|
|
|
|
|
|
 |
 |
 |
|
 |
|
 |
|
 |
|
 |
|
 |
|
|
Chronic pancreatitis
|
|
Earn Category I CME credit by reading this article and "Meeting the challenge of generalized anxiety disorder" and then successfully completing the post-test. Successful completion is defined as a cumulative score of at least 70% correct. This material has been reviewed and is approved for 1 hour of clinical Category I (Preapproved) CME credit by the AAPA. The term of approval is for 1 year from the publication date of December 2004. |
Learning objectives
|
Despite advances in our understanding of chronic pancreatitis (CP), much about the disease remains uncertain.1 Generally, CP is a disease in which progressive inflammation causes permanent structural or functional damage to the pancreas.2 Debilitating pain from CP is responsible for more than 120,000 outpatient visits and 56,000 hospitalizations each year in the United States.3,4 The disease is typically managed by gastroenterology and surgical specialists.
Long-term alcohol abuse is responsible for 80% of cases of CP, and discontinuing alcohol use can prevent further damage to the pancreas.5 Other causes of CP include genetic anomalies, tropical pancreatitis, severe elevation of triglyceride levels, hyperparathyroidism, pancreatic duct obstruction, and cystic fibrosis.1,6-8 All causes share a common final pathway of fibrosis, inflammatory infiltrates, and pancreatic cell loss.1
The most common features of CP are abdominal pain, steatorrhea, and diabetes,3,8,9 although the clinical presentation is often vague. Patients with CP typically present between the ages of 50 and 80 years,6,8 with men more commonly affected, and often after 3 or more decades of alcohol abuse.2,3 Cigarette smoking and a diet that is high in protein and fat and low in vitamins are also common lifestyle factors in patients who have CP.2
Suspected CP should be investigated with questions to the patient about alcohol use, medication use, pain, weight loss, stool character, and symptoms of diabetes. Family history and recent travel are also important because of possible hereditary and tropical etiologies of CP.2 Abdominal pain is the most common and earliest symptom, reported by up to 80% of those who have CP, and usually manifests after 10 years of subclinical disease.2,3,8 The pain is typically described as epigastric or nonspecific and lasts several hours or days or is intermittent.8 Pain commonly radiates to the back and is relieved with forward flexion. Intermittent pain is more common in the early stage of alcohol-related disease,2,6 and pain may diminish as exocrine dysfunction develops.2 Although the pathogenesis of pain from CP is not known, several theories have been suggested, including acute inflammation complicating chronic inflammation, elevated intrapancreatic or duct pressure, ischemia, duodenal inflammation, common bile duct stenosis, or neural changes.2,3,5,8 Pain may also be caused by pseudocysts and cholestasis.2
Up to 30% of patients with CP also have steatorrhea, usually occurring after 90% of the pancreas has been irreversibly damaged. The inability to properly digest fats results in diarrhea; bulky, greasy stools; and weight loss.8,9
Progressive pancreatic scarring causes symptoms of diabetes in 25% of patients. These symptoms—polyuria, nocturia, polydypsia, and polyphagia—are a finding of late CP.8,10
Complications in CP include pancreatic cancer, pseudocysts, portal hypertension, gastric varices, pancreatic ascites, duct stones and strictures (see "The anatomy and physiology of the pancreas"). Many complications manifest as a fairly sudden change in the character of pain.6 The most severe complication of CP is pancreatic carcinoma, which is almost always fatal.2,3,6,9,11 Patients who have had CP for at least 20 years have at least a 4% risk for pancreatic cancer. Smoking also contributes to the risk of pancreatic cancer. More than one fourth of patients develop pseudocysts8 due to pancreatic duct interference.12 These pseudocysts may rupture, lead to infection, or cause pressure on nearby structures.9 An obstructed splenic vein may cause portal hypertension and gastric varices. Pancreatic ascites can develop from duct leakage or pseudocyst rupture.
The anatomy and physiology of the pancreasThe pancreas is a retroperitoneal organ that lies posterior to the stomach in a deep position, so that biopsy is rarely used in the diagnosis of pancreatic disease. The right side of the pancreas, the head, lies within the proximal curve of the duodenum (see figure). This location is optimal for the release of digestive enzymes from the main pancreatic duct (MPD) into the duodenum. Enzymes from the MPD pass through the papilla of Vater, which is surrounded by the sphincter of Oddi. The left side of the pancreas is referred to as the tail. Numerous ductal branches connect to the MPD within the pancreatic head and tail. Typically, chronic pancreatitis (CP) damages duct side branches before damaging the MPD. The celiac plexus is responsible for the transmission of abdominal pain.
