CLASE PRACTICA NORMAL HOY PARA LOS GRUPOS A2 Y A4, NO FALTEN!!!!
quinta-feira, 14 de julho de 2011
quarta-feira, 13 de julho de 2011
segunda-feira, 11 de julho de 2011
Pancreatitis Aguda Fisiopato
Goldman: Cecil Medicine, 23rd ed.
PANCREATITIS
Chung Owyang
ACUTE PANCREATITIS Definition
Acute pancreatitis, which is an inflammatory disease of the pancreas, is characterized by a discrete episode of abdominal pain and elevated serum amylase and lipase levels. In contrast to chronic pancreatitis, which is characterized by changes in pancreatic structure and by persistence of dysfunction even after the precipitating cause has been corrected, acute pancreatitis is distinguished by complete restitution of the pancreas both morphologically and functionally after the derangements that precipitated the attack have been corrected.Epidemiology
The incidence of acute pancreatitis ranges from 1 to 5 per 10,000 per year. Among the many causes of acute pancreatitis ( Fig. 147-1 ), alcoholism and biliary tract disease are most frequent and account for more than 70% of cases. Rare causes are responsible for about 10% of cases, but in the remainder, the cause remains unknown.
| FIGURE 147-1 Factors associated with acute pancreatitis. ERCP = endoscopic retrograde cholangiopancreatography. |
Specific Causes Alcohol
Alcohol-induced acute pancreatitis usually occurs in patients who consume large quantities of alcohol for 5 to 10 years before the first attack ( Chapter 31 ). However, a recent study has indicated that an increased risk for alcoholic pancreatitis may occur with as little as 25 g (or two drinks) per day. In individuals who use large amounts of alcohol, acute pancreatitis develops in only 5 to 10%. A polymorphism in the detoxifying enzyme uridine 5-diphosphate (UDP) glucuronyl transferase (UGT1A7★3) confers an increased risk for alcoholic pancreatitis. Environmental factors or cofactors such as smoking and consumption of a high-fat diet may also affect a person's susceptibility to the disease. Several mechanisms may contribute to the development of alcoholic pancreatitis, including abnormal sphincter of Oddi spasm in the presence of stimulated pancreatic secretion, obstruction of small ductules by proteinaceous plugs, and direct toxic effects of alcohol metabolic byproducts. Alcohol may also change the amounts of potentially damaging proteases in pancreatic secretions. Increased amounts of lysosomal enzymes and an increased trypsinogen–pancreatic trypsin ratio have been reported in the pancreatic juice of alcoholic patients.Gallstones
The frequency of acute pancreatitis is inversely proportional to the size of gallstones ( Chapter 159 ). Persistence of stones in the bile duct or ampulla is associated with more severe disease. An impacted gallstone may permit reflux of bile into the pancreatic duct or occlude the duct's orifice. Microlithiasis (crystals in bile) may cause recurrent pancreatitis, although the precise mechanism remains unknown. Microlithiasis is common after prolonged fasting, total parenteral nutrition ( Chapter 236 ), rapid weight loss, and the use of drugs such as octreotide or ceftriaxone. Microlithiasis may be identified by the presence of sludge by ultrasonography (US) or the presence of birefringent cholesterol crystals in bile; the diagnosis should be considered in patients who have recurrent bouts of apparently idiopathic pancreatitis.Pancreatic Obstruction
Obstruction of pancreatic secretion is a less common cause of acute pancreatitis. Sphincter of Oddi dysfunction is associated with increases in sphincter pressure caused by increased smooth muscle tone or fibrotic stricturing. Pancreas divisum results from failure of the ventral and dorsal ducts to join during fetal development; the small accessory duct of Santorini and minor papillae may produce high outflow resistance. Sphincter of Oddi dysfunction or pancreas divisum has been reported in more than 25% of patients with idiopathic pancreatitis in some series, although whether this association is causal or coincidental is difficult to determine. Pancreatitis has been reported in up to 10% of patients with pancreatic cancer ( Chapter 204 ), but it is usually mild. Older patients with unexplained pancreatitis should undergo careful evaluation to exclude a minute pancreatic cancer amenable to resection.Drugs and Toxins
Toxins and drugs that have been implicated in acute pancreatitis include insecticides, methanol, organophosphates, and the venom of a scorpion found in the West Indies. Some of these agents cause pancreatitis by overstimulation of the pancreas via cholinergic pathways. The most prominent family of drugs causing pancreatitis are immunosuppressants, including azathioprine and its major metabolite (6-mercaptopurine), cyclosporine, and tacrolimus. Drugs used to treat acquired immunodeficiency syndrome (AIDS), such as trimethoprim-sulfamethoxazole, pentamidine, and 2′,3′-dideoxyinosine (ddI), may cause severe pancreatitis. Furosemide, thiazide diuretics, angiotensin-converting enzyme inhibitors, sulfasalazine, and oral 5-aminosalicylic acid appear to be rare causes of pancreatitis. Therapy with estrogens is associated with a dose-dependent increase in triglyceride levels and with pancreatitis. Tetracycline has been linked to pancreatitis, usually in patients with fatty liver. Other drugs such as corticosteroids, methyldopa, procainamide, nitrofurantoin, metronidazole, and interleukin-2 (IL-2) have also been implicated, but their causal relationship is less certain.Metabolic Factors
Attacks of acute pancreatitis are associated with hypertriglyceridemia, including familial forms ( Chapter 217 ). Serum triglyceride levels higher than 1000 mg/dL may precipitate attacks of acute pancreatitis, and lowering serum triglyceride levels to less than 200 mg/dL can prevent pancreatitis. It is currently believed that pancreatitis occurs as a result of the harmful effects of fatty acids released into the pancreatic circulation or parenchyma by the action of pancreatic lipase. Hypercalcemia secondary to hyperparathyroidism, immobilization, multiple myeloma, or total parenteral nutrition has been linked to hyperamylasemia but probably causes pancreatitis infrequently.Genetic Factors
In patients with a family history of pancreatitis, the possibility of familial pancreatitis should be considered. This autosomal dominant disorder has a penetrance of about 80%. The majority of patients have their first symptoms before reaching 20 years of age, with attacks frequently precipitated by alcohol, high fat intake, or emotional disturbances. Patients with this disorder also have a higher risk for pancreatic cancer. The most common genetic defect is an arginine-histidine substitution (R122H) at 7q35, the site of the trypsinogen gene, that results in resistance to trypsin hydrolysis, but other mutations involving the trypsinogen gene can also predispose to pancreatitis. Sporadic genetic mutations occur, and up to 11% of mutation-positive individuals may be silent carriers. Mutation in the pancreatic trypsin inhibitor gene (serine protease inhibitor, kazal type 1; SPINK1) may also predispose to pancreatitis. Loss of function of the inhibitor gene may impair inhibition of activated trypsin within acinar cells. The relatively common SPINK1 missense mutation in codon N34S is probably a disease modifier rather than a cause of pancreatitis because the prevalence of the N34S SPINK1 gene mutation (≈2%) is far greater than the prevalence of pancreatitis (0.006%) and the pancreatitis phenotype is no different with either a homozygous or heterozygous N34S SPINK1 gene mutation. However, specific SPINK1 mutations combined with other inherited mutations, such as mutations of the calcium-sensing receptor gene, may cause pancreatitis. Mutations in the cystic fibrosis transmembrane regulator (CFTR; Chapter 89 ) can cause pancreatitis. Classically, cystic fibrosis results in pulmonary disease and pancreatic insufficiency in 20% of patients, but rarely pancreatitis. Recently, a second phenotype, including recurrent acute pancreatitis and early-onset chronic pancreatitis, has been identified in heterozygotic patients without pulmonary disease.Trauma and Iatrogenic Factors
