Pancreatitis

Medical and Surgical Management

David B. Adams, Peter B. Cotton, Nicholas J. Zyromski, John A. Windsor, David B. Adams, Peter B. Cotton, Nicholas J. Zyromski, John A. Windsor

• Publisher: Wiley-Blackwell
• Year: 2017
• Print ISBN: 9781118917121
• eBook ISBN: 9781118924914
• Edition: 1
• Topic: Medicine
• Subtopic: Gastroenterology & Hepatology

Pancreatitis: medical and surgical management provides gastroenterologists and GI surgeons, both fully qualified and in training, with a focused, evidence-based approach to the most exciting developments in the diagnosis and clinical management of pancreatitis.

Focusing mainly on the rapidly changing and innovative medical and surgical strategies to manage the disease, new surgical procedures such as endoscopic biliary intervention and minimally invasive necrosectomy to exciting new medical therapies like Antiprotease, Lexipafant, probiotics and enzyme treatment are all discussed.

Full colour throughout, with over 250 colour illustrations and with reference to the latest clinical guidelines from the AGA, ACG and UEGW at all times, it is an essential consultation tool for all those managing patients with this increasingly common condition.

Chapter 1
Epidemiology and genetics of pancreatitis

David C. Whitcomb

Division of Gastroenterology, Hepatology and Nutrition, Departments of Medicine, Cell Biology & Physiology, and Human Genetics, University of Pittsburgh/UPMC, Pittsburgh, PA, USA

Definition

Chronic pancreatitis (CP) can be defined as “a continuing inflammatory disease of the pancreas, characterized by irreversible morphological change, and typically causing pain and/or permanent loss of function” [1]. This definition is intentionally pragmatic, as developed by the members of the Pancreatic Society of Great Britain and Ireland in March 1983 in Cambridge, England as a pretext to the morphology-based Cambridge classification of CP severity [1]. The definition is vague but has stood the test of time and has been followed in consensus statements by nearly all societies and expert groups for the subsequent two decades.

The pragmatic nature of the Cambridge definition speaks to the challenges in defining a syndrome with multiple etiologies, variable features, unpredictable clinical course, and inadequate treatment [2]. As a morphology-based definition, it also ignores key histologic, clinical, and functional features that dominate the definitions from the Marseilles meetings [3, 4] and ignores the possibility of “minimal change” CP [5a], functional changes such as pancreatitis-associated chronic pain syndrome and/or pancreatic insufficiency, or autoimmune pancreatitis. Furthermore, the definition is independent of etiology, it cannot differentiate progressive disease from old scars from a bout of acute pancreatitis (AP), and it has little prognostic value. A new, two-part mechanistic definition of CP has been proposed that focuses on disruption of the normal injury → inflammation → resolution → regeneration sequence. The definition includes the essence of CP, “Chronic pancreatitis is a pathologic fibro-inflammatory syndrome of the pancreas in individuals with genetic, environmental and/or other risk factors who develop persistent pathologic responses to parenchymal injury or stress,” and the characteristics of CP, “Common features of established and advanced CP include pancreatic atrophy, fibrosis, pain syndromes, duct distortion and strictures, calcifications, pancreatic exocrine dysfunction, pancreatic endocrine dysfunction, and dysplasia.” This new definition opens the door to new diagnostic criteria that distinguishes CP from other disorders with CP-like features, provides a method for diagnosing “early CP,” and may improve methods of mechanism-based therapies – which is the goal of personalized medicine [5b].

Burden of disease

Epidemiologists struggle to determine the incidence and prevalence of CP – in part because of the vague definitions and different detection approaches [6, 7]. Administrative data, such as ICD-9 codes used in the United States, have limited value because the same code, 577.1, is used for recurrent acute pancreatitis (RAP) as well as CP. Indeed, authoritative studies of the burden of digestive diseases in the United States found it impossible to distinguish AP from CP using public records and grouped the two entities into one big problem [8].

Autopsy studies using histologic criteria such as duct ectasia, periductal fibrosis, ductular proliferation, acinar ductular metaplasia, and interstitial inflammation or fibrosis suggest that the incidence of CP is as high as 12–14% [9, 10], with abnormal fibrosis in up to 39% [10]. Histologic changes suggestive of CP are even more prevalent in patients with very common chronic disorders such as renal disease (up to 56%) [9] and diabetes mellitus (DM) (∼7% by clinical evaluation but much higher in diabetes autopsy databases such as nPOD [11] – noting the problem of reverse causality [12]). However, it is well recognized that interstitial inflammation and fibrosis alone are not sufficient to make a diagnosis of CP [13].

The emergence and widespread use of sensitive abdominal imaging techniques has helped standardize epidemiological approaches when morphologic criteria are used. While morphology is not the only criteria used in epidemiology studies, it does serve as an equalizing factor. Thus, the burden of CP in terms of disease prevalence from more recent surveys is more useful.

In the United States the best estimate comes from Minnesota, where the age-adjusted prevalence of CP was estimated at 41.8 cases per 100,000 population [7]. In contrast to earlier studies, the prevalence between males and females was similar, as reported in the North American Pancreatitis Study 2 (NAPS2) reports [14, 15]. In Japan the prevalence of CP was similar to the United States, with 36.9 cases per 100,000 population [16]. In France the prevalence of CP was 26.4 cases per 100,000 population [17], with a strong male predominance. The lowest prevalence was in China, which was only 3 cases of CP per 100,000 population in 1996 but had risen rapidly to 13.5 per 100,000 population by 2003 [18]. The highest rates were in Southern India, where the prevalence of CP is 114–200 per 100,000 population [19]. In addition to difference in prevalence, there are marked differences in rates of the etiologic diagnoses, with alcoholic and idiopathic being the most common causes in all studies. Alcohol etiology is consistently more common in men than in women.

