Continuing inflammatory disease of pancreas characterised by irreversible morphological change typically causing pain and/or permanent loss of function.
Prevalence of chronic pancreatitis in
Olmsted County, Minnesota, USA, in 2006, stratified by sex (part a) and age and aetiology (part b) per 100,000 individuals | Yadav, D., Timmons, L., Benson, J. T., Dierkhising, R. A. & Chari, S. T. Incidence, prevalence, and survival of chronic pancreatitis: a population-based study. Am. J. Gastroenterol. 106, 2192–2199 (2011). This is one of the few systematic, population-based studies on the epidemiology of chronic pancreatitis.
Toxic-Metabolic, Idiopathic, Genetic, Autoimmune, Recurrent and Severe Acute Pancreatitis, Obstructive (TIGAR-O) classification system:
Categorizes known causes and factors that contribute to chronic pancreatitis.
TIGAR-O risk factor classification system | AP, acute pancreatitis; CFTR, cystic fibrosis transmembrane conductance regulator; CP, chronic pancreatitis; IBD, inflammatory bowel disease; PBC, primary biliary cirrhosis; SAPE, sentinel acute pancreatitis event; SPINK1, serine protease inhibitor kazal-type 1; TIGAR-O, Toxic-Metabolic, Idiopathic, Genetic, Autoimmune, Recurrent and Severe Acute Pancreatitis, Obstructive. | Pandol SJ, Gorelick FS, Gerloff A, et al. : Alcohol abuse, endoplasmic reticulum stress and pancreatitis. 2010;28(6):776–82. 10.1159/000327212
Pathophysiology of chronic pancreatitis: a) Anatomy of the pancreas. The pancreas consists of an exocrine and an endocrine compartment. The exocrine tissue is composed of acini, which are involved in the secretion of digestive enzymes, and ducts, which transport these enzymes to the intestine and which secrete large volumes of alkaline fluid, whereas the endocrine compartment contains the Islets of Langerhans (which are involved in the secretion of pancreatic hormones including insulin, glucagon and somatostatin). Anatomically, the pancreas is divided into the head, neck and body. b) Pathophysiology of chronic pancreatitis. Insults such as alcohol and tobacco initiate the first episode of acute pancreatitis, which is characterized by the recruitment of inflammatory cells. Continued insults lead to recurrent attacks of acute pancreatitis, which activate pancreatic stellate cells and initiate pancreatic fibrogenesis, ultimately resulting in chronic pancreatitis in most individuals. Notably, these insults cause histopathological changes in the pancreas in a substantial proportion of individuals, most of whom remain asymptomatic and only a few of whom develop clinical disease. Organ complications include biliary obstruction, duodenal obstruction, portal vein thrombosis, vascular aneurysms and bleeding. Pseudocysts can also develop in the course of the disease, causing further symptoms. Potential causes of pain in chronic pancreatitis include increased pressure in the ductal system and/or neuroplastic changes. A pancreatic resection specimen of a patient with chronic pancreatitis (inset) shows hypertrophy and dystrophy of the nerves (asterisks) surrounded by extensive fibrotic tissue and lymphocyte infiltrates (arrows). | Kleeff, J., Whitcomb, D., Shimosegawa, T. et al. Chronic pancreatitis. Nat Rev Dis Primers 3, 17060 (2017). https://doi.org/10.1038/nrdp.2017.60
Histological characteristics of alcoholic chronic pancreatitis: a) Early-stage
disease with well-preserved pancreatic parenchyma with moderate perilobular,
interlobular and periductal fibrosis, and focal intralobular fibrosis (lower left). Lobuli are represented by ‘L’ and ducts by asterisks. b) Histological image of a cystically dilated duct
(centre) with flattened epithelium, periductal (white arrows) and perilobular fibrosis
(asterisk), and a blood vessel with a thickened wall (black arrow). c) End-stage chronic pancreatitis with complete atrophy of the acinar cells, paucicellular fibrosis with prominent islets (arrows) and nerves (arrowheads). d) Large interlobular duct with
squamous metaplasia | Kleeff, J., Whitcomb, D., Shimosegawa, T. et al. Chronic pancreatitis. Nat Rev Dis Primers 3, 17060 (2017). https://doi.org/10.1038/nrdp.2017.60
Histological characteristics of autoimmune pancreatitis. a) Massive obliteration of the lobular architecture with diffuse fibrosis, abundant inflammatory infiltrates and stenosis of a medium-sized duct (asterisk) in autoimmune pancreatitis type 1. b) Detail of storiform fibrosis in autoimmune pancreatitis type 1. c) Core needle biopsy sample
of a patient with autoimmune pancreatitis type 1 showing massive lymphoplasmacellular infiltration and fibrosis.
