**5. ERCP when and to whom in ABP?**

Before 1978 when Classen [43] first did ERCP and endoscopic sphincterotomy in acute pancreatitis, ERCP was considered as contraindicated in AP. Thereafter, this dogma has changed by Safrany and his collegeus [44] who did ERCP in 15 cases with ABP in 1980. They detected impacted stone at AV in 8 patients and in 7 of them, they showed choledochal stone and removed the stones in all the patients. None of the patients developed any complications and discharged withn a short period after ERCP procedure. After 1980, case series have been reported in this area and first randomized controlled study about this subject was published by Neoptolemos and his collegues in 1986 [3]. In 1993, Fan and et al. [45] published a report in which they investigated the effects of early ERCP on progression of AP. The authors showed that early ERCP was useful only in patients with biliary sepsis compared to conservative group if there is an existing biliary pathology both in mild and severe cases of AP. However, early ERCP did not introduce declined morbidity and mortality when all other etiologies of AP had been included in the study cohort.

Nonetheless, many complications associated with ERCP have been reported in the following years and when and to whom ERCP questions became subject to many researches. ERCP and endoscopic sphincteratomy can make the situation worse in a patient with AP since therapautic ERPC had been reported to have 10% morbidity and 0.1% mortality rates [46, 47]. Additioanlly in patients with AP, there is potential risk of technical failure in ERCP procedure due to edema in the AV and duodenum itself.

For this reason, both the timing of ERCP and detrmining the correct patient who needs this procedure carry the utmost importance. In 2013, International Pancreas Union and American Pancreas Union published together 'the management guideliness of AP' and the suggestions about biliary system problems were written as follows [31]:

1."ERCP is not indicated in predicted mild biliary pancreatitis without cholangitis. (GRADE 1A, strong agreement). ERCP is probably not indicated in predicted severe biliary pancreatitis without cholangitis (GRADE 1B, strong *Endoscopic Retrograde Cholangiopancreatography in Acute Biliary Pancreatitis DOI: http://dx.doi.org/10.5772/intechopen.96545*

agreement). ERCP is probably indicated in biliary pancreatitis with common bile duct obstruction (GRADE 1C,strong agreement) ERCP is indicated in patients with biliary pancreatitis and cholangitis (GRADE 1B, strong agreement)


Therefore, we will discuss the subject of bliary tree management in patients with AP as subtitiles; 1-Mild pancreatitis in the absence of cholangitis and persistent cholestasis. 2- Severe pancreatitis in the absence of cholangitis and persistent cholestasis 3- Acute pancreatitis together with the presence of cholangitis and persistent cholestasis. We will also discuss; 4- U-ERCP versus E-ERCP and 5-the role of elective ERCP 3 days after patient's admission to prevent recurrence of AP.

### **5.1 ERCP in patients without cholangitis or persistent cholestasis**

The first randomized controlled trial in this field is published by Neoptolemus et al. in 1986 [3]. No relationship was found related to pancreatitis complications and mortality between the conservative treatment group and the ERCP group in mild acute biliary pancreatitis patients in this study and in the meta-analysis which contains 4 randomized controlled studies of Sharma et al. [48]. The patients were stratified by the severity of pancreatitis in the study of Burstow et al. [49] but the patients with or without cholangitis were not analyzed separately and eventually, a strong tendency to decrease pancreatitis complications has been suggested in patients with mild acute biliary pancreatitis, although this is not statistically significant (OR 0.67; 95% CI, 0.43, 1.03; P = 0.06). Another meta-analysis of 5 randomized controlled studies including 702 patients, which compared the conservative treatment and E-ERCP in acute biliary pancreatitis patients by Morietti et al. [50] showed no effect on pancreatitis complications (1.8% (95% CI -5.6% to 9.3%); p = 0.6). Since there is no mortality in patients with mild pancreatitis, a comparison could not be made in this regard. Petrov et al. [51] did not demonstrate any statistically significant difference between the E-ERCP group and the conservative treatment group in terms of reducing complications of pancreatitis in neither mild nor severe acute pancreatitis in their metaanalysis of 5 randomized controlled studies including 717 patients. A systematic review by Geenen et al. that published in Pancreatology in 2013 [52] examined the guidelines and meta-analysis in this field till then, reported that U or E-ERCP±ES had no place in mild acute biliary pancreatitis. As we do in our clinical practice, Elective ERCP (EL-ERCP) might be performed before the cholecystectomy only in case, the stuck stones in AV have escaped back into the choledoc and if this is proved by MRCP or EUS.

