LETTER TO THE EDITOR Classification of the Severity of Acute Pancreatitis: How Much Is Really Needed for a New Classification? To the Editor: e read with great interest the article by Dellinger and coworkers,1 reporting a new international classification of acute pancreatitis (AP) severity, and the editorial by Bradley.2 These are very excellent articles, and the associated conclusions and recommendations are based on a review by investigators with long-standing interest in AP diagnosis and treatment.3 A global Webbased survey was conducted and a dedicated international symposium was organized to bring contributors from different disciplines together and discuss the concept and definitions. Furthermore, the authors state that, in an attempt to buttress justification for areas of the proposal lacking sufficient clinical evidence, expert opinion was solicited. According to Bradley,2 we believe that the definition of an expert coworker seems rather lenient in that the inclusion criterion was the publication of a single article on AP in the most recent period. Because of the extreme diversity of potential clinical courses in patients with AP, and because of the wide range of organs and tissues that may become involved, few other diseases require the degree of flexibility in management as that required from those clinicians who undertake the care of patients with AP. We believe that there are important reasons to define and stratify the severity of AP.4 First, on admission, it is important to identify patients with potentially severe AP who require aggressive treatment.5,6 Second, in a secondary care setting, clinicians need to identify such patients for possible transfer to specialist care. Third, for specialists who receive such referrals, there are advantages to stratifying these patients into subgroups based on the presence of persistent organ failure (OF) and local and/or systemic complications.
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Disclosure: The authors did not receive any financial support or commercial sponsorship. All authors were involved in drafting the manuscript and revising it critically for important intellectual content and have given final approval of the version to be published. Furthermore, all authors have participated sufficiently in the work to take public responsibility for its content. C 2014 Wolters Kluwer Health, Inc. All Copyright rights reserved. ISSN: 0003-4932/14/26104-e0101 DOI: 10.1097/SLA.0000000000000625
As a result of improvements in AP management, including better diagnostics and treatment modalities,7 disease-related mortality has declined during the past 2 decades. Overall, 85% of patients have interstitial AP and approximately 10% of these patients experience a transient OF.8 In contrast, about one fifth of patients develop a severe AP, and a third of these patients have infected necrosis, which is still associated with a mortality rate exceeding 30%.9 Such necrosis formation is best assessed by contrast-enhanced computed tomography.10,11 According to the Atlanta system of classification, severe AP is associated with multiple OF.12 Median OF prevalence in necrotizing pancreatitis is 54%; moreover, mortality in OF absence is zero, with single OF 3%, and with multiple of 47%. Patients with severe AP should be nursed in a critical care setting; identifying the cohort of patients who require critical care support is vital to rationalize health care resources, as it would not be feasible or appropriate to manage all patients with AP in such an environment. For this reason, scoring systems and other variables can be used, in conjunction with regular clinical review, to ensure prompt and timely intervention. Moreover, several challenges and controversies remain in the management of this disease, including how best to predict OF, the use and timing of diagnostic tests, and the type and timing of surgical intervention. Furthermore, we still do not know why AP remains mild in some patients whereas other patients experience multiple complications. The widely used Atlanta classification categorizes AP as mild or severe.12 AP without parenchymal necrosis is referred to as interstitial or edematous AP and is usually mild. Patients are classified as having severe AP if they meet any of the criteria proposed.12 Although the Atlanta classification has proved useful over the years, many of the definitions proved confusing and have not been accepted or used by the pancreatic community. Better understanding of the pathophysiology of pancreatic necrosis, improved diagnostic imaging of the pancreatic parenchyma and peripancreatic collections, and the development of minimally invasive radiologic, endoscopic, and operative techniques for the management of complications have made it necessary to revise the Atlanta classification.4,9,13 In addition, AP is a dynamic, evolving process, and the recognition of 2 different peaks in mortality reflects the 2 distinctly different clinical phases of the evolution of the disease not recognized by the Atlanta classification.9,14 The authors state that the Atlanta definitions of AP severity are ingrained in the lexicon of pancreatologists but are suboptimal because these definitions are based on empiric description of occurrences that are merely associated
Annals of Surgery r Volume 261, Number 4, April 2015
