ACUTE PANCREATITIS INTRODUCTION • The pancreas is an elongated organ that lies in the back of the mid-abdomen.

It is responsible for producing digestive juices and certain hormones, including insulin, the main hormone responsible for regulating blood sugar. • Acute pancreatitis refers to inflammation of the pancreas and is associated with sudden onset of severe abdominal pain. • It usually develops as a result of passage of gallstones through the common bile duct or after regular consumption of alcohol for a number of years. • Several additional causes of acute pancreatitis have been described due to a variety of medications, genetic diseases, infectious agents, postoperative states, endoscopic procedures involving the pancreatic and bile ducts, and other types of injury to the pancreas. • Most attacks of acute pancreatitis do not lead to complications, and most people recover uneventfully with supportive medical care. • However, in a small proportion of people, acute pancreatitis takes a more serious course that requires intensive medical care. In all cases, it is essential to determine the underlying cause of acute pancreatitis and, if possible, to treat this condition to prevent a recurrence. • Because the severity and course of acute pancreatitis can vary widely from person to person, the treatment of this condition is individualized. CAUSES OF ACUTE PANCREATITIS • There are many possible underlying causes of acute pancreatitis, but 60 to 75 percent of all cases are caused by gallstones or alcohol abuse. • Gallstone pancreatitis — Because the gallbladder and pancreas share a drainage duct, gallstones that lodge in this duct can prevent the normal flow of pancreatic enzymes and trigger acute pancreatitis. • Gallstone pancreatitis is more common in women than in men. • Alcoholic pancreatitis — Alcohol is also a common cause of acute pancreatitis. • Alcoholic pancreatitis is more common in men, and usually occurs in individuals with long-standing alcohol abuse. • Drug-induced pancreatitis — A large number of drugs used to treat medical conditions can trigger acute pancreatitis; for example, dideoxyinosine, DDI (used for treating AIDS), 6-mercaptopurine, 6-MP (an immunosuppressant drug), and angiotensin-converting enzyme (ACE) inhibitors (used for treating high blood pressure). • Post-ERCP — Endoscopic retrograde cholangiopancreatography (ERCP) is an endoscopic test that involves the injection of dye into the bile duct and pancreatic duct. • Acute pancreatitis develops in about 3 to 5 percent of people who undergo ERCP. • Certain characteristics of the patients, such as female sex and younger age, make them more prone to develop this complication.

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Certain types of procedures also may increase the risk, particularly complicated procedures that can cause trauma to the pancreatic duct. Most cases of ERCP-induced pancreatitis are mild. Hereditary conditions — Acute pancreatitis can be caused by hereditary conditions, for example, familial hypertriglyceridemia (high blood triglyceride levels) and hereditary pancreatitis. The genetic basis for hereditary pancreatitis is rapidly being uncovered, and some specific tests are already available. These conditions may cause acute pancreatitis in children. Idiopathic — No underlying cause can be identified in about 20 percent of people with acute pancreatitis. This condition is called idiopathic pancreatitis. Only about 3 percent of people will experience additional attacks over time, a condition called idiopathic recurrent pancreatitis. Other causes — In rare cases, acute pancreatitis is caused by infections, such as mumps or viral hepatitis, or by abdominal injury.

SYMPTOMS • Sudden, constant pain in the upper part of the abdomen is a hallmark of acute pancreatitis, although other medical conditions can also cause this pain pattern. • In about half of all people who experience pain during acute pancreatitis, the pain wraps around the trunk and also involves the back in a band-like pattern. • The pain typically lasts days and is often relieved by leaning forward. In mild cases of acute pancreatitis, the pain may be limited to slight abdominal tenderness, and about 5 to 10 percent of people with acute pancreatitis do not experience any pain at all. • In people with gallstone pancreatitis, gallbladder pain may occur before pancreatic pain. • Gallbladder pain (referred to as biliary colic) is typically described as a moderately severe pain in the right upper region of the abdomen extending to the back and right shoulder. • The pain gradually rises in intensity and may be accompanied by nausea and vomiting. • Although the term "colic" implies that the pain is intermittent, it typically is steady. • Gallbladder pain lasts six or eight hours at most and often follows a meal. • In people with alcoholic pancreatitis, the symptoms of acute pancreatitis often occur one to three days after an alcohol binge or after stopping drinking. • The pain of acute pancreatitis is accompanied by nausea and vomiting in about 90 percent of people. In severe cases of acute pancreatitis, the initial symptom may be shock or coma. DIAGNOSIS • The diagnosis of acute pancreatitis can be challenging because the signs and symptoms of other medical conditions can mimic those of pancreatitis.

