Chronic Pancreatitis

Written by Egle Dieninyte

Definition

Chronic pancreatitis is defined by continuous inflammation of the pancreas, resulting in fibrosis, loss of acinar and islet cells. This ongoing inflammation and progressive parenchymal atrophy can manifest in abdominal pain, maldigestion due to exocrine pancreatic insufficiency, diabetes mellitus due to endocrine pancreatic insufficiency, and increases the risk of pancreatic cancer.

The clinical presentation varies according to the disease stage. In contrast to the previous view of acute and chronic pancreatitis as distinct entities, current evidence suggests that acute, relapsing pancreatitis and chronic pancreatitis represent a continuum of related and overlapping conditions.¹

Epidemiology

The reported annual incidence of chronic pancreatitis is relatively consistent across countries worldwide, ranging from 5 to 14 per 100,000 individuals. The estimated prevalence is approximately 30-50 per 100,000 individuals and rises with age, with a median age at diagnosis between 51 and 58 years. Onset at younger ages, including childhood, is often associated with a genetic predisposition. Traditionally, chronic pancreatitis has been considered to be more common in men, particularly those who consume excessive alcohol, with a frequency up to five times higher in men than women. Overall, the incidence of chronic pancreatitis appears to be rising over the past decade, likely due to improved diagnosis, as alcohol and smoking rates have remained relatively stable.^1,²

Etiology

A commonly used classification system for chronic pancreatitis is termed “TIGAR-O”, and refers to toxic-metabolic, idiopathic, genetic, autoimmune, recurrent acute pancreatitis and obstructive causes of chronic pancreatitis.

The most common cause of chronic pancreatitis is alcohol abuse, accounting for 40-70% of cases in Western countries and similar rates in Japan. Alcohol increases the risk of acute pancreatitis, especially during withdrawal periods, and may promote an altered inflammatory response to recurrent acute attacks.¹

Tobacco smoking is another major independent risk factor that accelerates disease progression with a pooled relative risk of 2.8 for current smokers. This risk increases proportionally with smoking intensity and decreases after cessation.¹

In western countries, 20-50% of chronic pancreatitis cases have other etiologies including:¹

Genetic – mutations and polymorphisms that predispose individuals to disease progression, with common genetic alterations in the PRSS1, CFTR and SPINK1 genes
Obstructive causes like pancreatic tumors, scars, ductal stones, pancreas divisum or other ductal anatomy variations that can lead to inflammation upstream of the obstruction
Metabolic disorders such as hyperlipidemia
Autoimmune pancreatitis (AIP)– encompassing inflammatory conditions that respond to steroid therapy
Recurrent acute pancreatitis, especially severe necrotizing episodes, leading to chronic disease
Idiopathic – refers to cases where thorough evaluation fails to identify the underlying disease cause.

Pathophysiology

The pathophysiology of chronic pancreatitis is complex and incompletely understood, with several pathways acting together or independently. It involves acinar cell injury, acinar stress responses, duct dysfunction, persistent or altered inflammation, and neuro-immune crosstalk. Over time, this results in progressive loss of functional tissue due to atrophy and fibrotic replacement. Consequently, patients experience recurrent or constant abdominal pain, diabetes mellitus reflecting endocrine insufficiency, and maldigestion as a result of exocrine insufficiency.¹

Clinical presentation and Diagnosis

The presentation of chronic pancreatitis is marked by abdominal pain, functional loss and structural pancreatic changes visible on imaging studies. However, these findings are only evident in late-stage disease, when most of the pancreatic parenchyma is fibrosed.

Diagnosis in the early-stage is challenging, as changes are subtle, ill-defined and overlap those of other disorders. Later stages are characterized by variable fibrosis and calcification of the pancreatic parenchyma; dilatation, distortion and stricturing of the pancreatic ducts, and can be complicated by pseudocysts; intrapancreatic bile duct strictures; narrowing of the duodenum; and superior mesenteric, portal and/or splenic vein thrombosis.¹

Chronic pancreatitis should be considered in patients with typical chronic abdominal pain and a history of acute pancreatitis, alcohol abuse, or a family history for the disease, especially when presenting with signs of exocrine or endocrine insufficiency. Imaging studies, preferably high-quality computed tomography with pancreatic protocol or magnetic resonance imaging/magnetic resonance cholangiopancreatography, are the best initial diagnostic tests to evaluate morphological changes in the pancreas. In case of equivocal imaging results and suspected chronic pancreatitis, endoscopic ultrasound should be performed. Exocrine function of the pancreas can be tested either directly, by the administration of a stimulatory hormone, or indirectly, e.g. testing fecal elastase levels.

