Data on the prevalence of gallstones in the United States indicate that only about 30% of people with cholelithiasis come to surgery. Symptoms of gallstone disease generally do not change in severity. Each year, about 2% of patients with asymptomatic gallstones develop symptoms, usually biliary colic rather than one of the complications of gallstone disease. Patients with chronic biliary colic tend to have symptoms of the same level of severity and frequency. The present practice of operating only on symptomatic patients, leaving the millions without symptoms alone, seems appropriate. A question is often raised about what to advise the asymptomatic patient found to have gallstones during the course of unrelated studies. The presence of either of the following portends a more serious course and should probably serve as a reason for prophylactic cholecystectomy: (1) large stones (> 2 cm in diameter), because they produce acute cholecystitis more often than small stones; and (2) a calcified gallbladder, because it so often is associated with carcinoma. However, most asymptomatic patients have no special features. If coexistent cardiopulmonary or other problems increase the risk of surgery, operation should not be considered. For the average asymptomatic patient, it is not reasonable to make a strong recommendation for cholecystectomy. The tendency, however, is to operate on younger patients and temporize in the elderly.
GALLSTONES & CHRONIC CHOLECYSTITIS (BILIARY COLIC)
Chronic cholecystitis is the most common form of symptomatic gallbladder disease and is associated with gallstones in nearly every case. In general, the term cholecystitis is applied whenever gallstones are present regardless of the histologic appearance of the gallbladder. Repeated minor episodes of obstruction of the cystic duct cause intermittent biliary colic and contribute to inflammation and subsequent scar formation. Gallbladders from symptomatic patients with gallstones who have never had an attack of acute cholecystitis are of two types: (1) In some, the mucosa may be slightly flattened, but the wall is thin and unscarred and, except for the stones, appears normal. (2) Others exhibit obvious signs of chronic inflammation, with thickening, cellular infiltration, loss of elasticity, and fibrosis. The clinical history in these two groups cannot always be distinguished, and inflammatory changes may also be found in patients with asymptomatic gallstones.
Biliary colic, the most characteristic symptom, is caused by transient gallstone obstruction of the cystic duct. The pain usually begins abruptly and subsides gradually, lasting for a few minutes to several hours. The pain of biliary colic is usually steady—not intermittent, like that of intestinal colic. In some patients, attacks occur postprandially; in others, there is no relationship to meals. The frequency of attacks is quite variable, ranging from nearly continuous trouble to episodes many years apart. Nausea and vomiting may accompany the pain.
Biliary colic is usually felt in the right upper quadrant, but epigastric and left abdominal pain are common, and some patients experience precordial pain. The pain may radiate around the costal margin into the back or may be referred to the region of the scapula. Pain on top of the shoulder is unusual and suggests direct diaphragmatic irritation. In a severe attack, the patient usually curls up in bed, changing position frequently in order to be more comfortable.
During an attack, there may be tenderness in the right upper quadrant, and, rarely, the gallbladder is palpable.
Fatty food intolerance, dyspepsia, indigestion, heartburn, flatulence, nausea, and eructations are other symptoms associated with gallstone disease. Because they are also frequent in the general population, their presence in any given patient may only be incidental to the gallstones.
An ultrasound scan of the gallbladder should usually be the first test. Gallstones can be demonstrated in about 95% of cases, and a positive reading for gallstones is almost never in error.
About 2% of patients with gallstone disease have normal ultrasound studies. Therefore, if the clinical suspicion of gallbladder disease is high and these two tests are negative, the patient should be studied by ERCP (to opacify the gallbladder in the search for stones) or duodenal intubation and examination of duodenal bile for cholesterol crystals or bilirubinate granules.
Gallbladder colic may be strongly suggested by the history, but the clinical impression should always be verified by an ultrasound study. Biliary colic may simulate the pain of duodenal ulcer, hiatal hernia, pancreatitis, and myocardial infarction.
An EKG and a chest x-ray should be obtained to investigate cardiopulmonary disease. It has been suggested that biliary colic may sometimes aggravate cardiac disease, but angina pectoris or an abnormal EKG should rarely be indications for cholecystectomy.
Right-sided radicular pain in the T6-T10 dermatomes may be confused with biliary colic. Osteoarthritic spurs, vertebral lesions, or tumors may be shown on x-rays of the spine or may be suggested by hyperesthesia of the abdominal skin.
An upper gastrointestinal series may be indicated to search for esophageal spasm, hiatal hernia, peptic ulcer, or gastric tumors. In some patients, the irritable colon syndrome may be mistaken for gallbladder discomfort. Carcinoma of the cecum or ascending colon may be overlooked on the assumption that postprandial pain in these conditions is due to gallstones.
Chronic cholecystitis predisposes to acute cholecystitis, common duct stones, and adenocarcinoma of the gallbladder. The longer the stones have been present, the higher the incidence of all of these complications. Complications are infrequent, however, and the presence of gallstones is not reason enough for prophylactic cholecystectomy in a person with asymptomatic or mildly symptomatic disease.
Avoidance of offending foods may be helpful.
Cholesterol gallstones in the gallbladder can be dissolved in some cases by chronic treatment with ursodiol, which reduces the cholesterol saturation of bile by inhibiting cholesterol secretion. The resulting undersaturated bile slowly dissolves the solid cholesterol in the gallstones.
Unfortunately, bile salt therapy has marginal efficacy. The gallstones must be small (eg, < 5 mm) and devoid of calcium (ie, nonopaque on CT scans), and the gallbladder must opacify on oral cholecystography (an indication of unobstructed flow of bile between bile duct and gallbladder). About 15% of patients with gallstones are candidates for treatment. Dissolution is achieved within 2 years in about 50% of highly selected patients. Stones recur, however, in 50% of cases within 5 years. In general, dissolution therapy—alone or in conjunction with lithotripsy—is used very rarely except in the prevention of gallstones in susceptible populations, such as following weight loss surgery.
Cholecystectomy is indicated in most patients with symptoms. The procedure can be scheduled at the patient’s convenience, within weeks or months after diagnosis. Active concurrent disease that increases the risk of surgery should be treated before operation. In some chronically ill patients, surgery should be deferred indefinitely.
Cholecystectomy is most often performed laparoscopically, but when the laparoscopic approach is contraindicated (eg, too many adhesions) or unsuccessful, it may be performed through a laparotomy. The difference consists of 4 fewer days in the hospital and fewer weeks off work when done laparoscopically. Regardless of how it is done, operative cholangiography may be included to evaluate for common duct stones. If stones are found, common duct exploration may be performed (see under choledocholithiasis).
Serious complications and deaths related to the operation itself are rare. The operative death rate is about 0.1% in patients under age 50 and about 0.5% in patients over age 50. Most deaths occur in patients recognized preoperatively to have increased risks. The operation relieves symptoms in 95% of cases.
BR Early versus delayed laparoscopic cholecystectomy for uncomplicated biliary colic. Cochrane Database Syst Rev 2013 Jun 30 ;6:CD007196.
ESSENTIALS OF DIAGNOSIS
Acute right upper quadrant pain and tenderness
Fever and leukocytosis
Palpable gallbladder in one-third of cases
Nonopacified gallbladder on radionuclide excretion scan
Sonographic Murphy sign
In 80% of cases, acute cholecystitis results from obstruction of the cystic duct by a gallstone impacted in Hartmann’s pouch. The gallbladder becomes inflamed and distended, creating abdominal pain and tenderness. The natural history of acute cholecystitis varies, depending on whether the obstruction becomes relieved, the extent of secondary bacterial invasion, the age of the patient, and the presence of other aggravating factors such as diabetes mellitus. Most attacks resolve spontaneously without surgery or other specific therapy, but some progress to abscess formation or free perforation with generalized peritonitis.
The pathologic changes in the gallbladder evolve in a typical pattern. Subserosal edema and hemorrhage and patchy mucosal necrosis are the first changes. Later, PMNs appear. The final stage involves development of fibrosis. Gangrene and perforation may occur as early as 3 days after onset, but most perforations occur during the second week. In cases that resolve spontaneously, acute inflammation has largely cleared by 4 weeks, but some residual evidence of inflammation may last for several months. About 90% of gallbladders removed during an acute attack show chronic scarring, although many of these patients deny having had any previous symptoms.
The cause of acute cholecystitis is still partially conjectural. Obstruction of the cystic duct is present in most cases, but in experimental animals, cystic duct obstruction does not result in acute cholecystitis unless the gallbladder is filled with concentrated bile or bile saturated with cholesterol. There is also evidence that trauma from gallstones releases phospholipase from the mucosal cells of the gallbladder. This is followed by conversion of lecithin in bile to lysolecithin, which is a toxic compound that may cause more inflammation. Bacteria appear to have a minor role in the early stages of acute cholecystitis, even though most complications of the disease involve suppuration.
