Early versus Delayed Laparoscopic Cholecystectomy for Mild Acute Biliary Pancreatitis: A Systematic Review and Meta-Analysis

doi:10.21203/rs.3.rs-3576846/v1

Download PDF

Research Article

Early versus Delayed Laparoscopic Cholecystectomy for Mild Acute Biliary Pancreatitis: A Systematic Review and Meta-Analysis

https://doi.org/10.21203/rs.3.rs-3576846/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this latest preprint version

Background Laparoscopic cholecystectomy (LC) is widely accepted as the definitive therapeutic approach for MABP, primarily aiming to reduce recurrent biliary complications. However, the optimal timing of LC remains a matter of debate. The aim of this study was to evaluate the efficacy and safety of early laparoscopic cholecystectomy (ELC) versus delayed laparoscopic cholecystectomy (DLC) in patients with mild acute biliary pancreatitis (MABP).

Methods The PubMed, Embase, Scopus, and CENTRAL databases were systematically searched for randomized clinical trials (RCTs) comparing ELC with DLC in patients with MABP from inception to August 1, 2023. The primary outcome was recurrent biliary events. Secondary outcomes included postoperative complications, readmissions, and length of stay (LOS). The pooled risk ratio (RR) or standardized mean difference (SMD) of data was calculated using the random-effects model.

Results Fifteen RCTs with 1616 patients enrolled between 2010 and 2022 were included. High-certainty evidence from nine RCTs demonstrated a significantly lower risk of recurrent biliary events in patients who underwent ELC during the waiting time compared to DLC (RR=0.128[0.063, 0.262], P<0.001). For secondary outcomes, ELC in patients with MABP was associated with a significantly lower readmission rate (RR=0.382[0.182, 0.801], P=0.011) and shorter LOS (SMD=-2.026[-2.854, -1.198], P<0.001) than DLC. Subgroup analysis indicated that patients with ELC had a significantly lower rate of postoperative complications in accordance with the Atlanta criteria, MABP, and >4 weeks subgroup.

Conclusions ELC emerges as a generally safe and effective strategy in reducing recurrent biliary events, postoperative complications, readmission, and length of stay for patients with MABP.

Acute biliary pancreatitis

Laparoscopic cholecystectomy

Biliary complications

Meta-analysis

Acute pancreatitis (AP) is a prevalent gastrointestinal disorder, with a global incidence of 34 cases per 100,000 person-years.[1] The primary etiologies include gallstones, alcohol, and iatrogenic factors. Among AP subtypes, acute biliary pancreatitis (ABP) predominates, accounting for 50% of cases. Approximately 80% of AP cases display mild to moderate pancreatitis according to the revised Atlanta criteria, with roughly one-fifth advancing to severe pancreatitis, accompanied by a 20% mortality rate.[2, 3]

Laparoscopic cholecystectomy (LC) is the established therapeutic strategy for ABP, primarily aiming to reduce the risk of recurring biliary events, including biliary colic, acute cholecystitis, and recurrent pancreatitis.[4, 5] While delayed cholecystectomy is recommended for severe ABP cases,[6] the optimal timing of LC for patients with mild ABP (MABP) remains debated.[7, 8]

Current guidelines recommend LC within 2–4 weeks post-MABP discharge to prevent recurrent biliary events that could lead to readmission, increased morbidity, and additional costs.[9–15] Nevertheless, many institutions tend to postpone LC for 6–12 weeks, awaiting normalization of laboratory values and relief of abdominal pain due to concerns about complications associated with early surgical intervention.[16] Previous studies have endorsed early LC (ELC) as an effective treatment for MABP patients, leading to reduced recurrent biliary events, postoperative complications, readmission, and length of stay. However, a uniform consensus on the precise timing of ELC has not been established. The ELC rates during index admission remain relatively low, approximately 9%-23%, compared to delayed LC (DLC) for MABP patients.[17, 18]

Although several randomized controlled trials (RCTs) have compared ELC versus DLC in MABP patients, most had limited sample sizes and inconsistent reporting of outcomes.[19–33] To address these knowledge gaps, we conducted a comprehensive meta-analysis of all available RCTs comparing the timing of LC in patients with MABP to generate high-quality evidence and guide clinical practice.

This study adhered to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines.[34] The study protocol was developed in collaboration with clinical and research experts and registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42023393910). Institutional review board approval and participant consent were not required for this review of previously published research.

Data Sources and Selection

PubMed, Embase, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL) were systematically searched for RCTs investigating the timing of cholecystectomy for ABP patients from inception to August 1, 2023. MeSH terms "cholecystectomy" and "pancreatitis" were used. Reference lists of retrieved articles and relevant studies were manually reviewed by two independent researchers (S.K.Z and Y.Z) to identify additional eligible resources not captured initially.

ELC was defined as LC performed within 1 week of AP onset. MABP diagnosis relied on Ranson’s criteria,[35] revised Atlanta criteria,[36] or computed tomography severity index (CTSI).[37] Inclusion criteria encompassed MABP patients treated with cholecystectomy, randomized controlled trial design, clinical outcome comparisons between ELC and DLC, adequate and extracted clinical data, and original high-quality English articles. Exclusion criteria involved non-randomized controlled trials, patients aged < 18 or pregnant, patients with prior gallbladder removal, other pancreatitis origins or severe AP, unavailable usable clinical outcome data, non-English publications, case letters, editorials, expert opinions, conference abstracts, case reports, reviews, and duplicate articles. Two investigators independently reviewed abstracts and full-text articles, resolving discrepancies through consensus.