Possible complications of chronic pancreatitis

Management

The main goals in managing chronic pancreatitis are to alleviate symptoms like pain, and treat exocrine and endocrine insufficiency, as well as prevent disease progression and complications. A step-up approach combining medical, endoscopic and surgical therapies is recommended for managing the various aspects of chronic pancreatitis, with careful multi-disciplinary evaluation at each stage to determine the optimal next treatment step.¹

Pain Management

Pain is the most common and debilitating symptom with detrimental effects on the quality of life. For pancreatic pain, the approach follows the WHO analgesic ladder, starting with simple analgesics and progressing to opioids if needed.¹ Opioid rotation is often required due to adverse effects. Adjuvant medications like antidepressants and anticonvulsants (e.g. pregabalin) may provide additional pain relief.

Invasive therapies are frequently required for pain due to ductal obstruction by stones and/or strictures. These includes endoscopic procedures such as sphincterotomy, stent insertion, stone removal and extracorporeal shockwave lithotripsy (ESWL). Surgery in the form of drainage or resection procedures is often needed for refractory cases.^1,2

Endoscopic Treatment

Endoscopic therapies for chronic pancreatitis are aimed at improving pancreatic juice outflow by eliminating the cause of ductal obstruction (i.e., strictures or stones). The cases most suitable for endoscopic treatment have clear evidence of ductal obstruction: main pancreatic duct stricture with upstream dilation of the duct or stones in the pancreatic head or body. Endoscopic interventions include sphincterotomy, pancreatic stone removal and pancreatic duct stenting. Pancreatic stone removal often requires accessory devices such as extracorporeal shock wave lithotripsy or cholangioscopy with laser lithotripsy.

Patient selection is important; a short disease duration, no alcohol/smoking, non-severe pain, absence of a duct stricture, and complete clearance of stones/ strictures after initial treatment results in the best outcomes after endotherapy.²

The clinical response should be evaluated at 6-8 weeks after endoscopic/ESWL treatment. If unsatisfactory, the patient’s case should be re-discussed in a multidisciplinary team and surgical options should be considered.²

Surgery

Surgical interventions aim to provide pain relief, treat complications like biliary/duodenal obstruction, and prevent further pancreatic injury. Options include drainage procedures like longitudinal pancreaticojejunostomy and resection procedures like duodenum-preserving pancreatic head resection.¹The selection of surgery type depends on the features of chronic pancreatitis in individual patient, such as pancreatic duct diameter, presence of multiple strictures and pseudotumorous mass.

Early surgery, before the development of severe disease, may offer better outcomes in terms of pain control, preservation of endocrine/exocrine function, and lower pancreatic cancer risk compared to delayed surgery.¹

Exocrine Insufficiency

Exocrine pancreatic insufficiency is a sign of late-stage disease and usually occurs after more than 5 years of disease progression. Marked exocrine insufficiency leads to maldigestion of fat and protein, in turn, leading to weight loss.

Pancreatic enzyme replacement therapy with enteric-coated pancreatic enzyme preparations in adequate doses are prescribed to relieve maldigestion symptoms like steatorrhea and nutritional deficiencies caused.¹ If non-enteric-coated preparation is chosen, acid suppression is required to avoid acid denaturation of lipase.

Endocrine Insufficiency

Chronic pancreatitis could result in loss of pancreatic isles. This so called diabetes mellitus type 3c is marked by loss of insulin production, as well as other regulatory hormones, such as glucagon and pancreatic polypeptide. These patients can have severe blood glucose level swings (“brittle diabetes mellitus”), and generally require insulin to control hyperglycemia.

References

[1] Kleeff J, Whitcomb DC, Shimosegawa T, et al. Chronic pancreatitis. Nat Rev Dis Primers. 2017;3:17060. doi:10.1038/nrdp.2017.60
[2] Dumonceau J-M, Delhaye M, Tringali A, et al. Endoscopic treatment of chronic pancreatitis: European Society of Gastrointestinal Endoscopy (ESGE) Guideline – Updated August 2018. Endoscopy. 2019;51:179-193. doi:10.1055/a-0822-0832