The exocrine pancreas secretes approximately 1 L of water, bicarbonate, and digestive enzymes each day. Digestive enzymes such as trypsin, chymotrypsin, and carboxypolypeptidase are responsible for the degradation of proteins. These enzymes generally remain inactive until reaching the duodenum. Amylase is a type of enzyme that breaks down carbohydrates. Lipase, cholesterol esterase, and phospholipase aid in fat digestion. The digestive enzymes for carbohydrate and fat degradation are activated by trypsin after reaching the duodenum. Exocrine dysfunction due to CP results in malabsorption of fat and subsequent steatorrhea. Damage to pancreatic endocrine function is a late finding in CP. Endocrine function controls the metabolism of glucose, protein, and lipids. Cells of the islets of Langerhans release endocrine hormones directly into the blood. Insulin promotes storage of energy in the form of glycogen and fat and is important in protein production. Glucagon, secreted from alpha cells, inhibits insulin secretion from beta cells and allows production of glucose from gluconeogenesis and glycogenolysis. Furthermore, glucagon causes activation of adipose cell lipase. Somatostatin, a less abundant hormone, prevents both glucagon and insulin secretion. |
The diagnosis of CP is primarily based on clinical findings, laboratory assessment, and imaging studies. Although a history of epigastric pain, steatorrhea, and symptoms of diabetes offer strong clinical support for the diagnosis, most patients present with pain only. The differential diagnosis includes pancreatic carcinoma, acute pancreatitis, cholecystitis, and bowel obstruction or infarction. Although a gastroenterology referral is usually warranted in cases of suspected CP, the initial investigation to rule out the disease can be performed in the primary care setting.
Clinically suspected CP should be investigated with noninvasive and inexpensive tests first (see "Choosing the right diagnostic tests"). One option is to measure serum trypsin and fecal elastase levels and to order transabdominal ultrasonography (TUS). Although these are less sensitive for CP than other more invasive tests, abnormal results eliminate the need for further testing. In addition, TUS can be used to help rule out cholecystitis. If suspicion for CP remains high despite normal results of noninvasive tests, a CT should be obtained to eliminate acute pancreatitis and bowel abnormalities from the differential diagnosis. If the CT is inconclusive and clinical suspicion remains, consider endoscopic ultrasonography (EUS) or endoscopic retrograde cholangiopancreatography (ERCP).10 EUS is associated with fewer complications than ERCP.13
Choosing the right diagnostic testsBecause few structural and functional changes are seen in early chronic pancreatitis (CP), diagnostic testing is more useful for advanced disease, when CP is clinically apparent.1 The initial step in investigating suspected CP involves obtaining lab tests that measure pancreatic function. If these test results do not support the diagnosis despite a suggestive clinical picture, imaging studies may be ordered. Although patients suspected of having CP should be referred to a gastroenterologist, primary care is the appropriate venue for initiating noninvasive tests. Laboratory tests for CP measure either the amount of pancreatic secretion (direct testing) or the effect of a pancreatic enzyme (indirect testing). Those that measure pancreatic secretion offer greater sensitivity in early disease.1 Serum pancreatic enzyme levels serve as markers of pancreatic function; although amylase and lipase levels are usually normal in CP, low levels of trypsin may be found in patients with severe disease.1,2 This test has poor sensitivity, but it is inexpensive, low risk, and widely available. The test for fecal elastase requires only a single stool sample.2 Tests that measure enzyme effects are sensitive only in severe or long-term disease.1 A fecal fat test, for example, is considered the gold standard for the detection of steatorrhea, which is not specific for CP.1,2 Other indirect tests of pancreatic function are limited by lack of sensitivity and availability.1-3 Serum fasting glucose levels and glucose tolerance tests are not useful in making the diagnosis of CP but may be used to monitor treatment. Imaging studies Endoscopic retrograde cholangiopancreatography (ERCP) is considered the gold standard of imaging studies for CP, with 90% sensitivity and specificity for the disease2,3 (see figure). ERCP involves endoscopy with subsequent cannulation of the papilla of Vater. The main pancreatic duct is then injected with contrast material.4 Imaging with ERCP is limited to duct anatomy, which is frequently altered in late CP.5,6 The clinical role of ERCP is primarily to confirm a diagnosis of CP, map pancreatic duct anatomy, rule out pseudocysts and neoplastic lesions, locate duct stones, and identify duct leaks or fistulas.3,5,7 ERCP is highly invasive, however, and 5% to 10% of patients undergoing this procedure later develop acute pancreatitis.2,8 Other possible complications include bleeding, sepsis, and duct perforation.6 Sedation is required and the procedure is expensive. ERCP is currently being used less as a means of diagnosis because safer alternatives such as endoscopic ultrasonography (EUS) are now available.5