Clinical Outcomes

The primary outcome was recurrent biliary events requiring hospital readmission post-index hospitalization, including gallstone colic, cholecystitis, and recurrent pancreatitis. Secondary outcomes included perioperative endoscopic retrograde cholangiopancreatography (ERCP), postoperative complications, conversion to open cholecystectomy (COC), operative time, readmissions, and length of stay (LOS). Clinicopathological data such as age, BMI, WBC, AST, ALT, CRP, amylase, lipase, and total bilirubin were collected.

Subgroup Analyses

In this study, three prespecified subgroups were defined, based on ABP grading criteria (Ranson's criteria, revised Atlanta criteria, or CTSI). A post hoc subgroup analysis compared trials enrolling mild ABP patients against those with mild/moderate ABP, and trials with ELC within 4 weeks against those with ELC beyond 4 weeks in the DLC group.

Data Extraction and Risk of Bias Assessment

Two investigators (S.K.Z and Y.Z) independently extracted clinical data using a standardized form. All data were extracted directly from the publications, and authors were contacted for additional information if necessary. Risk of bias for included RCTs was assessed RoB2.[38] Risk assigned as low, some concerns, or high based on trial protocols, flowcharts, and reporting standards. Disagreements were resolved through consensus.

Strength of Evidence

The strength of evidence was evaluated using modified GRADE criteria.[39] The ratings were based on the study limitations, consistency, directness, precision, and reporting bias. Overall grade assigned as high, moderate, low, or insufficient, based on investigator consensus.

Data Synthesis and Analysis

Clinical data were recorded in an Excel spreadsheet (Microsoft Corporation). Risk ratio (RR) and standardized mean difference (SMD) with 95% confidence intervals (CIs) assessed clinical efficacy. The Cochran Q test and Higgins I² statistic were used to evaluate the heterogeneity among studies, with I² values exceeding 25%, 50%, and 75% indicating low, moderate, and high heterogeneity, respectively. Random-effects models applied in cases of significant heterogeneity. Subgroup analysis and sensitivity analysis were performed to explore the sources of heterogeneity. Publication bias was assessed through Begg's funnel plots and Egger's tests, with trim and fill analysis if needed. Data analyses were conducted using STATA 14.0 (Stata Corporation, TX, USA). P < 0.05 was considered statistically significant.

Study Selection and Characteristics

A comprehensive literature search initially identified 23,904 relevant articles, which were narrowed down to 15 eligible studies involving 1616 patients in the final meta-analysis.[19–33] The PRISMA flow diagram illustrating this process is depicted in Fig. 1. Among these studies, 2 were multicenter RCTs, and 13 were monocenter RCTs. These studies spanned diverse regions: USA, China, Netherlands, etc. Sample sizes ranged from 50 to 264, with 811 undergoing ELC and 805 undergoing DLC for ABP. ABP severity assessment was based on Ranson's criteria (5 studies), revised Atlanta criteria (9 studies), and CT severity index (1 study). Ten studies enrolled patients with mild pancreatitis, while 5 enrolled those with mild to moderate. LC was performed over 4 weeks post-diagnosis in 9 studies (Table 1).

Table 1

The main characteristics of the included studies in the meta-analysis.
First author	Year	Region	Study design	Criteria of ABP	Severity of ABP	Sample Size		Definition
First author	Year	Region	Study design	Criteria of ABP	Severity of ABP	ELC	DLC	ELC	DLC
Aboulian A et al	2010	USA	Multicentric RCT	Ranson's criteria	Mild	25	25	< 48h	> 48h
Abbas A et al	2013	Pakistan	Monocentric RCT	Ranson's criteria	Mild /Moderate	31	31	< 9d	> 6w
Zhao X et al	2013	China	Monocentric RCT	Ranson's criteria	Mild	30	30	< 48h	> 48h
Costa DW et al	2015	Netherlands	Monocentric RCT	Atlanta criteria	Mild	128	136	< 72h	25-30d
Jee SL et al	2016	Malaysia	Monocentric RCT	Atlanta criteria	Mild /Moderate	38	34	SA	> 6w
Abou-Sheishaa MS et al	2018	Egypt	Monocentric RCT	Ranson's criteria	Mild	50	46	< 72h	25-30d
Noel R et al	2018	Sweden	Monocentric RCT	Atlanta criteria	Mild	32	34	SA	> 6w
Omar MA et al	2018	Egypt	Monocentric RCT	Atlanta criteria	Mild	70	61	< 72h	> 6w
Mageed SAA et al	2019	Egypt	Monocentric RCT	Atlanta criteria	Mild	41	39	< 48h	> 6w
Mueck KM et al	2019	USA	Monocentric RCT	Atlanta criteria	Mild	49	48	< 48h	> 48h
Riquelme F et al	2019	Chile	Monocentric RCT	Atlanta criteria	Mild	26	26	< 72h	> 72h
Davoodabadi A et al	2020	Iran	Monocentric RCT	Ranson's criteria	Mild /Moderate	104	104	< 48h	> 1w
Noaman A et al	2021	India	Monocentric RCT	Atlanta criteria	Mild /Moderate	40	40	< 24h	> 6w
Chaudhari S et al	2022	India	Monocentric RCT	CTSI	Mild /Moderate	50	50	< 2w	> 2w
Facundo HG et al	2022	Spain	Multicentric RCT	Atlanta criteria	Mild	97	101	7d	4w
Abbreviations: RCT, randomized controlled trials; ABP, acute biliary pancreatitis; CTSI, computed tomography severity index; SA, same admission; ELC, early laparoscopic cholecystectomy; DLC, delayed laparoscopic cholecystectomy.

