Strengthening the clinical applicability and methodological rigor in the recommendations for the management of high-surgical risk patients with acute cholecystitis

Dear Editor,

We read with great interest the recent evidence-based consensus statement on the management of high-surgical risk patients with acute cholecystitis (AC) following percutaneous cholecystostomy (PC)^[1]. This international Delphi study provides ten valuable statements supported by a targeted literature review and consolidated multidisciplinary expertise from interventional radiologists, gastroenterologists, and surgeons. However, in our view several critical clinical and methodological issues remain unresolved by this work. We followed the TITAN guideline to report the use of artificial intelligence (Supplementary Digital Content Appendix 1, available at: http://links.lww.com/JS9/E733)^[2].

First, the definition of high-surgical risk patients remains ambiguous. The Tokyo guidelines 2018 refer to the Charlson comorbidity index and American Society of Anesthesiologists Physical Status in risk assessment, as also noted in this consensus statement. However, there exist still several constraints that need attention. The terminology and criteria related to the risk level remain inconsistent (Table 1)^[3], with the exact assessment procedures varying across settings. Alternative, surgical risk prediction indicators based on, for example, frailty, gallbladder inflammation intensity and complications, altered anatomy, immunosuppression, and the POSSUM Physiological Score, have also been shown to reflect the risk of surgery accurately and objectively. Although multiple systematic reviews (SRs) on this topic exist, most fail to define a clear criteria on who should not undergo surgery.

Table 1.

Terms and definitions for the assessment of surgical risk among acute cholecystitis patients used in existing studies

Study	Terms and their definitions
Clinical guidelines	Patient risk stratification varies in AC guidelines. 2024 SICUT guideline defined three groups: (a) high-risk: age ≥ 80 years, ASA ≥ grade III, age-adjusted CCI ≥ IV, or Karnofsky score < 50; (b) critically ill: present in septic shock, i.e., a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality; (c) unfit for surgery: age ≥ 80 years, ASA ≥ grade III, age-adjusted CCI score ≥ IV, or Karnofsky score < 50 associated with severe or end-stage disease. According to 2024 EAHPBA, ANS, WSES guideline the main accepted indication for PC is AC without being able to undergo surgery due to comorbidities (unfit for surgery and/or shock or severe sepsis); these guidelines do not recommend to use fragility (ASA III and IV) as an indication for PC.
Systematic reviews	Several SRs have concluded that PC was effective in high-risk AC patients, but most did not specify in their methods section what they meant by high risk, and few conducted data syntheses or provided conclusive findings. One 2023 SR found that surgical risk assessment methods and definitions differed across studies, the most common being the ASA scale. One 2013 Cochrane SR defined patients with ASA physical status classification III to V with AC as having high-risk status irrespective of the disease severity.
Clinical trials	Definitions included terms such as high-risk, very high-risk, high surgical risk, complicated, anesthetic-risk, unfit for surgery, poor surgical candidates, and critically ill, by considering different factors (like age, CCI, ASA-PS, Karnofsky score, POSSUM, APACHE II, SOFA, or complex anatomical considerations). Most trials did however not report this information, or only mentioned high risk for surgery due to severe comorbidities without further explanation.

AC: acute cholecystitis; APACHE: acute physiology and chronic health evaluation; ASA-PS: American Society of Anesthesiologists Physical Status; CCI: Charlson Comorbidity Index; EAHPBA: European-African Hepato-Pancreato-Biliary Association; PC: percutaneous cholecystostomy; POSSUM: Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity; SICUT: Italian Society of Emergency Surgery and Trauma; SOFA: Sequential Organ Failure Assessment; SR: systematic review; WSES: World Society of Emergency Surgery.

