A critical decrease in dominant frequency and clinical outcome after catheter ablation of persistent atrial fibrillation.

BACKGROUND: Termination of persistent atrial fibrillation (AF) by radiofrequency ablation (RFA) is associated with a high probability of freedom from AF but requires extensive ablation and long procedure times. OBJECTIVE: The purpose of this study was to determine whether a critical decrease in the dominant frequency (DF) of AF is a sufficient endpoint for RFA of persistent AF. METHODS: Antral pulmonary vein isolation (APVI) followed by RFA of complex fractionated atrial electrograms (CFAEs) in the atria and coronary sinus was performed in 100 consecutive patients with persistent AF. The DF of AF in lead V1 and in the coronary sinus was determined by fast Fourier transform (FFT) analysis at baseline and before termination of AF to identify a critical decrease in DF predictive of sinus rhythm after RFA. RESULTS: A > or =11% decrease in DF had the highest accuracy in predicting freedom from atrial arrhythmias, with a sensitivity of 0.71 and a specificity of 0.82 (P <.001). At a mean follow-up of 14 +/- 3 months after one ablation procedure, sinus rhythm was maintained off antiarrhythmic drugs in 8/35 (23%) and 20/26 (77%) of patients with a <11% and > or =11% decrease in DF, respectively (P <.001). Sinus rhythm was maintained in 24/39 patients (62%) in whom RFA terminated AF. The duration of RFA and total procedure time were longer in patients with AF termination (95 +/- 23 and 358 +/- 87 minutes) than in patients with a <11% decrease in the DF (77 +/- 16 and 293 +/- 70 minutes) or > or =11% decrease in DF (80 +/- 17 and 289 +/- 73 minutes), respectively (P <.01). Among the variables of age, gender, left atrial diameter, duration of AF, left ventricular ejection fraction, duration of RFA, a > or =11% decrease in DF, and termination of AF, a > or =11% decrease in DF (odds ratio = 9.89, 95% confidence interval [CI] 2.84-34.47) and termination during RFA (OR = 4.38, 95% CI 1.50-12.80) were the only independent predictors of freedom from recurrent atrial arrhythmias. CONCLUSION: In a retrospective analysis of consecutive patients with persistent AF, a decrease in the DF of AF by 11% in response to APVI and ablation of CFAEs was associated with a probability of maintaining sinus rhythm that was similar to that when RFA terminates AF.

Progressive increase of genetic alteration in urinary bladder cancer by combined allelotyping analysis and comparative genomic hybridization.

Bladder cancer is the ninth most common cancer in the world. Urothelial carcinoma (formerly known as transitional cell carcinoma) comprises the majority of bladder cancers. In order to decipher the genetic alteration leading to the carcinogenesis of urothelial cancer, we performed genome-wide allelotyping analysis using 384 microsatellite markers spanning 22 autosomes together with comparative genomic hybridization (CGH) in 21 urothelial cancer. High frequency of allelic imbalance was observed in chromosome arm 1q (61.9%), 3p (61.9%), 4q (66.67%), 8p (57.14%), 9p (76.2%) and 9q (66.67%). Allelic imbalance with frequency above average was also observed in chromosome arm 2q, 10p, 10q, 11p, 11q, 12q, 13q, 15q, 17p and 19q. The allelic imbalance of each case and fractional allelic loss for each chromosome was associated with higher tumor grade and stage (P<0.05). We have also delineated several minimal deletion regions on chromosome 3p, 4q, 8p, 9p, 9q, 11p, 13q, 16q and 17p. By CGH analysis, common chromosomal alterations included gain of 1p, 1q, 12q, 16p, 17q and 19p as well as loss of 4q and 9p in most of the cases. Our findings may provide valuable information to locate putative oncogenes and tumor suppressor genes in the carcinogenesis of bladder cancer in this locality.

A randomized assessment of the incremental role of ablation of complex fractionated atrial electrograms after antral pulmonary vein isolation for long-lasting persistent atrial fibrillation.

