Patient Selection

Selection of patients for oral dissolution therapy is a function of the stage of gallstone disease, gallbladder function, and the characteristics of the stones. Selection criteria are summarized in Table 66-1. Oral dissolution therapy should be considered for patients with uncomplicated gallstone disease, including those with mild, infrequent biliary pain. Patients with severe or frequent biliary pain and patients with complications of gallstones, including cholecystitis, pancreatitis, and cholangitis, should not be treated with oral dissolution therapy; these patients should be referred for surgery. In addition, the gallbladder must function and the cystic duct must be patent to allow unsaturated bile and stones to clear from the gallbladder. The patency of the cystic duct is usually evaluated by oral cholecystography. More recently, stimulated cholescintigraphy and functional ultrasonography have been used. These latter modalities assess cystic duct patency as well as gallbladder function.

Table 66-1 Selection Criteria for Oral Bile Acid Dissolution Therapy

* Either stimulated cholescintigraphy or functional ultrasonography may be done.

The characteristics of the stones play an important role in determining the efficacy of dissolution treatment. Oral dissolution therapy works only on cholesterol stones. Although verifying the composition of gallstones can be difficult, the appearance of stones on plain films or computed tomography (CT) images can be useful. Cholesterol stones are radiolucent on conventional radiographs, and they are hypodense or isodense to bile and lack stone calcification on CT images.¹⁵ During oral cholecystography, the specific gravity of cholesterol stones is less than or equal to that of contrast-enriched bile, thereby resulting in stone buoyancy.¹⁶ The number of stones does not influence the success of oral dissolution therapy; however, only patients with stones that occupy less than one half of the gallbladder volume should be considered for treatment. Although oral dissolution therapy has been effective in stones up to 10 mm in diameter, results are best in stones less than 5 mm in size.^17,18 The ideal stones for oral dissolution treatment are shown in Figure 66-1.

Figure 66-1. A and B, Gallstones for which oral dissolution therapy is appropriate: A, ultrasonogram showing small gallstones; B, multiple small cholesterol stones. C and D, Gallstones for which oral dissolution therapy is inappropriate: C, radiopaque gallstones on a plain film; D, large pigmented gallstones.

Therapeutic Regimens

Ursodeoxycholic acid (ursodiol) is the preferred drug for oral dissolution treatment. It is taken in a dose of 10 to 15 mg/kg of body weight per day. Nighttime dosing is more effective and is associated with better patient compliance than mealtime dosing.¹⁹ Unlike chenodeoxycholic acid (chenodiol), ursodeoxycholic acid is well tolerated and has no important side effects. Treatment should continue until stone dissolution is documented by two consecutive negative ultrasonograms at least one month apart. Treatment should be stopped if the patient does not tolerate the drug or experiences a complication of gallstones during therapy or if the stones fail to dissolve after six months or dissolve only partially after six months with lack of progression to complete dissolution by two years.

Efficacy

With ursodeoxycholic acid, complete dissolution is achieved in 20% to 70% of patients. The variability in the reported response rates is a function of differences in patient selection, doses of bile acid, treatment times, and diagnostic techniques used to document stone dissolution.^9,10,20,21 A meta-analysis of all randomized trials of dissolution treatment showed stone dissolution in 37% of patients.⁹ The frequency of stone dissolution was 29% for stones larger than 10 mm, 49% for stones smaller than 10 mm, and 70% for stones less than 5 mm. The time to resolution varies among patients, with a median rate of 0.7 mm per month.¹¹ Improvement in symptoms occurs before stones have dissolved completely. In addition, long-term treatment has been reported to decrease the risk of biliary pain and acute cholecystitis, independent of gallstone dissolution.¹⁸ Despite initial dissolution of stones in properly selected patients, the rate of gallstone recurrence after oral dissolution therapy is 50% after five years, with most recurrences within the first two years.^5,7 The risk is lower in patients with a solitary stone than in those with multiple stones.

Patient Selection

Because shock-wave lithotripsy is usually combined with oral dissolution therapy, patient selection criteria for shock-wave lithotripsy are similar to those for oral dissolution treatment and are summarized in Table 66-2. Gallbladder function and cystic duct patency are required and are demonstrated by oral cholecystography, functional ultrasonography, or stimulated cholescintigraphy (see Chapter 65). Lithotripsy should be considered only for patients with mild, uncomplicated biliary pain. Pregnant patients and patients on anticoagulants should not undergo lithotripsy. Shock-wave lithotripsy is reserved for patients with a solitary stone, measuring less than 2 cm in size.^6,24 Because only cholesterol stones are reliably cleared by the addition of oral dissolution therapy, stones should have radiographic features, such as radiolucency, suggestive of cholesterol stones.

