Laser lithotripsy for the treatment of bile duct stones

INTRODUCTION — Gallstone disease continues to be a major health problem throughout the world. The prevalence of cholelithiasis varies widely by geographic region, and this variation may be attributable to both genetic and dietary factors (table 1). Some patients have gallstones in their biliary ductal system, which, in the vast majority of cases, can be removed endoscopically. (See "Gallstones: Epidemiology, risk factors and prevention".)

A variety of methods have been devised for extracting gallstones that are not easily removable using standard methods (ie, a retrieval basket or a balloon). As a general rule, these methods crush and/or fragment the stone (known as lithotripsy). In addition to laser light, methods include mechanical, electrohydraulic (EHL), and extracorporeal shock wave lithotripsy [1-5].

This topic will discuss the mechanism, equipment, indications, technique, and efficacy of laser lithotripsy for the treatment of bile duct stones. Other methods for treating bile duct stones including mechanical and electrohydraulic lithotripsy are discussed separately. (See "Endoscopic management of bile duct stones" and "Electrohydraulic lithotripsy in the treatment of bile and pancreatic duct stones".)

The use of extracorporeal shock wave lithotripsy for the treatment of pancreatic stones is also discussed separately. (See "Extracorporeal shock wave lithotripsy for pancreatic stones".)

The nonsurgical management of gallbladder stones is discussed separately. (See "Overview of nonsurgical management of gallbladder stones".)

INDICATIONS — Large stones lodged within the bile duct may require fragmentation before they can be removed endoscopically. The development of endoscopic sphincterotomy revolutionized the ways in which common bile duct stones were treated by permitting stone extraction from the bile duct with baskets or balloon catheters via a therapeutic side-viewing endoscope [6,7].

The fragmentation of large bile duct stones has been traditionally accomplished using mechanical lithotripsy, which is successful in most patients. The advantages of mechanical lithotripsy include its ease of use and widespread availability [8]. (See "Endoscopic management of bile duct stones", section on 'Mechanical lithotripsy'.)

However, for some patients, gallstones resist conventional fragmentation due to size (>2 cm), consistency (eg, bilirubin stones), anatomical position (eg, impaction), or accessibility (eg, intrahepatic stones) (table 2) [9]. Shock wave technology circumvents many of these limitations. Shock waves can be generated outside the bile duct (extracorporeal shock wave lithotripsy) and within the bile duct using electrohydraulic or laser technology [4,10,11].

Laser lithotripsy allows for precise targeting, thereby reducing the risk of bile duct injury [12-17].  

HOW LASER SYSTEMS WORK

Pulsed laser — Pulsed laser systems are most efficient at fragmenting stones and reducing the risk of injury to the surrounding tissue. Laser light is monochromatic, coherent, and collimated, creating a narrow beam of energy suitable for therapeutic applications in many medical conditions [18]. Laser-tissue interactions produced by medical lasers primarily involve photocoagulation, photothermal ablation (vaporization), and photochemical ablation.

The underlying principle of laser lithotripsy is the generation of a high-energy shock wave capable of fragmenting intraductal gallstones (picture 1). Pulsed laser systems reduce the risk of thermal injury significantly since power peaks may reach the gigawatt range (1 billion W), but only for fractions of a second [19]. This is accomplished by using a small amount of energy delivered during an extremely short pulse duration. Prior to the availability of pulsed lasers, the continuous-wave lasers (eg, cw-Nd:YAG) were inefficient for stone fragmentation because they caused drilling effects in the gallstones and thermal melting instead of lithotripsy. In addition, cw-lasers emit radiation energy over a long period of time, which may lead to increasing temperatures on the stone surface and surrounding tissue [18].

Photodisruption induced by ultrashort pulses of laser light is also gaining wider attention as an effective treatment for intraductal gallstones (picture 2).

Generation of a shock wave — Focusing the laser light to a power density of >100 billion W/cm2 achieves so-called "nonlinear optical effects" in which electrons are torn away from their atomic nuclei and matter is transformed into a plasma state (a gaseous collection of ions and free electrons) at the stone surface and within adjacent fluid. The plasma expands at supersonic speed, inducing a spherical shock wave. Oscillation of the plasma bubble (cavitation) may cause further mechanical effects, such as tensile or compressive waves directed at the stone. This transformation of optical energy into mechanical energy is commonly called "optical breakdown" (picture 2).