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The diagnosis is usually based upon careful consideration of a person's medical history, the signs and symptoms noted during a physical examination, and the results of specific diagnostic tests. Once a diagnosis of acute pancreatitis is made, additional tests are used to determine the underlying cause. This step ensures that a person will receive the correct treatment to prevent pancreatitis from recurring. Additional tests also help predict the likely course of pancreatitis over time. This step is important because in a small percentage of people with acute pancreatitis, the condition will progress to a more serious condition called severe acute pancreatitis, often referred to as "necrotizing pancreatitis". If tests suggest that necrotizing pancreatitis is likely, early intensive medical treatment may help improve the prognosis. Medical history — A medical history often provides clues about the underlying cause of acute pancreatitis. Your doctor will ask about any previous symptoms of gallstones and about your alcohol intake because these two factors account for the majority of cases of acute pancreatitis. Your doctor will also ask if you have other medical conditions, if you take any medications, and if any family members have experienced similar symptoms. Physical examination — Your doctor will perform a physical examination to check for the signs and symptoms of acute pancreatitis. These signs and symptoms vary with the severity of the attack, and their number and extent can help predict the course of pancreatitis. Your doctor will ask about abdominal pain, nausea, and vomiting, and will check for other signs and symptoms of acute pancreatitis, including fever, rapid heart rate, and shallow breathing or difficulty breathing. You will also be checked for less common signs and symptoms, including bruise-like areas on the stomach or back, jaundice (yellowish discoloration of the skin), red nodules under the skin, inflammation of the leg veins, and pain and inflammation of the joints.

DIAGNOSTIC TESTS • Diagnostic tests help confirm the presence of acute pancreatitis and predict the likely course of the condition. It is important to discuss the timing, usefulness, and risks of various tests with your doctor. • The extent of testing is usually tailored to the severity of acute pancreatitis and the most likely underlying causes. • Pancreatic enzymes — During acute pancreatitis, enzymes that normally flow from the pancreas into the digestive tract leak out of the pancreas and into the bloodstream. Tests can detect two of these enzymes—amylase and lipase—in the blood. • Serum amylase — A serum amylase test determines levels of amylase in a blood sample. Marked increase (more than three times the upper limit of normal) in the levels of amylase strongly suggest the diagnosis of acute pancreatitis. This is the most commonly used test to aid the diagnosis of acute pancreatitis. Levels of amylase in

