Clinical Pancreatology for Practising Gastroenterologists and Surgeons. Группа авторов

any invasive intervention is performed [4]. Taking into account this finding as well as the fact that ERCP is associated with a significant risk of procedure‐related complications (including a mortality rate of around 1%), accurate selection of the appropriate candidates for intervention as well as the optimal timing for endoscopy is very important. While these issues are still open for debate, there has been significant progress with regard to individualizing treatment modalities for patients with AP. Opie [5] reported the first case of impacted biliary stone at the level of the papilla in a patient with severe ABP more than a century ago and numerous subsequent case series have explored the pathophysiology of biliary pancreatitis [6,7]. Animal model studies have shown that ligating the pancreatic duct, thus simulating obstruction caused by an impacted stone at the level of the papilla, leads to pancreatic injury followed by systemic inflammation; furthermore, the degree of histological injury is related to the duration of the obstruction, while decompression of the duct is associated with improved outcomes [8]. It is currently believed that persistent obstruction of the pancreatic duct, which arises either through spasm of the sphincter of Oddi or by the impaction of a stone at the level of the papilla in patients with a common biliopancreatic channel (Figure 13.1), is correlated with a more severe course of disease and extensive pancreatic injury [9]. Furthermore, patients who do not have a patent Santorini duct and minor papilla are especially vulnerable to this mechanism of pancreatic injury [10]. This simple mechanistic model encouraged several studies exploring whether surgical [11] or endoscopic [12] relief of pancreatic duct obstruction could alter the course of ABP. Decompression through either surgical sphincteroplasty or endoscopic sphincterotomy were the main therapeutic modalities employed in these studies, which also explored the optimal timing of intervention. The promising results of these early endeavors were not confirmed by later studies, which showed mixed results for early endoscopic interventions in ABP [13–15]. The main reason for the conflicting data from earlier endoscopic studies is the heterogeneity in (i) inclusion criteria (especially time from onset of symptoms and inclusion of patients with ongoing cholangitis), (ii) timing of intervention (usually ranging between 24 and 72 hours after admission), and (iii) type of endoscopic intervention (especially with regard to the use of sphincterotomy in cases without radiological evidence of retained bile duct stones) between the compared trials. Despite differences in methodology, most trials involving urgent (<24 hours) or early (<72 hours) ERCP [16,17] demonstrate that only about one‐third of patients undergo biliary sphincterotomy for persistent common bile duct (CBD) stones. In fact, patients with acute cholangitis complicating the course of ABP constitute the only subgroup of patients consistently shown to benefit from early endoscopic intervention [16]. However, patients who do not develop cholangitis but show persistent CBD stones after an initial attack of ABP are also candidates for endoscopic therapy, with the timing of the intervention depending on several factors, such as the need for cholecystectomy and the local expertise of the medical team. As such, the timing of ERCP in ABP is one of the key points in managing these patients.

Figure 13.1 (a, b) Impacted stone at the level of the papilla.

      Source: courtesy of Guido Costamagna.

      Urgent ERCP

Ongoing biliary obstruction in ABP patients is diagnosed based on clinical signs such as worsening abdominal pain and jaundice, coupled with liver function test abnormalities [18], while fever in this clinical setting usually points to acute cholangitis. There is also a potential role for urgent endoscopic ultrasound (EUS) for the diagnosis of CBD stones in the case of ABP, as shown by a recent study where EUS was performed within 48 hours of admission [19]. In the setting of ongoing biliary obstruction, especially if there is evidence of superimposed cholangitis, urgent ERCP is strongly advocated by current guidelines, usually within 48 hours of admission but with an indication for decompression within 12 hours for severe cases with associated septic shock [20,21] (Figure 13.2). Technically, ERCP in the setting of AP seems to be more technically challenging, probably due to local edema which complicates selective cannulation of the CBD. A recent large multicenter trial reporting on the outcomes of ERCP in a real‐life setting showed a rate of successful cannulation of the CBD of only 84% in ABP [22], well below the currently recommended standard of 95% [23]. Interestingly, there is some additional data suggesting that pancreatic stenting, even in cases where CBD cannulation and/or sphincterotomy cannot be performed, could lower overall complication rate, even in patients with predicted severe attacks of APB [24]. However, urgent ERCP is currently reserved for patients with clear evidence of obstruction, with the American Gastroenterological Association (AGA) guideline explicitly discouraging urgent ERCP outside this indication, all the while recognizing the low quality of available evidence in this field [1].

      Elective ERCP

The main challenge in cases of ABP without ongoing biliary obstruction remains to identify those patients with retained CBD stones who are clear candidates for elective ERCP after resolution of the initial attack. Abdominal ultrasound and computed tomography (CT) are the most commonly used diagnostic modalities in the setting of ABP, but their diagnostic accuracy in detecting CBD stones is limited, which is particularly relevant in the case of false‐negative results [25]. Traditionally, ERCP is considered the gold standard for diagnosing CBD stones, but its diagnostic capabilities have to be balanced against the non‐negligible rate of procedure‐related adverse events. The emergence of novel imaging methods, such as magnetic resonance cholangiopancreatography (MRCP) and EUS, have almost obviated the need for diagnostic ERCP in the case of CBD stones. Recent data suggests that MRCP performed on the seventh day after an initial episode of APB has a high positive predictive value (>93%) in detecting persistent CBD stones [4]. EUS has also been shown to have high accuracy in detecting CBD stones, which is especially useful for avoiding unnecessary ERCP in patients with intermediate risk of CBD stones [26]. Actually, EUS shows higher sensitivity than endoscopic cholangiography alone, probably because radiological evaluation during ERCP can miss diminutive stones that can easily be demonstrated on EUS. EUS is also more sensitive than MRCP in detecting small stones (<5 mm) [27]. When considering an elective intervention for clearance of retained CBD stones, the physician should take into account the patient’s condition (i.e. ongoing local or systemic complications of the initial episode of ABP) and the need for additional interventions such as cholecystectomy or pseudocyst drainage. Decisions regarding the timing of ERCP in this setting are usually made by a multidisciplinary team, on a case‐by‐case basis, with no clear‐cut guidelines available for most clinical situations, especially in the case of patients recovering from severe attacks of pancreatitis [28]. The AGA currently recommends index cholecystectomy as standard of care for all patients with ABP who are deemed fit for surgery [1]. Concomitant gallstones and CBD stones can be managed by a variety of strategies including preoperative, intraoperative or postoperative ERCP as well as laparoscopy‐assisted CBD exploration which obviates the need for ERCP. In the absence of evidence‐based data to clearly favor one approach over another [29], the main factors in choosing either one of these strategies is usually the infrastructure and expertise available in each center. In the particular case of APB patients showing both gallbladder and CBD stones, there is evidence supporting both a combined surgical and endoscopic intervention at index admission [30] as well as a two‐step strategy, with ERCP at index admission followed by cholecystectomy at a later date [31]. Except for the case of severely ill patients, it seems reasonable to consider ERCP plus sphincterotomy at index admission to avoid recurrent attacks of APB [30].

Figure 13.2 Role of endoscopic therapy in the setting of acute biliary pancreatitis.