Primary Outcomes

Recurrent biliary events

The primary outcome focused on recurrent biliary events, including biliary colic, acute cholecystitis, and recurrent pancreatitis during the waiting phase for LC. Data from 9 studies (1195 participants) showed a significantly lower risk of recurrent biliary events with ELC (3.17%) compared to DLC (30.08%) (RR = 0.128, 95% CI: 0.063 to 0.262, P < 0.001, Fig. 2A), supported by moderate evidence (Additional file 1: Table S1) and showing low heterogeneity (I² = 46.2%). Subgroup analyses based on ABP criteria, severity, and time of LC consistently supported the reduced risk of recurrent biliary events (Additional file 1: Table S2-S4).

Biliary colic

Biliary colic, the most common recurrent event, had an incidence of approximately 0.83% in the ELC group and 16.47% in the DLC group. High-quality evidence from seven studies (1019 participants) indicated a significant reduction in the incidence of biliary colic for ELC compared to DLC (RR = 0.083, 95% CI: 0.039 to 0.181, P < 0.001, I² = 0%, Fig. 2B). Subgroup analyses for different ABP criteria, severity, and time of LC consistently supported this finding (Additional file 1: Table S2-S4).

Acute cholecystitis

Six RCTs reported data on acute cholecystitis in MABP patients awaiting cholecystectomy. High-quality evidence indicated a significantly lower risk of acute cholecystitis for ELC compared to DLC (RR = 0.176, 95% CI: 0.053 to 0.583, P = 0.004, I² = 0%, Fig. 2C). Subgroup analyses based on ABP criteria, and the time of LC showed similar results (Additional file 1: Table S2 and S4). However, when considering the severity of ABP, ELC did not significantly reduce the risk of acute cholecystitis in the MABP group (Additional file 1: Table S3).

Recurrent pancreatitis

Seven RCTs with 1,119 participants demonstrated that ELC significantly reduced the risk of recurrent pancreatitis compared to DLC (RR = 0.223, 95% CI: 0.112 to 0.447, P < 0.001, I² = 0%, Fig. 2D), supported by moderate evidence (Additional file 1: Table S1). This result remained consistent across subgroup analyses based on ABP criteria, severity, and time of LC (Additional file 1: Table S2-S4). Overall, these robust analyses consistently affirm the advantage of ELC over DLC in mitigating the risk of recurrent biliary events in patients with MABP.

Secondary Outcomes

Clinicopathological features

Considering the importance of laboratory normalization during the waiting phase before LC in patients with MABP, we aimed to examine the potential correlation between the timing of LC and various clinicopathological features. High-quality evidence revealed no significant correlation between the timing of LC and any of the mentioned features (Additional file 1: Table S5). However, it's noteworthy that significant heterogeneity was observed in the results related to ALT, CRP, amylase, lipase, and total bilirubin, indicating the necessity for further validation of conclusions regarding these specific features through additional investigations.

Perioperative ERCP

In recent years, there has been an increasing trend in the utilization of ERCP and sphincterotomy for the management of ABP.[40] In our analysis, we analyzed data from 10 trials involving 1246 patients, focusing on the perioperative utilization of ERCP for bile duct stones. Based on high-quality evidence, our findings revealed no significant difference in perioperative ERCP utilization between the ELC and DLC groups, with low heterogeneity observed (RR = 0.846, 95% CI: 0.642 to 1.115, P = 0.235, I² = 33.7%, Table 2). Despite the absence of significant differences, we conducted subgroup analyses based on based on different criteria and the severity of ABP, and time of LC, yielding consistent results that confirm no significant difference in ERCP usage between ELC and DLC groups (Additional file 1: Table S2-S4).

Table 2

Correlation between the timing of cholecystectomy and clinical outcomes.
Clinical parameters	No. of studies	No. of patients	RR/SMD (95% CI)	P-value	Heterogeneity
Clinical parameters	No. of studies	No. of patients	RR/SMD (95% CI)	P-value	I²	P-value
Recurrent biliary events	9	1195	0.128 (0.063 to 0.262)	< 0.001	46.2%	0.062
Biliary colic	7	1019	0.083 (0.039 to 0.181)	< 0.001	0%	0.723
Acute cholecystitis	6	845	0.176 (0.053 to 0.583)	0.004	0%	0.879
Recurrent pancreatitis	7	911	0.223 (0.112 to 0.447)	< 0.001	0%	0.967
Perioperative ERCP	10	1246	0.846 (0.642 to 1.115)	0.235	33.7%	0.138
COC	9	1175	1.108 (0.627 to 1.958)	0.725	0%	0.883
Operative time	11	1344	0.100 (-0.145 to 0.345)	0.424	79.1%	< 0.001
Postoperative complications	15	1616	0.701 (0.476 to 1.033)	0.072	8.9%	0.357
Readmission	10	1258	0.382 (0.182 to 0.801)	0.011	35.1%	0.127
Length of stay	13	1436	-2.026 (-2.854 to -1.198)	< 0.001	97.7%	< 0.001
Abbreviations: SMD, standardized mean difference; COC, conversion to open cholecystectomy.