Tissue effects — Laser-induced shock waves are ideally supposed to hit gallstones precisely within the biliary tree without affecting the biliary epithelium. However, in clinical practice, stone targeting under direct vision or fluoroscopic control can be difficult or impossible due to anatomic variations, bouncing fragments, or floating debris. Although nonlinear optical breakdown does not cause significant thermal energy exposure to the bile duct wall, potential hazards exist during laser lithotripsy [20,21]. Several in vitro and in vivo animal studies have demonstrated that deep penetration or perforation can occur if the laser fiber has perpendicular contact with the bile duct (picture 3). The extent of damage does not seem to differ depending upon laser systems (dye lasers versus solid-state lasers) or laser fibers (bare fiber versus optomechanical coupling), but is clearly worsened with increasing pulse energies and exposure time. Direct tissue contact should be avoided during laser lithotripsy.

EQUIPMENT — Lasers used for lithotripsy are:

●Pulsed solid-state lasers (eg, q-switched neodymium:YAG [20], alexandrite, holmium:YAG [22]), or

●Flashlamp-pumped pulsed dye lasers (eg, coumarin dye, rhodamine-6G dye).

While initially the coumarin and rhodamine dye lasers were commonly used, the holmium:YAG laser and the frequency-doubled double-pulse neodymium:YAG laser have become the preferred option for biliary lithotripsy both in the United States and throughout Europe [3,23-25]. Both systems are commercially available. They have both advantages and disadvantages with regard to efficiency, tissue side effects, light transmission fibers, maintenance, and cost [3].

Because of the substantial cost of laser lithotriptors, we suggest limiting routine use to centers that specialize in the treatment of gallstone disease.

Cholangioscopy — Single-operator cholangioscopy is the most convenient and easy-to-handle approach to the biliary system allowing for safe and effective biliary laser lithotripsy under direct visual control [26-28]. With the advent of direct visualization of the intraductal stones, laser fibers, and subsequent stone fragmentation by endoscopic cholangioscopy, interest in stone tissue detection systems declined [29-35]. (See "Cholangioscopy and pancreatoscopy".)

The rationale for a stone tissue detection system was to provide laser systems with a "feedback" mechanism to avoid accidental laser radiation to the biliary epithelium during laser lithotripsy [36]. The stone tissue detection system works by either sensing that the fiber is not in contact with the stone if the intensity of the backscattered light is below a predefined threshold or by examining stone autofluorescence to allow for stone tissue differentiation [37].

TECHNIQUE

Safety precautions — Staff using medical lasers should have formal training in laser safety involving all aspects of the biologic effects and hazards of laser irradiation. Laser safety regulations should be enacted and thoroughly followed. Those interested in using lasers should attend training courses on laser principles including basic laser physics, laser tissue interaction, clinical applications, and opportunities for hands-on experience.

During laser operation, a laser warning sign should be posted at the door and the door should be kept closed. Laser eye protectors should be available at all times. Prior to inserting the optical fiber into the endoscopic delivery system, the laser should be adjusted and calibrated for output power and then placed in the off or stand-by mode. The laser fiber should be secured to the endoscope to prevent inadvertent dislodgement.

Hepatobiliary access — The biliary tree can be accessed by several different routes: peroral, transhepatic, or less commonly, laparoscopic [3,38-40]. Peroral ERCP with a duodenoscope is the standard approach to access the bile duct for performing stone fragmentation (picture 4) [2,36]. No randomized studies have been performed that directly evaluate stone fragmentation and ductal clearance rates depending on the route of hepatobiliary access. However, in rare clinical settings where ERCP is unsuccessful, a percutaneous transhepatic approach can achieve access to the bile duct or to the stones (eg, patients with giant stones in a tortuous biliary system, stones above severe biliary strictures, intrahepatic stones, or cholangiolithiasis after liver transplantation) [3,11,41]. Balloon enteroscopy-assisted ERCP has also been used for direct cholangioscopy over a guidewire through the balloon overtube. Large gallstones can then be exposed to intraductal laser lithotripsy [42].

Because of the inherent risk of complications associated with the creation of a cutaneobiliary fistula (eg, subcapsular liver hematoma, hemobilia, biliary infection), the percutaneous approach should be limited to cases not amenable to retrograde procedures [9]. Although the percutaneous transhepatic approach has been increasingly used, it is still considered to be more invasive and time-consuming compared to the peroral approach. (See "Percutaneous transhepatic cholangioscopy".)

Fragmentation procedure — Stone targeting and laser-induced disintegration can be performed under fluoroscopic or direct visual (endoscopic) control. In an attempt to enhance procedural safety, the tip of the frequency-doubled double pulse neodymium YAG (FREDDY) laser fiber has been tagged with a radiopaque marker for fluoroscopic control [43].

