Biliary Tract Disease

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[edit] Biliary Tract Disease

Nezam H. Afdhal

The major function of the gallbladder is the interprandial storage and concentration of hepatic bile, which consists of cholesterol, bile salts, and phospholipids. Bile is also the major excretory route for excess cholesterol and organic compounds metabolized in the liver. Postprandially, fat in the duodenum results in the release of the hormone cholecystokinin, which in turn triggers contraction of the gallbladder with ejection of concentrated gallbladder bile through the cystic duct and then the ampulla of Vater into the duodenum. The gallbladder is lined by simple absorptive columnar mucosa whose major functions are the absorption of water and the secretion of mucin glycoprotein and hydrogen ions. The majority of disorders of the gallbladder relate to an inability to maintain cholesterol solubility, resulting in gallstones and their complications.

[edit] CHOLELITHIASIS

[edit] Epidemiology

Because the greatest risk factor for the development of gallstones is increasing age, the incidence of gallstones is on the rise. In the United States, approximately 30 million people have gallstones, and approximately 1 million new cases are diagnosed annually. According to the National Institutes of Health, nearly 900,000 cholecystectomies were performed in 1996, with an estimated health care cost of over $5 billion. Although gallstones can be classified into cholesterol stones and pigmented stones, each with distinct mechanisms of pathogenesis, the vast majority (more than 75%) of gallstones in Western countries are primarily composed of cholesterol.^[1]

[edit] Pathophysiology

[edit] Cholesterol Gallstones.

Three simultaneous defects are necessary for cholesterol gallstone formation: (1) secretion of a cholesterol-supersaturated bile by the liver; (2) nucleation of cholesterol monohydrate crystals from gallbladder bile; and (3) gallbladder stasis with an adequate residence time of crystals within the gallbladder so that they can grow to a size that prevents them from being expelled from the biliary tract.^[2][3] The majority of patients have all three defects, but in certain clinical situations one particular factor may predominate^[1][4] (Table 103-1). Recognition of the pathophysiologic mechanism of gallstone formation in high-risk groups has led to attempts at prophylaxis. Ursodeoxycholic acid, an orally administered, naturally occurring, hydrophilic bile acid, completely prevented gallstone formation in a group of obese patients rapidly undergoing weight loss (more than 20 kg/16 weeks), whereas the incidence was 25% in similar patients receiving placebo. The use of cholecystokinin (CCK) and CCK analogs in long-term total parenteral nutrition (TPN) has been associated with a reduction in gallstone formation secondary to TPN-induced biliary stasis.

Table 103-1 Pathophysiology of Cholesterol Gallstone Formation in High-risk Patients

[edit] Pigmented Stones.

Pigmented stones make up approximately 20% to 25% of cases of cholelithiasis in Western industrialized nations. Pigmented stones are more common in elderly patients, in patients after cholecystectomy, and in those who reside in the Orient. Although the two types of pigment stones, brown and black, are primarily composed of calcium bilirubinate, they occur in very different clinical settings. Black stones are formed in the gallbladder and are more common in patients with chronic hemolysis, cirrhosis, or alcoholism and in those receiving TPN. Black stones have an irregular surface, are usually small and hard, and consist of fully cross-linked calcium bilirubinate. Brown stones are usually formed within the bile ducts, consist of calcium bilirubinate, mucin, and cholesterol, and are often soft and friable. Brown stones are more common in the Orient, particularly in patients with cholangiohepatitis, a condition associated with infection by Opisthorchis sinensis, a liver fluke (Fig. 103-1). In the United States, brown stones usually occur in patients after cholecystectomy in which bile may be chronically infected with microorganisms that are able to deconjugate bilirubin, such as Escherichia coli.

Figure 103-1 Percutaneous transhepatic cholangiogram after placement of stent across large stone in right hepatic duct, obstructing entire right hepatic system in Chinese immigrant with Oriental cholangiohepatitis.

[edit] Biliary Sludge.

