Gallstone Disease: Choledocholithiasis, Cholecystitis, and Gallstone Pancreatitis

Stone Types

Cholesterol stones are the most common type of stone encountered in the biliary system, accounting for approximately 80% of gallstones. These stones form through an interplay of altered gallbladder absorption and secretion, bile stasis related to gallbladder dysmotility, cholesterol supersaturation in bile, and precipitation of calcium. Cholesterol stones are typically yellow in color and nodular ( Fig. 53.1 ). There are numerous well-established risk factors for the development of cholesterol stones. Modifiable risk factors include diet, sedentary lifestyle, rapid weight loss, obesity, and dyslipidemia, whereas nonmodifiable risk factors include ethnicity, genetics, advanced age, and female gender. In addition, certain medications have been associated with increased risk of cholesterol stones due to their effect of increasing bile concentrations of cholesterol (e.g., oral contraceptives, estrogen, clofibrate) or by leading to biliary stasis by inhibiting gallbladder contraction (e.g., octreotide). Cholesterol stones typically present as cholelithiasis or secondary choledocholithiasis.

Pigment stones account for approximately 20% of gallstones. Pigment stones can be further classified into brown pigment stones or black pigment stones ( Fig. 53.2 ). Brown pigment stones are largely composed of calcium bilirubinate, and contain cholesterol and fatty acid soaps as well. Major risk factors that can precipitate the formation of brown pigment stones include any process resulting in biliary stasis and/or an infectious process. Examples include primary sclerosing cholangitis (PSC), chronic biliary obstruction from non-PSC strictures, and bacterial infections of the biliary tree, such as seen in recurrent pyogenic cholangitis. Other risk factors include conditions allowing for colonization of the biliary tree with enteric bacteria, such as indwelling biliary stents, prior biliary sphincterotomy, biliary-enteric anastomosis, and periampullary diverticula. As such, brown pigment stones typically present as primary choledocholithiasis. Black pigment stones consist of calcium bilirubinate with mucin glycoproteins. They form in the gallbladder and thus present as either cholelithiasis or secondary choledocholithiasis. Major patient risk factors include a history of hemolytic disease, such as sickle cell disease, or chronic liver disease.

Diagnosis

The clinical presentation of acute cholecystitis typically manifests as right upper quadrant abdominal pain with associated fever and leukocytosis. The classic physical exam finding is that of Murphy's sign. To assess for Murphy's sign, the examiner places their hand at the patient's right upper quadrant and palpates deeply, in the region of the gallbladder fossa under the liver edge. The patient is then asked to inspire deeply. As the diaphragm descends on inspiration, the inflamed gallbladder will approach the examiner's hand, resulting in increased pain and discomfort and typically resulting in the patient quickly halting the inspiratory effort.

No one piece of clinical, physical, or laboratory finding is sufficient to make a diagnosis of acute cholecystitis. Thus, imaging is typically utilized to support the clinical suspicion and diagnosis of acute cholecystitis. Transabdominal ultrasound (TAUS) is an easy, noninvasive, and cost-effective tool in the evaluation of patients with suspected cholecystitis. Typical findings of acute cholecystitis on TAUS include gallbladder wall thickening and edema, pericholecystic fluid, and distention or hydrops of the gallbladder. In addition, a sonographic Murphy's sign can be elicited with the ultrasound transducer. A large systematic review reported a sensitivity for TAUS in diagnosing acute cholecystitis 88%. TAUS is particularly sensitive in detecting the presence of cholelithiasis, with reported sensitivity as high as 98%. Another imaging modality commonly employed in the evaluation for possible acute cholecystitis is a nuclear scintigraphy test called cholescintigraphy. In this test, technetium-labeled hepatic iminodiacetic acid (HIDA) in injected intravenously and acts as a radiolabeled tracer. The HIDA is taken up by hepatocytes and excreted in the bile. The tracer can then be visualized as it fills the bile ducts and gallbladder. Failure of the gallbladder to fill implies cystic duct obstruction, as would be expected when cholecystitis is suspected. Multiple studies demonstrate the superiority of cholescintigraphy to TAUS in diagnosing acute cholecystitis, with reported sensitivities ranging from 90% to 97%.

