Risk Factors for Post-ERCP Cholangitis in Patients with Pancreatic Cancer from a Single Referral Center in Iran

Cholangitis is relatively uncommon (Boey & Way, 1980). Any condition that leads to stasis or obstruction of bile in the common bile duct (CBD), including benign or malignant stricture, parasitic infection, or extrinsic compression by the pancreas, can result in bacterial infection and cholangitis (Lam et al., 1978; Boey & Way, 1980). Choledocholithiasis is the most common cause of acute cholangitis, followed by endoscopic retrograde cholangiopancreatography [ERCP], and tumors. After ERCP 1-3% of patients develop cholangitis (O’Connor et al., 1982a: 1982b). Obstruction of the bile duct by tumor or stones can facilitate bacterial colonization; subsequent instrumentation has resulted in bacteremia rates mean 18.0% (O’Connor et al., 1982a: 1982b; Gerecht et al., 1989). The highest bacteremia rates are seen in therapeutic ERCP (Gerecht et al., 1989). In purely diagnostic ERCP, the bacteremic rate is lower at 8% (O’Connor et al., 1982b; Gerecht et al., 1989). Partial obstruction is associated with a higher rate of infection than complete obstruction (Boey & Way, 1980; Lam et al., 1978). Risk of cholangitis is increased if dye is injected retrograde (Boey & Way, 1980). Mortality of cholangitis is high due to the predisposition


Introduction
Cholangitis is relatively uncommon (Boey & Way, 1980).Any condition that leads to stasis or obstruction of bile in the common bile duct (CBD), including benign or malignant stricture, parasitic infection, or extrinsic compression by the pancreas, can result in bacterial infection and cholangitis (Lam et al., 1978;Boey & Way, 1980).Choledocholithiasis is the most common cause of acute cholangitis, followed by endoscopic retrograde cholangiopancreatography [ERCP], and tumors.After ERCP 1-3% of patients develop cholangitis (O'Connor  et al., 1982 a : 1982 b ).
Obstruction of the bile duct by tumor or stones can facilitate bacterial colonization; subsequent instrumentation has resulted in bacteremia rates mean 18.0% (O'Connor et al., 1982 a : 1982 b ; Gerecht et al.,  1989).The highest bacteremia rates are seen in therapeutic ERCP (Gerecht et al., 1989).In purely diagnostic ERCP, the bacteremic rate is lower at 8% (O'Connor et al., 1982 b ;  Gerecht et al., 1989).Partial obstruction is associated with a higher rate of infection than complete obstruction (Boey & Way, 1980;Lam et al., 1978).Risk of cholangitis is increased if dye is injected retrograde (Boey & Way, 1980).
Nevertheless the prevention of post-ERCP cholangitis is crucial especially in patients with pancreatic cancer that may be result in a decreased burden of disease.For this recognition of contributing risk factors is necessary.Therefore, this study was designed to determine the contributing risk factors for post-ERCP cholangitis in patients with pancreatic cancer to program for reduction of disease by controlling and modifying the risk factors.

Materials and Methods
This study was performed as a descriptive-analytical cross-sectional survey.From 2005 to 2010, 110 consecutive cases of pancreatic cancer attending to a tertiary referral centre (Taleghani Hospital), Tehran, Iran were recruited.These patients had an initial diagnosis of malignant biliary obstruction that the final diagnosis was pancreatic cancer according to radiology and clinical findings.The staging was performed according to CT Scan and EUS and the decision of inability to resection was made according to surgery and anesthesiology consultations.Then the patients underwent stenting via ERCP by metallic or plastic stents in a random manner.
The study was approved by medical ethics committee of Shahid-Beheshti University of Medical Sciences, Tehran, Iran.The inclusion criteria were having unresectable pancreatic cancer with a performance status of more than three on the Eastern Cooperative Oncology Group Scale.The patients candidate for surgical resection or any type of chemotherapy or radiation-therapy, those who had undergone laparatomy 30 days before the intervention or those in poor general condition were excluded.
Data from 110 patients were analyzed using SPSS (version 13.0) software [Statistical Procedures for Social Sciences; Chicago, Illinois, USA].Differences were tested by Exact Fisher test, Independent-Sample-T test, Chi-Square test, and Logistic Regression analysis and were considered statistically significant at P values less than 0.05.
In a study by Vandervoort et al. (2002) in United States, data were collected prospectively on patient characteristics and endoscopic techniques from 1223 ERCPs performed at a single referral center.Independent risk factors for post-ERCP cholangitis were identified as a history of recurrent pancreatitis, previous ERCP-related pancreatitis, multiple cannulation attempts, pancreatic brush cytology, and pain during the procedure.However, none of these factors were identified as risk factors in our study.Cheng et al. (2006) performed a similar study in United States on 1115 subjects.They found that female gender, history of recurrent idiopathic pancreatitis, pancreas divisum, SOM, difficult cannulation, and major papilla sphincterotomy (either biliary or pancreatic) were not multivariate risk factors for post-ERCP cholangitis.We found similar results.
Freeman et al. ( 2001) evaluated 1963 consecutive ERCP procedures.Combinations of patient characteristics including female gender, normal serum bilirubin, recurrent abdominal pain, and previous post-ERCP pancreatitis placed patients at increasingly higher risk of pancreatitis, regardless of whether ERCP was diagnostic, manometric, or therapeutic.However our results were different from them.Christoforidis et al. (2002) in Greece evaluated 556 consecutive patients under ERCP.Age less than 50 years, history of relapsing pancreatitis, pancreatic duct opacification, and difficulty in obtaining bile duct cannulation all proved be significant predictive risk factors for the development of either hyperamylasemia or pancreatitis.In contrast, additional procedures and sphincterotomy seemed to reduce the likelihood of both complications.However we found different results (Christoforidis et al., 2002).
Complications and technical failures of ERCP cause significant morbidity and, occasionally, mortality (Palazzo et al., 1995;Kama et al, 1999).An understanding of patient-and procedure-related risks is important for decision making with regard to whether or how ERCP should be performed.Cholangitis is avoidable with adequate biliary drainage.Because success rates are higher and complication rates lower for endoscopists performing large volumes of ERCP, ERCP should be concentrated as much as possible among endoscopists with adequate experience.Patients with a high risk for complications may be best served by referral to an advanced center.