Early versus delayed laparoscopic cholecystectomy for uncomplicated biliary colic

  • Conclusions changed
  • Review
  • Intervention

Authors


Abstract

Background

Uncomplicated biliary colic is one of the commonest indications for laparoscopic cholecystectomy. Laparoscopic cholecystectomy involves several months of waiting if performed electively. However, people can develop life-threatening complications during this waiting period.

Objectives

To assess the benefits and harms of early versus delayed laparoscopic cholecystectomy for people with uncomplicated biliary colic due to gallstones.

Search methods

We searched the Cochrane Central Register of Controlled Trials in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until March 2013.

Selection criteria

We included only randomised clinical trials, irrespective of language and publication status.

Data collection and analysis

Two authors independently extracted the data. We sought to include data on short-term mortality (30-day mortality or in-hospital mortality), bile duct injury, other serious adverse events, quality of life, conversion to open cholecystectomy, length of hospital stay, operating time, and return to work. We planned to calculate the risk ratio with 95% confidence interval (CI) for dichotomous outcomes and mean difference (MD) with 95% CI for continuous outcomes using RevMan and based on intention-to-treat analysis when data were available. Since only one trial contributed data to this review, Fisher's exact test was used for binary outcomes. A P value of < 0.05 was considered statistically significant.

Main results

Only one trial including 75 participants (average age: 43 years; females: 65% of participants), randomised to early laparoscopic cholecystectomy (less than 24 hours after diagnosis) (n = 35) or delayed laparoscopic cholecystectomy (mean waiting period of 4.2 months) (n = 40), contributed information to this review. The trial had a high risk of bias. Information on the outcome mortality was available for the 75 participants. Information on serious adverse events was available for 68 participants (28 people in the early group and 40 people in the delayed group). The other outcomes were available for 28 participants in the early laparoscopic cholecystectomy group and 35 participants in the delayed laparoscopic cholecystectomy group. There were no deaths in the early group (0/35) (0%) versus 1/40 (2.5%) in the delayed laparoscopic cholecystectomy group (P > 0.9999). There was no bile duct injury in either group. There were no serious adverse events related to the surgery in either group. During the waiting period, complications developed in the delayed laparoscopic cholecystectomy group. The complications that the participants suffered included pancreatitis (n = 1), empyema of the gallbladder (n = 1), gallbladder perforation (n = 1), acute cholecystitis (n = 2), cholangitis (n = 2), obstructive jaundice (n = 2), and recurrent biliary colic (requiring hospital visits) (n = 5). In total, 14 participants required hospital admissions for the above symptoms. All of these admissions occurred in the delayed group as all the participants were operated on within 24 hours in the early group. The proportion of people who developed serious adverse events was 0/28 (0%) in the early group, which was significantly lower than in the delayed laparoscopic cholecystectomy group 9/40 (22.5%) (P = 0.0082). This trial did not report quality of life or return to work. There was no significant difference in the proportion of people who required conversion to open cholecystectomy in the early group 0/28 (0%) compared with the delayed group (6/35 or 17.1%) (P = 0.0743). There was a statistically significant shorter hospital stay in the early group than in the delayed group (MD -1.25 days, 95% CI -2.05 to -0.45). There was a statistically significant shorter operating time in the early group than the delayed group (MD -14.80 minutes, 95% CI -18.02 to -11.58).

Authors' conclusions

Based on evidence from only one high-bias risk trial, it appears that early laparoscopic cholecystectomy (less than 24 hours after diagnosis of biliary colic) decreases the morbidity during the waiting period for elective laparoscopic cholecystectomy (mean waiting time 4.2 months), the hospital stay, and operating time. Further randomised clinical trials are necessary to confirm or refute these findings, and to determine if early laparoscopic cholecystectomy is better than the delayed laparoscopic cholecystectomy if the waiting time is shortened further.

摘要

背景

早期及延期腹腔鏡膽囊切除術治療膽管絞痛的比較

膽管絞痛是腹腔鏡膽囊切除術最常見的適應症之一。如果有選擇性的實施手術,腹腔鏡膽囊切除術則需等待幾個月。但是,在此等待期間,病人可能發展成威脅生命的併發症。

目標

評估早期及延期腹腔鏡膽囊切除術治療因膽囊結石引起的膽管絞痛病人的利弊。

搜尋策略

我們搜尋截至2008年3月之前的The Cochrane HepatoBiliary Group Controlled Trials Register, Cochrane Library的The Cochrane Central Register of Controlled Trials、 MEDLINE、EMBASE和Science Citation Index Expanded。

選擇標準

我們只收納隨機臨床試驗,不受語言和發表狀態的限制。

資料收集與分析

兩位作者獨立摘錄數據。我們計畫使用RevMan 4.2,根據治療意向,評估二分法結果的風險比率(risk ratio),風險差異(risk difference),及其95%信賴區間(CI);連續性結果以加權平均差(WMD),及95% CI計算。

主要結論

只有一個共75位病人的試驗比較早期腹腔鏡膽囊切除術 (24小時之內) (n = 35)和延期腔鏡膽囊切除術(平均等待4.2個月) (n = 40)符合本次文獻回顧的資格。本次試驗具有較高的偏誤風險。在延期組 (平均4.2個月)的等待時間裏,病人遭受的併發症包括嚴重急性胰腺炎,最終導致死亡(1),膽囊積膿(1),膽囊穿孔(1),急性膽囊炎(2), 膽管炎(2)阻塞性黃疸(2),需要住院觀察的復發性膽管絞痛(5)。早期組 (0%)開腹膽囊切除術的轉院率低於延期組(8/40或 20%) (p = 0.0172)。 和延期組(WMD −14.80 分鐘, 分別是95% CI −18.02 −11.58和−1.25 天, 95% CI −2.05 – 0.45)相比,早期組的手術時間和住院日明顯更短。延期組在平均等待的4.2個月期間,有14位病人(35%) 需要住院18次治療和膽囊結石有關的症狀。這就等於每個月每100個人裏有11個人住院。

作者結論

根據唯一一次偏誤風險高的試驗,早期腹腔鏡膽囊切除術(診斷為膽管絞痛的24小時之內)似乎能夠降低實施選擇性腹腔鏡膽囊切除術之後,等待期間的發病率,降低開腹膽囊切除術的轉院率,減少手術時間和住院日。對此發現需要進一步的隨機臨床試驗給予確認或反對。