Most cases of trauma-induced pancreatitis occur as a result of blunt rather than penetrating injury. Postoperative pancreatitis is most frequently associated with procedures that involve manipulation of the pancreas or the periampullary region, or both. Reduced vascular perfusion (e.g., shock), as may occur when surgical procedures are associated with hypotension or hypoperfusion, can also precipitate acute pancreatitis. Hyperamylasemia and abdominal pain are common after endoscopic retrograde cholangiopancreatography (ERCP) ( Chapter 136 ), but evidence of significant pancreatitis occurs in less than 5% of patients undergoing ERCP.Miscellaneous and Idiopathic Factors
Other unusual causes of pancreatitis include autoimmune diseases, renal and cardiac transplantation, and infections with mumps ( Chapter 392 ) and coxsackieviruses ( Chapter 402 ). Cytomegalovirus infection ( Chapter 399 ) can cause acute inflammation of the pancreas in patients with AIDS ( Chapter 412 ). Although about 20% of patients are still classified as having unexplained pancreatitis, the wider use of sphincter of Oddi manometry, biliary crystal analysis, and genetic testing should reduce this percentage in the future.Pathobiology
Pathologically, two morphologic classifications are recognized: acute interstitial pancreatitis and acute hemorrhagic pancreatitis. The latter type is associated with much higher morbidity and mortality. The precise mechanisms responsible for acute pancreatitis are not well understood. However, the fundamental mechanism for transformation of the initial injury into pancreatitis appears to be intracellular activation of digestive enzymes and autodigestion. The complex cascade of cellular events leading to acute pancreatitis begins in the pancreatic acinar cells. Intracellular conversion of pancreatic zymogens into active enzymes most likely involves several pathways, including (1) cleavage of trypsinogen to trypsin by the lysosomal hydrolase cathepsin B, (2) disruption of intracellular Ca2+ signaling, and (3) trypsinogen autoactivation. In experimental models, hyperstimulation of the pancreas may result in the fusion of lysosome and zymogens within large vacuoles, followed by activation of enzymes and acute intracellular injury. Cathepsin B is a lysosomal enzyme capable of activating trypsinogen to trypsin. Trypsin then catalyzes the conversion of many proenzymes into active forms, which in turn are responsible for the major systemic complications of acute pancreatitis. Intracellular Ca2+ may also play an important role in the initiation of acute pancreatitis. A rise in intracellular Ca2+ and disruption of acinar cell Ca2+ signaling occur in pancreatitis that is induced by cerulean hyperstimulation and by pancreatic duct obstruction; this rise is associated with vacuolization of acinar cells and autoactivation of trypsinogen mediated by the translocation of vacuolar adenosine triphosphatase to membrane compartments in the acinar cell and the resulting acidification of intracellular compartments. The pancreas has several safety mechanisms to cope with the problem of autoactivation of zymogens. One mechanism is the pancreatic secretory trypsin inhibitor (PSTI), which is found in secretory granules. PSTI binds with the active site of trypsin in a ratio of 1 : 1 and inhibits trypsin activity. When more than 10% of the trypsinogen is activated, this inhibitory mechanism becomes ineffective. Thus, any disorders or agents that adversely affect or overwhelm this protective mechanism can cause pancreatitis. During pancreatitis, inflammatory mediators, including cytokines (such as tumor necrosis factor-α and platelet-activating factor) and chemokines (such as IL-6), are generated and released. These agents stimulate the recruitment of inflammatory cells, enhance the activation and adherence of inflammatory cells to the vascular wall, or cause direct cell injury. Generation of pro-inflammatory mediators can lead to the systemic inflammatory response syndrome (SIRS; Chapters 107 and 109 ). Marked leukocyte activation can result in distant organ injury and the development of multisystem organ failure. SIRS and pancreatic infection are the two major causes of death from acute pancreatitis.Clinical Manifestations
The typical symptoms of acute pancreatitis are abdominal pain, nausea, and vomiting. Pain usually develops first and remains constant, without the waxing and waning pattern typical of intestinal or renal colic ( Chapter 134 and see Table 134-2 ). The pain is frequently located in the epigastrium with radiation to the midback region; it typically lasts for hours to days and is not relieved by vomiting. Abdominal findings vary with the severity of the attack, from minimal local tenderness to marked generalized rebound tenderness, guarding, and abdominal distention. Bowel sounds are frequently diminished or absent because of intestinal ileus. Jaundice can occur even without stone-induced pancreatitis as a result of compression of the common bile duct by the edematous pancreas. With severe attacks, hypotension, tachypnea, tachycardia, and hyperthermia may be noted. Fever is usually less than 38.5° C. Examination of the skin may reveal tender areas of induration and erythema resulting from subcutaneous fat necrosis. In severe necrotizing pancreatitis, large ecchymoses may occasionally appear in the flanks (Grey Turner's sign) or the umbilical area (Cullen's sign); these ecchymoses are caused by blood dissecting from the retroperitoneally located pancreas along the fascial planes.Diagnosis Laboratory Findings Serum Amylase
The diagnosis of acute pancreatitis is based on clinical findings and supported by an elevation in serum amylase and lipase. Most, but not all patients with acute pancreatitis have hyperamylasemia. Typically, the serum amylase level rises rapidly over the initial 2 to 12 hours of an attack and then slowly declines to its normal values over the next 3 to 5 days. The magnitude of hyperamylasemia has no prognostic value. Hyperamylasemia is not specific to pancreatitis, but marked elevations in serum amylase (more than three times the upper limit of normal) support the diagnosis of pancreatitis in a patient with severe abdominal pain. Apart from acute pancreatitis, modest hyperamylasemia may result from small bowel obstruction, perforation, or infarction; a perforated duodenal ulcer; or liberation of amylase into the circulation from nongastrointestinal sources such as the lung, fallopian tubes, and salivary glands ( Table 147-1 ). Alternatively, hyperamylasemia may result from release of amylase from certain tumors or be caused by reduced renal clearance of amylase secondary to renal failure. Pancreatic hyperamylasemia can occur after ERCP or after passage of common duct stones, even in the absence of pancreatitis. Macroamylasemia, an unusual but not rare condition, can occasionally cause isolated elevation of the serum amylase level. In this condition, amylase is bound to an abnormal serum protein; the complex is not cleared by the kidney and results in hyperamylasemia. Macroamylasemia should be suspected when hyperamylasemia is associated with low urinary amylase levels. Hypertriglyceridemia may spuriously depress serum amylase measurements; diluting the serum unmasks the increased serum amylase level.
