Chronic Pancreatitis

CP results from long-standing pancreatic inflammation and leads to irreversible destruction of pancreatic tissue with fibrin deposition and loss of exocrine and endocrine function.

• Chronic ethanol consumption accounts for about 70% of cases in Western society; 10% result from other causes, and 20% are idiopathic.
• The exact pathogenesis is unknown. Activation of pancreatic stellate cells by toxins, oxidative stress, and/or inflammatory mediators appears to be the cause of fibrin deposition.
• Abdominal pain may be caused in part by increased pancreatic parenchymal pressure from obstruction, inflammation, and necrosis. Compression of pancreatic nerve fibers after a meal, along with continuous firing of peripheral and central neurons, may explain the burning and shooting pain of CP.
• Malabsorption of protein and fat occurs when capacity for enzyme secretion is reduced by 90%. A minority of patients develop complications, including pancreatic pseudocyst, abscess, and ascites or common bile duct obstruction, leading to cholangitis or secondary biliary cirrhosis.

CLINICAL PRESENTATION

• The main features of CP are abdominal pain, malabsorption, weight loss, and diabetes. Jaundice occurs in ~10% of patients.
• Patients typically report deep, penetrating epigastric or abdominal pain that may radiate to the back. Pain often occurs with meals and at night and may be associated with nausea and vomiting.
• Steatorrhea and azotorrhea occur in most patients. Steatorrhea is often associated with diarrhea and bloating. Weight loss may occur.
• Pancreatic diabetes is a late manifestation commonly associated with pancreatic calcification.

DIAGNOSIS

Diagnosis is based primarily on clinical presentation and either imaging or pancreatic function studies. Noninvasive imaging includes abdominal ultrasound, computed tomography (CT), and magnetic resonance cholangiopancreatography (MRCP). Invasive imaging includes endoscopic ultrasonography (EUS) and ERCP.

• Serum amylase and lipase are usually normal or only slightly elevated but may be increased in acute exacerbations.
• Total bilirubin, alkaline phosphatase, and hepatic transaminases may be elevated with ductal obstruction. Serum albumin and calcium may be low with malnutrition.
• Pancreatic function tests include ✓ Serum trypsinogen (7 g/day is abnormal; stool must be collected for 72 hours) ✓ Secretin stimulation (evaluates duodenal bicarbonate secretion) ✓ 13C-mixed triglyceride breath test.

DIAGNOSIS

Goals of Treatment: Goals for uncomplicated CP are to relieve abdominal pain, treat complications of malabsorption and glucose intolerance, and improve quality of life.

Nonpharmacologic Therapy : Lifestyle modifications should include abstinence from alcohol and smoking cessation.

• Advise patients with steatorrhea to eat smaller, more frequent meals and reduce dietary fat intake.
• Patients who do not consume adequate calories from their normal diet may be given whole protein or peptide-based oral nutritional supplements.
• Invasive procedures and surgery are used primarily to treat uncontrolled pain and the complications of chronic pancreatitis. Pharmacologic Therapy
• Pain management should begin with oral nonopioid analgesics such as acetaminophen or a nonsteroidal anti-inflammatory drug administered on a scheduled basis before meals to help decrease postprandial pain.
• A trial of pancreatic enzyme supplementation for pain relief may be given prior to adding opioids.
• If these measures fail, add low-potency oral opioids (e.g., hydrocodone) to nonopioid analgesics. Tramadol has also been used. Severe pain unresponsive to these therapies necessitates use of other opioids (e.g., codeine, morphine sulfate, oxycodone, or hydromorphone). Unless contraindicated, use oral opioids before parenteral, transdermal, or other dosage forms. In patients with pain that is difficult to manage, consider nonopioid modulators of chronic pain (e.g., pregabalin, selective serotonin reuptake inhibitors and tricyclic antidepressants).
• Pancreatic enzyme supplementation and reduction in dietary fat intake are the primary treatments for malabsorption due to CP . This combination enhances nutritional status and reduces steatorrhea. The enzyme dose required to minimize malabsorption is 25,000 to 40,000 units of lipase administered with each meal. The dose may be increased to a maximum of 75,000 units per meal. Products containing enteric-coated microspheres or mini microspheres may be more effective than other dosage forms.