2020 World Society of Emergency Surgery updated guidelines for the diagnosis and treatment of acute calculus cholecystitis
2020年世界急診外科學會更新急性結石性膽囊炎診療指南

Abstract  抽象

Background  背景

Acute calculus cholecystitis (ACC) has a high incidence in the general population. The presence of several areas of uncertainty, along with the availability of new evidence, prompted the current update of the 2016 WSES (World Society of Emergency Surgery) Guidelines on ACC.
急性結石性膽囊炎（acute calculus cholecystitis， ACC）在一般人群中的發病率較高。幾個不確定領域的存在，以及新證據的可用性，促使 2016 年 WSES（世界急診外科學會）ACC 指南的當前更新。

Materials and methods  材料和方法

The WSES president appointed four members as a scientific secretariat, four members as an organization committee and four members as a scientific committee, choosing them from the expert affiliates of WSES. Relevant key questions were constructed, and the task force produced drafts of each section based on the best scientific evidence from PubMed and EMBASE Library; recommendations were developed in order to answer these key questions. The quality of evidence and strength of recommendations were reviewed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria (see https://www.gradeworkinggroup.org/). All the statements were presented, discussed and voted upon during the Consensus Conference at the 6th World Congress of the World Society of Emergency Surgery held in Nijmegen (NL) in May 2019. A revised version of the statements was voted upon via an online questionnaire until consensus was reached.
WSES 主席任命了四名成員作為科學秘書處、四名成員作為組織委員會和四名成員作為科學委員會，他們是從 WSES 的專家附屬機構中選出的。構建了相關的關鍵問題，工作組根據 PubMed 和 EMBASE 圖書館的最佳科學證據製作了每個部分的草稿;為了回答這些關鍵問題，制定了建議。使用推薦評估、制定和評估分級（GRADE）標準審查證據質量和推薦強度（見 https://www.gradeworkinggroup.org/）。 所有發言均於 2019 年 5 月在奈梅亨（荷蘭）舉行的世界急診外科學會第六屆世界大會共識會議上發表、討論和投票。通過在線調查問卷對發言的修訂版本進行投票，直到達成共識。

Results  結果

The pivotal role of surgery is confirmed, including in high-risk patients. When compared with the WSES 2016 guidelines, the role of gallbladder drainage is reduced, despite the considerable technical improvements available. Early laparoscopic cholecystectomy (ELC) should be the standard of care whenever possible, even in subgroups of patients who are considered fragile, such as the elderly; those with cardiac disease, renal disease and cirrhosis; or those who are generally at high risk for surgery. Subtotal cholecystectomy is safe and represents a valuable option in cases of difficult gallbladder removal.
手術的關鍵作用已得到證實，包括在高危患者中。與 WSES 2016 指南相比，儘管有相當大的技術改進，但膽囊引流的作用有所減少。早期腹腔鏡膽囊切除術 （ELC） 應儘可能成為護理標準，即使是在被認為脆弱的患者亞組中，例如老年人;患有心臟病、腎病和肝硬化的人;或那些通常處於手術高風險的人。膽囊次全切除術是安全的，在膽囊切除困難的情況下是一個有價值的選擇。

Conclusions, knowledge gaps and research recommendations
結論、知識差距和研究建議

ELC has a central role in the management of patients with ACC. The value of surgical treatment for high-risk patients should lead to a distinction between high-risk patients and patients who are not suitable for surgery. Further evidence on the role of clinical judgement and the use of clinical scores as adjunctive tools to guide treatment of high-risk patients and patients who are not suitable for surgery is required. The development of local policies for safe laparoscopic cholecystectomy is recommended.
ELC 在 ACC 患者的管理中起著核心作用。手術治療對高危患者的價值應導致區分高危患者和不適合手術的患者。需要進一步證明臨床判斷的作用以及使用臨床評分作為輔助工具來指導高危患者和不適合手術治療的患者。建議制定安全腹腔鏡膽囊切除術的地方政策。

Background  背景

The estimated overall prevalence of gallstones is 10–15% in the general population, with some differences across countries. Between 20 and 40% of patients with gallstones will develop gallstone-related complications, with an incidence of 1–3% annually; acute calculus cholecystitis (ACC) is the first clinical presentation in 10–15% of the cases [1,2,3,4,5,6]. Cholecystectomy is the most common therapeutic approach for ACC and is considered the standard of care for gallstone disease for the majority of patients. However, considering the heterogeneity of clinical scenarios, the variability in hospital facilities and in the availability of expertise, the management of patients with right upper quadrant abdominal pain may vary.
膽結石在普通人群中的總體患病率估計為 10-15%，各國之間存在一些差異。20%-40%的膽結石患者會出現膽結石相關併發症，每年發生率為 1-3%;急性結石膽囊炎（acute calculus cholecystitis， ACC）是 10-15%的病例的首發臨床表現[1,2,3,4,5,6]。 膽囊切除術是 ACC 最常見的治療方法，被認為是大多數患者膽結石病的標準治療。然而，考慮到臨床情況的異質性、醫院設施的可變性和專業知識的可用性，右上腹痛患者的治療可能會有所不同。

In 2016, the World Society of Emergency Surgery (WSES) published the first edition of their guidelines for ACC [7], which presented different diagnostic and therapeutic algorithms, compared with the Tokyo Guidelines (TG), known at that time as Tokyo Guidelines 2013 (TG13) [8]. In particular, the direct link between diagnostic criteria for ACC, severity classification and therapeutic indications described in the TG13 are limited by lack of quality evidence. The approach of the WSES guidelines was to simplify the initial management of patients presenting with suspected ACC. The literature review, the discussion of the relevant evidence and the statements made during the consensus conference (CC) held in Jerusalem in 2015 (Third WSES International Congress) supported surgery as the gold standard treatment for all patients with ACC, with two exceptions: patients who refuse surgery, and patients for whom surgery would be considered as ‘very high risk’, although no clear consensus was reached on this second issue. Moreover, the 2016 WSES Guidelines on ACC included discussions on unclear areas, such as diagnosis, evaluation of the surgical risk and appropriate management of associated common bile duct stones (CBDS).
2016 年，世界急診外科學會（WSES）發佈了第一版 ACC 指南[7]，與當時稱為東京指南（TG）相比，提出了不同的診斷和治療演算法[8]。特別是，由於缺乏高質量證據，ACC 的診斷標準、嚴重程度分類和 TG13 中描述的治療適應症之間的直接聯繫受到限制。WSES 指南的方法是簡化疑似 ACC 患者的初始管理。文獻綜述、相關證據的討論以及 2015 年在耶路撒冷舉行的共識會議 （CC）（第三屆 WSES 國際大會）期間發表的聲明支持手術作為所有 ACC 患者的金標準治療方法，但有兩個例外：拒絕手術的患者和手術被視為「極高風險」的患者， 儘管在第二個問題上沒有達成明確的共識。此外，2016 年 WSES ACC 指南包括對不明確領域的討論，例如診斷、手術風險評估和相關膽總管結石 （CBDS） 的適當管理。

In 2017, the WSES joined the Italian Society for Geriatric Surgery during a CC regarding the management of ACC in the elderly, with the aim of investigating this subgroup of fragile patients, considered at ‘very high risk’ for surgery. There was lack of agreement supporting the surgical management of ACC in the elderly and considering old age as a contraindication for surgery by itself. The authors found substantial lack of high-quality studies on this topic [9].
2017 年，WSES 在關於老年人 ACC 管理的 CC 期間加入了義大利老年外科學會，旨在調查這一被認為具有「極高風險」手術的脆弱患者亞組。缺乏支援老年人 ACC 手術治療的一致意見，並將老年視為手術本身的禁忌症。作者發現，關於該主題的高品質研究嚴重缺乏[9]。

The WSES, after evaluating the 2018 edition of the TG (TG18) on ACC [10], found that this new edition reached conclusions that were closer to the recommendations of the 2016 WSES guidelines on ACC, especially in terms of a more liberal indication for surgery including grade 3 ACC. However, some differences remain when comparing the WSES guidelines and the TG (all editions), as evident in the recommendations in the current updated guidelines. A combined event, WSES and TG group could be an opportunity to share experiences considering different perspectives.
WSES 在評估了 2018 年版 TG（TG18）關於 ACC 的[10]后發現，這個新版本得出的結論更接近 2016 年 WSES 關於 ACC 的指南的建議，特別是在更寬鬆的手術適應症方面，包括 3 級 ACC。然而，在比較 WSES 準則和 TG（所有版本）時，仍然存在一些差異，正如當前更新準則中的建議所表明的那樣。WSES 和 TG 小組的聯合活動可以成為分享考慮不同觀點的經驗的機會。

Since the publication of the 2016 WSES Guidelines and the TG18, the management of the high-risk patients with ACC was investigated in a randomized controlled trial (RCT), known as the CHOCOLATE trial [11]. Loozen and collaborators compared cholecystectomy to percutaneous catheter drainage in high-risk surgical patients. This research group has joined with other experts in contributing to this edition of the WSES guidelines on ACC.
自 2016 年 WSES 指南和 TG18 發佈以來，一項隨機對照試驗（randomized controlled trial， RCT）對 ACC 高危患者的管理進行了研究，即 CHOCOLATE 試驗[11]。Loozen 和合作者將膽囊切除術與經皮導管引流術在高危手術患者中進行了比較。該研究小組與其他專家一起為本版 WSES 關於 ACC 的指南做出了貢獻。

Materials and methods  材料和方法

In 2018, the Scientific Board of the 6thWorld Congress of the WSES endorsed its president to organize a CC on ACC in order to update the previous WSES Guidelines. The WSES president appointed four members as a scientific secretariat, four members as an organization committee and four members as a scientific committee, choosing them from the expert affiliates of the WSES. Relevant key questions regarding the diagnosis and treatment of ACC were developed and divided into seven sections, in order to analyse the topic and update the guidelines with the currently available evidence. Under the supervision of the scientific secretariat, a bibliographic search related to these questions was performed, using electronic search of PubMed and EMBASE databases in May 2019, with no date or language restrictions. An additional manual search of the literature was performed by members of the working groups involved in the analysis of the papers and the development of the guidelines. The topics and sections, the key questions and the related key words used to develop the update on ACC are available in Table 1.
2018 年，第六屆世界 WSES 大會科學委員會批准其主席組織一次關於 ACC 的 CC，以更新以前的 WSES 指南。WSES 主席任命了四名成員作為科學秘書處，四名成員作為組織委員會，四名成員作為科學委員會，他們是從 WSES 的專家附屬機構中選出的。制定了有關 ACC 診斷和治療的相關關鍵問題，並將其分為七個部分，以便分析該主題並根據當前可用的證據更新指南。在科學秘書處的監督下，於 2019 年 5 月使用 PubMed 和 EMBASE 資料庫的電子檢索，對這些問題進行了書目檢索，沒有日期或語言限制。參與論文分析和準則制定的工作組成員對文獻進行了額外的人工檢索。表 1 提供了用於制定 ACC 更新的主題和部分、關鍵問題和相關關鍵字。

Table 1 Sections/topics, key questions and key words
表1 各節/專題、關鍵問題和關鍵詞

Before the CC, the statements and recommendations were reviewed by the representatives responsible for each of the sections, creating a draft version of the guidelines. The quality of evidence and strength of recommendations were reviewed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria (see https://www.gradeworkinggroup.org/). Specifically, the quality of evidence was graded as ‘High’, ‘Moderate’, ‘Low’ or ‘Very low’ and the strength of a recommendation was indicated as either ‘Strong’ or ‘Weak’. Consensus had previously been defined as 70% or more of the votes being in agreement. During the 6th World Congress of the WSES held in Nijmegen, the Netherlands in May 2019, each question was discussed and voted upon by the audience (votes were either ‘agree’ or ‘disagree’). The percentage of agreement was recorded immediately; in case of disagreement, the statement was modified following discussion. After the CC, the president and representatives reviewed the guidelines in response to the comments and the revised version of the statements was voted upon via an online questionnaire until consensus was reached. Throughout the period of the elaboration of the current guidelines, repeated literature searches were carried out in order to maximize the inclusion of relevant evidence (last literature search: May 2020).
在 CC 之前，負責每個部分的代表審查了聲明和建議，並創建了指南的草案版本。使用推薦評估、制定和評估分級（GRADE）標準審查證據質量和推薦強度（見 https://www.gradeworkinggroup.org/）。 具體來說，證據品質被分級為“高”、“中”、“低”或“非常低”，推薦的強度被標記為“強”或“弱”。以前，共識被定義為 70% 或更多的選票同意。2019 年 5 月在荷蘭奈梅亨舉行的第六屆 WSES 世界大會期間，每個問題都由觀眾討論和投票（投票為“同意”或“不同意”）。同意的百分比立即記錄下來;如有分歧，經討論後修改了該聲明。CC 之後，主席和代表根據意見審查了指導方針，並通過在線問卷對聲明的修訂版本進行了投票，直到達成共識。在制定現行指南的整個過程中，為了最大限度地納入相關證據，我們進行了反覆的文獻檢索（最後一次文獻檢索：2020 年 5 月）。

These Guidelines should be considered an adjunctive tool for decision making, but they are not a substitute for the surgeon’s judgement in specific clinical situations.
這些指南應被視為決策的輔助工具，但它們不能替代外科醫生在特定臨床情況下的判斷。

In Appendix 1, the reader can find the summary of statements with short explanation of the supporting scientific evidence while details are in the body of the paper. Figure 1 represents the 2020 WSES flowchart for the management of ACC patients.
在附錄 1 中，讀者可以找到陳述摘要，並簡要解釋支持科學證據，而詳細資訊則在論文正文中。圖 1 代表了 2020 年 WSES ACC 患者管理流程圖。

Fig. 1  圖1

2020 WSES Flowchart for the management of patients with acute calcolus cholecystitis
2020 年 WSES 急性結石性膽囊炎患者管理流程圖

The WSES committee for guidelines development is responsible for the continuous evaluation of evidence available about acute cholecystitis. The present guidelines will be updated in case of significant changes based on new evidence.
WSES 指南制定委員會負責持續評估有關急性膽囊炎的現有證據。如果根據新證據發生重大變化，本指南將進行更新。

Section 1. Diagnosis of ACC
第 1 節。ACC 的診斷

1.1 As no feature has sufficient diagnostic power to establish or exclude the diagnosis of ACC, it is recommended not to rely on a single clinical or laboratory finding. #QoE: high; SoR: strong#
1.1 由於沒有任何特徵具有足夠的診斷能力來確定或排除 ACC 的診斷，因此建議不要依賴單一的臨床或實驗室發現。#QoE：高;SoR：強#

1.2 For the diagnosis of ACC, we suggest using a combination of detailed history, complete clinical examination, laboratory tests and imaging investigations. However, the best combination is not known. #QoE: very low; SoR: weak#
1.2 對於 ACC 的診斷，我們建議結合詳細病史、完整的臨床檢查、實驗室檢查和影像學檢查。然而，最好的組合尚不清楚。#QoE：非常低;SoR：弱#

Comment: useful features for the diagnosis of ACC are:
評論：診斷 ACC 的有用功能是：

• History and clinical examination: fever, right upper quadrant pain or tenderness, vomiting or food intolerance; Murphy’s sign
  病史和臨床檢查：發熱、右上腹疼痛或壓痛、嘔吐或食物不耐受;墨菲的標誌

• Laboratory tests: elevated C-reactive protein, elevated white blood cell count
  實驗室檢查：C 反應蛋白升高，白細胞計數升高

• Imaging: signs suggestive of gallbladder inflammation
  影像學檢查：提示膽囊炎症的體征

The recommendations of the 2016 WSES guidelines were mainly based on two studies: a systematic review and meta-analysis by Trowbridge et al. [12] and a prospective diagnostic study by Eskelinen et al. [13]. This evidence, although flawed by the limitations described below, remains relevant and the associated statement remains valid.
2016 年 WSES 指南的建議主要基於兩項研究：Trowbridge 等[12]的系統評價和 meta 分析，以及 Eskelinen 等[13]的前瞻性診斷研究。該證據儘管存在下述限制的缺陷，但仍然具有相關性，相關陳述仍然有效。

The paper by Trowbridge et al. [12] included 17 studies, which reported a quantitative assessment of history, physical examination and/or laboratory tests for the diagnosis of acute cholecystitis. The results showed that, with the exception of Murphy’s sign (positive likelihood ratio—LR 2.8; 95% CI 0.8–8.6) and right upper quadrant tenderness (negative LR0.4; 95% CI 0.2–1.1)—although the 95% confidence intervals included 1.0 in both cases, none of the clinical signs or laboratory tests showed LRs higher than 1.6 or negative LRs lower than 0.4. Limitations were identified in a possible selection bias, as patients with abdominal pain and patients with a suspected diagnosis of acute cholecystitis were included in the study, and in a heterogeneous definition of the diagnosis of acute cholecystitis.
Trowbridge 等[12]的論文納入了 17 項研究，這些研究報告了對急性膽囊炎診斷病史、體格檢查和/或實驗室檢查的定量評估。結果顯示，除了墨菲征（陽性似然比-LR 2.8;95% CI 0.8-8.6）和右上腹壓痛（陰性 LR0.4;95%CI 0.2-1.1）外，儘管兩種病例的 95%置信區間均為 1.0，但臨床體征或實驗室檢查均未顯示 LR 高於 1.6 或陰性 LR 低於 0.4。由於腹痛患者和疑似診斷為急性膽囊炎的患者被納入研究，並且在急性膽囊炎診斷的異質性定義中，在可能的選擇偏倚中發現了局限性。

The article by Eskelinen et al. [13] evaluated more than 1300 patients and revealed a good diagnostic yield with a combination of findings from history, physical examination and laboratory tests, reporting a positive LR of 25.7 and a negative LR of 0.24.
Eskelinen 等[13]的文章評估了 1300 多名患者，綜合病史、體格檢查和實驗室檢查結果，診斷率良好，報告 LR 陽性為 25.7，LR 陰性為 0.24。

The TG criteria for the diagnosis of cholecystitis include clinical signs, laboratory tests and imaging features [14]. After the publication of the paper by Yokoe et al. in 2012 [15] reporting 91.2% sensitivity and 96.9% specificity, three studies reporting the validation of the TG diagnostic criteria were found. Although published in 2017, one study focused on the TG07 rather than the more recent TG13 [16]. A cross-sectional study [17] evaluated the validity of fever, inflammatory markers and US findings as a validation of the TG13 criteria. At multivariate analysis, only neutrophil count was statistically associated with the diagnosis of acute cholecystitis (p <0.0001), with a 70% sensitivity and 65.8% specificity. Overall, accuracy of the TG13 criteria was low at 60.3%. The TG13 correctly predicted 83.1% of all confirmed ACC, but over-diagnosed ACC in 62.5% of normal gallbladders. More than half of eligible patients did not undergo US and were excluded from the study; this represents a major source of potential selection bias. A cross-sectional study on the possible limitations of the TG 13 has reported a 53.4% sensitivity in diagnosing acute cholecystitis [18]. However, some uncertainty regarding the sample population and the lack of detail in sensitivity calculation indicates that the data should be interpreted with caution. The revision of the TG criteria performed in 2018 did not include a clinical evaluation of the diagnostic criteria [14]. Considering the heterogeneity of these findings, the reliability of the TG13 criteria for the diagnosis of ACC appears to be limited.
TG 診斷膽囊炎的標準包括臨床體征、實驗室檢查和影像學特徵[14]。在 Yokoe 等人於 2012 年發表論文[15]報告靈敏度為 91.2%，特異性為 96.9%后，發現了三項研究報告了 TG 診斷標準的驗證。儘管發表於 2017 年，但一項研究的重點是 TG07，而不是最近的 TG13[16]。一項橫斷面研究 [17] 評估了發熱、炎症標誌物和 US 結果作為 TG13 標準驗證的有效性。在多因素分析中，只有中性粒細胞計數與急性膽囊炎的診斷有統計學意義（p <0.0001），靈敏度為 70%，特異性為 65.8%。總體而言，TG13 標準的準確率較低，為 60.3%。TG13 正確預測了 83.1% 的確診 ACC，但在 62.5% 的正常膽囊中過度診斷了 ACC。超過一半的符合條件的患者沒有接受超聲治療，被排除在研究之外;這是潛在選擇偏差的主要來源。一項關於 TG 13 可能局限性的橫斷面研究報告稱，診斷急性膽囊炎的敏感性為 53.4%[18]。然而，樣本群體的一些不確定性和敏感性計算中缺乏細節表明應謹慎解釋數據。2018 年對 TG 標準的修訂不包括對診斷標準的臨床評估[14]。考慮到這些發現的異質性，TG13 診斷 ACC 標準的可靠性似乎有限。