Biliary sludge is most often identified by ultrasound examination of the gallbladder as echogenic material that layers out in the dependent portion of the gallbladder and is composed of a mixture of mucin, cholesterol crystals, and calcium bilirubinate granules (Fig. 103-2). Previously assumed to be a completely benign, incidental finding usually associated with conditions of impaired gallbladder emptying (e.g., TPN, pregnancy), it is now recognized that 30% of patients with sludge develop gallstones and that biliary sludge can result in complications of gallstone disease (e.g., pancreatitis, cholangitis). In a study of 23 patients on TPN, sludge developed in 30% by 3 weeks, in 50% by 4 weeks, and in 100% after more than 6 weeks. Stones formed in almost half (43%) of patients who developed sludge. Half these patients developed complications necessitating cholecystectomy after a mean of 43 days.^[5][6]

Figure 103-2 A, Longitudinal ultrasound scan of gallbladder demonstrating gallstone. Characteristic shadowing occurs from base of stone. B, Longitudinal ultrasound scan demonstrating sludge within gallbladder. Unlike stones, sludge casts no acoustic shadow.

Although biliary sludge formed during pregnancy disappears in the majority (60%) of patients after delivery, postpartum ultrasound examinations have demonstrated the persistence of sludge in 20% of patients and the formation of gallstones in the remaining 20%. Therefore biliary sludge should be considered part of the clinically relevant spectrum of gallstone disease. On occasion, especially in patients with idiopathic pancreatitis, sludge may not be visible by imaging tests, and examination of gallbladder bile during endoscopic retrograde cholangiopancreatography (ERCP) for small cholesterol crystals (microlithiasis) is required to make the diagnosis. These patients with recurrent pancreatitis respond well to cholecystectomy.

[edit] Clinical Presentation

Gallstones are usually asymptomatic within the gallbladder. They may transiently obstruct the cystic duct, however, producing biliary colic or, with more significant obstruction, cholecystitis and its complications. Stones small enough to pass into the common bile duct may obstruct there; the most common site is at the ampulla, where obstruction may be associated with the development of cholangitis or gallstone pancreatitis. Since none of the treatments for any of these conditions is without risk, a knowledge of their natural history and the treatment options is essential (Fig. 103-3).^[7] The assessment of patients with gallstones is based on whether they are symptomatic.

Figure 103-3 Natural history and management of gallstones.

[edit] Asymptomatic Gallstones.

Many medical centers once performed a cholecystectomy when gallstones were found, regardless of whether the patient had symptomatic cholelithiasis. This was especially true for patients with diabetes, a condition thought to increase the risk of complications of cholecystitis and cholangitis. In the past 5 years, however, a thorough evaluation of the natural history of asymptomatic gallstones has altered this approach. With rare exceptions, cholecystectomy is not required for most patients with asymptomatic cholelithiasis. Patients with asymptomatic gallbladder stones have a 2% to 3% risk of developing biliary pain each year for the first 10 years after the diagnosis of stones. After 10 years the risk decreases to less than 1% annually. Postmortem studies have demonstrated that of known gallstone patients, the cause of death is related to gallstone disease in fewer than 3%. In general, therefore, surgical treatment for gallstones is recommended only for patients with symptomatic disease.

[edit] Symptomatic Gallstones.

In patients whose conditions become symptomatic, the most common presentation is biliary colic. Biliary colic is not colicky in nature. It is usually steady, intense, and located in the right upper quadrant, although the pain may be referred to the right shoulder or scapular region, the midepigastrium, or elsewhere in the chest or abdomen. Peptic symptoms, belching, bloating, fatty food intolerance, and chronic pain should not be confused with biliary colic. The patient has no associated laboratory abnormalities. In 60% of cases the acute attack resolves spontaneously. Recurrent attacks of pain may occur in up to 70% of patients weeks to years after the initial episode. Biliary complications, such as acute cholecystitis, cholangitis, and gallstone pancreatitis, occur in 10% to 20% of patients with symptomatic gallstones. For these reasons, treatment, usually cholecystectomy, is often advised for patients with symptomatic gallstones.

