Acute pancreatitis

doi:10.1016/S0140-6736(14)60649-8

The Lancet

Volume 386, Issue 9988, 4–10 July 2015, Pages 85-96

https://doi.org/10.1016/S0140-6736(14)60649-8 Get rights and content

Summary

Acute pancreatitis, an inflammatory disorder of the pancreas, is the leading cause of admission to hospital for gastrointestinal disorders in the USA and many other countries. Gallstones and alcohol misuse are long-established risk factors, but several new causes have emerged that, together with new aspects of pathophysiology, improve understanding of the disorder. As incidence (and admission rates) of acute pancreatitis increase, so does the demand for effective management. We review how to manage patients with acute pancreatitis, paying attention to diagnosis, differential diagnosis, complications, prognostic factors, treatment, and prevention of second attacks, and the possible transition from acute to chronic pancreatitis.

Introduction

In this Seminar, we provide a comprehensive and balanced account of the advances since the 2008 Seminar in The Lancet on acute pancreatitis,³ highlight areas of controversy or international differences in practice, and describe concepts underlying the disease. The annual incidence of acute pancreatitis ranges from 13 to 45 per 100 000 people (appendix).⁴ In patients treated in hospital in the USA in 2009, acute pancreatitis was the most frequent principal discharge diagnosis in gastrointestinal disease and hepatology.⁵ The number of discharges with acute pancreatitis as principal diagnosis was 30% higher than in 2000. Acute pancreatitis was the second highest cause of total hospital stays, the largest contributor to aggregate costs, and the fifth leading cause of in-hospital deaths, showing the importance of accurate data for the disorder.

Section snippets

Causes

Gallstones and alcohol misuse are the main risk factors for acute pancreatitis (appendix). During 20–30 years, however, the risk of biliary pancreatitis is unlikely to be more than 2% in patients with asymptomatic gallstones⁶ and that of alcoholic pancreatitis is unlikely to exceed 2–3% in heavy drinkers.⁷ Other factors, possibly genetic, therefore probably play a part. Drugs represent an additional cause of acute pacreatitis⁸ (panel 1 and appendix).

Smoking might increase the risk of acute

Mechanisms of cellular injury

Pancreatic duct obstruction, irrespective of the mechanism, leads to upstream blockage of pancreatic secretion, which in turn impedes exocytosis of zymogen granules (containing digestive enzymes) from acinar cells. Consequently, the zymogen granules coalesce with intracellular lysosomes to form condensing or autophagic vacuoles containing an admixture of digestive and lysosomal enzymes. The lysosomal enzyme cathepsin B can activate the conversion of trypsinogen to trypsin. Findings from studies

Classification

The Atlanta classification⁴⁵ is the standard classification of the severity of acute pancreatitis. The recently published revised classification⁴⁶ provides definitions of the clinical and radiologic severity of acute pancreatitis. Clinical severity of acute pancreatitis is stratified into three categories: mild, moderately severe, and severe (table 2).

Patients with mild acute pancreatitis (no organ failure or systemic or local complications) usually do not need pancreatic imaging and are

Main diagnostic procedures

Clinicians are interested in confirmation of the diagnosis and exclusion of differential diagnoses (appendix). In accordance with the revised Atlanta classification, acute pancreatitis can be diagnosed if at least two of the following three criteria are fulfilled: abdominal pain (acute onset of persistent and severe epigastric pain, often radiating to the back); serum lipase (or amylase) activity at least three-times the upper limit of normal; or characteristic findings of acute pancreatitis on

Therapy

The patient's management begins on the emergency ward, where acute pancreatitis has to be confirmed, the risk stratified, and basic treatment initiated. This treatment includes early fluid resuscitation, analgesia, and nutritional support (appendix). Patients undergoing volume resuscitation should have the head of the bed raised, undergo continuous pulse oximetry, and receive supplemental oxygen. Supplemental oxygen has been shown to more than half mortality in patients older than 60 years.⁶³

