Saudi Journal of Gastroenterology
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Year : 1996  |  Volume : 2  |  Issue : 1  |  Page : 29-38
Management of gallstones

Department of Medicine, College of Medicine, King Saud University, Riyadh 11461, Saudi Arabia

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Asymptomatic patients with gallbladder stones rarely develop complications and therefore do not require treatment; in contrary, symptomatic patients should he treated. Nowadays, several approaches are available to treat gallbladder and ductal stones using surgical techniques. chemical dissolvents, frag­mentation, endoscopic and percutancous approaches. The choice of approach is influenced by the site, size and chemical composition of stone, as well as the age, general condition and desire of patient. Surgi­cal approaches are considered as the primary method of treatment. Nonsurgical treatment is considered in patients at high risk and patients unwilling to undergo surgery. The main concern of non-surgical treat­ment is the high recurrence rate, especially after dissolution.

How to cite this article:
Al Mofleh IA. Management of gallstones. Saudi J Gastroenterol 1996;2:29-38

How to cite this URL:
Al Mofleh IA. Management of gallstones. Saudi J Gastroenterol [serial online] 1996 [cited 2022 Jul 2];2:29-38. Available from:

Until recently, open cholecystectomy and bile duct exploration have been the standard treat­ment for stones of the gallbladder and associated bile duct stones. The introduction of new mod­alities for treatment of gallbladder and bile duct stones including laparoscopic cholecystectomy, endoscopic techniques, extra-and intra-corporeal lithotripsy and chemical, oral or contact dissolu­tion, examplify a great progress to gallstones man­agement. Laparoscopic cholecystectomy has gained wide popularity and has become the gold standard treatment for gallstones [1],[2] . Endos­copic sphincterotomy is the method of choice for retained ductal stones, acute cholangitis, acute biliary pancreatitis, and ductal stones in high risk patients with a high clearance rate of up to 90%.

Combination of endoscopic sphincterotomy with lithotripsy helps to clear majority of the remaining stones [3] . Asymptomatic stones do not require treatment. Management of symptomatic stones is summarized in [Figure - 1] and [Table - 1].

   Operative Approaches Top

Surgery is still the primary treatment for gallbladder stones, and other nonsurgical techniques provide alternative methods [4] .

Open cholecystectomy (OC)

Till few years back, OC was the choice available for treatment of gallbladder stones. It has effi­ciently been performed for over one century to manage gallstone disease with low mortality rates ranging from 0.1-1 % [5],[6] . The mortality increases in patients over 70 years of age and in patients with septic complications to 2.3 and 6.2%, respectively. The increase in mortality rate in the elderly has usually been due to cardiac and pulmonary conditions [5] .

Mini-cholecystectomy (MC)

Is a modified OC with small, four to six cms transverse incision, which has safely been per­formed with a short mean hospital stay of 1.5 days [7] , and faster return to work after an average of 18.6 days [8] . Postsurgical anesthesia requirement has been less, compared to standard OC [8] .

Laparosocopic cholecystectomy (LC)

The development of LC in 1987-88 significantly influenced the gallstone management, and in a short time, it has become the gold standard method [9] . The indications for cholecystectomy have not been altered with the introduction of LC [10] . In contrary, LC has recently been safely per­formed in conditions previously considered as contraindications for it. including complicated gallstone disease [11] , sickle cell disease [12] , pre­gnancy [13] and obesity [14] . The intolerance of peritoneal insufflation in cardiac and respiratory diseases represent the only contraindication for LC [15] . It has been safe with rates of 0-02 %, 2­5% and 3-6% for mortality, conversion to OC and postoperative complications, respectively [9] .

Biliary trauma at a rate of 0.2-1.3% has been the major complication of LC [16],[17] . Biliary trauma has been related to anatomical and techni­cal problems. It may be reduced, but not pre­vented by performing intraoperative cholangiog­raphy and laparoscopic ultrasonography [10] . Also needle-and trocar-induced large vessels injuries have been accompanied with mortality at a rate of (0.05%) 8.8% [18] . Further important complications contributing to increased mortality have included instrumentation-related gastroin­testinal injuries with a mortality rate of 4.6% [18] .