Which initial imaging technique should be used in case of a suspected diagnosis of ACC?
如果疑似診斷為 ACC，應使用哪種初始影像學技術？

1.3 We recommend the use of abdominal ultrasound (US) as the preferred initial imaging technique, in view of its cost-effectiveness, wide availability, reduced invasiveness and good accuracy for gallstones disease. #QoE: high; SoR: strong#
1.3 鑒於腹部超聲 （US） 具有成本效益、廣泛可用性、侵入性小且對膽結石疾病準確性好，我們建議使用腹部超聲 （US） 作為首選的初始成像技術。#QoE：高;SoR：強#

Comment: abdominal US is a reliable investigation method; however, it may be of limited utility to rule in or rule out the diagnosis of ACC according to the adopted US criteria.
評價：腹部超聲檢查是一種可靠的檢查方法;然而，根據採用的美國標準排除或排除 ACC 的診斷可能效用有限。

Neither meta-analysis nor studies with adequate quality of evidence have been published on this topic since the publication of the 2016 WSES guidelines.
自 2016 年 WSES 指南發佈以來，既沒有關於該主題的薈萃分析，也沒有發表具有足夠證據品質的研究。

In 2012, Kiewet et al. published a systematic review and meta-analysis [19] of diagnostic performance of different imaging techniques in ACC; abdominal ultrasound was not as accurate as it is for the diagnosis of gallstones. The meta-analysis was based on the results of 26 studies including a total of 2847 patients. The sensitivity in individual studies ranged from 50 to 100% and specificity from 33 to 100%. Summary sensitivity and specificity were 81% (95% CI 75 to 87%) and 83% (95% CI 74 to 89%), respectively. However, strong heterogeneity in the diagnostic performance of abdominal US was reported: the inconsistency index was 80% for sensitivity and 89% for specificity. Notwithstanding these limitations, the widespread availability, lack of invasiveness, lack of exposure to ionizing radiation and the reduced costs make abdominal US the preferred initial imaging technique in suspected ACC.
2012 年，Kiewet 等發表了一項關於不同成像技術在 ACC 中的診斷性能的系統評價和 meta 分析[19];腹部超聲不如膽結石的診斷準確。該薈萃分析基於 26 項研究的結果，共涉及 2847 名患者。個別研究的敏感性範圍為 50% 至 100%，特異性範圍為 33% 至 100%。總敏感性和特異性分別為 81%（95%CI 75-87%）和 83%（95%CI 74-89%）。然而，據報導，腹部超聲的診斷性能存在很強的異質性：敏感性的不一致指數為 80%，特異性的不一致指數為 89%。儘管存在這些局限性，但廣泛的可用性、無創性、缺乏電離輻射暴露以及成本降低使腹部超聲成像成為疑似 ACC 的首選初始成像技術。

Published data from eight cross-sectional studies [20,21,22,23,24,25,26,27] confirmed the heterogeneity of diagnostic values, diagnostic index and standard reference for the final diagnosis of ACC. Traditional US presented wide ranges of sensitivity (from 26 to 100% [20,21,22,23,24,25,26]), specificity (from 62 to 88.1% [22,23,24,25,26,27]), positive predictive value (PPV) and negative predictive value (NPV 35% to 93.7% and 52% to 97.1%, respectively), as well as positive LR (1.29 to 4.7) and negative LR (0.16 to 0.93) [23, 24]. Global accuracy has been reported in two studies and varied from 70.1 to 79% [26, 27].
8 項橫斷面研究[20,21,22,23,24,25,26,27] 的已發表數據證實了 ACC 最終診斷的診斷值、診斷指標和標準參考的異質性。傳統超聲治療的敏感性範圍很廣（從 26%到 100%[20,21,22,23,24,25,26]）、特異性（從 62%到 88.1%[22,23，24,25,26,27]）、陽性預測值（PPV）和陰性預測值（NPV 分別為 35%至 93.7%和 52%至 97.1%），以及陽性 LR（1.29 至 4.7）和陰性 LR（0.16 至 0.93）[23,24]。 兩項研究報告了全球準確性，從 70.1% 到 79% 不等 [26， 27]。

In one study, the absence of gallstones was used to rule out the diagnosis of acute cholecystitis in patients presenting to the emergency department for suspected cholecystitis [23]. Overall, the sensitivity of the simplified definition of a positive ultrasonography test was100%, as compared to the standard definition, i.e. the presence of gallstones and at least one of the ultrasonography signs of acute cholecystitis, which showed a sensitivity of 87% (95% CI 66–97%) and specificity of 82 (95% CI 74–88%); prevalence was less than 15%, NPV was 97% (95% CI 93–-99%) and PPV was low at 44% (95% CI 29–59%).
一項研究發現，在因疑似膽囊炎而急診就診的患者中，沒有膽結石被用來排除急性膽囊炎的診斷[23]。總體而言，與標準定義相比，超聲檢查陽性的簡化定義的敏感性為 100%，即存在膽結石和至少一種急性膽囊炎的超聲體征，其敏感性為 87%（95%CI 66-97%），特異性為 82（95%CI 74-88%）;患病率低於 15%，NPV 為 97% （95% CI 93–-99%），PPV 低至 44% （95% CI 29–59%）。

Considering the limits of abdominal US, one study has evaluated new ultrasonography criteria for the diagnosis of acute cholecystitis. Kim et al. [26] evaluated the added value of point shear-wave elastography (pSWE) in the diagnostic performance of conventional US for the diagnosis of ACC. Based on the assumption that transient increase in hepatic blood flow observed in case of acute cholecystitis increases liver stiffness, the authors proposed to use a measure of liver stiffness by pSWE and to evaluate its diagnostic yield for ACC in a two-observer analysis. Compared to conventional US, pSWE significantly increased diagnostic accuracy (area under the curve—AUC from 79 to 96.3% and from 77 to 96.2%, p < 0.001) and specificity (from 62 to 95%, p < 0.001). The difference in sensitivity was not significant, being 88 versus 92% (p = 0.45) in the US only group and 86–92% (p = 0.26) in the US plus pSWE group. Although the results appear promising, the technique requires expertise; moreover, 18.5% of patients were excluded due to a potential limitation of the technique, therefore reducing the external validity of the study.
考慮到腹部超聲的局限性，一項研究評估了診斷急性膽囊炎的新超聲標準。Kim 等[26]評估了點剪切波彈性成像（pSWE）在常規超聲診斷 ACC 診斷性能中的附加值。基於在急性膽囊炎病例中觀察到的肝血流量短暫增加會增加肝臟硬度的假設，作者建議使用 pSWE 測量肝臟硬度，並在雙觀察者分析中評估其對 ACC 的診斷率。與傳統超聲相比，pSWE 顯著提高了診斷準確性（曲線下面積——AUC 從 79%到 96.3%，從 77%到 96.2%，p < 0.001）和特異性（從 62%到 95%，p < 0.001）。敏感性差異不顯著，僅美國組為 88%vs92%（p= 0.45），美國加 pSWE 組為 86-92%（p = 0.26）。儘管結果看起來很有希望，但該技術需要專業知識;此外，由於技術的潛在局限性，18.5% 的患者被排除在外，從而降低了研究的外部有效性。

Another study by Ra et al. [27] has reported the use of superb microvascular imaging (SMI) in the diagnosis of acute cholecystitis. The SMI technique is similar to Color-Doppler US and is used to detect the micro vasculature and slow flow of the liver, using a special filtering technique. The authors hypothesised that hyperaemic changes within the gallbladder bed of the liver, detected by SMI, and may be used for the diagnosis of acute cholecystitis. This inter-observer study on 54 patients showed a significant increase of the AUC from 72.9 to 85% (p = 0.02) with the use of SMI. The need for specific expertise, the small number of patients and the poor reference standard limit the significance of this study.
Ra 等[27]的另一項研究報導了超微血管成像（SMI）在急性膽囊炎診斷中的應用。SMI 技術類似於彩色多普勒超聲，用於檢測肝臟的微脈管系統和緩慢流動，使用特殊的過濾技術。作者假設，通過 SMI 檢測到肝膽囊床內的充血性變化，可用於診斷急性膽囊炎。這項針對 54 名患者的觀察者間研究表明，使用 SMI 後，AUC 從 72.9%顯著增加到 85%（p = 0.02）。對特定專業知識的需求、患者數量少和參考標準差限制了本研究的重要性。

What is the role of other imaging techniques (e.g. Hepatobiliary iminodiacetic acid - HIDA scan, Abdominal Computed Tomography - CT scan and Magnetic Resonance Imaging - MRI) in the diagnosis of ACC?
其他成像技術（例如 肝膽亞氨基二乙酸 - HIDA 掃描、腹部計算機斷層掃描 - CT 掃描和磁共振成像 - MRI）在 ACC 的診斷中的作用是什麼？

1.4 We suggest the use of further imaging for the diagnosis of ACC in selected patients, depending on local expertise and availability. Hepatobiliary iminodiacetic acid (HIDA) scan has the highest sensitivity and specificity for the diagnosis of ACC as compared to other imaging modalities. Diagnostic accuracy of computed tomography (CT) is poor. Magnetic resonance imaging (MRI) is as accurate as abdominal US. #QoE: moderate; SoR: strong#
1.4 我們建議根據當地的專業知識和可用性，對特定患者使用進一步的影像學檢查來診斷 ACC。與其他成像方式相比，肝膽亞氨基二乙酸 （HIDA） 掃描對 ACC 的診斷具有最高的敏感性和特異性。計算機斷層掃描 （CT） 的診斷準確性較差。磁共振成像 （MRI） 與腹部超聲成像一樣準確。#QoE：中等;SoR：強#

Comment: in clinical practice, HIDA scan utilisation is limited due to the required resources and time.
評論：在臨床實踐中，由於所需的資源和時間，HIDA 掃描的使用受到限制。

No study with a high level of evidence was published on this topic since the publication of the 2016 WSES guidelines.
自 2016 年 WSES 指南發佈以來，沒有發表關於該主題的高水準證據研究。

A cross-sectional study [28] evaluated the incremental benefits of cystic duct enhancement detected by CT for the diagnosis of cholecystitis in patients without visibly impacted gallstones. When considering cystic duct enhancement, the accuracy and sensitivity of the diagnosis increased significantly, while no significant difference was reported for specificity. Interestingly, diagnostic accuracy increased for the less experienced radiologist, from 75.4 to 87.3% (p = 0.015). However, this case control study has some methodological flaws limiting its quality.
一項橫斷面研究[28]評估了 CT 檢測到的膽囊管增強術對無明顯阻生膽結石患者膽囊炎診斷的增量益處。在考慮膽囊管增強術時，診斷的準確性和敏感性顯著提高，而特異性沒有顯著差異。有趣的是，經驗不足的放射科醫生的診斷準確率從 75.4% 提高到 87.3% （p = 0.015）。然而，該病例對照研究存在一些方法學缺陷，限制了其品質。

A study considering only patients with a definitive diagnosis of acute cholecystitis compared the diagnostic sensitivities of US, CT and HIDA scan [20]. The results confirmed the higher sensitivity of HIDA over US and CT with respective values of 84.2%, 67.3% and 59.8% (p = 0.017). No difference was found when comparing CT and US (p = 0.09).
一項僅考慮明確診斷為急性膽囊炎的患者的研究比較了超聲掃描、CT 掃描和 HIDA 掃描的診斷敏感性[20]。結果證實，HIDA 的靈敏度高於 US 和 CT，分別為 84.2%、67.3% 和 59.8% （p = 0.017）。比較 CT 和 US 時沒有發現差異 （p = 0.09）。

A study comparing sensitivity of CT and US [21] showed different results, reporting higher sensitivity of CT, compared with US(92% vs. 79%, p = 0.015). In this study, a retrospective cohort of patients was added based on prospectively collected data from patients with a diagnosis of ACC confirmed by pathology or intra-operative findings. Indication for CT and timing between index and reference standards were not reported.
一項比較 CT 和超聲敏感性的研究[21]顯示了不同的結果，報告 CT 的敏感性高於超聲（92% vs. 79%，p = 0.015）。在這項研究中，根據前瞻性收集的經病理學或術中發現確診為 ACC 的患者的數據，增加了一個回顧性患者佇列。沒有報告 CT 的指征以及索引和參考標準之間的時間。

One study on a time-saving HIDA scan technique reported a high inter-rate agreement (Cohen’s kappa coefficient = 0.92) between the novel time-saving technique and the conventional examination [29]. Two other studies reported diagnostic values of HIDA scan as 86.7–89.3% for sensitivity and 66.8–79% for specificity [21, 22].
一項關於節省時間的 HIDA 掃描技術的研究報告稱，新型省時技術與常規檢查之間存在很高的速率間一致性（Cohen 的 kappa 係數=0.92）[29]。另外兩項研究報告稱，HIDA 掃描的診斷價值為 86.7-89.3%的靈敏度和 66.8-79%的特異性[21,22]。

Section 2. Associated common bile duct stones: which tools to use for suspicion and diagnosis at presentation?
第2節。相關膽總管結石：就診時使用哪些工具進行懷疑和診斷？

Choledocholithiasis, i.e. the presence of common bile duct stones (CBDS), is reported to occur in 10% to 20% of gallstone cases, with lower incidence, ranging from 5 to 15 %, in case of ACC [30,31,32,33]. Investigations for CBDS require time and may delay surgical treatment. Due to the relatively low incidence of CBDS during ACC, the main issue is to select patients with a high likelihood of CBDS, who would benefit from further diagnostic tests and removal of CBDS. An uncommon condition that mimics CBDS is Mirizzi syndrome, which occurs in less than 1% of patients with gallstones. Preoperative investigations may help in the diagnosis, although the vast majority of cases are identified at surgery [34, 35].
據報導，膽總管結石，即存在膽總管結石（common bile duct stones， CBDS），發生率為 10%-20%，ACC 的發病率較低，為 5%-15%[30,31,32,33]。CBDS 的調查需要時間，並且可能會延誤手術治療。由於 ACC 期間 CBDS 的發生率相對較低，主要問題是選擇 CBDS 可能性較高的患者，他們將受益於進一步的診斷測試和去除 CBDS。一種模仿 CBDS 的不常見疾病是 Mirizzi 綜合征，這種情況發生在不到 1% 的膽結石患者中。術前檢查可能有助於診斷，但絕大多數病例是在手術中發現的[34,35]。

The only new study on this topic was a cross-sectional study on the role of liver function tests (LFTs) [36]. The authors evaluated the role of LFTs and the role of early follow-up in the diagnosis of CBDS in ACC. The most reliable LFT was gamma-glutamyl transpeptidase (GGT), with a sensitivity of 80.6% and a specificity of 75.3%, using a cut-off level of 224 IU/L. PPV was 50%, while NPV was 91.4%. The results also showed a significant decrease of LFTs within the non-CBD groups at 4-day follow-up, which was not evident in the ACC + CBDS group—with the exception of alanine aminotransferase (ALT). Moreover, in the CBDS group, all LFTs values improved significantly after the removal of the CBDS at a mean follow-up time of 4.3 days.
關於該主題的唯一新研究是一項關於肝功能測試（LFT）作用的橫斷面研究[36]。作者評估了 LFT 的作用和早期隨訪在 ACC 中 CBDS 診斷中的作用。最可靠的 LFT 是γ-谷氨醯轉肽酶（GGT），靈敏度為 80.6%，特異度為 75.3%，臨界值為 224 IU/L，PPV 為 50%，NPV 為 91.4%。結果還顯示，在 4 天的隨訪中，非 CBD 組的 LFT 顯著減少，這在 ACC + CBDS 組中並不明顯——丙氨酸轉氨酶 （ALT） 除外。此外，在 CBDS 組中，在平均隨訪時間為 4.3 天時，去除 CBDS 后，所有 LFTs 值均顯著改善。

One flaw of the study is that index diagnosis depends to some extent on the reference standard. Given the retrospective design of the study, it should be considered that the diagnosis of CBDS is assessed with endoscopic retrograde cholangio-pancreatography (ERCP), which is mainly prompted by the presence of elevated LFTs; this may represent a source of bias. No systematic intra-operative cholangiography (IOC) was performed.
該研究的一個缺陷是指數診斷在某種程度上取決於參考標準。鑒於該研究的回顧性設計，應考慮 CBDS 的診斷是通過內窺鏡逆行胰膽管造影 （ERCP） 評估的，這主要是由 LFT 升高引起的;這可能代表偏見的來源。未進行系統的術中膽管造影 （IOC）。

Are elevated LFTs or bilirubin sufficient for the diagnosis of CBDS in patients with ACC?
LFTs 或膽紅素升高是否足以診斷 ACC 患者的 CBDS？

2.1 We recommend against the use of elevated LFTs or bilirubin as the only method to identify CBDS in patients with ACC, in which case we recommend performing further diagnostic tests. #QoE: moderate; SoR: strong#
2.1 我們建議不要使用升高的 LFT 或膽紅素作為識別 ACC 患者 CBDS 的唯一方法，在這種情況下，我們建議進行進一步的診斷測試。#QoE：中等;SoR：強#

Historically, LTFs have played a major role in determining the presence of CBDS. However, the majority of published studies did not consider patients with ACC and included asymptomatic gallstones. Normal LFTs have a NPV of 97%, whereas the PPV of any abnormal LFTs is only 15% [37]. The elevation of LFTs is a poor tool for the prediction of CBDS, even in patients without ACC; the literature ranging from 25 to 50% [30, 38, 39]. In patients with ACC, LFTs may be altered due to the acute inflammatory process of the gallbladder and the biliary tree, rather than direct biliary obstruction; a proportion ranging between 15 and 50% of patients with ACC show elevation in LFTs without CBDS. Song et al. demonstrated that 424 out of 1178 patients with ACC had increased LFTs, namely ALT and aspartate transaminase (AST) greater than twice reference levels. Of these, only 246 (58%) had CBDS [40]. Chang et al. showed that 51% and 41% of patients with ACC without CBDS had elevated ALT and AST, respectively. However, increased bilirubin levels with leucocytosis may predict gangrenous cholecystitis [41]. Padda et al. found that approximately 30% of patients with ACC without CBDS had abnormal alkaline phosphatase (ALP) and/or bilirubin, and 50% had abnormal ALT. Among patients with ACC and CBDS, 77% had raised ALP, 60% had abnormal bilirubin and 90% had elevated ALT; multivariate analysis showed that increased common bile duct size and elevated ALT and ALP were predictors of CBDS [42]. The diagnostic accuracy increases for cholestasis tests, such as serum bilirubin, with the duration and the severity of obstruction. Specificity of serum bilirubin levels for CBDS was 60% with a cut-off level of 1.7 mg/day and 75% with a cut-off level of 4 mg/dl [38]; however, mean level of bilirubin in patients with CBDS is generally lower (1.5 to 1.9 mg/dl) [30, 39].
從歷史上看，LTF 在確定 CBDS 的存在方面發揮了重要作用。然而，大多數已發表的研究沒有考慮 ACC 患者，而是包括無癥狀膽結石。正常 LFT 的 NPV 為 97%，而任何異常 LFT 的 PPV 僅為 15%[37]。LFT 的升高是預測 CBDS 的不良工具，即使在沒有 ACC 的患者中也是如此;文獻範圍為 25% 至 50% [30， 38， 39]。在 ACC 患者中，LFT 可能由於膽囊和膽道樹的急性炎症過程而改變，而不是直接的膽道梗阻;15% 至 50% 的 ACC 患者在沒有 CBDS 的情況下表現出 LFT 升高的比例。Song 等人證明，1178 名 ACC 患者中有 424 名的 LFT 升高，即 ALT 和天冬氨酸轉氨酶 （AST） 超過參考水準的兩倍。其中，只有 246 人（58%）擁有 CBDS[40]。Chang 等人表明，沒有 CBDS 的 ACC 患者中，分別有 51%和 41%的 ALT 和 AST 升高。然而，白細胞增多伴膽紅素水準升高可能預示壞疽性膽囊炎[41]。Padda 等人發現，大約 30% 的沒有 CBDS 的 ACC 患者鹼性磷酸酶 （ALP） 和/或膽紅素異常，50% 的 ALT 異常。在 ACC 和 CBDS 患者中，77% 的 ALP 升高，60% 的膽紅素異常，90% 的 ALT 升高;多變數分析表明，膽總管大小增加以及 ALT 和 ALP 升高是 CBDS 的預測因數[42]。膽汁淤積試驗（如血清膽紅素）的診斷準確性隨著梗阻的持續時間和嚴重程度而提高。 血清膽紅素水準對 CBDS 的特異性為 60%，臨界值為 1.7mg/d，臨界值為 75%，臨界值為 4mg/dl[38];然而，CBDS 患者的平均膽紅素水準通常較低（1.5-1.9mg/dl）[30,39]。

