Clinical practice guidelines for acute pancreatitis in the United States and Japan: similarities and differences

Acute pancreatitis (AP) is defined as sudden inflammation that occurs in the pancreas (1-4). Although most cases of AP are mild, approximately 20% of patients develop severe acute pancreatitis (SAP), which is potentially lethal (3,4). Because of the rapid expansion of knowledge regarding the pathogenesis, diagnosis, and treatment of AP, remaining apprised of the latest information regarding clinical practice can be challenging. Clinical practice guidelines are published statements proposed by a panel of experts and include recommendations regarding the optimal diagnosis and treatment of disease (5). Therefore, many clinicians rely on clinical practice guidelines for patient management. Recently, the American College of Gastroenterology (ACG) published clinical practice guidelines for AP management (1). However, in Japan, clinicians often rely on the 2021 Japanese clinical practice guidelines when managing AP (2). The ACG and Japanese clinical practice guidelines for AP share various recommendations regarding diagnosis, severity assessment, and management of this condition; however, these guidelines also have significant differences. Therefore, this editorial article discusses these similarities and differences.

According to both the ACG and Japanese guidelines, diagnosis of AP is made when cases meet two or three of the following criteria: abdominal pain compatible with AP; increased serum amylase or lipase levels; and characteristic findings observed during abdominal imaging (1,2). Both guidelines state the superiority of evaluating lipase rather than amylase because lipase is specifically associated with pancreatic abnormalities (1,2). The ACG guidelines state that serum amylase or lipase levels must be at least three times the upper limit of normal, whereas the Japanese guidelines do not mention this threshold (1,2). Additionally, the Japanese guidelines recommend the examination of urinary trypsinogen-2 to allow a prompt diagnosis (1,2). However, Japanese gastroenterologists usually perform blood and imaging examinations simultaneously for patients when the suspicion of AP is high. Therefore, the usefulness of the urinary trypsinogen-2 examination may be limited. Despite their slight differences, the ACG and Japanese clinical practice guidelines share some recommendations for the diagnosis of AP.

Imaging studies such as ultrasonography, endoscopic ultrasonography (EUS), computed tomography (CT), and magnetic resonance imaging are not necessary for diagnosing AP. However, because cholelithiasis and excessive alcohol consumption are the two leading causes of AP (1-4), both guidelines recommend early and urgent endoscopic retrograde cholangiopancreatography (ERCP) for diagnosing biliary pancreatitis (1,2).

Because approximately 20% of patients with AP develop life-threatening SAP, clinicians should determine the severity of AP and predict the possibility of progression at the time of diagnosis (1-4). Although both the ACG and Japanese guidelines emphasize assessing the severity of AP, there are significant differences in the assessment methods. According to the Japanese guidelines, a scoring system is used to assess the severity of AP (2). This scoring system comprises prognostic factors [older age, systemic inflammatory response syndrome (SIRS) findings, increased serum levels of C-reactive protein (CRP) or lactate dehydrogenase, thrombocytopenia, hypocalcemia, renal dysfunction, reduced PaO₂ levels, and base excess] and the CT grade as assessed by contrast-enhanced CT (2). Importantly, prognostic factors and the CT grade are independent parameters of the severity assessment, and SAP in patients with AP can be determined based on the CT grade alone, even if no prognostic factors are present (2). In contrast, the ACG guidelines define SAP as the presence of organ failure and/or pancreatic necrosis, not dependent upon the scoring system, even when the clinical findings associated with severe cases, such as SIRS, are observed (1). Thus, one of the prominent differences between the ACG and Japanese guidelines is that the Japanese guidelines (but not the ACG guidelines) rely on the aforementioned scoring system, which comprises not only patient characteristics, SIRS, and laboratory findings but also contrast-enhanced CT findings. Such differences in the assessment of AP severity may be partially explained by the fact that contrast-enhanced CT is easily performed in most hospitals in Japan. Notably, a simple SIRS score is as effective as a complicated score obtained using the scoring system (6). To prove the utility of the Japanese scoring system for assessing severity, randomized clinical trials (RCTs) that address clinical outcomes with or without the use of this scoring system need to be performed. Despite significant differences in the assessment and prediction of SAP, both guidelines recommend that a severity assessment should be performed repeatedly up to 48 hours after admission, even for mild AP (1,2). In particular, the Japanese guidelines refer to the importance of repeated assessments in accordance with the flowchart and checklist for the management of AP (referred to as the Pancreatitis Bundle 2021) (2,7).

