Chronic Pancreatitis

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 increases the 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 chronic pancreatitis, so it suggests 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

Compared to other illnesses, 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 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 2 main theories on the pathogenesis of chronic pancreatic disease. One theory is 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 reveals 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, precipitated protein may also be seen in the ducts. The distortion of the ductal system can lead to a 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, indicating the presence of a pseudocyst. Signs of malnutrition are common in long-standing cases.

Evaluation

Basic lab studies for chronic pancreatitis include a CBC, BMP, LFTs, lipase, amylase, lipid panel, and a fecal-elastase-1 value. Lipase and amylase levels can be elevated but usually normal secondary to significant pancreatic scarring and fibrosis. Of note, amylase and lipase values should not be considered diagnostic or prognostic.

In children, 1 should perform genetic testing for CFTR.

In cases where chronic autoimmune pancreatitis is suspected, inflammatory markers, including ESR, CRP, ANA, RF, antibodies, and immunoglobulins, can be obtained. To work steatorrhea, a 72-hour quantitative fecal fat is the gold standard (whereby values greater than 7 gm per day are confirmatory). Alternatively, 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.

The MRCP is the premier diagnostic imaging study because it can reveal calcifications (hallmark signs), pancreatic enlargement, ductal obstruction, or dilation. MRCP has higher sensitivity and specificity for chronic pancreatitis than 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 no steatorrhea or plain films do not reveal calcifications. However, many hospitals are currently trending towards using MRCPs instead and relying on ERCPs 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 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

• A CT scan is ideal for imaging the abdomen and assessing pancreas morphology.
• A 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 help assess ductal compliance and exocrine function.
• Endoscopic ultrasound can assess ductal and parenchymal changes early in 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 and replacing fat-soluble vitamins and pancreatic enzymes are generally recommended. 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 benefits of using medium-chain triglycerides. Surgery should be considered in patients who fail medical therapy and continue to have pain.[1][11][13](B3)

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 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. Still, the operative mortality can exceed 10%, and the quality of life is impaired without a functioning pancreas. Today, interventional radiology can 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

Differential diagnoses to consider and rule out regarding chronic pancreatitis include the following: peptic ulcer disease, cholelithiasis, biliary obstruction/biliary colic, acute pancreatitis, pancreatic malignancy, pseudocyst, and 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. Major complications include pseudocyst formation, mechanical bile duct obstruction, and duodenum obstruction. Additional 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 the disease course)

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