Chronic Pancreatitis


Chronic Pancreatitis

  • characterized by recurrent or persistent abdominal pain and exocrine and endocrine pancreatic insufficiency

  1. Pathology
    • pathologic findings include acinar loss, glandular shrinkage, fibrosis, inflammation, calcification, ductal strictures, and intraductal protein plugs

  2. Etiology
    1. Alcohol Abuse
      • most common etiology in developed countries (60% to 70% of cases)
      • many years (6 to 12) of heavy drinking are required before the development of clinical disease
      • only 3% to 7% of heavy drinkers develop chronic pancreatitis, suggesting that factors other than alcohol are also responsible
      • smoking increases the risk of alcohol-induced chronic pancreatitis
      • most frequent among men, with a peak incidence between 35 and 45 years

      1. Pathogenesis
        1. Protein Hypersecretion
          • alcohol increases the total protein concentration in pancreatic juice
          • precipitation of protein plugs occurs in the pancreatic ducts
          • calcium may precipitate in the protein plugs, resulting in intraductal stones
          • as a result of obstruction, acinar cells are no longer able to secrete pancreatic enzymes

        2. Pancreatic Stellate Cells (PSC)
          • quiescent fibroblasts found at the base of acinar cells
          • once stimulated, they release multiple inflammatory mediators such as TGF-β, TNF-α, PDGF, IL-1
          • it is postulated that alcohol stimulates PSCs, which results in chronic inflammation and pancreatic fibrosis

    2. Pancreatic Duct Obstruction
      • pancreatic duct will be dilated
      • intraductal plugs and stones are unusual
      • causes include traumatic stricture, stenosis of the sphincter of Oddi, pancreas divisum

    3. Tropical Pancreatitis
      • occurs primarily in poor areas of Africa and Asia
      • typically occurs in young adults
      • may be related to nutritional deficiencies or toxin ingestion

    4. Genetic Causes
      • pancreatic enzyme activation is strictly controlled
      • mutations in proteins that regulate this activation increase the risk of chronic pancreatitis
      • PRSS1 and SPINK1 mutations lead to the premature activation of trypsinogen
      • heterozygous mutations in the cystic fibrosis transmembrane receptor (CFTR) predisposes to chronic pancreatitis

    5. Miscellaneous Causes
      • autoimmune pancreatitis
      • idiopathic chronic pancreatitis occurs in up to 30% of cases

  3. Clinical Manifestations
    • clinic tetrad consisting of abdominal pain, weight loss, steatorrhea, and diabetes

    1. Symptoms
      1. Abdominal Pain
        • chief complaint in 95% of patients
        • located in the midepigastrium, and often radiates to the back
        • described as boring or aching
        • in some patients the pain is continuous and unremitting; in others it is episodic and resembles the pain of acute pancreatitis
        • most patients require analgesic drugs, and many become addicted to narcotics
        • the mechanism of the pain is uncertain - proposed etiologies include ductal hypertension, ischemia and acidosis, or inflammation of intrapancreatic nerves

      2. Exocrine Insufficiency
        • 90% of the gland must be dysfunctional before steatorrhea and diarrhea develop
        • majority of patients with long-standing chronic pancreatitis develop exocrine insufficiency

      3. Weight Loss
        • occurs in 75% of patients
        • since food usually aggravates the pain, the reason for weight loss is decreased intake rather than malabsorption

      4. Endocrine Insufficiency
        • 33% of patients become insulin-dependent diabetics
        • diabetes develops much later than pain and exocrine insufficiency
        • hypoglycemia can be a life-threatening problem in alcoholics with irregular eating habits

      5. Additional Clinical Problems
        • obstruction of the distal common bile duct can result in obstruction or cholangitis
        • duodenal obstruction can result from extensive scarring in the head of the pancreas
        • splenic vein thrombosis can result in UGI bleeding from gastric varices
        • chronic pancreatitis is a risk factor for pancreatic cancer, and distinguishing between the two remains a challenging clinical problem

  4. Diagnosis
    • suspected on clinical grounds and confirmed by imaging studies

    1. Abdominal X-ray
      • pathognomonic, but only 30% of patients with chronic pancreatitis will have pancreatic calcifications seen on plain x-ray
      • calcifications are located in the ducts, not the parenchyma

      KUB - Calcifications of Chronic Pancreatiis
    2. CT Scan
      • findings include pancreatic duct dilation, parenchymal atrophy, calcifications
      • useful to assess for complications: pseudocysts, splenic and portal vein thrombosis, splenic and pancreaticoduodenal artery pseudoaneurysms

      CT - Dilated Pancreatic Duct
      Dilated Pancreatic Duct

    3. MRCP
      • secretin MRCP is particularly useful for evaluating intraductal strictures and pancreatic duct disruption

      MRCP - Dilated Pancreatic Duct with Obstructing Stone
      Dilated Pancreatic Duct with Obstructing Stone

    4. ERCP
      • rarely used as a diagnostic test
      • primarily used for endoscopic therapy for ductal stones and strictures

    5. Endoscopic Ultrasound
      • highest resolution test to visualize the pancreatic parenchyma and ducts
      • most accurate test to diagnose chronic pancreatitis in the earliest stages
      • may be used to obtain tissue to differentiate chronic pancreatitis from pancreatic cancer

  5. Management
    1. Pain Control
      • requires total abstinence from alcohol and smoking
      • pancreatic enzyme replacement, by suppressing CCK release, relieves pain in some patients
      • a low-fat diet supplemented with medium chain triglycerides also improves pain in some patients

