Effect Of RDW On Diagnosis And Prognosis Of Patients With Biliary Stricture

BackgroundIt may be difficult to discriminate patients with benign biliary stricture (BBS) frommalignant biliary stricture (MBS). The biliary lesions are located inside of bile duct, whichcan not be easily observed by ordinary methods. The clinical features of BBS and MBSare similar. The sensitivity and specificity of several methods used for diagnosis of BBSand MBS are not ideal. The gold standards of BBS and MBS are from pathology. However,the positive rate of standard brush cytology is only about45%. EUS-FNA is only useful inpatients with mass around bile duct and may have the risk of metastasis. Although IDUS isuseful for the diagnosis of BBS and MBS, it can not obtain the tissues for pathologicalexamination. Some new techniques, such as new-generation cholangioscope, SPYGLASSand CLE, are promising methods but have some limitations (e.g. expensive and technically challenging). The serum tumor marker CA199and CEA are suboptimal for thediagnosis of MBS although widely used. Thus, it is necessary to find new methods toimprove the diagnostic effect of biliary stricture.Many patients with MBS undergoing palliative therapy of ERCP or PTCD do notreceive further management, which is due to late-stage of diseases without the chance ofsurgery, poor status unsuitable for chemo-radiotherapy or economic problems. The overallsurvival (OS) and related risk factors of this group of patients are not clear. It is helpful tochoose right stent type and appropriate therapeutic method by predicting the OS ofpatients undergiong ERCP.Recently, it has been shown that RDW can not only be used to guide the diagnosis ofanemia, but also able to discriminate MBS from BBS. It is the prognosis-related factor ofseveral diseases. The role of RDW in MBS was briefly reported by only one study, whichshowed that RDW was upregulated in patients with MBS. Does RDW in patients withdifferent biliary stricture sites or different etiologies make difference? Is RDW comparableor superior to traditional tumor marker CA199or CEA? Is there any relationship betweenRDW and the OS of patients after successful ERCP? All of these questions are unknown.AimThis study included two aims:1, to investigate the diagnostic value of RDW inpatients with MBS or BBS;2, to investigate the effect of RDW on OS of MBS patientsafter ERCP.MethodsPart one: Patients with biliary stricture admitted in Xijing Hospital of DigestiveDiseases form January2009to August2012were enrolled. The criteria of MBS includedone of the following evidences:1, pathological results were malignant by EUS-FNA,ultrasound or CT guided puncture or surgery;2, Invasive sign of vascular, distal organ ornear GI tract was found by different image or endoscopic modalities;3, consistentprogression demonstrated by imaging or death during follow-up in six months. Thecriteria of BBS was that no malignancy was found by pathology and no progression was detected within one year of follow-up. The imaging and blood test resources of patients onthe beginning of diagnosis of MBS or BBS were collected, including routine bloodanalysis, CA199, CEA, clinical symptoms, images, ERCP data and pathological results,etc. The biliary stricture site was divided into proximal or distal based on the lesionlocated above or below cystic duct. The etiologies of MBS included cholangiocarcinoma,gallbladder carcinoma, ampullary carcinoma, pancreatic carcinoma, hepatocellulercarcinoma and metastatic diseases etc. The etiologies of BBS included trauma of surgery,chronic pancreatitis, liver transplantation, PSC and choledochal cyst, etc. The difference ofRDW, clinical and imaging data between MBS and BBS was analyzed.Part two: Patients with MBS admitted in Xijing Hospital of Digestive Diseases formAugust2012to December2013were enrolled. The criteria of MBS was the same asmentioned above. The exclusion criteria included:1, metal or plastic stents were insertedbefore the enrollment;2, benign or indetermine biliary stricture;3, patients underwentsurgical resection, chemo-or radiotherapy after ERCP. The OS was determined byfollow-up through