Reassessing cholecystectomy timing in gallstone-related acute cholangitis

Abstract

In this article, we discussed the article by Sohail et al, published in a recent issue of the World Journal of Gastrointestinal Endoscopy. This study highlights the benefits of performing cholecystectomy (CCY) during the same hospitalization for patients with acute cholangitis (AC) associated with gallstones. Specifically, same-admission CCY is associated with significantly lower 30-day readmission rates compared with interval CCY. Furthermore, it has been associated with reduced mortality rates and reduced recurrence of biliary symptoms. Despite these advantages, the procedure is chosen in only a minority of eligible patients. This gap between evidence and practice highlights the need for updated clinical guidelines and further research to optimize the timing of CCY in the management of AC.

Key Words: Cholecystectomy; Timing; Gallstone; Acute cholangitis; Surgery

Core Tip: Performing cholecystectomy during the same hospitalization for gallstone-related acute cholangitis significantly reduces 30-day readmission and mortality rates. Despite these benefits, the procedure is underutilized, highlighting the need for updated guidelines and further research to standardize early surgical intervention in appropriate patients.

TO THE EDITOR

Gallstone-related acute cholangitis (AC) is a biliary emergency, mainly caused by gallstone obstruction and is characterized by high morbidity and mortality rates[1]. Although endoscopic retrograde cholangiopancreatography (ERCP) for decompression is the first choice of treatment, it often fails to successfully treat AC, leading to persistence or recurrence of gallstones in the gallbladder. This can result in high rates of recurrence or other biliary events. In these cases, both the Tokyo 2018 guidelines and the European Society of Gastrointestinal Endoscopy guidelines recommend elective cholecystectomy (CCY) after biliary decompression to prevent these complications[2-4]. However, the available guidelines do not specify the optimal timing of CCY, i.e. whether it should be performed during the same hospitalization (index admission) or delayed to a subsequent admission (interval CCY). Several studies have explored this question, highlighting the benefits of early CCY in preventing recurrent biliary events. However, in clinical practice, same-admission CCY is significantly underused, and is performed in less than 15% of cases.

Despite the existence of prior studies on the timing of CCY for gallstone-related AC, Sohail et al[5] makes a significant contribution by leveraging national-level data to offer a comprehensive, large-scale comparison of same-admission CCY vs interval CCY outcomes. Specifically, utilizing the National Readmission Database (NRD), they studied 30-day readmission rates, in-hospital mortality, length of stay (LOS), and associated costs in patients hospitalized for gallstone-related AC. These results can significantly contribute to the selection of the best time period for intervention.

FINDINGS

The analysis by Sohail et al[5] encompasses data from 124964 patients hospitalized for gallstone-related AC between 2016 and 2020. Their key findings highlight substantial benefits of same-admission CCY over interval CCY.

Patient and hospital characteristics

Same-admission CCY was more frequently performed in younger patients (mean age 66.9 years vs 69.89 years) with fewer comorbidities.

Most same-admission procedures were conducted in teaching hospitals (77.36%), reflecting the concentration of resources and expertise required for early surgical interventions.

Readmission rates

The 30-day all-cause readmission rate for patients undergoing same-admission CCY was 5.56%, nearly half that observed in the interval CCY group (11.50%).

The most common cause of readmission in both groups was sepsis, however, recurrent AC was the second most frequent cause in the interval CCY group, reflecting the inadequacy of delaying surgical intervention.

Mortality and morbidity

Patients in the same-admission CCY group exhibited significantly lower mortality rates during both the index admission (1.18% vs 3.17%) and readmissions (2.53% vs 4.52%).

Additionally, the interval CCY group demonstrated a higher prevalence of severe comorbid conditions, such as chronic heart failure (16.97% vs 13.33%) and end-stage renal disease (2.2% vs 1.6%), which likely contributed to poorer outcomes.

Resource utilization

Same-admission CCY was associated with longer LOS during the index admission (7.4 days vs 6.5 days) and higher initial hospitalization costs ($29522 vs $24014). However, readmissions for the interval CCY group resulted in higher costs ($17672 vs $14166) and collectively accounted for $118 million in expenditures compared to $7.12 million in the same-admission CCY cohort.

The study highlights that while same-admission CCY increases short-term costs, these are offset by substantial reductions in readmission-related expenditures and associated morbidity.

These findings collectively underscore the superiority of same-admission CCY in reducing readmissions, mortality, and long-term healthcare costs, despite its association with higher initial resource utilization.

CLINICAL IMPLICATIONS

The findings of Sohail et al[5] support the use of same-entry CCY as the preferred management strategy for gallstone-related AC, as it offers multiple clinical benefits. Specifically, this technique can achieve a significant reduction in recurrent biliary events and related readmissions. Furthermore, the improved mortality and morbidity outcomes in the same-entry CCY group highlight the advantages of early surgery. Although same-entry CCY may be initially more costly due to prolonged hospitalization and surgical costs, it is a more cost-effective option as it prevents costly readmissions for complications such as sepsis and recurrent AC.

