Continuing Education Activity

Chronic pancreatitis is a progressive inflammatory disorder that leads to irreversible destruction of exocrine and endocrine pancreatic parenchyma caused by atrophy and/ or replacement with fibrotic tissue. Functional consequences include severe abdominal pain, diabetes mellitus, and malabsorption. This activity describes the etiology, pathophysiology, evaluation, and management of chronic pancreatitis and highlights the role of an interprofessional team in caring and rehabilitation of affected patients.

Objectives:

• Describe the clinical presentation of patients with chronic pancreatitis.
• Outline the evaluation and grading of patients with chronic pancreatitis.
• Explain the treatment strategies for chronic pancreatitis.
• Summarize interprofessional team strategies for improving care coordination and communication to advance the evaluation and management of chronic pancreatitis and optimize outcomes.

Introduction

The pancreas is an accessory organ of digestion known to have dual functions in the endocrine and exocrine systems. It is necessary for the hydrolysis of macromolecules including proteins, carbohydrates, and fats (in combination with bile from the common bile duct). The pancreas has a main pancreatic duct running through the length of it, an accessory duct, and many various cell types. The ducts can become blocked, or they can be genetically deformed. During constant inflammation, scarring and fibrosis of the ducts lead to permanent damage to many structures, impairing its secretory functions.

Chronic pancreatitis is a progressive inflammatory disease of the pancreas that affects both functions of the pancreas. For example, when the exocrine function is affected, patients will present with pancreatic insufficiency, steatorrhea, and weight loss. Pancreatic insufficiency results when greater than 90% of the organ is damaged. The incidence depends on the severity of disease and can be as high as 85% in severe chronic pancreatitis. On the other hand, impairment of the endocrine function of the pancreas will eventually result in pancreatogenic diabetes (Type 3c diabetes).

Chronic pancreatitis is unlike acute pancreatitis. The latter presents with acute onset abdominal pain radiating to the back. Patients with chronic pancreatitis may be asymptomatic for long periods of time. At other times, they may also have unrelenting abdominal pain with breakthrough pain requiring hospitalization. This disease process varies from acute pancreatitis in another way, in other words, histologically. The types of inflammatory cells present are different. Acute pancreatitis has a predominance of neutrophils, while chronic pancreatitis has more mononuclear infiltrates.[1][2][3]

Etiology

Causes of chronic pancreatitis include alcohol abuse, ductal obstruction (malignancy, stones, trauma), genetics (cystic fibrosis, hereditary pancreatitis), chemotherapy, and autoimmune diseases such as systemic lupus erythematosus (SLE) or autoimmune pancreatitis. New studies are finding that deficiencies in certain vitamins and antioxidants may be linked to the disease.[4][5]

The most common cause is alcohol consumption. The alcohol increase secretion of proteins from acinar cells, causing the fluid to become viscous, leading to ductal obstruction, acinar fibrosis, and atrophy. Fortunately, less than 10% of alcoholics develop

Inchronic pancreatitis, suggesting that other mechanisms play a role in the pathology.

Other common causes include:

• Hypercalcemia
• Hyperlipidemia (usually types 1 and V)
• Nutrition
• Obstruction of the duct (either congenital or acquired)
• Medications

Epidemiology

When compared to other illnesses, the incidence of chronic pancreatitis is hard to identify. In cases where the disease is secondary to alcohol, it can go largely undiagnosed since chronic pancreatitis is progressive. The diagnosis can take a long time to be discovered. The latest epidemiological report in 2014 estimated an incidence that has been consistent over the years. However, the prevalence might be underestimated. Further studies are needed.[6][7]

In the US, the condition affects African Americans more frequently than caucasians. In addition, chronic pancreatitis due to alcohol is more common in males, whereas that due to hyperlipidemia is more common in females. The median age at diagnosis is 45.

Pathophysiology

The pathogenesis of chronic pancreatitis seems to involve genetic factors and environmental factors. Studies have identified pancreatitis susceptibility genes associated with loss of function mutations. There are two main theories on the pathogenesis of chronic pancreatic disease. One theory is that of impaired bicarbonate secretion which cannot respond to the increased secretion of pancreatic proteins. These abundant proteins subsequently combine to form plugs within the lobules and ducts. This leads to calcification and stone formation. The other theory involves intraparenchymal activation of digestive enzymes within the pancreatic gland (possibly due to genetics or external influences such as alcohol). One recent study proposes that alcohol diminishes the cell's ability to respond to calcium signaling. This alters the feedback mechanism and promotes a cycle leading to cell death.[8][9]

Histopathology

Histopathology will reveal a marked increase in the connective tissue around the lobules and ducts. The acini architecture is often distorted and fibrosis is common in the later stages. Plus of precipitated protein may also be seen in the ducts. The distortion of the ductal system can lead to "chain of lakes' appearance on the CT scan.