[edit] Diagnosis

Although pain in the right upper quadrant should always raise suspicion for gallstone-related disease, it is not pathognomonic for these conditions (Box 103-1). Acute hepatitis is often associated with pain in this location, which results from acute hepatic inflammation stretching the liver capsule. The liver edge is often tender. Characteristically, transaminase levels in viral or toxin-mediated hepatitis are elevated at least 5 to 10 times normal, compared with less than twice normal in cholecystitis and with normal values in biliary colic. Using the symptom and laboratory complex to differentiate between alcoholic hepatitis and acute cholecystitis, however, can be more difficult. Although alcoholic hepatitis is usually associated with characteristic hepatic enzyme elevations, both conditions generally produce low levels of transaminases, and both may be associated with fever and leukocytosis. Taking a thorough history is essential. Although classically producing midepigastric pain, peptic ulcer disease may also present with pain in the right upper quadrant. Unlike pain of biliary origin, however, peptic symptoms often improve or resolve with antacid therapy. Rarely, appendicitis, colitis, or terminal ileitis may also present with right upper quadrant pain.

Atypical presentations of biliary tract disease may occur as well. Pain may rarely occur in the right lower quadrant, left upper quadrant, or even the chest, where it may occasionally be confused with angina pectoris.

[edit] Management

In general, treatment of gallstone disease is directed at alleviating symptoms and preventing complications. Medical and surgical options for symptomatic gallstone disease have expanded in the last 15 years. Whereas surgery can permanently resolve disease associated with gallbladder stones of any size, number, and makeup, medical therapy can be used only in specific situations, with significant risk of recurrence after discontinuation of therapy. Medical therapy still is occasionally recommended in certain patients, particularly those with extremely high surgical risk.

[edit] Surgery.

Surgery has historically been the mainstay of treatment for symptomatic gallstone disease. Cholecystectomy is generally a very safe procedure with an overall mortality rate of 0.1% to 0.3%. It relieves the characteristic biliary type of pain in approximately 90% of patients and prevents future recurrences. In addition, cholecystectomy is also responsible for the incidental discovery and removal of early gallbladder cancers. Before 1987, cholecystectomy was performed only as an open procedure through one of several possible laparotomy incisions. The operative mortality rates for elective open cholecystectomy in men are estimated at 0.11% for those under age 30, 0.24% for those 31 to 40, 0.54% for those 41 to 50, 1.22% for those 51 to 60, 2.73% for those 61 to 70, 6.15% for those 71 to 80, and 13.84% for those aged 81 to 90.^[7] Women are apparently more tolerant of this procedure, since their mortality rates are approximately half those in men at all age groups. Elective (“late”) surgery, performed 6 to 8 weeks after an episode of biliary colic or uncomplicated acute cholecystitis, had formerly been preferred over earlier surgery because actively inflamed tissues were believed to complicate surgery and increase the risk of secondary complications. Prospective randomized controlled trials, however, have demonstrated that early surgery is associated with lower morbidity and mortality rates.

Although open cholecystectomy is relatively safe and simple, laparoscopic cholecystectomy, first performed in 1987, now accounts for 90% of all cholecystectomies performed in the United States.^[8] Laparoscopic surgery reduces patient hospitalization, time away from work, and postoperative pain and complications. Bile duct injuries are no more common with laparoscopic than with open surgery. Conversion from a laparoscopic to an open approach is necessary in approximately 5% of patients because of difficulty in identifying anatomy, excessive bleeding, or intraoperative complications. Open cholecystectomy is still the preferred route in patients with peritonitis, sepsis, severe acute pancreatitis, and end-stage cirrhosis. Initially it was thought that laparoscopic cholecystectomy would reduce the cost of gallstone disease to both the patient and society. Although each patient's unit cost has decreased, however, annual total cholecystectomy costs are rising because of an increase in laparoscopic procedures.

Cholecystectomy should only be performed in symptomatic patients. Large clinical series have confirmed that laparoscopic cholecystectomy is as safe and effective as open cholecystectomy for gallstone disease.^[8]

[edit] Postcholecystectomy Syndrome.