with severity.1 However, it is now clear that some of the information included in the classification was subject to different interpretations and that criteria of severity as defined by the Atlanta Symposium have not been used in a uniform fashion in recent publications. We believe that areas of major concern are as follows: (1) criteria for severe AP included OF and/or local complications, (2) distinction between transient OF and persistent OF, and (3) extent of pancreatic necrosis and peripancreatic collections. A recent revision of the Atlanta classification and definitions has been published by Acute Pancreatitis Classification Working Group to update the terminology and provide simple functional clinical and morphologic classifications.9 The consensus classification offers a comprehensive classification of AP severity and peripancreatic collections. New information on severity and radiologic descriptions of pancreatic and peripancreatic collections is provided. Finally, the classification differentiates acute peripancreatic fluid, pancreatic pseudocyst, acute necrotic collections, and walled-off necrosis. The revised classification of AP identified 2 phases of the disease: early and late. Severity is classified as mild, moderate, or severe. Mild AP, the most common form, has no OF, local or systemic complications, and usually resolves in the first week. Moderately severe AP is defined by the presence of transient OF, local complications, or exacerbation of comorbid disease. Severe AP is defined by persistent (>48 hours) OF. OF is defined as a score of 2 or more for 1 of these 3 organ systems using the modified Marshall scoring system.15 Reading the article, we have set ourselves some questions. First, is yet another classification of AP severity really needed? Second, why not revise and expand the Atlanta classification? Third, because it is perceived that there is a need to differentiate forms of disease on the basis of local and systemic determinants, is there a need to define 4 classes of gravity? In the proposed determinant-based classification of AP severity, the authors state that the definitions used for the categories of severity are based on attributes of the local (absent, sterile, or infected glandular or periglandular necrosis) and systemic determinants (absent, transient, or persistent OF) and possibility of interaction between the determinants during the same AP episode.1 The authors highlight the eventuality that, beyond these local and systemic determinants of severity, other occurrences should be considered and complications should not be used for the purpose of classifying the severity. In the revised Atlanta classification, exacerbation of preexisting comorbidity, such as chronic lung diseases, diabetes, obesity, or coronary www.annalsofsurgery.com | e101
Copyright © 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Annals of Surgery r Volume 261, Number 4, April 2015
Brisinda et al
artery disease, precipitated by AP is defined as a systemic complication.9 Furthermore, the authors distinguish between persistent OF— the defining feature of severe AP—and other systemic complications, which can be related to exacerbation of the underlying preexisting diseases.9 An important feature of the revised classification is the recognition that AP is an evolving, dynamic condition and that the severity may change during the course of the disease. In the early phase of disease, systemic inflammatory response syndrome or OF indicates potentially severe disease. If the patient improved rapidly during the early phase without OF and without local or systemic complications and has no persistent OF, the disease is defined as moderately severe AP. On the contrary, if the patient develops persistent OF, the disease is defined as severe AP and is associated with very high morbidity and mortality rates. We cannot understand the need to include in this classification of severity the class “critical AP.” From the definition, these patients would be those with the greatest degree of severity of disease—patients in whom AP is characterized by the presence of infected pancreatic necrosis and persistent OF. In our opinion, in these patients with severe disease from the onset, a classification of severity is less useful; it seems obvious that in these patients, the mortality rate is close to 100% often even in the presence of aggressive and intensive treatment. In accordance with Bradley,2 we believe that the stratification system proposed is empirically based upon clinical observations of local and systemic events. Furthermore,
e102 | www.annalsofsurgery.com
according to Bradley, we believe that clinical application of the new proposed determinantbased classification relies heavily on the diagnosis of pancreatic and peripancreatic necrosis, arbitrarily defined as necrosis in either or both pancreatic parenchyma and peripancreatic fat, using contrast-enhanced computed tomography to demonstrate any area of nonenhancement. Giuseppe Brisinda, MD Anna Crocco, MD Piero Giustacchini, MD Department of Surgery Catholic University School of Medicine University Hospital Agostino Gemelli Rome, Italy [email protected]
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REFERENCES 1. Dellinger EP, Forsmark CE, Layer P, et al. Determinant-based classification of acute pancreatitis severity: an international multidisciplinary consultation. Ann Surg. 2012;256:875–880. 2. Bradley EL, III. Atlanta redux: revisiting the severity stratification system for acute pancreatitis. Ann Surg. 2012;256:881–882. 3. Dellinger EP, Tellado JM, Soto NE, et al. Early antibiotic treatment for severe acute necrotizing pancreatitis: a randomized, double-blind, placebocontrolled study. Ann Surg. 2007;245:674–683. 4. Brisinda G, Vanella S, Crocco A, et al. Severe acute pancreatitis: advances and insights in assessment of severity and management. Eur J Gastroenterol Hepatol. 2011;23:541–551. 5. Wu BU, Johannes RS, Sun X, et al. The early prediction of mortality in acute pancreatitis: a large population-based study. Gut. 2008;57:1698–1703. 6. Petrov MS, Vege SS, Windsor JA. Global survey of controversies in classifying the severity of
12.