About 20% of cases of acute cholecystitis occur in the absence of cholelithiasis (acalculous cholecystitis). Some of these are due to cystic duct obstruction by another process such as a malignant tumor. Rarely, acute acalculous cholecystitis results from cystic artery occlusion or primary bacterial infection by Escherichia coli, clostridia, or, occasionally, Salmonella typhi. Most cases occur in patients hospitalized with some other illness; acute acalculous cholecystitis is particularly common in trauma victims (civilian or military) and in patients receiving total parenteral nutrition. Small-vessel occlusion occurs early, and unless treatment is given promptly, the disease progresses rapidly to gangrenous cholecystitis and septic complications, at which point the death rate is high.
The first symptom is abdominal pain in the right upper quadrant, sometimes associated with referred pain in the region of the right scapula. In 75% of cases, the patient will have had previous attacks of biliary colic, at first indistinguishable from the present illness. However, in acute cholecystitis, the pain persists and becomes associated with abdominal tenderness. Nausea and vomiting are present in about half of patients, but the vomiting is rarely severe. Mild icterus occurs in 10% of cases. The temperature usually ranges from 38°C to 38.5°C. High fever and chills are uncommon and should suggest the possibility of complications or an incorrect diagnosis.
Right upper quadrant tenderness is present, and in about a third of patients the gallbladder is palpable (often in a position lateral to its normal one). Voluntary guarding during examination may prevent detection of an enlarged gallbladder. In others, the gallbladder is not enlarged because scarring of the wall restricts distention. If instructed to breathe deeply during palpation in the right subcostal region, the patient experiences accentuated tenderness and sudden inspiratory arrest (Murphy sign).
The leukocyte count is usually elevated to 12,000-15,000/mL. Normal counts are common, but if the count goes much above 15,000, one should suspect complications. A mild elevation of the serum bilirubin (in the range of 2-4 mg/dL) is common, presumably owing to secondary inflammation of the common duct by the contiguous gallbladder. Bilirubin values above this range would most likely indicate the associated presence of common duct stones. A mild increase in alkaline phosphatase may accompany the attack. Occasionally, the serum amylase concentration transiently reaches 1000 units/dL or more.
A plain x-ray of the abdomen may occasionally show an enlarged gallbladder shadow. In 15% of patients, the gallstones contain enough calcium to be seen on the plain film.
Ultrasound scans show gallstones, sludge, and thickening of the gallbladder wall, and the ultrasonographer can determine even better than the clinician whether the point of maximum tenderness is over the gallbladder (ultrasonographic Murphy sign). This last finding is often absent, however, when the gallbladder is gangrenous. Usually, ultrasound is the only test needed to make the diagnosis of acute cholecystitis.
If additional diagnostic information is desirable (eg, if ultrasound is equivocal or negative), a radionuclide excretion scan (eg, HIDA scan) should be performed. This test cannot demonstrate gallstones, but if the gallbladder is imaged, acute cholecystitis is ruled out except in rare cases of acalculous cholecystitis (the test is positive in most cases of acute acalculous cholecystitis). Imaging of the duct but not the gallbladder supports the diagnosis of acute cholecystitis. A few false positives are seen in advanced gallstone disease without acute inflammation and in acute biliary pancreatitis.
The differential diagnosis includes other common causes of acute upper abdominal pain and tenderness. An acute peptic ulcer with or without perforation might be suggested by a history of epigastric pain relieved by food or antacids. Most cases of perforated ulcer demonstrate free air under the diaphragm on an x-ray. An emergency upper gastrointestinal series may help.
Acute pancreatitis can be confused with acute cholecystitis, especially if cholecystitis is accompanied by an elevated amylase level. Furthermore, HIDA scans fail to outline the gallbladder in most cases of acute biliary pancreatitis. Sometimes the two diseases coexist, but pancreatitis should not be accepted as a second diagnosis without specific findings.
Acute appendicitis in patients with a high cecum may closely simulate acute cholecystitis.
Severe right upper quadrant pain with high fever and local tenderness may develop in acute gonococcal perihepatitis (Fitz–Hugh–Curtis syndrome). Clues to the proper diagnosis may be found in tenderness in the adnexa, vaginal discharge that shows gonococci on a Gram-stained smear, and a disparity between the patient’s high fever and her general lack of toxicity.
The major complications of acute cholecystitis are empyema, gangrene, and perforation.
In empyema (suppurative cholecystitis), the gallbladder contains frank pus, and the patient becomes more toxic, with high spiking fever (39-40°C, chills, and leukocytosis greater than 15,000/mL. Parenteral antibiotics should be given, and percutaneous cholecystostomy or cholecystectomy should be performed.
Perforation may take any of three forms: (1) localized perforation with pericholecystic abscess; (2) free perforation with generalized peritonitis; and (3) perforation into an adjacent hollow viscus, with the formation of a fistula. Perforation may occur as early as 3 days after the onset of acute cholecystitis or not until late in the second week. The total incidence of perforation is about 10%.
1. Pericholecystic abscess
Pericholecystic abscess, the most common form of perforation, should be suspected when the signs and symptoms progress, especially when accompanied by the appearance of a palpable mass. The patient often becomes toxic, with fever to 39°C and a leukocyte count above 15,000/mL, but sometimes there is no correlation between the clinical signs and the development of local abscess. Cholecystectomy and drainage of the abscess can be performed safely in many of these patients, but if the patient’s condition is unstable, percutaneous cholecystostomy is preferable.
Free perforation occurs in only 1%-2% of patients, most often early in the disease when gangrene develops before adhesions wall off the gallbladder. The diagnosis is made preoperatively in less than half of cases. In some patients with localized pain, sudden spread of pain and tenderness to other parts of the abdomen suggests the diagnosis. Whenever it is suspected, free perforation must be treated by emergency laparotomy. Abdominal paracentesis may be misleading and has proved to be of little diagnostic usefulness. Cholecystectomy should be performed if the patient’s condition will permit; otherwise, cholecystostomy is done. The death rate depends partly on whether the cystic duct remains obstructed or the stone becomes dislodged after perforation. The former leads to a purulent peritonitis that is lethal in 20% of cases. In the latter, a true bile peritonitis ensues and over 50% of patients die. The earlier operation is performed, the better the prognosis.
3. Cholecystenteric fistula
If the acutely inflamed gallbladder becomes adherent to adjacent stomach, duodenum, or colon and necrosis develops at the site of one of these adhesions, perforation may occur into the lumen of the gut. The resulting decompression often allows the acute disease to resolve. If the gallbladder stones discharge through the fistula and if they are large enough, they may obstruct the small intestine (gallstone ileus; see below). Rarely, patients vomit gallstones that have entered the stomach through a cholecystogastric fistula. In most patients, the acute attack subsides and the cholecystenteric fistula is clinically unsuspected.
Cholecystenteric fistulas do not usually cause symptoms unless the gallbladder is still partially obstructed by stones or scarring. Neither oral nor intravenous cholangiograms will opacify the gallbladder or the fistula, but the latter may be shown on upper gastrointestinal series, where it must be differentiated from a fistula due to perforated peptic ulcer. Malabsorption and steatorrhea have been reported in isolated cases of cholecystocolonic fistulas. Steatorrhea in this situation could be due either to absence of bile in the proximal bowel following diversion into the colon or, more rarely, to excess bacteria in the upper intestine.
Symptomatic cholecystenteric fistulas should be treated by cholecystectomy and closure of the fistula. The majority is discovered incidentally during cholecystectomy for symptomatic gallbladder disease.
Intravenous fluids should be given to correct dehydration and electrolyte imbalance, and a nasogastric tube should be inserted. For acute cholecystitis of average severity, parenteral cefazolin (2-4 g daily) should be given. Parenteral penicillin (20 million units daily), clindamycin, and an aminoglycoside should be given for severe disease. Single-drug therapy using imipenem is a good alternative.
There are acute options for the treatment of acute cholecystitis. Since the disease resolves with antibiotics and supportive care in about 60% of cases, one approach is to manage the patient expectantly, with a plan to perform elective cholecystectomy after recovery, reserving surgery during the acute attack for those with severe or worsening disease. This approach is untenable in acute acalculous cholecystitis.