翻譯人

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

對膽囊結石疼痛實施早期腹腔鏡摘除術,可以降低等待期間的發病率;降低開腹摘除膽囊的轉換率,降低手術時間和住院日,但是需要實施偏誤風險低的試驗:對症狀性膽囊結石摘除膽囊是最常見的對腹部實施的手術。腹腔鏡膽囊切除術通常在延期的基礎上治療膽囊結石疼痛(膽囊沒有發炎),例如膽管絞痛, 但是可以作為緊急手術。病人在等待手術的過程中,可能會發展成威脅生命的併發症。本次文獻回顧,我們確定一次偏見風險高的試驗(意思是,系統誤差的風險較高),隨機挑選 75 位有膽管絞痛需要立即手術(診斷後24小時內)或擇期手術 (平均等待4.2個月)的病人。由於擇期手術組在等待手術期間,出現和膽囊結石有關的併發症,所以14位病人(35%)至少需要緊急入院治療一次。總體看,4.2個月內,40位病人有18位病人住院治療。這就等於每個月100位病人裏有11個人住院治療。擇期手術導致更多的人需要開腹手術 (擇期手術組20%比照緊急手術組0%);手術時間 (擇期手術組大約增加15分鐘)和住院日 (擇期手術組延長1天)更長。 需要實施進一步的低偏差風險(系統誤差的低風險)隨機臨床試驗。

Résumé scientifique

Cholécystectomie laparoscopique précoce versus retardée pour la colique biliaire simple

Contexte

La colique biliaire simple est l'une des indications les plus courantes pour une cholécystectomie laparoscopique. La cholécystectomie laparoscopique implique une attente de plusieurs mois si elle est réalisée de manière élective. Cependant, les personnes peuvent développer des complications menaçant le pronostic vital durant cette période d'attente.

Objectifs

Évaluer les bénéfices et les préjudices de la cholécystectomie laparoscopique précoce versus retardée pour les personnes atteintes d'une colique biliaire simple en raison de calculs biliaires.

Stratégie de recherche documentaire

Nous avons effectué une recherche dans le registre Cochrane des essais contrôlés dans The Cochrane Library, ainsi que dans MEDLINE, EMBASE et Science Citation Index Expanded jusqu'à mars 2013.

Critères de sélection

Nous n'avons inclus que des essais cliniques randomisés indépendamment de la langue utilisée et du statut de publication.

Recueil et analyse des données

Deux auteurs ont extrait les données de manière indépendante. Nous avons cherché à inclure des données sur la mortalité à court terme (mortalité à 30 jours ou mortalité à l'hôpital), les lésions du canal biliaire ou d'autres événements indésirables graves, la qualité de vie, le passage à la cholécystectomie ouverte, la durée de l'hospitalisation, le temps d'opération et le retour au travail. Nous avions prévu de calculer le risque relatif avec un intervalle de confiance (IC) à 95 % pour les variables dichotomiques et la différence moyenne (DM) avec IC à 95 % pour les données continues à l'aide du logiciel RevMan sur la base d'une analyse en intention de traiter lorsque les données étaient disponibles. Du fait qu'un seul essai a fourni des données pour cette revue, le test exact de Fisher a été utilisé pour les données binaires. Une valeur P de < 0,05 a été considérée comme statistiquement significative.

Résultats principaux

Seul un essai portant sur 75 participants (âge moyen : 43 ans ; femmes : 65 % des participants), randomisés pour recevoir une cholécystectomie laparoscopique précoce (moins de 24 heures après le diagnostic) (n = 35) ou une cholécystectomie laparoscopique retardée (période d'attente moyenne de 4,2 mois) (n = 40), a fourni des informations pour cette revue. L'essai présentait un risque élevé de biais. Les informations sur le critère de jugement de la mortalité ont été disponibles pour les 75 participants. Les informations sur les événements indésirables graves ont été disponibles pour 68 participants (28 personnes dans le groupe précoce et 40 personnes dans le groupe retardé). Les autres résultats ont été disponibles pour 28 participants dans le groupe de la cholécystectomie laparoscopique précoce et pour 35 participants dans le groupe de la cholécystectomie laparoscopique retardée. Aucun décès n'a été constaté dans le groupe précoce (0/35) (0 %) versus 1/40 (2,5 %) dans le groupe de la cholécystectomie laparoscopique retardée (P > 0,9999). Il n'y a eu de lésions du canal biliaire dans aucun des deux groupes. Il n'y a eu d'événements indésirables graves liés à l'opération dans aucun des deux groupes. Durant la période d'attente, des complications se sont développées dans le groupe de la cholécystectomie laparoscopique retardée. Les complications subies par les participants comprenaient une pancréatite (n = 1), un empyème de la vésicule biliaire (n = 1), une perforation de la vésicule biliaire (n = 1), une cholécystite aiguë (n = 2), une cholangite (n = 2), une jaunisse obstructive (n = 2) et une colique biliaire récurrente (nécessitant des consultations à l'hôpital) (n = 5). Au total, 14 participants ont dû être hospitalisés en raison des symptômes ci-dessus. Toutes ces admissions sont intervenues dans le groupe retardé, car tous les participants ont été opérés sous 24 heures dans le groupe précoce. La proportion de personnes ayant développé des événements indésirables graves a été de 0/28 (0 %) dans le groupe précoce, ce qui a été significativement plus faible que dans le groupe de la cholécystectomie laparoscopique 9/40 (22,5 %) (P = 0,0082). Cet essai n'a pas rapporté la qualité de vie ou le retour au travail. Il n'y a pas eu de différence significative dans la proportion de personnes ayant nécessité un passage à la cholécystectomie oucholécystectomie laparoscopiquerte dans le groupe précoce 0/28 (0 %) comparé au groupe retardé (6/35 ou 17,1 %) (P = 0,0743). On a constaté une durée d'hospitalisation inférieure de façon statistiquement significative dans le groupe précoce par rapport au groupe retardé (DM -1,25 jours, IC à 95 % -2,05 à -0,45). On a constaté une durée d'opération inférieure de façon statistiquement significative dans le groupe précoce par rapport au groupe retardé (DM -14,80 minutes, IC à 95 % -18,02 à -11,58).