History and Physical

Chronic pancreatitis can present with prolonged abdominal pain with intermittent pain-free periods, weight loss, and relief of abdominal pain when leaning forward. However, in some cases, patients can be asymptomatic. Nausea, vomiting, and steatorrhea or greasy, foul-smelling, difficult-to-flush stools can also occur. Glucose intolerance or pancreatic diabetes is another finding later in the disease process. These are classic presentations in patients with a past medical history of alcohol abuse, tobacco use, malignancy (with ductal obstruction), hyperlipidemia, systemic disease, autoimmune disease, cystic fibrosis, among others).

Other symptoms include weight loss, diarrhea, and steatorrhea.

During an acute attack, the patient may draw the knees towards the chest to relieve the pain. Sometimes a mass may be palpated indication presence of a pseudocyst. Signs of malnutrition are common in long-standing cases.

Evaluation

Basic lab studies for chronic pancreatitis can include a CBC, BMP, LFTs, lipase, amylase, lipid panel and a fecal-elastase-1 value. Lipase and amylase levels can be elevated, but they are usually normal secondary to significant pancreatic scarring and fibrosis. Of note, amylase and lipase values should not be considered diagnostic nor prognostic.

In children, one should perform genetic testing for CFTR.

In cases where chronic autoimmune pancreatitis is suspected, inflammatory markers including ESR, CRP as well as ANA, RF, antibodies, and immunoglobulins can be obtained. To workup steatorrhea, a 72-hour quantitative fecal fat is the gold standard (whereby values greater than 7 gm per day is confirmatory). As an alternative, a fecal elastase-1 level can be obtained from a single random stool sample to help evaluate pancreatic insufficiency. This is the most sensitive and specific alternative to the qualitative fecal fat test available.

The MRCP is the premier diagnostic imaging study because it can reveal calcifications (hallmark sign), pancreatic enlargement, ductal obstruction or dilation. MRCP has higher sensitivity and specificity for chronic pancreatitis than does the transabdominal ultrasound or plain films (though both can reveal calcifications). Management could also include a CT scan of the abdomen as an alternative.

ERCP has been the traditional test of choice in diagnosing chronic pancreatitis. It is used when there is no steatorrhea or when plain films do not reveal calcifications. However, currently, many hospitals are trending towards using MRCPs instead and are relying on ERCP only when therapeutic intervention is needed. Endoscopic ultrasound is another imaging modality that can be used to diagnose the disease.[10][11][12]

Tests to assess the pancreas

Tests to assess pancreatic function are sensitive but need to be done early. Duodenal aspirates can help determine the output of amylase, pancreatic bicarbonate, and lipase. The pancreatic duct can be cannulated during ERCP and the pancreatic juice can be assessed for the same parameters.

Current Guidelines

• CT is the ideal test to image the abdomen and assess pancreas morphology
• CT scan can also help exclude other pathologies
• MRCP is indicated when the CT is normal
• Secretin stimulated MRCP can define subtle changes in the ducts, and also helps assessment of ductal compliance and exocrine function.
• Endoscopic ultrasound can be used to assess ductal and parenchymal changes early in the course of the disease.

Treatment / Management

The goal of treatment is to decrease abdominal pain and improve malabsorption. Pain is secondary to inflammation, neuropathic mechanisms, and blocked ducts. Eating small, frequent low-fat meals is generally recommended along with replacement of fat-soluble vitamins and pancreatic enzymes. In cases where pain relief is not achieved with enzyme replacement treatment and dietary modification, non-opioid regimens should be utilized (TCA, NSAIDs, pregabalin) initially before starting a trial of opioids. Studies regarding the benefit of antioxidants are unconfirmed. New studies show some benefit of using medium-chain triglycerides. Surgery should be considered in patients who fail medical therapy and continue to have pain.[1][11][13]

The patient's behavior has to be modified to prevent exacerbation of the disorder. Patients must cease alcohol and discontinue smoking.

Inpatient care is often required for patients with chronic pain and anorexia. These patients often require narcotics and nutritional supplementation.

Pancreatic enzymes are usually taken with a meal and help lower the pain. However, the benefits of pancreatic enzymes still remain questionable.

Surgery is required for:

• Pancreatic abscess, fistula or pseudocyst
• Pancreatic ascites
• Mechanical obstruction of the common bile duct
• Stenosis of the duodenum leading to gastric outlet obstruction
• Variceal bleeding due to splenic vein thrombosis

Surgery to resect the pancreas can produce good results in the hands of experienced surgeons, but the operative mortality can exceed 10% and the quality of life is impaired without a functioning pancreas.

Today, interventional radiology can be used to manage most complications including drainage and stent placement.

Celiac ganglion blockade can be performed to decrease pain but this is an invasive procedure with a risk of paralysis due to transverse myelopathy. Endoscopic methods of celiac nerve blocks have not been beneficial.