13.
14.
15.
acute pancreatitis. Eur J Gastroenterol Hepatol. 2012;24:715–721. Babu RY, Gupta R, Kang M, et al. Predictors of surgery in patients with severe acute pancreatitis managed by the step-up approach. Ann Surg. 2013;257:737–750. Singh VK, Wu BU, Bollen TL, et al. Early systemic inflammatory response syndrome is associated with severe acute pancreatitis. Clin Gastroenterol Hepatol. 2009;7:1247–1251. Banks PA, Bollen TL, Dervenis C, et al. Classification of acute pancreatitis—2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013;62:102–111. Kim YS, Lee BS, Kim SH, et al. Is there correlation between pancreatic enzyme and radiological severity in acute pancreatitis? World J Gastroenterol. 2008;14:2401–2405. Lankisch PG, Struckmann K, Assmus C, et al. Do we need a computed tomography examination in all patients with acute pancreatitis within 72 h after admission to hospital for the detection of pancreatic necrosis? Scand J Gastroenterol. 2001;36:432–436. Bradley EL, III. A clinically based classification system for acute pancreatitis. Summary of the International Symposium on Acute Pancreatitis, Atlanta, GA, September 11 through 13, 1992. Arch Surg. 1993;128:586–590. Mounzer R, Langmead CJ, Wu BU, et al. Comparison of existing clinical scoring systems to predict persistent organ failure in patients with acute pancreatitis. Gastroenterology. 2012;142:1476–1482; quiz e15–e16. Singh VK, Wu BU, Bollen TL, et al. A prospective evaluation of the bedside index for severity in acute pancreatitis score in assessing mortality and intermediate markers of severity in acute pancreatitis. Am J Gastroenterol. 2009;104: 966–971. Marshall JC, Cook DJ, Christou NV, et al. Multiple organ dysfunction score: a reliable descriptor of a complex clinical outcome. Crit Care Med. 1995;23:1638–1652.
C 2014 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
W
Disclosure: The authors did not receive any financial support or commercial sponsorship. All authors were involved in drafting the manuscript and revising it critically for important intellectual content and have given final approval of the version to be published. Furthermore, all authors have participated sufficiently in the work to take public responsibility for its content. C 2014 Wolters Kluwer Health, Inc. All Copyright rights reserved. ISSN: 0003-4932/14/26104-e0101 DOI: 10.1097/SLA.0000000000000625
As a result of improvements in AP management, including better diagnostics and treatment modalities,7 disease-related mortality has declined during the past 2 decades. Overall, 85% of patients have interstitial AP and approximately 10% of these patients experience a transient OF.8 In contrast, about one fifth of patients develop a severe AP, and a third of these patients have infected necrosis, which is still associated with a mortality rate exceeding 30%.9 Such necrosis formation is best assessed by contrast-enhanced computed tomography.10,11 According to the Atlanta system of classification, severe AP is associated with multiple OF.12 Median OF prevalence in necrotizing pancreatitis is 54%; moreover, mortality in OF absence is zero, with single OF 3%, and with multiple of 47%. Patients with severe AP should be nursed in a critical care setting; identifying the cohort of patients who require critical care support is vital to rationalize health care resources, as it would not be feasible or appropriate to manage all patients with AP in such an environment. For this reason, scoring systems and other variables can be used, in conjunction with regular clinical review, to ensure prompt and timely intervention. Moreover, several challenges and controversies remain in the management of this disease, including how best to predict OF, the use and timing of diagnostic tests, and the type and timing of surgical intervention. Furthermore, we still do not know why AP remains mild in some patients whereas other patients experience multiple complications. The widely used Atlanta classification categorizes AP as mild or severe.12 AP without parenchymal necrosis is referred to as interstitial or edematous AP and is usually mild. Patients are classified as having severe AP if they meet any of the criteria proposed.12 Although the Atlanta classification has proved useful over the years, many of the definitions proved confusing and have not been accepted or used by the pancreatic community. Better understanding of the pathophysiology of pancreatic necrosis, improved diagnostic imaging of the pancreatic parenchyma and peripancreatic collections, and the development of minimally invasive radiologic, endoscopic, and operative techniques for the management of complications have made it necessary to revise the Atlanta classification.4,9,13 In addition, AP is a dynamic, evolving process, and the recognition of 2 different peaks in mortality reflects the 2 distinctly different clinical phases of the evolution of the disease not recognized by the Atlanta classification.9,14 The authors state that the Atlanta definitions of AP severity are ingrained in the lexicon of pancreatologists but are suboptimal because these definitions are based on empiric description of occurrences that are merely associated