CT is noninvasive and offers 75% sensitivity for CP.3 CT images can detect changes in pancreatic size, duct dilation, and numerous complications such as pseudocysts, varices, splenic enlargement, and biliary obstruction.3,4 It is most reliable, however, in the detection of duct calcification. Since calcification is a late finding in CP, use of CT is generally limited to severe or long-standing disease.2,4 MRI is also used in the diagnosis of CP.4 Duct anatomy, pancreatic parenchyma, and surrounding fluid can be observed with or without the use of contrast.3 In general, its demonstration of structural change is similar to that of CT, but MRI cannot detect calcifications.4 Magnetic resonance cholangiopancreatography (MRCP), however, can provide additional detail to ductal imaging. MRCP has a quality that is close to that of ERCP and it offers a noninvasive alternative.2-4 Despite these advances, MRI is still considered to be an inappropriate test for the diagnosis of early disease.2 Transabdominal ultrasonography (TUS) is a nonspecific diagnostic tool for CP because of the deep position of the pancreas.8 In some cases, TUS can detect abnormal size, calcifications, duct dilation, and pseudocysts. Like CT, TUS is most useful in detecting calcifications, but it is only sensitive with severe CP.4 This method is also limited by the presence of bowel gas.4,9 EUS is a sensitive tool that overcomes the limitations of TUS because an endoscope with a transducer is placed directly in the bowel lumen. This position displaces bowel gas and provides an extremely close view of the pancreas.8 EUS can be utilized to view the pancreatic ducts as well as the entire pancreas parenchyma.2,9 The safety of EUS is comparable to that of gastroscopy with serious complications occurring in only 1 out of 2,000 examinations.8,9 In contrast to gastroscopy, EUS requires sedation, more time, and an endoscope with a slightly increased diameter. EUS should be performed only by a skilled gastroenterologist.2,9 1. Chowdhury RS, Forsmark CE. Review article: Pancreatic function testing. Aliment Pharmacol Ther. 2003;17:733-750. 2. Vlodov J, Tenner SM. Acute and chronic pancreatitis. Prim Care. 2001;28: 607-628. 3. Mitchell RM, Byrne MF, Baillie J. Pancreatitis. Lancet. 2003;361:1447-1455. 4. Remer EM, Baker ME. Imaging of chronic pancreatitis. Radiol Clin North Am. 2002;40:1229-1242,v. 5. Turner MA. The role of US and CT in pancreatitis. Gastrointest Endosc. 2002;56(6 suppl):S241-S245. 6. Venu RP, Brown RD, Halline AG. The role of endoscopic retrograde cholangiopancreatography in acute and chronic pancreatitis. J Clin Gastroenterol. 2002;34:560-568. 7. Lehman GA. Role of ERCP and other endoscopic modalities in chronic pancreatitis. Gastrointest Endosc. 2002;56(6 suppl):S237-S240. 8. Wallace MB, Hawes RH. Endoscopic ultrasound in the evaluation and treatment of chronic pancreatitis. Pancreas. July 2001;23:26-35. 9. Sahai AV. EUS and chronic pancreatitis. Gastrointest Endosc. 2002;56(4 suppl): S76-S81. |
Only surgery can rule out pancreatic cancer, which has many of the presenting features of CP, such as pain, weight loss, and a hard, enlarged pancreas noted on the physical exam. Imaging studies can demonstrate evidence of cancer, but only a limited resection and drainage can provide a definite diagnosis.2
The primary goal of treatment in CP is pain relief. Although an initial trial of an NSAID is a reasonable approach, almost all patients with CP eventually require narcotics.8 Limiting the prescribing of pain medication to one practitioner may help to prevent narcotic abuse.3 Nonnarcotic pain modulators such as gabapentin and selective serotonin reuptake inhibitors may also be beneficial for refractory pain.6 Referral to a pain clinic or for psychological support may be appropriate in some cases.8
Treatment for steatorrhea is pancreatic enzymes—lipase 28,000 U and trypsin 10,000 U—taken with each meal.3,6,8 A histamine (H2) receptor antagonist or proton pump inhibitor must also be taken to suppress gastric acid and prevent enzyme degradation. Fat intake should be limited to less than 25 g/d.6,8 Vitamin supplementation, including B12 and the fat-soluble vitamins A, E, and K, may be tried for refractory steatorrhea. Managing the use of exogenous pancreatic enzymes is straightforward and also safe for the patient.