| Amylase | Lipase | |
|---|---|---|
| Pancreatitis | ↑ | ↑ |
| Intestinal injury/obstruction | ↑ | ↑ |
| Biliary stone | ↑ | ↑ |
| Tubo-ovarian disease | ↑ | Normal |
| Renal failure | ↑ | ↑ |
| Macroamylasemia | ↑ | Normal |
| Parotitis | ↑ | Normal |
Amylase activity in blood is composed of isoenzymes from both the pancreas and salivary glands. Pancreatic isoamylase normally accounts for approximately 40% of total serum amylase activity. In acute pancreatitis, serum pancreatic isoamylase increases substantially. Unfortunately, such increases can also occur in conditions other than acute pancreatitis, including intestinal injury and renal insufficiency, thereby rendering its measurement nonspecific.Serum Lipase
During acute pancreatitis, serum lipase levels increase in parallel with serum amylase levels. The lipase level remains elevated longer and thus may help diagnose pancreatitis after an attack has passed. Additionally, lipase levels are normal in patients with macroamylasemia and parotitis. Though not entirely specific for pancreatitis, serum lipase has supplanted amylase as the single test of choice for the diagnosis of pancreatitis.Other Blood Tests
Routine laboratory tests in patients with moderate to severe acute pancreatitis usually reveal leukocytosis. Transient mild hyperglycemia is common and occurs when excess glucagon is released from alpha cells of the islets of Langerhans. Hypocalcemia is generally caused by extravasation of nonionized, albumin-bound calcium from inflamed retroperitoneal and, at times, peritoneal surfaces; this form of hypocalcemia is common, usually causes no symptoms, and requires no treatment. In necrotizing pancreatitis, hypocalcemia can be more severe because of loss of ionized calcium within areas of fat necrosis in the pancreas and peripancreatic tissue. Hyperbilirubinemia and elevations in serum aminotransferase and alkaline phosphatase levels are seen in up to 50% of patients as a result of either compression of the common bile duct by the inflamed pancreas or the nonobstructive cholestasis that accompanies severe illness. In the presence of pancreatitis, an increase in liver enzyme values, especially alanine aminotransferase to more than three times normal, suggests a biliary cause. Hypoalbuminemia may occur as a result of extravasation of albumin from inflamed retroperitoneal and peritoneal surfaces. The serum triglyceride level should be measured in all patients because of its etiologic implications and to interpret unexpectedly normal serum amylase levels. Serum triglyceride levels less than 500 mg/dL are unlikely to be a cause of pancreatitis. For example, most individuals who abuse alcohol have moderate, but transient elevations in triglyceride levels, probably as an epiphenomenon but not as the cause of pancreatitis.Urine Tests
The urinary amylase–to–creatinine clearance ratio increases from 3% to approximately 10% in acute pancreatitis. Even moderate renal insufficiency interferes with the accuracy and specificity of this test. Excretion of urinary amylase is not increased in patients with macroamylasemia. Thus, other than to diagnose macroamylasemia, urinary amylase and the amylase–to–creatinine clearance ratio are not used clinically.Imaging Chest and Abdominal Radiographs
Standard and upright chest and abdominal radiographs should be obtained in patients suspected of having acute pancreatitis. Chest radiographs may show pleural effusions and basilar atelectasis. Bilateral pulmonary opacification with a normal-sized heart is the hallmark of adult respiratory distress syndrome (ARDS; Chapter 105 ). Abdominal radiographs should be obtained to exclude nonpancreatic diseases such as intestinal perforation. Intestinal gas patterns may indicate ileus, which may sometimes appear as an isolated dilated loop of small bowel overlying the pancreas (a sentinel loop) or dilation of the transverse colon with abrupt termination of the gas column at the splenic flexure (colon cutoff sign) when the inflammatory process affects the phrenicocolic ligament.Ultrasound and Computed Tomography
US and computed tomography (CT) play important roles in the diagnosis and management of acute pancreatitis. US is the single best noninvasive test for detecting cholelithiasis ( Chapters 134 and 135 ), although it is less reliable for direct visualization of a bile duct stone. An inflamed pancreas may appear hypoechoic on US because of edema in the parenchyma. However, visualization of the pancreas is limited by intestinal gas or adipose tissue in 30 to 40% of patients. CT is the primary modality for evaluating the extent and local complications of pancreatitis. Pancreatic inflammation may be seen as pancreatic enlargement, inhomogeneity of the pancreatic parenchyma, or fluid infiltrating the peripancreatic fat in 90% of patients ( Fig. 147-2 ). Dynamic CT during bolus administration of intravenous contrast is useful to evaluate the severity of pancreatitis because it can demonstrate the poor pancreatic perfusion that is suggestive of pancreatic necrosis ( Fig. 147-3 ). The CT finding of necrosis identifies patients who are at higher risk for pancreatic infection and death ( Table 147-2 ).
