Cholecystitis in most cases requires a surgical intervention. The optimal timing of surgery is open for debate. Immediate or semi-acute cholecystectomy provides the quickest relief of symptoms but may technically be more challenging and may thus hold an increased risk of surgical complications. Alternatively the operation can be postponed for several weeks aiming for improved circumstances, but accepting the risk of interval relapse or complications of biliary obstruction. Delayed surgery also introduces the potential difficulty of handling tissue changes due to inflammation and scarring. Which strategy provides most safety and at the same time reduces the duration of symptoms most effectively is the issue underlying this literature analysis

Summary of Findings

Early cholecystectomy compared with delayed cholecystectomy for acute cholecystitis

Population: Patients with acute cholecystitis

Intervention: Early cholecystectomy (<72h)

Comparator: Delayed cholecystectomy

_{^1. Inconsistency: serious. Point estimates vary widely, The direction of the effect is not consistent between the included studies; Imprecision: very serious. Overlap of both limits of the 95% confidence interval with the minimal clinically important difference;}

_{^2. Risk of Bias: serious. Inadequate concealment of allocation during randomization process, resulting in potential for selection bias, Inadequate/lack of blinding of participants and personnel, resulting in potential for performance bias, Inadequate/lack of blinding of outcome assessors, resulting in potential for detection bias; Inconsistency: serious. The direction of the effect is not consistent between the included studies; Imprecision: very serious. Overlap of both limits of the 95% confidence interval with the minimal clinically important difference;}

_{^3. Risk of Bias: serious. Inadequate concealment of allocation during randomization process, resulting in potential for selection bias, Inadequate/lack of blinding of participants and personnel, resulting in potential for performance bias, Inadequate/lack of blinding of outcome assessors, resulting in potential for detection bias; Imprecision: very serious. Overlap of both limits of the 95% confidence interval with the minimal clinically important difference;}

_{^4. Risk of Bias: serious. Inadequate concealment of allocation during randomization process, resulting in potential for selection bias, Inadequate/lack of blinding of participants and personnel, resulting in potential for performance bias, Inadequate/lack of blinding of outcome assessors, resulting in potential for detection bias; Imprecision: serious. Overlap of the lower limit of the 95% confidence interval with the minimal clinically important difference;}

_{^5. Risk of Bias: serious. Inadequate concealment of allocation during randomization process, resulting in potential for selection bias, Inadequate/lack of blinding of participants and personnel, resulting in potential for performance bias, Inadequate/lack of blinding of outcome assessors, resulting in potential for detection bias;}

_{^6. Risk of Bias: serious. Inadequate concealment of allocation during randomization process, resulting in potential for selection bias, Inadequate/lack of blinding of participants and personnel, resulting in potential for performance bias, Inadequate/lack of blinding of outcome assessors, resulting in potential for detection bias; Inconsistency: serious. The direction of the effect is not consistent between the included studies; Imprecision: serious. Wide confidence intervals;}

_{^7. Risk of Bias: serious. Inadequate concealment of allocation during randomization process, resulting in potential for selection bias, Inadequate/lack of blinding of participants and personnel, resulting in potential for performance bias, Inadequate/lack of blinding of outcome assessors, resulting in potential for detection bias;}

_{^8. Risk of Bias: serious. Inadequate concealment of allocation during randomization process, resulting in potential for selection bias, Inadequate/lack of blinding of participants and personnel, resulting in potential for performance bias, Inadequate/lack of blinding of outcome assessors, resulting in potential for detection bias; Inconsistency: serious. The direction of the effect is not consistent between the included studies; Imprecision: serious. Overlap of the lower limit of the 95% confidence interval with the minimal clinically important difference;}

_{^9. Imprecision: very serious. Low number of patients, Only data from one study.}

Description of studies

A total of two systematic reviews and four additional randomized controlled trials were included in the analysis of the literature. Important study characteristics and results are summarized in table 2. The assessment of the risk of bias is summarized in the risk of bias tables (under the tab ‘Evidence tabellen’).

Systematic reviews

Wu (2023) performed a systematic review to investigate differences in efficacy, safety, and potential benefits between early laparoscopic cholecystectomy (ELC) and delayed laparoscopic cholecystectomy (DLC) in patients with acute cholecystitis. PubMed, Springer, and Cochrane Library were searched for studies published between January 1^st 1999 and January 1^st 2022. Randomized controlled trials or retrospective comparative studies which compared ELC to DLC irrespective of age, and which analyzed at least one of the primary outcomes were included in the systematic review. In total, the systematic review included 34 studies, of which 21 were RCTs. This analysis only included the RCTs that used <72 hours for the ELC group. 