COC

The rate of COC was evaluated based on data from nine studies involving 1175 patients. In the ELC group, the rate of COC was 4.24%, while it was 3.76% in the DLC group. High-quality evidence indicated no significant difference in the rate of COC between the ELC and DLC groups, with low heterogeneity observed (RR = 1.108, 95% CI: 0.627 to 1.958, P = 0.725, Table 2). This conclusion was further supported by moderate evidence (Additional file 1: Table S1). Notably, our analysis showed low heterogeneity among the studies (I² = 0%, P = 0.883). Subgroup analyses considering different factors produced consistent results, further supporting the lack of a significant difference in the rate of COC between the ELC and DLC groups (Additional file 1: Table S2-S4).

Operative time

In this meta-analysis, we evaluated the comparative operative time between ELC and DLC based on data from 11 studies involving 1344 patients. The pooled data revealed no significant difference in operative time between the two groups, with a SMD of 0.10 and a 95%CI ranging from − 0.145 to 0.345, resulting in a non-significant P-value of 0.424 (Table 2). The evidence quality for this outcome was adjudicated as moderate (Additional file 1: Table S1). Nevertheless, our analysis indicated substantial heterogeneity across the included studies (I² = 79.1%, P < 0.001). Subgroup analyses consistently indicated no significant difference in operative time between the ELC and DLC groups (e Additional file 1: Table S2-S4). However, it is worth noting that the operative time in the DLC group was shorter compared to the ELC group, except for three studies.[19, 22, 23] These instances could contribute to the observed heterogeneity in the overall analysis.

Postoperative complications

Postoperative complications, including bile leak, bleeding, pancreatitis, pseudocyst, or other systemic issues, were assessed in 15 studies involving 1616 patients. The meta-analysis revealed no significant difference in the incidence of postoperative complications between ELC (6.17%) and DLC (9.19%) groups, with low heterogeneity (RR = 0.701, 95% CI: 0.476 to 1.033, P = 0.072, I² = 8.9%, Fig. 3A). The evidence quality for this outcome was rated as high (Additional file 1: Table S1). To explore potential influencing factors, subgroup analyses indicated a significantly lower rate of postoperative complications in the ELC group compared to the DLC group in the Atlanta criteria, MABP, and > 4 weeks subgroup (Fig. 3B-3D and Additional file 1: Table S2-S4). These findings provide valuable insights into specific scenarios where ELC may offer advantages in reducing the rate of postoperative complications compared to DLC.

Readmission

Ten studies involving 1258 patients were included to evaluate the relationship between timing of LC and readmission rates. Pooled results revealed that ELC was correlated with a diminished risk of readmission (RR = 0.382, 95%CI: 0.182 to 0.801, P = 0.011, I² = 35.1%, Fig. 3E). This finding was substantiated by moderate-quality evidence (Additional file 1: Table S1). Furthermore, subgroup analyses provide additional evidence that ELC is associated with a reduced risk of readmission across different patient populations and timing of LC (Additional file 1: Table S2-S4). Collectively, these findings reinforce the notion that ELC might be a preferred approach to mitigate the likelihood of readmission.

Length of stay (LOS)

A comprehensive analysis of 14 studies involving 1516 patients was conducted to investigate the comparative LOS between the ELC and DLC groups. Apart from one study with missing data, the pooled results showed that patients who underwent ELC had significantly shorter LOS (SMD=-2.026, 95% CI: -2.854 to -1.198, P < 0.001, Fig. 3F) compared to patients who underwent DLC. This finding was supported by moderate-quality evidence (Additional file 1: Table S1). However, it is important to acknowledge the potential risk of publication bias and a high degree of heterogeneity (I² = 97.7%, P < 0.001). Despite the observed heterogeneity, the consistent findings across all subgroups (Additional file 1: Table S2-S4) suggest a clear trend favoring shorter hospital stays for patients undergoing ELC compared to DLC.

Risk of bias

In this meta-analysis, we evaluated bias of risks in the included studies, following the guidelines from the Cochrane Handbook for Systematic Reviews of Interventions (Additional file 1: Table S6). Three studies did not adequately report their random sequence generation method, resulting in a classification of "some concerns" regarding selection bias.[23, 27, 28] In Davoodabadi's trial, non-random allocation of patients introduced a "high" risk of bias in this domain.[30] Furthermore, four studies exhibited incomplete outcome data. Specifically, Jee's trial[23] and Facundo's trial[33] rated as having "some concerns", whereas Noel's trial[25] and Omar's trial[26] were classified as having a "high" risk for performance bias. Nevertheless, it's noteworthy that the risk of deviation from intended interventions, outcome measurements, and selective reporting were deemed "low" across all eligible studies.

