Evidence-based, cost-effective management of choledocholithiasis and cholangitis: An algorithm of the Journal of Trauma and Acute Care Surgery emergency general surgery algorithms working group

This is an algorithm developed by the Journal of Trauma and Acute Care Surgery Emergency General Surgery (EGS) Algorithms working group1 addressing the diagnosis and management of choledocholithiasis (CDL), including cholangitis, in adult patients. It is based on published peer-reviewed evidence and expert opinion of the working group and represents a safe and sensible approach that can be implemented at most centers. The algorithm (Fig. 1) is annotated with letters; the corresponding text includes rationale and citations of supporting literature. This article is not a comprehensive summary of the literature, and the algorithm is not a substitute for the clinical judgment and experience of the bedside clinician; it should not be considered the “standard of care.” We recognize that there will be patient, personnel, institutional, and situational factors that may warrant or require deviation from the algorithm. We encourage institutions to use these recommendations to formulate local protocols. The annotated algorithm is intended to (a) serve as a quick bedside reference for clinicians, (b) foster more detailed patient care protocols that will allow for prospective data collection and analysis to identify best practices, and (c) generate research projects to answer specific questions concerning decision making in the management of adults with CDL and cholangitis.Figure 1: Management algorithm. RUQ, right upper quadrant; H&P, history and physical exam; US, ultrasound; CBC, complete blood count; LFTs, liver function tests; GI, gastroenterology.Gallstones are present in 10% to 20% of the US population, and approximately one-third of these individuals will develop symptoms.2 Diseases of the gallbladder are the second most common EGS condition and the most costly overall.3 The most common complication of gallstones is acute cholecystitis (AC), which has been addressed in a previous publication by this group.4 Choledocholithiasis has been reported in 10% to 15% of patients with symptomatic gallstones, and up to 20% of patients with AC.5 Surgeons will also encounter CDL when managing patients with biliary pancreatitis,6 and unsuspected common bile duct (CBD) stones are found in 2% to 5% of patients undergoing cholecystectomy (CCY).7,8 Despite the frequency of the problem, the diagnosis and treatment of CDL is not standardized, due to management by different specialties (surgery, medicine, and gastroenterology) and variations in resources and skill sets between hospitals and providers. The algorithm (Fig. 1) offers an evidence-based, cost-effective approach. TABLE 1 - High- and Intermediate-Risk Criteria for CDL, as Identified by the ASGE10 High-risk criteria Common bile duct stone on ultrasound or cross-sectional imaging Total bilirubin >4 mg/dL and dilated common bile duct Ascending cholangitis Intermediate-risk criteria Abnormal liver function tests Age >55 years Dilated common bile duct on ultrasound The evaluation of a patient presenting with right upper quadrant or epigastric abdominal pain, jaundice, or digestive complaints begins with a careful history and complete physical examination. The targeted workup for gallstone-related diseases includes a right upper quadrant ultrasound (US) examination and laboratory tests including complete blood count, liver function tests, and lipase. The liberal use of CT in the evaluation of abdominal pain may result in the diagnosis of gallstone-related disease without US. An ECG should be considered in patients at risk for acute coronary syndrome. The presenting symptoms of CDL or other biliary obstruction may be similar to those of symptomatic cholelithiasis or AC, and the problems often coexist. The suspicion for biliary obstruction is raised when patients have jaundice or report pruritis, pale stool, or dark urine. Pain or jaundice may be intermittent if small stones are passed into the duodenum after pressure builds up in the CBD. Elevations of bilirubin and alkaline phosphatase are consistent with biliary obstruction and require further evaluation; however, normal values do not rule it out. Leukocytosis with or without abnormal transaminases may be due to AC but could also herald cholangitis. A dilated CBD is often found in patients with CDL. The normal ductal diameter is estimated at 1 mm per decade of life (e.g., 4 mm in a 40-year-old); a diameter twice normal is indicative of an obstructive process.9 Based on the history and physical, laboratory evaluation, and US, patients may be classified as low, intermediate, or high risk for CDL or biliary obstruction. High- and intermediate-risk criteria identified by the American Society for Gastrointestinal Endoscopy (ASGE) are listed in Table 1, and warrant further evaluation with magnetic resonance cholangiopancreatography (MRCP), endoscopic ultrasonography (EUS), or endoscopic retrograde cholangiopancreatography (ERCP) in the nonoperative/preoperative setting; or surgeon-performed intraoperative cholangiography (IOC) or intraoperative ultrasonography (IOUS).10 Further diagnostic evaluation is currently not recommended in those with low probability as the costs and risks outweigh the likelihood and benefit of detecting unsuspected CDL.11–13 The Sunflower Study is a randomized clinical trial (7471 patients enrolled, 12-month