively correlated with tumor classification and TNM stage (P < 0.05), but not with tumor number (P > 0.05). Five-year survival in the group with higher Bmi-1 expression was 50.8%, while it was 78.5% in the group with lower Bmi-1 expression (P < 0.05). Patients with higher Bmi-1 expression had shorter survival time, whereas patients with lower Bmi-1 expression had longer survival time (P < 0.05).ConclusionExpression of Bmi-1 was greater in bladder cancers than in the adjacent normal tissues. The examination of Bmi-1 protein expression is potentially valuable in prognostic evaluation of bladder cancer.

Modified Technique of Radical Inguinal Lymphadenectomy for Penile Carcinoma: Morbidity and Outcome

PURPOSE Classic radical inguinal lymphadenectomy is associated with significant morbidity. Modified inguinal lymphadenectomy has been used to decrease the complication rate but it may compromise the oncological effect and depends on the use of intraoperative frozen sections, which may be inaccurate. We modified the technique of radical inguinal lymphadenectomy to decrease postoperative complications without compromising oncological effectiveness. MATERIALS AND METHODS We performed 150 modified radical inguinal dissections in 75 patients with penile carcinoma from February 1999 to September 2008. Patients underwent modified radical inguinal dissection characterized by an S-shaped incision, precisely separating layers using an anatomical landmark and preserving the fascia lata. The boundaries of dissection are the same as those of radical inguinal lymphadenectomy. Survival and morbidity data were retrospectively analyzed, and survival probabilities were calculated. RESULTS Followup ranged from 12 to 113 months. Overall 3-year survival was 92%, and for N0, N1, N2 and N3 disease it was 100%, 100%, 85% and 57.1%, respectively. A total of 37 complications occurred including wound infection (1.4%), skin necrosis (4.7%), lymphedema (13.9%), seroma (2.0%), lymphocele (2.0%) and deep venous thrombosis (0.7%). CONCLUSIONS Morbidity related to groin dissection in patients with penile carcinoma can be decreased and oncological effectiveness can be preserved using this modified inguinal dissection technique.

Decreased expression of dual-specificity phosphatase 9 is associated with poor prognosis in clear cell renal cell carcinoma

BackgroundThe molecular mechanisms involved in the development and progression of clear cell renal cell carcinomas (ccRCCs) are poorly understood. The objective of this study was to analyze the expression of dual-specificity phosphatase 9 (DUSP-9) and determine its clinical significance in human ccRCCs.MethodsThe expression of DUSP-9 mRNA was determined in 46 paired samples of ccRCCs and adjacent normal tissues by using real-time qPCR. The expression of the DUSP-9 was determined in 211 samples of ccRCCs and 107 paired samples of adjacent normal tissues by immunohistochemical analysis. Statistical analysis was performed to define the relationship between the expression of DUSP-9 and the clinical features of ccRCC.ResultsThe mRNA level of DUSP-9, which was determined by real-time RT-PCR, was found to be significantly lower in tumorous tissues than in the adjacent non-tumorous tissues (p < 0.001). An immunohistochemical analysis of 107 paired tissue specimens showed that the DUSP-9 expression was lower in tumorous tissues than in the adjacent non-tumorous tissues (p < 0.001). Moreover, there was a significant correlation between the DUSP-9 expression in ccRCCs and gender (p = 0.031), tumor size (p = 0.001), pathologic stage (p = 0.001), Fuhrman grade (p = 0.002), T stage (p = 0.001), N classification (p = 0.012), metastasis (p = 0.005), and recurrence (p < 0.001). Patients with lower DUSP-9 expression had shorter overall survival time than those with higher DUSP-9 expression (p < 0.001). Multivariate analysis indicated that low expression of the DUSP-9 was an independent predictor for poor survival of ccRCC patients.ConclusionTo our knowledge, this is the first study that determines the relationship between DUSP-9 expression and prognosis in ccRCC. We found that decreased expression of DUSP-9 is associated with poor prognosis in ccRCC. DUSP-9 may represent a novel and useful prognostic marker for ccRCC.