OBJECTIVES: This study sought to determine whether ablation of complex fractionated atrial electrograms (CFAEs) after antral pulmonary vein isolation (APVI) further improves the clinical outcome of APVI in patients with long-lasting persistent atrial fibrillation (AF). BACKGROUND: Ablation of CFAEs has been reported to eliminate persistent AF. However, residual pulmonary vein arrhythmogenicity is a common mechanism of recurrence. METHODS: In this randomized study, 119 consecutive patients (mean age 60 +/- 9 years) with long-lasting persistent AF underwent APVI with an irrigated-tip radiofrequency ablation catheter. Antral pulmonary vein isolation resulted in termination of AF in 19 of 119 patients (Group A, 16%). The remaining 100 patients who still were in AF were randomized to no further ablation and underwent cardioversion (Group B, n = 50) or to ablation of CFAEs in the left atrium or coronary sinus for up to 2 additional hours of procedure duration (Group C, n = 50). RESULTS: Atrial fibrillation terminated during ablation of CFAEs in 9 of 50 patients (18%) in Group C. At 10 +/- 3 months after a single ablation procedure, 18 of 50 (36%) in Group B and 17 of 50 (34%) in Group C were in sinus rhythm without antiarrhythmic drugs (p = 0.84). In Group A, 15 of 19 patients (79%) were in sinus rhythm. A repeat ablation procedure was performed in 34 of 100 randomized patients (for AF in 30 and atrial flutter in 4). At 9 +/- 4 months after the final procedure, 34 of 50 (68%) in Group B and 30 of 50 (60%) in Group C were in sinus rhythm without antiarrhythmic drugs (p = 0.40). CONCLUSIONS: Up to 2 h of additional ablation of CFAEs after APVI does not appear to improve clinical outcomes in patients with long-lasting persistent AF.

Relationship between the spectral characteristics of atrial fibrillation and atrial tachycardias that occur after catheter ablation of atrial fibrillation.

BACKGROUND: During catheter ablation of complex fractionated atrial electrograms, persistent atrial fibrillation (AF) may convert to an atrial tachycardia (AT). OBJECTIVE: The purpose of this study was to investigate the possible mechanisms of AT by examining the spectral and electrophysiologic characteristics of AF and ATs that occur after catheter ablation of AF. METHODS: The subjects of this study were 33 consecutive patients with persistent AF who had conversion of AF to AT during ablation of AF (group I) and 20 consecutive patients who underwent ablation of persistent AT that developed more than 1 month after AF ablation (group II). Spectral analysis of the coronary sinus (CS) electrograms and lead V(1) was performed during AF at baseline, before conversion, and during AT. The spatial relationship between the AT mechanism and ablation sites was examined. RESULTS: A spectral component with a frequency that matched the frequency of AT was present in the baseline periodogram of AF more often in group I (52%) than in group II (20%, P = .02). Ablation resulted in a decrease in the dominant frequency of AF but not in the frequency of the spectral component that matched the AT. There was a significant direct relationship between the baseline dominant frequency of AF and the frequency of AT in the CS in group I (r = 0.76, P <.0001) but not in group II (r = 0.38, P = .09). ATs were macroreentrant in 64% and 60% of patients in groups I and II, respectively (P = .8). The AT site was more likely to be distant (>1 cm) from AF ablation sites in group I (70%) than in group II (35%, P = .007). CONCLUSION: The findings of this study suggest that ATs observed during ablation of AF often may be drivers of AF that become manifest after elimination of higher-frequency sources and fibrillatory conduction.

A fourteen-year review of radical cystectomy for transitional cell carcinoma demonstrating the usefulness of the concept of lymph node density.

OBJECTIVE: We studied the long-term outcome of radical cystectomy for transitional cell carcinoma and evaluated prognostic factors for disease specific survival. MATERIALS AND METHODS: A retrospective review was carried out for all cystectomies performed for transitional cell carcinoma between 1989 and 2002. Disease specific survival was correlated to patient, pathological and operative factors as well as to adjuvant therapy. RESULTS: Of the 133 cystectomies included, 100 were male and 33 were female patients. The median age was 69 years (range 43 to 86). The median follow up was 20 months (range 0 to 158). With univariate analysis, pT stage, N stage, lymph node density, carcinoma in-situ, surgical margin and post-operative radiotherapy to distant metastasis were predictive of disease specific survival. On the other hand, with multivariate analysis, only pT stage, lymph node density and post-operative radiotherapy to distant metastasis were predictive of disease specific survival. Within the group of node positive disease, lymph node density also predicted disease specific survival with both univariate and multivariate analyses. Patients with lymph node density 20% or below showed better disease specific survival. CONCLUSIONS: pT stage and lymph node density were found to be the most important predictive factors for disease specific survival after cystectomy in the Asian population.