A recent meta-analysis reported the diagnostic accuracy of serum bilirubin and serum ALP at two cut-off values for each test. Serum bilirubin at a cut-off of 22.23 μmol/L had a sensitivity of 0.84 (95% CI 0.65 to 0.94) and a specificity of 0.91 (95% CI 0.86 to 0.94). Bilirubin at a cut-off of greater than twice the normal limit, had a sensitivity of 0.42 (95% CI 0.22 to 0.63) and a specificity of 0.97 (95% CI 0.95 to 0.99). For ALP at a cut-off of greater than 125 IU/L, sensitivity was 0.92 (95% CI 0.74 to 0.99) and specificity was 0.79 (95% CI 0.74 to 0.84). For ALP at a cut-off of greater than twice the normal limit, sensitivity was 0.38 (95% CI 0.19 to 0.59) and specificity was 0.97 (95% CI 0.95 to 0.99) [43].
最近的一項薈萃分析報告了每次測試在兩個臨界值下的血清膽紅素和血清 ALP 的診斷準確性。臨界值為 22.23μmol/L 時，血清膽紅素的敏感性為 0.84（95%CI 0.65-0.94），特異性為 0.91（95%CI 0.86-0.94）。膽紅素臨界值大於正常限值的兩倍時，敏感性為 0.42（95%CI 0.22-0.63），特異性為 0.97（95%CI 0.95-0.99）。對於臨界值大於 125 IU/L 的 ALP，敏感性為 0.92（95%CI 0.74-0.99），特異性為 0.79（95%CI 0.74-0.84）。對於臨界值大於正常限值 2 倍的 ALP，敏感性為 0.38（95%CI 0.19-0.59），特異性為 0.97（95%CI 0.95-0.99）[43]。

Which imaging features are predictive of CBDS in patients with ACC?
哪些影像學特徵可以預測 ACC 患者的 CBDS？

2.2 We suggest considering the visualization of a stone in the common bile duct at transabdominal US as a predictor of CBDS in patients with ACC. #QoE: very low; SoR: weak#
2.2 我們建議考慮將經腹超聲時膽總管結石的可視化作為 ACC 患者 CBDS 的預測指標。#QoE：非常低;SoR：弱#

2.3 An increased diameter of common bile duct, an indirect sign of stone presence, is not sufficient to identify ACC patients with CBDS and we therefore recommend performing further diagnostic tests. #QoE: high; SoR: strong#
2.3 膽總管直徑增加（結石存在的間接跡象）不足以識別患有 CBDS 的 ACC 患者，因此我們建議進行進一步的診斷測試。#QoE：高;SoR：強#

Abdominal US is the preferred imaging technique for the diagnosis of ACC; the common bile duct can be visualized and investigated at the same time. A meta-analysis by Gurusamy et al. investigated the diagnostic potential of US [43]: sensitivity ranged from 0.32 to 1.00 with a summary sensitivity of 0.73 (95% CI 0.44 to 0.90), while specificity ranged from 0.77 to 0.97 with a summary specificity of 0.91 (95% CI 0.84 to 0.95).
腹部超聲是診斷 ACC 的首選影像學技術;膽總管可以同時可視化和檢查。Gurusamy 等的一項 meta 分析調查了超聲[43]的診斷潛力：敏感性範圍為 0.32 至 1.00，總敏感性為 0.73（95%CI 0.44 至 0.90），特異性範圍為 0.77 至 0.97，總特異性為 0.91（95%CI 0.84 至 0.95）。

In a retrospective analysis, Boys et al. [44] found that the mean common bile duct diameter seen at abdominal US in ACC patients without and with CBDS was 5.8 and 7.1 mm, respectively (p = 0.004). A CBD diameter larger than 10 mm was associated with a 39 % incidence of CBDS, while diameter smaller than 9.9 mm was associated with CBDS in 14%. The authors concluded that common bile duct diameter is not sufficient on its own to identify patients having significant risk for CBDS.
在一項回顧性分析中，Boys 等[44]發現，在沒有和有 CBDS 的 ACC 患者中，腹部超聲觀察到的平均膽總管直徑分別為 5.8 和 7.1 mm（p = 0.004）。直徑大於 10 毫米的 CBD 與 39% 的 CBDS 發生率相關，而直徑小於 9.9 毫米的 CBDS 與 14% 的 CBDS 發生率相關。作者得出的結論是，膽總管直徑本身不足以識別具有 CBDS 重大風險的患者。

Which tests should be performed to assess the risk of CBDS in patients with ACC?
應該進行哪些測試來評估 ACC 患者患 CBDS 的風險？

2.4 In order to assess the risk for CBDS, we suggest performing liver function tests (LFTs), including ALT, AST, bilirubin, ALP, GGT and abdominal US in all patients with ACC. #QoE: low; SoR: weak#
2.4 為了評估 CBDS 的風險，我們建議對所有 ACC 患者進行肝功能測試 （LFT），包括 ALT、AST、膽紅素、ALP、GGT 和腹部超聲。#QoE：低;SoR：弱#

Several scores for the prediction of CBDS have been proposed and validated; however, none of the proposed scores is specific for ACC. The implementation of these predictive scores in clinical practice remains poor [38,39,40]; all scores consider different combinations of the same clinical variables. Barkun et al. [38] combined age > 55 years, elevated serum bilirubin, dilated common bile duct and evidence of CBDS; Menezes et al. [45] combined age > 55 years, male sex, ascending cholangitis, dilated common bile duct, CBDS and abnormal LFTs; Soltan et al. [46] included history of symptomatic disease, abnormal liver function tests, dilated common bile duct and presence of CBDS; Sun et al. [47] included male sex, abnormal liver function test and dilated common bile duct; Sarli et al. [48] combined positive AUS and abnormal liver function tests.
已經提出了幾個用於預測 CBDS 的分數並得到了驗證;然而，建議的分數都不是針對 ACC 的。這些預測評分在臨床實踐中的實施仍然很差[38,39,40]; 所有分數都考慮了相同臨床變數的不同組合。Barkun 等[38]合併年齡> 55 歲，血清膽紅素升高，膽總管擴張和 CBDS 證據;Menezes 等[45]合併年齡> 55 歲，男性，升性膽管炎，膽總管擴張，CBDS 和 LFT 異常;Soltan 等[46]包括有癥狀的疾病史、肝功能檢查異常、膽總管擴張和 CBDS 的存在;Sun 等[47]包括男性、肝功能檢查異常和膽總管擴張;Sarli 等[48]合併了 AUS 陽性和肝功能檢查異常。

The American Society of Gastrointestinal Endoscopy and the Society of American of Gastrointestinal Endoscopic Surgeons combined the published validated clinical scores and proposed a risk stratification of CBDS in three different classes, defined as follows: low risk (< 10%), moderate risk (10 to 50%) and high risk (> 50%) of CBDS [49] (see Table 2). This proposed classification has clear clinical implications: patients with a low risk of CBDS should be operated on without further investigation; patients with moderate risk should be evaluated with a second-level examination, either preoperatively with endoscopic US (EUS) or magnetic resonance cholangiopancreatography (MRCP) or intraoperatively with laparoscopic US (LUS) or IOC, in order to select patients who need stone removal; finally, according to local expertise, laparoscopic transcystic CBD exploration is a valuable option. Patients with high risk of CBDS should undergo preoperative diagnostic and therapeutic ERCP. See Fig. 1 for the flowchart of management of ACC.
美國胃腸內窺鏡學會和美國胃腸內窺鏡外科醫生協會結合了已發表的經過驗證的臨床評分，提出了 CBDS 在三個不同類別中的風險分層，定義如下：CBDS 的低風險（< 10%）、中度風險（10%至 50%）和高風險（> 50%）[49]（見表 2).這種擬議的分類具有明確的臨床意義：CBDS 風險低的患者應在不進一步檢查的情況下進行手術;中度風險患者應進行二級檢查評估，術前採用內鏡超聲檢查（EUS）或磁共振胰膽管造影（MRCP）或術中腹腔鏡超聲（LUS）或 IOC，以選擇需要取石的患者;最後，根據當地的專業知識，腹腔鏡經囊 CBD 探索是一個有價值的選擇。CBDS 高風險患者應接受術前診斷和治療性 ERCP。見圖。1 為行政管理委員會的管理流程圖。

Table 2 Risk factors and classification of risk for CBDS (modified from Maple et al. 2010)
表 2 CBDS 的風險因素和風險分類（修改自 Maple 等人，2010 年）

What is the best tool to stratify the risk for CBDS in patients with ACC?
對 ACC 患者 CBDS 風險進行分層的最佳工具是什麼？

2.5 We suggest stratifying the risk of CBDS according to the proposed classification modified from the American Society of Gastrointestinal Endoscopy and the Society of American Gastrointestinal Endoscopic Surgeon Guidelines. #QoE: very low; SoR: weak#
2.5 我們建議根據美國胃腸內窺鏡學會和美國胃腸內窺鏡外科醫生協會指南修改的擬議分類對 CBDS 的風險進行分層。#QoE：非常低;SoR：弱#

ASGE guidelines remains a valuable tool for the diagnosis and the management of CBDS in patients with ACC [49]. According to their classification, high-risk patients have a probability of having CBDS exceeding 50%, which in turn means that up to 49% of patients undergoing ERCP will not have evidence of CBDS and, given the potential complications of ERCP, this may not be considered acceptable. For this reason, we would recommend more cautious approach: only patients with evidence of CBDS at abdominal US should be considered at high risk of CBDS and should undergo diagnostic and therapeutic ERCP directly; patients with total serum bilirubin > 4 mg/dl or enlarged common bile duct diameter at US with concomitant bilirubin level 1.8 to 4 mg/dl should be considered as moderate risk and should undergo second level investigation such as endoscopic ultrasound (EUS) or magnetic resonance cholangiopancreatography (MRCP), laparoscopic ultrasound (LUS) or IOC, in order to avoid the complications related to ERCP. See Table 2 for the modified risk stratification.
ASGE 指南仍然是 ACC 患者 CBDS 診斷和管理的寶貴工具[49]。根據他們的分類，高危患者的 CBDS 概率超過 50%，這反過來意味著多達 49%的接受 ERCP 的患者將沒有 CBDS 的證據，考慮到 ERCP 的潛在併發症，這可能被認為是不可接受的。出於這個原因，我們建議採取更謹慎的方法：只有腹部超聲有 CBDS 證據的患者才應被視為 CBDS 的高風險患者，並應直接接受診斷和治療性 ERCP;血清總膽紅素> 4 mg/dl 或膽總管直徑增大且膽紅素水準為 1.8 至 4 mg/dl 的患者應被視為中度風險，並應接受二級檢查，如超聲內鏡（EUS）或磁共振胰膽管造影（MRCP）、腹腔鏡超聲（LUS）或 IOC，以避免與 ERCP 相關的併發症。修改後的風險分層見表 2。

Which actions are warranted in patients with ACC and at moderate risk for CBDS?
對於 ACC 患者和 CBDS 中等風險的患者，需要採取哪些行動？

2.6 We recommend that patients with moderate risk for CBDS undergo one of the following: preoperative magnetic resonance cholangiopancreatography (MRCP), preoperative endoscopic ultrasound (EUS), intraoperative cholangiography (IOC), or laparoscopic ultrasound (LUS), depending on local expertise and availability. #QoE: high; SoR: strong#
2.6 我們建議 CBDS 中度風險的患者接受以下檢查之一：術前磁共振胰膽管造影 （MRCP）、術前超聲內鏡 （EUS）、術中膽管造影 （IOC） 或腹腔鏡超聲 （LUS），具體取決於當地的專業知識和可用性。#QoE：高;SoR：強#

Two preoperative imaging techniques are available for the detection of CBDS, namely MRCP and EUS. These diagnostic tests, according to the ASGE guidelines [49] should be reserved for patients with moderate risk for CBDS and have been shown to delay definitive ACC treatment [44]. On the other hand, these tests could exclude the presence of CBDS with high diagnostic accuracy, thereby avoiding further inappropriate invasive procedures, such as ERCP or IOC and therefore their complications. In fact, the implementation of these techniques resulted in a reduction of ERCP by 30 to 75% in non-selected patients [50, 51]. A Cochrane meta-analysis compared these two different techniques [52]: both had good diagnostic accuracy, showing summary sensitivities of 95% for EUS and 93% for MRCP and a summary specificity of 97% and 96%, respectively. As noted by some authors, considerations other than diagnostic efficacy, such as local availability, costs, expertise and delay of surgery, might play an important role in the decision making during the diagnostic work-up [53].
有兩種術前成像技術可用於檢測 CBDS，即 MRCP 和 EUS。根據 ASGE 指南[49]，這些診斷測試應保留給 CBDS 中度風險的患者，並且已被證明可以延遲 ACC 的根治性治療[44]。另一方面，這些測試可以排除具有高診斷準確性的 CBDS 的存在，從而避免進一步的不適當的侵入性手術，例如 ERCP 或 IOC，從而避免其併發症。事實上，這些技術的實施使非選定患者的 ERCP 減少了 30%-75%[50,51]。 一項 Cochranemeta 分析比較了這兩種不同的技術[52]：兩者的診斷準確性都很好，EUS 的總敏感性分別為 95%和 MRCP 的 93%，總特異性分別為 97%和 96%。正如一些作者所指出的，診斷效果以外的考慮因素，如當地可獲得性、費用、專業知識和手術延遲，可能在診斷檢查期間的決策中發揮重要作用[53]。

Which actions are warranted in patients with ACC and at high risk for CBDS?
對於 ACC 患者和 CBDS 高風險患者，需要採取哪些行動？

2.7 We recommend that patients with high-risk for CBDS undergo preoperative ERCP, IOC or LUS, depending on the local expertise and the availability of the technique. #QoE: high; SoR: strong#
2.7 我們建議 CBDS 高風險患者接受術前 ERCP、IOC 或 LUS，具體取決於當地的專業知識和技術的可用性。#QoE：高;SoR：強#

ERCP has both a diagnostic and a therapeutic role in the management of CBDS, but it is an invasive procedure with potential severe complications. The literature underscores the risks of diagnostic ERCP. Morbidity associated with diagnostic ERCP includes pancreatitis, cholangitis, bleeding, duodenal perforation and allergic reaction to contrast medium. Complications occur in 1 to 2% and increase to 10% when associated with sphincterotomy [54,55,56,57]. On the other hand, IOC significantly increases the length of surgery [58] and requires dedicated staff in the operating room, while this may not be available, especially in the acute setting with unplanned surgery. Positive findings on IOC often lead to intraoperative management of CBDS with additional operative time.
ERCP 在 CBDS 的管理中既具有診斷作用，也具有治療作用，但它是一種具有潛在嚴重併發症的侵入性手術。文獻強調了診斷性 ERCP 的風險。與診斷性 ERCP 相關的發病率包括胰腺炎、膽管炎、出血、十二指腸穿孔和對造影劑的過敏反應。併發症發生率為 1%-2%，與括約肌切開術相關時增加至 10%[54,55,56,57]。 另一方面，IOC 顯著增加了手術時間[58]，並且需要手術室有專門的工作人員，但這可能無法提供，尤其是在有計劃外手術的急性情況下。IOC 的陽性發現通常會導致 CBDS 的術中管理，並增加手術時間。

A recently published meta-analysis compared ERCP and IOC [58]. The summary sensitivity for ERCP was 0.83 (95% CI 0.72 to 0.90) and specificity was 0.99 (95% CI 0.94 to 1.00). For IOC, the summary sensitivity was 0.99 (95% CI 0.83 to 1.00) and specificity was 0.99 (95% CI 0.95 to 1.00). Sensitivities showed a weak statistical difference (p = 0.05); however, due to the low quality and the methodology of the included studies, the two diagnostic techniques should be considered equivalent. LUS is a useful method for intraoperative detection of CBDS [59]. A meta-analysis has shown that IOC and LUS have the same pooled sensitivity and similar pooled specificity for the detection of CBDS [60]. As in the case of IOC, intraoperative evidence of CBDS with LUS leads to intraoperative management of common bile duct with increased operative time.
最近發表的一項 meta 分析比較了 ERCP 和 IOC[58]。ERCP 的總敏感性為 0.83（95%CI 0.72-0.90），特異性為 0.99（95%CI 0.94-1.00）。對於 IOC，總敏感性為 0.99（95%CI 0.83-1.00），特異性為 0.99（95%CI 0.95-1.00）。敏感性顯示出微弱的統計差異（p = 0.05）;然而，由於納入研究的品質和方法較低，這兩種診斷技術應被視為等效的。LUS 是術中檢測 CBDS 的有用方法[59]。一項薈萃分析表明，IOC 和 LUS 對 CBDS 的檢測具有相同的匯總靈敏度和相似的匯總特異性[60]。與 IOC 的情況一樣，CBDS 與 LUS 的術中證據導致膽總管的術中管理，手術時間增加。

Which is the appropriate treatment of CBDS in patients with ACC?
ACC 患者 CBDS 的合適治療方法是什麼？

2.8 We recommend removing CBDS, either preoperatively, intraoperatively, or postoperatively, according to the local expertise and the availability of several techniques. #QoE; high; SoR: strong#
2.8 我們建議根據當地的專業知識和幾種技術的可用性，在術前、術中或術后去除 CBDS。#QoE;高;SoR：強#

CBDS could be removed with several techniques and a variation of timing (see Fig. 1): preoperative ERCP with sphincterotomy, intraoperative ERCP with sphincterotomy, laparoscopic or open common bile duct exploration, post-operative ERCP with sphincterotomy. A systematic review assessed the differences between these techniques [61]. No differences in terms of morbidity, mortality and success rate were reported. Therefore, these techniques can be considered suitable options, depending on local expertise and availability. Another meta-analysis compared preoperative and intraoperative (rendez-vous technique) ERCP with sphincterotomy [62]. These two techniques were equal in terms of safety and efficacy; the intraoperative technique reduced the risk for post-ERCP pancreatitis, but required dedicated staff and prolonged the length of surgery.
CBDS 可以通過多種技術和不同的時間來去除（見圖。1）：術前 ERCP 聯合括約肌切開術，術中 ERCP 聯合括約肌切開術，腹腔鏡或開放膽總管探查術，術后 ERCP 聯合括約肌切開術。一項系統評價評估了這些技術之間的差異[61]。在發病率、死亡率和成功率方面沒有差異。因此，這些技術可以被認為是合適的選擇，具體取決於當地的專業知識和可用性。另一項 meta 分析比較了術前和術中（會合技術）ERCP 與括約肌切開術[62]。這兩種技術在安全性和有效性方面是相等的;術中技術降低了 ERCP 後胰腺炎的風險，但需要專門的工作人員並延長了手術時間。