The preferred plan is to perform cholecystectomy in all patients unless there are specific contraindications to operation (eg, serious concomitant disease). Four controlled trials have supported this approach with the following data: (1) the incidence of technical complications is no greater with early surgery; (2) early surgery reduces the total duration of illness by approximately 30 days, length of hospitalization by 5-7 days, and direct medical costs by several thousand dollars; and (3) the death rate is slightly lower with early surgery because of earlier treatment for some patients whose condition would have worsened during expectant management.
The following are the major factors that affect the decision (Figure 25–8): (1) whether the diagnosis is established; (2) the general health of the patient as modified by coexistent disease or the present illness; and (3) signs of local complications of acute cholecystitis. The diagnosis should be clear-cut and the patient optimally prepared; if perforation or empyema is suspected, emergency surgery is indicated.
Scheme for the management of acute cholecystitis.
In about 30% of cases, the diagnosis of acute cholecystitis is established but the general condition of the patient is unsatisfactory. If possible, surgery should be postponed in these cases until the ancillary disease is controlled. Expectant management cannot be rigidly adhered to, however, if the manifestations of cholecystitis worsen.
About 10% of patients require emergency treatment. These are generally clinical situations in which the disease appears to have become complicated or is about to. High fever (39°C), marked leukocytosis (> 15,000/mL), or chills suggest suppurative progression. Acalculous acute cholecystitis should automatically be placed in this category. When the patient’s general condition is poor, percutaneous catheter cholecystostomy is the preferable treatment. Patients in better overall health should be treated by cholecystectomy.
The sudden appearance of generalized abdominal pain may indicate free perforation. Appearance of a mass while the patient is under observation may be a sign of local perforation and abscess formation. Changes of this sort are indications for emergency surgery.
Cholecystectomy is the preferable operation in acute cholecystitis, and it can be performed laparoscopically in about 50% of patients. Operative cholangiography should be performed in most cases, and the common bile duct explored if appropriate indications are present (see section on choledocholithiasis). Patients with severe acute cholecystitis who are in poor condition for emergency cholecystectomy should be treated by percutaneous cholecystostomy. Percutaneous cholecystostomy may also be the preferred therapy for acute acalculous cholecystitis. A catheter inserted under ultrasound or CT guidance is allowed to drain the gallbladder of its bile or pus. The resulting decompression controls the acute disease, including any local infection, but the gallstones cannot be removed. Therefore, cholecystectomy should be performed after the patient recovers in order to avoid recurrent attacks. Cholecystectomy is definitive therapy in the patient with acalculous cholecystitis.
The overall death rate of acute cholecystitis is about 5%. Nearly all of the deaths are in patients over age 60 or those with diabetes mellitus. In the older age group, secondary cardiovascular or pulmonary complications contribute substantially to the death rate. Uncontrolled sepsis with peritonitis and intrahepatic abscesses are the most important local conditions responsible for death.
Common duct stones are present in about 15% of patients with acute cholecystitis, and some of the more seriously ill patients have simultaneous cholangitis from biliary obstruction. Acute pancreatitis may also complicate acute cholecystitis, and the combination carries a greater risk.
Patients who develop the suppurative forms of gallbladder disease such as empyema or perforation are less likely to recover. Earlier admission to the hospital and early cholecystectomy reduce the chances of these complications.
BR Early versus delayed laparoscopic cholecystectomy for uncomplicated biliary colic. Cochrane Database Syst Rev 2013 Jun 30 ;6:CD007196.
BR Percutaneous cholecystostomy for high-risk surgical patients with acute calculous cholecystitis. Cochrane Database Syst Rev 2013 Aug 12 ;8:CD007088.
Emphysematous cholecystitis is a rare condition in which bubbles of gas from anaerobic infection appear in the lumen of the gallbladder, its wall, the pericholecystic space, and, on occasion, the bile ducts. Clostridia species are the most commonly implicated organisms, but other gas-forming anaerobes such as E coli or anaerobic streptococci may be found. Three times as many men as women are affected, and 20% of patients have diabetes mellitus. In contrast to the usual form of acute cholecystitis, the disease probably is a bacterial infection from the earliest moment. In many cases, the gallbladder contains no stones.
The disease begins with sudden and rapidly progressive right upper quadrant pain. Fever and leukocytosis reach high levels quickly, and the patient is considerably more toxic than is usually the case in acute cholecystitis. On examination, a mass can usually be found in the right upper quadrant.
Plain films of the abdomen show tissue emphysema outlining the gallbladder and, in some cases, an air-fluid level in the lumen. The clinical and x-ray pictures are characteristic enough so that the diagnosis is usually obvious. If the changes on plain films are equivocal, a CT scan may bring them out.
The patient should be treated with high doses of antibiotics effective against clostridia and the other species mentioned above. Emergency surgical treatment should follow the initial resuscitative measures. Cholecystectomy can be safely performed in most cases, but the most critically ill might fare better with cholecystostomy. The types of complications are the same as in other forms of acute cholecystitis, but illness is more severe and death rates are higher.
BR Percutaneous cholecystostomy for high-risk surgical patients with acute calculous cholecystitis. Cochrane Database Syst Rev 2013 Aug 12 ;8:CD007088.
Gallstone ileus is mechanical intestinal obstruction caused by a large gallstone lodged in the lumen. It occurs more often in women, and the average patient age is about 70 years.
The patient usually presents with obvious small bowel obstruction, either partial or complete. The obstructing gallstone enters the intestine through a cholecystenteric fistula located in the duodenum, colon, or, rarely, the stomach or jejunum. The gallbladder may contain one or several stones, but stones that cause gallstone ileus are almost always 2.5 cm or more in diameter. The lumen in the proximal bowel will allow most of these large calculi to pass caudally until the ileum is reached. Obstruction of the large intestine may follow passage of a gallstone through a fistula at the hepatic flexure or may occur even after the stone has traversed the entire small bowel.
In most patients, the findings on physical examination are typical of distal small bowel obstruction. Obstruction of the duodenum or jejunum may give a perplexing clinical picture because of the lack of distention. Right upper quadrant tenderness and a mass may be present in some cases, but the distended abdomen may be difficult to examine accurately.
In addition to dilated small intestine, plain films of the abdomen may show a radiopaque gallstone, and unless one is alert to the possibility of gallstone ileus, the ectopic stone can be a puzzling finding. In about 40% of cases, careful examination of the film will reveal gas in the biliary tree, a manifestation of the cholecystenteric fistula. When the clinical picture is unclear, an upper gastrointestinal series should be obtained, which will demonstrate the cholecystoduodenal fistula and verify intestinal obstruction.
The proper treatment is emergency laparotomy and removal of the obstructing stone through a small enterotomy. The proximal intestine must be carefully inspected for the presence of a second calculus that might cause a postoperative recurrence. The gallbladder should be left undisturbed at the original operation.
Once the patient has recovered, an elective cholecystectomy should be scheduled if the patient complains of chronic gallbladder symptoms. On this basis, interval cholecystectomy will be required in about 30% of patients. The fistula itself is rarely the source of trouble and closes spontaneously in most patients.
The death rate from gallstone ileus remains about 20%, largely because of the poor general condition of elderly patients at the time of laparotomy. In many cases, the patient has developed cardiac or pulmonary complications during a preoperative delay when the diagnosis was unclear.
CHOLANGITIS (BACTERIAL CHOLANGITIS)
Bacterial infection of the biliary ducts always signifies biliary obstruction, since in the absence of obstruction even heavy bacterial contamination of the ducts fails to produce symptoms or pathologic changes. The block to flow may be partial or, less commonly, complete. The principal causes are choledocholithiasis, biliary stricture, and neoplasm. Less common causes are chronic pancreatitis, ampullary stenosis, pancreatic pseudocyst, duodenal diverticulum, congenital cyst, and parasitic invasion. Iatrogenic cholangitis may complicate transhepatic or T tube cholangiography. Not all obstructing lesions are followed by cholangitis, however. For example, biliary infection develops in only 15% of patients with neoplastic obstruction. The likelihood of cholangitis is greatest when the obstruction occurs after the duct has acquired a resident bacterial population.
With obstruction, ductal pressure rises, and bacteria proliferate and escape into the systemic circulation via the hepatic sinusoids. Experimentally, the incidence of positive blood cultures with ductal infection is directly proportionate to the absolute height of the pressure in the duct.