d) Immunohistochemistry for CD138 showing abundant plasma cell infiltrates with periductal localization (arrows)
in autoimmune pancreatitis type 1. e) Immunohistochemistry for IgG4 showing abundant IgG4-positive cells in
autoimmune pancreatitis type 1. f) Granulocytic epithelial lesions of an interlobular medium-sized duct with a ruptured
epithelium (arrow) in autoimmune pancreatitis type 2 | Kleeff, J., Whitcomb, D., Shimosegawa, T. et al. Chronic pancreatitis. Nat Rev Dis Primers 3, 17060 (2017). https://doi.org/10.1038/nrdp.2017.60
Conceptual model of disease progression linked to the mechanistic definition of chronic pancreatitis.
This model organizes the genetic and environmental risk factors, the role of recurrent injury or stress, and the normal and abnormal response to the injury–inflammation–resolution–regeneration sequence. | CP, chronic pancreatitis;
PDAC,pancreatic ductal adenocarcinoma. | Whitcomb, D. C. et al. Chronic pancreatitis: an international draft consensus proposal for a new mechanistic definition. Pancreatology 16, 218–224 (2016).
Abdominal pain Intermittent/chronic Severe Intense stabbing pain Upper abdominal region Lasts for hours Progressive to severe/debilitating stage May radiate to back Alleviating factor: eating (high-fat foods specially) Stool Indigestion Weight loss Weak bones Vision problems Easy bruising Skin rashes
Pancreatic pseudocysts: Ductal obstruction → ↑ Pressure & leakage → Fluid accumulation Haemorrhage: May be into the peritoneal cavity, into pancreatic duct leading to hemosuccus pancreaticus, into the pseudocyst, or into the GI tract due to pseudoaneurysm. Pancreatic fistula & effusion: Drain output of any measurable volume of fluid on or after postoperative day 3 with amylase > 3x serum amylase activity. Commonly occurs after external drainage of pseudocyst. Pancreatic ascites: Due to leak from pancreatic duct or from pseudocyst Pancreatic malignancy (adenocarcinoma) (5% over 20-years): Suspected in patients who have recurrence of symptoms (recurrent pain, jaundice, weight loss, or anorexia) after surgery for CP
Biliary stricture (BS) (6%): Common in advanced CP and have a variable clinical presentation ranging from an incidental finding to overt jaundice and cholangitis Duodenal obstruction (1.2 %): Due to head inflammatory mass and later due to ischemia, a pseudocyst, groove pancreatitis, or fibrosis. These present with a prolonged history of vomiting and barium studies typically show a long constricting lesion of the duodenum, and endoscopy reveals reactive inflammatory changes in a narrowed duodenum. Splenic vein thrombosis (SVT) (12%): Due to perivenous inflammation. However most remain asymptomatic
Exocrine & endocrine deficiency:
Pancreatogenic diabetes (type 3c DM) (70%): Recurrent inflammation destroys α & β-cells of pancreas Pancreatic insufficiency: Indigestion, (fat soluble) vitamins A, D. E, K deficiency, steatorrhoea
Ideal test to image the abdomen and assess pancreas morphology and exclude other pathologies
CT imaging in chronic pancreatitis: Post-contrast CT image of severe chronic pancreatitis shows ductal stones (white arrows in part a and part b) within the dilated pancreatic duct (orange arrow; part b) | Kleeff, J., Whitcomb, D., Shimosegawa, T. et al. Chronic pancreatitis. Nat Rev Dis Primers 3, 17060 (2017). https://doi.org/10.1038/nrdp.2017.60
ERCP (Endoscopic retrograde cholangiopancreatography) “Chain-of-lakes” pattern: Due to stenosis + dilatation of ducts MRCP (Magnetic resonance cholangiopancreatography) with secretin stimulation (investigation of choice)
ERCP and MRCP imaging in chronic pancreatitis: a) Endoscopic retrograde cholangiopancreatography (ERCP) showing moderate chronic pancreatitis as evidenced by a slightly dilated duct (white arrows) and visible side branches (orange arrows). b,c) Magnetic resonance cholangiopancreatography (MRCP) imaging shows abnormal pancreatic duct (white arrows; part b) and enables the visualization of multiple abnormal side branches after secretin injection (white arrows; part c). Note the bile duct in part b and part c (green arrows) | Kleeff, J., Whitcomb, D., Shimosegawa, T. et al. Chronic pancreatitis. Nat Rev Dis Primers 3, 17060 (2017). https://doi.org/10.1038/nrdp.2017.60
Endoscopic ultrasound (EUS):
Assess ductal and parenchymal changes early in the course of the disease.