The main advantages of LC have been: minimal wound pain, short hospital stay (mean. two days), early return to work (within a week) and cosmetic aspects [19] .

Although transcystic and choledochostomy approaches have been performed to remove duc­tal stones, laparoscopic techniques have not yet finally solved this problem [9] .

Minimally-invasive procedures

Less invasive procedures such as percutaneous cholecystostomy have the advantage of being per­formed under local anesthesia for treatment of acute cholecystitis, gallbladder empyema and per­forated gallbladder with a local abscess especially, in the elderly and high risk patients [20] .

Cholecystolithotomy is another less invasive procedure that can he performed using percutan­eous transhepatic, transperitoneal and laparos­copic access. It has been successfully performed in 89 out of 100 patients presented with acute gallstone complication and in high risk patients. Complications in the form of cholangitis and sub­hepatic biliary collection have occurred in 13% of patients [8] .

   Endoscopic Approach Top

Since the introduction of endoscopic approach of common bile duct stones over two decades ago, this method has become the most widely-accepted nonsurgical diagnostic and therapeutic approach of ductal stones. It has been considered as the treatment of choice in postcholecystectomy­retained bile duct stones with an effective stone clearance in up to 90% of patients [21] . Further­more, endoscopic retrograde cholangiopan­creatography (ERCP) with sphincterotomy has been the appropriate method in the elderly and high risk patients with ductal stones, as well as the emergency procedure for acute cholangitis or biliary pancreatitis [22]. In the small proportion (10%) of patients with failure to clear the bile duct by conventional means due to the large stone size, stone impaction or stricture, mechanical fragmen­tation is achieved in approximately 85% of these patients [23] . Nasobiliary intubation [24] and endoprosthesis [25] are effective and safe methods that reduce complications and avoid urgent surgery in patients with unsuccessful stone clearance. Long-term endoscopic stenting has been found to be an effective and safe alternative in the event of failure to clear stones in the frail and elderly patients [25] .

Cotton, et al referred to a recent prospective series of 1,921 patients treated with sphincterotomy to remove stones. The overall morbidity has been 5.8%, of which 0.6% were severe, with 0.2% mortality [10] . Pancreatitis has been the frequent direct procedure-related com­plication. Perforation and hemorrhage are rather less frequent [26] .

ERCP should be performed before LC, in patients with substantial suspicion of ductal stones and after LC in the presence of stones [10] .

   Lithotripsy Top

At present, a variety of lithotriptors have been used to fragment gallstones. These lithotriptors are used alone or in combination with endoscopic approaches or chemical dissolvents.

Mechanical lithotriptor (ML)

Compared to other forms, ML is a practical and cheap device that can easily be used in all endos­copy units performing ERCP and sphinctero­tomy. Over 85% successful fragmentation rates have been reported [23],[27] . The success rate of lithotripsy is in a reciprocal correlation with stone size as only 25% of stones larger than 2.5 cms in diameter have been successfully fragmented [28] . The success rate can be further improved by the use of larger and stronger baskets [27] . Mechani­cal lithotripsy is reliable and safe [23] . Therefore, it should be the method of choice for managing bile duct stones, that cannot be retrieved by con­ventional endoscopic techniques.

Laser lithotripsy (LL)

Fifteen years ago, Orii et al, in Japan reported the first fragmentation of bile duct stones using a continuous wave Neodymium YAG (CW Nd: YAG) laser through a percutaneous-transhepatic access [29] . The use of CW Nd: YAG for litho­tripsy is limited by its thermal injuries, induced by the continuous release of a high energy amount. This thermal damage has been reduced by the use of a flashlamp pulsed Nd: YAG Laser system which can be used under direct endoscopic vision or under radiological screening. To further reduce the thermal effect on the tissue, special baskets and balloons have been developed. In the first successful endoscopic retrograde Laser lithotomy of ductal stones in man, using a flashlamp pulsed Nd: YAG Laser, 1064, nm wavelength, eight of nine stones have been fragmented and in six, retrieved without complications [30] . The disad­vantage of the flashlamp pulsed Nd: YAG is reflected by the large stone fragments.