Section 3. Surgical treatment of ACC
第 3 節。ACC 的手術治療

The literature updated from the 2016 WSES Guidelines on ACC showed no remarkable publications to change the meaning of previous statements edited by the WSES in 2016 [7]; however, they have been reviewed to ensure the best available evidence.
根據 2016 年 WSES 關於 ACC 的指南更新的文獻顯示，沒有顯著的出版物改變 WSES 在 2016 年編輯的先前聲明的含義[7];然而，它們已經過審查以確保獲得最佳證據。

Which is the preferred first line of treatment for patients with ACC?
ACC 患者的首選一線治療是什麼？

When should laparoscopic cholecystectomy be avoided in patients with ACC?
ACC 患者何時應避免腹腔鏡膽囊切除術？

3.1 We recommend laparoscopic cholecystectomy as the first-line treatment for patients with ACC. #QoE: high; SoR: strong#
3.1 我們推薦腹腔鏡膽囊切除術作為 ACC 患者的一線治療。#QoE：高;SoR：強#

Comment: A low complication rate and shortened hospital stay are the major advantages.
點評：併發症發生率低、住院時間短是主要優點。

3.2 We recommend avoiding laparoscopic cholecystectomy in case of septic shock or absolute anaesthesiology contraindications. #QoE: high; SoR: strong#
3.2 我們建議避免在感染性休克或絕對麻醉禁忌症的情況下進行腹腔鏡膽囊切除術。#QoE：高;SoR：強#

Laparoscopic cholecystectomy is generally considered the standard technique for the removal of gallstones. Local inflammation, especially in gangrenous and emphysematous ACC, has been considered to increase the risk of bile duct injuries, blood loss, operative time, general morbidity and mortality rates in comparison with open surgery [63]. As technical difficulties usually decrease with experience and improvements in surgical technique and instrumentation, the hesitation to safely perform laparoscopic cholecystectomy in ACC has decreased over the years.
腹腔鏡膽囊切除術通常被認為是切除膽結石的標準技術。與開放手術相比，局部炎症，尤其是壞疽性和肺氣腫性 ACC 被認為會增加膽管損傷的風險、失血量、手術時間、一般併發症發生率和死亡率[63]。由於技術難度通常會隨著手術技術和器械的經驗和改進而減少，因此多年來對 ACC 中安全進行腹腔鏡膽囊切除術的猶豫有所減少。

Despite several studies, ranging from case series to randomized prospective clinical trials, confirming the feasibility and safety of laparoscopic cholecystectomy in the treatment of patients with ACC [64,65,66,67,68,69,70,71,72,73], a recent survey on intra-abdominal infection, the CIAOW study [74], showed unexpected results. It was a worldwide survey of 68 medical institutions during a 6-month study period demonstrating that 48.7% of patients with ACC still underwent open surgery.
儘管有幾項研究，從病例系列到隨機前瞻性臨床試驗，證實了腹腔鏡膽囊切除術治療 ACC 患者的可行性和安全性[64,65,66,67,68,69,70,71,72,73]， 但最近一項關於腹腔內感染的調查，CIAOW 研究[74]，顯示出意想不到的結果。這是一項在為期 6 個月的研究期間對 68 家醫療機構進行的全球調查，結果顯示 48.7% 的 ACC 患者仍接受開放手術。

Nevertheless, evidence has clearly shown the safety of laparoscopic cholecystectomy in ACC. A recent systematic review, comparing open versus laparoscopic cholecystectomy, summarized the available evidence, underlining the limitations and providing a qualitative and quantitative analysis of the included studies. Of 651 studies, 10 were included after qualitative analysis (published between 1993 and 2012): four RCTs, two prospective non-randomized studies, and four retrospective trials, including 1374 patients (677 by laparoscopy vs. 697 by open surgery).
然而，有證據清楚地表明腹腔鏡膽囊切除術在 ACC 中的安全性。最近的一項系統評價比較了開放膽囊切除術與腹腔鏡膽囊切除術，總結了現有證據，強調了局限性，並對納入的研究進行了定性和定量分析。在 651 項研究中，有 10 項經過定性分析（發表於 1993 年至 2012 年）后納入：4 項 RCT、2 項前瞻性非隨機研究和 4 項回顧性試驗，包括 1374 名患者（677 例腹腔鏡手術，697 例開放手術）。

Laparoscopic cholecystectomy in ACC was associated with a lower complication rate and with a shorter hospital stay. There were no differences for the same-admission cholecystectomy in terms of morbidity, operative time and intraoperative blood loss and bile leakage; however, the laparoscopic approach showed a decrease in mortality rate, postoperative hospital stay, wound infection and pneumonia. Moreover, the operative time progressively became shorter in laparoscopy when data were analysed its instances between 1998 and 2007 [75].
ACC 的腹腔鏡膽囊切除術與較低的併發症發生率和較短的住院時間相關。同入院膽囊切除術在發病率、手術時間、術中失血、膽漏方面無差異;然而，腹腔鏡入路顯示死亡率、術后住院時間、傷口感染和肺炎均有所降低。此外，當對 1998 年至 2007 年間的數據進行分析時，腹腔鏡手術的手術時間逐漸縮短 [75]。

A reaffirmation of the safety of laparoscopic cholecystectomy for ACC was shown in another systematic review comparing early laparoscopic cholecystectomy (ELC) and delayed laparoscopic cholecystectomy (DLC), including seven discordant meta-analyses and systematic reviews published from 2004 to 2015. The conclusions were that no differences in mortality, bile duct injury, bile leakage, overall complications and conversion to open surgery were seen. However, ELC had a significant reduction in wound infection, hospitalisation, duration of surgery and quality of life [76].
另一項比較早期腹腔鏡膽囊切除術 （ELC） 和延遲腹腔鏡膽囊切除術 （DLC） 的系統評價重申了腹腔鏡膽囊切除術對 ACC 的安全性，包括 2004 年至 2015 年發表的七項不一致的薈萃分析和系統評價。結論是，在死亡率、膽管損傷、膽漏、總體併發症和轉換為開放手術方面沒有差異。然而，ELC 在傷口感染、住院率、手術時間和生活品質方面有顯著降低[76]。

TG18 widened the indications for laparoscopic cholecystectomy when compared with TG13, as they supported same-admission laparoscopic cholecystectomy for patients with all three severity grades of ACC [77, 78]. This is in line with the recommendations of the 2016 WSES Guidelines [7].
與 TG13 相比，TG18 擴大了腹腔鏡膽囊切除術的適應症，因為它們支援對所有三個嚴重程度的 ACC 患者進行同入院腹腔鏡膽囊切除術[77,78]。 這符合 2016 年 WSES 指南 [7] 的建議。

In summary, the review of the relevant recent literature confirmed strong support for the recommendation that laparoscopic cholecystectomy should be attempted in cases of ACC. Critical patient conditions, such as septic shock or anaesthesiology contraindication, are reasons to avoid laparoscopic cholecystectomy.
綜上所述，近期相關文獻的綜述證實了對 ACC 病例應嘗試腹腔鏡膽囊切除術的建議的強烈支援。危重患者情況，如感染性休克或麻醉禁忌症，是避免腹腔鏡膽囊切除術的原因。

Is laparoscopic cholecystectomy safe and feasible for patients with ACC who have liver cirrhosis, are older than 80 years or are pregnant?
腹腔鏡膽囊切除術對於患有肝硬化、80 歲以上或懷孕的 ACC 患者是否安全可行？

3.3 We suggest performing laparoscopic cholecystectomy for ACC patients with Child’s A and B cirrhosis, patients with advanced age (including more than 80 years old) and patients who are pregnant. #QoE: low; SoR: weak#
3.3 我們建議對患有兒童 A 型和 B 型肝硬化的 ACC 患者、高齡患者（包括 80 歲以上）和妊娠患者進行腹腔鏡膽囊切除術。#QoE：低;SoR：弱#

Patients with liver cirrhosis
肝硬化患者

In cases of liver cirrhosis, surgical dissection could be difficult and there is a higher risk of bleeding and other serious complications. Unfortunately, the available evidence on both open and laparoscopic cholecystectomy for ACC in patients with liver cirrhosis is limited. Therefore, we mainly accept evidence that comes from elective procedures performed for biliary colic or chronic cholecystitis. According to a meta-analysis published by de Goede et al., elective laparoscopic cholecystectomy in patients with child A or B cirrhosis was associated with significantly fewer postoperative complications, a shorter duration of hospitalisation and a shorter time to resume a normal diet, when compared to the open technique [79]. Lucidi et al. recommended laparoscopic cholecystectomy as the first-choice approach in cirrhotic patients. However, recommendation for laparoscopic cholecystectomy in patients with child C cirrhosis is unclear [80]. Nevertheless, other studies showed that laparoscopic cholecystectomy in these cirrhotic patients was associated with a significantly prolonged duration of surgery and an increase in operative blood loss, conversion rate, length of hospital stay and overall morbidity and mortality when compared with non-cirrhotic patients [81]. In cirrhotic patients, the morbidity associated with laparoscopic cholecystectomy is directly related to the Child-Pugh score [82, 83].
在肝硬化的情況下，手術解剖可能很困難，並且出血和其他嚴重併發症的風險更高。不幸的是，關於肝硬化患者 ACC 的開放膽囊切除術和腹腔鏡膽囊切除術的現有證據有限。因此，我們主要接受來自膽絞痛或慢性膽囊炎擇期手術的證據。根據 de Goede 等發表的一項 meta 分析，與開放技術相比，兒童 A 或 B 型肝硬化患者的擇期腹腔鏡膽囊切除術術后併發症顯著減少，住院時間縮短，恢復正常飲食時間縮短[79]。Lucidi 等人推薦腹腔鏡膽囊切除術作為肝硬化患者的首選方法。然而，兒童 C 型肝硬化患者對腹腔鏡膽囊切除術的推薦尚不清楚[80]。然而，其他研究表明，與非肝硬化患者相比，這些肝硬化患者腹腔鏡膽囊切除術與手術時間顯著延長、手術失血量、轉化率、住院時間以及總體發病率和死亡率增加有關[81]。在肝硬化患者中，腹腔鏡膽囊切除術的發病率與 Child-Pugh 評分直接相關[82,83]。

In patients with advanced cirrhosis and severe portal hypertension, specific technical difficulties may be encountered due to the presence of a portal cavernoma, the difficulty in dissecting the Calot’s triangle and the gallbladder hilum, the presence of adhesions and neovascularization or difficulty in controlling bleeding from the liver bed. Subtotal cholecystectomy is a valid option to avoid some of these difficulties [84, 85].
在晚期肝硬化和嚴重門靜脈高壓症患者中，由於存在門靜脈海綿狀血管瘤、難以解剖卡洛特三角和膽囊門、存在粘連和新生血管或難以控制肝床出血，可能會遇到特定的技術困難。膽囊次全切除術是避免其中一些困難的有效選擇[84,85]。

In conclusion, the laparoscopic approach should be the first choice for cholecystectomy in child A and B patients. The approach to patients with child C or uncompensated cirrhosis remains a matter of debate. As a first recommendation, cholecystectomy should be avoided in these patients, unless clearly indicated, such as in ACC not responding to conservative management [80].
總之，腹腔鏡入路應是兒童 A 和 B 患者膽囊切除術的首選。兒童 C 或無代償期肝硬化患者的治療方法仍然是一個有爭議的問題。作為首例建議，除非有明確指征，否則應避免對這些患者進行膽囊切除術，例如 ACC 對保守治療無反應[80]。

Patients over 80 years old
80歲以上患者

The true clinical relevance of age is difficult to assess and the impact of old age on the clinical outcomes in cases of surgical abdominal pathology is largely unknown.
年齡的真正臨床相關性很難評估，並且老年對腹部外科病變病例臨床結果的影響在很大程度上是未知的。

In 2017, the WSES and the Italian Society for Geriatric Surgery developed a CC and a consequent set of guidelines on this topic. Only retrospective studies have focused their interest on elderly patients with ACC. In general, no RCTs are available, population sizes of the studies were small and distributed over a long period of time. It should be noted that the prevalence of elderly people with ACC could increase in the future, due to the improvement in life expectancy and the consideration that the risk of biliary stones increases with age. Some of the recommendations were derived from evidence describing the general population, which includes the elderly. The level of evidence for surgery, timing and risk assessment ranged from 2 to 3, and the grade of recommendation ranged from B to C according the 2011 Oxford classification “(https://www.cebm.net/wp-content/uploads/2014/06/CEBM-Levels-of-Evidence-2.1.pdf.)”. With these limitations, the conclusion supported laparoscopic cholecystectomy for ACC in elderly patients, after considering the intrinsic surgical risk, life expectancy and the rate of relapse in cases of conservative management; and frailty scores, in the absence of a single universally accepted score, were evaluated as adjunctive tools to better characterize elderly patients in the clinical situation [9].
2017 年，WSES 和義大利老年外科學會制定了 CC 和隨後的一套關於該主題的指南。只有回顧性研究才將興趣集中在老年 ACC 患者身上。一般來說，沒有可用的隨機對照試驗，研究的人群規模很小，並且分佈在很長一段時間內。應該指出的是，由於預期壽命的提高以及考慮到膽道結石的風險隨著年齡的增長而增加，未來患有 ACC 的老年人的患病率可能會增加。一些建議來自描述普通人群（包括老年人）的證據。根據 2011 年牛津分類“（https://www.cebm.net/wp-content/uploads/2014/06/CEBM-Levels-of-Evidence-2.1.pdf.）”，手術、時機和風險評估的證據等級為 2 至 3 級，推薦等級為 B 級至 C 級。由於這些局限性，在考慮保守治療病例的內在手術風險、預期壽命和復發率后，結論支援腹腔鏡膽囊切除術治療老年患者 ACC;在缺乏單一普遍接受的評分的情況下，虛弱評分被評估為輔助工具，以更好地表徵臨床情況下的老年患者[9]。

More recently, Wiggins et al. have published a retrospective study based on an administrative national database of all consecutive patients aged over 80, who were admitted for ACC in England between 1997 and 2012. It included a very large number of patients (47,500). On index admission, non-operative treatment was carried out for 89.7% of the patients. Then, 7.5% had a cholecystectomy, and the remaining 2.8% had a cholecystostomy. The three groups were slightly different in mean age (83, 85 and 85 years, respectively) and the Charlson Comorbidity Index was below 2 in 87.5%, 83.1% and 83.2%, respectively. When surgery was compared to non-operative management (NOM) and to cholecystectomy, the mortality rate showed a trend favouring surgical management. The 30-day mortality rates were 11.6% for surgery, 9.9% for NOM (p < 0.001) and 13.4% for cholecystectomy (p < 0.001); the 90-day mortality rates were 15.6% for surgery, 16.1% for NOM (p > 0.05) and 22.5% for cholecystectomy (p < 0.001); the 1-year mortality rates were 20.8% for surgery, 27.1% for NOM and 37% for cholecystostomy (p < 0.001). It should be noted that this study showed a readmission rate of more than 50% after conservative management, which probably contributed to the increased mortality rate at 90 days and 1 year in this group. Interestingly, the proportion of cholecystectomies performed laparoscopically increased from 27 to 59% between 2006 and 2012. Moreover, multivariate analysis showed that, among the surgical group at the index admission, laparoscopy played an independent protective role, with an 84% relative risk reduction in 30-day mortality (OR 0.16, 95% CI 0.10–0.25) when compared to open cholecystectomy. In the discussion, the authors pointed out that the results could have some relationship with the fact that they came from a nation in which early cholecystectomy in ACC patients, regardless of age, is applied only in 15.7% of cases, as compared to 52.7% in the USA [86].
最近，Wiggins 等人發表了一項回顧性研究，該研究基於 1997 年至 2012 年間在英國因 ACC 入院的所有 80 歲以上連續患者的國家行政資料庫。它包括非常多的患者（47,500 人）。指數入院時，89.7%的患者進行了非手術治療。然後，7.5% 的人接受了膽囊切除術，其餘 2.8% 的人接受了膽囊造口術。三組平均年齡（分別為 83 歲、85 歲和 85 歲）略有差異，查爾森合併症指數分別低於 2，分別為 87.5%、83.1%和 83.2%。當將手術與非手術治療 （NOM） 和膽囊切除術進行比較時，死亡率顯示出有利於手術治療的趨勢。手術的 30 天死亡率為 11.6%，NOM 為 9.9% （p < 0.001），膽囊切除術為 13.4% （p < 0.001）;手術 90 d 死亡率為 15.6%，NOM 為 16.1%（p > 0.05），膽囊切除術為 22.5%（p < 0.001）;手術的 1 年死亡率為 20.8%，NOM 的 1 年死亡率為 27.1%，膽囊造口術的 1 年死亡率為 37% （p < 0.001）。需要注意的是，這項研究表明，保守治療后再入院率超過 50%，這可能是導致該組 90 天和 1 年死亡率增加的原因。有趣的是，2006 年至 2012 年間，腹腔鏡膽囊切除術的比例從 27% 增加到 59%。此外，多因素分析顯示，在指數入院的手術組中，腹腔鏡檢查發揮了獨立的保護作用，與開放式膽囊切除術相比，30 天死亡率的相對風險降低了 84%（OR 0.16,95% CI 0.10-0.25）。 在討論中，作者指出，這些結果可能與以下事實有關：這些結果可能與以下事實有關：在該國家，ACC 患者，無論年齡大小，早期膽囊切除術僅應用於 15.7%的病例，而美國為 52.7%[86]。

With a decreased cut-off at 70 years old for the definition of elderly patients, the safety of ELC in ACC has also been supported by Loozen et al. in a systematic review and meta-analysis published in 2017. The cumulative morbidity and mortality were 24% and 3%, respectively, and there was a higher rate of complications for non-elderly patients. The protective role of laparoscopy is therefore confirmed; however, the authors highlight that there are limitations to their findings, in that there was an absence of prospective studies included in the review [11].
隨著老年患者定義的臨界值在 70 歲時降低，Loozen 等人在 2017 年發表的一項系統評價和薈萃分析中也支援了 ELC 在 ACC 中的安全性。累積發病率和死亡率分別為 24%和 3%，非老年患者的併發症發生率更高。腹腔鏡檢查的保護作用因此得到證實;然而，作者強調他們的研究結果存在局限性，因為本綜述中沒有納入前瞻性研究[11]。

In conclusion, despite the low quality of evidence, the studies detailed here universally favour ELC for elderly patients, even for patients older than 80 years of age. Due to the generally small functional reserve in the elderly, care should be taken to ensure that a prompt therapeutic decision is taken and that a high level of expertise is provided, both intraoperatively and during the postoperative management.
總之，儘管證據品質較低，但本文詳述的研究普遍有利於老年患者，甚至 80 歲以上的患者也支援 ELC。由於老年人的功能儲備通常較小，因此應注意確保及時做出治療決定，並在術中和術后管理期間提供高水準的專業知識。

Patients who are pregnant
懷孕的患者

The literature evidence for pregnant patients is limited. The incidence of ACC during pregnancy varies among reports, ranging from one case per 1600 pregnancies to one case per 10,000 pregnancies. However, ACC during pregnancy is the second reason for non-obstetrical abdominal emergency surgery after appendicitis [87, 88].
妊娠患者的文獻證據有限。懷孕期間 ACC 的發病率因報告而異，從每 1600 例妊娠 1 例到每 10,000 例妊娠 1 例不等。然而，妊娠期 ACC 是闌尾炎后非產科腹部急診手術的第二個原因[87,88]。