After cholecystectomy, fewer than 5% of patients have recurrent or persistent abdominal pain months to years later. Persistence or early recurrence of pain may imply, however, that the initial diagnosis of gallbladder-related pathology causing the pain was incorrect. Biliary sources of postcholecystectomy pain include retained common bile duct stones, postsurgical bile duct strictures, and sphincter of Oddi dysfunction. Although controversial, sphincter of Oddi dysfunction after cholecystectomy appears to be more common in women and may result in typical biliary pain months to years after surgery. Elevated pressures (greater than 40 mm Hg) within the sphincter of Oddi result in intermittent biliary obstruction at the sphincter's level. In addition to their pain, affected patients may demonstrate: (1) a dilated common bile duct, (2) delayed emptying (more than 45 minutes) of contrast material from the duct after ERCP, and (3) hepatic enzyme elevations (usually low grade), especially during episodes of pain. Approximately 95% of patients with two of the three findings appear to respond to biliary sphincterotomy, with resolution of biliary-type pain.

[edit] Medical Therapy.

The nonsurgical approaches to gallstone disease include bile acid dissolution therapy and fragmentation of stones with extracorporeal shock wave lithotripsy (ESWL). These approaches offer the benefit of potentially avoiding surgery in patients at high risk of significant morbidity and mortality from cholecystectomy. Nonsurgical measures have important disadvantages, however, especially high recurrence rates after discontinuation of therapy. At present, fewer than 10% of patients with symptomatic gallstones are suitable candidates for nonsurgical therapy.

[edit] Bile Acid Dissolution Therapy.

Oral dissolution therapy should be considered for patients with suspected cholesterol gallstones and high surgical risk. Oral dissolution agents include ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA). Although both work by reducing cholesterol secretion into bile and enhancing cholesterol solubilization, UDCA also inhibits cholesterol crystal nucleation. Because these agents have no effect on calcium bilirubinate stones, candidates for therapy should have noncalcified (cholesterol) gallstones. In addition, an oral cholecystogram should reveal a functioning gallbladder and thus these agents' ability to reach the gallbladder lumen. UDCA is more expensive than CDCA, but CDCA may be associated with diarrhea and hepatotoxicity in a significant number of patients. Combination therapy with both agents reduces the cost and diminishes side effects without substantially affecting dissolution rates. The ideal patient for oral dissolution is not obese and has small (less than 1 cm), floating stones. Success rates in such patients are as high as 70% total dissolution at 1 year. Biliary colic is alleviated in the majority of patients, even those who do not have complete dissolution. Gallstone recurrence is about 10% per year over the first 5 years, and the role of maintenance therapy is unclear. Gallstones, when they recur, are often small and again symptomatic.

[edit] Contact Dissolution Therapy.

Direct instillation into the gallbladder of powerful cholesterol-solubilizing solvents, such as methyltertbutyl ether (MTBE) and ethyl propionate (EP), has been associated with almost 100% dissolution of cholesterol gallstones. A major drawback of this therapy is the need to catheterize the gallbladder directly by a radiologically placed percutaneous catheter. MTBE is more toxic and volatile than EP and can cause damage to the duodenal mucosa, with drowsiness and hemolysis when systemically absorbed. Automated pump systems can decrease operator and patient contact with the solvents, reduce spillage of solvent from the gallbladder, and result in complete dissolution of large stones in hours. If delivery systems can be further perfected, this therapy may benefit critically ill patients unable to withstand surgery.

[edit] Extracorporeal Shock Wave Lithotripsy and Oral Bile Acid Therapy.

ESWL is similar to that used for fragmentation of renal calculi. Shock waves are produced by lithotriptors and delivered to the gallbladder using ultrasonic guidance. Oral bile acid therapy is begun simultaneously because the resulting stone fragments are more amenable to dissolution therapy and because such therapy promotes bile acid flow for enhanced clearance of stone fragments. ESWL has had variable success; experience in the United States has demonstrated 50% stone clearance, compared with greater than 90% in West Germany.^[9] Successful lithotripsy is more likely to occur when stones are radiolucent, solitary, and less than 2 cm in size. Normal gallbladder motility is required for fragment passage. Although the addition of ESWL to dissolution therapy for large stones is theoretically better than either alone, ESWL has risks. Through the process of fragmentation, larger stones become smaller and may more easily pass into the cystic and common bile ducts, where they may cause acute obstruction. In the 6 months after ESWL, severe biliary pain was noted in 1.5%, acute cholecystitis in 1.0%, and acute pancreatitis in 1.5% of patients. Also, the high costs of lithotriptors have made access prohibitive for many centers. Because of these factors, ESWL has not gained its initially expected acceptance.