The symptoms of cholangitis (sometimes referred to as Charcot’s triad) are biliary colic, jaundice, and chills and fever, though a complete triad is present in only 70% of cases. Laboratory findings include leukocytosis and elevated serum bilirubin and alkaline phosphatase levels. The predominant organisms in bile (in approximately decreasing frequency) are E coli, Klebsiella, Pseudomonas, Enterococci, and Proteus. Bacteroides fragilis and other anaerobes (eg, Clostridium perfringens) can be detected in about 25% of cases, and their presence correlates with multiple previous biliary operations (often including a biliary enteric anastomosis), severe symptoms, and a high incidence of postoperative suppurative complications. Anaerobes are nearly always seen in the company of aerobes. Two species of bacteria can be cultured in about 50% of cases. Bacteremia probably occurs in most cases, and blood cultures obtained at the appropriate time contain the same organisms as the bile. Early in an attack, an ultrasound scan will often give useful diagnostic information. Further workup (THC, ERCP, etc) can proceed later after the acute manifestations are brought under control. Cholangiography is dangerous during active cholangitis.
The term suppurative cholangitis has been used for the most severe form of this disease, when manifestations of sepsis overshadow those of hepatobiliary disease. The diagnostic pentad of suppurative cholangitis consists of abdominal pain, jaundice, fever and chills, mental confusion or lethargy, and shock. The diagnosis is often missed because the signs of biliary disease are overlooked.
Most cases of cholangitis can be controlled with intravenous antibiotics. A cephalosporin antibiotic (eg, cefazolin, cefoxitin) is the drug of choice in the average mild to moderately severe case. If disease is severe or progressively worsens, an aminoglycoside plus clindamycin or metronidazole should be added to the regimen.
For patients with severe cholangitis or unremitting cholangitis despite antibiotic therapy, the bile duct must be promptly decompressed. Most cases of severe acute cholangitis are associated with choledocholithiasis, for which the best treatment consists of emergency endoscopic sphincterotomy. In the uncommon case where this is unsuccessful, laparotomy is indicated in order to decompress the bile duct. Cholangitis accompanying neoplastic obstruction may be managed by insertion of a transhepatic drainage catheter into the bile duct. A cholangiogram should not be obtained because the procedure could worsen sepsis.
Urgent intervention (eg, endoscopic sphincterotomy, percutaneous transhepatic drainage, or operative decompression) is required in about 10% of patients with acute cholangitis. The remaining 90% are eventually treated by elective surgery or endoscopic sphincterotomy following antibiotic therapy and a thorough diagnostic evaluation.
SM, the Tokyo Guidelines Revision Committee. TG13: updated Tokyo guidelines for the management of acute cholangitis and cholecystitis. J Hepatobiliary Pancreat Sci 2013 Jan;20(1):1–7.
Approximately 15% of patients with stones in the gallbladder harbor calculi within the bile ducts. Common duct stones are usually accompanied by others in the gallbladder, but in 5% of cases, the gallbladder is empty. The number of duct stones may vary from one to more than 100.
There are two possible origins for common duct stones. The evidence suggests that most cholesterol stones develop within the gallbladder and reach the duct after traversing the cystic duct. These are called secondary stones. Pigment stones may have a similar pedigree or, more often, develop de novo within the common duct. These are called primary common duct stones. About 60% of common duct stones are cholesterol stones and 40% are pigment stones. The latter are, on the average, associated with more severe clinical manifestations.
Patients may have one or more of the following principal clinical findings, all of which are caused by obstruction to the flow of bile or pancreatic juice: biliary colic, cholangitis, jaundice, and pancreatitis (Figure 25–9). It seems likely, however, that as many as 50% of patients with choledocholithiasis remain asymptomatic.
The natural history of common duct stones. Of every 100 patients with gallbladder stones, 15 will have common duct stones, which will produce the spectrum of syndromes illustrated. Note that the individual syndromes overlap, indicating that they may appear together in various combinations.
The common duct may dilate to 2-3 cm proximal to an obstructing lesion, and truly huge ducts develop in patients with biliary tumors. In choledocholithiasis or biliary stricture, the inflammatory reaction restricts dilation, so the dilatation is less marked. Dilation of the ductal system within the liver can also be limited by cirrhosis.
Biliary colic is the result of rapid rises in biliary pressure whether the block is in the common duct or neck of the gallbladder. Gradual occlusion of the duct—as in cancer—rarely produces the same kind of pain as gallstone disease.
Choledocholithiasis may be asymptomatic or may produce sudden toxic cholangitis, leading to a rapid demise. The seriousness of the disease parallels the degree of obstruction, the length of time it has been present, and the extent of secondary bacterial infection (see Cholangitis, above). Biliary colic, jaundice, or pancreatitis may be isolated findings or may occur in any combination along with signs of infection (cholangitis).
Biliary colic from common duct obstruction cannot be distinguished from that caused by stones in the gallbladder. The pain is felt in the right subcostal region, epigastrium, or even the substernal area. Referred pain to the region of the right scapula is common.
Choledocholithiasis should be strongly suspected if intermittent chills, fever, or jaundice accompanies biliary colic. Some patients notice transient darkening of their urine during an attack even though jaundice is not evident.
Pruritus is usually the result of persistent long-standing obstruction. The itching is more intense in warm weather when the patient perspires and is usually worse on the extremities than on the trunk. It is much more common with neoplastic obstruction than with gallstone obstruction.
The patient may be icteric and toxic, with high fever and chills, or may appear to be perfectly healthy. A palpable gallbladder is unusual in patients with obstructive jaundice from common duct stone because the obstruction is transient and partial, and scarring of the gallbladder renders it inelastic and nondistensible. Tenderness may be present in the right upper quadrant but is not often as marked as in acute cholecystitis, perforated peptic ulcer, or acute pancreatitis. Tender hepatic enlargement may occur.
In cholangitis, leukocytosis of 15,000/mL is usual, and values above 20,000/mL are common. A rise in serum bilirubin often appears within 24 hours after the onset of symptoms. The absolute level usually remains under 10 mg/dL, and most are in the range of 2-4 mg/dL. The direct fraction exceeds the indirect, but the latter becomes elevated in most cases. Bilirubin levels do not ordinarily reach the high values seen in malignant tumors because the obstruction is usually incomplete and transient. In fact, fluctuating jaundice is so characteristic of choledocholithiasis that it fairly reliably differentiates between benign and malignant obstruction.
The serum alkaline phosphatase level usually rises and may be the only chemical abnormality in patients without jaundice. When the obstruction is relieved, the alkaline phosphatase and bilirubin levels should return to normal within 1-2 weeks, with the exception that the former may remain elevated longer if the obstruction was prolonged.
Mild increases in AST and ALT are often seen with extrahepatic obstruction of the ducts; rarely, AST levels transiently reach 1000 units.
Radiopaque gallstones may be seen on plain abdominal films or CT scans. Ultrasound scans will usually show gallbladder stones and, depending on the degree of obstruction, dilatation of the bile duct. Ultrasound and CT scans are insensitive in the search for stones in the common duct. ERCP is indicated if the patient has had a previous cholecystectomy. If cholecystectomy has not been performed, cholangiography should be part of operative management. Some clinicians choose preoperative ERCP for patients scheduled for cholecystectomy in order to clear the common bile duct. If ERCP is not technically successful, the surgeon will be forced to convert to open common bile duct exploration to clear the duct of stones.
Bilirubin values above 10 mg/dL are so uncommon in choledocholithiasis that when this finding is present, cholangiography should be performed to rule out the possibility of neoplastic obstruction.
The workup should consider the same possibilities in differential diagnosis as for cholecystitis.
Serum amylase levels above 500 units/dL can result from acute pancreatitis, acute cholecystitis, or choledocholithiasis. Other manifestations of pancreatic disease should be documented before an unqualified diagnosis of pancreatitis is accepted.
Alcoholic cirrhosis or acute alcoholic hepatitis may present with jaundice, right upper quadrant tenderness, and leukocytosis. The differentiation from cholangitis may be impossible from clinical data. A history of a recent binge suggests acute liver disease. A percutaneous liver biopsy may be specific.
Intrahepatic cholestasis from drugs, pregnancy, chronic active hepatitis, or primary biliary cirrhosis may be difficult to distinguish from extrahepatic obstruction. ERCP would be appropriate to make the distinction, particularly if other studies (eg, ultrasound scan) failed to provide evidence of gallstone disease. If jaundice has persisted for 4-6 weeks, a mechanical cause is probable. Since most patients improve during this interval, persistent jaundice should never be assumed to be the result of parenchymal disease unless a normal cholangiogram rules out obstruction of the major ducts.
Intermittent jaundice and cholangitis after cholecystectomy are compatible with biliary stricture, and the distinction requires ERCP.
Biliary tumors usually produce intense jaundice without biliary colic or fever, and once it begins, the jaundice rarely remits.