The development of the pulsed-dye and quality­switched Nd: YAG Lasers with reduced or absent thermal damage and the capability to fragment the stones in small particles, denotes further prog­ress towards efficacy and safety of Laser lithot­ripsy [30] . Coumarin- flashpumped pulsed-dye Laser with a wavelength of 504 nm has been used with a high efficacy and safety [31],[32],[33] . Complete bile duct clearance has been achieved in 33 of 35 patients [34] . A very high successful lithotripsy rate (97%) has been achieved by employing a new rhodamin-flashlamp pumped pulsed-dye Laser with 594 nm wavelength and automatic stone rec­ognition, which is safely used without optimal or even absent visualization. The Laser fiber diame­ter of 0.25 or 0.30 mm allows the use of endoscopic retrograde or percutaneous transhepatic access. Complications have occurred in nine percent in the form of mild cholangitis, that promptly responded to antibiotics [35] .

With the progress in Laser lithotripsy and the availability of efficient and safe Laser lithotrip­tors, more acceptance and application will be feas­ible, provided the cost problems will be solved.

Electrohydraulic lithotripsy (EHL)

This method has been first used to fragment uri­nary bladder stones and adapted in 1975. for lithotripsy of gallstones [36] . Electrohydraulic lithotripsy has been applied in adjunction with percutaneous and peroral fiberoptic endoscopes permitting visualization to minimize trauma to the common bile duct [37],[38] . A high lithotripsy suc­cess rate exceeding 95% of hepato- and choledocholithiasis has been reported [39] . Hemobilia has been encountered in 24% of patients undergoing transhepatic EHL [40] .

In comparison to other lithotriptors, EHL has not been widely used due to associated technical problems, thermal injuries and risk of perforation [27] .

Extracorporeal shock-wave lithotripsy (ESWL)

Ten years ago (1985), ESWL has been adapted for treatment of gallstones [41] . Nowadays, it has become an established technique for gall­bladder and ductal stone fragmentation in several countries. Symptomatic non-complicated gallstones in patients at risk for surgery or anes­thesia and in patients unwilling to undergo surgery are considered for ESWL [42],[43] . For successful fragmentation, patients undergoing ESWL should meet its selection criteria. The cystic duct should be patent and stones should be radiolu­cent, one to three with a maximal cumulative diameter of 30 mm [44] . In vitro studies to evaluate parameters determining efficacy of ESWL for gallstone fragmentation revealed that the number, the total volume of stones and to a lesser degree, their chemical composition are the major determinants of successful lithotripsy [45] . The fragment size is usually larger than two mm. Approximately 60% of patients have frag­ments ≤ 5 mm maximum diameter after the last ESWL session performed by electromagnetic sys­tem [46] ). Therefore, ESWL has been combined with bile acids to treat cholesterol stones of the gallbladder [41],[47] .

The 12-month stone free-rate after ESWL with adjuvant bile acid litholysis of single radiolucent stones up to 20 mm has been 68- 84%, [48],[49] 13-75% for single stones with 20-30 mm, diameter [50],[51] and 25-65% for multiple stones [48],[52] .

Three types of extracorporeal shock wave lithotriptors have been used. The electrohy­draulic, the piezoelectric and electromagnetic lithotriptors. The efficacy of these lithotriptors is comparable [43],[46] .

Extracorporeal shock wave lithotripsy has been associated with minor side effects in the form of local petechial bleeding, asymptomatic liver hematoma and transient hematuria [44] . Asymptomatic transient aminotransaminase ele­vation has been found in 20% and transient gallbladder wall edema in 4.3% of patients [46] . Other side effects have included: mild cholangitis, pancreatitis, hemobilia [53] and upper gastroin­testinal erosions [54] .

Combined ESWL and bile acids treatment has been considered as a good alternative for surgery. However, it has been of limited applicability due to cost, long duration of treatment and follow-up and the high rate of recurrence [10]

   Chemical Dissolution Top

Oral dissolvents

Bile acid treatment may be used as an alterna­tive treatment for surgery in a minority of patients 10-30% [8] . Litholysis is effective in patients with small (< 15 mm) radiolucent stones in a function­ing gallbladder. A complete dissolution is obtained in approximately 40% after two years of initiation of treatment [42] . A higher rate (55%) of dissolution has been reported in a group of appropriately-selected compliant patients, who tolerated an adequate treatment course [55] .