[edit] Complications

[edit] Acute Cholecystitis.

Acute inflammation of the gallbladder and adjacent peritoneum usually occurs as a result of a stone impaction within the cystic duct. Affected individuals have a history of biliary colic. The pain associated with cholecystitis is similar in location to colic but is usually more severe and persistent, lasting at least 6 hours. In the absence of complications such as gangrene or perforation, fevers are usually low grade and rigors uncommon. The right upper quadrant is very tender, and localized rebound may be present. On examination the patient cannot take a deep breath while the physician's hand is palpating the right upper quadrant because of increased pain as the gallbladder descends to touch the hand (Murphy's sign). Bilirubin levels may be elevated, but jaundice is rare. Transaminase levels are rarely greater than three times normal. Leukocytosis with band forms is common. Radiologic imaging is recommended to confirm the diagnosis and to rule out complications such as gallbladder perforation or gangrenous cholecystitis. Ultrasound usually demonstrates stones, gallbladder distention, wall thickening, and localized edema but is often nondiagnostic. Cholescintigraphy, using^99mTc-hepatic iminodiacetic acid (HIDA) analogs, is more sensitive than ultrasound for uncomplicated cholecystitis, characteristically demonstrating nonvisualization of the gallbladder in patients with acute cholecystitis. In most cases, however, ultrasound is usually recommended before HIDA scanning because of its added sensitivity in evaluating the anatomy adjacent to the gallbladder. Although most patients with acute cholecystitis respond to conservative management, surgery is recommended because of the high recurrence rate and significant incidence of complications. In patients with a prohibitively high acute surgical risk, a drainage tube can be placed by radiologic guidance into the gallbladder (percutaneous cholecystostomy) during the acute period.

Complications of acute cholecystitis include gangrenous cholecystitis, emphysematous cholecystitis, and gallbladder perforation. Although their presentation is usually associated with a higher incidence of fevers, rigors, and peritoneal signs, these problems may not appear different from those in uncomplicated cholecystitis and thus may not be suspected before surgery. These complications have a significantly increased incidence of morbidity and mortality that necessitates emergency surgery. Gangrenous cholecystitis implies necrosis of the gallbladder wall. The diagnosis is suggested during cholescintigraphy by visualization of a rim of increased radioactivity around the gallbladder and within the adjacent hepatic parenchyma. Diabetic and elderly patients appear to be at increased risk of developing emphysematous cholecystitis, a severe form of acute cholecystitis associated with gas-forming organisms, particularly Clostridium perfringens. Emphysematous cholecystitis is suggested by the findings of gas bubbles within the gallbladder wall or lumen on plain radiographs and by irregular, indistinct shadowing from the gallbladder on ultrasound (Fig. 103-4). All diabetic persons with symptoms of acute cholecystitis should have a plain film of the abdomen to search for emphysema. Gangrenous and emphysematous forms of cholecystitis greatly increase the risk of gallbladder perforation.

Figure 103-4 Ultrasound demonstration of air within lumen of gallbladder and adjacent hepatic parenchyma in diabetic patient with emphysematous cholecystitis.

Other complications of calculous cholecystitis include gallstone ileus, a gallstone obstruction of the distal small bowel that usually results from erosion of a gallstone through the gallbladder wall into the duodenal bulb. The most common site of bowel obstruction is the ileocecal valve. Bouveret's syndrome occurs when the stone obstructs the duodenal bulb, producing gastric outlet obstruction. Another rare complication of cholecystitis is Mirizzi's syndrome, in which bile duct obstruction occurs secondary to stone impaction within the cystic duct when the impacted stone and its secondary inflammatory mass impinge on the lumen of the adjacent bile duct.

[edit] Choledocholithiasis.

Stones within the bile duct usually originate in the gallbladder but may arise de novo (see earlier discussion on brown pigment stones). Up to 15% of patients with cholelithiasis develop choledocholithiasis. Although it is occasionally asymptomatic, the characteristic presentation is jaundice and cholestatic biochemical serum studies. Bilirubin levels rise in proportion to the degree of obstruction, are primarily the direct (conjugated) form, and may be elevated 20 to 30 times normal values. Alkaline phosphatase levels are usually three to six times normal but may be only mildly elevated. In contrast to the generally benign course in most patients with incidentally found gallbladder stones, 25% to 50% of patients with bile duct stones may develop serious complications of obstruction (i.e., cholangitis, gallstone pancreatitis); therefore bile duct stones should always be removed.