Long-standing ductal infection can produce intrahepatic abscesses. Hepatic failure or secondary biliary cirrhosis may develop in unrelieved obstruction of long duration. Since the obstruction is usually incomplete and intermittent, cirrhosis develops only after several years in untreated disease. Acute pancreatitis, a fairly common complication of calculous biliary disease, is discussed in Chapter 26. Rarely, a stone in the common duct may erode through the ampulla, resulting in gallstone ileus. Hemorrhage (hemobilia) is also a rare complication.
Patients with acute cholangitis should be treated with systemic antibiotics and other measures as described in the preceding section; this usually controls the attack within 24-48 hours. If the patient’s condition worsens or if marked improvement is not observed within 2-4 days, endoscopic sphincterotomy or surgery and common bile duct exploration should be performed.
The typical patient presents with mild cholangitis and evidence on ultrasound scans of gallbladder stones. Laparoscopic cholecystectomy is indicated and, depending on the experience of the surgeon, laparoscopic exploration of the common duct if an operative cholangiogram or laparoscopic ultrasound demonstrates the expected common duct stones. Laparoscopic common duct exploration is usually accomplished through the cystic duct (which may have to be dilated), but when the common duct is enlarged (> 1.5 cm), it may be accomplished through a choledochotomy incision, just as in open surgery. Eventually, nearly all cases of common duct stones should be manageable by laparoscopic techniques, but at this stage the requisite laparoscopic skills are not available in most hospitals. If the surgeon thinks the common duct stones cannot be removed laparoscopically, it is probably best to remove the gallbladder laparoscopically and the common duct stones by endoscopic sphincterotomy. If the stones cannot be removed by sphincterotomy, a second (open) operation may be necessary.
There is also a lack of consensus regarding the importance of operative cholangiography or ultrasound during cholecystectomy when there are no clues suggesting stones in the duct. In such cases the chances of finding a stone are only 3%-5%, and some consider the effort unwarranted. On the other hand, operative cholangiograms also provide confirmation of the biliary anatomy, which contributes to avoidance of bile duct injuries, and the natural history of the few overlooked stones is worrisome. Therefore, we side with those who perform operative cholangiography liberally in such cases.
When the common duct is explored through the cystic duct and gallstones are removed, the cystic duct must be ligated, but a drainage catheter is not usually left within the common duct. When the common duct is explored through a choledochotomy (either during a laparoscopic or open operation), a T tube is usually left in the duct, and cholangiograms are taken a week or so postoperatively. Any residual stones discovered on these postoperative x-rays can be extracted 4-6 weeks later through the T tube tract.
Patients with common duct stones who have had a previous cholecystectomy are best treated by endoscopic sphincterotomy. Using a side-viewing duodenoscope, the ampulla is cannulated, and a 1-cm incision is made in the sphincter with an electrocautery wire. The opening created in the sphincter permits stones to pass from the duct into the duodenum. Endoscopic sphincterotomy is unlikely to be successful in patients with large stones (eg, > 2 cm), and it is contraindicated in the presence of stenosis of the bile duct proximal to the sphincter. Laparotomy and common duct exploration are required in a few cases.
Stones in the intrahepatic branches of the bile duct can usually be removed without difficulty during common duct exploration. In some cases, however, one or more of the intrahepatic ducts have become packed with stones, and the associated chronic inflammation has produced stenosis of the duct near its junction with the common hepatic duct. It is often impossible in these cases to clear the duct of stones, and if the disease involves only one lobe (usually the left lobe), hepatic lobectomy is indicated.
This term has been used to signify the heterogeneous group of disorders affecting patients who continue to complain of symptoms after cholecystectomy. It is not really a syndrome, and the term is confusing.
The usual reason for incomplete relief after cholecystectomy is that the preoperative diagnosis of chronic cholecystitis was incorrect. The only symptom entirely characteristic of chronic cholecystitis is biliary colic. When a calculous gallbladder is removed in the hope that the patient will gain relief from dyspepsia, fatty food intolerance, belching, etc, the operation may leave the symptoms unchanged.
The presenting symptom may be dyspepsia or pain. An organic cause for the symptoms is more likely to be discovered in patients with severe episodic pain than in those with other complaints. Abnormal liver function studies, jaundice, and cholangitis are other manifestations that indicate residual biliary disease. Patients with suspicious findings should be studied by ERCP or THC. Choledocholithiasis, biliary stricture, and chronic pancreatitis are the most common causes of symptoms. Occasionally, there is sufficient evidence to implicate sphincter of Oddi dysmotility as a cause of pain. Relief of pain may follow endoscopic sphincterotomy. Stenosis of the hepatobiliary ampulla, a long cystic duct remnant, and neuromas have been blamed for continued symptoms.
CARCINOMA OF THE GALLBLADDER
Carcinoma of the gallbladder is an uncommon neoplasm that occurs in elderly patients. It is associated with gallstones in 70% of cases, and the risk of malignant degeneration correlates with the length of time gallstones have been present. The tumor is twice as common in women as in men, as one would expect from the association with gallstones.
Most primary tumors of the gallbladder are adenocarcinomas that appear histologically to be scirrhous (60%), papillary (25%), or mucoid (15%). Dissemination of the tumor occurs early by direct invasion of the liver and hilar structures and by metastases to the common duct lymph nodes, liver, and lungs. In an occasional case, where carcinoma is an incidental finding after cholecystectomy for gallstone disease, the tumor is confined to the gallbladder as a carcinoma in situ or an early invasive lesion. Most invasive carcinomas, however, have spread by the time of surgery, and spread is virtually certain if the tumor has progressed to the point where it causes symptoms.
The most common presenting complaint is of right upper quadrant pain similar to previous episodes of biliary colic but more persistent. Obstruction of the cystic duct by tumor sometimes initiates an attack of acute cholecystitis. Other cases present with obstructive jaundice and, occasionally, cholangitis due to secondary involvement of the common duct.
Examination usually reveals a mass in the region of the gallbladder, which may not be recognized as a neoplasm if the patient has acute cholecystitis. If cholangitis is the principal symptom, a palpable gallbladder would be an unusual finding with choledocholithiasis alone and should suggest gallbladder carcinoma.
CT and ultrasound scans may demonstrate the extent of disease, but more often they show only gallstones.
The correct diagnosis is made preoperatively in only 10% of cases.
Obstruction of the common duct may produce multiple intrahepatic abscesses. Abscesses in or next to the tumor-laden gallbladder are frequent.
The incidence of gallbladder cancer has decreased in recent years as the frequency of cholecystectomy has increased. It has been estimated that one case of gallbladder cancer is prevented for every 100 cholecystectomies performed for gallstone disease.
If a localized carcinoma of the gallbladder is recognized at laparotomy, cholecystectomy should be performed along with en bloc wedge resection of an adjacent 3-5 cm of normal liver and dissection of the lymph nodes in the hepatoduodenal ligament. If a small invasive carcinoma overlooked during cholecystectomy for gallstone disease is later discovered by the pathologist, reoperation is indicated to perform a wedge resection of the liver bed plus regional lymphadenectomy. Some surgeons also recommend that the common duct be included routinely (ie, even in the absence of gross invasion) in the lymph node dissection for any lesion that involves the full thickness of the gallbladder wall. In the few cases when cancer has not penetrated the muscularis mucosae, cholecystectomy alone should suffice. More extensive hepatectomies (eg, right lobectomy) are not worthwhile. Lesions that invade the bile duct and produce jaundice should be resected if possible. When not, a stent should be inserted endoscopically or percutaneously. There is little that surgery can offer in cases with hepatic metastases or more distant spread.
Radiotherapy and chemotherapy are not effective palliative measures. About 85% of patients are dead within a year after diagnosis.
The 10% of patients who presently survive more than 5 years consist of those whose carcinoma was an incidental finding during cholecystectomy for symptomatic gallstone disease and those in whom an aggressive resection has removed all gross tumor.
et al.. National trends in the management and survival of surgically managed gallbladder adenocarcinoma over 15 years: a population-based analysis. J Gastrointest Surg 2010 Oct;14(10):1578–1591.
et al.. Endoscopic ultrasound-guided fine-needle aspiration biopsy in the evaluation of bile duct strictures and gallbladder masses: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2011 Feb;23(2):113–120.