Conclusions des auteurs

D'après les preuves issues d'un seul essai présentant un risque de biais important, il semble que la cholécystectomie laparoscopique précoce (moins de 24 heures suivant le diagnostic de la colique biliaire) réduise la morbidité durant la période d'attente pour la cholécystectomie laparoscopique élective (temps d'attente moyen 4,2 mois), l'hospitalisation et la durée de l'opération. De nouveaux essais cliniques randomisés sont nécessaires pour confirmer ou infirmer ces résultats et pour déterminer si la cholécystectomie laparoscopique précoce est plus efficace que la cholécystectomie laparoscopique retardée si le temps d'attente est réduit davantage.

Plain language summary

Early versus delayed laparoscopic cholecystectomy for uncomplicated biliary colic

The liver produces bile which has many functions including assisting in the elimination of waste processed by the liver and digestion of fat. The bile is temporarily stored in the gallbladder (an organ situated underneath the liver) before it reaches the small bowel. Concretions in the gallbladder are called gallstones. Gallstones are present in about 5% to 25% of the adult western population. Between 2% and 4% become symptomatic in a year. The symptoms include pain related to the gallbladder (uncomplicated biliary colic), inflammation of the gallbladder (cholecystitis), obstruction to the flow of bile from the liver and gallbladder into the small bowel resulting in jaundice (yellowish discolourisation of the body usually most prominent in the white of the eye, which turns yellow), bile infection (cholangitis), and inflammation of the pancreas, an organ which secretes digestive juices and harbours the insulin secreting cells which maintain blood sugar levels (pancreatitis). Removal of the gallbladder (cholecystectomy) is currently considered the best treatment option for people with symptomatic gallstones. This is generally performed by keyhole surgery (laparoscopic cholecystectomy). Gallbladder pain is one of the indications for laparoscopic cholecystectomy and can occur suddenly, with symptoms of intense pain in the right upper tummy which may or may not be associated with other symptoms such as heartburn. This is called biliary colic. Because of the limited resources available in a state-funded health system, the people with biliary colic are added to a waiting list and operated on electively. However, delaying the surgery exposes the people to the risk of complications related to gallstones. The review authors set out to determine whether it is preferable to perform early laparoscopic cholecystectomy (within two weeks of people presenting to doctors with symptoms) or delayed laparoscopic cholecystectomy (more than two weeks after people present to doctors with symptoms). A systematic search of the medical literature was performed in order to identify studies which provided information on the above question. The authors obtained information from randomised trials only since such types of trials provide the best information if conducted well. Two authors independently identified the trials and collected the information.

Only one trial including 75 participants (average age: 43 years; females: 65% of participants) provided information for this review. In this trial, 35 participants underwent early laparoscopic cholecystectomy (less than 24 hours after diagnosis) and 40 participants underwent delayed laparoscopic cholecystectomy after an average waiting period of approximately four months. The treatment that the participants underwent was determined by a method similar to the toss of a coin. This trial was at high risk of bias (systematic errors or errors in study design which may influence the conclusions). There were no deaths in the early group (0 out of 35) (0%) and there was one death (1 out of 40) (2.5%) in the delayed laparoscopic cholecystectomy group. This difference between the groups was not significantly different. There were no serious complications related to the surgery in either group. During the waiting period, 9 out of 40 participants (22.5%) developed gallstone-related serious complications. Five participants in the delayed group revisited the hospital because of recurrent gallbladder pain. In total, 14 participants required hospital admissions for the above symptoms. All of these participants were from the delayed group. All the participants in the early group were operated on within 24 hours. The proportion of participants who developed serious complications was significantly lower in the early group than the proportion of participants in the delayed laparoscopic cholecystectomy group. Quality of life and return to work were not reported in this trial. There was no significant difference in the proportion of participants who required conversion to open removal of the gallbladder. The hospital stay was significantly shorter (by about one day) in the early group than the delayed group. The operating time was significantly shorter (by about 15 minutes) in the early group than the delayed group.

Based on evidence from only one high-bias risk trial, it appears that early laparoscopic cholecystectomy performed within 24 hours of diagnosis of biliary colic decreases serious complications, hospital stay, and operating time compared with delayed laparoscopic cholecystectomy with an average waiting time of four months. Further well designed, randomised clinical trials are necessary to confirm or refute these findings.

Résumé simplifié

Cholécystectomie laparoscopique précoce versus retardée pour la colique biliaire simple

Le foie produit de la bile qui a de nombreuses fonctions, dont celle d'aider à l'élimination des déchets traités par le foie et à la digestion des graisses. La bile est temporairement stockée dans la vésicule biliaire (un organe situé sous le foie) avant d'atteindre l'intestin grêle. Les concrétions dans la vésicule biliaire sont appelées des calculs biliaires. Les calculs touchent environ 5 % à 25 % de la population adulte occidentale. Entre 2 % et 4 % deviennent symptomatiques en l'espace d'un an. Les symptômes comprennent une douleur liée à la vésicule biliaire (colique biliaire simple), l'inflammation de la vésicule biliaire (cholécystite), l'obstruction de l'écoulement de la bile depuis le foie et la vésicule biliaire dans l'intestin grêle, entraînant une jaunisse (décoloration jaunâtre du corps, généralement très prononcée dans le blanc de l'œil, qui devient jaune), l'infection biliaire (cholangite) et l'inflammation du pancréas, un organe qui sécrète des sucs digestifs et renferme les cellules sécrétant l'insuline qui maintient le taux de sucre dans le sang (pancréatite). L'ablation de la vésicule biliaire (cholécystectomie) est actuellement considérée comme la meilleure option de traitement pour les personnes ayant des calculs biliaires symptomatiques. Elle est généralement réalisée par une opération cœlioscopique (cholécystectomie laparoscopique). La douleur liée à la vésicule biliaire est l'une des indications d'une cholécystectomie laparoscopique et peut survenir soudainement avec des symptômes de douleur intense dans la partie supérieure droite du ventre, qui peuvent ou non être associés à d'autres symptômes, tels que des brûlures d'estomac. C'est ce que l'on appelle une colique biliaire. En raison des ressources limitées disponibles dans un système de santé financé par l'état, les personnes atteintes d'une colique biliaire sont ajoutées sur une liste d'attente et opérées de manière élective. Cependant, le fait de retarder l'opération expose les personnes au risque de complications liées aux calculs biliaires. Les auteurs de la revue ont cherché à déterminer s'il était préférable de réaliser une cholécystectomie laparoscopique de façon précoce (dans les deux semaines suivant la consultation chez le médecin des personnes présentant des symptômes) ou une cholécystectomie laparoscopique retardée (plus de deux semaines après la consultation chez le médecin des personnes présentant des symptômes). Une recherche systématique dans la littérature médicale a été effectuée afin d'identifier des études fournissant des informations sur la question ci-dessus. Les auteurs ont obtenu des informations à partir d'essais randomisés uniquement, car ce type d'essais fournissent les meilleures informations s'ils sont bien réalisés. Deux auteurs ont identifié les essais et recueilli les informations de manière indépendante.