Disease-specific survival after radical lymphadenectomy for penile cancer: Prediction by lymph node count and density

OBJECTIVE To investigate the value of removed lymph node (LN) count and LN density (LND) for predicting disease-specific survival (DSS) rate following radical lymphadenectomy in patients with penile cancer. METHODS We retrieved data from 146 patients who were surgically treated between 2002 and 2012. receiver-operating characteristic curve analysis was used to calculate the optimal cutoff value of LN count and LND for predicting DSS rate. LND was analyzed as a categorical variable by grouping patients with pN+tumors into 2 categories. Multivariate Cox regression analysis was used to test the effect of various variables on DSS rate based on collinearity in various models. RESULTS Median follow-up was 42 months. Overall, 75 patients (51.4%) had pN0 disease, and 71 patients (48.6%) had pN+disease. The optimal cutoff value of LN count and LND were 16% and 16%, respectively. Among patients with pN0 tumors, the number of LNs removed (≥16 LNs) was an independent significant predictor of DSS rate in univariate and multivariate analyses (all P<0.05). Stratifying pN+ patients as above versus below the LND threshold demonstrated significant differences in 5-year DSS: 81.2% versus 24.4% (P < 0.001). In multivariate models including known prognostic factors, LND was a statistically significant independent predictor of DSS rate (hazard ratio = 4.31 and 3.96 for above vs. below the LND threshold, respectively). CONCLUSIONS The removal of at least 16 LNs was associated with a significantly longer DSS rate in patients with pN0 penile cancer. Additionally, an LND above 16% is an independent predictor of DSS rate in patients with pN+tumors. Further independent validation is required to determine the clinical usefulness of LN count and LND in this patient population.

Casein Kinase 2 Inhibition Attenuates Androgen Receptor Function and Cell Proliferation in Prostate Cancer Cells

Casein kinase 2 (CK2) is constitutively active with dual specificity and exists as a hetero‐tetrameric complex of α, α′, and β subunits. Its aberrant expression and elevated activity have been linked to many human cancers, including prostate cancer. As an effort to develop new chemotherapy for prostate cancers, in this study, we tested the effects of tetra‐bromo‐cinnamic acid (TBCA), a newly synthetic CK2‐selective CK2 inhibitor, on androgen receptor (AR) transactivation, cell proliferation, and viability in multiple prostate cancer cell lines.

Fascia Lata Preservation During Inguinal Lymphadenectomy for Penile Cancer: Rationale and Outcome

OBJECTIVE To investigate local groin recurrence and morbidity associated with fascia lata preservation during inguinal lymphadenectomy (LAD) for penile carcinoma. METHODS Between January 2002 and December 2011, 201 inguinal dissections with preservation of the fascia lata were performed in 104 patients with clinical disease staged at ≤N2. The dissection boundaries were the same as those for radical inguinal LAD. All superficial inguinal nodes were removed en bloc. The cribriform fascia near the femoral canal was divided, and the deep inguinal lymph nodes were dissected. The fascia lata was completely preserved and sutured to the subcutaneous tissue. Sartorius muscle transposition was eliminated. Survival and morbidity data were retrospectively analyzed, and survival probabilities were calculated. RESULTS The median operative time for unilateral inguinal LAD was 45 minutes (range, 40-60 minutes). Median follow-up was 36 months (range, 10-130 months). A mean number of 12.5 nodes were removed per groin. One patient (1%) had a recurrence outside the borders of the fascia lata after 7 months of follow-up. The 3-year disease-free survival rate was 92.1% (100% for pN0, 91.3% for pN1, 80% for pN2, and 33.3% for pN3 disease). A total of 59 complications (29.3%) occurred, including wound infection (2.5%), skin necrosis (5.5%), lymphedema (11.8%), seroma formation (1.5%), lymphocele (5%), paresthesia (3.5%), and deep venous thrombosis (0.5%). CONCLUSION Inguinal dissections with preservation of the fascia lata for penile carcinoma patients without extranodal extension is as effective as the classic dissection technique but decreases complications related to groin dissection.

Renal plasmacytoma: Report of a rare case and review of the literature

Renal plasmacytoma is extremely rare, presenting diagnostic challenges due to its unusual location and non-specific or absent symptoms. To the best of our knowledge, only 24 cases of renal plasmacytoma have been reported in the literature. The present study reports a case of primary renal plasmacytoma in a 46-year-old female patient. Computed tomography (CT) revealed that the mass was located in the lower pole of the left kidney and metastasis was detected in an enlarged para-aortic lymph node. Following careful preparation, a partial nephrectomy was performed and the retroperitoneal lymph node was resected. A pathological examination revealed a renal parenchyma with lymph node involvement; this was confirmed by immunohistochemistry and nested polymerase chain reaction (PCR). Consequently, a diagnosis of a renal extramedullary plasmacytoma (EMP) was proposed. Following this unexpected diagnosis, various examinations were performed, but there was no evidence of systemic plasma cell disease. The patient refused further therapy, including external beam radiotherapy and chemotherapy. Abdominal CT was performed three months post-surgery and did not reveal any relapse. The patient remains disease-free at nine months post-surgery. The current study also presents a review of the literature. Although the general prognosis and outcome of EMP is good, a follow-up examination is recommended due to the possibility of relapse or progression to plasma cell neoplasm (PCN).