Given the current lack of clear recommendations in major guidelines, including the Tokyo 2018 and European Society of Gastrointestinal Endoscopy guidelines, this study advocates for revising existing protocols to emphasize the benefits of same-admission CCY, particularly for stable surgical candidates, thereby reducing variability in clinical practice and improving overall outcomes. Finally, Sohail et al[5] enhances decision-making by identifying risk factors for higher readmission rates in patients with CCY intervals, such as elevated Charlson comorbidity index (CCI) scores and comorbidities such as chronic heart failure and end-stage renal disease, providing valuable information to clinicians to optimize surgical planning and patient selection.

COMPARISON WITH EXISTING LITERATURE

The benefits of early CCY have been demonstrated by numerous studies regardless of etiology. These data support that there are no significant differences between the primary and secondary outcomes of the intervention, however, early intervention is superior in several areas. Friis et al[6], through a systematic review of the literature, support that the choice of early CCY is accompanied by lower conversion rates of surgery and the risk of reoccurrence and progression of disease in the interval between ERCP and surgery, without increasing mortality or complications. Gurusamy et al[7] showed after a meta-analysis of the available data that for people with AC that early intervention shortens the total hospital stay, although this is supported by trials with high risk of bias. Bagepally et al[8] also demonstrated through a meta-analysis that early intervention is also associated with lower rates of biliary complications. Khan et al[9] studied the role of CCY after endoscopic sphincterotomy in the management of choledocholithiasis in high-risk patients through a meta-analysis and demonstrated that early CCY should be performed after ERCP as it is associated with lower rates of subsequent recurrent cholecystitis, cholangitis, and biliary colic down the road even in high-risk surgical patients. Finally, Qi et al[10] support through their meta-analysis findings that early laparoscopic CCY following ERCP is the preferred approach for patients with concurrent cholecystolithiasis and choledocholithiasis, as it leads to better clinical outcomes compared to delayed laparoscopic CCY. Table 1 summarizes key studies comparing early vs delayed CCY, detailing the number of studies, total participants, relative risk for mortality and complications, and differences in hospital LOS. The findings consistently favor early CCY in reducing complications and hospital stay.

Table 1 Summary of studies comparing early vs delayed cholecystectomy.

Study ID	Number of studies	Total participants	Early CCY/delayed CCY	Relative risk for mortality	Relative risk for other findings	Length of stay (mean difference)
Gurusamy et al[7]	6	488	244/244	-	Complications: RR 1.29; 95%CI: 0.61 to 2.72; Conversion: RR 0.89; 95%CI: 0.63 to 1.25; Operating time: MD -1.22 minutes; 95%CI: -3.07 to 0.64; Return to work time: MD -11.00 days; 95%CI: -19.61 to -2.39	Not specified
Khan et al[9]	7	916	455/461	1.43 (0.93-2.18), I2 = 9%	Biliary colic and cholecystitis: RR 9.82 (4.27-22.59), I2 = 0%; Cholangitis and recurrent jaundice: RR 2.16 (1.14-4.07), I2 = 0%	MD -2.70 days (95%CI: -4.71 to -0.70)
Bagepally et al[8]	39	4483	2265/2218	0.74 (0.48-1.15)	Pain: RR 0.38 (95%CI: 0.20-0.74); Cholangitis: RR 0.52 (95%CI: 0.28-0.97); Total biliary complications: RR 0.33 (95%CI: 0.20-0.55)	MD -3.00 days (95%CI: -3.99 to -2.02)
Qi et al[10]	7	711	332/379	Not specified	Conversion rate: RR 0.38 (95%CI: 0.19 to 0.74), P = 0.005, I2 = 0%; Complications: RR 0.48 (95%CI: 0.29 to 0.79), P = 0.004, I2 = 17%; Operation time: MD -6.2 minutes (95%CI: -27.2 to -5.2), P = 0.004, I2 = 97%	Not specified

CCY: Cholecystectomy; RR: Relative risk.