| FIGURE 147-2 Typical computed tomography scan in a patient with acute non-necrotizing pancreatitis. After intravenous contrast injection, the normally enhancing pancreatic parenchyma can be seen separately from the nonenhancing peripancreatic fluid that surrounds the pancreatic tail. (Courtesy of Poonputt Chotiprasidhi.) |
| FIGURE 147-3 Typical computed tomography scan in a patient with necrotizing pancreatitis. Peripancreatic and retroperitoneal edema, as well as large nonenhancing areas of necrosis (arrow), are visible in the body and tail of the pancreas. This degree of necrosis is classified as grade D (see Table 147-2 ). |
| Ranson's Criteria[*] | Simplified Glasgow Criteria[†] | CT Criteria[‡] | ||
|---|---|---|---|---|
| On admission | Within 48 hr of admission | A. Normal | ||
| Age >55 yr | Age >55 yr | B. Enlargement | ||
| WBC >16,000/μL | WBC >15,000/μL | C. Pancreatic inflammation | ||
| AST >250 U/L | LDH >600 U/L | D. Single fluid collection | ||
| LDH >350 U/L | Glucose >180 mg/dL | E. Multiple fluid collection | ||
| Within 48 hr after admission | Albumin <3.2 g/dL | |||
| Glucose >200 mg/dL | Ca2+ <8 mg/dL | |||
| HCT decrease by >10% | Arterial PO2 <60 mm Hg | |||
| BUN increase by >5 mg/dL | BUN >45 mg/dL | |||
| Ca2+ <8 mg/dL | ||||
| Arterial PO2 <60 mm Hg | ||||
| Base deficit >4 mEq/L | ||||
| Fluid sequestration >6 L | ||||
| AST = aspartate aminotransferase; BUN = blood urea nitrogen; Ca2+ = serum calcium level; HCT = hematocrit; WBC = white blood count. |
Magnetic Resonance Imaging and Endoscopic Retrograde Cholangiopancreatography
Magnetic resonance imaging (MRI) is probably equivalent to CT for imaging an acutely inflamed pancreas. MRI is better than CT for distinguishing between an uncomplicated pseudocyst and one that contains necrotic debris. Though more expensive and less accessible, MRI is preferred in patients who are pregnant or have contrast allergies. In patients with suspected biliary pancreatitis, magnetic resonance cholangiopancreatography (MRCP) may identify more than 90% of bile duct stones. ERCP is not useful for establishing the diagnosis of acute pancreatitis, but it is very useful to diagnose and treat persistent bile duct stones in acute pancreatitis. It should also be used in the investigation of patients with unexplained recurrent pancreatitis. It is especially useful for the diagnosis of mild chronic pancreatitis, pancreas divisum, or sphincter of Oddi disease. However, it should be noted that pancreatitis occurs in about 5% of patients undergoing ERCP. This risk for pancreatitis increases significantly in female patients with normal serum bilirubin, patients suspected of sphincter of Oddi dysfunction, and those with a previous history of post-ERCP pancreatitis. In fact, patients with the lowest probability of harboring truly obstructive pathology are at the highest risk for the development of pancreatitis after ERCP, even if the procedure is performed for diagnosis alone. Because new techniques such as MRCP and endoscopic ultrasound (EUS) have accuracy rates rivaling that of ERCP, they may be preferable to ERCP for patients with equivocal evidence of biliary obstruction, especially those at high risk for post-ERCP pancreatitis.Differential Diagnosis
Acute pancreatitis must be distinguished from a number of conditions that cause upper abdominal pain, nausea, and vomiting (see Table 134-1 )—especially a perforated viscus, bowel obstruction, mesenteric ischemia, and cholecystitis ( Chapters 145 , 146 , and 159 ). Each of these processes can be marked by elevated serum amylase/lipase levels and be difficult to distinguish from acute pancreatitis. Features that favor the diagnosis of acute pancreatitis include greater than a one- to two-fold elevation in the serum amylase level, CT evidence of pancreatic inflammation, lack of free air on an abdominal plain radiograph or CT scan, and improvement with nonoperative treatment. If doubt persists and clinical deterioration continues, surgical intervention may be necessary to establish the diagnosis.Evaluation of Severity
Among the 200,000 patients admitted to hospitals each year in the United States with acute pancreatitis, approximately 20% have severe acute pancreatitis. In contrast to mild acute pancreatitis, which has a mortality rate of less than 1%, the death rate for severe acute pancreatitis is much higher: 10% with sterile pancreatitis and 25% with infected pancreatic necrosis. Thus it is important to establish the severity of acute pancreatitis to predict the patient's course and anticipate complications. Prognostic information from specific laboratory tests, clinical and physiologic assessment, and CT should guide the use of prophylactic antibiotics, urgent bile duct imaging, and early ERCP.Laboratory Tests
Routine blood tests such as serum amylase/lipase or white blood cell counts provide little prognostic information, whereas markers such as serum or urinary trypsinogen activation peptide (TAP) and C-reactive protein may help separate mild pancreatitis from severe pancreatitis. The TAP assay, which is an indirect measure of the amount of active trypsin, appears to discriminate between mild and severe disease. Urinary TAP can accurately predict the severity of acute pancreatitis 24 hours after onset and may be used as a single marker to assess severity in clinical practice. Neutrophil-specific elastase and IL-6 are released from inflammatory cells and are elevated in blood during the first 12 hours of acute pancreatitis; their elevation correlates with the severity of pancreatitis. C-reactive protein is induced by IL-6 and is a later marker to distinguish patients with severe disease on the second hospital day. A peak of more than 210 mg/L on days 2 to 4 or more than 120 mg/L at the end of the first week may be as predictive as the multiple factor scoring system (see the next section).Clinical and Physiologic Evaluation
A number of scoring systems can predict the morbidity and mortality of acute pancreatitis. Ranson's criteria, which are the most well known (see Table 147-2 ), include 11 characteristics. The five that are assessed at admission reflect the intensity of the inflammatory response, whereas the six evaluated during the initial 48 hours reflect serious complications, including fluid shifts, cardiovascular instability, and end-organ failure. In general, patients with fewer than two criteria have less than 1% mortality. Conversely, patients with more than six positive criteria have an increased likelihood of pancreatic necrosis and infection, as well as a higher mortality rate. The Glasgow system, which can be calculated anytime within the first 48 hours of hospitalization, measures only eight parameters (see Table 147-2 ) but appears to have prognostic accuracy similar to that of Ranson's criteria. The Acute Physiology and Chronic Health Evaluation (APACHE) II system uses 14 routinely measured parameters to produce a numerical score based on a patient's deviation from the normal range; however, it is more complex and difficult to use outside an intensive care unit. Both standard CT and contrast-enhanced CT provide useful