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the blood rise within 6 to 12 hours after acute pancreatitis begins and remain elevated for three to five days in uncomplicated attacks. Tissues other than the pancreas also produce amylase. However, during acute pancreatitis, blood levels of this enzyme are often more than three times the upper limit of normal, and this pattern helps differentiate most cases of acute pancreatitis from other conditions that increase blood amylase levels. Concomitant elevation of the serum lipase also helps to confirm the diagnosis. Occasionally, markedly elevated levels of amylase can occur in the absence of pancreatitis due to the combination of amylase with another protein in the blood. This combined amylase-protein complex cannot be eliminated by the kidneys and leads to elevated amylase levels in the blood. This condition, macroamylasemia, is benign and can be diagnosed by a blood test or a urine test; the absence of amylase in the urine in the presence of high levels in the blood suggests macroamylasemia. Unnecessary and costly testing for pancreatitis can be avoided if this condition is diagnosed. Serum lipase — The serum lipase test determines levels of lipase in a blood sample. Elevated serum lipase levels help to confirm the pancreatic origin of elevated serum amylase levels. Markers of inflammation — Rising blood levels of some substances signal inflammation, although these markers are non-specific because they do not point to the source of inflammation. These markers include C-reactive protein (CRP), neutrophil elastase, procalcitonin, tumor necrosis factor, and interleukin-6 (IL-6). Ongoing studies are determining if levels of inflammatory markers help predict the course of acute pancreatitis. At the present time, these markers are not routinely used. Liver enzymes — Liver enzymes can sometimes be helpful for determining the cause of pancreatitis. For example, elevated levels of alanine aminotransferase (ALT) at the onset of symptoms suggest that a person has gallstone pancreatitis. Although often referred to as liver function tests, these enzymes are not true indicators of the status of liver function. Imaging tests — Imaging tests provide information about the structure of the pancreas, the ducts that drain the pancreas and gallbladder, and the tissues surrounding the pancreas. Abdominal X-ray — In acute pancreatitis, an x-ray of the abdomen may reveal a normal appearance of the digestive tract or abnormalities that are characteristic of acute pancreatitis. These abnormalities include paralysis of regions of the small intestine and spasm of part of the colon. In severe cases, both the small intestine and colon may cease to function. An abdominal x-ray may also point to other conditions that mimic acute pancreatitis, such as blockage of the intestine and a tear in the intestinal wall. Chest X-ray — About one-third of people with acute pancreatitis have abnormalities on a chest x-ray. These abnormalities may include elevation of the diaphragm (the large muscle that separates the abdomen and the chest), collection of fluid in the chest cavity, collapse of the base of the lungs, and inflammation of the lungs.

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Abdominal ultrasound — An abdominal ultrasound test can also aid the diagnosis of acute pancreatitis. This test is particularly useful for identifying gallstones in the gallbladder or in the ducts that drain the gallbladder as the cause of acute pancreatitis. However, this test cannot identify the more serious abnormalities associated with moderate and severe pancreatitis. Computerized tomography scan — The computerized tomography (CT) scan is the most useful radiology test for diagnosing acute pancreatitis. This test is often done if conditions other than pancreatitis are suspected, if conservative medical care fails to relieve the symptoms of acute pancreatitis, or if complications such as necrotizing pancreatitis are suspected. The CT scan is especially useful for determining the extent of pancreatitis. It can identify enlargement or abnormal contours of the pancreas, inflammation of the tissues surrounding the pancreas, collection of fluid around the pancreas, and collection of gas in the pancreas or in the tissues behind the pancreas. The type and number of these abnormalities have been found to correspond to the severity of pancreatitis. Magnetic Resonance Imaging Scan (MRI) — MRI may be used to diagnose acute pancreatitis, to assess the severity of disease, to identify complications of pancreatitis such as fluid collections and areas of necrosis or dead tissue. An MRCP (magnetic resonance cholangiopancreatography), which can be performed along with an MRI, can identify the bile duct and pancreatic duct as well as small gall stones within the bile duct. This information can help guide further treatment. However, MRI may not be easily available in all the centers and sick patients sometimes find it difficult to undergo this procedure as it is time-consuming (>30 minutes). Endoscopic retrograde cholangiopancreatography — As mentioned above, ERCP can cause acute pancreatitis. However, it may also provide helpful information in people who are suspected of having pancreatitis due to gallstones or other problems with the bile or pancreatic ducts. In addition, ERCP permits treatment of some causes of pancreatitis. An example is removal of a gallstone that has become impacted in the common bile duct. Fine needle aspiration — In this procedure, a thin needle is used to collect tissue/fluid in and around the pancreas, usually under CT guidance. This is recommended if the patient has a persistent fever or necrotizing pancreatitis fails to improve or worsens despite treatment. The small sample of pancreatic tissue/fluid that is removed is sent for laboratory analysis, including staining for bacteria and culture. This analysis can help determine if the damaged pancreatic tissue has become infected. If infection is present in dead pancreatic tissue, further treatment may involve removal of the dead tissue by surgery. Serum triglyceride levels — A serum triglyceride test determines blood levels of the fat-like triglycerides. This test is useful for diagnosing familial hypertriglyceridemia or simple hypertriglyceridemia in adults. In patients with pancreatitis due to hypertriglyceridemia, the triglyceride levels are usually very high (>1000 mg/dL with upper limit of normal being 150 mg/dL).