Managing diabetes in late CP can be challenging, particularly in patients who continue to drink alcohol.6 Treatment is usually with insulin.3
In some cases, pain and complications that do not respond to medical treatment may be relieved through the use of ERCP or EUS.12 Guided by ERCP, surgeons use catheters, guide wires, and stents to dilate pancreatic duct strictures, remove duct stones, and drain pseudocysts. EUS is used in pseudocyst drainage and celiac plexus block,4 usually with triamcinolone or bupivacaine.6 Administration of prophylactic antibiotics before pseudocyst drainage is appropriate because bacteria may be introduced into the retroperitoneal space.12 Although ERCP and EUS are promising, comparative trials with surgical procedures are lacking.14
Approximately 50% of patients with CP require surgery,6 most often for intractable pain, although surgery may be required in suspected malignancy, nonresolving common bile duct or duodenal stenosis, pseudoaneurysms, uncontrolled vascular erosions, large pancreatic pseudocysts, intractable internal pancreatic fistulas, and wasting disease.2 Surgical drainage of an abnormally dilated main pancreatic duct provides pain relief in approximately 80% of patients. Estimates are that one third of patients develop diabetes after pancreatic surgery.5,15
Current recommendations are that patients with CP should undergo annual EUS with fine-needle aspiration to screen for malignancy.6 Resection should be offered if dysplastic lesions or carcinoma in situ is discovered.6
REFERENCES
1. Remer EM, Baker ME. Imaging of chronic pancreatitis. Radiol Clin North Am. 2002;40:1229-124,v.
2. Strate T, Knoefel WT, Yekebas E, Izbicki JR. Chronic pancreatitis: etiology, pathogenesis, diagnosis, and treatment. Int J Colorectal Dis. March 2003;18:97-106.
3. Banks PA. Epidemiology, natural history, and predictors of disease outcome in acute and chronic pancreatitis. Gastrointest Endosc. 2002;56(6 suppl):S226-S230.
4. Wallace MB, Hawes RH. Endoscopic ultrasound in the evaluation and treatment of chronic pancreatitis. Pancreas. July 2001;23:26-35.
5. Cooperman AM. Surgery and chronic pancreatitis. Surg Clin North Am. 2001;81:431-455.
6. Mitchell RM, Byrne MF, Baillie J. Pancreatitis. Lancet. 2003; 361:1447-1455.
7. Okazaki K, Chiba T. Autoimmune related pancreatitis. Gut. July 2002;51:1-4.
8. Vlodov J, Tenner SM. Acute and chronic pancreatitis. Prim Care. 2001;28:607-628.
9. Witt H, Becker M. Genetics of chronic pancreatitis. J Pediatr Gastroenterol Nutr. February 2002;34:125-136.
10. Chowdhury RS, Forsmark CE. Review article: Pancreatic function testing. Aliment Pharmacol Ther. 2003;17:733-750.
11. Whitcomb DC, Pogue-Geile K. Pancreatitis as a risk for pancreatic cancer. Gastroenterol Clin North Am. 2002;31:663-678.
12. Lehman GA. Role of ERCP and other endoscopic modalities in chronic pancreatitis. Gastrointest Endosc. 2002;56(6 suppl): S237-S240.
13. Sahai AV. EUS and chronic pancreatitis. Gastrointest Endosc. 2002;56(4 suppl):S76-S81.
14. Venu RP, Brown RD, Halline AG. The role of endoscopic retrograde cholangiopancreatography in acute and chronic pancreatitis. J Clin Gastroenterol. 2002;34:560-568.
15. Reber HA. Surgery for acute and chronic pancreatitis. Gastrointest Endosc. 2002;56(6 suppl):S246-S248.
Erin Connelly. Chronic pancreatitis: Debilitating for the patient, frustrating to manage. JAAPA December 2004;17:14-18.
Copyright © 2004, Advanstar Medical Economics Healthcare Communications at Montvale, NJ 07645-1742. All rights reserved.