As a result, there is consensus that U or E-ERCP±ES is not indicated in mild acute biliary pancreatitis without cholangitis [31, 33–35].

## **5.2 Emergency ERCP in severe acute biliary patients without cholangitis or persistent cholestasis**

ERCP in acute biliary pancreatitis is still a controversial issue, and there no consensus about it. As mentioned before, clinical and animal studies showed that if the biliary obstruction is not terminated within 48 hours, the pathology progresses to necrosis and then organ failure occurs. Therefore, the first studies demonstrated that U or E-ERCP decreased the mortality and morbidity in severe acute pancreatitis patients compared to the control group [53]. In 1997, Fölsch et al. [54] reported that especially deaths due to respiratory failure were more common in the E-ERCP group than the control group in their randomized controlled trial about the role of E-ERCP in acute biliary pancreatitis. The APEC study [4] that includes 232 patients from 26 centers published in July 2020 compared U-ERCP and conservative treatment, and this study changed the paradigm. Besides, acute biliary pancreatitis patients with cholangitis excluded from the APEC study and no significant difference demonstrated between two groups in regard of local or systemic complications of pancreatitis. Whereas, the cholangitis and recurrent attacks of pancreatitis were more common in the U-ERCP group than the conservative treatment group. This is because the criteria for persistent cholestasis or cholangitis were fever, serum bilirubin levels greater than 2.3 mg / dl, commom bile duct width greater than 8 millimeters in patients younger than 75 years and 1 centimeter in patients older than 75 years, and the presence of stones in common bile duct in this study. Another cause of these findings were that it was unclear whether MRCP or EUS, which are the most sensitive methods in detecting stones in choledoc, were performed or not.

Some conflicting results were obtained in the meta-analysis of randomized controlled trials about the role of emergency ERCP in acute biliary pancreatitis, according to the including and excluding criteria of the involved randomized controlled trials and whether subgroup analysis is done or not. Petrov et al. [55] published a meta-analysis in 2008 including 7 randomized controlled trials with 450 patients about the effects of E-ERCP on acute biliary pancreatitis without cholangitis, and they indicated that emergency ERCP has no effect on local complications of pancreatitis in neither mild nor severe pancreatitis. Van Santvoort et al. [56] compared E-ERCP with conservative treatment in patients with and without cholangitis in their randomized controlled trial and demonstrated that in patients without cholestasis, ERCP (29/75 patients: 39%) was not associated with reduced complications (45% vs. 41%, P = 0.814, multivariate adjusted OR: 1.36; 95% CI: 0.49–3.76; P = 0.554) or mortality (14% vs. 17%, P = 0.754, multivariate adjusted OR: 0.78; 95% CI: 0.19–3.12, P = 0.734).

A meta-analysis by Tse et al. [1] which contains 5 randomized controlled studies, indicated that unweighted pooled mortality rates for participants were 9.6% in the early routine ERCP strategy and 4.9% in the early conservative management strategy in patients without cholangitis. Three years after this meta-analysis, Burstow et al. [49] analyzed 11 RCTs consisting of 1314 patients (conservative management = 662, ERCP = 652). There was a near significant decrease in mortality for the ERCP group compared with conservatively managed patients with severe pancreatitis [odds ratio (OR) 0.45; 95% confidence interval (CI), 0.19, 1.09; P = 0.08]. In patients with mild pancreatitis, mortality results were comparable for both groups (OR 0.66; 95% CI, 0.02, 28.75; P = 0.83). Overall complications were

### *Endoscopic Retrograde Cholangiopancreatography in Acute Biliary Pancreatitis DOI: http://dx.doi.org/10.5772/intechopen.96545*

significantly reduced in the ERCP group in severe pancreatitis patients (OR 0.32; 95% CI, 0.17,0.61; P = 0.00). The authors' comments about this meta-analysis are as follows: this meta-analysis demonstrates a significant decrease in complications in patients with severe ABP managed with early ERCP/ES compared with conservative management. As far as the mortality is concerned, no significant decrease was observed in mortality even in severe ABP patients treated with early ERCP/ES.