Clinical features

The clinical features of CP include recurrent and chronic inflammation, fibrosis, duct distortion, pseudocysts, atrophy, pancreatic exocrine insufficiency, DM, multiple pain patterns, stones, and risk of pancreatic cancer. These features vary with etiology and environmental factors, and none of them are present in all patients – except for when duct distortion is used as the diagnostic criteria as in the Cambridge definition [1].

Diagnosis

Using the Cambridge definition of CP, a “clinical” diagnosis of CP can usually be made without ambiguity when significant morphologic features are documented. The problem with the Cambridge definition is the requirement of “irreversible morphological change” in the pancreas, how it is defined, and when it occurs. Indeed, patients may have symptoms of CP for 5–10 years before irreversible morphologic changes are documented, resulting in presumably unnecessary pain, anxiety, uncertainty, suffering, and numerous diagnostic tests. The result of the process is a “diagnosis,” with continued symptomatic treatment. Furthermore, the consequence of classifying CP based on morphologic criteria is that, while all investigators and clinicians agree on what end-stage CP looks like, they continue to sharply disagree on the border between “normal” and “abnormal” and on the minimal required features.

Many experts also deviate from the Cambridge definition, recognizing the limitations of morphology alone and the possibility of minimal change CP with prominent functional features such as pancreatic juice with low bicarbonate concentrations or pancreatitis-like pain syndromes. This view is supported by the clinical improvement in some patients diagnosed with minimal change pancreatitis and pain who find relief with total pancreatectomy and islet autotransplantation (TPIAT) [20–23]. These differences in perspectives on traditional views of CP make a consensus definition of early CP nearly impossible, with a ripple effect of making the criteria for early diagnosis somewhat arbitrary.

Animal models of early CP

The use of model organisms to understand human diseases remains a critical component of biomedical research. A good model should be a simplified version of something that reflects its primary components and is useful to study its characteristics under a variety of conditions. In the case of CP, animal models demonstrated that multiple injuries and inflammation resulted in parenchymal pathology, including scaring, but did not provide insight into human disease, which appeared stochastic in onset and highly variable in progression, clinical features, and outcomes. Thus, animal models provided insight into downstream pathology but failed to provide insight into etiologies, susceptibility, and variable progression.

Genetic risk factors for CP

In 1996 we discovered that hereditary pancreatitis (HP), a rare,...

Table of contents

• Cover
• Title Page
• Copyright
• Table of Contents
• List of contributors
• Chapter 1: Epidemiology and genetics of pancreatitis
• Chapter 2: Part A: Pathobiology of the acinar cell in acute pancreatitis
• Chapter 2: Part B: Locoregional pathophysiology in acute pancreatitis: pancreas and intestine
• Chapter 2: Part C: Pathophysiology of systemic inflammatory response syndrome and multiorgan dysfunction syndrome in acute pancreatitis
• Chapter 3: Diagnosis, prediction, and classification
• Chapter 4: Medical treatment
• Chapter 5: Nutritional treatment in acute pancreatitis
• Chapter 6: Gallstone pancreatitis: diagnosis and treatment
• Chapter 7: Treatment of local complications
• Chapter 8: Treatment of systemic complications and organ failure
• Chapter 9: Specific treatment for acute pancreatitis
• Chapter 10: Sequelae of acute pancreatitis
• Chapter 11: History of chronic pancreatitis
• Chapter 12: Part A: Epidemiology and pathophysiology: epidemiology and risk factors
• Chapter 12: Part B: Epidemiology and pathophysiology: genetic insights into pathogenesis
• Chapter 12: Part C: Pancreatic stellate cells: what do they tell us about chronic pancreatitis?
• Chapter 12: Part D: Autoimmune pancreatitis: an update
• Chapter 12: Part E: Etiology and pathophysiology: tropical pancreatitis
• Chapter 12: Part F: Mechanisms and pathways of pain in chronic pancreatitis
• Chapter 13: Part A: Imaging of chronic pancreatitis
• Chapter 13: Part B: Endoscopic ultrasonography in chronic pancreatitis
• Chapter 14: Part A: Pancreatic enzyme replacement therapy (PERT)
• Chapter 14: Part B: Nutritional treatment: antioxidant treatment
• Chapter 14: Part C: Pancreatogenic diabetes: etiology, implications, and management
• Chapter 14: Part D: Nutrition without a pancreas: how does the gut do it?
• Chapter 15: Part A: Endoscopic management of chronic pancreatitis
• Chapter 15: Part B: Shocking and fragmenting pancreatic ductal stones
• Chapter 15: Part C: Endoscopic management: celiac plexus blockade
• Chapter 16: Part A: A brief history of modern surgery for chronic pancreatitis
• Chapter 16: Part B: Surgery for chronic pancreatitis: indications and timing of surgery
• Chapter 16: Part C: Chronic pancreatitis: surgical strategy in complicated diseases
• Chapter 16: Part D: Surgery for chronic pancreatitis: pancreatic duct drainage procedures
• Chapter 16: Part E: Surgical management: resection and drainage procedures: Chronic pancreatitis – hybrid procedures
• Chapter 16: Part F: The role of pancreatoduodenectomy in the management of chronic pancreatitis
• Chapter 17: Part A: Total pancreatectomy and islet cell autotransplantation: patient selection
• Chapter 17: Part B: Total pancreatectomy and islet cell autotransplantation: the science of islet cell preservation, from pancreas to liver
• Chapter 17: Part C: Total pancreatectomy and islet cell autotransplantation: long-term assessment of graft function
• Index
• End User License Agreement