Zhenghua Ju

Association of Low Expression of Notch-1 and Jagged-1 in Human Papillary Bladder Cancer and Shorter Survival

PURPOSE We investigated the expression of Notch receptors and ligands in normal bladder transitional epithelium and transitional cell carcinoma of the bladder. We also explored its clinical and pathological implications. MATERIALS AND METHODS The expression of Notch-1 to 3, Jagged-1 and Delta-like-1 was detected respectively in 70 cases of bladder carcinoma, 10 of normal urothelium and the 2 cell lines T24 and BIU-87 using immunohistochemistry. Reverse transcriptase-polymerase chain reaction and Western blot were used to assay the expression level of Notch-1 and Jagged-1. The predictive value of this expression for prognosis was investigated by Kaplan-Meier curves and Cox proportional hazards analysis in a multivariate model. RESULTS All 5 kinds of Notch factors were intensively stained in normal bladder transitional epithelium immunohistochemically but expression was significantly decreased in tumor tissues. Moreover, expression of the 5 genes in papillary tumors was lower than in invasive tumors but only Notch-1 and Jagged-1 showed a statistically significant difference. Postoperative disease-free survival time in patients with low Notch-1 plus Jagged-1 expression was significantly shorter than that in patients with other expression patterns in papillary tumors (p = 0.014). Multivariate Cox proportional hazards model analysis identified Jagged-1 expression as an independent prognostic factor for disease-free survival (RR 3.09, p = 0.011). CONCLUSIONS The Notch family expression pattern in papillary bladder transitional cell carcinoma is different from that in invasive bladder transitional cell carcinoma. Low expression of Notch-1 as well as Jagged-1 is potentially a useful marker for survival in patients with papillary bladder transitional cell carcinoma.

Laparoscopic Adrenalectomy for Beginners Without Open Counterpart Experience: Initial Results Under Staged Training

OBJECTIVES To develop a staged laparoscopic training program for beginners to perform laparoscopic adrenalectomy (LA) and to determine its safety and feasibility. METHODS From January 2002 to October 2007, 5 beginners (postgraduate years 1-5) without previous experience in open adrenalectomy were selected randomly to receive the staged laparoscopic training, including box-trainer, animal model, and mentor-initiated clinical training. During the clinical training, the trainees acted as the camera holder first, and then selectively performed simple operations, such as laparoscopic renal cyst unroofing. Finally, they performed 30 LAs independently under the mentors supervision using the technique of anatomic retroperitoneoscopic adrenalectomy. The clinical data of the 30 LAs performed by each the trainees (150 LAs total) were collected and compared with the data from the initial 30 LAs of the mentor. RESULTS All LAs were completed successfully. No procedure required conversion to open surgery. The median operative time of the trainees was 82.3 minutes (range 59-133), which was obviously shorten than the mentors (median operative time 131.5 minutes, range 73-230, P < .001). The learning curve among the trainees was shorter compared with that of the mentor. No major complications were observed. The minor intraoperative and postoperative complication rate for the trainees was 0.67% and 6.7%, respectively, not significantly different from those of the mentor (0% and 3.3%, respectively; both P > .05). All complications developing in patients treated by the trainees required only conservative therapy. CONCLUSIONS It was safe and feasible for beginners without previous open counterpart experience to perform LA using staged training.

Association of DNA polymorphisms within the CYP11B2/CYP11B1 locus and postoperative hypertension risk in the patients with aldosterone-producing adenomas.