Other Gallstone-Related Conditions

Aside from cholecystitis, gallstones can result in a number of other gallbladder conditions. When gallstones are impacted in the gallbladder neck or cystic duct, they may cause extrinsic compression of the adjacent common hepatic duct. The resulting bile duct obstruction typically presents as obstructive jaundice, with dilation of the upstream biliary tree (common hepatic duct and intrahepatic bile ducts), a condition referred to as Mirizzi syndrome. Type I Mirizzi syndrome occurs when there is external compression on the common hepatic duct, whereas Type II Mirizzi occurs when the impacted stone erodes through the gallbladder wall, creating a cholecysto-choledochal fistula ( Figs. 53.3 and 53.4 ). Recognition or suspicion of Type II Mirizzi syndrome is key, as this condition requires surgical repair of the bile duct injury in addition to a cholecystectomy, and thus traditionally is managed via an open surgical approach.

Large gallstones (typically ≥2 cm) that erode into the luminal GI tract by means of a cholecysto-enteral fistula can lead to mechanical intestinal obstruction. Bouveret syndrome is a rare condition characterized by a large, often single, gallstone eroding through the gallbladder wall into the proximal duodenum by way of a cholecysto-duodenal fistula. Once present in the lumen, the stone can result in a mechanical gastric outlet obstruction ( Fig. 53.5 ). Furthermore, should the stone subsequently dislodge and pass to the deep small bowel, it may again become impacted at the ileocecal valve with subsequent small bowel obstruction, thus resulting in a condition termed gallstone ileus . These conditions whereby cholecysto-enteral fistulas form are classically preceded by cholecystitis, with formation of adhesions between the gallbladder and small bowel, followed by pressure necrosis of a large gallstone, resulting in fistula formation and erosion of the stone in the GI lumen. In fact, there are numerous case reports of cholecysto-colonic fistula development resulting in gallstone erosion directly into the colon, with subsequent colonic obstruction.

The presence of cholelithiasis has long been recognized as a risk factor for the development of gallbladder cancer. Gallstones are present in up to 90% of cases of gallbladder cancer. Numerous epidemiologic studies demonstrate that the presence of gallstones can increase the risk for subsequent gallbladder cancer. Fortunately, the incidence of gallbladder cancer remains quite low (approximately 1%) in patients with a history of cholelithiasis. Factors that confer an increased risk of developing gallbladder cancer include stones larger than 3 cm and longer duration of cholelithiasis. However, given the high prevalence of gallstones and very low incidence of gallbladder cancer, screening is currently not recommended.

Therapy for Cholecystitis and Symptomatic Cholelithiasis

The mainstay of treatment for the vast majority of patients with cholecystitis and symptomatic cholelithiasis is surgical cholecystectomy. Since its introduction in the mid 1980's, laparoscopic cholecystectomy has become the standard first-line treatment for cholecystitis. Laparoscopy allows for a less invasive approach, with associated fewer overall adverse events, reduced cost, decreased length of hospital stay, and increased patient satisfaction, compared to its predecessor of open surgical resection.