Preoperative Albumin to Globulin Ratio (AGR) as prognostic factor in renal cell carcinoma

Background: Malnutrition and systemic inflammatory response are frequently associated with prognosis in patients with several types of cancer, including renal cell carcinoma (RCC). The study is aimed to investigate the ability of preoperative serum albumin to globulin ratio (AGR) to predict the long-term mortality of RCC patients. Methods: The study is a retrospective study of an unselected cohort of 895 RCC patients who underwent a curative radical or partial nephrectomy at the Department of Urology in the Sun Yat-Sen University Cancer Center between January 2000 and December 2012 and had documented preoperative serum total protein and albumin (ALB) levels. The preoperative AGR was calculated as the ratio of ALB to (total protein-ALB) and its association with other clinical indices was assessed using survival analysis. Results: Low preoperative AGR was associated with older population, lower hemoglobin, higher total protein, lower ALB, lower body mass index and advanced stage. The univariate and multivariate Cox analyses demonstrated that preoperative AGR was an independent prognostic indicator of overall survival (OS) (hazard ratio (HR): 0.63, 95% confidence interval (CI): 0.43 to 0.93, P=0.022). In addition, patients with low preoperative AGR at pT1-2, pT3-4, pN0, pN1, pM0 and pM1 stages had significantly shorter OS than patients with high preoperative AGR. Conclusion: Preoperative AGR is a proven objective, reproducible, inexpensive survival predictor of RCC patients following surgical resection and should be considered for routine clinical use.

A Modified Technique for Neourethral Anastomosis in Orthotopic Neobladder Reconstruction

OBJECTIVES To introduce a modified technique for urethral anastomosis in orthotopic neobladder reconstruction. METHODS Between January 2002 and August 2008, about 141 consecutive patients (130 men and 11 women) underwent total cystectomy and orthotopic neobladder reconstruction in which a modified technique was used to anastomosed the caudal-most part of the intestinal neobladder directly to the urethral remnant. The emptying of the neobladder, the early and late complications at the urethral anastomosis was evaluated. RESULTS Mean patient age at surgery was 58.4 years (range, 33-83) and median follow-up was 42 months (range, 4-83 months). Early urine leakage at the vesicourethral anastomosis developed in 1 patient, and was cured by extending catheter drainage. A total of 138 patients had good emptying of the neobladder, with residual urine volume < 50 mL. Three patients had residual urine volume > 100 mL, and achieved good emptying after intermittent catheterization once a week for 6-12 months. No late complications occurred at the urethral anastomosis site. Daytime continence was good or satisfactory in 97.0% of patients and night-time continence was good or satisfactory in 88.5% of patients. CONCLUSIONS The clinical outcome of our modified technique for urethral anastomosis in orthotopic neobladder substitution was excellent, but the advantage of this technique needs prospective controlled study.

Tumor PD-L1 expression is correlated with increased TILs and poor prognosis in penile squamous cell carcinoma

ABSTRACT Despite its rare incidence worldwide, penile squamous cell carcinoma (PeSCC) still presents with significant morbidity and mortality due to the limited treatment options for advanced patients, especially those in developing countries. The program death-1 (PD-1)/PD-1 ligand (PD-L1) axis has been demonstrated to play an important role in tumor immune escape, and immunotherapies targeting this pathway have shown great success in certain cancer types. Here, we analyzed the expression pattern of PD-L1 in tumor cells and tumor-infiltrating lymphocytes (TILs) in PeSCC with a multi-center cohort. We found that the majority of PeSCCs (53.4%) were PD-L1-positive and that high PD-L1 expression in tumor cells was associated with a poor prognosis. Notably, PD-L1 expression in tumor cells was significantly associated with the extent of TILs and CD8+ TILs. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) showed that PD-L1 was positively correlated with interferon-gamma (IFNγ) and CD8+ gene expression. Moreover, we defined the constitutive and inducible surface expression of PD-L1 in newly established primary PeSCC cell lines. Interestingly, two PeSCC cell lines had high intrinsic PD-L1 expression. Another cell line showed low PD-L1 expression, but the PD-L1 expression could be induced by IFNγ stimulation. Overall, our data showed that high PD-L1 expression in penile tumor cells indicated a poor prognosis. The upregulation of PD-L1 in PeSCC included both extrinsic and intrinsic mechanisms. These findings indicated that the PD-1/PD-L1 axis might be a potential therapeutic target for patients with penile squamous cell carcinoma.