Seul un essai portant sur 75 participants (âge moyen : 43 ans ; femmes : 65 % des participants) a fourni des informations pour cette revue. Dans cet essai, 35 participants ont subi une cholécystectomie laparoscopique précoce (moins de 24 heures après le diagnostic) et 40 participants ont subi une cholécystectomie laparoscopique retardée après une période d'attente moyenne d'environ quatre mois. Le traitement que les participants ont subi a été déterminé par une méthode semblable à pile ou face. Cet essai présentait un risque de biais élevé (erreurs systématiques ou erreurs dans le plan d'étude qui peuvent influer sur les conclusions). Il n'y a eu aucun décès dans le groupe précoce (0 sur 35) et on a constaté un décès (1 sur 40) (2,5 %) dans le groupe de la cholécystectomie laparoscopique retardée. Cette différence entre les groupes n'était pas significative. Il n'y a eu de complications graves liées à l'opération dans aucun des deux groupes. Durant la période d'attente, 9 participants sur 40 (22,5 %) ont développé de graves complications liées à la vésicule biliaire. Cinq participants dans le groupe retardé se sont de nouveau rendus à l'hôpital en raison d'une douleur récurrente liée à la vésicule biliaire. Au total, 14 participants ont dû être hospitalisés en raison des symptômes ci-dessus. Tous appartenaient au groupe retardé. Tous les participants du groupe précoce ont été opérés sous 24 heures. La proportion de participants ayant développé des complications graves a été significativement inférieure dans le groupe précoce par rapport à la proportion de participants dans le groupe de la cholécystectomie laparoscopique retardée. La qualité de vie et le retour au travail n'ont pas été rapportés dans cet essai. Il n'y a eu aucune différence significative en termes de proportion de participants ayant nécessité un passage à une ablation ouverte de la vésicule biliaire. L'hospitalisation a été significativement plus courte (d'environ un jour) dans le groupe précoce par rapport au groupe retardé. La durée de l'opération a été significativement plus courte (d'environ 15 minutes) dans le groupe précoce par rapport au groupe retardé.

D'après les preuves issues d'un seul essai présentant un risque de biais important, il semble que la cholécystectomie laparoscopique précoce réalisée dans les 24 heures suivant le diagnostic de la colique biliaire réduise les complications graves et le temps d'opération comparé à la cholécystectomie laparoscopique retardée d'un temps d'attente moyen de quatre mois. De nouveaux essais cliniques randomisés bien conçus sont nécessaires pour confirmer ou infirmer ces résultats.

Notes de traduction

Traduit par: French Cochrane Centre 7th August, 2013
Traduction financée par: Pour la France : Minist�re de la Sant�. Pour le Canada : Instituts de recherche en sant� du Canada, minist�re de la Sant� du Qu�bec, Fonds de recherche de Qu�bec-Sant� et Institut national d'excellence en sant� et en services sociaux.

Summary of findings(Explanation)

Summary of findings for the main comparison. Early versus delayed laparoscopic cholecystectomy for uncomplicated biliary colic
  1. 1 The trial was at high risk of bias.
    2 The confidence intervals overlapped 1 and either 0.75 or 1.25 or both.
    3 The number of events in the intervention and control group was fewer than 300.
    4 The total number of participants in the intervention and control group was fewer than 400.

Early laparoscopic cholecystectomy compared to delayed laparoscopic cholecystectomy for uncomplicated biliary colic
Patient or population: participants with biliary colic.
Settings: secondary or tertiary.
Intervention: early laparoscopic cholecystectomy.
Comparison: delayed laparoscopic cholecystectomy.
OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of participants
(studies)
Quality of the evidence
(GRADE)
Assumed riskCorresponding risk
Delayed laparoscopic cholecystectomy Early laparoscopic cholecystectomy
Mortality 25 per 1000 9 per 1000
(0 to 226)
RR 0.38
(0.02 to 9.03)
75
(1 study)
⊕⊝⊝⊝
very low 1,2,3
Serious adverse events 225 per 1000 16 per 1000
(0 to 277)
RR 0.07
(0 to 1.23)
68
(1 study)
⊕⊝⊝⊝
very low 1,3
Conversion to open cholecystectomy 171 per 1000 17 per 1000
(2 to 279)
RR 0.1
(0.01 to 1.63)
63
(1 study)
⊕⊝⊝⊝
very low 1,2,3
Hospital stay (days)The mean hospital stay (days) in the control groups was
2.31 days
The mean hospital stay (days) in the intervention groups was
1.25 lower
(2.05 to 0.45 lower)
 63
(1 study)
⊕⊝⊝⊝
very low 1,4
Operating time (minutes)The mean operating time (minutes) in the control groups was
49.9 minutes
The mean operating time (minutes) in the intervention groups was
14.8 lower
(18.02 to 11.58 lower)
 63
(1 study)
⊕⊝⊝⊝
very low 1,4
*The basis for the assumed risk is the median control group risk in the study. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio.
GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

Background

Description of the condition

About 5% to 25% of the adult western population have gallstones (GREPCO 1984; GREPCO 1988; Bates 1992; Halldestam 2004). The annual incidence of gallstones is about 1 in 200 people (NIH 1992). Only 2% to 4% of people with gallstones become symptomatic with biliary colic (pain), acute cholecystitis (inflammation), obstructive jaundice, or gallstone pancreatitis in a year (Attili 1995; Halldestam 2004). Cholecystectomy (removal of gallstones) is the preferred option in the treatment of symptomatic gallstones (Strasberg 1993). Every year 1.5 million cholecystectomies are performed in the US and 60,000 in the UK (Dolan 2009; HES 2011). Approximately 80% of the cholecystectomies are performed laparoscopically (by keyhole surgery) (Ballal 2009). Biliary colic (pain in the right upper abdomen lasting for more than half an hour) is one of the symptoms related to gallstones (Berger 2000), and uncomplicated biliary colic is the commonest indication for cholecystectomy (Glasgow 2000). Although such pain may also be present in people with acute cholecystitis, the people with acute cholecystitis have inflammation of the gallbladder and hence may have fever and an elevated neutrophil count, which indicate inflammation.