In the subset of patients who may not be suitable for surgery, such as those with sepsis, hemodynamic instability, or other comorbidities precluding safe administration of anesthesia, a nonsurgical approach to managing cholecystitis is required. Percutaneous drainage of the gallbladder is a technique that is widely available and effective for rapid drainage of an inflamed and/or infected gallbladder. Two percutaneous approaches exist. Percutaneous cholecystostomy involves the use of radiologic imaging (either TASU or computed tomography [CT]) to locate the gallbladder, identify an avascular window for puncture, and allow for the placement of a percutaneous drainage catheter directly into the gallbladder. Technical success rates are typically at or near 100% and clinical success rates of 78% to 95% have been reported. Percutaneous drainage placement does have a number of associated downsides. Major procedural-related adverse events include bleeding, pneumothorax, bile peritonitis, and inadvertent displacement of the drainage catheter occur in up to 12% of patients. Lastly, long-term indwelling drainage catheters are associated with diminished quality of life in patients unfit for surgery. An alternative percutaneous approach involves simple aspiration of the gallbladder, without placement of a drainage catheter, and thus avoidance of its attendant risks. This has the advantage of being able to be performed bedside, with smaller gauge needles, fewer adverse events, and the ability to repeat the intervention if necessary. Overall, the percutaneous approach to emergent drainage of the gallbladder allows for stabilization of the severely ill patient, as well as resolution of local inflammation in severe cases, thus potentially avoiding the need for emergency surgery in high-risk individuals and/or avoidance of open surgical resection in patients with extensive pericholecystic inflammation.

A number of endoscopic options exist as an alternative to the traditional surgical or percutaneous approaches to managing cholecystitis and symptomatic cholelithiasis. These include transpapillary drainage of the gallbladder, EUS-guided transmural drainage of the gallbladder, and natural orifice transluminal endoscopic surgery (NOTES).

Endoscopic transpapillary nasogallbladder drainage involves the use of ERCP to gain transpapillary wire access to the gallbladder, followed by placement of a nasogallbladder tube, allowing for both drainage and irrigation of the infected gallbladder. The technique involves standard biliary cannulation, followed by selective guidewire cannulation of the cystic duct and the gallbladder. Given the varied locations of the cystic duct take-off, as well as the small caliber and tortuosity of the cystic duct, a variety of tools and techniques have been described to successfully achieve gallbladder access. These include the use of standard cannulating catheters, standard sphincterotomes, and sphincterotomes with the ability to rotate and/or “swing” in opposite directions to allow for directed wire placement both into the cystic duct orifice, as well as navigating the wire across the cystic duct. There is no favored guidewire size, as the use of 0.035-, 0.025-, and 0.018-inch guidewires with a hydrophilic tip have been reported. Itoi et al (2010) reported using either a 0.025- or 0.018-inch guidewire in patients with left-sided distribution or deformation of the cystic duct. Once gallbladder access is achieved, a 5-Fr or 7-Fr nasogallbladder drain can be placed over the wire. Multiple large retrospective series have been published, reporting a technical success rate of 71% to 89% and a clinical success rate of 69%to 89%. Two prospective series demonstrated a technical success of 82% to 91.9% and a clinical success of 70.6% to 87%. Overall, adverse events associated with endoscopic transpapillary nasogallbladder drainage occur in up to 14% of cases. Reported adverse events associated with this technique include cystic duct perforation, gallbladder perforation, cholangitis, sepsis, inadvertent removal of the nasogallbladder drain, as well as post-ERCP pancreatitis, and sphincterotomy-related bleeding.

Endoscopic transpapillary gallbladder stenting is similar to nasogallbladder drainage, with the exception that it has the advantages of internal placement of drainage tubes, allowing for physiologic drainage, and no risk of inadvertent dislodgement of the drain ( Fig. 53.6 ). Wire guided cannulation technique is similar to that for nasogallbladder drainage. Most series report the use of 5-Fr or 7-Fr double-pigtail plastic stents. Glessing et al (2015) described the use of the Johlin pancreatic wedge stent (Cook Medical, Bloomington, IN), which is made of a softer polyurethane material compared to standard double-pigtail stents. In addition to being softer, these stents are fenestrated, available in 8.5-Fr and 10-Fr sizes, as well as lengths up to 22 cm. Multiple large retrospective series report technical success rates ranging from 90% to 100%, and clinical success rates of 64% to 100%. Lee et al (2011) reported their prospective experience of transpapillary gallbladder stent placement in 29 patients, using a 7-Fr × 15-cm double pigtail stent. Technical success was 79% and clinical success was 100% in the group with successful stent placement. Median follow-up was 586 days, during which time 20% of patients developed late adverse events including distal stent migration, cholangitis, and recurrent biliary pain. Overall, adverse events associated with gallbladder stenting have been reported in up to 16% of cases.

