| Background and Objects:As a common malignancy of the urinary system, the diagnostic methods of bladder cancer are varied. Cystoscopy and biopsy is the most reliable method of diagnosis of bladder cancer. But it’s invasive, relatively inconvenient and expensive that make it unaccepted. Urine cytology test is one of the main methods for bladder cancer diagnosis and postoperative follow-up. Thanks to its convenient and high specificity, urine cytology has been widely used in clinical practice since 1945 proposed by Papanicolaou and Marshall. But limited to the preparation technology, the smears of conventional cytology are thik, unclear and few diagnostic cells, which result in low sensitivity. With the advent of liquid-based cytology in the late 1990s, the cytological preparation technology has a quanlitative leap. The standardized automated production procedures was applied to reduce the dependence of conventional cytological smear quality on technology and experience. The special fixative of liquid-based cytology decreases cell degradation, removes mucus, white and red blood cells and enriches diagnostic cells to improve the smear quality. The effect of liquid-based cytology has been widely recognized in gynecological screening for cervical cancer. Application research in the field of nongynaecology including in the diagnosis of bladder cancer has been widely carried out recently.Objective:1. Review on the progress of urine specimen in bladder cancer diagnosis; 2. Assess the value of liquid-based cytology in the diagnosis of bladder cancer by comparing the urine liquid-based cytology and conventional cytology examination results which come from 124 inpatients in Nanfang Hospital.3. To evaluate the diagnostic value of liquid-based cytology for bladder cancer by a Meta-Analysis of liquid-based cytology and conventional cytology in diagnosis of bladder cancer.Methods1. Review on the progress of urine specimen in bladder cancer diagnosis Find documents and other relevant information on the advances of urine specimens in bladder cancer diagnosis and then make an overview.2. Comparison of diagnostic value in bladder cancer between Surepath liquid-based cytology and conventional cytologyThis study collected 124 inpatients in Nanfang Hospital from May 2015 to February 2016, who were suspected of bladder cancer. The second fresh morning urine specimens of all patients were taken at least 100 ml before cystoscopy and catheterization. The specimens were averaged divided and undertaken Surepath liquid-based cytology and conventional cytology examination randomly. According to the pathological results, the sensitivity, specificity and other diagnostic effect of liquid-based cytology and conventional cytology were calculated. p<0.05 was considered statistically significant.3. Meta-Analysis of diagnostic value of liquid-based cytology and conventional cytology in bladder cancerA systematic review of the literature using PubMed, EMBASE, Web of Science, The Cochrane Library, CNKI, WANFANG and VIP was performed by various relevant search terms in december 2015. The english search terms were:bladder cancer, bladder tumor, bladder neoplasm, bladder carcinoma, liquid-based cytology, autocyte prep, thin layer, thinprep, surepath, mo no layer and the Chinese search terms:膀胱肿瘤、膀胱癌、膀胱尿路上皮癌、膀胱移行细胞癌、液基细胞学.Reference Cochrane Collaboration Handbook developed search strategies to retrieve all studies on comparing the diagnostic value of bladder cancer between liquid-based cytology and conventional cytology. Screen literature according to the inclusion and exclusion criterias. Data extracted included study characteristics, sensitivity, specificity, false negative rate, false positive rate, accuracy rate, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, integrated area under the receiver operating characteristic curve (the area under the curve, AUC) and Q* index. QUADAS (quality assessment of diagnostic accuracy studies) was used to evaluate the quality of literature. All assessments of the quality of trials and data extraction were performed independently by 2 authors using a prespecified data abstraction forms, the third author’s opinion was used in case of any controversy. Use the Cochrane Collaboration’s RevMan 5.3 and Meta-Disc 1.4 software to analyse. All the results needed to make statistical analys like tests for heterogeneity, sensitivity analysis to make sure the results of Meta-Analysis was stable and reliable.Results1. Review on the progress of urine specimen in bladder cancer