Specifically, regarding the optimal timing of elective laparoscopic CCY after AC, the data are consistent with the findings of Sohail et al[5], in favor of early CCY. Li et al[11] found that the early group was characterized by a significantly lower rate of intraoperative (28.8% vs 9.4%, P = 0.029) and postoperative (42.5% vs 15.6%, P = 0.007) complications. Hoilat et al[12], calculated the 30-day readmission rate, 30-day mortality, 90-day readmission rate, and the length of hospital stay between the two groups, showing findings similar to Sohail et al[5], further strengthening the choice of early intervention. Early intervention is also supported by the findings of Discolo et al[13], which support this option due to the lower risk of developing recurrent cholangitis and a lower rate of post-operative complications. Severance et al[14], emphasize that the delayed group is characterized by a greater likelihood of CCI greater than 3 (P = 0.002), require pre-operative endoscopic sphincterotomy (P < 0.002), need pre-operative insertion of a ductal stent (P < 0.03), and had more postoperative complications (P = 0.04). Finally, these findings are supported by two other studies[15,16], indicating that early CCY is an effective procedure as an initial and definite management of acute gallstone cholangitis, which reduces both the length of hospital stay and the rates of complications and readmissions. Therefore, it should be preferred to delayed intervention.

BARRIERS TO EARLY CCY

Despite the evidence in favor of early intervention, there is a significant underuse of this technique, with Sohail et al[5] noting that it was performed in only 14.67% of cases. This may be due to a variety of factors. Initially, logistical challenges are an obstacle to the adoption of this technique. Limited availability of operating rooms, anesthesia teams, and surgical staff can delay scheduling, especially in high-volume centers. In addition, the experience of the surgeons is one of the reasons for delaying intervention in these complex patients. In addition, a particularly important factor that tends to delay intervention is patient-specific factors, such as serious comorbidities that increase surgical risk. The lack of established guidelines to regulate the optimal time of intervention leads to inconsistent application of best practices. Finally, the fear of increased inflammation that can make surgery more difficult and higher risk is often a barrier to performing early intervention, however, the available data contradict this argument as they highlight the significantly lower mortality and morbidity rates of patients undergoing early intervention.

CRITICAL ANALYSIS OF THE STUDY

The study by Sohail et al[5] provides valuable information on the timing of CCY for patients with AC associated with gallstones. Using the NRD, the study includes a significant sample size, enhancing the generalizability of its findings. It is the largest study in terms of patient numbers, significantly expanding the available literature. Its focus on clinically important outcomes, such as 30-day readmission rates, in-hospital mortality, LOS, and hospital costs, is another strength of the study. However, the study is also characterized by certain limitations.

As a retrospective analysis using the National Readmission Database, the study is inherently limited in its ability to establish causality. Associations observed between same-admission CCY, and improved outcomes may be influenced by confounding factors not fully accounted for in the analysis. The reliance on International Classification of Diseases, Tenth Revision (ICD-10) codes to identify cases and outcomes introduces the potential for coding errors or inconsistencies. Such errors could affect the accuracy of reported readmission rates, comorbidity prevalence, and resource utilization metrics. The database lacks detailed clinical information, such as the severity of AC (e.g., Tokyo grade), laboratory results, imaging findings, and intraoperative complications. This absence limits the ability to fully contextualize the outcomes and determine how disease severity influenced surgical decisions.

Patients who did not undergo same-admission CCY likely represent a sicker cohort with higher surgical risks, which could partly explain the higher readmission and mortality rates in the interval CCY group. The study acknowledges this potential bias but is unable to fully adjust for unmeasured confounders. While the large, nationally representative data set strengthens the external validity of the findings, some patient populations, such as those treated in non-teaching or resource-limited hospitals, may be underrepresented. In addition, out-of-hospital CCYs or readmissions that occur in different states are not recorded, potentially underestimating the true impact of interval CCY. The study does not explore how factors such as socioeconomic status, geographic location, or access to specialized surgical care influence the timing of CCY or patient outcomes. These variables may play a critical role in determining the feasibility of same-admission CCY for certain populations.

FURTHER INVESTIGATION

While the study by Sohail et al[5] provides significant evidence supporting same-admission CCY for patients with gallstone-related AC, several areas warrant further research to optimize patient care. Initially, randomized trials are needed between the two CCY options to confirm the benefits observed in retrospective analyses. These trials could also clarify any confounding factors. Subgroup analyses could also be performed to study which subgroups benefit most from each option. Factors such as age, comorbidities, severity of AC, and risk profiles for surgery should be considered to develop tailored guidelines that effectively balance risks and benefits.

It is also necessary to analyze the long-term outcomes of each option, including quality of life, recurrence rates of biliary complications beyond 30 days, and overall survival. Finally, it is necessary to investigate factors such as availability of surgical expertise, operating room scheduling, and institutional protocols, and other hospital and logistical factors that influence the feasibility and outcomes of same-admission CCY can inform policy decisions and resource allocation.

CONCLUSION

The study by Sohail et al[5] aims to answer the question of when to intervene in gallstone-related AC, demonstrating that same-admission CCY is associated with reduced 30-day readmission rates, lower mortality, and potential cost savings compared with interval CCY. These findings reinforce the existing literature supporting early surgical intervention in gallstone-related disease. However, same-admission CCY is underutilized in clinical practice, highlighting the need for updated guidelines and clinician education.