The diagnostic criteria and tools are the same used for the general population [89], but it is of note that leucocytosis during pregnancy could be misleading, and that the Murphy sign could be difficult to evaluate in the late part of the third trimester.
診斷標準和工具與一般人群相同[89]，但需要注意的是，妊娠期白細胞增多可能具有誤導性，並且在妊娠晚期可能難以評估 Murphy 征。

The best option for the management of ACC should be chosen considering a balance among the following factors: the risk of complications from ACC, limitations on medication availability depending on the trimester, the risk of relapse, the risk of other specific conditions which may occur during pregnancy and the time until delivery or maturation of the foetus.
選擇 ACC 管理的最佳選擇應考慮以下因素之間的平衡：ACC 併發症的風險、根據妊娠期對藥物可用性的限制、復發風險、懷孕期間可能發生的其他特定疾病的風險以及胎兒分娩或成熟的時間。

In general, in the absence of contraindications, surgery is suggested as first-line therapy in order to avoid complications and potential drug toxicity for the foetus. Retrospective studies stated that recurrent ACC or pancreatitis can occur in 10% of patients, while miscarriage can occur in 10–20% of patients [90]. NOM is an alternative option, but it must be highlighted that there is a risk of higher incidence of spontaneous abortion, threatened abortion, and premature birth when compared to patients who underwent cholecystectomy [91].
一般來說，在沒有禁忌症的情況下，建議手術作為一線治療，以避免併發症和對胎兒的潛在藥物毒性。回顧性研究表明，10%的患者可發生復發性 ACC 或胰腺炎，而 10%-20%的患者可發生流產[90]。NOM 是另一種選擇，但必須強調的是，與膽囊切除術患者相比，自然流產、先兆流產和早產的發生率更高[91]。

One systematic review and meta-analysis focused on the comparison of open cholecystectomy with laparoscopic cholecystectomy during pregnancy [92]. The authors selected 11 studies, all of which were retrospective: two from national databases, one from a state database and the others were retrospective from single- or multiple- institutions. The analysis included 10,632 patients (1219 open; 9413 laparoscopic). The outcomes were as follows:
一項系統評價和 meta 分析側重於妊娠期開放膽囊切除術與腹腔鏡膽囊切除術的比較[92]。作者選擇了 11 項研究，所有這些研究都是回顧性的：兩項來自國家資料庫，一項來自州資料庫，其他來自單一或多個機構的回顧性研究。該分析包括 10,632 名患者（1219 名開放患者;9413 名腹腔鏡患者）。結果如下：

• Outcomes for the mother: death occurred in 1 open versus 0 laparoscopic cases; complications (including caesarean section, dilatation and curettage, hysterectomy, maternal dehydration and pre-eclampsia) were 3.5% in laparoscopic cases vs. 8.2% in open cases, with an odds ratio (OR) of 0.42 (95% CI 0.33–0.53, p < 0.001).
  母親的結局：1 例腹腔鏡手術例死亡，0 例腹腔鏡手術死亡;腹腔鏡病例的併發症（包括剖腹產、擴張和刮宮、子宮切除術、產婦脫水和先兆子痫）為 3.5%，開放病例為 8.2%，比值比 （OR） 為 0.42（95% CI 0.33–0.53，p < 0.001）。

• Outcomes for the foetus: 1 death out of 161 patients (0.6%) in laparoscopic cases versus 4 deaths from 93 patients (4.3%) in open cases, with an OR of 0.39 (95% CI 0.07–2.19, p = 0.29); the complications (including foetal loss, foetal distress, threatened preterm delivery and preterm birth) were 346 out of 8807 laparoscopic cases (3.9%) vs. 139 out of 1161 open cases (12.0%), with an OR of 0.42 (95%; 0.28–0.63, p < 0.001).
  胎兒結局：腹腔鏡手術 161 例患者中有 1 例死亡（0.6%），開放病例 93 例患者中有 4 例死亡（4.3%），OR 為 0.39（95%CI 0.07-2.19，p = 0.29）; 併發症（包括胎兒丟失、胎兒窘迫、先兆早產和早產）在 8807 例腹腔鏡病例中為 346 例 （3.9%），而 1161 例開放病例中有 139 例 （12.0%），OR 為 0.42 （95%; 0.28–0.63，p < 0.001）。

• Surgical complications (including bile duct injury, bile duct leaking, solid organ or hollow viscus injury, pulmonary and wound infections, and hernias): 901 out of 9413 laparoscopic cases (9.6%) versus 211 out of 1219 open cases (17.3%), with an OR of 0.45 (95% CI 0.25–0.82, p = 0.01).
  手術併發症（包括膽管損傷、膽管滲漏、實體器官或中空內臟損傷、肺部和傷口感染以及疝氣）：9413 例腹腔鏡病例中有 901 例（9.6%），1219 例開放病例中有 211 例（17.3%），OR 為 0.45（95%CI 0.25-0.82，p = 0.01）。

• Preterm delivery (< 37-week gestation): 11 out of 127 laparoscopic cases (8.7%) versus 5 out of 78 open cases (6.4%), with an OR of 1.35 (95% CI 0.41–5.14; p = 0.59).
  早產（< 妊娠 37 周）：127 例腹腔鏡病例中有 11 例（8.7%），78 例開放病例中有 5 例（6.4%），OR 為 1.35（95%CI 0.41-5.14;p = 0.59）。

• The Apgar score at 5 minutes was the same.
  5分鐘時的阿普加得分相同。

In 2018, another Japanese nationwide retrospective cohort study reported similar results [93].
2018 年，另一項日本全國性回顧性佇列研究報告了類似的結果[93]。

With the limitations of the quality of the studies, laparoscopy should be suggested for the treatment of symptomatic gallstones including ACC. The vast majority of studies suggests the second trimester until the initial part of the third trimester as the best time to perform laparoscopic cholecystectomy, as there is a higher risk of miscarriage and toxic effect of anaesthesia in the first trimester, while concerns are related to the size of the uterus in the third trimester [92,93,94].
由於研究品質的局限性，應建議腹腔鏡治療包括 ACC 在內的有癥狀的膽結石。絕大多數研究表明，妊娠中期至妊娠晚期初期是進行腹腔鏡膽囊切除術的最佳時間，因為妊娠早期流產的風險和麻醉的毒性作用較高，而擔憂與妊娠晚期子宮的大小有關[92，93,94]。

A systematic review and set of guidelines from the British Society for Gynaecological Endoscopy, endorsed by the Royal College of Obstetricians and Gynaecologists, have been published in 2019 and they summarize the discussion, confirming the benefits of ELC over non-operative treatment, especially in the second trimester [95].
英國婦科內鏡學會（British Society for Gynaecological Endoscopy）於 2019 年發表了一套系統綜述和一套指南，並得到了英國皇家婦產科醫師學會的認可，並總結了討論，證實了 ELC 相對於非手術治療的益處，尤其是在妊娠中期[95]。

Which surgical strategies should be adopted in case of difficult anatomic identification of structures during cholecystectomy for ACC?
如果 ACC 膽囊切除術期間結構的解剖學識別困難，應採取哪些手術策略？

3.4 We recommend laparoscopic or open subtotal cholecystectomy in situations in which anatomic identification is difficult and in which the risk of iatrogenic injuries is high. #QoE: moderate; SoR: strong#
3.4 在解剖學識別困難且醫源性損傷風險較高的情況下，我們建議進行腹腔鏡或開放性次全膽囊切除術。#QoE：中等;SoR：強#

Reasons for a ‘difficult gallbladder’ vary, and can be related to obesity, adhesions, acute or chronic inflammation, distended gallbladder and liver cirrhosis. Due to the diversity of reasons and the variability of approaches among surgeons, a review conducted in 2011 showed no consensus on the ideal way to deal with a difficult gallbladder. The options include subtotal cholecystectomy, fundus first cholecystectomy, perioperative cholangiogram, open conversion or a combination of these options [96].
“膽囊困難”的原因各不相同，可能與肥胖、粘連、急性或慢性炎症、膽囊擴張和肝硬化有關。由於外科醫生原因的多樣性和方法的差異，2011 年進行的一項審查顯示，對於處理困難膽囊的理想方法尚未達成共識。這些選擇包括膽囊次全切除術、眼底首次膽囊切除術、圍手術期膽管造影、開腹轉換或這些選擇的組合[96]。

In this section, we focus on subtotal cholecystectomy, which is an option when the critical view of safety [97] cannot be obtained. In 2015, a systematic review and meta-analysis by Elshaer et al. reported that subtotal cholecystectomy was performed using laparoscopic (72.9%) open (19.0%) and laparoscopic converted to open (8.0%) techniques. In this study including over 1200 patients, the most common indications were severe cholecystitis (72.1%), followed by gallstones in liver cirrhosis and portal hypertension (18.2%) and empyema or a perforated gallbladder (6.1%). They concluded that subtotal cholecystectomy might be helpful during the surgical management of difficult cholecystectomy; also considering that it achieves morbidity rates comparable to those reported for total cholecystectomy in straightforward cases. The quality of evidence is limited, due to the absence of prospective randomized studies, which are not expected to be easily performed in the future [85].
在本節中，我們將重點介紹膽囊次全切除術，這是無法獲得安全性[97]的批判性觀點時的一種選擇。2015 年，Elshaer 等人的一項系統評價和薈萃分析報告稱，使用腹腔鏡 （72.9%） 開放 （19.0%） 和腹腔鏡轉換為開放 （8.0%） 技術進行膽囊次全摘術。在這項包括 1200 多名患者的研究中，最常見的適應症是嚴重膽囊炎 （72.1%），其次是肝硬化和門靜脈高壓症中的膽結石 （18.2%） 以及膿胸或膽囊穿孔 （6.1%）。他們得出的結論是，膽囊次全切除術可能有助於困難膽囊切除術的手術治療;還考慮到它的發病率與簡單病例中報告的全膽囊切除術相當。由於缺乏前瞻性隨機研究，證據品質有限，預計未來不容易進行[85]。

Support for subtotal cholecystectomy has also been reported from other studies. In a retrospective study on severely difficult gallbladders [98], 105 patients who underwent laparoscopic cholecystectomy were matched with 46 patients who underwent subtotal laparoscopic cholecystectomy. The authors observed no bile duct injury in the subtotal cholecystectomy group, but four instances in the complete cholecystectomy group. Bile leakage was greater in the subtotal group due to difficulty in the cicatrisation on the remaining gallbladder stump; however, bile leakage was managed easily by abdominal drainage or in combination with endoscopic biliary prosthesis placement.
其他研究也報導了對膽囊次全切除術的支援。一項關於重度膽囊困難的回顧性研究[98]，將 105 例腹腔鏡膽囊切除術患者與 46 例腹腔鏡次全膽囊切除術患者進行了匹配。作者在膽囊次全切除術組中沒有觀察到膽管損傷，但在完全膽囊切除術組中觀察到四例膽管損傷。由於剩餘膽囊殘端棘裂困難，亞全組膽漏較多;然而，膽汁滲漏可以通過腹部引流或與內窺鏡膽道假體放置相結合來輕鬆控制。

A recent nation-based database study evaluating 290,855 cases between 2003 and 2014 showed an increased use of subtotal cholecystectomy from 0.1 to 0.52% for open subtotal cholecystectomy and from 0.12 to 0.28% for laparoscopic cholecystectomy. The conversion rate from laparoscopic to open total cholecystectomy decreased from 10.5 to 7.6%. Interestingly, the teaching hospitals significantly increased the rate of subtotal cholecystectomy [99]. Furthermore, it should be highlighted that there are different techniques to achieve subtotal cholecystectomy: this aspect could add some difficulty in analysing data from different studies [100].
最近一項基於國家的資料庫研究評估了 2003 年至 2014 年間的 290,855 例病例，結果顯示，開放性膽囊次全切除術的膽囊次全切除術的使用率從 0.1% 增加到 0.52%，腹腔鏡膽囊切除術的使用率從 0.12% 增加到 0.28%。腹腔鏡全膽囊切除術到開放式全膽囊切除術的轉化率從 10.5% 下降到 7.6%。有趣的是，教學醫院顯著提高了膽囊次全切除術的發生率[99]。此外，應該強調的是，有不同的技術可以實現膽囊次全切除術：這方面可能會增加分析不同研究數據的難度[100]。

The quality of the available evidence ranges from low to moderate. However, the concordance of all the evidence, the large application of the technique globally, with the important clinical impact on patient safety, and the current absence of opportunities to achieve a better level of evidence strongly supports the recommendation for subtotal cholecystectomy in cases of difficult gallbladder.
現有證據的品質從低到中等不等。然而，所有證據的一致性、該技術在全球範圍內的廣泛應用、對患者安全的重要臨床影響以及目前缺乏獲得更好證據水平的機會，強烈支援在膽囊困難的情況下進行膽囊次全切除術的建議。

When should conversion from laparoscopic to open cholecystectomy be considered in patients with ACC?
ACC 患者何時應考慮從腹腔鏡膽囊切除術轉換為開放性膽囊切除術？

3.5 We recommend conversion from laparoscopic to open cholecystectomy in case of severe local inflammation, adhesions, bleeding from the Calot’s triangle or suspected bile duct injury. #QoE: moderate; SoR: strong#
3.5 如果出現嚴重的局部炎症、粘連、卡洛特三角出血或疑似膽管損傷，我們建議從腹腔鏡轉換為開放式膽囊切除術。#QoE：中等;SoR：強#

This recommendation should be supported by studies in which the patients with difficult gallbladder have been randomized to conversion or to different laparoscopic procedures. However, this type of study is unlikely to be performed.
這一建議應得到研究的支援，在這些研究中，膽囊困難患者被隨機分配到轉換或接受不同的腹腔鏡手術。然而，這種類型的研究不太可能進行。

The present update of the WSES Guidelines on ACC clarifies that, in 2016, the reasons for conversion were used as a proxy in the absence of high-quality studies; we maintained the same approach for the current version of the guidelines [7, 101, 102].
目前關於 ACC 的 WSES 指南的更新澄清了，在 2016 年，在缺乏高品質研究的情況下，轉換的原因被用作代理;對於當前版本的指南，我們保持了相同的方法 [7， 101， 102]。

When expertise in difficult instances of laparoscopic cholecystectomy is ensured, the conversion is not a failure and it represents a valid option to be considered. The quality of the evidence is moderate. However, the absence of opportunities to achieve a higher quality of evidence, along with the broadly used conversion to open surgery and the clinical impact on patients’ safety, suggests a strong recommendation for conversion to open surgery after laparoscopy has been attempted at the best institutional level available. Nevertheless, according to Gupta et al., surgeons should adopt a philosophy of safe laparoscopic cholecystectomy. Understanding the mechanisms related to specific complications may help elaborating strategies to avoid or reduce those complications; in this context, the surgeon should define, in their own personal armamentarium, the indications for a bailout techniques among the available options [103, 104].
當確保腹腔鏡膽囊切除術困難病例的專業知識時，轉換不會失敗，而是值得考慮的有效選擇。證據品質中等。然而，由於缺乏獲得更高品質證據的機會，以及廣泛使用的向開放手術的轉換以及對患者安全的臨床影響，表明強烈建議在可用的最佳機構層面嘗試在腹腔鏡檢查后轉換為開放手術。然而，根據 Gupta 等人的說法，外科醫生應該採用安全的腹腔鏡膽囊切除術的理念。瞭解與特定併發症相關的機制可能有助於制定避免或減少這些併發症的策略;在這種情況下，外科醫生應在自己的個人武器庫中定義可用選項中的救助技術適應症 [103， 104]。

Section 4. Timing of cholecystectomy in people with ACC
第 4 節。ACC 患者膽囊切除術的時機

When is the optimal timing for laparoscopic cholecystectomy in patients with ACC?
ACC 患者腹腔鏡膽囊切除術的最佳時機是什麼時候？

4.1 In the presence of adequate surgical expertise, we recommend ELC be performed as soon as possible, within 7 days from hospital admission and within 10 days from the onset of symptoms. #QoE: moderate; SoR: strong#.
4.1 在有足夠手術專業知識的情況下，我們建議儘快進行 ELC，入院后 7 天內和癥狀出現后 10 天內。#QoE：中等;SoR：強#。

Comment: ELC so defined is preferable to intermediate laparoscopic cholecystectomy (ILC, performed between 7 days of hospital admission and 6 weeks) and DLC (performed between 6 weeks and 3 months).
評論：如此定義的 ELC 優於中間腹腔鏡膽囊切除術（ILC，在入院 7 天至 6 周之間進行）和 DLC（在 6 周至 3 個月之間進行）。

4.2 We suggest DLC to be performed beyond 6 weeks from the first clinical presentation, in case ELC cannot be performed (within 7 days of hospital admission and within 10 days of onset of symptoms). #QoE: very low; SoR: weak#.
4.2 我們建議在首次臨床表現后 6 周後進行 DLC，以防無法進行 ELC（入院后 7 天內和癥狀出現后 10 天內）。#QoE：非常低;SoR：弱#。

Surgery is currently the recommended treatment in people with acute cholecystitis. Conservative management with fluids, analgesia and antibiotics is an option for people with mildly symptomatic acute cholecystitis (i.e. people without peritonitis or those who have worsening clinical condition). In a RCT with long-term follow-up of 14 years, about 30% of patients treated conservatively developed recurrent gallstone-related complications and 60% of patients had undergone cholecystectomy subsequently [105, 106]. The study included only 33 patients and had high risk of bias [105, 106]. Therefore, until new high-quality evidence becomes available, laparoscopic cholecystectomy is considered the recommended treatment for patients who are fit to undergo surgery.
手術是目前急性膽囊炎患者的推薦治療方法。對於癥狀輕微的急性膽囊炎患者（即沒有腹膜炎的人或臨床狀況惡化的人），使用液體、鎮痛和抗生素進行保守治療是一種選擇。一項長期隨訪 14 年的 RCT 顯示，保守治療的患者中約 30%出現復發性膽結石相關併發症，60%的患者隨後接受了膽囊切除術[105,106]。 該研究僅納入了 33 例患者，且偏倚風險較高[105,106]。 因此，在獲得新的高質量證據之前，腹腔鏡膽囊切除術被認為是適合接受手術的患者的推薦治療方法。

In patients with moderate or severely symptomatic cholecystitis or in those with mildly symptomatic acute cholecystitis who prefer surgery, laparoscopic cholecystectomy is preferred over open cholecystectomy [75]. The timing of laparoscopic cholecystectomy in these patients is controversial. A Cochrane review published in 2013 concluded that ELC for acute cholecystitis seems safe and may shorten the total hospital stay [107].
對於中度或重度癥狀性膽囊炎患者，或首選手術的輕度癥狀急性膽囊炎患者，腹腔鏡膽囊切除術優於開放式膽囊切除術[75]。這些患者腹腔鏡膽囊切除術的時機存在爭議。2013 年發表的一項 Cochrane 系統綜述得出結論，ELC 治療急性膽囊炎似乎是安全的，並可能縮短總住院時間[107]。