The meta-analysis and systematic review about the comparison of E-ERCP and conservative treatment in acute biliary pancreatitis by Coutinho et al. [57] reported that; the pain and fever resolved in a shorter time, the hospitalization time was shorter with reduced complications and hospital costs were lower in the E-ERCP group than the conservative treatment group. Uy et al. [58] performed a meta-analysis including 2 randomized controlled trials that compares the E-ERCP (n = 177) and the conservative treatment (n = 163) in acute biliary pancreatitis. This meta-analysis revealed low mortality rates for both mild and severe pancreatitis in the ERCP group (RR = 1.92, 95% CI: 0.86–4.32) whereas the morbidity rates were similar in both groups (RR = 0.95, 95% CI: 0.74–1.22). Moretti et al. [50] demonstrated that ERCP had no effect on complications in mild pancreatitis however, ERCP reduced the complications in severe pancreatitis but it did not have any effect on mortality rates in their meta-analysis including 5 prospective randomized trials with 702 patients. Geenen et al. [52] preformed a review including 12 international guidelines and 8 meta-analysis. Although 3 meta-analysis and 1 guideline recommended against ERCP in acute biliary pancreatitis, 7 out of 11 guidelines recommended routine E-ERCP in severe acute biliary pancreatitis regardless of the presence of cholangitis, and they agreed on the lack of consensus about routine E-ERCP in severe acute biliary pancreatitis. However, the 4 main international guidelines that we evaluated (2 out of them belonged the same group but published at different times) recommended against the emergency ERCP in acute biliary pancreatitis without cholangitis because it did not significantly reduce mortality and morbidity compared to the conservative treatment group [31, 33–35]. Contrary to these guidelines, another guideline of the United Kingdom publishe in 2005 [32] has controversial suggestions about E-ERCP in severe acute biliary pancreatitis without cholangitis as; "*Urgent therapeutic endoscopic retrograde cholangiopancreatography (ERCP) should be performed in patients with acute pancreatitis of suspected or proven gall stone etiology who satisfy the criteria for predicted or actual severe pancreatitis, or when there is cholangitis, jaundice, or a dilated common bile duct.* ".

Because of the lack of statically significant data about the reduction in local and systemic complications or mortality rates of pancreatitis by emergency ERCP in severe acute biliary pancreatitis from many RCTs and meta-analyzes until to date, international guidelines referring to these results indicated that U- or E-ERCP have no benefit in every patient with severe acute biliary pancreatitis unless cholangitis is present. The ESGE guideline published in 2018 [33] explains why ERCP should not be performed in a patient with severe pancreatitis without cholangitis: "*A possible explanation why urgent ERCP with sphincterotomy within 24 h did not show an advantage over conservative treatment could be that the opportunity to positively influence the disease course had already passed at the time of the ERCP despite the fact that it was performed early. Animal models have shown that trypsinogen activation within the pancreas occurs within10 min after chemically inducing pancreatitis. It is well known that most bile duct stones in patients with gallstone pancreatitis cause only temporary obstruction and pass spontaneously into the duodenum. This temporary obstruction already initiates pancreatitis and data from animal models show that this includes intrapancreatic trypsin activation, rupturing of vacuoles releasing active trypsin, and pancreatic autodigestion*. I*n the current trial, urgent ERCP was done after a median* 

*29 h after onset of symptoms and common bile duct stones were found in 43% of patients. Even this narrow time window might already be too long to prevent pancreatitis from deteriorating by performing an urgent ERCP with sphincterotomy".*