Two bile acids, chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA) are commonly used to treat cholesterol gallstones. Chenodeoxycholic acid has been used clinically for cholesterol gallstone lysis since 1972 [56] . At an optimal dose both CDCA (15 mg/kg/day) and UDCA (10 mg/kg/day) have similar efficacy. While UDCA has minor or no side effects, CDCA treatment is associated with a number of side effects such as diarrhea, skin rash, hepatotoxicity and mild increase in the low-density lipoprotein cholesterol [57] . These side effects can be avoided by a combination of both bile acids, which have been found to be effective and safe in doses of 7­7.5 and 5-6.5 mg/kg/day for CDCA and UDCA, respectively [58],[59] . Furthermore, combination of CDCA and UDCA, and the bedtime adminis­tration has enhanced the effect of bile acid therapy [59] .

Recently, UDCA in combination with 3­hydroxy-3-methylglutaryl coenzyme A (HMG­CoA) reductase inhibitors such as simavastatin and lovastatin have been found to lower choles­terol saturation [60],[61] . Furthermore, combina­tion of UDCA with menthol has been more effec­tive compared to UDCA alone with a complete dissolution rate of 53 and 38%, respectively within 15-16.9 months. Both regimens have been found to be free of side effects [62] .

Dissolution of gallstones with bile acid combi­nations is an alternative medical treatment in a small, selected number of patients with poor sur­gical risk or unwillingness to undergo surgery. The high recurrence rate after therapy cessation, the narrow selection criteria, the long duration of treatment and follow-up have limited their wide application.

Direct contact dissolution

Two direct contact chemical agents, methyl tert-butyl ether and monooctanoin have been used to dissolve gallbladder and ductal cholesterol gallstones. Another contact dissolvent, ethylenediamine tetra-acetic acid (EDTA) is used to treat brown pigment stones of the bile duct.

Methyl tert-butyl ether (MTBE)

Gallstones litholysis, using MTBE has been introduced in 1985 [63] . Methyl tert-butyl ether is instilled into the gallbladder through a percutane­ous transhepatic route or through retrograde endoscopic route using a nasobiliary tube. It has been found to be very effective with a stone dissol­ution rate exceeding 95% [64] . Also, common bile duct stones have been dissolved with a com­plete clearance in eight of ten patients [65] . Due to impossible prevention of spillage into the intes­tine and rapid absorption, MTBE cannot be gen­erally recommended for choledocholithiasis. Complete dissolution usually, is achieved within few hours of repeated MTBE infusion and aspira­tion. This is correlated with the number of stones and it has been shorter for a single, compared to multiple stones. The mean perfusion time is 10 hours [62] . Litholysis with MTBE is considered as an effective and safe alternative for surgery in high risk patients. The unwanted effects have been minor and rarely (7%) required treatment. The main side effects have included leucocytosis, hypertran­saminasemia, bile leak and hemobilia [62] .


This contact dissolvent has been used to dis­solve cholesterol gallstones in the common bile duct and to a lesser extent, gallbladder stones with a lower dissolving capability compared to MTBE. Unlike MTBE, monooctanoin has not been widely used for litholysis due to the long perfusion time needed (10-30 days) [66] , low efficacy rate and the frequently encountered side effects. Mild undesirable effects have often occurred in the form of abdominal pain, vomiting and diarrhea, as well as biliary and duodenal ulcerations. Serious side effects such as ulcer bleeding, obstructive jaundice, pancreatitis and pulmonary edema have been reported in four percent of patients [68].

Ethylenediaminetetraacetic acid (EDTA)

Monooctanoin and more frequently, MTBE are used to dissolve cholesterol gallstones in gallbladder and common bile duct. Bile duct stones forming de novo in the common bile duct, are often brown pigment stones. These are approached by using contact dissolvents i.e. EDTA, which chelates calcium from calcium bilirubinate and form soluble sodium bilirubinate. The number of patients treated with EDTA is not large with stone dissolution of 40-70% of stones. In vitro studies, combination of EDTA with vari­ous detergents, thiols or urea, enhanced its dissol­ving capability [69] .

