Accurate grading of the severity of acute pancreatitis is important for clinical practice and research. In clinical practice, accurate staging helps to correctly assess the severity of the disease, monitor the progression of the disease, and develop treatment strategies. And in clinical research, accurate staging has a great impact on the correct patient population and the validity of experimental results.
For more than a century, the severity of acute pancreatitis has been simply classified as mild and severe, and the definitions of mild and severe have not been unified. In recent years, studies have found that there are different subgroups of heavy pancreatitis, and the prognosis of patients in different subgroups is very different, and the limitations of the dichotomy between light and heavy slowly emerge.
I. The proposed Atlanta typing of acute pancreatitis and the challenges it faces
In 1992, a global conference on acute pancreatitis was held in Atlanta, GA. In this meeting, experts from all over the world discussed the grading of acute pancreatitis and proposed a typing standard, which is also called the Atlanta typing.
The Atlanta typing divides acute pancreatitis into two types: mild and severe. The diagnostic criteria for severe acute pancreatitis is the presence of organ failure or local complications in the patient. Organ failure assesses the circulatory, respiratory, and renal systems, but also includes gastrointestinal bleeding, DIC, and metabolic disturbances.
Local complications included pancreatic necrosis, pancreatic abscess, and pancreatic pseudocysts. The development of severe acute pancreatitis is predicted if the patient has an APACHE II score of ≥8 at 24h and a Ranson score of ≥3 within 48h. In contrast, mild acute pancreatitis is pancreatitis without organ failure and local complications.
The Atlanta staging is a milestone in the clinical workup of acute pancreatitis. It is the first widely accepted academic staging of acute pancreatitis, providing a concise framework process for clinical research and comparing data across institutions to provide a best practice system for the management of pancreatitis. At the same time, the Atlanta typing provided a clear clinical definition of the local complications of pancreatitis.
However, since the introduction of the Atlanta staging, it has also been accompanied by skepticism. First, some scholars believe that a human A-PACHE II score of ≥8 in patients with acute pancreatitis does not predict severe pancreatitis.
A multicenter study from Italy and the United States enrolled 326 patients with acute pancreatitis, and they found that nearly one-third of patients with acute edematous pancreatitis had an APACHE II score higher than 8 at 24h, while two-thirds of patients with necrotizing pancreatitis did not have an APACHE II score of 8 at admission. Therefore, the APACHE II score at 24h of hospitalization is indeed a limited predictor of the severity of pancreatitis.
Secondly, in the Atlanta staging, only the organ in which organ failure occurs is defined, and the time of onset of organ failure is not mentioned. Now, more and more studies are focusing on the duration of organ failure. Recent series of studies suggest that the duration of organ failure is an important factor reflecting the severity of acute pancreatitis, and the duration of organ failure ≥48h is a risk factor for pancreatic necrotic tissue infection and death in patients with pancreatitis.
A review of 447 papers on the grading and definition of the severity of acute pancreatitis from 1993 to 2006 revealed that many papers have misinterpreted the Atlanta classification, such as confusing the predictors of severe pancreatitis (APACHE II score ≥8 and Ranson score ≥3) with the actual determinants (organ failure and local complications) The definition of organ failure observation organ as well as multi-organ failure is also widely debated.
The Atlanta staging has been proposed for more than 20 years. During this period, there have been significant breakthroughs in the understanding of the pathophysiology, course and treatment of acute pancreatitis, so it is clearly inappropriate to still use the 20-year-old typology.
The proposal of determinants-based staging of acute pancreatitis
In 2009, Professors Max Petrov and John Windsor of the University of Auckland, New Zealand, proposed the concept of four-level staging of acute pancreatitis.
Firstly, according to the 10-year data of acute pancreatitis from Mayo Clinic, the morbidity and mortality rate of patients with local pancreatic complications without organ failure is only 2%, and it is necessary to distinguish this group of patients from severe pancreatitis and define them as medium-sized pancreatitis. Critical pancreatitis.
Meanwhile, Max Petrov conducted a meta-analysis of determinants of severity of pancreatitis in 14 studies with 1478 patients with acute pancreatitis. The study showed that the mortality rate was 30% in patients with combined organ failure, 32% in patients with pancreatic necrotic tissue infection, and up to 46% in patients with both pancreatic necrotic tissue infection and organ failure.
In this study, the mortality rate was significantly higher in patients with organ failure and pancreatic necrotic tissue infection (RR=1.94, 95% CI: 1.32-2.85, P<0.01); the mortality rate was much higher in patients with pancreatic necrotic tissue infection than in patients without aseptic necrosis (RR=1.84, 95% CI: 1.40-2.41, P<0.01); the mortality rate was significantly higher in patients with pancreatic necrotic tissue infection and pancreatic necrotic tissue infection (RR=1.84, 95% CI: 1.40-2.41, P<0.01); the mortality rate was significantly higher in patients with pancreatic necrotic tissue infection. Patients with pancreatic necrotic tissue infection in combination with organ failure had a significantly higher mortality rate (43% vs. 11%, RR=2.65, 95% CI: 1.30-5.40. P<0.01).
This meta-analysis provides strong evidence-based medical evidence for the proposed new grading criteria for pancreatitis and clarifies two determinants of the severity of acute pancreatitis — pancreatic necrotic tissue infection and organ failure.