Two prospective randomized trials compared endoscopic transpapillary nasogallbladder drainage to transpapillary gallbladder stenting in patients with acute cholecystitis. Itoi et al (2015) studied 73 patients, reporting a clinical success of 86.5% in the nasogallbladder drain group compared to 77.8% in the stenting group ( p > 0.05, nonsignificant [NS]), in their intention-to-treat analysis. Adverse events included one postsphincterotomy bleed and one post-ERCP pancreatitis in the nasogallbladder drain group, and one post-ERCP pancreatitis in the stent group. The authors did note patients receiving the gallbladder stent reported a significantly lower patient discomfort score compared to those receiving the nasobiliary drain. Yang et al (2016) studied 35 patients, demonstrating a clinical success rate of 70.6% in the nasogallbladder drain group compared to 83.3% in the stenting group ( p > 0.05, NS), in their intention-to-treat analysis. Adverse events included one cystic duct perforation, one severe post-ERCP pancreatitis, and one inadvertent drain pull in the nasogallbladder drain group, and one mild post-ERCP pancreatitis in the stent group.

Overall, in expert hands, endoscopic transpapillary nasogallbladder drain placement and gallbladder stent placement appear to be equivalent in terms of technical and clinical success rates. One potential downside to gallbladder stenting is that gallbladder irrigation to dissolve/remove blood and debris is not feasible, unlike in nasogallbladder drain placement. As such, this can potentially increase the risk of subsequent recurrence of cholecystitis and biliary symptoms. Recurrent cholecystitis after transpapillary gallbladder stenting has been reported to occur in 0% to 11.8% of patients. One potential strategy to minimize this risk is to place a nasogallbladder drain at initial endoscopy to allow for optimal drainage, irrigation, and possibly clearance of debris in the gallbladder, and then convert this drain to a stent once the acute inflammation resolves.

One advantage of transpapillary gallbladder stents is that they can remain in place indefinitely. In contrast to plastic CBD stents, which should be changed every 3 months to decrease the risk of cholangitis secondary to stent occlusion, there is no evidence that routine drainage of transpapillary gallbladder stents decreases the risk for recurrent biliary type pain or acute cholecystitis. Our practice has been to change the stents on an as-needed basis for the recurrence of symptoms regardless of etiology (calculous vs. acalculous). Additionally, despite lack of prospective data demonstrating an advantage of biliary sphincterotomy, we routinely perform biliary sphincterotomy in conjunction with stent placement with the thought that this may facilitate biliary drainage around the stent even in the setting of stent occlusion.

One potential challenge with attempting transpapillary gallbladder drainage pertains to the potential difficulty in achieving gallbladder access in the setting of cholecystitis. This may be secondary to the inability to identify the cystic duct on cholangiogram, and/or due to cystic duct obstruction and inability to advance a wire into the gallbladder. An emerging solution to this conundrum is the use of direct cholangioscopy to identify the cystic duct takeoff and simultaneously guide placement of a wire across the cystic duct into the gallbladder. A handful of case reports and one case series have demonstrated the feasibility and success of this technique using single-operator cholangioscopy systems.