MTBE is the most commonly used and effective contact litholytic agent which can be considered as an alternative for surgery in high risk patients. In contrast monooctanoin's safety and efficacy are much lower. EDTA and combination solutions require further clinical evaluation.

   Recurrence and Prevention Top

The major disadvantage of stone dissolution and lithotripsy is the high recurrence rate. Up to 50% of patients develop stone recurrence within five years after cessation of bile acid therapy and rarely thereafter [55] . Recurrence rate after MTBE litholysis has been reported to be even higher [70] . In contrast, recurrence rate has been lower, following ESWL [71] . Factors determining recurrence are unknown, [55] however, presence of multiple primary stones [72] and duration of treatment until complete stone dissolution [73] have been incriminated as the important deter­minants of stone recurrence.

Similar to primary stone formation, the pathogenesis of stone recurrence is multifactorial. Bile supersaturation, nucleation defect, gallblad­der function and motility should be considered when planning for a successful treatment and recurrence prevention. Ideally, drugs used for treatment and prevention of gallstones should, in addition to their desaturating and nucleation inhibiting effects, control gallbladder function and motility [74] . A single agent with all of these characteristics, is not yet available. However, the following drugs with various modes of actions have been used either single or combined with others:

   Cdca Top

Through its inhibitory effect on HMG-CoA reductase activity, it decreases the cholesterol synthesis and subsequently, saturation index [75] . Furthermore, CDCA dissolves cholesterol in micells [58] . A low dose of CDCA or UDCA is not sufficient to prevent gallstone recurrence [76] .

   Udca Top

The mechanism of action of UDCA differs from that of CDCA. It enhances the hepatic conversion of cholesterol to bile acids [77] . It also enhances cholesterol transport as liquid crystals [58] . Fur­thermore, UDCA has an inhibitory action on the prostaglandins and biliary glycoprotein concen­tration which is the possible explanation for its action on decreasing the saturation index.

Aspirin and NSAIDs

Through inhibition of glycoprotein secretion by the gallbladder and probably their effect on gallbladder motility, NSAIDs inhibit the nuclea­tion and therefore, may be beneficial for the pre­vention of stone formation in patients at risk and prevention of recurrence. This has been shown by a group of regular NSAID users who have been followed up for a mean of 33 months, compared to control [78] . In another study, aspirin inhibited biliary glycoprotein concentration and prevented saturation index rise [78] .


Its prokinetic effect on the biliary system has been studied in animals and in man. It has shown an inhibitory effect on papilla sphincter motility, thus enhancing bile flow [79] . Similarly in patients with postcholecystectomy syndrome, biliary drainage was promoted by cisapride [80] . These data have suggested that cisapride may also be beneficial in the prevention of stone formation and recurrence. Further experimental and clinical evaluations may help to identify its role in preven­tion.


The role of diet in the prevention of new stone formation and stone recurrence is not clear.' A study evaluating the effect of vegetarian diet on gallstone formation in women suggested a strong, independent protective effect [81] . This has not been confirmed by the recent study of the British­Belgian gallstone group in patients put on high fiber, low-refined carbohydrate diet [76] .

   Treatment of Gallstones Recurrence Top

Recurrent stones have almost been similar in their characteristics to primary stones. They may be multiple, small, radio.lucent and responded to bile acid treatment [72] . Recurrent cholesterol gallstones are treated with single full dose or com­bined half dose of each of bile acids. Bile acid therapy has been reviewed by Lanzini [59] . The optimum dose has been 15 mg/kg/day for CDCA, 10 mg/kg/day for UDCA and 5-7 mg/kg/day for combined UDCA and CDCA, respectively, at bedtime until a complete dissolution has been achieved for a minimum of two years. At the end of four years, 80% of treated patients remained free of stones.

Bile acid therapy has dissolved 47% and with appropriate patients selection, 55% of stones. Combined bile acid therapy has been considered as the treatment of choice for most patients [55] . Administration of a combined CDCA, UDCA regimen at bedtime has prevented nocturnal bile saturation and enhanced the therapy efficacy [59].

   References Top

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Correspondence Address:
Ibrahim A Al Mofleh
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Saudi Arabia
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