OBJECTIVES Hypertension often persists after adrenalectomy for primary aldosteronism. Traditional factors associated with postoperative hypertension were evaluated, but whether genetic determinants were involved remains poorly understood. The aim of this study was to investigate the association of DNA polymorphisms within steroid synthesis genes (CYP11B2, CYP11B1) and the postoperative resolution of hypertension in Chinese patients undergoing adrenalectomy for aldosterone-producing adenomas (APA). METHODS Ninety-three patients with APA were assessed for postoperative resolution of hypertension. All patients were genotyped for rs1799998 (C-344 T), intron 2 conversion, rs4539 (A2718G) within CYP11B2 and rs6410 (G22 5A), rs6387 (A2803G) within CYP11B1. The associations between CYPB11B2/CYP11B1 polymorphisms and persistent postoperative hypertension were assessed by multivariate analysis. RESULTS CYP11B2-CYP11B1 haplotype was associated with persistent postoperative hypertension in Chinese patients undergoing adrenalectomy with APA (P = .006). Specifically, the rs4539 (AA) polymorphism was associated with persistent postoperative hypertension (P = .002). Multivariate logistic regression revealed the common haplotypes H1 (AGACT), H2 (AGAWT), and H3 (AGAWC) were associated with the persistent postoperative hypertension (P = .01, 0.03, 0.005 after Bonferroni correction). Additional predictors of persistent postoperative hypertension included duration of hypertension (P <.0005), family history of hypertension (P = .001), and elevated systolic blood pressure (P = .015). CONCLUSIONS The rs4539 (AA), H1, H2, and H3 are genetic predictors for postoperative persistence of hypertension for Chinese patients treated by adrenalectomy with APA. DNA polymorphisms at CYP11B2/B1 locus may confer susceptibility to postoperative hypertension of patients with APA.

Relationship between the expression of RASSF1A protein and promoter hypermethylation of RASSF1A gene in bladder tumor

SummaryTo investigate the relationship between the expression of RASSF1A protein and promoter hypermethylation of RASSF1A gene, RASSF1A protein expression was measured by Western blotting in 10 specimens of normal bladder tissues and 23 specimens of bladder transitional cell carcinoma (BTCC). The promoter methylation in BTCC and normal bladder tissues was detected by methylation-specific PCR (MSP). The results showed that the expression level of RASSF1A protein was significantly lower in BTCC tissues than that in normal bladder tissues. However, it was not correlated with its clinical stages and pathological grades. The frequency of promoter methylation of RASSF1A gene was higher in BTCC tissues than that in normal bladder tissues. In 14 patients with the aberrant promoter methylation, 13 showed loss or low expression of RASSF1A protein. It is concluded that RASSF1A gene promoter methylation may contribute to the low level or loss of RASSF1A protein expression, the inactivation of RASSF1A gene and the genesis of BTCC. But, it may bear no correlation with its clinical stages and pathological grades.To investigate the relationship between the expression of RASSF1A protein and promoter hypermethylation of RASSF1A gene, RASSF1A protein expression was measured by Western blotting in 10 specimens of normal bladder tissues and 23 specimens of bladder transitional cell carcinoma (BTCC). The promoter methylation in BTCC and normal bladder tissues was detected by methylation-specific PCR (MSP). The results showed that the expression level of RASSF1A protein was significantly lower in BTCC tissues than that in normal bladder tissues. However, it was not correlated with its clinical stages and pathological grades. The frequency of promoter methylation of RASSF1A gene was higher in BTCC tissues than that in normal bladder tissues. In 14 patients with the aberrant promoter methylation, 13 showed loss or low expression of RASSF1A protein. It is concluded that RASSF1A gene promoter methylation may contribute to the low level or loss of RASSF1A protein expression, the inactivation of RASSF1A gene and the genesis of BTCC. But, it may bear no correlation with its clinical stages and pathological grades.

DNA polymorphisms in exon 1 and promoter of the CDH1 gene and relevant risk of transitional cell carcinoma of the urinary bladder

To investigate the association between DNA polymorphisms, including single‐nucleotide polymorphisms (SNPs) and insertion/deletion polymorphisms, in exon 1 and promoter of the CDH1 gene, and the risk of transitional cell carcinoma (TCC) of the urinary bladder (TCCB).

The single needle method for urethrovesical anastomosis with strengthened posterior fixation during laparoscopic radical prostatectomy