After the formation of the new grading framework, a global network survey of pancreatic experts was conducted on controversial issues encountered in grading. Pancreatic experts were listed as authors of clinical research papers on acute pancreatitis published between 2006 and 2010, retrieved from MEDLINE.
Invitations were sent by e-mail to 528 pancreatic specialists in 55 countries, and a total of 240 pancreatic specialists from 49 countries representing their regions participated in the survey. Then a new grading scheme was discussed and definitions were standardized at Pancreatic Disease International.
About 100 specialists attended the meeting and participated in the discussion. Based on the results of the global pancreatitis expert network survey and the international meeting, the new classification scheme was finalized and published in Annals of Surgery in 2012.
Key points of acute pancreatitis staging based on determinants and interpretation
The new classification is based on factors that are causally related to the severity of acute pancreatitis. These factors are called “determinants” and include both local and systemic factors.
(i) Local determinants
The local determinant of severity is pancreatic and/or peripancreatic tissue necrosis, which is summarized as pancreatic (peripancreatic) necrosis. It is defined as follows.
1. Pancreatic (peripancreatic) necrosis refers to the presence of necrotic tissue in the pancreas and/or peripancreatic area. The necrotic tissue may be solid or semi-solid (partially liquid) with no encapsulation on the image.
2. Sterile pancreatic (peripancreatic) necrosis refers to the lack of evidence of infection at the site of necrosis.
3. Infected pancreatic (peripancreatic) necrosis means the presence of at least one of the following: CT suggestive of pancreatic or peripancreatic bubbles; positive bacterial culture results of pancreatic or peripancreatic necrotic tissue obtained by image-guided fine needle aspiration; positive bacterial culture results of pancreatic or peripancreatic necrotic tissue obtained by first drainage and/or necrotic tissue removal.
(ii) Systemic determinants
The systemic determinants of severity are the distant organ dysfunction caused by acute pancreatitis, which is summarized as organ failure. It is defined as follows.
1. Organ failure: its definition is based on the worst evaluation of 3 organ systems (cardiovascular, renal, and respiratory) within 24h. For patients without prior organ dysfunction, organ failure is defined as a SOFA score ≥2 or the following criteria: cardiovascular system: need for positive inotropic drugs; renal system: creatinine ≥171umol/L (≥2.0mg/dl); respiratory system: PaO2/FiO2 ≤300mmHg (40kPa).
2, sustained organ failure: refers to the same organ system failure lasts or exceeds 48h.
3, temporary organ failure: refers to the same organ system failure lasting less than 48h.
(C) Severity grading
Severity grading is based on local and systemic determinants and the interconnection of the two determinants. Clinical events other than these local and systemic determinants of severity are complications and cannot be used for severity grading. They are defined as follows.
1, Mild acute pancreatitis: characterized by the absence of pancreatic (peripancreatic) necrosis as well as organ failure.
2, Medium acute pancreatitis: characterized by the presence of aseptic pancreatic (peripancreatic) necrosis and/or temporary organ failure.
3. Heavy acute pancreatitis: characterized by the presence of infected pancreatic (peripancreatic) necrosis or persistent organ failure.
4. Critical acute pancreatitis: characterized by infected pancreatic (peripancreatic) necrosis combined with persistent organ failure.
IV. Exploration of the advantages of acute pancreatitis typing based on determinants
This new staging is based on two main principles. First, it is based on direct factors of severity rather than factors that predict severity. Clearly, the use of a multifactor scoring system in Atlanta staging was an important advancement more than 20 years ago when imaging techniques were immature and the importance of organ failure in acute pancreatitis was not yet fully recognized.
However, the multifactor score is only a predictor of the severity of pancreatitis. Moreover, these scoring systems are subject to significant errors, which limits their use in clinical practice and clinical research patient recruitment. Nevertheless, the prediction of severity still has some clinical value, and to improve its clinical utility, the direct predictor of severity, pancreatic (peripancreatic) necrosis and/or organ failure, should be predicted.
Recent studies have found that angiopoietin-2 can predict the onset of persistent organ failure. This is important for the timely identification of critically ill patients. Currently, patients are often not admitted to the ICU in a timely manner because of the inability to predict the onset of dangerous events such as organ failure.
Second, the definition of this new staging is based solely on factors that are causally related to severity, namely pancreatic (peripancreatic) necrosis and organ failure. In contrast, empirical classification often associates non-causal factors such as prolonged hospital stay, worsening complications, need for special interventions, and death with severity grading.
There has been too much literature reporting a statistical correlation between many factors and severity of pancreatitis disease. Perhaps these factors do have a statistical correlation with severity, but these are not causally related to severity. Applying these factors to grading criteria is not meaningful and may be clinically misleading.
The advantages of a determinants-based grading of acute pancreatitis will become apparent over time as patients are treated, clinical processes are conducted, and clinical experience is gained. For now, the great advantages of this new typing are its simplicity and ease of grasp, uniformity of criteria, clarity of definition, and ease of disease course monitoring and communication among clinicians. In clinical studies, this new classification will facilitate the homogeneity of patient groups and the evaluation of efficacy.