Radiologic identification of biliary tract stones is not as sensitive as for gallstones. Ultrasound examinations demonstrate stones within the bile duct in 20% to 50% of cases but have an 80% sensitivity for demonstrating bile duct dilation, a marker for extrahepatic obstruction. Magnetic resonance cholangiography (MRCP) is a novel technique with an ability to detect small stones in the gallbladder comparable to more invasive tests such as ERCP. In experienced centers, MRCP can detect more than 90% of common bile duct stones greater than 5 mm in size. Bile duct dilation occurs in virtually all cases of chronic obstruction (i.e., malignancy) but may take up to 2 weeks to develop in some patients with acute obstruction from stones. Thus a patient with acute obstruction who initially had nondilated ducts on ultrasound may benefit from repeating the examination 2 weeks later. Cholangiography is the most sensitive test for identification of dilation, stones, and other causes of obstruction. Cholangiography can be performed by the gastroenterologist (ERCP), the radiologist (percutaneous transhepatic cholangiography [PTC]), or the surgeon during surgery. ERCP and PTC have very high success rates, can be performed in elective and emergency situations, and can obviate the need for surgery. ERCP is successful in obtaining a cholangiogram in more than 90% of cases and is generally preferred by most patients and physicians because it is more comfortable for the patient and allows for therapeutic intervention during the same session.

Endoscopic stone removal is performed by making a small cut in the ampulla, a sphincterotomy, to enlarge this opening to the bile duct. A basket or balloon can then be introduced into the bile duct through the ERCP scope to clear the duct of stones. In the hands of an experienced endoscopist, this procedure has an 85% to 90% success rate, with complications such as pancreatitis, perforation, and bleeding occurring in 2% to 5% of cases. The most common complication, pancreatitis, occurs in approximately 2% and is usually mild.

PTC is successful in demonstrating the bile ducts in more than 95% of cases when the intrahepatic ducts are dilated but significantly less when they are not. Stones can be removed by choledocholithotomy, but several weeks are required to form a dilated tract across the liver and into the bile duct, through which the stone can be removed or manipulated.

[edit] Cholangitis.

The biliary tree is normally an open, sterile system that behaves as a closed system when obstructed. Regardless of the cause of obstruction, impaired biliary excretion into the intestine results in jaundice and the spilling of conjugated bilirubin into the urine. When bacteria are introduced into the system, as occurs often with stones and occasionally with malignancy, the resulting closed system behaves as an abscess. In addition to jaundice, the patient develops significant inflammation of the bile duct, often with abdominal pain, intermittent fevers and rigors, and jaundice. These three form the classic symptom triad of cholangitis, referred to as Charcot's triad. Although obstructive cholangitis is frequently referred to as pus under pressure, frank pus (suppuration) is not usually seen within the bile duct. The term suppurative cholangitis, however, is used to refer to severe cholangitis, regardless of the presence or absence of pus. This condition is an emergency, requiring emergency ductal decompression. Reynold's pentad, which adds hypotension and altered mental status to the signs of Charcot's triad, is considered pathognomonic for suppurative cholangitis. Clinical findings suspicious for suppurative cholangitis include fever above 104° F, hypotension, abdominal rebound, leukocytosis greater than 20,000/mm³, and bilirubin over 9 mg/dl. A mortality rate of 40% has been associated with suppurative cholangitis, compared with 10% in the less toxic cases.

The intermittent fevers and rigors seen with cholangitis are presumed to result from bacteremia. Although the bile in 90% of affected individuals contains many different microbes, blood cultures are positive in 40% of patients and usually for only one strain of organism. The most common organisms are Escherichia coli (60%), Klebsiella pneumoniae (30% to 40%), Bacteroides fragilis (5% to 10%), and Enterococcus faecalis (5% to 10%). Initial antibiotic therapy is usually broad based and empiric to cover these organisms. Antibiotic coverage should also be widened to include Pseudomonas aeruginosa, if the patient has recently had an ERCP, since scope contamination by P. aeruginosa has been reported. Although all patients should receive antibiotic and intravenous fluids, the mainstay of treatment is biliary decompression. This can be achieved by ERCP with sphincterotomy or stone extraction, by stenting (placing a drainage tube across the site of obstruction via the endoscope), by PTC, or by surgery. ERCP or PTC should be used initially. Even when the condition cannot be cured (i.e., by removal of stones), these treatments may allow for long-term palliation of an otherwise moribund patient.