Borzellino (2021) performed a systematic review to explore the hypothesis that immediate cholecystectomy (within 24h) could reduce post-operative complications when compared with delayed cholecystectomy. PubMed, Cochrane Library, Embase, and ChlinicalTrials.gov were searched. Randomized trials comparing different timings of laparoscopic cholecystectomy were included if the criteria for diagnosis of acute cholecystitis, the population, timing for surgery, and data on post-operative complications were reported. In total, fifteen studies were included in the systematic review. This analysis only included four RCTs in addition to the systematic review of Wu (2023).

Randomized controlled trials

Yadav (2023) performed a randomized controlled trial to compare early laparoscopic cholecystectomy with delayed laparoscopic cholecystectomy in patients with acute cholecystitis. The study was conducted on patients admitted to SMS Hospital in Jaipur, India. The inclusion criteria were: eighteen years of age and older, either sex, acute symptoms and a diagnosis of acute cholecystitis based on clinical and laboratory investigations, confirmed cases of cholelithiasis by USG/CT/MRCP, and written informed consent. 

Lal (2021) performed a randomized controlled trial to compare outcomes between early and delayed laparoscopic cholecystectomies. The study was conducted on patients admitted to ESI-PGIMSR and Model Hospital in New Delhi, India. The inclusion criteria were: age from eighteen to 60 years of either sex, ASA grade I and II. 

Mustafa (2016) performed a randomized controlled trial to compare early versus delayed laparoscopic cholecystectomy in patients with acute cholecystitis. The study was conducted at Ghurki Trust Teaching Hospital in Lahore, Pakistan. The inclusion criteria were: right upper quadrant pain and tenderness for more than six hours with fever >100 degrees Fahrenheit and total leukocyte count >10.000/mm³, and confirmed diagnosis on abdominal ultrasound showing presence of gall stones, distended gallbladder and gallbladder wall thickness >3mm.

Faizi (2013) performed a randomized controlled trial to compare early and interval laparoscopic cholecystectomy. The study was conducted on patients admitted to Nishtar Hospital Multan or Ali Shirazi Hospital Sahiwal in Pakistan. The inclusion criteria were: diagnosis of acute cholecystitis on the basis of history, clinical examination, and investigations.

Table 2. Characteristics of included studies

_{*For further details, see risk of bias table in the appendix}

Results

Quality of life (critical)

None of the studies reported the outcome measure quality of life.

Complications (critical)

Postoperative complications

Two systematic reviews reported the outcome measure postoperative complications (Borzellino, 2021; Wu, 2023). Of the 466 patients who underwent early cholecystectomy, 47 (10.1%) patients had a postoperative complication, compared with 60 of the 501 patients (12.0%) who underwent delayed cholecystectomy (Figure 1). The risk ratio was 0.81 (95% CI 0.46 to 1.43), in favor of the patients who underwent early cholecystectomy. The risk difference was -0.01 (95% CI -0.09 to 0.06), in favor of the patients who underwent early cholecystectomy. This difference is not considered clinically relevant.

_{Figure 1. Postoperative complications for early cholecystectomy versus delayed cholecystectomy in patients with acute cholecystitis}

_{Z: p-value of overall effect; df: degrees of freedom; I²: statistical heterogeneity; CI: confidence interval}

Wound infection

One systematic review and three individual studies reported the outcome measure wound infection (Borzellino, 2021; Faizi, 2013; Lal, 2021; Yadav, 2023). Of the 175 patients who underwent early cholecystectomy, 13 patients (7.4%) had a wound infection, compared with 29 of the 175 patients (16.6%) who underwent delayed cholecystectomy (Figure 2). The risk ratio was 0.45 (95% CI 0.33 to 0.62), in favor of the patients who underwent early cholecystectomy. The risk difference was -0.08 (95% CI -0.25 to 0.09), in favor of the patients who underwent early cholecystectomy. This difference is not considered clinically relevant.

_{Figure 2. Wound infection for early cholecystectomy versus delayed cholecystectomy in patients with acute cholecystitis}

_{Z: p-value of overall effect; df: degrees of freedom; I²: statistical heterogeneity; CI: confidence interval}

Bile leak

One systematic review and one individual study reported the outcome measure bile leak (Borzellino, 2021; Lal, 2021). Of the 120 patients who underwent early cholecystectomy, 1 patient (0.8%) had bile leak, compared with 2 of the 120 patients (1.7%) who underwent delayed cholecystectomy (Figure 3). The risk ratio was 0.70 (95% CI 0.03 to 16,56), and the risk difference was -0.01 (95% CI -0.07 to 0.04), in favor of the patients who underwent early cholecystectomy. This difference is not considered clinically relevant.