The next evolutionary step in the endoscopic management of cholecystitis has been the development of EUS-guided transmural gallbladder drainage (EUS-GBD). First described in 2007, this technique mirrors that of EUS-guided transmural pseudocyst drainage and has the advantages of placement of internalized, larger diameter stents. EUS is used to first locate the gallbladder, followed by EUS-guided puncture of the gallbladder, typically with a 19-gauge needle in a transgastric or transduodenal approach. A guidewire can be placed through the needle into the gallbladder lumen. Once the needle is removed, various devices such as bougies, balloons, or electrosurgical knives can be placed over the guidewire to dilate the newly created cholecysto-gastric fistula or cholecysto-duodenal fistula. Finally, biliary endoprostheses such as double pigtail stents, covered metal biliary stents, or dedicated lumen-apposing metal stents (LAMS) can be placed across the tract to allow for gallbladder drainage into the GI lumen.

Initial reports described the placement of nasogallbladder drains and/or plastic double-pigtail stents across the fistulous tract. One early concern with this technique however, is that unlike most pancreatic pseudocysts that are amenable to transmural endoscopic drainage, the gallbladder is typically not adherent or apposed to the GI lumen wall. This poses the potential risk of leakage of pus and bile around the stents into the peritoneum, as well as risk of stent migration as the two lumens move away from each other with peristalsis and respiration. As such, to mitigate this risk, the use of covered metal biliary stents has become the favored approach. Widmer et al (2014) described the use of a fully covered self-expanding metal stent with antimigratory fins in three patients with symptomatic gallbladder obstruction secondary to underlying pancreatic cancer.

The true breakthrough in EUS-GBD drainage came with the development of dedicated endoprostheses designed specifically for transmural drainage. These devices, dubbed LAMS, are short (1 cm long) and have dumbbell shaped flanges. Upon expansion, the two flanges catch and appose their respective lumen walls, allowing for fistula development. Currently available LAMS are fully covered, thus preventing spillage of luminal contents across the tract. In addition, they are specifically designed to fit through the working channel of a therapeutic linear echoendoscope. Lastly, the lumen of the LAMS is wide enough (10 mm or 15 mm) to allow insertion of standard endoscopes through the stent and into the gallbladder lumen, facilitating further intervention such as irrigation, debridement, and stone removal.

In 2011, Jang et al reported their experience with a modified covered self-expandable metal stent (SEMS) (BONA-AL Standard Sci Tech Inc, Seoul, Korea). This stent is a partially covered metal stent, 10 mm in diameter, and 4 to 7 cm in length. The flares on the end of each stent were modified by enlarging them to 22 mm external diameter and placing them at a 90-degree angulation to prevent migration once in place. In 15 patients with acute cholecystitis, technical success rate was reported in 10/10 cases from a transgastric approach, and 5/5 cases from a transduodenal approach. All patients had a clinical response as well. Two patients experienced pneumoperitoneum. Choi et al (2014) reported long-term outcomes in 63 patients who underwent gallbladder drainage with this device. Technical and clinical success was reported in 98% of cases. Adverse events included one patient with a perforation, and two patients with pneumoperitoneum. Long-term outcome data was available in 56 patients, with a median follow-up of 275 days. There was no recurrence of biliary symptoms or cholecystitis in 54/56 (96%) cases over this time frame. Late adverse events were encountered in four (8.4%) patients, which included stent migration and stent occlusion. Overall, cumulative stent patency was 86% at 3 years. The authors concluded that EUS-GBD with a SEMS for acute cholecystitis showed excellent long-term outcomes and may be considered a viable definitive treatment in patients who are not surgical candidates or are suffering from advanced malignancy. Of note, the BONA-AL stent used in these two studies is not available in the Unites States.