diagnosisLiquid-based cytology and urine tumor markers are the main research directions of diagnosis in bladder cancer by urine specimens in recent years. The liquid-based cytology is a new cytological production technology, which maintains the advantages of high specificity of cytology and improves the quality of smears at the same time. It is better than conventional cytology in the diagnosis of bladder cancer in early stage, but the more sensitive one is in dispute. Urine tumor markers because of its high sensitivity have been widespread concerned. Nuclear matrix protein 22, bladder cancer antigen, immunoCyt and fluorescence in situ hybridization technique have been approved by Food and Drug Administration for bladder cancer testing. But the specificity of tumor markers is not high. Thus scholars carried out relevant research which combined liquid-based cytology and bladder tumor markers in bladder cancer test. The relevant research found joint detection can improve diagnostic sensitivity, while maintaining high specificity.2. Comparison of diagnostic value in bladder cancer between Surepath liquid-based cytology and conventional cytologyAccording to the final pathology and cytology results of 124 inpatients, we find that the sensitivity (55.6%) and accuracy (71.0%) of Surepath liquid-based cytology in bladder cancer are significantly better than conventional cytology. But the specificity, positive predictive value and negative predictive value of both are no significantly different. The sensitivity (84.6%) of Surepath liquid-based cytology in high grade urothelial carcinoma is significantly higher than that in the low grade ones. In muscle invasive and non-muscle invasive bladder cancer, the sensitivity of Surepath liquid-based cytology in the former (75.8%) is significantly higher than the latter (29.2%). The sensitivity of Surepath liquid-based cytology and conventional cytology are 19.4% and 0.0% in low grade urothelial carcinoma,84.6% and 48.7% in high grade urothelial carcinoma,29.2% and 0.0% in non-muscle invasive bladder cancer and 75.8% and 45.5% in muscle invasive bladder cancer respectively. We find that Surepath liquid-based cytology is all significantly better than conventional cytology.3. Meta-Analysis of diagnostic value of liquid-based cytology and conventional cytology in bladder cancerFive studies on the diagnostic value of liquid-based cytology and conventional cytology for bladder cancer were included.3.1 Study on the diagnostic value of liquid-based cytology for bladder cancerThe threshold test of included studies shows spearman correlation coefficient is 0.20 and p value is 0.75, which suggest there is no threshold effect. Test for heterogeneity p=0.18, I2=36.2%. The results show no non-threshold effect heterogeneity among studies, so fixed effects model analysis has been used. The sensitivity (66%) and specificity (98%), positive likelihood ratio (34.20), and negative likelihood ratio (0.35), diagnostic odds ratio (101), AUC (0.83), Q* index (0.77) of liquid-based cytology in bladder cancer are presented. The results suggest that the diagnostic performance of liquid-based cytology for bladder cancer is moderate.3.2 Comparing the sensitivity of liquid-based cytology and conventional cytologyThe sensitivity of liquid-based cytology and conventional cytology are 66.0% and 52.2%. Test for heterogeneity p=0.18, I2=36%, the results show medium heterogeneity between studies. So fixed and random effects model analysis have been used respectively. The results show significant difference between the sensitivity of two groups (OR 1.81,95% CI (1.28-2.57), p<0.05). The sensitivity of liquid-based cytology is higher than conventional cytology.3.3 Comparing the specificity of liquid-based cytology and conventional cytologyThe specificity of liquid-based cytology and conventional cytology are 98.33% and 99.07%. Test for heterogeneity p=0.76, P=0%, the results show no significant heterogeneity between studies. So fixed effects model analysis has been used. The results show no significant difference between the specificity of two groups (RD-0.01,95%CI (-0.02～0.01),p=0.29). Sensitivity analyses of high quality studies show a similar result.3.4 Comparing the false negative rate of liquid-based cytology and conventional cytologyThe false negative rate of liquid-based cytology and conventional cytology are 34.39% and 47.72%. Test for heterogeneity p=0.18,I2=36%, the results showed medium heterogeneity between studies. So fixed and random effects model analysis have been used