Genetic tests — Genetic tests are useful for diagnosing hereditary forms of pancreatitis. Examples include genetic tests for mutations of the hereditary pancreatitis gene.

TREATMENT • The goals of treatment of acute pancreatitis are to alleviate pancreatic inflammation and to correct the underlying cause. • Treatment usually requires hospitalization for at least a few days. • The specific treatment measures used depend upon whether a person has mild or moderate to severe pancreatitis. • Mild pancreatitis — Mild pancreatitis is typically self-limited, and the symptoms usually resolve with simple supportive care, which entails monitoring, drugs to control the pain, and intravenous fluids. Although doctors typically discourage eating during the first few days, most people with mild pancreatitis are able to gradually resume eating within three to seven days. • Moderate to severe pancreatitis — Moderate to severe pancreatitis requires more extensive monitoring and supportive care. In cases of necrotizing pancreatitis, treatment may also entail antibiotics and surgery. • Monitoring — Moderate to severe pancreatitis can lead to potentially life-threatening complications, including damage of the heart, lung, and kidneys. Patients who develop kidney failure may need dialysis until kidney function returns. Those who have severe lung injury may need to be on a ventilator (a machine that facilitates breathing). • People with pancreatitis of this severity may be closely monitored in an intensive care unit where advanced supportive care is available if needed. • Intravenous fluids — Intravenous fluids can help prevent the dehydration that often results from moderate to severe pancreatitis. • Feeding and eating — Studies suggest that early enteral feeding (feeding through a tube advanced into the middle part of the small intestine) may actually help prevent infections, reduce the likelihood of complications, and lessen the severity of pancreatitis. • Parenteral feeding (feeding through an intravenous line placed in the upper chest) is an alternative for people who cannot tolerate enteral feeding or who cannot get enough nutrients with enteral feeding. • People with moderate to severe pancreatitis can resume eating gradually once the pain resolves and bowel functions return to normal. • Antibiotics — About 30 percent of people with severe acute pancreatitis will develop an infection of the damaged pancreatic tissue. Antibiotics can prevent this infection and control infections that are already present. Studies have shown that antibiotics reduce the likelihood of infection and death in people with severe necrotizing pancreatitis.

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This treatment may entail intravenous antibiotics and oral antibiotics. Because these antibiotics increase the risk of fungal infection, treatment may also include antifungal drugs. Necrosectomy — Acute pancreatitis is sometimes complicated by extensive damage to the pancreatic tissue and/or infection. In these cases, doctors usually recommend removal of the damaged and/or infected tissue, a procedure referred to as a "necrosectomy." It can be performed by open surgical procedure or at times by less invasive procedures, e.g., endoscopic or radiologic placement of drainage tubes into the area. Whether the procedure should be done surgically or by a non-surgical procedure depends upon the clinical condition of the patient and the expertise available in the hospital. Specific treatments of gallstone pancreatitis — In people who have gallstone pancreatitis, the treatment of pancreatitis is usually coupled with the treatment of gallstones. Endoscopic papillotomy — Most gallstones that cause attacks of acute pancreatitis clear on their own, but some stones cause prolonged blockage that leads to complications. In people with gallstone pancreatitis who also have jaundice (yellowing of the skin) or a gallbladder infection, a procedure called endoscopic papillotomy can be used to quickly relieve the obstruction. In contrast, this procedure is not necessary for people who have already passed their gallstones. Because many patients are very ill, doctors sometimes place a stent (a thin plastic tube) to drain the obstructed bile duct rather than attempting to remove the stone. Placement of a stent is usually faster and safer than endoscopic papillotomy. Surgery — Gallstone pancreatitis recurs in 30 to 50 percent of people after an initial attack of pancreatitis. Doctors usually recommend cholecystectomy (surgical removal of the gallbladder) to prevent this recurrence. This surgery can now be performed through a tiny incision in the abdominal wall, a procedure called laparoscopic cholecystectomy. During surgery, the ducts joining the gallbladder, pancreas, and small intestine are examined for residual gallstones. If any stones remain after surgery, they can be detected and removed during endoscopic retrograde cholangiopancreatography (ERCP).