Description of the intervention

In countries like the UK, where health care is funded by the government, people with biliary colic are put on a waiting list and operated on electively several months after the diagnosis. The waiting time for elective cholecystectomy varies depending upon the resources available, but it is generally between four months and 12 months (Rutledge 2000; Somasekar 2002; Lawrentschuk 2003; Salman 2005). However, people may develop complications as a result of the gallstones including pancreatitis, cholangitis, choledocholithiasis, and recurrent attacks of biliary colic and cholecystitis while waiting for surgery (Rutledge 2000; Lawrentschuk 2003; Vetrhus 2002). These complications can even be life-threatening. Studies have shown that laparoscopic cholecystectomy that is done for biliary colic has a lower conversion rate to open cholecystectomy and lower morbidity than that performed after an attack of cholecystitis (Glasgow 2000; Peng 2005). Early laparoscopic cholecystectomy for biliary colic is clinically effective in preventing the serious complications of gallstones (Salman 2005).

How the intervention might work

The intervention works by preventing the exposure of the people to the complications of gallstones, as the gallstones and the gallbladder are removed before the people develop gallstone-related complications.

Why it is important to do this review

The timing of laparoscopic cholecystectomy for uncomplicated biliary colic is an important issue since preventable gallstone-related complications have to be avoided using the limited resources available. This review is an update of our previous review published in 2008 (Gurusamy 2008).

Objectives

To assess the benefits and harms of early versus delayed laparoscopic cholecystectomy for people with uncomplicated biliary colic due to gallstones.

Methods

Criteria for considering studies for this review

Types of studies

We included all randomised clinical trials that compared early and delayed laparoscopic cholecystectomy in people with uncomplicated biliary colic (irrespective of language, blinding, publication status, or sample size). We excluded the quasi-randomised and non-randomised studies because there are no harms specifically attributable to the early laparoscopic cholecystectomy. In addition to the selection bias in quasi-randomised and non-randomised studies, there may be recall bias as people who developed biliary complications may recall having biliary colic earlier and hence may be classified as delayed laparoscopic cholecystectomy group while those who did not develop complications may be classified as early laparoscopic cholecystectomy people, which will erroneously magnify the benefits of early laparoscopic cholecystectomy. Conversely, some people who are in the delayed laparoscopic cholecystectomy group who undergo surgery because of the suspicion of complications may be misclassified as early laparoscopic cholecystectomy group, which can erroneously reduce the benefits of the early laparoscopic cholecystectomy.

Types of participants

Patients with uncomplicated biliary colic due to gallstones, who were eligible to undergo laparoscopic cholecystectomy. We also planned to include people with recurrent attacks of uncomplicated biliary colic provided that these people did not have any episodes of acute cholecystitis, obstructive jaundice, or pancreatitis.

Types of interventions

We included trials comparing early versus delayed laparoscopic cholecystectomy (irrespective of the size and the number of ports, abdominal lift, or open or closed method of induction of pneumoperitoneum) for uncomplicated biliary colic. Early laparoscopic cholecystectomy was defined as laparoscopic cholecystectomy performed within two weeks of the onset of biliary colic that was severe enough to necessitate surgical referral. Delayed laparoscopic cholecystectomy was defined as laparoscopic cholecystectomy that was planned to be performed after two weeks of onset of biliary colic which necessitated surgical referral. The choice of the timing of surgery was arbitrary but included the time for planning the surgery. We included only laparoscopic cholecystectomy for this review since laparoscopic cholecystectomy is the first line of treatment for biliary colic, and the incidence of surgery-related morbidity and most of the other outcomes used in this review are different between open and laparoscopic cholecystectomy.

Types of outcome measures

Primary outcomes
  1. All-cause mortality (90-day mortality or in-hospital mortality and long-term mortality).

  2. Bile duct injury.

  3. Serious adverse events. Adverse events are defined as any untoward medical occurrence not necessarily having a causal relationship with the treatment, but resulting in a dose reduction or discontinuation of treatment (ICH-GCP 1997). Serious adverse events are defined as any event that would increase mortality; is life-threatening; requires inpatient hospitalisation; results in a persistent or significant disability; or any important medical event which might have jeopardised the participant or requires intervention to prevent it. Bile duct injury also falls under the category of serious adverse events and as it is a long-term disability, we have also selected it as a separate outcome.

  4. Quality of life (three months).

Secondary outcomes
  1. Conversion to open cholecystectomy.

  2. Total hospital stay.

  3. Operating time.

  4. Return to work.

In addition to the above outcomes, we collected the information reported in the trial on the complications occurred during the waiting time in participants undergoing delayed laparoscopic cholecystectomy.

Search methods for identification of studies

Electronic searches

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded (Royle 2003) until March 2013. We have given the search strategies in Appendix 1 with the time spans for the searches.

Searching other resources

We also searched the references of the identified trials to identify further relevant trials.

Data collection and analysis

Selection of studies

KG and RK independently identified the trials for inclusion. We have listed the excluded studies with the reasons for exclusion.

Data extraction and management

KG and RK independently extracted the following data.

  1. Year and language of publication.

  2. Country.

  3. Year of study.

  4. Inclusion and exclusion criteria.

  5. Sample size.

  6. Population characteristics such as age and sex ratio.

  7. Details of intervention and control.

  8. Co-interventions.

  9. Outcomes (listed above).

  10. Risk of bias (described below).

Assessment of risk of bias in included studies

We independently assessed the risk of bias in the trials without masking the trial names. We followed the instructions given in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011) and the Cochrane Hepato-Biliary Group Module (Gluud 2013). Due to the risk of biased overestimation of beneficial intervention effects in randomised trials with high risk of bias (Schulz 1995; Moher 1998; Kjaergard 2001; Wood 2008; Lundh 2012; Savović 2012; Savović 2012a), we assessed the trials for the following risk of bias domains.