_{Figure 3. Bile leak for early cholecystectomy versus delayed cholecystectomy in patients with acute cholecystitis}

_{Z: p-value of overall effect; df: degrees of freedom; I²: statistical heterogeneity; CI: confidence interval}

Bile duct injury

One systematic review and three individual studies reported the outcome measure bile duct injury (Faizi, 2013; Jan, 2016; Mustafa, 2016; Yadav, 2023). Of the 210 patients who underwent early cholecystectomy, 17 patients (8.1%) had bile duct injury, compared with 19 of the 210 patients (9.0%) who underwent delayed cholecystectomy (Figure 4). The risk ratio was 1.04 (95% CI 0.07 to 15.79), in favor of the patients who underwent delayed cholecystectomy. The risk difference was -0.07 (-0.27 to 0.13), in favor of the patients who underwent early cholecystectomy. This difference is considered clinically relevant.

_{Figure 4. Bile duct injury for early cholecystectomy versus delayed cholecystectomy in patients with acute cholecystitis}

_{Z: p-value of overall effect; df: degrees of freedom; I²: statistical heterogeneity; CI: confidence interval}

Blood loss

Three individual studies reported the outcome measure blood loss (Lal, 2021; Mustafa, 2016; Yadav, 2023). The mean difference in blood loss between the 185 patients who underwent early cholecystectomy and the 185 patients who underwent delayed cholecystectomy was -14.47 mL (95% CI -99.46 to 70.52), in favor of the patients who underwent early cholecystectomy (Figure 5). This difference is considered clinically relevant.

_{Figure 5. Blood loss for early cholecystectomy versus delayed cholecystectomy in patients with acute cholecystitis}

_{Z: p-value of overall effect; df: degrees of freedom; I²: statistical heterogeneity; CI: confidence interval}

Length of hospital stay (important)

Total length of hospital stay

Two systematic reviews and two individual studies reported the outcome measure total length of hospital stay (Borzellino, 2021; Lal, 2021; Wu, 2023; Yadav, 2023). The mean difference in total length of hospital stay between the 616 patients who underwent early cholecystectomy and the 651 patients who underwent delayed cholecystectomy was -3.85 days (95% CI -5.15 to -2.55), in favor of the patients who underwent early cholecystectomy (Figure 6). This difference is considered clinically relevant.

_{Figure 6. Total length of hospital stay for early cholecystectomy versus delayed cholecystectomy in patients with acute cholecystitis}

_{Z: p-value of overall effect; df: degrees of freedom; I²: statistical heterogeneity; CI: confidence interval}

Postoperative length of hospital stay

Two systematic reviews and one individual studies reported the outcome measure postoperative length of hospital stay (Borzellino, 2021; Lal, 2021; Wu, 2023). The mean difference in postoperative length of hospital stay between the 345 patients who underwent early cholecystectomy and the 278 patients who underwent delayed cholecystectomy was 0.16 days (95% CI -1.09 to 1.41), in favor of the patients who underwent delayed cholecystectomy (Figure 7). This difference is not considered clinically relevant.

_{Figure 7. Postoperative length of hospital stay for early cholecystectomy versus delayed cholecystectomy in patients with acute cholecystitis}

_{Z: p-value of overall effect; df: degrees of freedom; I²: statistical heterogeneity; CI: confidence interval}

Conversion rate (important)

Two systematic reviews and four individual studies reported the outcome measure conversion rate (Borzellino, 2021; Faizi, 2013; Jan, 2016; Lal, 2021; Wu, 2023; Yadav, 2023). Of the 641 patients who underwent early cholecystectomy, 34 patients (5.3%) underwent conversion, compared with 76 of the 676 patients (11.2%) who underwent delayed cholecystectomy. The risk ratio was 0.48 (95% CI 0.31 to 0.72), in favor of the patients who underwent early cholecystectomy (Figure 8). The risk difference was -0.04 (95% CI -0.09 to 0.00), in favor of the patients who underwent early cholecystectomy. This difference is not considered clinically relevant.

_{Figure 8. Conversion rate for early cholecystectomy versus delayed cholecystectomy in patients with acute cholecystitis}

_{Z: p-value of overall effect; df: degrees of freedom; I²: statistical heterogeneity; CI: confidence interva}l

Duration of surgery (important)

Two systematic reviews and three individual studies reported the outcome measure postoperative operation time (Borzellino, 2021; Lal, 2021; Mustafa, 2016; Wu, 2023; Yadav, 2023). The mean difference in operation time between the 583 patients who underwent early cholecystectomy and the 586 patients who underwent delayed cholecystectomy was -5.30 minutes (95% CI -19.10 to 8.49), in favor of the patients who underwent early cholecystectomy (Figure 9). This difference is not considered clinically relevant.