Endoscopic ultrasound images characterizing features of chronic pancreatitis: (a) Anechoic tubular structure with multiple hyperechoic structures with shadowing. Depicts a dilated main pancreatic duct with multiple calcified stones. (b) Anechoic tubular structure depicting dilated, irregular main pancreatic duct. (c) Diffuse echogenicity with hyperechoic foci with stranding. Depicts pancreatic lobularity with calcifications. | Pham, A., & Forsmark, C. (2018). Chronic pancreatitis: review and update of etiology, risk factors, and management. F1000Research, 7, F1000 Faculty Rev-607. https://doi.org/10.12688/f1000research.12852.1
Rosemont criteria (RC)
Standardization and definition of endosonographic features and thresholds for the diagnosis of chronic pancreatitis, and the grouping of criteria into major and minor importance categories
Guo, Jintao. Sun, Siyu. (2015). Endoscopic Ultrasound for the Diagnosis of Chronic Pancreatitis.
Pancreapedia: Exocrine Pancreas Knowledge Base, DOI: 10.3998/panc.2015.33
Chronic, unrelenting abdominal pain that is acutely worsening should entertain a differential diagnosis not limited to the following
Peptic ulcer disease (PUD) Cholelithiasis Biliary obstruction/biliary colic Acute pancreatitis Pancreatic malignancy Pseudocyst Chronic mesenteric ischemia
It is the primary aim of management before any other surgical intervention can be performed.
PERT (Pancreatic enzyme replacement therapy)
ERCP and pancreatic stent placement are established as therapy in pseudocyst, pancreatic fistula, main pancreatic duct injury, and pancreas divisum.
Endoscopic management of chronic pancreatitis: Drainage of a long stenotic segment of the pancreatic main duct (arrows; part a), by the insertion of a plastic stent (arrows; part b). A pancreatic pseudocyst with solid content is drained via the posterior wall of the stomach with a self-expanding metal stent (arrows; part c) under the guidance of endoscopic ultrasonography. CT scan showing near-complete resolution
ofthe pseudocyst (asterisk; part d) following the insertion of the stent (arrows; part d). | Kleeff, J., Whitcomb, D., Shimosegawa, T. et al. Chronic pancreatitis. Nat Rev Dis Primers 3, 17060 (2017). https://doi.org/10.1038/nrdp.2017.60
Extracorporeal shock wave lithotripsy (ESWL)
ESWL of obstructive pancreatic duct stones in patients with recurrent attacks can prevent further attacks.
Surgical management of chronic pancreatitis: a) Duodenum-preserving pancreatic head resection. Note that the pancreas is cut above the superior mesenteric vein and portal vein axis. b) Variant of the duodenum- preserving pancreatic head resection. Note that the pancreas is not cut above the superior mesenteric vein or portal vein axis and that the pancreatic duct is opened towards the pancreatic body and tail. c) Photograph of the intraoperative situs (surgical site) following a variant duodenum-preserving pancreatic head resection. The resection area is circled. The arrows mark the opened pancreatic duct | Kleeff, J., Whitcomb, D., Shimosegawa, T. et al. Chronic pancreatitis. Nat Rev Dis Primers 3, 17060 (2017). https://doi.org/10.1038/nrdp.2017.60
Showing advantages and disadvantages of commonly done surgical procedures | Pujahari A. K. (2015). Chronic Pancreatitis: A Review. The Indian journal of surgery, 77(Suppl 3), 1348–1358. https://doi.org/10.1007/s12262-015-1221-z
Chronic pancreatitis is attributed to alcohol abuse in the majority of cases. Tobacco smoking is an independent risk factor; other causes include genetic factors, metabolic disorders, chronic obstructive causes (for example, ductal stones), autoimmunity and idiopathic mechanisms. | Chronic pancreatitis. Nat Rev Dis Primers 3, 17061 (2017). https://doi.org/10.1038/nrdp.2017.61