Allocation sequence generation
  • Low risk of bias: sequence generation was achieved using computer random number generation or a random number table. Drawing lots, tossing a coin, shuffling cards, and throwing dice are adequate if performed by an independent person not otherwise involved in the trial.

  • Uncertain risk of bias: the method of sequence generation was not specified.

  • High risk of bias: the sequence generation method was not random.

Allocation concealment
  • Low risk of bias: the participant allocations could not have been foreseen in advance of, or during, enrolment. Allocation was controlled by a central and independent randomisation unit. The allocation sequence was unknown to the investigators (for example, if the allocation sequence was hidden in sequentially numbered, opaque, and sealed envelopes).

  • Uncertain risk of bias: the method used to conceal the allocation was not described so that the intervention allocations may have been foreseen in advance of, or during, enrolment.

  • High risk of bias: the allocation sequence was likely to be known to the investigators who assigned the participants.

Blinding of participants and personnel

It is impossible to blind the surgeons who perform the surgery. However, it is possible to blind the surgeons who monitor the participants after the operation. Such surgeons determine whether to investigate the participant further in the case of any symptoms. We did not expect blinding of participants in any of the trials since this would have involved sham operations in both groups, which may be unethical.

  • Low risk of bias: blinding was performed adequately, or the assessment of outcomes was not likely to be influenced by lack of blinding.

  • Uncertain risk of bias: there was insufficient information to assess whether blinding was likely to induce bias on the results.

  • High risk of bias: no blinding or incomplete blinding, and the assessment of outcomes was likely to be influenced by lack of blinding.

Blinding of outcome assessors
  • Low risk of bias: blinding was performed adequately, or the assessment of outcomes was not likely to be influenced by lack of blinding.

  • Uncertain risk of bias: there was insufficient information to assess whether blinding was likely to induce bias on the results.

  • High risk of bias: no blinding or incomplete blinding, and the assessment of outcomes was likely to be influenced by lack of blinding.

Incomplete outcome data
  • Low risk of bias: missing data were unlikely to make treatment effects depart from plausible values. Sufficient methods, such as multiple imputation, have been employed to handle missing data.

  • Uncertain risk of bias: there was insufficient information to assess whether missing data in combination with the method used to handle missing data were likely to induce bias on the results.

  • High risk of bias: the results were likely to be biased due to missing data.

Selective outcome reporting
  • Low risk of bias: all outcomes were predefined and reported, or all clinically relevant and reasonably expected outcomes were reported.

  • Uncertain risk of bias: it is unclear whether all predefined, clinically relevant and reasonably expected outcomes were reported. 

  • High risk of bias: one or more clinically relevant and reasonably expected outcomes were not reported, and data on these outcomes were likely to have been recorded.

For-profit bias
  • Low risk of bias: the trial appears to be free of industry sponsorship or other kind of for-profit support that may lead to manipulation of the trial design, conductance, or results of the trial. 

  • Uncertain risk of bias: the trial may or may not be free of for-profit bias as no information on clinical trial support or sponsorship is provided.

  • High risk of bias: the trial is sponsored by industry or has received other kind of for-profit support.

We considered trials to have a low risk of bias if we assessed all the above domains as being at low risk of bias. In all other cases, the trials were considered to have a high risk of bias.

Measures of treatment effect

For binary outcomes, we planned to calculate the risk ratio (RR) with 95% confidence interval (CI) in the presence of at least two trials included for the outcome. However, we used Fisher's exact test since only one trial contributed to the outcomes. We also planned to report the risk difference if it was different from the RR since risk difference allows meta-analysis of trials with zero events in both groups. For continuous variables, we calculated the mean difference (MD) with 95% CI for hospital stay; and we planned to calculate the standardised mean difference (SMD) with 95% CI for variables such as quality of life.

Unit of analysis issues

The unit of analysis was the aggregate data on participants with biliary colic who were about to undergo surgery according to the group to which they were randomised.

Dealing with missing data

We performed an intention-to-treat analysis (Newell 1992), whenever possible, for binary outcomes. For continuous outcomes, we used an available-case analysis. We planned to impute the standard deviation from P values according to the instructions given in the Cochrane Handbook for Systematic Reviews of Intervention (Higgins 2011) and used the median for the meta-analysis when the mean was not available. If it was not possible to calculate the standard deviation from the P value or the CIs, we planned to impute the standard deviation as the highest standard deviation in the other trials included under that outcome, fully recognising that this form of imputation will decrease the weight of the trial for calculation of mean differences and bias the effect estimate to no effect in the case of standardised mean difference (Higgins 2011).

Assessment of heterogeneity

We planned to examine the forest plot to visually assess heterogeneity. We planned to use overlapping of CIs to assess the heterogeneity visually. We planned to explore heterogeneity by the Chi2 test, with significance set at a P value of 0.10, and to measure the quantity of heterogeneity by the I2 statistic (Higgins 2002).

Assessment of reporting biases

We planned to use a funnel plot to explore bias if there were at least 10 trials included (Egger 1997; Macaskill 2001). We planned to use asymmetry in the funnel plot of trial size against treatment effect to assess this bias. We also planned to use the linear regression approach described by Egger et al to determine the funnel plot asymmetry (Egger 1997).

Data synthesis

Meta-analysis

We planned to perform the meta-analyses according to the recommendations of The Cochrane Collaboration (Higgins 2011) and the Cochrane Hepato-Biliary Group Module (Gluud 2013), using the software package Review Manager 5.2 (RevMan 2012). We planned to use a random-effects model (DerSimonian 1986) and a fixed-effect model (DeMets 1987). In the case of a discrepancy between the two models we planned to report both results; otherwise we planned to report only the results from the fixed-effect model.