Second, while this consensus statement gives recommendations on the indications, timing and approach of PC, and on the need of cholangiography before tube removal, the devil is in the details. Factors influencing the success of PC, such as pre-procedural imaging, operator’s expertise, drainage settings, and catheter type and number, are underexplored. The long-term management of AC patients who are not candidates for interval cholecystectomy remains also unclear. Recent studies have suggested that PC could be converted to internal drainage by endoscopic transpapillary gallbladder stenting or endoscopic ultrasound-guided gallbladder drainage to achieve prolonged biliary decompression. Success rates up to 100% have also been reported for other approaches, such as percutaneous cholecystoduodenal stenting, percutaneous cholecystolithotomy, and ERCP-assisted gallstone removal. However, concerns persist regarding serious complications, high gallstone recurrence rates and potential risks of malignancies.

Third, management of special subgroups such as the very elderly, pregnant or breastfeeding women, children and adolescents, and patients with surgically altered anatomy (for example, prior gastrectomy) is not addressed. These groups are often excluded from clinical trials due to ethical concerns, difficulties in acquiring informed consent, and the complexity of clinical conditions, and consequently the risk factors and optimal diagnostic and treatment approaches are unclear. Specifically, while advances in laparoscopic cholecystectomy have expanded surgical indications, the risk-benefit ratio for the necessity of cholecystectomy and timing in these populations remain uncertain.

Therefore, PC remains a challenging procedure. All of the above uncertainties underscore the need for individualized risk-benefit assessments and multidisciplinary management in this high-surgical risk population. A standard management algorithm is difficult to define based on currently existing evidence alone^[4]. It is crucial to address these gaps to enhance clinical decision-making. To improve clinical applicability and methodological rigor of future guidelines and consensus on this topic, we highlight the following two methodological considerations based on our experience.

Strengthening methodological rigor and transparency in the development of recommendations^[5], particularly in the systematic search of evidence: In this consensus document, 34 references were used to develop ten statements. The references included three guidelines, three reviews, two SRs, two randomized controlled trials (RCTs), and 24 observational studies of which only three were prospective. During our own independent search, we identified additional SRs with crucial information (e.g., Abdelhalim et al 2023; Ullah et al 2024; Terrone et al 2024; Wang et al 2023; Kourounis et al 2022; see Supplementary Digital Content Appendix 2, available at: http://links.lww.com/JS9/E734). Given the lack of RCTs in this field, evidence relies primarily on heterogeneous observational studies, most of which are retrospective with small sample sizes. We recommend that the developers exercise more caution in study selection and transparent reporting in methodology, incorporating findings from high-quality SRs. While these additional studies may not necessarily change the consensus statements, they could contribute to a comprehensive evidence synthesis and more precise effect estimates.

Incorporating a dedicated “research gaps or priorities” section in guidelines and consensus documents^[6]: According to the World Health Organization Guideline Handbook, knowledge gaps—where no evidence exists or significant uncertainty remains—should be explicitly described, along with potential research questions and methods for addressing them. This will facilitate new international, large-scale prospective studies with standardized protocols. For the management of high-surgical risk AC patients, identifying the optimal drainage method alone is insufficient, and more emphasis on individualized patient management, patients’ preferences and values, and multidisciplinary collaboration in the long-term care are necessary. In the future, standardized decision-making tools should be developed to mitigate variability in clinical judgment and support the development of an evidence ecosystem for gallbladder drainage.

Ethical approval

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Consent

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Sources of funding

The Project has received support from the National Key Research and Development Program of China (Grant/Award Number: 2022YFC2407405) and the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences – Research Unit of Evidenced-based Evaluation and Guidelines (Grant/Award Number: 2021RU017).

Author contributions

Q.L.S. was responsible for writing the manuscript; Y.L.C. and W.B.M. revised the manuscript. All authors participated in the final approval of the manuscript.

Conflicts of interest disclosure

All authors have no conflicts of interest to disclose.

Guarantor

Wenbo Meng.

Research registration unique identifying number (UIN)

Not applicable.

Provenance and peer review

None.

Data availability statement

Not applicable.