telephone. Resources of patients were collected as following: age,gender, clinical symptoms, imaging in the beginning of MBS and RDW. The criteria ofbiliary stricture site and etiologies were the same as mentioned above. The effects of RDWon the OS of all or subgroups of patients were analyzed.This study was a retrospectively, single-center study, which was approved byInstitutional Review Boards of Xijing Hospital. Proportions were compared using thechi-square test or Fisher exact test. Quantitative variables are expressed as means andstandard deviations and analyzed by t test between two groups. The correlations amongCEA, CA199and RDW were analyzed by Spearman method. The OS of MBS patientswere analyzed using Kaplan-Meier curves and the log-rank test. Univariable COXregression analysis was used to evaluate whether baseline characteristics were associatedwith the OS. All P values were two-sided and those <0.05were considered to besignificant. Analyses were performed with the SPSS software version17.0for Windows. ResultsPart one: Diagnostic value of RDW in patients with biliary stricture1.135MBS patients and55BBS patients were enrolled and compared. There wassignificant difference between the two groups regarding age, gender, main symptoms(all p<0.05).2. The values of RDW in MBS and BBS patients were0.160±0.022and0.140±0.015respectively. The value of RDW in MBS patients was significantly higherthan those of BBS patients. If cutoff value of RDW was set as0.15, the sensitivity andspecificity rate to diagnose MBS was47%and81%respectively.3. The value of RDW is significantly different among patients with different etiologies ofBBS. The BBS patients with live transplantation (0.160±0.012) and PSC (0.160±0.022)had higher RDW values than those with other diseases (all RDW<0.14, p<0.05).4. In patients with distal stricture, the value of RDW of malignant diseases was higherthan those of benign (0.157±0.022vs.0.139±0.015, p<0.001).5. When RDW and tumor markers were compared in MBS patients, there was nosignificant correlations between RDW and CA199(r=0.099, p=0.201) and betweenRDW and CEA (r=0.115, p=0.152).Part two: Prognostic value of RDW in MBS patients after ERCP1.152MBS patients were enrolled in this study. The mean age was67.1±11.1years old.58.5%of patients were male. Majority of patients (91.1%) had jaundice. The meanvalue of RDW in all MBS patients was0.160±0.030. The value of RDW in69.7%ofpatients was more than0.15. The OS of MBS patients with different etiologies varied.Comprared with cholangiocarcinoma, the OS of metastatic cancer (OR=3.63) andhepatocellular carcinoma were shorter and that of ampullary carcinoma is longer(OR=0.28).2. RDW value is correlated with the OS of MBS patients after ERCP (p<0.05). Themedian OS in patients with RDW<0.15was254days (95%CI:130.1-378.0days), which was longer than that of patients with RDW>=0.15(median OS128days,95%CI:82.1-174.0days).3. With the subgroup analysis of stricture site, it was shown that RDW value was relatedto the OS of MBS patients with distal stricture (p<0.05). The median OS in patientswith distal stricture and RDW<0.15was501days (95%CI:179.2-822.8days), whichwas longer than those with RDW>=0.15(median OS209days,95%CI:166.1-251.9days).4. With the subgroup analysis of different etiologies, RDW was related to the OS of MBSpatients with cholangiocarcinoma (p<0.05). The median OS in chogiocarnoma patientswith RDW<0.15was254days (95%CI:203.3-304.7days), which was longer thanthose with RDW>=0.15(median OS74days,95%CI:21.2-173.7days).Conclusion1. RDW is useful for the differential diagnosis of benign and malignant biliary stricture.The sensitivity and specificity for the diagnosis of MBS is47%and81%respectivelywith the RDW value more than0.15.2. RDW is an independent factor useful for the diagnosis of MBS, which is nor correlatedwith CA199or CEA.3. RDW value is a high risk factor for the poor OS of MBS patients after ERCP, which ismore meaningful in patients with distal stricture or cholangiocarcinoma. The medianOS of cholangiocarcinoma patients with RDW>0.15is less than3months.Implantation of plastic stent in this group of patients seems approprieate.