Table 66-2 Selection Criteria for Extracorporeal Shock-Wave Lithotripsy

* Either stimulated cholescintigraphy or functional ultrasonography may be done.

Therapeutic Approach

Patients usually are given sedatives and analgesics or are anesthetized and placed in the prone position to minimize the distance between the energy source and the stones and to eliminate interference from intestinal gas and the costal margin. Targeting and monitoring for fragmentation are accomplished with ultrasonography. Multiple treatment sessions are often required to achieve sufficient pulverization. Factors that predict the success of lithotripsy include the degree of fragmentation and gallbladder emptying.^25–27 Fragmentation depends on stone characteristics and the dose of the shock wave. Important stone characteristics include the size and number of stones as well as their structure and the presence of calcification.^25,28,29 The energy of shock waves, number of shock waves per session, and number of sessions also influence the success rate.^30,31 Ursodeoxycholic acid, 10 to 15 mg/kg of body weight per day, is administered orally to dissolve stone fragments, especially when residual stone fragments are larger than 2 mm in size, gallbladder function is poor, or the gallbladder has not cleared small fragments within three to six months of lithotripsy.³² An example of successful combined treatment is shown in Figure 66-2.

Figure 66-2. Ultrasonograms of a gallbladder with a single stone before (A), one day after (B), and six weeks after (C) extracorporeal shock-wave lithotripsy. Multiple small stone fragments seen one day after lithotripsy have disappeared six weeks after lithotripsy.

Efficacy

The percentage of patients who are free of stones after 6 and 12 months is 47% to 77% and 68% to 84%, respectively.^{24,25,33–37} Follow-up data reveal 27%, 41%, and 54% cumulative recurrence rates at 3, 5, and 10 years, respectively.³⁸ Recurrence is most often related to the presence of lithogenic bile and gallbladder dysmotility, rather than patient variables such as gender, age, and weight. Factors that predict higher rates of treatment failure include stones larger than 16 mm in size, multiple stones, and stones with a CT density of greater than 84 Hounsfield units.³⁹ Recurrent stones are usually small and multiple and cause recurrent biliary pain. Maintenance therapy with ursodeoxycholic acid after lithotripsy is not cost effective and has not been shown to be effective.^7,40

Side effects of lithotripsy include petechiae of the skin at the site of shock-wave delivery (8%), hematuria (4%), and liver hematomas (<1%). No long-term liver biochemical abnormalities have been noted. Biliary pain develops in approximately one third of patients; cystic duct obstruction develops in 5%; and complications of stone passage, such as biliary pancreatitis, develop in less than 2%.²⁵

Lithotripsy is more cost-effective in the elderly than in the young and less cost-effective in patients with multiple stones than in those with a single stone. When combined with ursodeoxycholic acid, lithotripsy is at least as cost-effective as open cholecystectomy for patients with small stones and less cost-effective for those with large stones.^41,42 When lithotripsy is compared with laparoscopic cholecystectomy, patients who undergo laparoscopic cholecystectomy experience a greater incremental improvement in quality of life at six months, whereas those who undergo lithotripsy have higher rates of recurrent stones and biliary symptoms.⁴³

Bile Duct Stones

Extracorporeal shock-wave lithotripsy has also been used in the management of choledocholithiasis. Intracorporeal electrohydraulic lithotripsy has been shown to be effective in this setting as well. These treatment options are reserved for patients who fail conventional endoscopic measures (see Chapter 70), mechanical lithotripsy, or surgical treatment of choledocholithiasis. Appropriate indications for shock-wave lithotripsy are large stones impacted in the bile duct that are not amenable to endoscopic extraction, intrahepatic stones, stones above a biliary stricture, cystic duct remnant stones, and bile duct stones associated with Mirizzi’s syndrome (compression of the common hepatic duct) (see Chapter 65). Selection of patients for shock-wave treatment of bile duct stones is similar to that for treatment of uncomplicated gallbladder gallstones.

The success rate for treatment of bile duct stones is 70% to 90%.^44–49 Most patients require endoscopic extraction of large stone fragments following treatment. Mild, transient hemobilia occurs in 10% of patients, and biliary sepsis develops in 4% following the procedure. Other complications are similar to those seen after lithotripsy for gallbladder stones. Because of the potential for septic complications, preprocedure endoscopic, nasobiliary, or percutaneous biliary drainage is performed. Antibiotics are given to minimize the risk of biliary sepsis.