A fourteen-year review of radical cystectomy for transitional cell carcinoma demonstrating the usefulness of the concept of lymph node density

OBJECTIVE: We studied the long-term outcome of radical cystectomy for transitional cell carcinoma and evaluated prognostic factors for disease specific survival. MATERIALS AND METHODS: A retrospective review was carried out for all cystectomies performed for transitional cell carcinoma between 1989 and 2002. Disease specific survival was correlated to patient, pathological and operative factors as well as to adjuvant therapy. RESULTS: Of the 133 cystectomies included, 100 were male and 33 were female patients. The median age was 69 years (range 43 to 86). The median follow up was 20 months (range 0 to 158). With univariate analysis, pT stage, N stage, lymph node density, carcinoma in-situ, surgical margin and post-operative radiotherapy to distant metastasis were predictive of disease specific survival. On the other hand, with multivariate analysis, only pT stage, lymph node density and post-operative radiotherapy to distant metastasis were predictive of disease specific survival. Within the group of node positive disease, lymph node density also predicted disease specific survival with both univariate and multivariate analyses. Patients with lymph node density 20 percent or below showed better disease specific survival. CONCLUSIONS: pT stage and lymph node density were found to be the most important predictive factors for disease specific survival after cystectomy in the Asian population.

Intravenous leiomyomatosis: two cases with different routes of tumor extension.

Intravenous leiomyomatosis is a rare smooth muscle tumor. We report two cases of intravenous leiomyomatosis that grew along different routes of the venous system into the inferior vena cava and the right atrium. The different route of extension makes a difference in the ease of excision of tumor masses. Using MEDLINE together with the references in each publication, we identified all cases of intracardiac leiomyomatosis reported in the English literature in the period between 1980 and 2003 and performed a brief review on this potentially lethal disease entity.

Frequent hypermethylation of promoter region of RASSF1A in tumor tissues and voided urine of urinary bladder cancer patients.

High frequency loss of 3p21.3 region where RASSF1A located was demonstrated in several tumors. We aimed to investigate the methylation status of RASSF1A and the frequency of LOH in 3p21.3 region in bladder cancer. Three bladder cancer cell lines, 40 cases of bladder TCC and 14 cases of paired voided urine samples were subjected to methylation analysis. By methylation specific PCR, complete methylation of promoter region of RASSF1A gene were detected in cell lines T24 and UMUC3. Demethylation treatment re-expressed RASSF1A in these 2 cell lines. Methylation of RASSF1A was also detected in 47.5% (19/40) of the TCC cases but not in 6 carcinoma in situ (CIS) or 6 normal urothelium samples. For LOH study, loss of 3p21.3 region was detected in 57.9% (11/19) of our cases. Interestingly, methylation of RASSF1A was found in 72.7% (8/11) of the cases with LOH but only in 12.5% (1/8) of the cases without LOH. Methylation of RASSF1A was detected in 50% (7/14) of voided urine samples, but not in normal control. It showed a higher sensitivity than conventional urine cytology in detecting cancer cells, especially for low grade cases. In conclusion, our results demonstrated a high frequency of RASSF1A methylation with frequent LOH in 3p21.3 region in bladder cancer. It suggested that it may be a potential tumor suppressor gene in this chromosomal region and can be silenced by promoter hypermethylation. Detection of aberrant gene methylation in routine voided urine was feasible and may provide a non-invasive and sensitive approach for cancer detection.

Hypermethylation of multiple genes in tumor tissues and voided urine in urinary bladder cancer patients.

PURPOSE: We aimed to investigate the methylation pattern in bladder cancer and assess the diagnostic potential of such epigenetic changes in urine. EXPERIMENTAL DESIGN: The methylation status of 7 genes (RARbeta, DAPK, E-cadherin, p16, p15, GSTP1, and MGMT) in 98 cases of bladder transitional cell carcinoma and 4 cases of carcinoma in situ was analyzed by methylation-specific PCR. Twenty-two cases had paired voided urine samples for analysis. RESULTS: In transitional cell carcinoma tumor tissues, aberrant methylation was frequently detected in RARbeta (87.8%), DAPK (58.2%), E-cadherin (63.3%), and p16 (26.5%), whereas methylation of p15 (13.3%), GSTP1 (5.1%), and MGMT (5.1%) is not common. No association between methylation status and grading or muscle invasiveness was demonstrated. In 22 paired voided urine samples of bladder cancer, methylation of DAPK, RARbeta, E-cadherin, and p16 could be detected in 45.5%, 68.2%, 59.1%, and 13.6% of the cases, respectively. The sensitivity of methylation analysis (90.9%) was higher than that of urine cytology (45.5%) for cancer detection. Methylation of RARbeta(50%), DAPK (75%), and E-cadherin (50%) was also detected in carcinoma in situ. In 7 normal urothelium samples and 17 normal urine controls, no aberrant methylation was detected except for RARbeta methylation in 3 normal urothelium samples (42.9%) and 4 normal urine samples (23.5%), respectively. CONCLUSIONS: Our results demonstrated a distinct methylation pattern in bladder cancer with frequent methylation of RARbeta, DAPK, E-cadherin, and p16. Detection of gene methylation in routine voided urine using selected markers appeared to be more sensitive than conventional urine cytology.