Publication bias and sensitivity analysis

In this study, we applied Begg's funnel plots and Egger's tests to evaluate publication bias. Most outcomes, including recurrent biliary events, postoperative complications, and readmission, displayed symmetrical Begg's funnel plots (Fig. 4A-4C). However, when exploring the association between the timing of LC and LOS, the Begg's funnel plot showed asymmetry. To address potential publication bias, a trim and fill analysis using a random-effects model showed a symmetrical funnel plot (Fig. 4D), and the pooled analysis maintained a significant association between the timing of LC and LOS (corrected SMD=-3.145, 95% CI: -4.490 to -1.800, P < 0.001). Furthermore, sensitivity analyses were performed for recurrent biliary events, postoperative complications, readmission, and LOS, indicating that excluding any individual study did not significantly alter the overall pooled relative risk (Fig. 5).

In this systematic review and meta-analysis encompassing 15 RCTs conducted between 2010 and 2022, ELC was found to be equally safe and effective compared to DLC to reduce recurrent biliary events, postoperative complications, readmission, and hospital length of stay following MABP. Moreover, ELC was not associated with an increase in the risk of perioperative ERCP usage, COC rate, and operative time. Our findings may provide valuable insights for making decisions regarding the optimal timing of LC for patients with MABP.

Recurrent biliary events, including biliary colic, acute cholecystitis, and recurrent pancreatitis, impose substantial challenges for patients following an episode of ABP, affecting up to 9–50% of individuals.[23] Symptomatic relief achieved through conservative management often fails to address the underlying cause of pancreatitis, prompting a shift towards surgical intervention. Our comprehensive analysis of 9 RCTs demonstrated a notable reduction in the risk of recurrent biliary events (3.17%) among ABP patients undergoing ELC compared to DLC (30.08%). Importantly, DLC not only amplifies the healthcare burden but also elevates the risk of recurrent pancreatitis, with reported rates during the waiting phase reaching up to 13.4%.[41] In particular, the risk of recurrent pancreatitis was significantly lower in the ELC group (1.43%) compared to the DLC group (8.21%), especially for MABP patients. These findings highlight the potential of ELC to effectively mitigate the burden of recurrent biliary events, particularly recurrent pancreatitis, during the waiting phase.

Historically, concerns regarding the technical complexities associated with ELC have raised apprehensions among surgeons, possibly contributing to an elevated rate of COC and postoperative complications. [42–45] Nevertheless, our meta-analysis of 13 RCTs defied these concerns, revealing that ELC and DLC exhibited comparable rates of COC and postoperative complications. Intriguingly, a subgroup analysis unveiled a reduction in postoperative complications for MABP patients according to the Atlanta criteria who underwent ELC. Moreover, DLC patients undergoing surgery beyond four weeks exhibited a decrease in postoperative complications. These findings suggest that both ELC and DLC approaches may yield favorable outcomes in reducing postoperative complications, necessitating tailored patient selection and thoughtful surgical planning.

A critical concern in the management of ABP pertains to readmission rates, ranging from 15–29%, often attributed to gallstone-related complications.[22, 46–48] Our analysis concurs with existing evidence, indicating that ELC is associated with a significantly reduced risk of readmission compared to DLC. Notably, a substantial reduction in the probability of recurrent pancreatitis was observed in the ELC group (2.19%) relative to the DLC group (9.29%), underscoring the potential of ELC to minimize the likelihood of readmission for MABP patients.

The Gallstone PANC Trial highlighted the benefit of ELC within 24 hours of admission, leading to reduced ERCP interventions and 30-day length of stay for patients with predicted ABP.[28] Our pooled data indicated that MABP patients who underwent ELC showed a significantly decreased length of stay compared to those undergoing DLC. Nonetheless, subgroup analysis revealed substantial heterogeneity within subgroups, with elusive underlying causes. We propose that the variance in medical systems and insurance structures across countries plays a key is a key factor influencing hospitalization duration. Thus, we exercise caution in definitively asserting that ELC consistently leads to reduced hospital length of stay. Additional in-depth investigation is warranted to understand the intricate dynamics between surgical timing, procedural approach, and the length of hospitalization, especially within diverse healthcare systems and insurance frameworks.

Limitations

We acknowledge several potential limitations in our meta-analysis. Firstly, the diverse criteria for diagnosing MABP among the included studies inherently reflect variations in disease severity among study populations. Secondly, the considerable variability in the definitions of ELC (ranging from 24 hours post-admission to 2 weeks following discharge) and DLC (spanning 2 to 6 weeks post-discharge) introduces complexities in interpreting and generalizing the results. Thirdly, while primary outcomes showed no significant heterogeneity, notable variability in secondary outcomes, such as length of stay, across all included trials adds complexity to the interpretation of our findings. Furthermore, our meta-analysis was restricted to only 5 RCTs involving patients with moderate pancreatitis, possibly limiting the generalizability of our results to a broader population. Considering these factors, a thorough understanding of the context and specific study characteristics within our meta-analysis is essential when interpreting the implications and conclusions drawn from our findings.