prognostic information. The CT severity index (see Table 147-2 ) correlates with the Ranson criteria for assessing severity. Contrast-enhanced CT can be used to evaluate the presence and extent of pancreatic necrosis, which correlates well with morbidity and mortality. In non-necrotizing acute pancreatitis, infection is very rare and mortality is less than 1% (see Fig. 147-2 ). Conversely, necrotizing pancreatitis (see Fig. 147-3 ) is associated with a 30 to 50% rate of infection, and mortality ranges between 10 and 30%. The Atlanta classification categorizes acute pancreatitis as mild or severe. Pancreatitis without parenchymal necrosis on CT scan is termed interstitial or edematous pancreatitis and is usually mild. Patients have severe acute pancreatitis if they have any of four criteria: (1) organ failure with one or more of the following: shock (systolic blood pressure <90 mm Hg), pulmonary insufficiency (Pao2 <60 mm Hg), renal failure (serum creatinine >2 mg/dL after hydration), or gastrointestinal tract bleeding (>500 mL in 24 hours); (2) local complications such as necrosis, pseudocyst, or abscess; (3) at least three of Ranson's criteria; or (4) at least eight of the APACHE II criteria.Treatment
| Because there is no proven therapy that directly affects pancreatic inflammation, the main treatment goal for acute pancreatitis is to provide supportive care, including fluid resuscitation, maintenance of optimal fluid balance, and close monitoring for signs of local and systemic complications ( Fig. 147-4 ). More than 80% of patients with acute pancreatitis have mild disease with no complications. Nasogastric suction is not necessary in mild pancreatitis, but it is recommended in the presence of vomiting and ileus. Patients with mild acute pancreatitis can generally begin oral feeding within a few days of the onset of pain. Three randomized control trials have demonstrated that enteral feeding is not only safe and feasible but also associated with fewer infectious complications and lower cost than parenteral nutrition is.[1] Nasogastric feeding is as safe as nasojejunal feeding, even with severe pancreatitis.[2] Parenteral nutrition is reserved for patients who cannot tolerate enteral feeding or in whom an adequate infusion rate cannot be reached within 2 to 4 days. Patients should receive sufficient analgesic medication for pain control. Abdominal pain may be treated with 50 to 100 mg of meperidine every 4 hours as needed. More severe pain requires hydromorphone (Dilaudid, 2 to 4 mg every 4 hours as needed), which has a longer half-life than meperidine and may be given parenterally by a patient-controlled anesthesia pump. Prophylactic antibiotic therapy is not indicated in patients with uncomplicated acute pancreatitis. Severe intravascular volume contraction and hypovolemia, which can be caused by exudation of fluid into the inflamed peripancreatic retroperitoneum, as well as by gastrointestinal fluid loss from vomiting and nasogastric suction, should be corrected promptly. Patients who are still hypotensive after adequate volume replacement require placement of central lines to allow more precise assessment and management of fluid and electrolyte requirements. Patients with severe necrotizing pancreatitis frequently have a high cardiac index and low peripheral vascular resistance typical of SIRS. Most patients with gallstone pancreatitis have a mild episode, do well, and can undergo cholecystectomy during the same admission. A meta-analysis of four randomized controlled trials showed that patients with severe acute pancreatitis who demonstrate evidence of acute cholangitis or progressive jaundice benefit from early ERCP for bile duct clearance.[3] The role of early ERCP in patients without biliary obstruction or cholangitis is unclear. The major indication for early surgical intervention is diagnostic uncertainty in the presence of an acute abdomen. Intestinal perforation or necrosis, which sometimes mimic hemorrhagic acute pancreatitis, can be confirmed and corrected only when laparotomy is performed. Infected necrosis (see later) also requires urgent intervention. Surgical débridement plus drainage is usually necessary. Hypertriglyceridemia may cause 1 to 4% of cases of acute pancreatitis. Every attempt should be made to lower serum triglyceride levels to less than 200 mg/dL, usually with a statin but with other medications as needed ( Chapter 217 ). Complications In patients who show evidence of smoldering persistent pancreatitis, every effort should be made to exclude infected pancreatic necrosis, an impacted gallstone in the duodenal ampulla, and a pseudocyst. If US does not demonstrate a pseudocyst or an enlarged pancreas, a CT scan is indicated. CT will often reveal structural abnormalities such as a pseudocyst, pancreatic necrosis, or dilated ducts that may have escaped detection.Local Complications Infected pancreatic necrosis should be suspected in patients who have moderate to severe acute pancreatitis and worsening of symptoms after initial improvement or in those in whom new fever (especially >38.5° C), marked leukocytosis, positive blood cultures or, other evidence of sepsis develops (see Fig. 147-4 ). If necrotic pancreatitis is suspected, an emergency abdominal CT scan with intravenous contrast enhancement should be performed. Pancreatic or peripancreatic infection, usually occurring at least 10 days after the onset of pancreatitis, develops in 40 to 70% of patients with pancreatic necrosis and is the leading cause of morbidity and mortality in patients with severe acute pancreatitis. A meta-analysis of eight randomized trials showed that prophylactic broad-spectrum antibiotics that penetrate pancreatic tissue reduce mortality in patients with severe acute pancreatitis.[4] If fever or leukocytosis persists or develops later than 7 to 10 days after diagnosis without an obvious source of infection, fine-needle aspiration of the necrotic area should be performed to exclude infection. The demonstration of polymorphonuclear cells and bacteria is highly suggestive of infected pancreatic necrosis and should lead to urgent surgical intervention because the mortality in conservatively treated patients with infected pancreatic necrosis is greater than 60%. Antibiotic therapy should be initiated or continued to cover gram-negative enteric and anaerobic organisms; antibiotics with high penetration into pancreatic tissue include imipenem-cilastatin, fluoroquinolones, and metronidazole. Standard regimens include imipenem, 500 mg intravenously three times daily, or pefloxacin, 400 mg intravenously twice daily, and/or metronidazole, 500 mg three times daily for 10 to 14 days.