[edit] Gallstone Pancreatitis.

Overall, approximately 40% of cases of acute pancreatitis are related to choledocholithiasis. Surgical series have demonstrated stones within the biliary tree in up to 75% of patients during the initial presentation of presumed gallstone pancreatitis but in as few as a third of such patients if evaluated after their pancreatitis has improved. The mechanism of pancreatic injury may be that of elevated pressure within the pancreatic duct as a result of more distal obstruction from stones and secondary inflammation.

The physician should suspect “gallstone” pancreatitis when a patient with acute, often recurrent pancreatitis has a present or past history of gallstones or common bile duct stones, especially when there are no other known risk factors for pancreatitis. Although patients classically complain of epigastric pain radiating to the back with nausea, vomiting, and anorexia, the symptoms and physical findings may be difficult to differentiate from those of acute cholecystitis. Acute cholecystitis occurs concomitantly with gallstone pancreatitis 5% of the time, so serum amylase levels should be measured in all patients with presumed cholecystitis. Elevation of alkaline phosphatase or bilirubin levels at the onset of an attack of pancreatitis often suggests gallstone pancreatitis but may also occur secondary to compression of the intrapancreatic portion of the common bile duct as it passes through an inflamed pancreas.

The diagnosis of gallstone pancreatitis is confirmed by cholangiography, usually by ERCP. Since the optimal timing for ERCP and possible sphincterotomy was controversial, however, studies compared early (within 24 to 72 hours of admission) vs. late ERCP with or without papillotomy for pancreatitis presumed secondary to choledocholithiasis. Complications, including biliary sepsis and death, were reduced when ERCP was performed early in patients with moderate to severe pancreatitis. A similar effect was shown for mild pancreatitis as well. When performed within 72 hours of admission in patients with severe pancreatitis, early intervention with ERCP also significantly reduced the length of hospitalization.^[10]

Based on these results, the present recommendation is ERCP with possible sphincterotomy performed within 48 hours of the onset of moderate to severe pancreatitis presumed secondary to choledocholithiasis. The treatment of mild pancreatitis is primarily supportive care. Affected patients require aggressive fluid resuscitation because of sequestration of fluids into the inflamed retroperitoneum and their inability to eat. Conservative management alone in patients with mild pancreatitis is associated with a success rate of approximately 80%.

[edit] ACALCULOUS DISEASES OF THE GALLBLADDER

[edit] Acute Acalculous Cholecystitis

Overall, approximately 5% to 15% of patients with acute cholecystitis have acalculous disease, but estimates are as high as 87% and 50%, respectively, in patients with acute cholecystitis postoperatively and in children. Most patients are older (over 55), and gender does not affect the incidence. Acalculous cholecystitis is most often seen in the intensive care unit in patients with multiorgan system failure, trauma (especially after major surgery), burns, and sepsis. Although in most patients the pathogenesis is unclear and is likely multifactorial in origin, the process is believed to be one of secondary infection in a functionally obstructed gallbladder. Rarely, primary infections of the gallbladder with Salmonella and Candida organisms and cytomegalovirus may cause this condition in patients with severe immunosuppression.

Regardless of the etiology, however, the clinical scenario is similar to that of acute calculous cholecystitis. Patients may become bacteremic and septic if the condition is not treated promptly. Delays in diagnosis or treatment have led to a high incidence of complications (e.g., gangrene, empyema, perforation) before surgery. The mortality rate may be at least twice as high in acalculous cholecystitis as in calculous disease because of the high incidence of comorbid conditions and the delay in diagnosis. The timely diagnosis of acute acalculous cholecystitis requires awareness of this entity and suspicion. Laboratory findings are similar to those seen in acute calculous cholecystitis; most patients demonstrate leukocytosis and mild elevations in the alkaline phosphatase, bilirubin, and transaminase levels. HIDA scanning confirms the diagnosis, and ultrasound may detect complications. Optimal treatment is emergency cholecystectomy, but a percutaneous cholecystectomy is alternative therapy in patients with extremely high surgical risk.