follow-up ongoing) aimed to establish the clinical and cost effectiveness of expectant management versus preoperative imaging with MRCP in patients with symptomatic gallstones undergoing laparoscopic CCY at low or moderate risk of CDL.14 Cholangitis may be associated with Charcot's triad of fever, right upper quadrant abdominal pain, and jaundice; or in more advanced sepsis, Reynolds' pentad including hypotension and altered mental status. It is important to note that the presence of Charcot’s classic triad has a high positive predictive value for cholangitis, but many cases of cholangitis exist when the triad is absent. In a systematic review of 16 studies, it had a specificity of 93%, but a sensitivity of just 36%.15 The diagnostic criteria for cholangitis, as outlined in the Tokyo Guidelines 2018 (TG18), are presented in Figure 2.16 The TG18 included a severity grading schema, defining moderate (Grade II) and severe (Grade III) cholangitis (Fig. 3).16 Cholangitis is associated with significant morbidity, and mortality as high as 12% overall. Clinical deterioration may be rapid if sepsis ensues,16,17 and earlier biliary drainage is associated with improved outcomes—particularly in more severe illness.18–20 The 2021 ASGE guideline on the management of cholangitis has conditional recommendations (based on low quality of evidence) for early ERCP (within 48 hours), and for biliary drainage combined with sphincterotomy and stone removal rather than biliary drainage with stent alone.21 For Grade II (moderate) severity, they recommended performing biliary drainage “immediately” after diagnosis, administration of antibiotics, and initiation of general supportive care. For Grade III (severe) cases, they recommended “organ support and emergency biliary drainage.” While prospective data to support these emergent timeframes are lacking, there are retrospective data indicating improved survival among the most ill patients when drainage is performed within 12 hours to 24 hours.18,19 This is a controversial issue and a recent comprehensive review concluded that additional high-quality clinical trials are needed to make clear recommendations.22 That being said, we support the general principle of timeliness in the TG18 recommendations.16 Following biliary drainage, CCY is recommended to avoid recurrent problems with CDL or other gallstone-related diseases.9,23–25 In the patient who is not a surgical candidate due to medical comorbidities or procedural risk, options include percutaneous gallbladder drainage (PT-GBD, i.e., cholecystostomy), endoscopic transpapillary gallbladder drainage (ETP-GBD, i.e., endobiliary stent), internal gallbladder drainage to a gastric/duodenal site with a lumen-apposing metal stent (LAMS, i.e., endoscopic ultrasound-guided gallbladder drainage, EUS-GBD),26,27 lithotripsy,28–30 or observation/expectant management. Figure 2: Tokyo Guidelines diagnostic criteria for cholangitis, reproduced with permission from Miura et al.16Figure 3: Tokyo Guidelines severity assessment criteria for cholangitis, reproduced with permission from Miura et al.16The PT-GBD, ETP-GBD, and LAMS/EUS-GBD procedures are effective in mitigating gallbladder infection and inflammation, and have generally been applied to patients with AC.4 There is a paucity of data pertaining to the scenario of CDL; but if stones are not removed, then CDL could recur. Percutaneous lithotripsy has been described for poor-risk patients with AC, particularly following PT-GBD.28 Extracorporeal shock-wave lithotripsy has been used with success for many years,29 but is less effective with very large stones. In this setting, cholangioscopy-guided lithotripsy appears to be more effective.30 Observation (a.k.a. watchful waiting) without any further intervention is associated with symptomatic recurrence in up to one-third of patients within a year, with many of those patients developing cholangitis requiring emergency interventions.31 However, there does not appear to be a significant mortality difference between operative and nonoperative groups, making watchful waiting a potentially viable option for those patients who are too high-risk for surgery or other procedures.32 Routine stent exchange every 3 months is recommended over on-demand stent exchange due to lower rates of recurrent cholangitis or biliary complications.33 F. In the setting of moderate or severe pancreatitis, CBD obstruction is an indication for intervention—typically ERCP and stone extraction. After the bile duct is cleared, the patient should receive supportive care and interval CCY should be done at an appropriate time.6,34 While current data support early (within 24–48 hours) same-admission CCY in the setting of mild pancreatitis, the literature regarding timing of CCY after moderate/severe pancreatitis does not lead to firm conclusions. Delaying surgery for 6 weeks—but performing it within 8 weeks—is recommended following necrotizing pancreatitis.6,34 Scheduling should be individualized, awaiting resolution of systemic inflammatory response and organ failure and ensuring adequate drainage of peripancreatic/pericholecystic fluid collections.6,34 G. Numerous studies in gallstone-related disease states have found that patients who are discharged with gallbladder in situ after a presentation related to symptomatic gallstones have a significant risk of recurrence of gallstone-related problems.4,6,9 Thus, patients with Grade I cholangitis, mild biliary pancreatitis, AC, symptomatic