Trial sequential analysis

We planned to use trial sequential analysis to control for random errors due to sparse data and repetitive testing of the accumulating data (CTU 2011; Thorlund 2011). The underlying assumption of trial sequential analysis is that testing for significance may be performed each time a new trial is added to the meta-analysis resulting in an increased risk of random errors (Brok 2008; Wetterslev 2008; Brok 2009; Thorlund 2009; Wetterslev 2009; Thorlund 2010). We planned to add the trials according to the year of publication, and if more than one trial was published in a year we planned to add the trials alphabetically according to the last name of the first author. We planned to construct the trial sequential monitoring boundaries on the basis of the required information size. These boundaries determine the statistical inference one may draw regarding the cumulative meta-analysis that has not reached the required information size; if the trial sequential monitoring boundary is crossed before the required information size is reached, firm evidence may perhaps be established and further trials may turn out to be superfluous. On the other hand, if the boundary is not surpassed, it may be necessary to continue doing trials in order to detect or reject a certain intervention effect (Wetterslev 2008; Wetterslev 2009).

We planned to apply trial sequential analysis (CTU 2011; Thorlund 2011) using a required sample size calculated from an alpha error of 0.05, a beta error of 0.20, a control event proportion obtained from the results, and a relative risk reduction of 20% for primary outcomes to determine whether more trials are necessary on this topic (if the trial sequential alpha-spending monitoring boundary or the futility zone is crossed, then no more trials are deemed necessary) (Brok 2008; Wetterslev 2008; Brok 2009; Thorlund 2009; Wetterslev 2009; Thorlund 2010). For continuous outcomes, we planned to calculate the required sample size from an alpha error of 0.05, a beta error of 0.20, the variance estimated from the meta-analysis results of low risk of bias trials, and a minimal clinically relevant difference of one day for hospital stay and 15 minutes for operating time.

Subgroup analysis and investigation of heterogeneity

We planned to perform the following subgroup analyses.

  • Trials with low risk of bias compared to trials with high risk of bias.

  • Patients who had episodes of biliary colic prior to the biliary colic that necessitated surgical referral and those who had biliary colic for the first time.

We planned to perform the Chi2 test for subgroup differences, setting a P value of 0.05 to identify any differences.

Sensitivity analysis

We planned to perform a sensitivity analysis by excluding the trials in which medians or standard deviations were imputed for the continuous outcomes.

Summary of findings table

We have summarised the results of all the outcomes in a summary of findings table prepared using GRADEPro 3.6 (http://ims.cochrane.org/revman/gradepro).

Results

Description of studies

Results of the search

We identified a total of 930 references through electronic searches of CENTRAL (n = 147), MEDLINE (n = 258), EMBASE (n = 362), and Science Citation Index Expanded (n = 163). We excluded 392 duplicates and 534 clearly irrelevant references through reading the abstracts. Four references were retrieved for further assessment. No reference was identified through scanning the reference list of the identified randomised trial. Two references (one study) were excluded due to the reason stated in the 'Characteristics of excluded studies'. Two of the four references retrieved for further assessment met the inclusion criteria. Of the two references to the two trials (Salman 2005; Macafee 2009), one trial with one reference provided data for this review (Salman 2005). We have shown the reference flow in Figure 1. We have given the details about the sample size; participants characteristics; the inclusion and exclusion criteria used in the trial; and the risk of bias of the included trials in the table 'Characteristics of included studies'.

Figure 1.

Study flow diagram.

Included studies

Participants

In the only trial that provided data, a total of 75 participants who had biliary colic were randomised to early laparoscopic surgery (less than 24 hours after diagnosis) (n = 35) or to delayed laparoscopic cholecystectomy (waiting list for elective surgery, mean waiting time 4.2 months) (n = 40) (Salman 2005). Of the 75 participants, seven participants in the early group and five participants in the delayed group were excluded after randomisation, and the demographic details were not available for these 12 participants. The proportion of females and the average age of the remaining participants in this trial were 65% and 43 years, respectively.

Intervention

Early laparoscopic surgery (less than 24 hours after diagnosis).

Controls

Delayed laparoscopic cholecystectomy (waiting list for elective surgery, mean waiting time 4.2 months), which could be considered 'treatment as usual' in many healthcare services (Somasekar 2002).

Outcomes

The main outcomes reported were mortality, serious adverse events, conversion to open cholecystectomy, hospital stay, and operating time. Mortality data were available for the 75 randomised participants. Data on serious adverse events were available for 68 participants (28 participants in the early laparoscopic cholecystectomy group and 40 participants in the delayed laparoscopic cholecystectomy group). The remaining outcomes were available for 63 participants (28 participants in the early laparoscopic cholecystectomy group and 35 participants in the delayed laparoscopic cholecystectomy group).

Risk of bias in included studies

Both trials were at high risk of bias. The risks of bias in the individual domains are presented in Figure 2 and Figure 3.

Figure 2.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Figure 3.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Both included trials were judged at low risk of bias due to adequate random sequence generation (Salman 2005; Macafee 2009). One trial was judged at low risk of bias due to adequate allocation concealment (Macafee 2009). Neither trial was judged at low risk of bias due to blinding of participants, personnel, or outcome assessors. One trial was judged at low risk of bias in the incomplete outcome data domain (Macafee 2009). One trial was judged at low risk of bias in the selective outcome reporting domain (Salman 2005). One trial was judged at low risk of bias in the for-profit bias domain (Macafee 2009).

Effects of interventions

See: Summary of findings for the main comparison Early versus delayed laparoscopic cholecystectomy for uncomplicated biliary colic

The results are summarised in the Summary of findings for the main comparison.

All-cause mortality

The only person who died belonged to the delayed group. The death was due to severe acute pancreatitis during the waiting time (for laparoscopic cholecystectomy). The difference between the two groups was not statistically significant (Fisher's exact test: P > 0.9999).

Bile duct injury

There was no bile duct injury in either group.

Serious adverse events

There were no other serious adverse events related to the surgery in either group. During the waiting period, complications developed in the delayed laparoscopic cholecystectomy group. The complications that the participants suffered included pancreatitis (n = 1), empyema of the gallbladder (n = 1), gallbladder perforation (n = 1), acute cholecystitis (n = 2), cholangitis (n = 2), obstructive jaundice (n = 2), and recurrent biliary colic (requiring hospital visits) (n = 5). In all, 14 participants required hospital admissions for the above symptoms. All of these occurred in the delayed group. The participants in the early laparoscopic cholecystectomy group were operated on within 24 hours. Pancreatitis, empyema of the gallbladder, gallbladder perforation, acute cholecystitis, cholangitis, and obstructive jaundice during the waiting period can be considered as serious adverse events. The proportion of participants who developed serious adverse events was 0/28 (0%) in the early laparoscopic cholecystectomy group and the proportion of participants was significantly lower than in the delayed laparoscopic cholecystectomy group 9/40 (22.5%) (Fisher's exact test: P = 0.0082).