An update of the literature searches was performed for the purpose of this guideline. Sixteen trials were identified in the update (including the trials originally included in the systematic review) [108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123]. The number of participants with acute cholecystitis was not reported in one of the trials [121]. In the remaining 15 trials, 1240 participants were included in 14 trials comparing ELC versus DLC [108,109,110,111,112,113,114,115, 117,118,119,120, 122, 123] and 618 participants were included in one trial comparing ELC versus intermediate laparoscopic cholecystectomy (ILC) [116]. The country; recruitment period; number of participants; the duration of symptoms; the timing of ELC, DLC and ILC; and the surgical experience are reported in Table 3. Overall, it appears that ELC was performed within 10 days of onset of symptoms in most trials.
為本指南的目的，對文獻檢索進行了更新。更新中確定了 16 項試驗（包括最初納入系統評價的試驗）[108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123]。 其中一項試驗未報告急性膽囊炎受試者人數[121]。在其餘 15 項試驗中，1240 名受試者被納入 14 項比較 ELC 與 DLC 的試驗[108,109,110,111,112,113,114,115,117,118,119,120,122,123]，618 名受試者納入 1 項比較 ELC 與中間腹腔鏡膽囊切除術（intermediate laparoscopic cholecystectomy， ILC）的試驗[116].國家;招聘期;參加人數;癥狀的持續時間;ELC、DLC 和 ILC 的時間安排;手術經驗見表 3。總體而言，在大多數試驗中，ELC 似乎是在癥狀出現后 10 天內進行的。

Table 3 Timing of cholecystectomy in people with ACC
表 3 ACC 患者膽囊切除術時機

There were no significant differences in mortality or conversion to open cholecystectomy between the three groups. The proportion of patients with serious adverse events was significantly higher in ILC compared to ELC in the only trial included in the comparison between ILC and DLC [116]. The number of serious adverse events was significantly less with ELC compared to DLC in the only trial comparing ELC with DLC that reported this information [111]. The total length of hospital stay (including all the admissions for treatment) was about 4 days shorter with ELC compared to DLC [109,110,111,112, 115, 117,118,119,120, 123], and about 5 days shorter with ELC compared to ILC [116]. The return to work was about 9 days sooner following ELC compared to DLC [109, 120].
三組之間死亡率或轉為開放式膽囊切除術的差異無統計學意義。在 ILC 和 DLC 比較中納入的唯一一項試驗中，ILC 組發生嚴重不良事件的患者比例顯著高於 ELC[116]。在唯一一項報告了 ELC 與 DLC 的比較試驗中，ELC 組的嚴重不良事件發生率顯著低於 DLC[111]。與 DLC 相比，ELC 組的總住院時間（包括所有入院治療時間）縮短約 4 日[109,110,111,112， 115， 117,118,119,120， 123]，ELC 組比 ILC 縮短約 5 日[116]。 與 DLC 相比，ELC 后重返工作崗位的時間大約早了 9 天[109,120]。

Overall, it appears that ELC performed within 7 days of hospital admission and within 10 days of onset of symptoms is superior to either ILC performed between 7 days of hospital admission and 6 weeks or DLC performed between 6 weeks and 3 months of the initial hospital admission for acute cholecystitis. Since blinding cannot be achieved in these comparisons and the outcomes were subjective, all the trials were deemed to be at high risk of bias. However, trials with low risk of bias are difficult to conduct in this comparison. Since the evidence was consistent across trials and outcomes, it appears highly likely that ELC is superior to either ILC or DLC. Therefore, despite the moderate quality evidence (which is mainly because of the lack of blinding in the trials), the recommendation for ELC is strong. However, it should be noted that the study authors described that ELC was more complex; therefore, it should be attempted only by experienced surgeons. Referral to centres with high surgical expertise should be considered if adequate surgical expertise is not available. If ELC cannot be performed, DLC appears to be better than ILC. Although, there is no evidence of difference between DLC and ILC, the ACDC trial comparing ELC versus ILC showed that a significant proportion of patients undergoing ILC developed serious adverse events [116]. Therefore, DLC may be preferable when ELC is not possible, although a proportion of patients with planned DLC approach may need unplanned earlier surgery (see Fig. 1) [107]. There are no trials comparing ILC and DLC and it is unlikely that they will performed, given the results of the ACDC trial [116]. Therefore, there is significant uncertainty whether DLC is better than ILC when ELC is not possible and the recommendation to perform DLC when ELC is not possible is weak.
總體而言，在入院后 7 天內和癥狀出現后 10 天內進行的 ELC 似乎優於在入院后 7 天至 6 周之間進行的 ILC 或在急性膽囊炎初次入院后 6 周至 3 個月之間進行的 DLC。由於這些比較無法實現盲法，並且結局是主觀的，因此所有試驗都被認為存在高偏倚風險。然而，在這種比較中很難進行偏倚風險低的試驗。由於證據在試驗和結局中是一致的，因此 ELC 似乎很可能優於 ILC 或 DLC。因此，儘管有中等質量的證據（主要是因為試驗中缺乏盲法），但對 ELC 的推薦是強烈的。然而，應該指出的是，研究作者描述 ELC 更為複雜;因此，只能由有經驗的外科醫生嘗試。如果沒有足夠的外科專業知識，應考慮轉診至具有高外科專業知識的中心。如果無法執行 ELC，則 DLC 似乎比 ILC 更好。雖然沒有證據表明 DLC 和 ILC 之間存在差異，但 ACDC 試驗比較了 ELC 與 ILC 的比較結果顯示，很大一部分 ILC 患者發生了嚴重不良事件[116]。因此，當無法進行 ELC 時，DLC 可能更可取，儘管一部分計劃採用 DLC 方法的患者可能需要計劃外的早期手術（見圖 199999 年）。1） [107]。目前尚無比較 ILC 和 DLC 的試驗，鑒於 ACDC 試驗的結果，它們不太可能進行[116]。 因此，當無法進行 ELC 時，DLC 是否優於 ILC 存在很大的不確定性，並且在無法進行 ELC 時進行 DLC 的建議較弱。

Section 5. Risk prediction in ACC
第 5 節。ACC 中的風險預測

How can the prognosis and surgical risk be assessed for patients with ACC?
如何評估 ACC 患者的預後和手術風險？

5.1 We cannot suggest the use of any prognostic model in patients with ACC.
5.1 我們不能建議在 ACC 患者中使用任何預後模型。

#QoE: very low; SoR: weak#
#QoE：非常低;SoR：弱#

Comment: There is currently significant uncertainty in the ability of prognostic factors and risk prediction models in predicting outcomes in patients with ACC.
評論：目前預後因素和風險預測模型預測 ACC 患者結局的能力存在很大的不確定性。

Cholecystectomy is currently the recommended treatment for patients with acute cholecystitis. Laparoscopic cholecystectomy is preferred over open cholecystectomy in patients with acute cholecystitis, but it is a major surgical procedure. While it is considered relatively safe, it is associated with a mortality rate between 0.1 and 1% [124,125,126], a risk of bile duct injury in approximately 0.2% to 1.5% of cases [125, 127] and a risk of major complications (such as myocardial infarction, heart failure, acute stroke, renal failure, pulmonary embolism, lung failure or postoperative shock) in between 6 and 9% of cases [124].
膽囊切除術是目前急性膽囊炎患者的推薦治療方法。對於急性膽囊炎患者，腹腔鏡膽囊切除術優於開放式膽囊切除術，但它是一項主要外科手術。雖然它被認為相對安全，但死亡率在 0.1%-1%之間[124,125,126]，膽管損傷風險約為 0.2%-1.5%[125,127]，6%-9%的病例有發生重大併發症（如心肌梗死、心力衰竭、急性腦卒中、腎功能衰竭、肺栓塞、肺衰竭或術后休克）的風險[124]。

Observation is an alternative option for patients with mildly symptomatic ACC (i.e. in patients without peritonitis or in those who have worsening symptoms). After a long-term follow-up of 14 years, about 30% of patients with mildly symptomatic acute cholecystitis who did not undergo cholecystectomy developed recurrent gallstone-related complications, compared with 3% of patients who underwent cholecystectomy. These differences were not significant for recurrent disease or overall complications [128]. However, 60% of patients had undergone surgery, and the study was small and carried a high risk of bias; therefore, there is lot of uncertainty as to whether it is better to perform surgery or observation in patients with mildly symptomatic acute cholecystitis.
對於輕度癥狀的 ACC 患者（即無腹膜炎患者或癥狀惡化的患者），觀察是另一種選擇。經過 14 年的長期隨訪，未進行膽囊切除術的輕症急性膽囊炎患者中，約有 30%出現復發性膽結石相關併發症，而接受膽囊切除術的患者中這一比例為 3%。這些差異對於復發性疾病或總體併發症並不顯著[128]。然而，60%的患者接受過手術，研究規模較小，偏倚風險高;因此，對於輕度癥狀的急性膽囊炎患者，手術或觀察哪個更好，存在很多不確定性。

Identification of patients at high risk of complications and mortality can help in optimising them prior to surgery or in deciding whether referral to high-volume centres and specialized centres, which may decrease the complications [129, 130], is appropriate. Informed decisions about whether to opt for surgery or observation can also be made if information on the risks is available.
識別併發症和死亡率高風險的患者有助於在手術前優化患者，或決定轉診至高容量中心和專科中心是否合適，這可能會減少併發症[129,130]。 如果有關於風險的資訊，也可以就選擇手術還是觀察做出明智的決定。

We performed a systematic review of studies reporting on the ability of prognostic factors or risk prediction models to predict important patient-related outcomes, such as mortality, complications and conversion to open surgery in patients with ACC [131]. In this systematic review and meta-analysis, we included 12 studies and 6827 patients in one or more analysis. Only a few factors (TG13, age, male gender, previous abdominal surgery, diabetes, hypertension and C-reactive protein) were reported in a format similar enough to allow comparisons between studies. The remaining factors were studied in single studies or using different thresholds. Therefore, there is no information on their reproducibility, and the results may be unreliable.
我們對報告預後因素或風險預測模型預測 ACC 患者重要患者相關結局（如死亡率、併發症和轉為開放手術）的能力的研究進行了系統評價[131]。在這項系統評價和 meta 分析中，我們納入了 12 項研究和 6827 名患者，納入了一項或多項分析。只有少數幾個因素（TG13、年齡、男性、既往腹部手術史、糖尿病、高血壓和 C 反應蛋白）以足夠相似的格式報告，以便研究之間進行比較。其餘因素在單一研究中或使用不同的閾值進行研究。因此，沒有關於其可重複性的資訊，結果可能不可靠。

Among the prognostic factors reported in at least two studies, TG13 grade 3 had an increased risk of all-cause mortality compared to grade 1. The risk increased from a median risk of 1.3% to 6.5% (95% CI 3.7–11.2). However, most studies included only people who underwent surgery, not all of whom were patients with ACC. There have been no RCTs of surgery versus observation in people with severe ACC. Laparoscopic cholecystectomy performed by experienced surgeons had lower major complication rates than percutaneous cholecystostomy with no planned cholecystectomy [11]. Therefore, it appears that, despite the increased risk of mortality in TG13 grade 3 compared to TG13 grade 1, surgery seems to be the preferred option when possible. However, referral to high volume centres and specialized centres may decrease the complications [129, 130] and resulting mortality, and should be considered in people with TG13 grade 3 acute cholecystitis.
在至少兩項研究報告的預後因素中，與 1 級相比，TG13 3 級的全因死亡風險增加。風險從中位風險 1.3%增加到 6.5%（95%CI 3.7-11.2）。然而，大多數研究僅納入接受手術的人，並非所有患者都是 ACC 患者。目前尚無在重度 ACC 患者中進行手術與觀察的隨機對照試驗。由經驗豐富的外科醫生進行腹腔鏡膽囊切除術的主要併發症發生率低於無計劃膽囊切除術的經皮膽囊造口術[11]。因此，儘管與 TG13 1 級相比，TG13 3 級的死亡風險增加，但在可能的情況下，手術似乎是首選。然而，轉診至高容量中心和專科中心可能會減少併發症[129,130]和由此導致的死亡率，TG13 3 級急性膽囊炎患者應考慮轉診。

Being male was associated with an increased risk of complications (from 10 to 15%; 95% CI 10.5–20.9) and an increased risk of conversion to open cholecystectomy (from 16 to 48.5%; 95% CI 27.5–70.0). The reasons for the difference in the complications and conversion between males and females are not clear, but may be due to a combination of increased skeletal muscle mass [132] (particularly in the trunk [133]) and increased visceral abdominal fat in males [132, 134, 135], which could make laparoscopic surgery more difficult, and a common delay in males seeking medical help due to a misguided perception of masculinity [136, 137], which could mean that the males had more severe disease than females at the time of presentation to the hospital. Previous upper abdominal surgery is a risk factor for conversion to open cholecystectomy. This is to be expected because of the intra-abdominal adhesions related to previous abdominal surgery [138]. An increased age had a minor increase in the conversion to open cholecystectomy, but the increase is cumulative, as elderly patients may have a clinically significant increase in conversion to open cholecystectomy compared with young people. Various confounding factors such as comorbidities and increased cumulative risk of upper abdominal surgery may contribute to the increased risk of conversion to open cholecystectomy.
男性與併發症風險增加（從 10%到 15%;95%CI 10.5-20.9）和轉換為開放膽囊切除術的風險增加（從 16%到 48.5%;95%CI 27.5-70.0）相關。男性和女性併發症和轉化率差異的原因尚不清楚，但可能是由於男性骨骼肌品質增加[132]（尤其是軀幹[133]）和內臟腹部脂肪增加[132,134,134,135]，這可能使腹腔鏡手術更加困難，以及由於對男性氣質的錯誤認知而導致男性尋求醫療説明的普遍延遲[136， 137]，這可能意味著男性在就診時比女性病情更嚴重。既往上腹部手術是轉為開放式膽囊切除術的危險因素。這是可以預料的，因為與既往腹部手術相關的腹腔內粘連[138]。年齡增加，向開放式膽囊切除術的轉化率略有增加，但這種增加是累積的，因為與年輕人相比，老年患者向開放式膽囊切除術的轉化率可能在臨床上顯著增加。各種混雜因素，例如合併症和上腹部手術的累積風險增加，可能會導致轉換為開放式膽囊切除術的風險增加。

However, it should be noted that the systematic review included only preoperative factors, and most of the studies included only patients undergoing cholecystectomy for ACC. Therefore, the findings of the review are applicable only for preoperative risk prediction in patients undergoing cholecystectomy for ACC.
但需要注意的是，系統評價僅包括術前因素，大多數研究僅納入因 ACC 而接受膽囊切除術的患者。因此，本綜述的結果僅適用於接受膽囊切除術治療 ACC 的患者的術前風險預測。

It should also be noted that most of the studies were retrospective, in which blinding of predictor or outcome measurement were not reported, and most of the studies were small.
還應該注意的是，大多數研究都是回顧性的，其中沒有報告預測因數或結局測量的盲法，而且大多數研究規模較小。

Overall, there is significant uncertainty in the ability of prognostic factors and risk prediction models in predicting outcomes in patients with ACC. TG13 grade 3 may be associated with greater mortality than grade 1 severity of acute cholecystitis. Despite the increased risk of mortality in TG13 grade 3 compared to TG13 grade 1, surgery seems to be the preferred option when possible. The TG18 adopted the TG13 severity grading criteria in predicting outcomes in patients with ACC [14].
總體而言，預後因素和風險預測模型預測 ACC 患者結局的能力存在顯著不確定性。TG13 3 級可能比急性膽囊炎的 1 級嚴重程度與更高的死亡率相關。儘管與 TG13 1 級相比，TG13 3 級的死亡風險增加，但如果可能的話，手術似乎是首選。TG18 採用 TG13 嚴重程度分級標準預測 ACC 患者的結局[14]。

High-quality studies are necessary to provide better information on the prognostic factors of patients with acute cholecystitis and to improve shared decision making.
高品質的研究對於提供有關急性膽囊炎患者預後因素的更好資訊並改善共同決策是必要的。

Section 6. Alternative treatment for patients with ACC who are not suitable for surgery: observation and techniques for gallbladder drainage
第 6 節。不適合手術的 ACC 患者的替代治療：膽囊引流的觀察和技術

When should Non-Operative Management be considered for patients with ACC?
ACC 患者何時應考慮非手術治療？

6.1 We suggest considering NOM, i.e. best medical therapy with antibiotics and observation, for patients refusing surgery or those who are not suitable for surgery. #QoE: low; SoR: weak#
6.1 我們建議考慮對拒絕手術或不適合手術的患者進行 NOM，即使用抗生素和觀察的最佳藥物治療。#QoE：低;SoR：弱#

6.2 We suggest considering alternative treatment options for patients who fail NOM and who still refuse surgery or patients who are not suitable for surgery. #QoE: low; SoR: weak#
6.2 對於 NOM 失敗但仍拒絕手術的患者或不適合手術的患者，我們建議考慮替代治療方案。#QoE：低;SoR：弱#

Schimdt et al. [105] published an RCT comparing observation and surgery in cases of ACC, with a long median follow-up time of 14 years. In their analysis, about 30% of patients with mildly symptomatic acute cholecystitis who did not undergo cholecystectomy developed recurrent gallstone-related complications, as compared with 3% of patients who underwent cholecystectomy, but these differences were not significant for recurrent disease or complications. Overall, 60% of patients had undergone surgery, while 40% avoided surgery. There are significant limitations in the study, as recognized by the authors: firstly, a relevant percentage of eligible patients (41%) were excluded from randomization; secondly, the reasons for the exclusion were not stated in the paper; thirdly, the definitions of dropout and failure within the observation group were not clear. Brazzelli et al. [139] published a systematic review of two RCTs comparing observation with surgery in patients with symptomatic gallstone disease (in the first study) and patients with ACC (in the second study). From a total of 201 patients, the results confirmed the high rate of gallstone-related complications within the observation group (RR 6.63, 95% CI 1.57–28.51, p = 0.01).The authors, although noting the substantial lack of good quality evidence, reported that a policy of surgery for all patients with ACC, when compared to a policy of observation followed by surgery for symptomatic patients, represents a costly but more effective choice. In conclusion, relevant uncertainty exists regarding the best management between surgery or observation in cases of ACC, especially in uncomplicated disease; observation and best medical therapy are likely to be safe, but this latter approach is characterised by a high incidence of recurrent disease.
Schimdt 等[105]發表了一項隨機對照試驗，比較了 ACC 病例的觀察和手術，中位隨訪時間長達 14 年。在他們的分析中，未接受膽囊切除術的輕度癥狀急性膽囊炎患者中約有 30% 出現復發性膽結石相關併發症，而接受膽囊切除術的患者中這一比例為 3%，但這些差異對於復發性疾病或併發症並不顯著。總體而言，60% 的患者接受了手術，而 40% 的患者避免了手術。正如作者所認識到的那樣，該研究存在重大局限性：首先，相關比例的符合條件的患者 （41%） 被排除在隨機化之外;其次，論文中沒有說明排除的原因;（3）觀察組對輟學和失敗的定義不明確。Brazzelli 等[139]發表了兩項隨機對照試驗的系統評價，比較了有癥狀的膽結石病患者（第一項研究）和 ACC 患者（第二項研究）的觀察與手術。從總共 201 名患者中，結果證實觀察組膽結石相關併發症發生率很高（RR 6.63,95% CI 1.57–28.51，p = 0.01）。 作者雖然注意到嚴重缺乏高質量的證據，但報告說，與對有癥狀患者進行觀察後手術的政策相比，對所有 ACC 患者進行手術是一種成本高但更有效的選擇。 總之，對於 ACC 病例，尤其是無併發症的疾病，手術或觀察之間的最佳管理存在相關的不確定性;觀察和最佳藥物治療可能是安全的，但后一種方法的特點是疾病復發率高。

Alternative treatment options may be considered for patients who fail NOM for ACC, also considering the individual patient’s characteristics and the clinical situation.
對於 ACC NOM 失敗的患者，可以考慮替代治療方案，同時還要考慮個體患者的特徵和臨床情況。

Which is the first-choice treatment for ACC in high risk patients?
高危患者 ACC 的首選治療方法是什麼？

6.3 Immediate laparoscopic cholecystectomy is superior to percutaneous transhepatic gallbladder drainage (PTGBD) in high risk patients with ACC. We recommend laparoscopic cholecystectomy as the first-choice treatment in this group of patients. #QoE: high; SoR: strong#
6.3 在高危 ACC 患者中，立即腹腔鏡膽囊切除術優於經皮經肝膽囊引流 （PTGBD）。我們推薦腹腔鏡膽囊切除術作為該組患者的首選治療方法。#QoE：高;SoR：強#