respectively. The results show significant difference between the false negative rate of two groups (OR 0.55,95%CI (0.39-0.78), p<0.05). The false negative rate of conventional cytology is higher than liquid-based cytology.3.5 Comparing the false positive rate of liquid-based cytology and conventional cytologyThe false positive rate of liquid-based cytology and conventional cytology are 1.67% and 0.93%. Test for heterogeneity p=0.76, P=0%, the results show no significant heterogeneity between studies. So fixed effects model analysis has been used. The results show no significant difference between the false positive rate of two groups (RD 0.01,95%CI (-0.01-0.02), p=0.29). Sensitivity analyses of high quality studies show a similar result.3.6 Comparing the accuracy rate of liquid-based cytology and conventional cytologyThe accuracy rate of liquid-based cytology and conventional cytology are 87.00% and 82.87%. Test for heterogeneity p=0.72, I2=0%, the results show no significant heterogeneity between studies. So fixed effects model analysis has been used. The results show significant difference between the accuracy rate of two groups (OR 1.40, 95%CI (1.06-1.85), p=0.02). The accuracy rate of liquid-based cytology is higher than conventional cytology. Sensitivity analyses of high quality studies show a similar result.3.7 Comparing the sensitivity of liquid-based cytology between different grade urothelial carcinomaThree of the included studies reported the sensitivity of liquid-based cytology in different grade urothelial carcinoma. The sensitivity of low grade and high grade urothelial carcinoma are 40.91% and 74.58%. Test for heterogeneity p=0.44, I2=0%, the results show no significant heterogeneity between studies. So fixed effects model analysis have been used. The results show significant difference between the sensitivity of two groups (OR 0.15,95%CI (0.06-0.36),p<0.05). The sensitivity of the high grade urothelial carcinoma is significant higher than the low grade.Conclusion1. Review on the progress of urine specimen in bladder cancer diagnosisUrine specimen has an important role in bladder cancer examination. With the continuous improvement of cytology technology and the discovery of the urinary bladder tumor markers, urine specimens will play a more important role in noninvasive test for bladder cancer. Liquid-based cytology not only maintains high specificity and improves the quality of smears, but also provides good specimens for subsequent immunohistochemistry test. It is worthy of further research and promotion.2. Comparison of diagnostic value in bladder cancer between Surepath liquid-based cytology and conventional cytologyIn our study, the sensitivity and accuracy of Surepath liquid-based cytology are significantly better than conventional cytology. But the specificity, positive predictive value and negative predictive value of both are no significant different. The sensitivity of Surepath liquid-based cytology in high grade urothelial carcinoma is significantly higher than that in low grade ones. In muscle invasive and non-muscle invasive bladder cancer, the sensitivity of Surepath liquid-based cytology in the former is significantly higher than the latter. Comparing the sensitivity of Surepath liquid-based cytology and conventional cytology in low-grade urothelial carcinoma, high-grade urothelial carcinoma, non-muscle invasive bladder cancer and muscle invasive bladder cancer, we find that Surepath liquid-based cytology have to be significantly better than conventional cytology. The results of our research seem to suggest that the applications in diagnosis of bladder cancer of Surepath liquid-based cytology should be promoted, recording the same specificity with relatively high sensitivity compared with conventional cytology.3. Meta-Analysis of diagnostic value of liquid-based cytology and conventional cytology in bladder cancerThe results of Meta-Analysis showed that the diagnostic performance of liquid-based cytology for bladder cancer is moderate. The sensitivity and accuracy rate of liquid-based cytology in bladder cancer are higher than conventional cytology. But the false negative rate of liquid-based cytology is lower than conventional cytology. The specificity and false positive rate present no significant difference. The sensitivity of liquid-based cytology in the high grade urothelial carcinoma is significant higher than the low grade. All above, liquid-based cytology would be a preferred cytology in diagnosis of bladder cancer. |
PDF Full Text Request