Technique

The technique of open cholecystectomy has not changed substantially since its first description. With the surgeon standing on the patient’s right side, a right subcostal (Kochar) incision is made two fingerbreadths below the right costal margin. Alternatively, a midline incision may be used. After exploring the abdomen and taking down any adhesions to the gallbladder, the gallbladder is dissected from the gallbladder fossa in a retrograde fashion, from the fundus down to the infundibulum. When the gallbladder has been mobilized, the cystic artery and duct are readily identified. A cholangiogram may be performed to look for bile duct stones or to confirm the anatomy. The cystic duct and artery are ligated and divided. An alternative approach is to perform a dissection of the Triangle of Calot structures, as is done during laparoscopic cholecystectomy (see later), prior to removing the gallbladder from the liver. The Triangle of Calot is the space bordered by the cystic duct, cystic artery, and inferior edge of the gallbladder. Dissection and identification of these structures permits safe division of the cystic duct and minimizes the chance of bile duct injury. The abdominal incision is then closed. Closed suction drains are rarely indicated after cholecystectomy.

Results

The risk of open cholecystectomy has declined over the years. The overall mortality rate of cholecystectomy in 35,373 patients operated on before 1932 was 6.6%.⁵³ This rate decreased to 1.8% by 1952.⁵⁴ Since then, the overall mortality rate for cholecystectomy has averaged about 1.5%. The mortality rate is considerably lower in patients operated on electively for biliary pain, with an average of less than 0.5% (Table 66-3).^55–57 The risk of death is several-fold higher when cholecystectomy is performed as an emergency for acute cholecystitis and when bile duct exploration is required (see Table 66-3). Additionally, the mortality rate is directly proportional to the patient’s age (Fig. 66-3). In a report of the entire Danish experience with cholecystectomy from 1977 to 1981, patients under the age of 50 years had a risk of death of 0.028% from elective cholecystectomy⁵⁶; the rate rose to 5.56% in patients older than 80 years of age. The experience in the United States has been similar. Of 11,808 patients who underwent cholecystectomy at the New York Hospital–Cornell Medical Center between 1932 and 1978, the risk of death from elective cholecystectomy for chronic cholecystitis was 0.1% in patients less than age 50 years and 0.8% in those 50 years of age or older.⁵⁷ In a later series, the overall mortality rate of 42,474 patients who underwent cholecystectomy in 1989 in California and Maryland was 0.17%.⁵⁸ In this series, the mortality rate in patients less than 65 years of age was 0.03%, compared with more than 0.5% in patients 65 years of age and older. Likewise, the morbidity rate, mean length of hospital stay, and average hospital charges were significantly higher in the older patients than in the younger group. Most mortality following cholecystectomy is related to cardiac disease, particularly myocardial infarction.

Table 66-3 Mortality Rates for Open Cholecystectomy as a Function of Clinical Setting

Figure 66-3. Relationship between age and risk of death from open cholecystectomy. Data include all patients operated on in Denmark between 1977 and 1981.

(Data from Bredesen J, Jorgensen T, Andersen TF, et al. Early postoperative mortality following cholecystectomy in the entire female population of Denmark, 1977-1981. World J Surg 1992; 16:530-5.)

Major complications after open cholecystectomy are rare. In a large survey of 28,621 patients who underwent cholecystectomy in the 1960s, complications occurred in 4.0%.⁵⁵ Subsequent studies have confirmed a 4.0% to 5.0% rate of perioperative morbidity.^59–61 Most complications are relatively minor, such as wound infections or seromas, urinary retention or infection, and atelectasis. Complications related specifically to cholecystectomy include bile leaks, bile duct injury, and acute pancreatitis. Of these complications, bile duct injury is the most serious and often requires endoscopic therapy and, in some cases, complicated and technically difficult surgical repair (see Chapter 70). Alternatively, bile duct injury can lead to benign biliary stricture formation and bile duct obstruction with secondary biliary cirrhosis and liver failure. The rate of bile duct injury during open cholecystectomy is not known precisely but has been estimated to be 1 in 200 to 600 cases.^62,63 Two ductal injuries occurred in 1200 cholecystectomies at the Cedars-Sinai Medical Center in Los Angeles from 1982 to 1988,⁶⁴ and no bile duct injuries occurred in 1252 patients who underwent elective cholecystectomy at two large North American and European centers.⁶⁵ In general, bile duct injuries are preventable complications and are commonly the result of inadequate surgical training, unrecognized variations in bile duct anatomy, or misidentification of normal anatomy. Unusual amounts of bleeding, severe inflammation, and emergency operations do not play as great a role in these injuries as might be supposed.