_{Figure 9. Operation time for early cholecystectomy versus delayed cholecystectomy in patients with acute cholecystitis}

_{Z: p-value of overall effect; df: degrees of freedom; I²: statistical heterogeneity; CI: confidence interval}

Mortality (important)

One study reported the outcome measure mortality (Lal, 2021). No mortality was reported in both the intervention and control groups. Therefore, there is no clinically relevant difference between the groups.

A systematic review of the literature was performed to answer the following question(s):

What are (un)favorable effects of immediate cholecystectomy in patients with acute cholecystitis versus delay of the operation?

Table 1. PICO

Relevant outcome measures

The guideline panel considered quality of life and complications (bile duct injury, persistence or relapse of cholecystitis, intra-abdominal infection (abscess), as critical outcome measures for decision making; and mortality, length of hospital stay, conversion rate, and duration of surgery as important outcome measures for decision making.

A priori, the guideline panel did not define the outcome measures listed above but used the definitions used in the studies.

The guideline panel defined the following as minimal clinically (patient) important differences:

• Mortality: ARD 1%.
• Complications: ARD 5%:
  • Wound infection: ARD 10%.
  • Bile leak: ARD 2% .
• Length of hospital stay: 1 day.
• Conversion rate: ARD 10%.
• Quality of life: verschil van 10% van de maximale score.
• Duration of surgery: 15 min.

Search and select (Methods)

A systematic literature search was performed by a medical information specialist using the following bibliographic databases: Embase.com and Ovid/Medline. Both databases were searched from 2000 to 19 January 2025 for systematic reviews, RCTs and observational studies. Systematic searches were completed using a combination of controlled vocabulary/subject headings (e.g., Emtree-terms, MeSH) wherever they were available and natural language keywords. The overall search strategy was derived from two primary search concepts: (1) acute cholecystitis; (2) delayed cholecystectomy. Duplicates were removed using EndNote software. After deduplication a total of 1214 records were selected for title/abstract screening. Initially, 46 studies were selected based on title and abstract screening. After reading the full text, 40 studies were excluded (see the exclusion table under the tab ‘Evidence tabellen’), and six studies were included.

1. Borzellino G, Khuri S, Pisano M, Mansour S, Allievi N, Ansaloni L, Kluger Y. Timing of early laparoscopic cholecystectomy for acute calculous cholecystitis: a meta-analysis of randomized clinical trials. World J Emerg Surg. 2021 Mar 25;16(1):16. doi:10.1186/s13017-21-00360-5. PMID: 33766077; PMCID: PMC7992835.
2. El-Kordy, M. M., Aboulyazid, A. S. B., & Mahmoud, A. F. A. (2019). Comparison of outcomes of early versus delayed laparoscopic cholecystectomy in acute calcular cholecystitis. The Egyptian Journal of Hospital Medicine, 76(5), 4162-4168.
3. Faizi, K. S., Ahmed, I., & Ahmad, H. (2013). Comparison of early versus delayed laparoscopic cholecystectomy: choosing the best. Pak J Medical Health Sci, 7, 212-5.
4. Jan, Y., Shah, M., Hussain, S., Din, W., & Khan, A. (2016). Variables affecting outcome of laparoscopic cholecystectomy in acute cholecystitis. Pak J Surg, 32(1), 16-21.
5. Lal, S., Rohitaj, R., Najim, M., Dua, M., Singh, V. K., & Chakravarti, S. (2021). Early and Delayed Laparoscopic Cholecystectomy in Acute Calculus Cholecystitis: A Prospective Randomized-comparative Study. World, 14(3), 150.
6. Mustafa, M. I. T., Mustafa, A. I. T., Chaudhry, S. M., & Mustafa, R. I. T. (2016). Early vs delayed 1laparoscopic cholecystectomy in acute cholecystitis. Pak J Med Health Sci, 10(2), 371-3.
7. Wu H, Liao B, Cao T, Ji T, Huang J, Luo Y, Ma K. Comparison of the safety profile, conversion rate and hospitalization duration between early and delayed laparoscopic cholecystectomy for acute cholecystitis: a systematic review and meta-analysis. Front Med (Lausanne). 2023 Dec 11;10:1185482. doi: 10.3389/fmed.2023.1185482. PMID: 38148916; PMCID: PMC10750350.
8. Yadav, Rahul & RAO, HARSHITA & GOEL, GAURAB. (2023). A RANDOMIZED COMPARATIVE STUDY OF EARLY AND DELAYED LAPAROSCOPIC CHOLECYSTECTOMY IN ACUTE CHOLECYSTITIS: A TERTIARY CENTER EXPERIENCE AND REVIEW OF LITERATURE. International Journal of Current Pharmaceutical Research. 78-82.10.22159/ijcpr.2023v15i5.3059.