cholelithiasis, or asymptomatic cholelithiasis with CDL, should have same admission CCY if they are surgical candidates. The pathway to definitive management is based on the probability of CDL. H. Although ERCP is considered the criterion standard for nonsurgical diagnosis of CDL, and it allows therapeutic intervention, it is not recommended as the first-line procedure in patients with intermediate (10–50%) probability of CDL. In addition to the resource utilization and logistics, there are risks including pancreatitis (10%), bleeding (0.3%–2%), cholangitis (0.5%–3%), cholecystitis (0.5%), duodenal perforation (0.08%–0.6%), and cardiopulmonary complications (4%–16%).35 Instead, the ASGE 2019 guidelines10 recommended diagnostic MRCP, EUS, or IOC, with the choice based on local expertise, availability of resources, and patient preference. Numerous studies have compared the accuracy of MRCP and EUS, with mixed results. A recent systematic review and meta-analysis found that there is little difference between EUS and MRCP with regard to specificity, but that EUS likely provides a higher sensitivity and accuracy for diagnosing CDL.36 In several other recent studies, EUS has been found to have better accuracy than MRCP.37–40 However, EUS has some downsides including user-dependency, specialist availability, logistical issues and cost. Given that the likelihood of having CBD stones is relatively low, and that surgeons can manage CBD stones in many cases (see below), we recommend early CCY with IOC or surgeon-performed IOUS in the intermediate-risk patient. I. The ASGE 2019 guidelines10 recommended prompt ERCP in patients with high-risk predictors for CDL. However, there is a high rate (nearly 45%) of discordance from ASGE guidelines in practice—specifically, a reluctance to perform ERCP first.12 The ASGE 2019 guideline revision was intended to improve the positive predictive value for CDL and decrease the use of diagnostic ERCP; however, validation studies have found that high-risk criteria cannot reliably identify patients for upfront ERCP.13 This has resulted in the desire to get “confirmatory” MRCP or EUS prior to ERCP, which wastes resources and delays definitive management. In recent years, the advantages of single-stage management have been reported. Intraoperative ERCP combined with CCY saves resources and shortens hospital length of stay.5,9,41,42 There has also been a resurgence of interest in laparoscopic CBDE (LCBDE), and several authors have described its safety and efficacy.5,9,43,44 We recommend either preoperative ERCP, or proceeding to CCY with IOC or IOUS. J. Once CBD stones are identified, there are several potential approaches for their management.5,9 These include: Watchful waiting ERCP before, after, or coincident with CCY CCY with CBDE There is an argument for watchful waiting in patients who have the incidental finding of CDL on imaging unrelated to right upper quadrant symptomatology. It is also known that many CBD stones identified on IOC will pass spontaneously.5,8 However, the ability to predict stone passage based on stone size or CBD diameter is not sufficient to recommend this strategy, particularly in symptomatic patients.8,45 There is no difference in efficacy, mortality, or morbidity between LCBDE and intraoperative (i.e., combined with CCY) ERCP.43,46,47 These single-stage procedures are preferable to CCY with preoperative or postoperative ERCP, as the patient can undergo a single anesthetic event and length of stay can be minimized. The barriers to wide adoption include the need to orchestrate the simultaneous presence of the surgeon and the gastroenterologist in the operating room for a dual procedure, and the technical difficulty of LCBDE. The performance of CBDE was on a downward trend for many years, from 40% of admissions for CDL in 1998 to less than 10% in 2013.48 Technological advancements such as fluoroscopy-guided, catheter-based transcystic LCBDE (TC-LCBDE) may help to reverse the trend. As an extension of IOC, balloon dilation and choledochoscopy allow stone removal via flushing, basket retrieval, electrohydraulic lithotripsy, and sphincteroplasty. Bosley et al.43 reported a success rate of 70% with this technique. Future research is warranted, to establish risks and outcomes. With the improved visualization and dexterity provided by robotic platforms it is also possible that direct surgical choledochotomy and exploration may again become practical. The “surgery first” approach is associated with decreased hospital length of stay, reduction in anesthesia episodes, and healthcare cost.43 In the unusual situation of multiple large CBD stones, ERCP and LCBDE may not be successful. In that setting, there may be consideration for open CBDE, lithotripsy or a temporizing procedure such as biliary stenting or percutaneous transhepatic drainage. This will need to be individualized. K. In a systematic review, among patients with gallbladder left in situ after ERCP with sphincterotomy, 37% had a gallstone-related complication and 26% required CCY.5,25 Patients who are not surgical candidates should have, at the minimum, clearance of the CBD. Options for gallstone management are as described in section “E;” they are all generally acceptable and are usually selected based on institutional resources, culture, and the skills and practice patterns of individual providers Watchful waiting is a reasonable strategy in those who do not have cholangitis or AC.49