MALIGNANT TUMORS OF THE BILE DUCT
ESSENTIALS OF DIAGNOSIS
Intense cholestatic jaundice and pruritus
Anorexia and dull right upper quadrant pain
Dilated intrahepatic bile ducts on ultrasound or CT scan
Focal stricture on transhepatic or retrograde endoscopic cholangiogram
Primary bile duct tumors are not more common in patients with cholelithiasis, and men and women are affected with equal frequency. Tumors appear at an average age of 60 years but may appear at any time between 20 and 80 years of age. More young people have been seen with this disease in recent years. Ulcerative colitis is a common associated condition, and in occasional cases bile duct cancer develops in a patient with ulcerative colitis who has been known to have sclerosing cholangitis for several years. Chronic parasitic infestation of the bile ducts in the Orient may be responsible for the greater incidence of bile duct tumors in that area.
Most malignant biliary tumors are adenocarcinomas located in the hepatic or common bile duct. The histologic pattern varies from typical adenocarcinoma to tumors composed principally of fibrous stroma and few cells. The acellular tumors may be mistaken for benign strictures or sclerosing cholangitis if adequate biopsies are not obtained. About 10% are bulky papillary tumors, which tend to be less invasive and less apt to metastasize.
At presentation, metastases are uncommon, but the tumor has often grown into the portal vein or hepatic artery.
The illness presents with gradual onset of jaundice or pruritus. Chills, fever, and biliary colic are usually absent, and except for a deep discomfort in the right upper quadrant the patient feels well. Bilirubinuria is present from the start, and light-colored stools are usual. Anorexia and weight loss develop insidiously with time.
Icterus is the most obvious physical finding. If the tumor is located in the common duct, the gallbladder may distend and become palpable in the right upper quadrant. The tumor itself is never palpable. Patients with tumors of the hepatic duct do not develop palpable gallbladders. Hepatomegaly is common. If obstruction is unrelieved, the liver may eventually become cirrhotic, and splenomegaly, ascites, or bleeding varices become secondary manifestations.
Since the duct is often completely obstructed, the serum bilirubin is usually over 15 mg/dL. Serum alkaline phosphatase is also increased. Fever and leukocytosis are not common, since the bile is sterile in most cases. The stool may contain occult blood, but this is more common with tumors of the pancreas or hepatopancreatic ampulla than those of the bile ducts.
Ultrasound or CT scans usually detect dilated intrahepatic bile ducts. THC or ERCP clearly depicts the lesion, and both are indicated in most cases. THC is of greater value, since it better demonstrates the ductal anatomy on the hepatic side of the lesion. With tumors involving the bifurcation of the common hepatic duct (Klatskin tumors), it is important to determine the proximal extent of the lesion (ie, whether the first branches of the lobar ducts are also involved). ERCP is of value with proximal tumors because if it shows concomitant obstruction of the cystic duct, the diagnosis will most often prove to be gallbladder cancer invading the common duct (not a primary common duct neoplasm). The typical pattern with distal bile duct cancers consists of stenosis of the bile duct with sparing of the pancreatic duct. Adjacent stenoses of both ducts (the double-duct sign) indicate primary cancer of the pancreas. MR cholangiopancreatography may be useful if high-quality studies are available.
Occasionally, bile samples obtained at the time of THC will show malignant cells on cytologic study, but this is not a particularly useful test since the diagnosis of cancer must be presumed from the cholangiographic findings and a negative cytologic study is unreliable. Angiography may suggest invasion of the portal vein or encasement of the hepatic artery. False positives may occur, however.
The differential diagnosis must consider other causes of extrahepatic and intrahepatic cholestatic jaundice. Choledocholithiasis is characterized by episodes of partial obstruction, pain, and cholangitis, which contrast with the unremitting jaundice of malignant obstruction. Bilirubin concentrations rarely surpass 15 mg/dL and are usually below 10 mg/dL in gallstone obstruction, whereas bilirubin levels almost always exceed 10 mg/dL and are usually above 15 mg/dL in neoplastic obstruction. A rapid rise of the bilirubin level to above 15 mg/dL in a patient with sclerosing cholangitis should suggest superimposed neoplasm. Dilatation of the gallbladder may occur with tumors of the distal common duct but is rare with calculous obstruction.
The combination of an enlarged gallbladder with obstructive jaundice is usually recognized as being due to tumor. If the gallbladder cannot be felt, primary biliary cirrhosis, drug-induced jaundice, chronic active hepatitis, metastatic hepatic cancer, and common duct stone must be ruled out. In general, any patient with cholestatic jaundice of more than 2 weeks’ duration whose diagnosis is uncertain should be studied by THC or ERCP. The finding of focal bile duct stenosis in the absence of previous biliary surgery is almost pathognomonic of neoplasm.
Patients without evidence of metastases or other signs of advanced cancer (eg, ascites) are candidates for laparotomy. The 30% of patients who do not qualify may be treated by insertion of a tube stent into the bile duct transhepatically under radiologic control or from the duodenum under endoscopic control. The tube is positioned so that holes above and below the tumor reestablish flow of bile into the duodenum. If both lobar ducts are blocked by a tumor at the bifurcation of the common hepatic duct, it is usually necessary to place a transhepatic tube into only one lobar duct. If the lesion blocks the takeoff of the segmental ducts, stents are rarely beneficial.
Laparotomy is indicated in most cases, however, with the objective of removing the tumor. Preoperative decompression of the bile duct with a percutaneous catheter to relieve jaundice does not lower the incidence of postoperative complications. At operation, which may be immediately preceded by diagnostic laparoscopy, the extent of the tumor should be determined by external examination of the bile duct and the adjacent portal vein and hepatic artery.
Tumors of the distal common duct should be treated by radical pancreaticoduodenectomy (Whipple procedure) if it appears that all tumor would be removed. Secondary involvement of the portal vein is the usual reason for unresectability of tumors in this location. Mid-common duct or low-hepatic duct tumors should also be removed if possible. If the tumor cannot be excised, bile flow should be reestablished into the intestine by a cholecystojejunostomy or Roux-en-Y choledochojejunostomy. The choice is based on technical considerations.
Tumors at the hilum of the liver should be resected if possible and a Roux-en-Y hepaticojejunostomy performed. The anastomosis is usually between hilum and bowel rather than between individual bile ducts and bowel. A curative operation nearly always requires resection of either the right or the left lobe of the liver and, in all cases, the caudate lobe. Extension into the lobar and segmental ducts and secondary involvement of the hepatic artery and portal vein are the most common reasons for inability to resect the tumor. Subtotal resections offer little in the way of palliation.
Postoperative radiotherapy is commonly recommended.
The average patient with adenocarcinoma of the bile duct survives less than a year. The overall 5-year survival rate is 15%. Following a thorough radical operation, 5-year survival is about 40%. Biliary cirrhosis, intrahepatic infection, and general debility with terminal pneumonitis are the usual causes of death. Palliative resections and stents may improve the length and quality of survival in this disease even though surgical cure is uncommon. Limited experience with liver transplantation for this disease has been discouraging: tumor has recurred postoperatively in most patients.
American Society for Gastrointestinal Endoscopy (ASGE) Standards of Practice Committee. The role of endoscopy in the evaluation and treatment of patients with biliary neoplasia. Gastrointest Endosc 2013 Feb;77(2):167–174.
S for the Japanese Association of Biliary Surgery; Japanese Society of Hepato-Biliary-Pancreatic Surgery; Japan Society of Clinical Oncology. Guidelines for the management of biliary tract and ampullary carcinomas: surgical treatment. J Hepatobiliary Pancreat Surg 2008;15(1):41–54.
BENIGN TUMORS & PSEUDOTUMORS OF THE GALLBLADDER
Various unrelated lesions appear on ultrasound as projections from the gallbladder wall. The differentiation from gallstones is based upon observing whether a shift in position of the projections follows changes in posture of the patient, since stones are not fixed. Cancer should be suspected in any polypoid lesion that exceeds 1 cm in diameter.
Most of these are not true neoplasms but cholesterol polyps, a local form of cholesterosis. Histologically, they consist of a cluster of lipid-filled macrophages in the submucosa. They easily become detached from the wall when the gallbladder is handled at surgery. It is not known whether cholesterol polyps are important in the genesis of gallstones. Some patients experience gallbladder pain, but whether this is related to the presence of the polyps per se or is a manifestation of functional gallbladder disease has not been established.
Inflammatory polyps have also been reported, but they are quite rare.
On cholecystography, this entity presents as a slight intraluminal convexity that is often marked by central umbilication. It is usually found in the fundus but may occur elsewhere. It is unclear whether adenomyomatosis is an acquired degenerative lesion or a developmental abnormality (ie, hamartoma). The following synonyms for this lesion appear in the literature: adenomatous hyperplasia, cholecystitis glandularis proliferans, and diverticulosis of the gallbladder. Although the condition is probably asymptomatic in many cases, adenomyomatosis can cause abdominal pain. Cholecystectomy should be performed in such patients.
