Post-ERCP pancreatitis, risk related to difficult biliary cannulation and primary sclerosing cholangitis

Endoscopic retrograde cholangiopancreatography (ERCP) is a key method to explore and treat diseases of the biliary and pancreatic ducts. ERCP facilitates treatment of bile duct stones, bile duct strictures (benign or malign), primary sclerosing cholangitis (PSC) -related strictures and ductal sampling, and bile leakage. ERCP indications in the pancreatic duct include chronic pancreatitis, strictures, pseudocysts, and fistulas. ERCP enables samples to be taken in suspected malignancies. With cholangioscopy or pancreatoscopy, it is possible also to visualize the ducts and take targeted biopsies. In the ERCP procedure, a flexible duodenoscope is introduced to the duodenum and the papilla major or minor is cannulated, normally with a guidewire, to direct the specimens to the duct explored. ERCP is an invasive procedure with higher complication rates than other endoscopic procedures. The most common complication is post-endoscopic retrograde cholangiography pancreatitis (PEP) with an incidence of 3-10%. Several risk factors for PEP have been established. Difficult biliary cannulation increases the risk of PEP. In a difficult cannulation situation, advanced cannulation methods, e.g. transpancreatic biliary sphincterotomy (TPBS) and double guidewire technique (DGW), can be performed. The long-term outcomes of these advanced techniques are unknown. Rectal non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as prophylaxis for PEP in the ERCP guidelines. PSC patients undergo ERCPs when suffering from jaundice or for detection of biliary dysplasia or when cholangiocarcinoma (CCA), which is highly associated with PSC, is suspected. The risk of CCA in PSC is almost 400-fold higher than in the general population. However, the majority of ERCP procedures in PSC are performed as a follow-up, thus, the risk of PEP and other procedure-related complications should be diminished. The role of NSAIDs in PEP risk of PSC patients is ambiguous. PSC is highly associated with inflammatory bowel diseases and autoimmune hepatitis, and these patients use immunosuppressive thiopurines as a maintenance therapy. Thiopurines are related to increased risk of acute pancreatitis, but their role in acute PEP is unknown. This thesis includes two studies on biliary cannulation techniques and two studies on PSC patients and the risk of PEP related to medical treatment. Patients were referred to Helsinki University Hospital (HUS), Meilahti Abdominal Centre Endoscopy Unit between 2007 and 2018. Study II also included patients from other Scandinavian hospitals. In Study I, historical data were collected retrospectively, and 104 patients were interviewed by phone as prospective cut point to determine the long-term outcome after TPBS. Ninety-nine patients were recruited as a control group. Only a few studies have been published on long-term follow-up in TPBS. According to our results, TPBS appears to be a safe procedure, with no difference in acute or long-term complications compared with the control group. Study II included TPBS and DGW patients in a multicentre randomized prospective investigation by the Scandinavian Association for Digestive Endoscopy group. The result revealed no difference in PEP rate between the two advanced methods, and TPBS seemed to be more effective in achieving deep biliary cannulation. Study III included a retrospective cohort of 2000 ERCPs performed on 931 PSC patients: 1000 ERCPs with rectal administration of 100 mg diclofenac prior to the ERCP, and 1000 ERCPs as a control group. No effect of rectal diclofenac on PEP rate was found. This study was the largest thus far concerning PSC patients and PEP prophylaxis with rectal NSAIDs. In retrospective Study IV, PSC patients were divided into two groups with propensity score matching: the study group (n=177) comprising patients with immunosuppressive thiopurines (azathioprine or mercaptopurine) and the control group containing similar patients (n=177) without thiopurines. No difference in PEP rate was found when comparing the two groups. Thiopurine use did not increase PEP risk. In conclusion, in difficult biliary cannulation TPBS is safe method with similar PEP rates to DGW. In PSC, rectal diclofenac seems to be ineffective in PEP prevention; however, immunosuppressive thiopurines do not increase the risk of PEP.