[edit] Hyperplastic Cholecytoses

Hyperplastic cholecytoses represent abnormalities of the gallbladder wall with an unclear etiology. They are usually clinically silent but may be associated with symptoms of cholelithiasis that respond to cholecystectomy. These conditions may be associated with the formation of nodules. When large in size, they may present as a fundal “polyp” on gallbladder ultrasound or oral cholecystogram. The most common forms of hyperplastic cholecytoses are cholesterolosis and adenomyomatosis. Gallbladder cholesterolosis, or cholesterosis, involves deposition of triglycerides and cholesterol within the gallbladder wall. These yellowish deposits lying within a mildly inflamed, reddened background have given rise to the term strawberry gallbladder. The deposits may form small polypoid projections that can break off and serve as seeds for gallstone formation. Gallstones are seen in 10% to 15% of patients with cholesterolosis, but this condition is present in a minority of all patients with gallstones. Adenomyomatosis, or adenomyosis, implies hyperplasia of the gallbladder mucosa and muscular coat. Gallbladder wall thickening can increase three to five times that of normal gallbladders. Intramural diverticula, crypts, or sinus tracts (Rokitansky-Aschoff sinuses) may be seen on ultrasound of the gallbladder, and adenomyosis may present as localized, segmental, or diffuse disease. The localized disease may produce a nodule that is sometimes referred to as an adenomyoma, a pseudotumor with no potential for neoplasia. The segmental form produces a constricting ring or septum in the fundus or body, and the diffuse form produces generalized thickening of the gallbladder wall. Hyalocalcinosis, also referred to as the porcelain gallbladder because of its eggshell appearance on plain film, ultrasound, or computed tomography (CT) scan, has been associated with a 22% chance of developing gallbladder cancer. Prophylactic cholecystectomy is generally recommended in these patients.

[edit] GALLBLADDER NEOPLASIA

Gallbladder cancer is the fifth most frequent digestive tract cancer. Epidemiologic studies have demonstrated an association between gallbladder cancer and gallstones. The risk associated with stones larger than 3 cm is estimated to be nine times that of 1-cm stones. Certain ethnic groups, in particular Native Americans and Mexicans, have increased risk over the general population. The risk is also increased in patients with the porcelain gallbladder and with anomalous connections between biliary and pancreatic ducts.

Primary gallbladder cancers are usually adenocarcinomas and are thought to arise in adenomatous polyps. Polyp size appears to be an important risk factor for the presence of carcinoma. In one study, all benign adenomas were less than 12 mm in diameter, whereas those with carcinomatous foci were greater than 12 mm. Most invasive carcinomas were more than 30 mm in diameter. The prognosis associated with gallbladder cancer is uniformly poor when the process has extended beyond the gallbladder wall, with 5-year survival rates of less than 5%. Although distant metastasis of the tumors occurs late, aggressive local extension of the disease along the biliary tract and into the liver is seen very early. This, in combination with late diagnosis, accounts for the poor survival. In general, surgery is curative only when a carcinoma is found incidentally during routine cholecystectomy for other indications. Curative surgery often involves not only cholecystectomy but also segmental or local liver resection. Because of the aggressive nature of this disease, its poor outcome, and the inability radiologically to differentiate early gallbladder cancers arising in a polyp from benign polyps or pseudotumors (as may occur in the hypertrophic cholecystoses), cholecystectomy should be performed when ultrasound or CT scanning demonstrates a focal, irregular thickening of the gallbladder wall or a polyp. Prophylactic cholecystectomy should be considered in patients with porcelain gallbladders and perhaps in young Native Americans with very large gallstones. Chemotherapeutic trials for gallbladder cancer have demonstrated no benefit. The use of external beam radiation therapy and local radiotherapy using implantable iridium (¹⁹²Ir) wires for patients with localized disease and pain or jaundice is being evaluated.

[edit] REFERENCES