These appear as pedunculated adenomatous polyps, true neoplasms that may be papillary or nonpapillary histologically. In a few cases they have been found in association with carcinoma in situ of the gallbladder.
BENIGN TUMORS OF THE BILE DUCTS
Benign papillomas and adenomas may arise from the ductal epithelium. Only 90 cases have been reported to date. The neoplastic propensity of the ductal epithelium is widespread, so the tumors are often multiple, and recurrence is common after excision. The affected duct must be radically excised for permanent cure to result.
BILE DUCT INJURIES & STRICTURES
Benign biliary injuries and strictures are caused by surgical trauma in about 95% of cases. The remainder result from external abdominal trauma or, rarely, from erosion of the duct by a gallstone. Prevention of injury to the duct depends on a combination of technical skill, experience, and a thorough knowledge of the normal anatomy and its variations in the hilum of the liver. The number of bile duct injuries has risen sharply in the past few years along with the shift from open to laparoscopic cholecystectomy.
The most common lesion consists of excision of a segment of the common duct as a result of mistaking it for the cystic duct. Partial transection, occlusion with metal clips, injury to the right hepatic duct, and leakage from the cystic duct are other examples. A full discussion of how these injuries occur and how they can be prevented is beyond the scope of this text.
A clean incision of the duct without additional damage is best managed by opening the abdomen and suturing the incision with fine absorbable suture material.
Manifestations of injury to the duct may or may not be evident in the postoperative period. Following laparoscopic surgery, bile ascites, manifested by abdominal distention, bloating, and pain plus mild jaundice, is the usual presentation, since the duct is usually open to the abdomen. The symptoms are relatively mild and may for a time mimic ileus until a worsening picture requires further investigation.
Injuries following open cholecystectomy more often present with intermittent cholangitis or jaundice as a consequence of a biliary stricture. The first clear-cut symptoms may not be evident for weeks or months after surgery.
Findings are not distinctive. Bile ascites produces abdominal distention and ileus and, rarely, true bile peritonitis with toxicity. The right upper quadrant may be tender but usually is not. Jaundice is usually present during an attack of cholangitis.
The serum alkaline phosphatase concentration is elevated in cases of stricture. The serum bilirubin fluctuates in relation to symptoms but usually remains well below 10 mg/dL.
Blood cultures are usually positive during acute cholangitis.
Bile ascites can be suspected on ultrasound or CT scan. Fluid should be aspirated, and if it is bile, the diagnosis is clear. THC and ERCP are necessary to depict the anatomy. After laparoscopic cholecystectomy, the most common pattern is a blocked (by a metal clip) lower duct and an upper duct draining freely into the abdomen. With a stricture, the findings most often consist of focal narrowing of the common hepatic duct within 2 cm of the bifurcation and mild to moderate dilatation of the intrahepatic ducts.
Choledocholithiasis is the condition that most often must be differentiated from biliary stricture because the clinical and laboratory findings can be identical. A history of trauma to the duct would point toward stricture as the more likely diagnosis. The final distinction must often await radiologic or surgical findings. THC or ERCP should be definitive.
Other causes of cholestatic jaundice may have to be ruled out in some cases.
Complications develop quickly if the leak is not controlled. Bile peritonitis and abscesses may form. With stricture, persistent cholangitis may progress to multiple intrahepatic abscesses and a septic death.
Bile duct injuries should be surgically repaired in all but a few patients who are likely to improve with a nonoperative approach. Excision of the damaged duct and Roux-en-Y hepaticojejunostomy is indicated for most acute and chronic injuries. The entire biliary tree must be outlined by cholangiograms preoperatively. The key to success is the thoroughness of the dissection and the ability ultimately to suture healthy duct to healthy bowel. This, in turn, depends on the experience of the surgeon with this particular operation.
When a definitive repair is technically impossible, the stricture may be dilated with a transhepatic balloon-tipped catheter. This is particularly applicable to patients with portal hypertension, whose hepatic hilum contains numerous venous collaterals that make operation hazardous.
The death rate from biliary injuries is about 5%, and severe illness is frequent. If the stricture is not repaired, episodic cholangitis and secondary liver disease are inevitable.
Surgical correction of the stricture should be successful in about 90% of cases. Experience at centers with a special interest in this problem indicates that good results can be obtained even if several previous attempts did not relieve the obstruction. There is essentially no place for liver transplantation in this disease.
SM A teaching program for the “culture of safety in cholecystectomy” and avoidance of bile duct injury. J Am Coll Surg 2013;217(4):751.
UNCOMMON CAUSES OF BILE DUCT OBSTRUCTION
Congenital Choledochal Cysts
About 30% of congenital choledochal cysts produce their first symptoms in adults, usually presenting with jaundice, cholangitis, and a right upper quadrant mass. Diagnosis can be made by THC or ERCP. The optimal surgical procedure is excision of the cyst and construction of a Roux-en-Y hepaticojejunostomy. If this is not technically possible or if the patient’s condition will not permit a prolonged operation, the cyst should be emptied of precipitated biliary sludge and a cystenteric anastomosis constructed. Congenital cysts of the biliary tree have a high incidence of malignant degeneration, which is another argument for excision rather than drainage.
Caroli’s disease, another form of congenital cystic disease, consists of saccular intrahepatic dilatation of the ducts. In some cases, the biliary abnormality is an isolated finding, but more often it is associated with congenital hepatic fibrosis and medullary sponge kidney. The latter patients often present in childhood or as young adults with complications of portal hypertension. Others have cholangitis and obstructive jaundice as initial manifestations. There is no definitive surgical solution to the problem except in rare cases with isolated involvement of one hepatic lobe, where lobectomy is curative. Intermittent antibiotic therapy for cholangitis is the usual regimen.
Hemobilia presents with the triad of biliary colic, obstructive jaundice, and occult or gross intestinal bleeding. Most cases in Western cultures follow several weeks after hepatic trauma with bleeding from an intrahepatic branch of the hepatic artery into a duct. It is seen with less frequency now, because the general principles of management of hepatic trauma are better understood. In the Orient, hemobilia usually follows ductal parasitism (Ascaris lumbricoides) or Oriental cholangiohepatitis. Other causes are hepatic neoplasms, rupture of a hepatic artery aneurysm, hepatic abscess, and choledocholithiasis. The diagnosis may be suspected from a technetium 99m-labeled red blood cell scan, but an arteriogram is usually required for diagnosis and planning of therapy. Sometimes the bleeding can be stopped by embolizing the lesion with stainless steel coils, Gelfoam, or autologous blood clot infused through a catheter selectively positioned in the hepatic artery. If this is unsuccessful, either direct ligation of the bleeding point in the liver or proximal ligation of an upstream branch of the hepatic artery in the hilum is required.
Pancreatitis can cause obstruction of the intrapancreatic portion of the bile duct by inflammatory swelling, encasement with scar, or compression by a pseudocyst. The patient may present with painless jaundice or cholangitis. Occasionally, a distended gallbladder can be felt on abdominal examination. Differentiation from choledocholithiasis and secondary acute pancreatitis depends on biliary x-rays or surgical exploration if the jaundice persists. Jaundice due to inflammation alone rarely lasts more than 2 weeks; persistent jaundice following an attack of acute pancreatitis suggests the development of a pseudocyst, underlying chronic pancreatitis with obstruction by fibrosis, or even an obstructing neoplasm.
Biliary obstruction from chronic pancreatitis may have few or no clinical manifestations. Jaundice is usually present, but the average peak bilirubin level is only 4-5 mg/dL. Some patients with functionally significant stenosis have persistently elevated alkaline phosphatase levels as the only abnormality; when surgical decompression of the bile duct is not performed, these patients often develop secondary biliary cirrhosis within a year or so. Diagnosis of stricture is made by ERCP, which shows a long stenosis of the intrapancreatic portion of the duct, proximal dilatation, and either a gradual or abrupt tapering of the lumen at the pancreatic border, occasionally accompanied by ductal angulation. If cholangiograms show stenosis and if alkaline phosphatase or bilirubin levels remain more than twice normal for longer than 2 months, the stenosis is functionally significant and unlikely to resolve and requires surgical correction. Choledochoduodenostomy is done in most cases. Cholecystoduodenostomy is unreliable because the cystic duct is often too narrow to provide continued biliary decompression.
Patients with obstructive jaundice and pseudocyst usually respond to surgical drainage of the pseudocyst. However, occasionally they do not respond, because chronic scarring—not the cyst—is the cause of obstruction. Procedures to drain both the bile duct and the pseudocyst are indicated if operative cholangiograms demonstrate persistent bile duct obstruction after the cyst has been decompressed.