[5] Management of clinically sterile pancreatic necrosis remains controversial; the necrotic tissue may resolve or gradually evolve into a pseudocyst or a region of organized pancreatic necrosis. In patients with persistent necrosis, 40% or more become infected during their course; others may experience persistent organ failure despite prolonged supportive care. Careful clinical monitoring and repeated dynamic CT scans are recommended to monitor the progression of necrotizing pancreatitis. If the condition deteriorates, surgery should be contemplated. Pancreatic pseudocysts occur in 10 to 20% of cases of acute pancreatitis. The diagnosis is most easily made by abdominal US or CT scan. Smaller cysts tend to disappear without specific treatment. Cysts that have been present for more than 6 weeks and are larger than 5 cm in diameter usually require treatment. The presence of severe pain, rapid expansion, or complications such as bleeding, leakage, or rupture may accelerate the need to intervene. Internal surgical drainage into the stomach or small intestine remains the most widely used treatment, but endoscopic or percutaneous drainage can be an attractive nonsurgical option. Acute pancreatitis can cause true pancreatic ascites, defined by the presence of large amounts of fluid that is rich in pancreatic amylase and protein and that results from a communication between the pancreatic duct or a pseudocyst and the peritoneal cavity ( Chapters 149 and 157 ). The site of ductal disruption is usually identified by ERCP. Acute pancreatitis may infrequently cause bleeding or thrombosis of peripancreatic vessels. Arterial hemorrhage occurs when a pseudocyst erodes into a pancreatic artery and transforms the pseudocyst cavity into a pseudoaneurysm. The diagnosis is made by CT scan and angiography; the bleeding artery can often be treated by embolization, but surgical intervention is sometimes required. The most common venous complication of pancreatitis is occlusion of the splenic vein, which may result in splenomegaly and gastric varices.Systemic Complications The two most important systemic complications of acute pancreatitis are renal and respiratory failure. Renal failure generally occurs as a result of hypovolemia and decreased renal perfusion ( Chapter 121 ). Prevention and treatment of pancreatitis-associated renal failure depend, to a large extent, on correction of fluid and electrolyte abnormalities. Mild and transient respiratory failure is believed to be the result of infradiaphragmatic inflammation, splinting of respiration, and atelectasis. Arterial hypoxemia with an arterial Po2 less than 70 mm Hg is often associated with mild respiratory alkalosis and is frequently noted in patients with severe acute pancreatitis; it is usually detected within the first 2 or 3 days of an attack. Hypoalbuminemia and fluid overload are probably important contributory factors. In most cases, the respiratory failure generally improves as the acute phase of pancreatitis ends. Some patients, however, progress to a more severe form of respiratory failure that resembles ARDS ( Chapter 105 ). This poor prognostic sign is frequently associated with a complicated clinical course or death (or both). Pancreatitis-associated ARDS results from injury to the alveolar membrane or degradation of surfactant by circulating enzymes, such as phospholipase, that may be released from the inflamed pancreas. Treatment is mainly supportive because specific therapy for pancreatitis-associated ARDS has not been defined.Surgical Therapy Infected pancreatic necrosis should be treated by surgical débridement. Outcomes are better if surgery is delayed until the necrosis has organized for at least 12 days and usually for about 4 weeks after the onset of pancreatitis,[6] when separation of tissue planes is easier and pancreatectomy can be avoided. In general, surgery is not indicated for patients with sterile necrosis unless clinical deterioration continues despite optimal medical care. In patients who are poor surgical candidates, minimal-access necrosectomy (débridement) by either CT-guided percutaneous or endoscopic routes has shown encouraging results. |
The natural history of pancreatitis is unpredictable and depends on the cause. In gallstone pancreatitis, cholecystectomy will prevent further attacks. Hyperparathyroidism, hyperlipidemia, and implicated drugs may cause or contribute to pancreatitis; elimination of these precipitants should prevent reoccurrence. With the exception of alcoholic pancreatitis, progression from acute to chronic pancreatitis is rare. In most cases of alcoholic pancreatitis, structural and functional abnormalities have generally already occurred, so pancreatic structure and function may continue to deteriorate despite alcohol abstinence, albeit at a slower pace. Nevertheless, alcohol abstinence will decrease the risk for future episodes of acute pancreatitis.CHRONIC PANCREATITIS Definition
Chronic pancreatitis is an inflammatory disease of the pancreas characterized by the presence of permanent and progressive morphologic or functional damage to the pancreas. Many patients have intermittent flares of acute pancreatitis. Sometimes, clinical distinction between acute recurrent pancreatitis, with restoration of normal pancreatic function and structure between attacks, and chronic pancreatitis may be difficult without structural or functional studies of the pancreas.Epidemiology
The prevalence of chronic pancreatitis in autopsy series is 0.04 to 5.0%, although it may be much higher in alcoholics. Chronic pancreatitis can be subdivided into calcifying pancreatitis and obstructive pancreatitis. Chronic calcifying pancreatitis is characterized by an irregular distribution of fibrosis and calcification within the pancreas, with varying degrees of obstruction of the primary and secondary pancreatic ducts. It is by far the most common form of chronic pancreatitis and may be associated with chronic alcoholic pancreatitis, tropical pancreatitis (see the next section), hereditary pancreatitis, pancreatitis secondary to hypercalcemia or hyperlipidemia, and idiopathic pancreatitis. Chronic obstructive pancreatitis is characterized by dilation of the ductal system, diffuse atrophy of the acinar parenchyma, and uniform fibrosis. It may be caused by pancreatic tumors, duct strictures, and possibly, pancreas divisum. In contrast to other forms of chronic pancreatitis, intraductal plugs or stones are rare or absent, and both structural and functional changes may improve when the obstruction is relieved.Specific Causes