The Axios stent (Boston Scientific, Marlborough, MA) is the only LAMS device available in the Unites States. The standard “cold” Axios device comes preloaded on an EUS needle-like delivery catheter. The standard technique for transmural gallbladder stent placement involves the identification of the gallbladder on EUS, transduodenal or transgastric puncture of the gallbladder using a 19-gauge needle, followed by passage of a 0.035-inch Jagwire through the needle and into the gallbladder lumen ( Fig. 53.7 ). The needle is then exchanged over the wire, leaving the wire in the gallbladder. The cholecysto-enteric fistula in then dilated, typically with a 6-Fr bougie dilator and/or a 4 to 6 mm biliary dilating balloon. Finally, the Axios delivery catheter is advanced over the wire, through the accessory channel of the therapeutic linear echoendoscope, and locked into place, similar to a standard EUS needle. The delivery catheter is then advanced across the fistulous tract under EUS guidance, followed by stepwise deployment of the inner distal flange, and then the outer proximal flange. Following deployment, the stent can be dilated to its final diameter using standard CRE dilating balloons (Boston Scientific); however this step is not always necessary, as the LAMS is a self-expanding type stent ( Video 53.1 ).

Small, retrospective case series have been published describing the use of the Axios stent for EUS-GBD. A 2013 report demonstrated technical success in 11/13 (84%) and clinical success in 11/11 (100%) patients. Ten of the eleven cases were transgastric. In 4/11 (36%) of patients, a tubular SEMS was placed in a coaxial fashion through the LAMS to ensure adequate drainage. During the same session, an endoscope was inserted through the stent lumen into the gallbladder to perform lavage and/or stone extraction. A total of two adverse events were noted in this series, one patient with hematochezia and another with right upper quadrant abdominal pain. There was no recurrence of cholecystitis during a median follow-up of 100 days. Irani et al reported on a multicenter experience in 15 patients. In this series, a transduodenal approach was favored in 14 cases, compared to one transgastric deployment. Technical success was 14/15 (93%) and clinical success 100%. One adverse event (fever) was noted. During a median follow-up of 160 days there was recurrence of cholecystitis in this group. It is noted that in six patients, an additional double-pigtail plastic stent was deployed through the LAMS to decrease the risk of hyperplastic tissue overgrowth at either end of the stent.

Walter et al (2016) reported the results of a multicenter prospective trial of the Axios stent in 30 patients with acute cholecystitis. Technical success was achieved in 27/30 (90%) of patients and clinical success in 26/27 (96%) patients. Recurrent cholecystitis due to stent obstruction was encountered in 7% of patients. Adverse events were encountered in 15/30 (50%) of patients, but the authors state that only 4 (13%) were possibly related to the stent or procedure. The 30-day mortality was 17% and the overall mortality was 23%. The authors state that 30-day mortality rate is comparable with that of percutaneous gallbladder drainage (15%). Their conclusion was that the high overall rate of adverse events was attributable to the overall morbid patient population of their study, as none of the patients were considered surgical candidates due to underling comorbidities.

In 2015, a modified version of the Axios stent was released with an electrocautery-enhanced tip. By allowing for direct puncture across lumen walls without the need for prior tract dilation, this “hot” Axios device allows for essentially a one-step delivery system without the need for multiple device exchanges ( Video 53.2 ). As such, the electrocautery-enhanced Axios can be placed without a guidewire.

Given the relatively widespread adoption of EUS-guided transmural pancreatic fluid collection drainage, the prospect of routine EUS-GBD with LAMS holds promise. However, the gallbladder is a hollow organ rather than a collection and thus once the inflammatory/infectious issues are resolved it will not shrink or collapse as would be expected in a pancreatic fluid collection. As a result, there are unique issues related to LAMS use. One issue is that of impaction of the gallbladder and/or stent with food, particularly when a transgastric approach is utilized. Mechanical friction of the LAMS against the mucosal surface of the gallbladder can induce bleeding (Todd Baron, personal communication). Epithelial overgrowth of the intraluminal portion of the LAMS has been reported as well. This “buried LAMS” phenomenon can result in stent occlusion and recurrent cholecystitis. In addition, this may result in technical difficulty in removing the buried stent. It is postulated that buried LAMS is most likely to occur when the stent is placed in the prepyloric antrum, as gastric motility in this location may result in traction on the stent and a hypertrophic tissue reaction, similar to that seen with the formation of inflammatory polyps of the stomach. One maneuver that has become adopted at some centers to minimize the risk of buried LAMS is to place one or two double pigtail stents inside the lumen of the LAMS. This may also decrease the risk of bleeding or food impaction.

