Chronic Pancreatitis

Aka: Chronic Pancreatitis

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II. Definitions

  1. Chronic Pancreatitis
    1. Permanent, progressive Pancreas tissue destruction with secondary dysfunction

III. Epidemiology

  1. Incidence: 4-12 per 100,000 per year, U.S.
  2. More common in men (by factor of 1.5-3 fold)
  3. Age of onset: 35-55 years old

IV. Pathophysiology

  1. Recurrent episodes of Acute Pancreatitis with exaggerated inflammatory response
  2. Profibrotic response persists with secondary pancreatic Collagen deposition and fibrosis
  3. Pain episodes may resolve once pancreatic function fails completely

V. Causes

  1. Chronic Alcoholism (most common U.S. cause, up to 70% of cases)
  2. Idiopathic (25% of cases)
  3. Autoimmune Pancreatitis (5-6% of cases)
    1. Inflammatory Bowel Disease
    2. Sjogren's Syndrome
    3. Primary Biliary Cirrhosis
  4. Hypertriglyceridemia
  5. Hyperparathyroidism or Hypercalcemia
  6. Hemochromatosis
  7. Hereditary Pancreatitis (most common in children)
    1. Cystic Fibrosis
    2. Various Autosomal Dominant and recessive genetic defects
  8. Occult neoplasm or other causes of pancreatic obstruction
  9. Chronic Renal Failure
  10. Medications
    1. See Medication Causes of Pancreatitis
  11. Severe, recurrent Pancreatitis
    1. Severe acute or recurrent Pancreatitis with Pancreas necrosis
    2. Post-radiation
    3. Vascular ischemia
  12. Anatomic abnormalities
    1. Sphincter of odi dysfunction
    2. Pancreas divisum

VI. Symptoms

  1. Abdominal Pain (80-90% of cases)
    1. Chronic, recurrent and disabling Abdominal Pain
    2. Midepigastric postprandial pain with radiation to the back
    3. Relieved on sitting upright or leaning forward
    4. Worse when eating
  2. Bowel malabsorption (once only 10% of exocrine function remains)
    1. Steatorrhea
    2. Weight loss
    3. Hyperglycemia (and Diabetes Mellitus)
    4. Vitamin Deficiency (uncommon)
      1. Deficiency of Vitamins A,D,E,K
      2. Vitamin B12 Deficiency

VII. Labs: Standard

  1. Pancreatic Enzymes
    1. Serum Amylase normal
    2. Serum Lipase normal
      1. Contrast with at least a 3 fold increase over normal in Acute Pancreatitis
  2. Liver Function Tests
    1. Increased Serum Bilirubin and Alkaline Phosphatase if biliary obstruction present
  3. Stool studies (Late findings)
    1. Steatorrhea (abnormal if fecal fat concentration >9.5% or >7 grams/day)
    2. Fecal elastase (Abnormal if <200 mcg/gram of stool)
  4. Serum Electrolytes (including Serum Calcium)
    1. Evaluate for Hyperparathyroidism (Hypercalcemia)
  5. Fasting Glucose (or Hemoglobin A1C)
    1. Glucose Intolerance or Diabetes Mellitus (50% of patients)
  6. Serum Lipids
    1. Evaluate for Hypertriglyceridemia
  7. Complete Blood Count
    1. May suggest infectious cause
  8. Autoimmune markers (consider)
    1. IgG4 Serum Antibody
    2. Antinuclear Antibody (ANA)
    3. Rheumatoid Factor (RF)
    4. Erythrocyte Sedimentation Rate (ESR)
    5. C-Reactive Protein (C-RP)

VIII. Labs: Pancreatic Exocrine Function

  1. Indications
    1. Evaluate for pancreatic exocrine insufficiency
    2. Tests are expensive (and in some cases invasive)
    3. Not recommended for routine workup
      1. May be indicated in non-diagnostic evaluation or on specialty Consultation
  2. Available tests
    1. Serum trypsinogen
      1. Abnormal if <20 ng/ml
    2. Fecal elastase
      1. Abnormal if <200 mcg/g stool
      2. High False Positive Rate (Test Sensitivity: >65%, Test Specificity: 55%)
    3. Fecal fat
      1. Requires 72 hour collection on 100 g fat/day diet
      2. Abnormal if >7 g/day
    4. Secretin Stimulation Test (most accurate test for pancreatic exocrine insufficiency)
      1. Peak bicarbonate concentration abnormal if <80 mEq/L in duodenal secretions