TG13 on ACC [140] considered gallbladder drainage as mandatory for patients with severe grade ACC (according to the Tokyo classification [10] of acute cholecystitis) and also suggested its use in the moderate grade if conservative treatment fail. The revised TG18, based on recent studies, proposed that severe-grade cholecystitis, under certain strict criteria, may be treated with laparoscopic cholecystectomy [10, 140]. A systematic review published in 2016 comparing percutaneous transhepatic gallbladder drainage (PTGBD) and cholecystectomy in critically ill patients reported no benefit for the use of PTGBD over cholecystectomy [141]. Six studies were analysed with a total of 337,500 patients. Mortality rate, length of hospital stay and number of readmissions for gallstone-related diseases were all significantly higher in the PTGBD group than in the cholecystectomy group. It should be noted that all included studies had a retrospective design, which makes the results prone to bias. Recently, the first randomized trial on this subject was published (the CHOCOLATE trial). The results showed that laparoscopic cholecystectomy is superior to PTGBD [11] also in high-risk patients with ACC. PTGBD was compared with ELC in critically ill patients (APACHE score 7–14) with ACC, in terms of efficacy and safety. Patients who underwent ELC had significantly fewer major complications, which were mainly recurrent biliary events. Five percent of patients who underwent ELC had complications, compared with 53% of patients who underwent PTGBD. Mortality was low and remained the same in both groups.
TG13 on ACC [140]認為，對於重度 ACC 患者（根據急性膽囊炎的東京分類[10]），膽囊引流是強制性的，如果保守治療失敗，則應將其用於中度。修訂后的 TG18 基於最近的研究，提出在某些嚴格標準下，重度膽囊炎可以通過腹腔鏡膽囊切除術治療[10,140]。2016 年發表的一項系統評價比較了經皮經肝膽囊引流（percutaneous transhepatic gallbladder drainage， PTGBD）和膽囊切除術在危重患者中的應用，結果顯示 PTGBD 與膽囊切除術相比沒有獲益[141]。分析了六項研究，共涉及 337,500 名患者。膽結石相關疾病的死亡率、住院時間和再入院次數均顯著高於膽囊切除術組。應該注意的是，所有納入的研究都採用了回顧性設計，這使得結果容易產生偏倚。最近，發表了第一項關於該主題的隨機試驗（CHOCOLATE 試驗）。結果表明，腹腔鏡膽囊切除術在 ACC 高危患者中也優於 PTGBD [11]。在 ACC 危重患者（APACHE 評分 7-14）中，PTGBD 與 ELC 在療效和安全性方面進行了比較。接受 ELC 的患者主要併發症明顯減少，主要是復發性膽道事件。接受 ELC 的患者中有 5% 出現併發症，而接受 PTGBD 的患者中這一比例為 53%。兩組的死亡率都很低，保持不變。

Early laparoscopic cholecystectomy also led to significantly less utilisation of health care resources. The trial concluded that immediate cholecystectomy in high-risk patients is safe and should be the standard of care.
早期腹腔鏡膽囊切除術也導致醫療保健資源的利用率顯著降低。該試驗得出的結論是，高危患者立即進行膽囊切除術是安全的，應該成為標準治療。

What is the role of gallbladder drainage in patients with ACC who are not suitable for surgery?
膽囊引流在不適合手術的 ACC 患者中有什麼作用？

6.4 We recommend performing gallbladder drainage in patients with ACC who are not suitable for surgery, as it converts a septic patient with ACC into a non-septic patient. #QoE: moderate; SoR: strong#
6.4 我們建議對不適合手術的 ACC 患者進行膽囊引流，因為它會將患有 ACC 的膿毒症患者轉變為非膿毒癥患者。#QoE：中等;SoR：強#

Patients who are not suitable for surgery, but who are septic due to gallbladder empyema, are effectively treated by PTGBD, as shown in the CHOCOLATE trial [11]. Gallbladder drainage decompresses the infected bile or pus in the gallbladder, removing the infected collection without removing the gallbladder. The removal of the infected material can result in reduced inflammation and in improvement of the clinical conditions. Several case series, both retrospective and observational, exist on cholecystostomy. A systematic review of the literature included 53 studies with 1918 patients outlining a high success rate of the procedure (85.6%) with a low procedure-related mortality rate (0.36%); however, the 30-day mortality rate was high at 15.4% [142]. A major limitation of the study was the inclusion of patients with both acute acalculous cholecystitis and ACC. A review of additional 27observational studies on cholecystostomy [143] showed significant heterogeneity in terms of inclusion criteria, results and conclusions reached by different authors. Considering these limitations, the reported in-hospital mortality and morbidity rates for cholecystostomy range from 4 to 50 % and from 8.2 to 62%, respectively.
不適合手術但因膽囊膿胸而出現膿毒症的患者，PTGBD 可有效治療，如 CHOCOLATE 試驗所示[11]。膽囊引流使膽囊中受感染的膽汁或膿液減壓，在不切除膽囊的情況下去除受感染的集合體。去除受感染物質可以減少炎症並改善臨床狀況。膽囊造口術存在幾個病例系列，包括回顧性和觀察性。對文獻的系統評價包括 53 項研究，涉及 1918 名患者，概述了手術成功率高 （85.6%）和手術相關死亡率低 （0.36%）;然而，30 天死亡率較高，為 15.4%[142]。該研究的一個主要局限性是納入了急性非結石性膽囊炎和 ACC 患者。對另外 27 項關於膽囊造口術的觀察性研究[143]的回顧顯示，在納入標準、結果和不同作者得出的結論方面存在顯著的異質性。考慮到這些局限性，報告的膽囊造口術院內死亡率和發病率分別為 4% 至 50% 和 8.2% 至 62%。

Gallbladder drainage may be an option in patients who failed conservative management after a variable time of 24 to 48 h and who present with strict contraindications for surgery. A prospective study by Barak et al. [144] reported that age over 70 years, diabetes, tachycardia and a distended gallbladder at admission are predictors for failure of NOM at 24-h follow-up, while a WBC of more than 15,000 cell/mm³, fever and age above 70 years were predictors for failure of NOM at 48-h follow-up.
膽囊引流可能是一種選擇，如果患者在 24 至 48 小時的可變時間後保守治療失敗，並且有嚴格的手術禁忌症。Barak 等[144]的一項前瞻性研究報告稱，年齡超過 70 歲、入院時糖尿病、心動過速和膽囊擴張是 24 h 隨訪時 NOM 失敗的預測因素，而白細胞超過 15,000 個細胞/mm³、發燒和年齡超過 70 歲是 48 h 隨訪時 NOM 失敗的預測因素。

No specific antibiotic regimen is to be prescribed alongside PTGBD and no evidence exists supporting the need for a specific antibiotic regimen. For the antimicrobial therapy, please refer to the dedicated section.
PTGBD 不得同時開具特定的抗生素治療方案，也沒有證據支援需要特定的抗生素治療方案。有關抗菌治療，請參閱專用部分。

Should delayed cholecystectomy be offered to patients with ACC after the reduction of perioperative risk?
圍手術期風險降低后，是否應該對 ACC 患者進行延遲膽囊切除術？

6.5 Delayed laparoscopic cholecystectomy is suggested after reduction of perioperative risks to decrease readmission for ACC relapse or gallstone-related disease. #QoE: very low; SoR: weak#
6.5 建議在降低圍手術期風險後進行延遲腹腔鏡膽囊切除術，以減少 ACC 復發或膽結石相關疾病的再入院。#QoE：非常低;SoR：弱#

De Mestral et al. published a large retrospective epidemiologic analysis in 2013, showing that 40% of patients underwent a DLC after PTGD; the 1-year readmission rate for patients who did not undergo DLC after PTGD was 49% with an in-hospital mortality rate of 1% [145]. No randomized trial currently exists comparing DLC to observation alone.
De Mestral 等人在 2013 年發表了一項大型回顧性流行病學分析，顯示 40% 的患者在 PTGD 後接受了 DLC;PTGD 后未接受 DLC 的患者的 1 年再入院率為 49%，院內死亡率為 1%[145]。目前尚無將 DLC 與單獨觀察進行比較的隨機試驗。

Can endoscopic gallbladder drainage be considered an alternative to PTGBD in patients with ACC who are not suitable for surgery?
對於不適合手術的 ACC 患者，內鏡下膽囊引流可以考慮替代 PTGBD 嗎？

6.6 In patients with ACC who are not suitable for surgery, endoscopic transpapillary gallbladder drainage (ETGBD) or ultrasound-guided transmural gallbladder drainage (EUS-GBD) should be considered safe and effective alternatives to PTGBD, if performed in high-volume centers by skilled endoscopists. #QoE: high; SoR: strong#
6.6 對於不適合手術的 ACC 患者，如果由熟練的內窺鏡醫師在大容量中心進行，則應將內窺鏡經狀膽囊引流術 （ETGBD） 或超聲引導下透壁膽囊引流術 （EUS-GBD） 視為 PTGBD 的安全有效的替代方案。#QoE：高;SoR：強#

ACC is a frequent event in urgent surgical settings, and the gold standard for its treatment is laparoscopic cholecystectomy [140, 146, 147]. However, some patients are unfit for surgery, and for them non-surgical drainage represents a suitable option, either as a bridge to subsequent surgery, once their clinical conditions improve, or as a definitive treatment for those who remain poor candidates for surgery. Non-surgical approaches include PTGBD and endoscopic procedures. Among these, alternatives are endoscopic transpapillary gallbladder drainage (ETGBD), with placement of a transpapillary naso-gallbladder drainage tube (ENGBD) or double-pigtails tent (EGBS), or transmural ultrasonography-guided gallbladder drainage (EUS-GBD) [148].
ACC 是緊急手術中的常見事件，其治療的金標準是腹腔鏡膽囊切除術[140,146,147]。 然而，有些患者不適合手術，對他們來說，非手術引流是一個合適的選擇，一旦他們的臨床狀況好轉，可以作為後續手術的橋樑，也可以作為那些仍然不適合手術的人的最終治療方法。非手術方法包括 PTGBD 和內窺鏡手術。其中，替代方法是內鏡下經性膽囊引流術（endoscopic transpapillary gallbladder drainage， ETGBD），置入經鼻膽囊引流管（transpapillary naso-gallbladder drainage tube， ENGBD）或雙辮子帳篷（double-pigtails tent， EGBS），或透壁超聲引導膽囊引流術（transmural ultrason-guide gallbladder drainage， EUS-GBD）[148]。

In a systematic review about options for endoscopic gallbladder drainage, Itoi et al. [149] reported a pooled technical success rate of ENGBD of 80.9% (95% CI 74.7–86.2) and a pooled clinical response rate of 75.3% (95% CI 68.6–81.2%). For EGBS, the results were 96% (95% CI 91.1–98.7) and 88% (95% CI 81.2–93.2), respectively. At that time, only small case-series were available for EUS-GBD, with reported technical and clinical success rates of 100% (95% CI 75.3–100).
在一項關於內鏡下膽囊引流方案的系統評價中，Itoi 等[149]報導了 ENGBD 的合併技術成功率為 80.9%（95%CI 74.7–86.2），合併臨床緩解率為 75.3%（95%CI 68.6–81.2%）。對於 EGBS，結果分別為 96%（95%CI 91.1–98.7）和 88%（95%CI 81.2–93.2）。當時，EUS-GBD 只有少量病例系列可用，報告的技術和臨床成功率為 100% （95% CI 75.3–100）。

Five years later, Itoi et al. [150], in a RCT of 73 consecutive patients with ACC, obtained overall technical success rates with ENGBD and EGBS of 91.9% and 86.1%, respectively, whereas the clinical success rates by intention-to-treat analysis were 86.5% and 77.8%, respectively. The authors argued that the lower clinical success rate may be ascribed to inadequate gallbladder drainage when large stones or pus were present, and to the use of small-diameter catheters or stents.
5 年後，Itoi 等[150]在一項針對 73 例連續 ACC 患者的隨機對照試驗中，ENGBD 和 EGBS 的總體技術成功率分別為 91.9%和 86.1%，而意向治療分析的臨床成功率分別為 86.5%和 77.8%。作者認為，較低的臨床成功率可能歸因於存在大結石或膿液時膽囊引流不足，以及使用小直徑導管或支架。

EUS-GBD has been compared, in terms of technical feasibility and efficacy, to PTGBD [151] inpatients with acute, high-risk or advanced stage cholecystitis who did not respond to initial medical treatment and could not undergo ELC. EUS-GBD and PTGBD showed similar technical (97% vs. 97%, p = 0.001) and clinical (100% vs. 96%, p = 0.0001) success rates, and similar rates of complications (7% vs. 1%, p = 0.492), indicating that EUS-GBD is a safe alternative to PTGBD in patients who are unsuitable for surgery.
在技術可行性和有效性方面，EUS-GBD 與 PTGBD [151]急性、高危或晚期膽囊炎住院患者進行了比較，這些患者對初始藥物治療無反應且不能接受 ELC。EUS-GBD 和 PTGBD 顯示出相似的技術（97% vs. 97%，p = 0.001）和臨床（100% vs. 96%，p = 0.0001）成功率，以及相似的併發症發生率（7% vs. 1%，p = 0.492），表明 EUS-GBD 是不適合手術的患者 PTGBD 的安全替代品。

Irani and co-workers [152] reached similar conclusions after a retrospective multicenter study, in which the technical success rates of EUS-GBD and PTGBD were 98% and 100% (p = 0.88), respectively. Moreover, the EUS-GBD group had a shorter in-hospital length of stay and fewer repeat interventions (p < 0.05).
Irani 及其同事[152]在一項回顧性多中心研究后得出了類似的結論，其中 EUS-GBD 和 PTGBD 的技術成功率分別為 98%和 100%（p = 0.88）。此外，EUS-GBD 組住院時間較短，重複干預次數較少（p < 0.05）。

Khan et al. [153], in a meta-analysis, evaluated the technical success rates and post-procedure adverse events of ETGBD compared with PTGBD. They found that the pooled OR for technical success of ETGBD versus PTGBD was 0.51 (95% CI 0.09–2.88; I² = 23%) and for post-procedures adverse events was 0.33 (95% CI 0.14–0.80; I² = 16%) in favour of ETGBD. The weighted pooled rates (WPRs) for EUS-GBD were as follows: technical success 93% (95% CI 87–96; I² = 0%), clinical success 97% (95% CI 93–99; I² = 0%), post-procedure adverse events 13% (95% CI 8–19; I² = 0%) and recurrent cholecystitis 4% (95% CI 2–9; I² = 0%).
Khan 等[153]在一項 meta 分析中，評估了 ETGBD 與 PTGBD 相比的技術成功率和術后不良事件。他們發現，ETGBD 與 PTGBD 技術成功的合併 OR 為 0.51（95%CI 0.09–2.88;I² = 23%），術后不良事件為 0.33（95%CI 0.14–0.80;I² = 16%），支援 ETGBD。EUS-GBD 的加權合併率（WPR）如下：技術成功率 93%（95%CI 87-96;I² = 0%），臨床成功率 97%（95%CI 93-99;I² = 0%），術后不良事件 13%（95% CI 8-19;I² = 0%）和復發性膽囊炎 4%（95% CI 2-9; 我 ² = 0%）。

In a prospective study on long term-follow up after EUS-GBD [154], the recurrence of cholecystitis was observed in 7.7% of cases, suggesting that this endoscopic procedure is a safe alternative in the treatment of acute cholecystitis in high-risk patients.
一項關於 EUS-GBD 后長期隨訪的前瞻性研究[154]發現，7.7%的病例觀察到膽囊炎復發，這表明這種內鏡手術是治療高危患者急性膽囊炎的安全替代方案。

EUS-GBD has also been proven to be a feasible technique for the conversion of percutaneous cholecystostomy [155]. The advantages of EUS-GBD over PTGBD include an internalization of bile, obviating the risk of recurrent cholecystitis following percutaneous catheter removal and the risk of bleeding, and being associated with less post-procedural pain [155, 156].
EUS-GBD 也被證明是經皮膽囊造口術轉換的可行技術[155]。EUS-GBD 相對於 PTGBD 的優勢包括膽汁內化，避免經皮導管拔除后膽囊炎復發的風險和出血風險，以及術后疼痛較少[155,156]。

A recent RCT by Teoh et al. [157] identified patients with ACC at very high risk for surgery as patients older than 80 years, with an ASA grade ≥ 3 or an age-adjusted Charlson Comorbidity score > 5 and/or a Karnofsky score < 50. The authors randomized them to receive either EUS-GBD with LAMS or PTGBD within 4 to 6 h from diagnosis. Although 30-day mortality was equivalent between the two study groups, the results were in favour of EUS-GBD, which was associated with less adverse events at 30-day (12.8% vs. 47.5%, p = 0.001) and at 1-year follow-up (25.6% vs. 77.5%, p < 0.001), with a reduced number of re-interventions at 30 days (2.6% vs. 30%, p = 0.001) and with a reduced number of episodes of recurrent cholecystitis (2.6% vs. 20%, p = 0.029).
Teoh 等[157]最近的一項隨機對照試驗將 ACC 患者確定為 80 歲以上、ASA 等級≥為 3 級或年齡調整后的 Charlson 合併症評分> 5 和/或 Karnofsky 評分< 50 的患者是手術風險極高的患者。作者將他們隨機分配在診斷后 4 至 6 小時內接受 EUS-GBD 和 LAMS 或 PTGBD。儘管兩個研究組之間的 30 天死亡率相當，但結果有利於 EUS-GBD，它在 30 天（12.8% vs. 47.5%，p = 0.001）和 1 年隨訪（25.6% vs. 77.5%，p < 0.001）時不良事件較少，30 天時的再次干預次數減少（2.6% vs. 30%， p = 0.001），復發性膽囊炎發作次數減少（2.6% vs. 20%，p = 0.029）。

6.7 If endoscopic transpapillary gallbladder drainage is performed, both endoscopic nasogatric endoscopic gallbladder drainage (ENGBD) and endoscopic gallbladder stenting (EGBS) should be considered suitable options, based on patient characteristics and on the endoscopist’s decision. #QoE: high; SoR: strong#
6.7 如果進行內鏡下經狀膽囊引流術，則應根據患者特徵和內鏡醫師的決定，考慮內鏡下鼻胃內鏡膽囊引流術 （ENGBD） 和內鏡膽囊支架置入術 （EGBS） 的合適選擇。#QoE：高;SoR：強#

Although ENGBD has certain advantages for patients in whom stent insertion is impossible or when there is stent dysfunction, it has two major drawbacks: the potential for inadvertent catheter dislodgement or patient removal, and discomfort. On the other hand, an indwelling stent may be suitable when there is a concern in patients with altered mental status or dementia [6]. A meta-analysis conducted in TG18 [140] found no statistically significant difference in technical success (OR 1.18; 95% CI 0.36–3.89), clinical success (OR 1.82; 95% CI 0.40–8.26), or adverse events rate (OR 1.49; CI 95% 0.29–3.81). Consequently, the advantages and disadvantages of each drainage method are considered approximately equal.
儘管 ENGBD 對於無法插入支架或支架功能障礙的患者具有一定的優勢，但它有兩個主要缺點：導管可能無意中移位或患者移除，以及不適。另一方面，當有精神狀態改變或失智患者需要關注時，留置支架可能適用[6]。一項 meta 分析在 TG18[140]中發現，技術成功率（OR 1.18;95%CI 0.36–3.89）、臨床成功率（OR 1.82;95%CI 0.40–8.26）或不良事件發生率（OR 1.49;CI 95% 0.29–3.81）。因此，每種排水方法的優缺點被認為大致相等。