In conclusion, our comprehensive analysis provides valuable insights into the optimal timing of LC for patients with MABP. ELC emerges as a secure and viable therapeutic strategy to mitigate the risk of recurrent biliary events, including recurrent pancreatitis, without incurring additional risks of postoperative complications or prolonged hospital length of stay. While certain complexities and limitations persist, the findings underscore the potential benefits of ELC in managing MABP, thereby aiding clinicians in informed decision-making and enhancing patient care.

Acknowledgements

None.

Author Contributions:

Dr Shikai Zhu had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: Yun Zhang and Shikai Zhu. Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: Yu Zhou and Shikai Zhu. Critical revision of the manuscript for important intellectual content: Feng Pu, Tang Zhao, Zhiqiang Kang, Zihan Xu, Xiaohong Zhang, Qing Wen. Statistical analysis: Yun Zhang, Qiu Zhang and Shikai Zhu. Administrative, technical, or material support: Haizhen Wang, Hongji Yang. Supervision: Shikai Zhu.

Funding

This work was supported by grant from National Natural Science Foundation of China (grant No. 81970825), Department of Science and Technology of Sichuan Province (grant No. 22JCQN0028), the Department of Chengdu Science and Technology (grant No. 2018YF05-01080-SN), National University Basic funding (grant No. ZYGX2021J034), Human Resources and Social Security of Sichuan Province (2021), and Chengdu Aikerui Technology Company (grant No. 2022HX026).

Ethics approval and consent to participate

Not applicable.

Consent for publication

All authors consent for this version of the paper to be published.

Availability of data and materials

Template data collection forms and data used for analyses can be made available on request.

Competing interests

The authors have no conflicts of interest regarding this study.

Author details

¹Organ Transplant Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China; ²Sichuan Provincial Key Laboratory for Clinical Immunology Translational Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China; ³Sichuan Provincial Key Laboratory for Human Disease Gene Study, Department of Laboratory Medicine, Center for Medical Genetics, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China; ⁴Department of Emergency, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China; ⁵Department of Cell and Molecular Pharmacology & Experimental Therapeutics, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina, USA; ⁶Department of Kidney Medicine, Cleveland Clinic Fairview Hospital, Cleveland, Ohio, USA.