Available devices permit adjustment of the laser fiber by providing an acoustic signal that indicates whether the fiber is in contact with the stone or tissue. However, these are not always reliable. Laser-induced lithotripsy coupled with an automatic stone tissue detection system permits stone fragmentation by means of fluoroscopy-assisted targeting, as in conventional ERCP, in a blind although intelligent fashion [36]. Refinements of the fragmentation procedure (eg, balloon-guided approach) are regularly reported [29,44].

The development of cholangioscopy and pancreatoscopy has allowed for visual control during laser lithotripsy. However, a major limitation to this approach is that it requires two dedicated and experienced endoscopists and fragile equipment [38]. The latter limitation has been addressed by the development of more robust cholangioscopy systems [45]. The limitations may be further overcome with the emergence of steerable 9Fr/7Fr/5Fr miniscopes that can be passed through the working channel of a standard endoscope [23,30,46,47]. However, regardless of the device used, the view is often obscured during stone disintegration due to floating fragments and sludge formation [26]. Adequate flushing is more easily achieved during the percutaneous compared to the peroral approach [48]. (See "Cholangioscopy and pancreatoscopy" and "Percutaneous transhepatic cholangioscopy".)

EFFICACY — Outcome data regarding laser lithotripsy for the treatment of retained papillary, bile duct, cystic duct, or intrahepatic gallstones are derived from observational studies that report success rates (ie, complete stone removal) ranging from 80 to 97 percent [23,49-52]. As examples:

●In a multicenter study of 69 patients who were treated with the holmium:YAG laser for biliary stones under direct visualization (ie, cholangioscopy using Spyglass system), stone clearance was achieved in 97 percent of patients [23]. Eighty-two percent of the stones were extrahepatic, 12 percent were intrahepatic, and 6 percent were in the cystic duct.

●Many patients in whom stone clearance was achieved remained free of stones during long-term follow-up [53]. Of 80 patients who were treated with laser lithotripsy for bile duct stones, 11 patients (16 percent) had a symptomatic stone recurrence. The presence of a bile duct stenosis and a body mass index below 25 kg/m² were associated with an increased risk for stone recurrence.

●In a study of percutaneous laser lithotripsy (holmium:YAG) for 18 liver transplant recipients with bile duct stones and casts, stones were removed in 17 patients (94 percent) but repeat interventions during the observation period of 55 months were common (61 percent) [54].

●In a study of 34 patients with cystic duct stones and Mirizzi syndrome who failed conventional stone extraction, single-session duct clearance was achieved in 32 patients (94 percent) using cholangioscopy-guided holmium laser lithotripsy [55]. (See "Mirizzi syndrome".)

Some evidence suggests that laser lithotripsy may be safer and more effective compared with other approaches (eg, mechanical lithotripsy), particularly for difficult-to-treat biliary stone disease [51,56-62]. As examples:

●In a systematic review of 35 studies including 1762 patients with bile duct stones, compared with EHL, laser lithotripsy was associated with higher rates of achieving stone fragmentation in single session (83 versus 71 percent) and shorter procedure time (54 versus 75 minutes) [60]. However, there are no randomized trials comparing laser lithotripsy with EHL [63].

●In a study of 32 patients with large common bile duct stones who failed sphincterotomy and/or endoscopic papillary balloon dilation, cholangioscopy-guided laser lithotripsy was associated with higher stone clearance rates compared with mechanical lithotripsy (100 versus 63 percent) [57].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Gallstones".)

SUMMARY AND RECOMMENDATIONS

●Indications – Large stones lodged within the bile duct require fragmentation before they can be removed endoscopically. This has been traditionally accomplished using mechanical lithotripsy, which is successful in most patients. For some patients, gallstones resist conventional fragmentation due to size (>2 cm), consistency (eg, bilirubin stones), anatomical position (eg, impaction), or accessibility (eg, intrahepatic stones) (table 2). Shock wave technology circumvents many of these limitations. Shock waves can be generated outside the bile duct (extracorporeal shock wave lithotripsy) and within the bile duct using electrohydraulic or laser technology. (See 'Indications' above.)

●How laser systems work – Pulsed laser systems are most efficient at fragmenting stones and reducing the risk of injury to the surrounding tissue. Laser lithotripsy permits precise targeting, thereby reducing the risk of bile duct injury. (See 'How laser systems work' above.)

●Equipment – Direct visualization by single-operator cholangioscopy is the most convenient and easy-to-handle approach to the biliary system, allowing for safe and effective biliary laser lithotripsy. (See 'Equipment' above.)

Limitations of laser lithotripsy include that it uses special equipment, requires expertise in advanced endoscopy and technical certification, increases overall cost, and may not be available in some centers.