Ampullary Dysfunction & Stenosis
Stenosis of the hepatopancreatic ampulla (ampullary stenosis) has been implicated as a cause of pain and other manifestations of ampullary obstruction and is often considered as a cause of postcholecystectomy complaints. Some cases are idiopathic, whereas others may be the result of trauma from gallstones. If the patient has secondary manifestations of biliary obstruction (eg, jaundice, increased alkaline phosphatase concentration, and cholangitis) in the absence of gallstones or some other obstructing lesion, and cholangiography shows dilatation of the common duct, ampullary stenosis is a plausible explanation. However, the diagnosis is more often proposed as a reason for upper abdominal pain without these more objective findings. Ampullary dysfunction is postulated in these cases.
Sphincter of Oddi dysfunction may be the cause of biliary-like pain and is often considered in patients who remain uncomfortable after cholecystectomy. The pathogenesis of the symptoms is thought to be similar to that of esophageal dysmotility and the irritable bowel syndrome. The patients typically experience severe, intermittent upper abdominal pain that lasts for 1-3 hours, sometimes following a meal.
Residual gallstone and pancreatic disease must first be ruled out. Ampullary dysfunction can then be diagnosed by sphincter of Oddi manometry. Patients are placed in one of three groups depending on the presence of three objective manifestations of biliary obstruction: abnormal liver function tests, prolonged (> 45 minutes) common bile duct emptying of contrast media after ERCP; and a common duct greater than 12 mm in diameter. Patients in group I have all three findings; patients in group II have one or two findings; and patients in group III have none of the findings. Group I patients are thought to have enough evidence of disease that sphincterotomy should be performed without manometry. Group I patients have abnormal motility so rarely that they should not be considered further for sphincterotomy. Thus, motility studies are most often of value in determining which of the group II patients will improve after sphincterotomy.
The abnormalities sought on the motility studies include an elevated (> 40 mm Hg) basal sphincter pressure and a paradoxic rise in sphincter pressure in response to CCK. The former is most reliable. About 50% of group II patients have elevated sphincter pressures, and these are the ones who benefit from sphincterotomy.
A scintigraphic test may be just as accurate. The patient is given a bolus of CCK followed by 99mTc-DISIDA. Gamma camera images of the liver and bile duct are obtained for 60 minutes. A scoring system (score: 0-12) is based on the rate of passage of the imaging agent past various relevant points (eg, appearance and clearance through the liver, bile duct, and bowel). The normal range is 0-5; abnormal is 6-12.
Sphincter of Oddi dysfunction is an uncommon explanation for abdominal pain, and it is appropriate to remain skeptical unless the objective findings of biliary obstruction are clear-cut. In well-selected cases, however, endoscopic sphincterotomy is beneficial.
AR Biliary sphincter of Oddi dysfunction: response rates after ERCP and sphincterotomy in a 5-year ERCP series and proposal for new practical guidelines. Eur J Gastroenterol Hepatol 2011;23(4):327–333.
Duodenal diverticula usually arise on the medial aspect of the duodenum within 2 cm of the orifice of the bile duct, and in some individuals the duct empties directly into a diverticulum. Even in the latter circumstance, duodenal diverticula are usually innocuous. Occasionally, distortion of the duct entrance or obstruction by enterolith formation in the diverticulum produces symptoms. Either choledochoduodenostomy or Roux-en-Y choledochojejunostomy is usually a safer method of reestablishing biliary drainage than attempts to excise the diverticulum and reimplant the duct.
When the worms invade the duct from the duodenum, ascariasis can produce symptoms of ductal obstruction. Air may sometimes be seen within the ducts on plain films. Antibiotics should be used until cholangitis is controlled, and anthelmintic therapy (mebendazole, albendazole, or pyrantel pamoate) should then be given. The acute symptoms usually subside with antibiotics, but if they do not, endoscopic sphincterotomy should be performed and attempts made to extricate the worms. If this is unsuccessful and the patient remains acutely ill, the duct should be emptied surgically.
Recurrent Pyogenic Cholangitis (Oriental Cholangiohepatitis)
Oriental cholangiohepatitis is a type of chronic recurrent cholangitis prevalent in coastal areas from Japan to Southeast Asia. In Hong Kong it is the third most common indication for emergency laparotomy and the most frequent type of biliary disease. The disease is currently thought to result from chronic portal bacteremia, with portal phlebitis antedating the biliary disease. E coli causes secondary infection of the bile ducts, which initiates pigment stone formation within the ducts.
Biliary obstruction from the stones gives rise to recurrent cholangitis, which, unlike gallstone disease in Western countries, may be unaccompanied by gallbladder stones. The gallbladder is usually distended during an attack and may contain pus.
Chronic recurrent infection often leads to biliary strictures and hepatic abscess formation. The strictures are usually located in the intrahepatic bile ducts, and for some unknown reason the left lobe of the liver is more severely involved. Intrahepatic gallstones are common, and their surgical removal may be difficult or impossible. Acute abdominal pain, chills, and high fever are usually present, and jaundice develops in about half of cases. Right upper quadrant tenderness is usually marked, and in about 80% of cases the gallbladder is palpable. ERCP or THC is the best way to study the biliary tree and can help in determining the need for surgery and the type of procedure.
Systemic antibiotics should be given for acute cholangitis. Surgical treatment consists of cholecystectomy, common duct exploration, and removal of stones. Sphincteroplasty should also be performed to allow any residual or recurrent stones to escape from the duct. A Roux-en-Y choledochojejunostomy is indicated for patients with strictures, markedly dilated ducts (eg, > 3 cm), or recurrent disease after a previous sphincteroplasty. The results of surgery are good in 80% of patients. Chronic intrahepatic stones and infection, which often involve only one lobe, may require hepatic lobectomy.
Although many patients are cured, prolonged illness from repeated infection is almost unavoidable once strictures have appeared or the intrahepatic ducts have become packed with stones.
Sclerosing cholangitis is a rare chronic disease of unknown cause characterized by nonbacterial inflammatory narrowing of the bile ducts. About 60% of cases occur in patients with ulcerative colitis, and sclerosing cholangitis develops in about 5% of patients with that disorder. Other less commonly associated conditions are thyroiditis, retroperitoneal fibrosis, and mediastinal fibrosis. The disease chiefly affects men 20-50 years of age. In most cases, the entire biliary tree is affected by the inflammatory process, which causes irregular partial obliteration of the lumen of the ducts. The narrowing may be confined, however, to the intrahepatic or extrahepatic ducts, though it is almost never so short as to resemble a posttraumatic or focal malignant stricture. The woody-hard duct walls contain increased collagen and lymphoid elements and are thickened at the expense of the lumen.
The clinical onset usually consists of the gradual appearance of mild jaundice and pruritus. Symptoms of bacterial cholangitis (eg, fever and chills) are uncommon in the absence of previous biliary surgery. Laboratory findings are typical of cholestasis. The total serum bilirubin averages about 4 mg/dL and rarely exceeds 10 mg/dL. ERCP is usually diagnostic, demonstrating ductal stenoses and irregularity, which often gives a beaded appearance. Liver biopsy may show pericholangitis and bile stasis, but the changes are nonspecific.
The complications of sclerosing cholangitis include gallstone disease and adenocarcinoma of the bile duct. The latter is most common in patients with ulcerative colitis. Furthermore, patients with ulcerative colitis and sclerosing cholangitis appear to be at greater risk for colonic mucosal dysplasia and colon cancer than those with ulcerative colitis not associated with sclerosing cholangitis.
Ursodiol (ursodeoxycholic acid), 10 mg/kg/d, improves liver function tests and symptoms. Cholestyramine will give relief from pruritus. Percutaneous transhepatic balloon dilatation can be of value to treat dominant strictures. In cases where the disease is largely confined to the distal extrahepatic duct and the proximal ducts are dilated, a Roux-en-Y hepaticojejunostomy may be indicated. For patients with severe intrahepatic involvement, hepatic transplantation should be considered.
The natural history of sclerosing cholangitis is one of chronicity and unpredictable severity. Some patients seem to obtain nearly complete remission after treatment, but this is not common. Bacterial cholangitis may develop after operation if adequate drainage has not been established. In these cases, antibiotics will be required at intervals. Most patients experience the gradual evolution of secondary biliary cirrhosis after many years of mild to moderate jaundice and pruritus. Liver transplantation is indicated when the disease becomes advanced. The results are good.