The ACG and Japanese guidelines share recommendations for the initial treatment for AP. Fluid therapy comprising isotonic crystalloids is important for patients with AP. Both guidelines are in agreement regarding the importance of fluid therapy. However, the ACG guidelines recommend that aggressive fluid therapy needs to be performed within 24 hours after admission, whereas the Japanese guidelines recommend that aggressive fluid therapy needs to be performed within 3 hours after admission (1,2). Whether aggressive fluid therapy is superior to moderate fluid therapy has not been demonstrated by RCTs (1,2). The ACG guidelines indicate that attention should be focused on volume overload caused by aggressive fluid therapy, particularly for patients with cardiovascular and/or renal comorbidities (1). Additionally, the ACG guidelines emphasize the importance of repeated assessments of fluid volume by monitoring the serum levels of blood urea nitrogen (1). Regarding fluid therapy for AP, aggressive and moderate fluid therapy defined as the volume/kg/h have not yet been defined. The optimal fluid volume for AP with or without comorbidities needs to be determined by future RCTs. Accumulating evidence has suggested that early initiation of enteral nutrition for the prevention of infectious complications and organ failure is more beneficial than total parenteral nutrition for patients with AP (8). Enteral feeding contributes to the maintenance of the gut barrier function, thereby inhibiting the translocation of gut microorganisms to the pancreas (8). Therefore, both guidelines recommend early initiation of enteral feeding; however, only the Japanese guidelines recommend early initiation of enteral feeding for patients with SAP (1,2). The ACG guidelines emphasize caution because the benefits of early enteral feeding for patients with AP that is predicted to progress to SAP have not been demonstrated by a large RCT (9). Nevertheless, both guidelines share most recommendations for fluid and nutritional therapies.

AP initiates sterile inflammation triggered by autodigestion of pancreatic tissues (3). Thus, pancreatic colonization by microorganisms is not involved in mild AP. In contrast, gut bacteria and fungi translocate to the pancreas because of an impaired intestinal barrier that occurs with disease progression; such pancreatic colonization by microorganisms underlies the development of SAP and pancreatic necrosis (3,4,10). Therefore, the ACG and Japanese guidelines do not recommend the administration of antibiotics to patients with AP with sterile or mild inflammation (1,2). Notably, only the ACG guidelines recommend prophylactic antibiotic administration for SAP (1,2). As a result, the use of antibiotics for AP remains a matter of debate; however, the utility of procalcitonin-based algorithms has been demonstrated (11). Recent progress in next-generation sequencing studies comprising blood and pancreatic samples could provide new insights regarding the identification of pathogenic bacteria and fungi and the development of case-specific antimicrobial therapies. There are major differences in the recommendations regarding interventional treatment for infected pancreatic necrosis. The Japanese guidelines recommend endoscopic or percutaneous drainage of infected pancreatic necrosis when it is encapsulated (2). Additionally, the Japanese guidelines recommend that endoscopic approaches, such as EUS-guided transluminal drainage followed by endoscopic necrosectomy, should be performed for infected encapsulated necrosis. The emphasis on EUS-guided approaches for infected pancreatic necrosis described by the Japanese guidelines may reflect that Japanese pancreatobiliary endoscopists are well-trained in the performance of EUS-based intervention techniques. Finally, according to both guidelines, the role of surgical debridement is limited (1,2).

AP is a major adverse event associated with ERCP, and its prevention is a critical issue for pancreatobiliary endoscopists. To prevent post ERCP pancreatitis at high risk patients, both the ACG and Japanese guidelines recommend rectal indomethacin and/or pancreatic stent placement (1,2).

In conclusion, the ACG and Japanese clinical guidelines for AP management have similarities and differences. Because of its high mortality rate, a simple assessment system for SAP needs to be established. The identification of pathogenic markers, genetic polymorphisms, and microorganisms associated with SAP may be useful for this purpose (3). In this regard, the Japanese guidelines recommend serum IL-6 concentration as a biomarker of SAP (2). However, the utility of IL-6 may be limited because serum CRP, which is an IL-6-dependent inflammatory mediator, is not always correlated with disease severity. Therefore, the clinical application of inflammatory mediators other than IL-6 as well as next-generation sequencing studies of bacteria and fungi and identification of genetic locus associated with SAP may enable the establishment of an accurate and simple assessment system for SAP.

Acknowledgments

The authors thank Ms. Yukiko Ueno for her administrative assistance.

Funding: This study was supported in part by the Smoking Research Foundation and Kindai University Research Enhancement (Nos. KD2208, KD2301, and KD2405).

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, HepatoBiliary Surgery and Nutrition. The article did not undergo external peer review.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-24-404/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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