Endoscopy is often used to relieve obstruction in the pancreatic duct but only works in 60% of patients.

Differential Diagnosis

Chronic, unrelenting abdominal pain that is acutely worsening should entertain a differential diagnosis not limited to peptic ulcer disease, cholelithiasis, biliary obstruction/biliary colic, acute pancreatitis, pancreatic malignancy, pseudocyst, chronic mesenteric ischemia, among others.

Prognosis

Poor prognosis is associated with continued alcohol use, smoking, and the presence of end-stage liver disease. At 10 years, there is a survival of 70%, which drops to 45% at 20 years. Pseudocyst formation, mechanical obstruction of the bile duct and duodenum are major complications. Addition complications include diabetes (30% of patients), development of gastric varices and pseudoaneurysm formation.

Complications

Chronic pancreatitis has many complications including:

• Formation of a pseudocyst, which can obstruct the bile duct
• Recurrent acute pancreatitis, especially in alcoholics who continue to drink
• Splenic venous thrombosis
• Pancreatic ascites or pleural effusion (rare)
• Pseudoaneurysms (rarely of the vessels close to the pancreas)
• Pancreatic diabetes (later in disease course)

Of note, patients with chronic pancreatitis are at increased risk of developing pancreatic cancer.

Deterrence and Patient Education

Patients diagnosed with chronic pancreatitis secondary to chronic alcohol use should be encouraged to avoid alcohol (and to stop smoking, if applicable). Follow up should take place within 1 to 2 months.

A low-fat diet with high protein and carbohydrates is recommended for patients with steatorrhea. The fat intake should be less than 20g/day or less. However, this can lead to malabsorption of fat-soluble vitamins and thus, oral supplements are necessary.

Pearls and Other Issues

Chronic pancreatitis is an inflammatory disease caused by multiple factors including genetic predisposition and external factors. It is different from acute pancreatitis in many ways. In acute pancreatitis, abdominal pain is usually sudden onset, while chronic pancreatitis can be painless or can be an unrelenting, dull pain with breakthrough episodes of acute pain. The pathophysiology is also different between the two diseases, but more importantly, workup for chronic pancreatitis does not have to include amylase and lipase levels. The MRCP is the test of choice in diagnosing chronic pancreatitis, and the goal of treatment is to control pain and manage malabsorption from pancreatic insufficiency. Severe pancreatic insufficiency should be managed with enzyme replacement, fat-soluble vitamin replacement and frequent, small meals. Decompression surgery can be considered in those with intractable pain who have failed medical therapy.

Enhancing Healthcare Team Outcomes

Chronic pancreatitis costs the healthcare system billions of dollars each year. These patients develop a wide range of complications including chronic pain and multiple admissions to the hospital are not unusual. The patients are generally managed by a team of healthcare professions that include a surgeon, gastroenterologist, radiologist, pain specialist, dietitian, pharmacist, and nurse. To reduce the morbidity and mortality of the disorder, the emphasis today is on behavior modification. Both the pharmacist and nurses play a critical role in educating the patient about the adverse effects of alcohol and tobacco smoking. By abstaining from alcohol, these patients can also obtain pain relief in the early stage of the disease. Patients who continue to drink alcohol, have a death rate 3 times higher than those who do not drink alcohol. For those who have malabsorption, the pharmacist should recommend the use of pancreatic enzymes. At the same time, the patients should be referred to an alcohol and chemical dependency program. Pharmacists will consult with the clinical team regarding the choice and dosing of pancreatic enzymes. The pharmacist should also recommend aids to stop tobacco and educate the patients on the benefits of a healthy diet. Referral to a pain specialist is necessary as many patients continually seek narcotics. A gastroenterology nurse should follow these patients to assess steatorrhea and body weight. A dietary consult should educate the patient on the importance of a low-fat diet and the need to take vitamin supplements.

Continual reassessment and monitoring of these patients is necessary to ensure that they abstain from alcohol.[14][15][16] (Level V) Only through a team approach can the morbidity of chronic pancreatitis be lowered.

Outcome

The outcome for patients with chronic pancreatitis depends on many factors such as smoking, age at diagnosis, continued use of alcohol, the presence of liver disease and other comorbidities. Data indicate that at 10 years, 70% of patients are alive and at 20 years, about 40% to 50% are alive. Furthermore, these patients also have a risk of developing pancreatic cancer in the future. With time, patients with chronic pancreatitis are also at risk of developing pseudocysts, pancreatic ascites, pleural effusions, portal hypertension, splenic vein thrombosis, and pseudoaneurysm. A significant number of these patients continue to have moderate to severe pain and malabsorption. Finally, about one-third of patients will end up with diabetes. For those who require surgery for a pseudoaneurysm, there are additional risks of death.[17][18] (Level V)