In the United States, alcohol consumption is by far the principal cause of chronic pancreatitis; it accounts for approximately 70% of all cases. In contrast to acute pancreatitis, gallstones do not cause chronic pancreatitis. Malnutrition-induced (tropical) pancreatitis is the most prevalent form of chronic pancreatitis in developing Asian and African countries. Consumption of cassava, a plant indigenous to these regions, may contribute to pancreatic injury by increasing serum thiocyanate levels, which subsequently increase cellular free radical production. Ingestion of a diet deficient in micronutrients and antioxidants then exposes the pancreas to injury by unopposed free radicals. In a minority of cases, chronic pancreatitis results from trauma or from prolonged metabolic disturbances such as hypercalcemia and hypertriglyceridemia. In rare instances, pancreatitis can be inherited as an autosomal dominant disease and be manifested as acute or chronic pancreatitis with prominent pancreatolithiasis. About 4 to 6% of patients with chronic pancreatitis have autoimmune pancreatitis associated with hypergammaglobulinemia, histologic evidence of lymphoplasmacytic infiltration, frequent coexistence of other autoimmune diseases, and a favorable response to steroid therapy. This disease typically occurs in older male patients who have painless jaundice and weight loss but not the typical severe abdominal pain of pancreatitis. Diabetes is common in patients with autoimmune pancreatitis (42 to 76%). Up to 50% of patients may have other autoimmune diseases such as Sjögren's syndrome, primary sclerosing cholangitis, inflammatory bowel disease, and retroperitoneal fibrosis. Most patients have normal or only mildly elevated levels of serum amylase and lipase with a cholestatic profile on liver function tests. IgG4, a subtype of IgG, may distinguish autoimmune pancreatitis from other pancreatic disorders with a sensitivity of 95% and a specificity of 97%. On CT scan, most patients have a diffusely enlarged pancreas without peripancreatic fat, phlegmonous changes, or pseudocysts. The hallmark findings on ERCP are diffuse or segmental irregular narrowing of the main pancreatic duct. Recent data indicate an increased incidence of heterozygotic mutations in the cystic fibrosis gene (CFTR) in patients with idiopathic chronic pancreatitis. In contrast to cystic fibrosis, which is usually accompanied by painless pancreatic insufficiency, these patients experience recurrent pancreatitis despite normal sweat test results and pulmonary function. Approximately 20% of cases of chronic pancreatitis are idiopathic. A bimodal age distribution in adolescents and the elderly suggests that there may be two distinct pathophysiologic causes.Pathobiology
The pathophysiologic mechanism responsible for chronic pancreatitis is unclear. Theories include stone and ductal obstruction, necrosis-fibrosis, toxic-metabolic, and oxidative stress. The stone and ductal obstruction theory stems from the observation that obstruction causes an increase in the basal secretion of pancreatic proteins and a decrease in trypsin inhibitor in experimental animal models. The proteins in pancreatic juice precipitate as protein plugs and block small ductules in a random fashion, thereby activating pancreatic enzymes that result in episodes of acute pancreatitis. In time, calcium is complexed to the protein plugs, which results in further structural deterioration of the pancreatic ducts and acinar tissue, infiltration of inflammatory cells, and eventual acinar atrophy and fibrosis of exocrine tissue. Lack of normal secretion of specific proteins that inhibit calcium carbonate stone formation has been proposed as a cause of stone formation and chronic pancreatitis. Though widely espoused, the stone and duct obstruction theory fails to explain why protein plugs are not found in all cases of chronic pancreatitis, especially in the early stages of disease. The necrosis-fibrosis hypothesis proposes that the inflammation and scarring from bouts of acute pancreatitis cause obstruction and stasis within the duct with the subsequent formation of stones. Chronic pancreatitis may require “two hits,” including the early formation of protein plugs and postnecrotic fibrosis, to result in ductular obstruction. The toxic-metabolic theory proposes that alcohol produces an accumulation of cytoplasmic lipid within the acinar cells, thereby leading to fatty degeneration, cellular necrosis, and eventually fibrosis. The oxidative stress theory suggests that the fundamental cause of pancreatic disease is overactivity of hepatic mixed-function oxidases, which can produce reactive molecules that induce oxidative damage. The pancreas is exposed to this “oxidative stress” through the systemic circulation or through reflux of bile into the pancreatic duct, and the result is recurrent inflammation and tissue damage. All four proposed models of chronic pancreatitis have scientific merit, but it is unlikely that all cases of chronic pancreatitis can be explained by a single theory.Clinical Manifestations
Abdominal pain (see Table 134-2 ), which is the major symptom of chronic pancreatitis, occurs in about 80% of patients. Pain may be intermittent or chronic, and it may continue, diminish, or disappear completely over time. Pain may actually improve as the severity of pancreatitis worsens. In about 15% of patients, chronic pancreatitis is relatively painless. Possible causes of pain include inflammation of the pancreas, increased intrapancreatic pressure, neural inflammation, and extrapancreatic causes such as stenosis of the common bile duct and duodenum. Weight loss occurs in more than 50% of patients. Initially, the major cause of weight loss is decreased caloric intake because of fear of aggravating the abdominal pain. In advanced chronic pancreatitis, weight loss is usually due to pancreatic insufficiency with malabsorption or uncontrolled diabetes. Diarrhea and steatorrhea secondary to inadequate digestion of fats occur when pancreatic lipase is reduced to less than 10% of normal levels, a reduction that indicates extensive structural damage ( Chapter 143 ). Amylase deficiency results in diminished carbohydrate digestion and leads to osmotic diarrhea. Maldigestion of proteins is caused by deficiency of protease. Even though maldigestion affects all nutrients, the most clinically significant problem concerns maldigestion of fat and fat-soluble vitamins (A, D, E, and K). Although glucose intolerance is common early in the course of chronic pancreatitis, clinical diabetes ( Chapter 247 ) occurs relatively late in the disease. Ketoacidosis and diabetic neuropathy are relatively uncommon in this form of diabetes. Management of pancreatic diabetes is often difficult because the loss of both insulin and glucagon makes for a brittle form of diabetes. Insulin requirements are generally lower than for most patients with genetic diabetes because insulin receptors are not downregulated and insulin antibodies are not initially present.Diagnosis
If chronic pancreatitis is suspected, imaging techniques such as US and CT scan may reveal diagnostic information in approximately 70 to 90% of cases. If these tests are equivocal or negative, ERCP should be performed to visualize abnormalities of the pancreatic duct that may not be visible by imaging techniques. Less invasive EUS or MRCP can substitute for ERCP. If findings on ultrasound, CT, and ERCP or EUS are normal, a secretin/cholecystokinin stimulation test, which may disclose evidence of mild chronic pancreatitis, may be useful, especially with small duct disease.Structural Studies