Annals of Surgery r Volume 261, Number 4, April 2015
with severity.1 However, it is now clear that some of the information included in the classification was subject to different interpretations and that criteria of severity as defined by the Atlanta Symposium have not been used in a uniform fashion in recent publications. We believe that areas of major concern are as follows: (1) criteria for severe AP included OF and/or local complications, (2) distinction between transient OF and persistent OF, and (3) extent of pancreatic necrosis and peripancreatic collections. A recent revision of the Atlanta classification and definitions has been published by Acute Pancreatitis Classification Working Group to update the terminology and provide simple functional clinical and morphologic classifications.9 The consensus classification offers a comprehensive classification of AP severity and peripancreatic collections. New information on severity and radiologic descriptions of pancreatic and peripancreatic collections is provided. Finally, the classification differentiates acute peripancreatic fluid, pancreatic pseudocyst, acute necrotic collections, and walled-off necrosis. The revised classification of AP identified 2 phases of the disease: early and late. Severity is classified as mild, moderate, or severe. Mild AP, the most common form, has no OF, local or systemic complications, and usually resolves in the first week. Moderately severe AP is defined by the presence of transient OF, local complications, or exacerbation of comorbid disease. Severe AP is defined by persistent (>48 hours) OF. OF is defined as a score of 2 or more for 1 of these 3 organ systems using the modified Marshall scoring system.15 Reading the article, we have set ourselves some questions. First, is yet another classification of AP severity really needed? Second, why not revise and expand the Atlanta classification? Third, because it is perceived that there is a need to differentiate forms of disease on the basis of local and systemic determinants, is there a need to define 4 classes of gravity? In the proposed determinant-based classification of AP severity, the authors state that the definitions used for the categories of severity are based on attributes of the local (absent, sterile, or infected glandular or periglandular necrosis) and systemic determinants (absent, transient, or persistent OF) and possibility of interaction between the determinants during the same AP episode.1 The authors highlight the eventuality that, beyond these local and systemic determinants of severity, other occurrences should be considered and complications should not be used for the purpose of classifying the severity. In the revised Atlanta classification, exacerbation of preexisting comorbidity, such as chronic lung diseases, diabetes, obesity, or coronary www.annalsofsurgery.com | e101
Copyright © 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Annals of Surgery r Volume 261, Number 4, April 2015
Brisinda et al
artery disease, precipitated by AP is defined as a systemic complication.9 Furthermore, the authors distinguish between persistent OF— the defining feature of severe AP—and other systemic complications, which can be related to exacerbation of the underlying preexisting diseases.9 An important feature of the revised classification is the recognition that AP is an evolving, dynamic condition and that the severity may change during the course of the disease. In the early phase of disease, systemic inflammatory response syndrome or OF indicates potentially severe disease. If the patient improved rapidly during the early phase without OF and without local or systemic complications and has no persistent OF, the disease is defined as moderately severe AP. On the contrary, if the patient develops persistent OF, the disease is defined as severe AP and is associated with very high morbidity and mortality rates. We cannot understand the need to include in this classification of severity the class “critical AP.” From the definition, these patients would be those with the greatest degree of severity of disease—patients in whom AP is characterized by the presence of infected pancreatic necrosis and persistent OF. In our opinion, in these patients with severe disease from the onset, a classification of severity is less useful; it seems obvious that in these patients, the mortality rate is close to 100% often even in the presence of aggressive and intensive treatment. In accordance with Bradley,2 we believe that the stratification system proposed is empirically based upon clinical observations of local and systemic events. Furthermore,
e102 | www.annalsofsurgery.com
according to Bradley, we believe that clinical application of the new proposed determinantbased classification relies heavily on the diagnosis of pancreatic and peripancreatic necrosis, arbitrarily defined as necrosis in either or both pancreatic parenchyma and peripancreatic fat, using contrast-enhanced computed tomography to demonstrate any area of nonenhancement. Giuseppe Brisinda, MD Anna Crocco, MD Piero Giustacchini, MD Department of Surgery Catholic University School of Medicine University Hospital Agostino Gemelli Rome, Italy [email protected]
7.