Technique

The operative team for laparoscopic cholecystectomy generally consists of a surgeon, assistant surgeon, scrub nurse, circulating nurse, and anesthesiologist. Patients are asked to void immediately prior to entering the operating room. Prophylactic antibiotics are not routinely administered to patients with uncomplicated gallstone disease, including biliary pain.⁶⁶ Patients with potential infectious complications of gallstones, including acute cholecystitis and cholangitis, and patients with long-standing symptoms or advanced age should receive antibiotics if these agents were not already started before surgery.⁶⁷ Sequential compression stockings are used to reduce the risk of lower extremity thromboembolism.

In order to view the abdominal contents and provide room for instruments, a space is developed by inducing a pneumoperitoneum with a nonflammable, physiologically benign gas such as carbon dioxide. Pneumoperitoneum is achieved by either a closed technique in which a Veress needle is inserted into the peritoneum through a small incision, followed by placement of an operating trocar, or by a direct, open technique in which the operating trocar is placed directly into the abdomen under direct visualization through a small incision. After the pneumoperitoneum has been established, a trocar is placed at the umbilicus and a laparoscope is introduced. Three additional trocars are placed in the upper abdomen under direct vision for insertion of operating instruments and retractors.

The current technique of laparoscopic cholecystectomy is best described as “the critical view” approach,⁶⁸ as summarized in Figure 66-4. In this approach, the entire hepatocystic triangle is dissected, exposing the cystic duct and artery, infundibulum of the gallbladder, and junction of the gallbladder and cystic duct before a cholangiogram is performed or the cystic duct and artery are divided. The assistant retracts the gallbladder fundus cephalad, anterior to the liver, and the infundibulum laterally. The surgeon, operating through the epigastric port, identifies and dissects the cystic duct and artery circumferentially. Special care must be taken to identify the junction of the cystic duct and gallbladder, to ensure that the bile duct has not been isolated inadvertently. Cholangiography is performed via cannulation of the cystic duct. If the cholangiogram shows normal anatomy and no evidence of choledocholithiasis, the cholangiocatheter is removed and the cystic duct and artery are divided between small metal clips. The gallbladder is then dissected out of the liver bed and delivered through the umbilical incision. Care is taken to avoid perforation of the gallbladder during its dissection from the liver because the spillage of gallstones and bile has been shown to increase the risk of postoperative fever and intra-abdominal abscess formation.⁶⁹ The operation concludes with evacuation of the pneumoperitoneum and closure of the incisions.

Figure 66-4. Laparoscopic cholecystectomy. A, Gallbladder in situ. B, Cephalad retraction of the fundus toward the right shoulder exposes the infundibulum of the gallbladder. C, Retraction of the infundibulum toward the right lower quadrant opens the hepatocystic triangle. The hepatocystic triangle is the area bordered by the cystic duct, gallbladder edge, and liver edge. D, Division of the peritoneum overlying the anterior and posterior aspects of the hepatocystic triangle exposes “the critical view.” E, Cholangiogram catheter in the cystic duct. F, Normal cholangiogram. G, Gallbladder removed from the gallbladder fossa with electrocautery.

Rationale for Cholangiography

Cholangiography during laparoscopic cholecystectomy has two main purposes. First, the cholangiogram may detect unsuspected bile duct stones. Second, the cholangiogram confirms the surgeon’s impression of the anatomy of the bile ducts. In the era before laparoscopic cholecystectomy, the value of routine cholangiography during cholecystectomy was debated, with some surgeons arguing in favor of its selective use.⁷⁰ Routine cholangiography has been criticized because of its relatively low yield, failure to identify all retained stones, occasional false-positive results, cost, and risk. Nevertheless, 8% to 16% of all patients with cholelithiasis harbor bile duct stones. Routine use of operative cholangiography detects unsuspected bile duct stones in about 5% of patients who undergo cholecystectomy and detects anatomic ductal abnormalities in 12%.⁷¹ During laparoscopic cholecystectomy, the two-dimensional video image and inability to palpate structures of the porta hepatitis make identification of the cystic duct–bile duct junction problematic. Cholangiography plays an especially important role in delineating bile duct anatomy prior to division of any important structures. Large population studies from Australia and Sweden have demonstrated the importance of routine intraoperative cholangiography in decreasing the frequency of major bile duct injuries.^72,73 The rate of bile duct injury during laparoscopic cholecystectomy when routine cholangiography is performed is 0.2% to 0.4%, compared with 0.4% to 0.6% when cholangiography is not performed routinely.^72–74 Routine cholangiography is cost effective when the cost associated with bile duct injuries is considered.⁷⁵ In addition, routine cholangiography permits earlier identification of intraoperative bile duct injuries, if they occur,⁷⁶ and thereby improves the rate of repair.