Necrosis

Prophylactic antibiotics are not indicated.87, 88, 89, 90 Surgical resection of pancreatic necroses can be achieved by open, laparoscopic, or staged necrosectomy (open-staged or closed-continuous lavage). These methods do not compete with, but rather complement, other techniques. No guidelines exist, but there is consensus that surgical intervention should be done—if at all—at a late stage, at least 2 weeks after the onset of pancreatitis.⁹¹

More conservative interventions than surgery now

Refeeding

Basic treatment of acute pancreatitis should be continued until the patient shows distinct clinical improvement (freedom from pain and normal body temperature and abdominal findings). No binding recommendation for severe acute pancreatitis exists; the decision is taken on an individual basis. In mild acute pancreatitis, oral feeding should be resumed as soon as possible according to the present European Society for Parenteral and Enteral Nutrition guidelines.¹¹¹ When and how this feeding should

Prevention

One study¹²⁷ showed that interventions by medical personnel (structured talks with patients by nurses trained to inform patients how and why they should stay abstinent) at 6-month intervals significantly lowered the recurrence rate of alcohol-induced pancreatitis within 2 years. In patients with mild biliary acute pancreatitis, cholecystectomy should be done before discharge. In patients with necrotising biliary acute pancreatitis, cholecystectomy should be postponed to prevent infection until

Conclusions

From the pathophysiological viewpoint, the consensus has been that exposure of acinar cells to injurious agents (alcohol or bile salts) perturbs a multitude of acinar functions (exocytosis, enzyme activation, lysosomal function, cytokine production, mitochondrial function, and autophagy); however, findings from studies suggest that the final common mechanism that mediates acinar cell death (irrespective of the cause of acute pancreatitis) might be aberrant intracellular calcium signalling.⁴⁴

Search strategy and selection criteria

We searched PubMed for the term “acute pancreatitis”, together with “aetiology”, “pathogenesis”, “prognostic parameters”, “complications”, “death”, “treatment”, or “prognosis”. We included articles in English, French, German, and Spanish from Jan 1, 2009 to Dec 31, 2013, together with highly cited older publications that seemed necessary for full understanding. Moreover, we included several sets of guidelines, two of which cover almost the whole range of acute pancreatitis—namely, those from

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SeminarAcute pancreatitis

Summary

Introduction

Section snippets

Causes

Mechanisms of cellular injury

Classification

Main diagnostic procedures

Therapy

Necrosis

Refeeding

Prevention

Conclusions

Search strategy and selection criteria

Lancet

Gastroenterology

Gastroenterology

Pancreatology

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Gastroenterology

Surgery

Pancreatology

Gastroenterology

Clin Gastroenterol Hepatol

Pancreatology

J Surg Res

Clin Gastroenterol Hepatol

Gastroenterology

Gastroenterology

Pancreatology

Gastroenterology

Clin Nutr

Pancreatology

Gastroenterology

Lancet

Gastrointest Endosc

American College of Gastroenterology guideline: management of acute pancreatitis

Am J Gastroenterol

IAP/APA evidence-based guidelines for the management of acute pancreatitis

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Burden of gastrointestinal disease in the United States: 2012 update

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What is the risk of alcoholic pancreatitis in heavy drinkers?

Pancreas

Drug-induced pancreatitis

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Cigarette smoking, smoking cessation and acute pancreatitis: a prospective population-based study

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Smoking and risk of acute and chronic pancreatitis among women and men: a population-based cohort study

Arch Intern Med

Patients with type 2 diabetes mellitus have higher risk for acute pancreatitis compared with those without diabetes

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Increased risk of acute pancreatitis in patients with type 2 diabetes: an observational study using a Japanese hospital database

PLoS One

Risk of acute pancreatitis in type 2 diabetes and risk reduction on anti-diabetic drugs: a population-based cohort study in Taiwan

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Acute pancreatitis