Perhaps the biggest question remaining regarding the technique of EUS-GBD with LAMS is whether the creation of a cholecysto-duodenal fistula or cholecysto-gastric fistula will have a major impact on future cholecystectomy in any one patient. It has been shown that the transmural placement of a small caliber 5-Fr drainage tube did not result in any significantly higher need for open cholecystectomy (9%) compared to patients undergoing percutaneous gallbladder drainage (12%, NS). However, LAMS are much larger in diameter (10 mm or 15 mm) and will produce a larger fistula. As such, it remains unclear if the creation of a larger fistula will lead to difficulties in performing laparoscopic resection, or if new, unanticipated challenges will be created. Baron et al (2015) reported a case of a patient with end-stage liver disease who underwent transduodenal placement of a 10-mm LAMS for management of acute cholecystitis. Five months later, when the patient underwent liver transplantation, a large duodenal defect was encountered upon take-down of the fistula and stent. Despite oversewing the defect, placing an omental patch, leaving in surgical drains, and keeping the patient on nasogastric tube suction for 2 weeks, a leak and abscess developed at the site. Ultimately, a large hepatic artery pseudoaneurysm developed at the site of the abscess necessitating aggressive vascular intervention and ultimately surgery.

EUS-GBD remains an emerging technique. Regardless of whether plastic stents, SEMS, or LAMS are chosen, the overall adverse event rate remains moderate at 12%. In a 2016 multicenter retrospective study involving 90 patients with acute cholecystitis, EUS-GBD had similar technical and clinical success with percutaneous transhepatic gallbladder drainage. It should be emphasized that EUS-GBD should be reserved as an option for nonsurgical candidates. Optimal patient selection—ideally within a multidisciplinary approach involving surgeons, endoscopists, and interventional radiologists—remains key in predicting the overall success of this intervention.

The final frontier in the minimally invasive approach to acute cholecystitis is that of natural orifice transluminal endoscopic surgery, or NOTES. In this technique, the abdominal cavity is accessed through a small incision of an internal organ, such as the stomach, rectum, or vagina, and the endoscopic surgical tools are advanced through this incision. Thus far, this technique has been performed in a limited number of centers throughout the world, with the majority being performed via a hybrid transvaginal approach with the use of a small transumbilical port to facilitate visualization. The major potential advantages of a NOTES approach are less pain, faster recovery time, and decrease in risk of wound healing, as well as the avoidance of a visible scar. However, two prospective trials comparing NOTES cholecystectomy to laparoscopic cholecystectomy failed to demonstrate any advantage to NOTES in terms of postoperative pain, recovery, length of stay, or complications. Further studies are needed to better identify the role of NOTES in the management of gallbladder disease.

Epidemiology/Incidence/Risk Factors/Pathophysiology

Choledocholithiasis refers to the presence of stones within the extrahepatic bile duct. This is a common clinical problem, with an estimated incidence of 5% to 20% at the time of cholecystectomy in patients with cholelithiasis. Choledocholithiasis can be primary or secondary. Secondary stones are those that originate within the gallbladder and migrate into the CBD via the cystic duct. In Western countries, secondary stones are much more common than primary bile duct stones. Primary stones refer to stones that form directly within the bile duct. Risk factors for primary bile duct stones include IgA deficiency, chronic infections of the biliary tree, and biliary dyskinesia. Primary bile duct stones can also occur in patients who have undergone biliary sphincterotomy, particularly in patients who have sphincterotomy stenosis. In this setting, duodenal contents can reflux into the bile duct and serve as a nidus for stone formation. Primary bile duct stones are usually soft and brown.