Results

Several large series have now described the experience with laparoscopic cholecystectomy (Table 66-4).^76–87 A review of the experience with laparoscopic cholecystectomy in the United States showed an operative mortality rate of 0.06%. Internationally, operative mortality rates have ranged from 0% to 0.15%. Conversion to an open procedure was required in 2.2% in the United States and 3.6% to 8.2% of patients internationally, generally because of inflammation that precludes safe dissection of the porta hepatis. Major morbidity occurred in approximately 5% of patients, and bile duct injuries occurred in 0.14% to 0.5% of patients. Operating time ranged from one to two hours. Initially, most patients were observed overnight after laparoscopic cholecystectomy, but same-day discharge has become standard for elective cases. Most patients return to full activities, including work, within one week.

Table 66-4 Experience with Laparoscopic Cholecystectomy

No randomized, prospective trials have compared the results of laparoscopic cholecystectomy with those of open cholecystectomy in the United States, nor are any likely. Patient enthusiasm for the laparoscopic approach and the rapid acceptance of the procedure by surgeons have made direct, controlled comparison of the two procedures difficult. Nonrandomized data from the United States and small, randomized trials from other countries support the contention that the laparoscopic approach is superior to the open approach.^59,88–92 In these analyses, the main benefits of the laparoscopic approach have included a shortened hospital stay, decreased pain, reduced disability, and reduced costs. Population studies have shown a substantial decline in cholecystectomy-related mortality rates following the introduction of the laparoscopic technique (Table 66-5).⁹³

Table 66-5 Cholecystectomy-Related Mortality in Maryland before (1989) and after (1992) the Introduction of Laparoscopic Cholecystectomy

Against the perceived benefits of laparoscopic cholecystectomy over the open approach is concern about unacceptably high complication rates, especially for bile duct injury. Although the exact frequency of bile duct injury around the world is not known, two lines of evidence suggest that the rate has declined. First, regional studies have demonstrated a decrease in the rate of bile duct injury as overall experience with laparoscopic cholecystectomy has increased (Fig. 66-5).⁹⁴ Curiously, however, the frequency of bile duct injury does not continue to fall with increasing experience of the individual surgeon, but rather plateaus.^95–97 Although duct injuries are more common early in an individual surgeon’s experience, they still occur in the hands of seasoned surgeons, albeit at a lower rate. As overall experience has increased, the rate of bile duct injury for laparoscopic cholecystectomy has approximated that seen with open cholecystectomy. Second, the number of patients with bile duct injury treated at tertiary referral medical centers has declined since the early days of laparoscopic cholecystectomy.⁹⁸ Introduction of laparoscopic cholecystectomy in the United States was rapid and may have exceeded the capability of the medical educational system to train all practitioners adequately. The initial relatively high rates of bile duct injury have been ascribed to a “learning curve.” This experience is a cautionary example for other new technologies that may be introduced into medical practice.

Figure 66-5. Effect of a surgeon’s experience on the risk of bile duct injury during laparoscopic cholecystectomy. The dramatic decline in risk as experience is gained has been attributed to a “learning curve.”

(Data adapted from Moore MJ, Bennett CL. The learning curve for laparoscopic cholecystectomy. The Southern Surgeons Club. Am J Surg 1995; 170:55-9.)

Concern has been raised about the increased use of laparoscopic cholecystectomy for gallstone disease when compared with historical rates for open cholecystectomy. In a defined health maintenance organization population in Pennsylvania, the rate of cholecystectomy increased from 1.35 per 1000 enrollees in 1988, just before the introduction of the laparoscopic approach, to 2.15 per 1000 enrollees in 1992, just after its introduction.⁹⁹ No significant changes in the rates of herniorrhaphy or appendectomy were observed. Similarly, statewide data from Maryland have shown that the rate of cholecystectomy rose from 1.69 per 1000 residents in 1987 to 1989 to 2.17 per 1000 residents in 1992,⁹³ and Scottish nationwide data have shown a 20% increase in the age-standardized rate of cholecystectomy.¹⁰⁰ The reasons for the increases in use are not yet clear. The consensus of experts in the field is that selection of patients for cholecystectomy should not be altered by the availability of the laparoscopic approach.