      1. Analgesics
        • non-narcotic analgesics should be used initially, but narcotic analgesics usually become necessary
        • long acting drugs (fentanyl patches) are more effective than short acting drugs
        • drug addiction often becomes a major management problem

    2. Steatorrhea
      • manifested by loose, greasy, foul-smelling stools
      • some patients can be managed by a low fat diet, but most will require pancreatic enzyme supplementation
      • the fat-soluble vitamins will also need to be supplemented

    3. Diabetes
      • occurs late in the course of the disease
      • since glucagon is also affected, there is an increased risk of hypoglycemia in patients who require insulin

Procedures for Chronic Pancreatitis

  1. Endoscopic Management
    • usually attempted first before surgery
    • strictures can be dilated and stented via ERCP
    • removal of pancreatic stones may require endoscopic or extracorporeal shock wave lithotripsy
    • pain relief is more likely in patients with strictures without stones

    ERCP with Pancreatic Duct Stent Placement
    Pancreatic Duct Stent

  2. Operative Management
    1. Indications
      • intractable pain is the most common indication for surgery
      • biliary or pancreatic duct obstruction
      • duodenal obstruction
      • pseudocyst or pseudoaneurysm formation
      • inability to rule out cancer

    2. Choice of Procedure
      • if the pancreatic duct diameter is greater than 7 mm, then a duct drainage procedure will usually relieve pain (lateral pancreaticojejunostomy)
      • if the pancreatic head is enlarged more than 4 cm in the A-P dimension, then a head resectional procedure should be chosen (Whipple procedure, duodenum-preserving pancreatic head resection)
      • duct drainage procedure can be combined with a head resectional procedure in selected patients (Frey procedure)
      • diffuse gland involvement without duct dilation may require a total pancreatectomy
      • resectional procedures exacerbate exocrine and endocrine insufficiency

      1. Dilated Pancreatic Duct
        1. Lateral Pancreaticojejunostomy (Puestow Procedure
          • most common procedure chosen for patients with a dilated pancreatic duct > 7 mm
          • > 80% of patients will have immediate pain relief
          • duct must be opened over the entire distance of the gland and all stones removed
          • anastomosis is created with a retrocolic Roux limb of jejunum
          • operation does not improve (or worsen) pancreatic exocrine and endocrine dysfunction
          • 30% of patients have recurrence of pain within 3 to 5 years
          • operation does not alter the natural history of chronic pancreatitis

          Puestow Procedure
          Puestow Procedure

        2. Pancreatic Head Resection with Lateral Pancreaticojejunostomy (Frey Procedure)
          • combines a duct drainage procedure with a ‘coring out’ of the pancreatic head
          • procedure of choice for patients with both a dilated pancreatic duct and an enlarged pancreatic head
          • neck of the pancreas is not resected, so bleeding from the underlying SMV and portal veins does not occur
          • preserves exocrine and endocrine function

          Frey Procedure
          Frey Procedure

      2. Nondilated Pancreatic Duct
        1. Pancreaticoduodenectomy
          • chosen for patients who have head-dominant chronic pancreatitis and biliary or duodenal obstruction
          • may be done as a standard Whipple procedure or a pylorus-sparing Whipple
          • in correctly chosen patients, 60% to 80% of patients will have pain relief at 5 years
          • chronic inflammation may cause adherence of the portal vein to the pancreas, making resection difficult and bloody

        2. Duodenum-Preserving Pancreatic Head Resection (Beger Procedure)
          • inflammatory mass in the head of the pancreas is resected
          • viability of the duodenum and bile duct is maintained by preserving the posterior branch of the gastroduodenal artery
          • neck of the pancreas is divided and only a small rim of tissue is left along the duodenum
          • reconstruction is by an end-to end pancreaticojejunostomy to the distal pancreas and pancreaticojejunostomy to the pancreatic remnant along the duodenum
          • if the pancreatic duct is also dilated, a lateral pancreaticojejunostomy can be performed

          Beger Procedure
          Beger Procedure

        3. Distal Pancreatectomy
          • limited to patients with disease confined to the body and tail of the pancreas (often secondary to trauma)
          • 40% to 80% pancreatectomy
          • resection extends no further than the level of the superior mesenteric vessels
          • because of severe inflammatory changes involving the splenic vessels. preserving the spleen is rarely possible or practical

        4. Total Pancreatectomy
          • reserved for patients with diffuse small duct disease or who have failed a lesser procedure
          • also required for patients with hereditary chronic pancreatitis
          • most effective procedure to eliminate pain
          • invariably results in labile diabetes
          • islet cell transplantation can mitigate the effects of surgically created diabetes, but is limited by its cost and lack of islet cell processing facilities

          Total Pancreatectomy with Islet Cell Transplantation
          Islet Cell Autotransplantation







References

  1. Sabiston, 20th ed., pgs 1531 - 1537
  2. Schwartz, 10th ed., pgs 1361 - 1375, 1382 - 1390
  3. Cameron, 13th ed., pgs 541 - 545
  4. UpToDate. Treatment of Chronic Pancreatitis. Steven D. Freedman, MD, PhD. Dec 20, 2018. Pgs 1 – 30
  5. UpToDate. Surgery for Chronic Pancreatitis. Katherine Morgan, MD, FACS. Apr 22, 2020. Pgs 1 - 22