Demonstration of diffuse, speckled calcification of the pancreas on a plain film of the abdomen is diagnostic of chronic pancreatitis, but the sensitivity of this finding is only 30 to 40%. US has a sensitivity of about 70% and a specificity of 90%, and the finding of chronic pancreatitis on US generally requires no confirmatory testing. Findings associated with mild chronic pancreatitis include an irregular contour of the gland, a reduction in echogenicity or echogenic foci in the parenchyma, and mild dilation of the duct. Calcification and dilation of the main pancreatic duct are suggestive of more severe chronic pancreatitis. CT is more sensitive than US but has comparable specificity. The most common diagnostic findings of chronic pancreatitis on CT include ductal dilation, calcifications, and cystic lesions. Other findings include enlargement or atrophy of the pancreas and heterogeneous density of the parenchyma. ERCP is commonly considered to be the most sensitive (≈90%) and specific (≈100%) diagnostic test for chronic pancreatitis. In minimal chronic pancreatitis, the branches and fine ducts show dilation and irregularity. Moderate pancreatitis is characterized by the additional finding of dilation, tortuosity, and stenosis of the main pancreatic duct. Advanced pancreatitis is defined by marked dilation of the main duct with total loss of the normal, tapered appearance; the secondary ducts are similarly dilated and blunted. ERCP should be reserved for patients in whom the diagnosis cannot be clearly established by other imaging techniques or those who have recurrent acute pancreatitis without an obvious cause. MRCP with or without stimulation of secretin is a useful alternative to ERCP when ERCP is contraindicated or not feasible because of technical difficulties. This imaging technique allows visualization of pancreatic ductal anatomy, peripancreatic fluid collections, and the pancreatic parenchyma. Although the quality, sensitivity, and specificity of MRCP currently vary greatly among centers, MRCP may replace ERCP in this setting as these technical limitations are overcome. EUS has equivalent sensitivity and specificity as ERCP without the risk of inducing pancreatitis. EUS-guided fine-needle aspiration can differentiate chronic pancreatitis from malignancy. As with ERCP, EUS should be used only when less invasive procedures fail to substantiate the diagnosis of chronic pancreatitis.Assessment of Pancreatic Exocrine Function
The simplest way to assess pancreatic exocrine function is quantitative 72-hour fecal fat measurement. Increased fat in stool (>7 g/day) occurs if exocrine secretion is reduced by more than 90%, but the test is neither sensitive nor specific ( Chapter 143 ). Among the pancreatic function tests, the secretin or cholecystokinin stimulation test with simultaneous collection of pancreatic secretions through a catheter positioned in the distal duodenum is most sensitive (sensitivity ≈90 to 95%). The collected fluid is assayed for bicarbonate (secretin stimulation) or lipase and trypsin. However, this test is time consuming (2 hours) and not widely available.Treatment
| Medical treatment is aimed mainly at control of pain and correction of malabsorption with adequate enzyme replacement. Most patients with autoimmune chronic pancreatitis respond dramatically to steroids with resolution of clinical symptoms and imaging abnormalities within 4 weeks. Prednisolone is usually initiated at 30 to 40 mg/day for 1 to 2 months and tapered by 5 mg every 2 to 4 weeks. In some patients, a maintenance dose of 5 to 10 mg/day of prednisolone may be needed to prevent relapse.Pain Control Pain control ( Fig. 147-5 ) includes avoidance of alcohol or the elimination of other offending agents (or both), use of analgesics, and celiac plexus block. Elevated (>500 mg/dL) triglyceride levels should generally be reduced beginning with a statin (e.g., atorvastatin starting at 10 to 20 mg/day), and implicated drugs, such as azathioprine, should be discontinued. It makes sense to eliminate these precipitants as possible causes of ongoing inflammation and pain. An initial trial of acetaminophen or nonsteroidal anti-inflammatory drugs (e.g., ibuprofen, 400 mg every 4 to 6 hours) is preferable, but patients may require opiate analgesics (e.g., hydrocodone, 10 mg every 6 hours as needed) ( Chapter 28 ). Concerns about addiction should not interfere with the goal of pain relief; a strong patient-physician relationship may prevent abuse of prescribed narcotics. Percutaneous radiologically or sonographically guided celiac plexus block can control pain from pancreatic cancer ( Chapter 204 ), but the procedure's occasional benefits almost never persist for more than a few months in patients with chronic pancreatitis. Oral pancreatic enzymes (25,000 to 30,000 units of lipase per meal) that are not enteric coated provide more protease activity in the proximal duodenum than do enteric-coated preparations and can reduce pain in a subset of patients with chronic pancreatitis, perhaps because the administration of trypsin or chymotrypsin can inhibit the intrinsic secretion of cholecystokinin and pancreatic enzymes. The greatest success (70%) is in patients with small duct disease rather than large duct disease (25%). The somatostatin analogue octreotide inhibits pancreatic secretion and has visceral analgesic effects. Clinical trials are under way to ascertain the utility of this drug in patients with painful chronic pancreatitis. Octreotide may also have a role in the management of refractory pancreatic fistulas or pseudocysts. Endoscopic therapy can control pain in some patients who have a prominent stricture in the proximal pancreatic duct. In most cases, dilation is followed by stent placement across the stricture. Pain improves in 55 to 100% of selected patients with an isolated proximal stricture during 2 to 69 months of follow-up. If all measures fail to relieve pain, surgery, which is superior to endoscopic drainage,[7] should be considered. Patients with ductal dilation have a 60% chance of obtaining pain relief if they undergo either partial resection with pancreaticojejunostomy or lateral pancreaticojejunostomy (modified Puestow procedure). In patients with ductal obstruction and dilation, the modified Puestow pancreaticojejunostomy relieves pain in about 60% of patients with morbidity less than 5% and mortality less than 2%. For patients with moderate to severe parenchymal disease and no ductal dilation, partial pancreatic resection can reduce pain in about 50% of cases.Management of Pancreatic Insufficiency Pancreatic steatorrhea should be treated with pancreatic enzyme replacement. At least 25,000 to 30,000 units of lipase per meal is necessary to provide adequate lipolysis, so patients must take 2 to 10 pills with each meal, depending on the preparation. Most patients achieve satisfactory nutritional status with this regimen and become relatively asymptomatic. A reduction in dietary fat can also help alleviate symptoms. In some patients, the use of enteric-coated preparations may be necessary because their gastric acid can destroy pancreatic enzymes; H2-receptor antagonists or proton pump inhibitors should be reserved for patients who cannot achieve adequate relief by other maneuvers. If all the measures just mentioned are ineffective, the diagnosis must be reaffirmed (by pancreatic function testing), and other contributing causes (celiac sprue, terminal ileal disease, or bacterial overgrowth) must be excluded. |
| FIGURE 147-5 Approach to a patient with chronic painful pancreatitis. ERCP = endoscopic retrograde cholangiopancreatography; ETOH = alcohol. |
Assinar:
Postagens (Atom)