8.
9.
10.
11.
REFERENCES 1. Dellinger EP, Forsmark CE, Layer P, et al. Determinant-based classification of acute pancreatitis severity: an international multidisciplinary consultation. Ann Surg. 2012;256:875–880. 2. Bradley EL, III. Atlanta redux: revisiting the severity stratification system for acute pancreatitis. Ann Surg. 2012;256:881–882. 3. Dellinger EP, Tellado JM, Soto NE, et al. Early antibiotic treatment for severe acute necrotizing pancreatitis: a randomized, double-blind, placebocontrolled study. Ann Surg. 2007;245:674–683. 4. Brisinda G, Vanella S, Crocco A, et al. Severe acute pancreatitis: advances and insights in assessment of severity and management. Eur J Gastroenterol Hepatol. 2011;23:541–551. 5. Wu BU, Johannes RS, Sun X, et al. The early prediction of mortality in acute pancreatitis: a large population-based study. Gut. 2008;57:1698–1703. 6. Petrov MS, Vege SS, Windsor JA. Global survey of controversies in classifying the severity of
12.
13.
14.
15.
acute pancreatitis. Eur J Gastroenterol Hepatol. 2012;24:715–721. Babu RY, Gupta R, Kang M, et al. Predictors of surgery in patients with severe acute pancreatitis managed by the step-up approach. Ann Surg. 2013;257:737–750. Singh VK, Wu BU, Bollen TL, et al. Early systemic inflammatory response syndrome is associated with severe acute pancreatitis. Clin Gastroenterol Hepatol. 2009;7:1247–1251. Banks PA, Bollen TL, Dervenis C, et al. Classification of acute pancreatitis—2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013;62:102–111. Kim YS, Lee BS, Kim SH, et al. Is there correlation between pancreatic enzyme and radiological severity in acute pancreatitis? World J Gastroenterol. 2008;14:2401–2405. Lankisch PG, Struckmann K, Assmus C, et al. Do we need a computed tomography examination in all patients with acute pancreatitis within 72 h after admission to hospital for the detection of pancreatic necrosis? Scand J Gastroenterol. 2001;36:432–436. Bradley EL, III. A clinically based classification system for acute pancreatitis. Summary of the International Symposium on Acute Pancreatitis, Atlanta, GA, September 11 through 13, 1992. Arch Surg. 1993;128:586–590. Mounzer R, Langmead CJ, Wu BU, et al. Comparison of existing clinical scoring systems to predict persistent organ failure in patients with acute pancreatitis. Gastroenterology. 2012;142:1476–1482; quiz e15–e16. Singh VK, Wu BU, Bollen TL, et al. A prospective evaluation of the bedside index for severity in acute pancreatitis score in assessing mortality and intermediate markers of severity in acute pancreatitis. Am J Gastroenterol. 2009;104: 966–971. Marshall JC, Cook DJ, Christou NV, et al. Multiple organ dysfunction score: a reliable descriptor of a complex clinical outcome. Crit Care Med. 1995;23:1638–1652.
C 2014 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2014 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