Petrov MS, Yadav D: Global epidemiology and holistic prevention of pancreatitis. Nat Rev Gastroenterol Hepatol 2019, 16(3):175–184.
Colvin SD, Smith EN, Morgan DE, Porter KK: Acute pancreatitis: an update on the revised Atlanta classification. Abdom Radiol (NY) 2020, 45(5):1222–1231.
Forsmark CE, Vege SS, Wilcox CM: Acute Pancreatitis. N Engl J Med 2016, 375(20):1972–1981.
Laswi H, Attar B, Kwei R, Ishaya M, Ojemolon P, Natour B, Darweesh M, Shaka H: Readmissions After Biliary Acute Pancreatitis: Analysis of the Nationwide Readmissions Database. Gastroenterology Res 2022, 15(4):188–199.
Hormati A, Ghadir MR, Alemi F, Eshraghi M, Dehghan K, Sarkeshikian SS, Ahmadpour S, Jabbari A, Sivandzadeh GR, Mohammadbeigi A: Efficacy of Common Bile Duct Stenting on the Reduction in Gallstone Migration and Symptoms Recurrence in Patients with Biliary Pancreatitis Who Were Candidates for Delayed Cholecystectomy. Dig Dis Sci 2022, 67(1):315–320.
Dedemadi G, Nikolopoulos M, Kalaitzopoulos I, Sgourakis G: Management of patients after recovering from acute severe biliary pancreatitis. World J Gastroenterol 2016, 22(34):7708–7717.
Dubina ED, de Virgilio C, Simms ER, Kim DY, Moazzez A: Association of Early vs Delayed Cholecystectomy for Mild Gallstone Pancreatitis With Perioperative Outcomes. JAMA Surg 2018, 153(11):1057–1059.
Liu JK, Braschi C, de Virgilio CM, Ozao-Choy J, Kim DY, Moazzez A: Early Cholecystectomy in Gallstone Pancreatitis Patients With and Without End Organ Dysfunction: A NQSIP Analysis. Am Surg 2022, 88(10):2579–2583.
Working Party of the British Society of G, Association of Surgeons of Great B, Ireland, Pancreatic Society of Great B, Ireland, Association of Upper GISoGB, Ireland: UK guidelines for the management of acute pancreatitis. Gut 2005, 54 Suppl 3:iii1-9.
Chinese Pancreatic Surgery Association CSoSCMA: [Guidelines for diagnosis and treatment of acute pancreatitis in China (2021)]. Zhonghua Wai Ke Za Zhi 2021, 59(7):578–587.
Lee SH, Choe JW, Cheon YK, Choi M, Jung MK, Jang DK, Jo JH, Lee JM, Kim EJ, Han SY et al: Revised Clinical Practice Guidelines of the Korean Pancreatobiliary Association for Acute Pancreatitis. Gut Liver 2022.
Ikeda M, Hamada S, Kikuta K, Takikawa T, Yoshida N, Matsumoto R, Tanaka Y, Kataoka F, Sasaki A, Tarasawa K et al: Acute Pancreatitis in Japan: Comparison of Before and After Revision of the Clinical Guidelines. Pancreas 2022, 51(3):261–268.
Working Group IAPAPAAPG: IAP/APA evidence-based guidelines for the management of acute pancreatitis. Pancreatology 2013, 13(4 Suppl 2):e1-15.
Krishna SG, Kruger AJ, Patel N, Hinton A, Yadav D, Conwell DL: Cholecystectomy During Index Admission for Acute Biliary Pancreatitis Lowers 30-Day Readmission Rates. Pancreas 2018, 47(8):996–1002.
Hallensleben ND, Timmerhuis HC, Hollemans RA, Pocornie S, van Grinsven J, van Brunschot S, Bakker OJ, van der Sluijs R, Schwartz MP, van Duijvendijk P et al: Optimal timing of cholecystectomy after necrotising biliary pancreatitis. Gut 2022, 71(5):974–982.
Aziz H, Segalini N, Ahmed Z, Ahmad S, Goodman MD, Hertl M: National Trends in Cholecystectomy and Endoscopic Retrograde Cholangiopancreatography During Index Hospitalization for Mild Gallstone Pancreatitis. World J Surg 2022, 46(3):524–530.
Crockett SD, Wani S, Gardner TB, Falck-Ytter Y, Barkun AN, American Gastroenterological Association Institute Clinical Guidelines C: American Gastroenterological Association Institute Guideline on Initial Management of Acute Pancreatitis. Gastroenterology 2018, 154(4):1096–1101.
Hwang SS, Li BH, Haigh PI: Gallstone pancreatitis without cholecystectomy. JAMA Surg 2013, 148(9):867–872.
Aboulian A, Chan T, Yaghoubian A, Kaji AH, Putnam B, Neville A, Stabile BE, de Virgilio C: Early cholecystectomy safely decreases hospital stay in patients with mild gallstone pancreatitis: a randomized prospective study. Ann Surg 2010, 251(4):615–619.
Arshad Abbas MU, Hafiz Ghulam Isnain, Irfan Javaid, Mahmood Ayyaz.: Early cholecystectomy vs delayed cholecystectomy for gall stone pancreatitis. Pakistan Journal of Pharmaceutical Sciences 2013, 7(1):87–89.
Zhao X, Chen DZ, Lang R, Jin ZK, Fan H, Wu TM, Li XL, He Q: Enhanced recovery in the management of mild gallstone pancreatitis: a prospective cohort study. Surg Today 2013, 43(6):643–647.
da Costa DW, Bouwense SA, Schepers NJ, Besselink MG, van Santvoort HC, van Brunschot S, Bakker OJ, Bollen TL, Dejong CH, van Goor H et al: Same-admission versus interval cholecystectomy for mild gallstone pancreatitis (PONCHO): a multicentre randomised controlled trial. Lancet 2015, 386(10000):1261–1268.
Jee SL, Jarmin R, Lim KF, Raman K: Outcomes of early versus delayed cholecystectomy in patients with mild to moderate acute biliary pancreatitis: A randomized prospective study. Asian J Surg 2018, 41(1):47–54.
Abou-Sheishaa MS BW, Abbas AE, Dawoud IE, Shaker MA, Albany ANA, Razek NAE, Basher M.: When to do laparoscopic cholecystectomy in mild acute biliary pancreatitis, Early or Late? Ann Emerg Surg 2018, 3(1):1031.
Noel R, Arnelo U, Lundell L, Hammarqvist F, Jumaa H, Enochsson L, Sandblom G: Index versus delayed cholecystectomy in mild gallstone pancreatitis: results of a randomized controlled trial. HPB (Oxford) 2018, 20(10):932–938.
Omar MA MN: Acute biliary pancreatitis-optimal time for cholecystectomy: a prospective randomized study. Clin Surg 2018, 3(2151).
Mageed SAA HM, Redwan AA.: Acute mild gallstone pancreatitis: timing of cholecystectomy. Int Surg J 2019, 6(4):1051–1055.
Mueck KM, Wei S, Pedroza C, Bernardi K, Jackson ML, Liang MK, Ko TC, Tyson JE, Kao LS: Gallstone Pancreatitis: Admission Versus Normal Cholecystectomy-a Randomized Trial (Gallstone PANC Trial). Ann Surg 2019, 270(3):519–527.
Riquelme F, Marinkovic B, Salazar M, Martinez W, Catan F, Uribe-Echevarria S, Puelma F, Munoz J, Canals A, Astudillo C et al: Early laparoscopic cholecystectomy reduces hospital stay in mild gallstone pancreatitis. A randomized controlled trial. HPB (Oxford) 2020, 22(1):26–33.
Davoodabadi A, Beigmohammadi E, Gilasi H, Arj A, Taheri Nassaj H: Optimizing cholecystectomy time in moderate acute biliary pancreatitis: A randomized clinical trial study. Heliyon 2020, 6(2):e03388.
Abu Noaman MC, Balkeshwarkumar Suman: Outcomes of early versus delayed cholecystectomy in patients with mild to moderate acute biliary pancreatitis: A randomised prospective study. European Journal of Molecular & Clinical Medicine 2021, 8(4):1860–1867.
Sandip kumar Chaudhari NP, Latif Bagwan: To evaluate the role of early vs delayed laparoscopic cholecystectomy in mild and moderate acute gall stone pancreatitis. European Journal of Molecular & Clinical Medicine 2022, 9(1):54–59.
Facundo HG, Montoliu RR, Coronado Llanos DR, Naval GS, Millan EL, Gordo SL, Bosch JH, Rodriguez SL, Baranera MM, Martinez SG: Cholecystectomy 7 days vs 4 weeks after mild biliary pancreatitis; looking a decrease the incidence of persistent choledocholithiasis and ERCP: A multicentric randomized clinical trial. Int J Surg 2022, 98:106207.
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan SE et al: The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021, 372:n71.
Ranson JH, Rifkind KM, Roses DF, Fink SD, Eng K, Spencer FC: Prognostic signs and the role of operative management in acute pancreatitis. Surg Gynecol Obstet 1974, 139(1):69–81.
Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG, Tsiotos GG, Vege SS, Acute Pancreatitis Classification Working G: Classification of acute pancreatitis–2012: revision of the Atlanta classification and definitions by international consensus. Gut 2013, 62(1):102–111.
Balthazar EJ: Acute pancreatitis: assessment of severity with clinical and CT evaluation. Radiology 2002, 223(3):603–613.
Sterne JAC, Savovic J, Page MJ, Elbers RG, Blencowe NS, Boutron I, Cates CJ, Cheng HY, Corbett MS, Eldridge SM et al: RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ 2019, 366:l4898.
Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, Schunemann HJ, Group GW: GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008, 336(7650):924–926.
Bilal M, Kline KT, Trieu JA, Saraireh H, Desai M, Parupudi S, Abougergi MS: Trends in same-admission cholecystectomy and endoscopic retrograde cholangiopancreatography for acute gallstone pancreatitis: A nationwide analysis across a decade. Pancreatology 2019, 19(4):524–530.
Ito K, Ito H, Whang EE: Timing of cholecystectomy for biliary pancreatitis: do the data support current guidelines? J Gastrointest Surg 2008, 12(12):2164–2170.
da Costa DW, Schepers NJ, Bouwense SA, Hollemans RA, van Santvoort HC, Bollen TL, Consten EC, van Goor H, Hofker S, Gooszen HG et al: Predicting a 'difficult cholecystectomy' after mild gallstone pancreatitis. HPB (Oxford) 2019, 21(7):827–833.
Johnstone M, Marriott P, Royle TJ, Richardson CE, Torrance A, Hepburn E, Bhangu A, Patel A, Bartlett DC, Pinkney TD et al: The impact of timing of cholecystectomy following gallstone pancreatitis. Surgeon 2014, 12(3):134–140.
Aksoy F, Demiral G, Ekinci O: Can the timing of laparoscopic cholecystectomy after biliary pancreatitis change the conversion rate to open surgery? Asian J Surg 2018, 41(4):307–312.
Sinha R: Early laparoscopic cholecystectomy in acute biliary pancreatitis: the optimal choice? HPB (Oxford) 2008, 10(5):332–335.
Yadav D, Lee E, Papachristou GI, O'Connell M: A population-based evaluation of readmissions after first hospitalization for acute pancreatitis. Pancreas 2014, 43(4):630–637.
Vipperla K, Papachristou GI, Easler J, Muddana V, Slivka A, Whitcomb DC, Yadav D: Risk of and factors associated with readmission after a sentinel attack of acute pancreatitis. Clin Gastroenterol Hepatol 2014, 12(11):1911–1919.
Garg SK, Campbell JP, Anugwom C, Wadhwa V, Singh R, Gupta N, Sanaka MR: Incidence and Predictors of Readmissions in Acute Pancreatitis: A Nationwide Analysis. Pancreas 2018, 47(1):46–54.