IX. Differential Diagnosis

  1. Common
    1. Acute Cholecystitis
    2. Choledocolithiasis (Common Bile Duct Stone)
    3. Acute Pancreatitis
    4. Mesenteric Ischemia
    5. Peptic Ulcer Disease
    6. Pancreatic Carcinoma
  2. Other Causes
    1. Gastroparesis
    2. Small Bowel Obstruction
    3. Irritable Bowel Syndrome
    4. Inflammatory Bowel Disease (e.g. Crohn's Disease)
    5. Malabsorption

X. Imaging

  1. Abdominal XRay
    1. Pancreatic calcifications (30-60% of cases)
  2. CT Abdomen (preferred first-line test)
    1. Pancreatic Pseudocyst
    2. Pancreatic duct dilatation (detects down to 7 mm duct dilitation)
    3. Pseudoaneurysm
    4. Pancreatitic necrosis
    5. Pancreatic parenchymal atrophy
    6. Pancreatic Mass
      1. Obtain tri-phasic pancreatic CT if Pancreatic Cancer is suspected
  3. Abdominal MRI and MR Cholangiopancreatography (MR/MRCP)
    1. Indicated for non-diagnostic CT imaging

XI. Diagnosis

  1. Endoscopic Ultrasound
    1. Preferred over ERCP due to much lower complication rate and high sensitivity
    2. Can be combined withg FNA biopsy to evaluate mass lesions for malignancy
  2. Endoscopic Retrograde Cholangiopancreatography (ERCP)
    1. Irregular dilation of main pancreatic duct
    2. Pruning of pancreatic duct branches
    3. Complications include Acute Pancreatitis, gastrointestinal Hemorrhage and Ascending Cholangitis

XII. Evaluation

  1. History, exam and laboratory findings consistent with Chronic Pancreatitis
    1. No findings of Acute Pancreatitis
    2. Differential Diagnosis considered
  2. Diagnosis
    1. Step 1: Start
      1. CT Abdomen with contrast
    2. Step 2: If non-diagnostic CT
      1. Abdominal MR/MRCP
    3. Step 3: If non-diagnostic MR/MRCP or if pancreatic mass identified requiring biopsy
      1. Endoscopic Ultrasound (and if indicated, biopsy)
    4. Step 4: If non-diagnostic endoscopic Ultrasound
      1. Obtain Pancreatic Exocrine function Tests
    5. Step 5: If non-diagnostic Pancreatic Exocrine function Tests
      1. Obtain Endoscopic Retrograde Cholangiopancreatography (ERCP)

XIII. Management: Medical

  1. Treat exacerbations as in Acute Pancreatitis
  2. Pain control
    1. Acetaminophen (Tylenol)
    2. NSAIDs
    3. Other-non-Opioids
      1. Tricyclic Antidepressants (e.g. Amitriptyline)
      2. SNRI (e.g. Venlafaxine, Duloxetine)
      3. Gabapentin or Pregabalin
    4. Cautious use of opiods
      1. High abuse potential and common outcome in chronic cases
    5. Denervation
      1. Celiac Nerve Block
      2. Transthoracic splanchniectomy
  3. Avoid exacerbating factors
    1. Abstain from Alcohol use
    2. Avoid Tobacco
  4. Dietary changes
    1. Follow Low Fat Diet
    2. Eat smaller meals
  5. Malabsorption Management (if steatorrhea)
    1. Pancreatic Enzyme Replacement
      1. Give 40,000 units of Lipase
    2. Proton Pump Inhibitor (or H2 Blocker)
    3. Consider one-time DEXA Scan (as well as Vitamin D level)
    4. Other Vitamin Supplementation (esp. fat soluble Vitamins, ADEK and B12)
      1. Vitamin D Supplementation
      2. Vitamin B12 Supplementation
  6. Treat comorbid conditions
    1. Diabetes Mellitus (common)
      1. Typically requires Insulin
    2. Major Depression (common)
      1. Antidepressants (e.g. SSRIs)
  7. Avoid non-indicated medications
    1. Allopurinol
    2. Antioxidants (e.g. Selenium, Beta Carotene, Vitamin C, Vitamin E)
    3. Octreotide
    4. Prokinetics (e.g. Erythromycin)
    5. Ahmed (2014) Cochrane Database Syst Rev (8): CD008945 [PubMed]
    6. Warshaw (1998) Gastroenterology 115(3): 765-76 [PubMed]