What is the role of endoscopic transmural ultrasound-guided gallbladder drainage (EUS-GBD) in patients with ACC who are not suitable for surgery?
內鏡下透壁超聲引導膽囊引流術（EUS-GBD）在不適合手術的 ACC 患者中的作用是什麼？

6.8 EUS-GBD with lumen-apposing self-expandable metal stents (LAMSs) should be preferred to ETGBD, if performed by skilled endoscopists. #QoE: moderate; SoR: strong#
6.8 如果由熟練的內窺鏡醫師進行，則應優選帶有管腔並置自膨脹金屬支架 （LAMS） 的 EUS-GBD，而不是 ETGBD。#QoE：中等;SoR：強#

In a recent meta-analysis, Khan et al. [153] found that the proportional difference of WPRs for technical success and clinical success between EUS-GBD versus ETGBD were 10% and 4%, respectively. This difference is explained by the fact that the transpapillary procedures may be technically challenging, due to the anatomy of the cystic duct or stone impaction. On the other hand, if the distance between the gallbladder and the enteric lumen is less than 1 cm, EUS-GBD appears to be safe and feasible [154,155,156]. This technique results in a permanent fistula formation between the gallbladder and the hollow viscus, facilitating anatomic bile drainage [158].
在最近的一項 meta 分析中，Khan 等[153]發現，EUS-GBD 與 ETGBD 之間 WPR 對技術成功和臨床成功的比例差異分別為 10%和 4%。這種差異的原因是，由於膽囊管或結石嵌塞的解剖結構，經手術在技術上可能具有挑戰性。另一方面，如果膽囊與腸腔之間的距離小於 1 cm，則 EUS-GBD 似乎是安全可行的[154,155,156]。 該技術導致膽囊和中空內臟之間形成永久性瘺管，促進解剖膽汁引流[158]。

A variety of plastic stents (straight, single, double-pigtail) and self-expandable metal stents (SEMSs) have been used during EUS-GBD with similar treatment outcomes. However, plastic and SEMSs are tubular stents not specifically designed for EUS-GBD procedures; therefore, bile leakage, stent occlusion and migration are potential adverse events [148, 159]. In order to overcome these limitations, modified stents with flared ends and LAMSs have been introduced [159, 160].
在 EUS-GBD 期間使用了多種塑膠支架（直支架、單尾纖、雙尾纖）和自膨脹金屬支架 （SEMS），具有相似的治療結果。然而，塑膠支架和 SEMS 是管狀支架，並非專門為 EUS-GBD 手術設計;因此，膽汁滲漏、支架閉塞和遷移是潛在的不良事件[148,159]。 為了克服這些限制，已經引入了帶有擴口端和 LAMS（LAMS）的改良支架[159,160]。

LAMSs are fully covered self-expandable metal stents with bilateral flanges specifically designed for EUS-guided, trans-enteric drainage of a pseudocyst or non-adherent fluid collections [148]. The theoretical advantage of LAMSs over other stents is the ability to approximate the gallbladder wall to the enteric lumen, ‘sealing off’ any potential bile leaks and preventing migration, thus providing a robust lumen anchorage [160]. Furthermore, the large diameter of LAMSs (10 mm and 15 mm) may allow access to the gallbladder with a slim endoscope with the purpose of removing stones, or taking biopsies [148].
LAMS 是全覆蓋的自膨脹金屬支架，帶有雙側法蘭，專門設計用於 EUS 引導的經腸引流假性囊腫或非粘附性積液 [148]。與其他支架相比，LAM 的理論優勢在於能夠將膽囊壁近似到腸腔，“封閉”任何潛在的膽汁滲漏並防止遷移，從而提供強大的管腔錨固[160]。此外，LAMS 的大直徑（10mm 和 15mm）可能允許使用細長內窺鏡進入膽囊，以去除結石或進行活檢[148]。

In a retrospective review of multi-center prospectively collected data, Irani et al. [160] achieved a technical success rate of 93% and a clinical success rate of 100% using LAMSs to decompress the gallbladder in patients who had ACC and who were poor surgical candidates. Dollhopf et al. [161], with a new LAMSs device, obtained technical and clinical success rates of 98.7% and 95.9%, respectively, with 10.7% of cases having adverse events.
在對多中心前瞻性收集數據的回顧性評價中，Irani 等[160]使用 LAMS 對 ACC 患者和不良手術候選者的膽囊減壓取得了 93%的技術成功率和 100%的臨床成功率。Dollhopf 等[161]使用新型 LAMSs 設備，技術和臨床成功率分別為 98.7%和 95.9%，其中 10.7%的病例發生不良事件。

6.9 If a EUG-GBD is performed using metal stents, we recommend their removal within 4 weeks, in order to avoid food impaction with subsequent high risk of recurrence of ACC. #QoE: low; SoR: weak#
6.9 如果使用金屬支架進行 EUG-GBD，我們建議在 4 周內將其移除，以避免食物嵌塞和隨後 ACC 復發的高風險。#QoE：低;SoR：弱#

The long-term deployment of metal stents in EUS-GBD could cause adverse events, including food impaction, which, by impairing bile flow, may induce recurrence of cholecystitis. There are several evidences [159, 162] that a well formed fistula might develop between the gallbladder and the gastrointestinal tract within four weeks using a conventional biliary SEMS as well as a LAMS.
在 EUS-GBD 中長期部署金屬支架可能會導致不良事件，包括食物嵌塞，這可能會損害膽汁流動，從而誘發膽囊炎的復發。有若干證據[159,162]表明，使用常規膽道 SEMS 和 LAMS 可能會在 4 周內在膽囊和胃腸道之間形成形成良好的瘺管。

Some authors [162] have argued that, in order to minimise the risk of recurrent cholecystitis or biliary leakage, LAMSs could be left in place for a longer period, without stent-related complications [13]. Although a more significant tissue reaction can be expected after a long stented well-time, it seems probable that stent location, whether gastric or duodenal, might also influence the degree of tissue overgrowth. The retroperitoneal location of the duodenum results in a more stable tract to the gallbladder than the stomach, in which peristaltic movements might result in a more pronounced tissue reaction, impairing the removal of the stent once the inflammatory process has subsided.
一些作者[162]認為，為了最大限度地降低膽囊炎復發或膽漏的風險，LAMS 可以長期放置，而不會出現支架相關併發症[13]。儘管在長時間的支架放置后可以預期會出現更顯著的組織反應，但支架位置（無論是胃還是十二指腸）似乎也可能影響組織過度生長的程度。十二指腸的腹膜后位置導致膽囊的導路比胃更穩定，其中蠕動運動可能會導致更明顯的組織反應，一旦炎症過程消退，就會損害支架的移除。

Section 7. Antibiotic treatment of ACC
第 7 節。ACC 的抗生素治療

Which is the optimal antibiotic treatment for patients with uncomplicated ACC?
對於無併發症的 ACC 患者，哪種抗生素治療是最佳的？

7.1 In uncomplicated ACC, we recommend against the routine use of postoperative antibiotics when the focus of infection is controlled by cholecystectomy. #QoE: high; SoR: strong#
7.1 對於無併發症的 ACC，當感染病灶通過膽囊切除術控制時，我們建議不要常規使用術后抗生素。#QoE：高;SoR：強#

An open-label non-inferiority prospective controlled trial by Regimbau et al. [163] randomized 414 patients who underwent cholecystectomy for uncomplicated ACC to either no antibiotics after surgery or continuation of the preoperative antibiotic regimen for 5 days. An imputed intention-to-treat analysis showed no difference in the incidence of postoperative infection rates: 17% (35 out of 207) in the no-treatment group compared with 15% (31 out of 207) in the antibiotic group (absolute difference 1.93%; 95% CI − 8.98–5.12).
Regimbau 等[163]的一項開放標籤非劣效性前瞻性對照試驗將 414 例因無併發症 ACC 而接受膽囊切除術的患者隨機分配至術后不使用抗生素或繼續術前抗生素治療 5 d 的患者。一項推算意向治療分析顯示，術后感染率沒有差異：不治療組為 17%（207 例中的 35 例），而抗生素組為 15%（207 例中的 31 例）（絕對差異為 1.93%;95%CI − 8.98-5.12）。

No studies were found on this topic since the publication of the 2016 WSES Guidelines on ACC.
自 2016 年 WSES ACC 指南發佈以來，沒有發現任何關於該主題的研究。

Which is the optimal antibiotic treatment for patients with complicated ACC?
對於複雜性 ACC 患者，哪種抗生素的最佳治療方法？

7.2 In complicated ACC, we recommend prescribing the antimicrobial regimen based on the presumed pathogens involved and the risk factors for major resistance patterns. #QoE: high; SoR: strong#
7.2 對於複雜的 ACC，我們建議根據所涉及的假定病原體和主要耐葯模式的危險因素開具抗菌治療方案。#QoE：高;SoR：強#

Empiric antibiotic treatment should be commenced according to the most frequently isolated microorganisms, taking into consideration the local trends of antibiotic resistance and the availability of drugs. In biliary infections, Gram-negative aerobes, such as Escherichia coli and Klebsiella pneumonia, and anaerobes, especially Bacteroides fragilis are the most commonly isolated bacteria [74, 164]. The potential pathogenicity of Enterococci in biliary sepsis remains unclear and specific coverage against these microorganisms is not routinely suggested for community-acquired biliary infections [165]. In case of immunosuppression, i.e. transplant patients, infection lead by Enterococcus spp. should be presumed and pre-emptively treated [166]. The main issue related to antibiotic resistance in biliary tract infections remains the production of extended spectrum beta-lactamase by Enterobacteriaceae; this is frequently found in community acquired infections in patients with previous exposure to antibiotics [74, 164].
應根據最常分離的微生物開始經驗性抗生素治療，同時考慮到當地抗生素耐藥性的趨勢和藥物的可用性。在膽道感染中，革蘭氏陰性需氧菌（如大腸埃希菌和肺炎克雷伯菌 ）和厭氧菌（尤其是脆弱擬桿菌 ）是最常分離的細菌[74,164]。 腸球菌在膽汁性膿毒症中的潛在致病性尚不清楚，對於社區獲得性膽道感染，通常不建議對這些微生物進行特異性覆蓋[165]。如果發生免疫抑制，即移植患者，應推測腸球菌屬感染並先發制人地治療[166]。與膽道感染中抗生素耐藥性相關的主要問題仍然是腸桿菌科產生超譜β-內醯胺酶;這常見於既往接觸過抗生素的患者的社區獲得性感染[74,164]。

Healthcare-related infections are commonly caused by resistant bacterial strains, requiring complex antibiotic regimens; the use of adequate broad-spectrum empiric therapy appears to be a crucial factor to reduce postoperative complications and deaths, especially in critically ill patients [166]. The efficacy of antibiotics in the treatment of biliary infections may be associated with their biliary concentration, although few clinical or experimental data exists supporting the use of antibiotics with biliary penetration for these patients. Nevertheless, in patients with obstructed bile duct, the biliary penetration of antibiotics may be poor and the actual bile concentrations are reached only in a small percentage of patients [167]. Biliary penetration of different antibiotics (indicated as the ratio of bile-to-serum concentrations) are listed in Table 4 [168].
與醫療保健相關的感染通常是由耐葯細菌菌株引起的，需要複雜的抗生素治療方案;使用充分的廣譜經驗性治療似乎是減少術后併發症和死亡的關鍵因素，尤其是危重患者[166]。抗生素治療膽道感染的療效可能與其膽道濃度有關，儘管很少有臨床或實驗數據支援對這些患者使用膽道穿透抗生素。然而，膽管阻塞患者中，抗生素的膽道滲透性可能較差，只有一小部分患者達到實際膽汁濃度[167]。不同抗生素的膽道穿透率（以膽汁與血清濃度的比值表示）見表 4[168]。

Table 4 Antimicrobial regimens suggested for ACC
表 4 ACC 推薦的抗菌方案

In the management of critically ill patients with ACC, the choice of the antimicrobial regimen may be challenging. In patients with sepsis of abdominal origin, the early administration of a correct empirical antimicrobial therapy has a significant impact on outcome [169]. Richè et al. prospectively studied a cohort of 180 consecutive patients with secondary generalized peritonitis and found that there was a significantly higher mortality rate in patients with septic shock than in those without septic shock (35% and 8%, respectively, OR 4.11; 95% CI 1.78–9.48, p = 0.0003) [170]. Furthermore, in patients with septic shock, the biliary origin of peritonitis was a risk factor for mortality at multivariate analysis (OR 3.5; 95% CI 1.09–11.70, p = 0.03). International guidelines for the management of severe sepsis and septic shock (the Surviving Sepsis Campaign) [171] recommend the administration of broad-spectrum intravenous antibiotics with good penetration into the presumed site of infection within the first hour. A recent CC (Sepsis-3) [172] proposed a new evidence-based definition of sepsis and septic shock, underscoring the importance of recognizing the septic focus and the infecting organism. In cases of biliary sepsis, drug pharmacokinetics may be significantly altered in patients with organ dysfunction and septic shock; therefore, the selection of antibiotics should be reassessed daily and be based on both the pathophysiological status of the patient and the pharmacokinetic properties of the specific drug [173]. No significant additional evidence was found since the publication of the 2016 WSES Guidelines on ACC (see Table 4 for recommended antibiotic regimens).
在 ACC 危重患者的管理中，抗菌方案的選擇可能具有挑戰性。對於腹部源性膿毒症患者，早期給予正確的經驗性抗菌治療對結局有顯著影響[169]。Richè等前瞻性研究了一組連續 180 例繼發性全身性腹膜炎患者，發現膿毒性休克患者的死亡率顯著高於非膿毒性休克患者（分別為 35%和 8%，OR 4.11;95%CI 1.78–9.48，p = 0.0003）[170]。 此外，在感染性休克患者中，腹膜炎的膽道起源是多因素分析中死亡的危險因素（OR 3.5;95% CI 1.09–11.70，p = 0.03）。 國際重度膿毒症和膿毒性休克治療指南（Surviving Sepsis Campaign）[171]建議在 1 小時內給予廣譜靜脈注射抗生素，並能很好地滲透到推測的感染部位。最近的 CC（Sepsis-3）[172]提出了膿毒症和膿毒性休克的新循證定義，強調了識別膿毒癥病灶和感染微生物的重要性。在膽汁性敗血症病例中，器官功能障礙和感染性休克患者的藥物藥代動力學可能會發生顯著改變;因此，應每天重新評估抗生素的選擇，並根據患者的病理生理狀態和特定藥物的藥代動力學特性[173]。自 2016 年 WSESACC 指南發佈以來，未發現顯著的額外證據（推薦的抗生素方案見表 4）。

What is the role of microbiological cultures and sensitivities in patients with ACC?
微生物培養和敏感性在 ACC 患者中的作用是什麼？

7.3 In patients with complicated ACC and patients at high risk for antimicrobial resistance, we recommend adapting the targeted antibiotic regimen to the results of microbiological analysis, ensuring adequate antimicrobial coverage. #QoE: moderate; SoR: weak#
7.3 對於複雜性 ACC 患者和抗菌素耐藥性高風險患者，我們建議根據微生物學分析結果調整靶向抗生素方案，確保足夠的抗菌素覆蓋率。#QoE：中等;SoR：弱#

Identifying the causative organism(s) is an essential step in the management of ACC, especially in patients at high risk for antimicrobial resistance, such as immunocompromised patients and those with healthcare-associated infections. The rate of positive bile culture (from either gallbladder culture or bile samples from the common bile duct) ranges from 29 to 54% in cases of ACC [174,175,176,177,178,179].
識別致病微生物是治療 ACC 的重要步驟，特別是對於抗菌素耐藥性高風險的患者，例如免疫功能低下的患者和醫療保健相關感染的患者。ACC 患者膽汁培養陽性率（膽囊培養或膽總管膽汁樣本）為 29%-54%[174,175,176,177,178,179]。

No additional studies have been found on this topic since the publication of the 2016 WSES Guidelines on ACC.
自 2016 年 WSES ACC 指南發佈以來，沒有發現關於該主題的其他研究。

Conclusions, knowledge gaps and research recommendations
結論、知識差距和研究建議

The WSES 2020 on ACC, based on the updated evidence, reinforces the pivotal role of ELC in the management of ACC, even in high-risk patients. The new developed algorithm, in our opinion, emphasizes the importance of two categories of patients: the high-risk patients and those who are not suitable for surgery.
基於最新證據，關於 ACC 的 WSES 2020 強化了 ELC 在 ACC 管理中的關鍵作用，即使在高危患者中也是如此。我們認為，新開發的演算法強調了兩類患者的重要性：高危患者和不適合手術的患者。

The CHOCOLATE Study [11] defined high-risk patients as those with an APACHE score 7–14; this high-quality study improved our understanding of the management of this complex cohort of patients. Its results are in favour of surgery, when compared with biliary drainage in high-risk patients with ACC. However, there is not a single and universally accepted definition of this high-risk patients group; therefore, accepting the suggestion coming from Loozen et al., it appears reasonable to recommend the development of local clinical pathways after deciding which of the available scores fits local needs and expertise.
CHOCOLATE 研究[11]將高危患者定義為 APACHE 評分為 7-14 分的患者;這項高品質的研究提高了我們對這一複雜患者佇列管理的理解。與膽道引流相比，其結果有利於手術治療高危 ACC 患者。然而，對於這一高危患者群體，沒有一個單一且普遍接受的定義;因此，接受 Loozen 等人的建議，在確定哪些可用分數適合當地需求和專業知識后，建議開發當地臨床路徑似乎是合理的。

In addition to the defined high-risk patients, the WSES proposes the category of patients who are not suitable for surgery. We suggest to include in this group all patients with ACC who are not fit for surgery, according to the specific surgeon’s judgement, and patients who are not amenable for surgical treatment, due to the presence of clinical conditions which are not classifiable with clinical or physiologic scores (Appendix 2). For this cohort of patients, surgery may be unsafe or impossible and gallbladder drainage may be the best suitable option in case of uncontrolled sepsis and/or failure of NOM.
除了定義的高危患者外，WSES 還提出了不適合手術的患者類別。我們建議將根據具體外科醫生的判斷不適合手術的所有 ACC 患者，以及由於存在無法用臨床或生理評分分類的臨床狀況而不適合手術治療的患者納入該組（ 附錄 2）。對於這組患者，手術可能是不安全的或不可能的，在膿毒癥不受控制和/或 NOM 失敗的情況下，膽囊引流可能是最合適的選擇。

Moreover, areas for important future research were identified. These include (1) high-quality studies on prognostic factors of ACC patients so as to improve shared decision making, (2) defining the best management option when ELC is not possible due to lack of surgical expertise or due to the duration of symptoms. This should include focus groups involving patients and clinicians, and using observational studies, and (3) defining the best option in the management of difficult operative scenarios. This needs a common language among researchers in order to obtain higher quality studies (in terms of classification of difficulties: e.g. adhesions with hollow viscus, difficulties in grasping the gallbladder, difficulties in view of safety, gangrene of the cystic duct, etc.).
此外，還確定了未來重要的研究領域。其中包括 （1） 對 ACC 患者預後因素進行高品質研究，以改善共同決策，（2） 當由於缺乏手術專業知識或癥狀持續時間而無法進行 ELC 時，確定最佳治療方案。這應包括涉及患者和臨床醫生的焦點小組，並使用觀察性研究，以及 （3） 確定管理困難手術場景的最佳選擇。這需要研究人員之間的共同語言才能獲得更高品質的研究（在困難分類方面：例如中空粘連、膽囊抓握困難、安全困難、膽囊壞疽等）。

Finally, the WSES strongly advocates the adoption of a policy for safe laparoscopic cholecystectomy and encourages the development of local pathways, based on the available evidence.
最後，WSES 強烈主張採用安全腹腔鏡膽囊切除術的政策，並鼓勵根據現有證據開發局部途徑。