No competing interests reported.

TableS1.docx
Additional file 1: Table S1. Summary of findings based on GRADE system.
TableS2.docx
Additional file 2: Table S2. Subgroup analysis for correlation between the timing of cholecystectomy and clinical outcomes
TableS3.docx
Additional file 2: Table S3. Subgroup analysis for correlation between the timing of cholecystectomy and clinical outcomes
TableS4.docx
Additional file 2: Table S4. Subgroup analysis for correlation between the timing of cholecystectomy and clinical outcomes
TableS5.docx
Additional file 3: Table S5. Correlation between the timing of cholecystectomy and clinicopathological features
TableS6.docx
Additional file 4: Table S6. Risk of bias in included RCTs

Download PDF

Version 1

posted

You are reading this latest preprint version

Early versus Delayed Laparoscopic Cholecystectomy for Mild Acute Biliary Pancreatitis: A Systematic Review and Meta-Analysis

Status:

Version 1

Abstract

Figures

Introduction

Methods

Data Sources and Selection

Clinical Outcomes

Subgroup Analyses

Data Extraction and Risk of Bias Assessment

Strength of Evidence

Data Synthesis and Analysis

Results

Study Selection and Characteristics

Primary Outcomes

Recurrent biliary events

Biliary colic

Acute cholecystitis

Recurrent pancreatitis

Secondary Outcomes

Clinicopathological features

Perioperative ERCP

COC

Operative time

Postoperative complications

Readmission

Length of stay (LOS)

Risk of bias

Publication bias and sensitivity analysis

Discussion

Limitations

Conclusions

Declarations

References

Additional Declarations

Supplementary Files

Status:

Version 1