XIV. Management: Procedures

  1. Extracorporeal Shock Wave Lithotripsy
    1. Consider in high pancreatic stone burden
  2. ERCP Indications
    1. Painful pancreatic duct stricture or gall stones (ERCP with stenting)
    2. Pseudocysts (ERCP for drainage)
      1. Effective in >70% of cases, and with similar pain relief as with riskier surgeries

XV. Management: Surgery

  1. Performed in up to 50% of longstanding Chronic Pancreatitis cases
  2. Surgical Indications
    1. Intractable pain refractory to ERCP and other measures (most common indication)
    2. Suspected Pancreatic Cancer
    3. Compression from surrounding tissue
    4. Biliary or pancreatic strictures
    5. Duodenal stenosis
    6. Pseudocysts refractory to endoscopic drainage
    7. Peritoneal or pleural fistulas
    8. Vascular complications (including Hemorrhage)
  3. Surgical procedures: Decompression for large duct disease
    1. Lateral pancreaticojejunostomy (most common)
      1. Longterm pain relief in >60% of patients
    2. Cystenterostomy (for pseudocyst)
    3. Sphincterotomy or spinchteroplasty
  4. Surgical procedures: Resective for pancreatic tumor or small duct disease
    1. Whipple Procedure or Pancreatoduodenectomy (most common surgery for Chronic Pancreatitis)
      1. Pain relief in 85% of Chronic Pancreatitis cases and <3% mortality
    2. Total pancreatectomy
      1. Procedure of last resort (high complication rate, poor efficacy in pain relief)
      2. Performed with autologous islet cell transplant

XVI. Complications

  1. Recurrent Acute Pancreatitis
  2. Chronic Abdominal Pain
    1. Narcotic Addiction (secondary to Chronic Pain)
  3. Vitamin B12 Malabsorption
    1. More common with Alcoholism, Cystic Fibrosis\
  4. Diabetes Mellitus
    1. Occurs in most patients within 5 years of onset Chronic Pancreatitis
  5. Non-Diabetic Retinopathy
    1. Vitamin A Deficiency
    2. Zinc Deficiency
  6. Osteoporosis (>23% of patients)
  7. Weight loss (>40% of patients)
  8. Gastrointestinal Bleeding
  9. Pancreatic carcinoma (very high risk, >25% of cases)
    1. Consider screening hereditary Pancreatitis patients starting at age 40 years old
    2. Screening with endoscopic Ultrasound, CT Abdomen, or ERCP
  10. Subcutaneous Fat Necrosis
  11. Pseudocyst
  12. Malabsorption and steatorrhea (>10%)
  13. Biliary duct, duodenal or gastric obstruction
  14. Pancreatic fistula (Ascites, Pleural Effusion)
  15. Pseudoaneurysm (esp. splenic artery)
  16. Fat soluble Vitamin Deficiency (Vitamins A, D, E, K) - rare

XVII. References

  1. Forsmark in Feldman (2006) Sleisenger & Fordtran's Gastrointestinal and Liver Disease, Chap 57
  2. Ahmad (2006) Curr Probl Surg 43: 127-238 [PubMed]
  3. Barry (2018) Am Fam Physician 97(6): 385-93 [PubMed]
  4. Fry (2007) Am J Surg 194: S45-S52 [PubMed]
  5. Nair (2007) Am Fam Physician 76: 1679-94 [PubMed]

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