SummaryThe single needle method for urethrovesical anastomosis with strengthened posterior fixation during laparoscopic radical prostatectomy was explored. The method was initiated by performing a fixing suture with a knot at 4 o’clock of the posterior lip of bladder neck, and another suture at nearby position was performed to leave the knot outside. From 5 o’clock to 8 o’clock, sutures were performed every one o’clock to secure posterior approximation, then every two o’clock a suture. To avoid a loose anastomosis, lock sutures were performed every 3 sutures. The needle was always driven full-thickness outside-in in the bladder neck and inside-out on the urethra. After completing the full circumference, the needle was drawn near the 4 o’clock and tied at the tail end. Any leakage could be closed with additional interrupted sutures. The clinical data of 89 patients who underwent this method were retrospectively compared with those of 23 patients who underwent the single knot method. The results showed that the anastomosis, operative and catheterization time was 17.6±4.7 min, 134.0±10.7 min and 6.5+1.6 days respectively. There were 3 temporal urinary leakages identified in 89 cases requiring prolonged catheterization. No urinary leak and anastomotic stricture was confirmed, and 95.2% patients had total urinary control. It was concluded that this method was simple and safe for urethrovesical anastomosis.The single needle method for urethrovesical anastomosis with strengthened posterior fixation during laparoscopic radical prostatectomy was explored. The method was initiated by performing a fixing suture with a knot at 4 o’clock of the posterior lip of bladder neck, and another suture at nearby position was performed to leave the knot outside. From 5 o’clock to 8 o’clock, sutures were performed every one o’clock to secure posterior approximation, then every two o’clock a suture. To avoid a loose anastomosis, lock sutures were performed every 3 sutures. The needle was always driven full-thickness outside-in in the bladder neck and inside-out on the urethra. After completing the full circumference, the needle was drawn near the 4 o’clock and tied at the tail end. Any leakage could be closed with additional interrupted sutures. The clinical data of 89 patients who underwent this method were retrospectively compared with those of 23 patients who underwent the single knot method. The results showed that the anastomosis, operative and catheterization time was 17.6±4.7 min, 134.0±10.7 min and 6.5+1.6 days respectively. There were 3 temporal urinary leakages identified in 89 cases requiring prolonged catheterization. No urinary leak and anastomotic stricture was confirmed, and 95.2% patients had total urinary control. It was concluded that this method was simple and safe for urethrovesical anastomosis.

A Multimodal Training Program for Laparoscopic Pyeloplasty

PURPOSE We introduced a multimodal training program for laparoscopic pyeloplasty (LP) and evaluated its safety, feasibility, and efficacy. METHODS The program consisted of box-trainer training, animal-model training, and operative training. Five trainees with different experiences in open pyeloplasty and laparoscopy were exposed to the program. The mentor performed objective and subjective evaluations at each stage to ensure the training quality and operation safety. The perioperative parameters of five groups of patients who underwent LP by the trainees independently were evaluated. RESULTS All trainees successfully finished the training program and independently performed five LPs under the supervision of the mentor. Five trainees spent different training times on the box-trainer and animal-model training,but acquired similar laparoscopic proficiency. There were no conversions to open procedures, transfusions, or deaths among the patients. No statistically significant difference was found in the operative time, estimated blood loss, postoperative hospital stay, and perioperative complications among the five trainees (P > 0.05). CONCLUSION The multimodal training program can be used to train residents to perform advanced LP through step-by-step training from box trainer to animal model to clinical practice. The mentor-initiated approach is important to guarantee the training quality and safety.

Expression of KAI1/CD82 and MRP-1/CD9 in transitional cell carcinoma of bladder.

The expression of KAI1/CD82 and MRP-1/CD9 in transitional cell carcinoma of bladder (TCCB) and its clinical significance were investigated. Immunohistochemistry was used to detect KAI1/CD82 and MRP-1/CD9 protein expression in 52 TCCB specimens. Correlation between the expression of KAI1/CD82 and MRP-1/CD9 to clinicopathologic factors was statistically analyzed. The results showed that the positive rate of KAI1/CD82 and MRP-1/CD9 in TCCB was 50% and 61.5%, respectively. The MRP-1/CD9 and KAI1/CD82 expression was significantly associated with grade of TCCB (P<0.05), but no correlation was found between MRP-1/CD9 or KAI1/CD82 expression and clinical stage of TCCB (P>0.05). The expression level of MRP-1/CD9 and KAI1/CD82 in recurrent TCCB samples was lower than that in non-recurrent samples (P<0.05). Meanwhile, the correlation between the KAI1/CD82 expression and MRP-1/CD9 expression was statistically significant (r=0.316, P<0.05). It was concluded that KAI1/CD82 and MRP-1/CD9 expression may be important prognostic indicators and potentially useful for assessing the biological behavior of TCCB.