Quality of life

This outcome was not reported by the included trial.

Conversion to open cholecystectomy

There was no significant difference in the proportion of participants who required conversion to open cholecystectomy in the early group 0/28 (0%) compared with the delayed group (6/35 or 17.1%) (Fisher's exact test: P = 0.0743). However, it should be noted that the participants with acute cholecystitis were excluded from the early group while performing these calculations.

Hospital stay

There was a statistically significant shorter hospital stay in the early group than the delayed group (MD -1.25 days, 95% CI -2.05 to -0.45).

Operating time

There was a statistically significant shorter operating time in the early group than the delayed group (MD -14.80 minutes, 95% CI -18.02 to -11.58).

Return to work

This outcome was not reported by the included trial.

Statistical variation

The issue of fixed-effect versus random-effects models does not arise since there was only one trial.

Subgroup analyses

Since there was only one trial, we could not perform subgroup analyses.

Sensitivity analysis

Since we did not impute the mean and standard deviation of hospital stay or operating time, we did not perform any sensitivity analysis.

Trial sequential analysis

We did not perform trial sequential analysis because of the presence of only one trial in this review.

Reporting bias

We did not produce a funnel plot because of the inclusion of only one trial in this review.

Discussion

Summary of main results

Surgery immediately after diagnosis of an uncomplicated benign condition is rarely available in a government-funded health system because of the limited availability of resources. The resources available are usually allocated to deal quickly with diseases with a potential to cause severe harm to the people.

This review has shown that placing the people with biliary colic on a waiting list for laparoscopic cholecystectomy may expose the people to serious harm and can even lead to fatal consequences. Furthermore, 35% of the participants with biliary colic required hospital admission at least once, and the rate of emergency admission per 100 persons per month was 11 in the delayed laparoscopic cholecystectomy group in the only trial included in this review (Salman 2005). Around 80% of the people being offered elective cholecystectomy in UK have biliary colic (Somasekar 2002). In a retrospective study from Canada, the rate of emergency hospital admission in people with biliary colic who have been placed on a waiting list for laparoscopic cholecystectomy was 3.6 per 100 people per month (Sobolev 2003). The rate of emergency admissions increased from 3 per 100 people per month in the first four weeks to 23 per 100 people per month after 40 weeks. In the UK, the mean waiting time for elective laparoscopic cholecystectomy is 12 months (Somasekar 2002). In this study (Somasekar 2002), 24% of the 156 people (80% of whom were placed on the waiting list for laparoscopic cholecystectomy for biliary colic) required emergency hospital admission. The rate of emergency hospital admission in this study was 2.5 admissions per 100 people per month. Another retrospective study in the USA reviewed the events during the waiting time for elective laparoscopic cholecystectomy (Rutledge 2000). In this study, 23% of the people developed complications of gallstone disease such as acute cholecystitis, pancreatitis, or jaundice during the waiting time. Those who developed complications had a 30% increase in operating time, 10-fold increase in hospital stay, and a four-fold increase in conversion to open cholecystectomy. The rate of emergency hospital admissions for biliary colic in the Rutledge 2000 was 13 per 100 people per month.

There are, however, resource implications. By following a policy of early laparoscopic cholecystectomy for biliary colic, all people with suspected biliary colic have to undergo urgent ultrasound. Ultrasound confirmation is essential, as the positive predictive value of biliary colic in the diagnosis of gallstones is only 50% (Berger 2000), that is, only half of the people suspected (by doctors) to have gallstones because of symptoms suggestive of biliary colic actually have gallstones. Once gallstones have been confirmed, the people must undergo the operation on an urgent basis before complications can arise. This may put a strain on the resources available (such as surgeons' time, operation theatre time, funds).

The choice of the time in the definition of early cholecystectomy was chosen arbitrarily. In the only trial included in this review, 20% of the participants who were diagnosed to have biliary colic had acute cholecystitis in spite of normal temperature and white cell count; and a lack of features of acute cholecystitis on ultrasound. The sensitivity of ultrasound in diagnosing acute cholecystitis varies from 60% (Bingener 2004) to 88% (Shea 1994). The sensitivity of clinical and laboratory values in the diagnosis of acute cholecystitis varies between 63% and 81% (Trowbridge 2003). Thus, it is possible that some people with acute cholecystitis may be included in the participant group of biliary colic. However, in a Cochrane review, the first two authors of this review found that early laparoscopic cholecystectomy for acute cholecystitis was safe provided it was carried out within a week of onset of symptoms (Gurusamy 2013). The safety of early laparoscopic cholecystectomy for acute cholecystitis beyond one week of onset of symptoms has not been established yet. So, it is advisable to perform early laparoscopic cholecystectomy within a week of onset of symptoms of uncomplicated biliary colic. In order to achieve this, it may be necessary to educate the people to identify biliary colic; general practitioners to refer the people with suspected biliary colic urgently for ultrasound; and to educate the radiologists (physicians responsible for ultrasonography) on the importance of the urgent ultrasound.

The reason for the post-randomisation dropouts was different between the two groups. The participants in the early laparoscopic cholecystectomy group were excluded because they had acute cholecystitis whereas the participants in the delayed laparoscopic cholecystectomy group were excluded because of complications such as gallbladder perforation, empyema of gallbladder, acute severe pancreatitis, cholangitis, obstructive jaundice, and acute cholecystitis. While we attempted to include these participants in the analyses, as far as possible, we could not include them for outcomes such as operating time and hospital stay. Particular attention has to be drawn to acute cholecystitis in the two groups. The trial authors mentioned that the two cases of acute cholecystitis were operated on laparoscopically in the delayed laparoscopic cholecystectomy group but did not mention anything about the proportion of participants who required conversion to open cholecystectomy in the early group. When we assumed a conversion rate of 20% for participants with acute cholecystitis in the early group (Gurusamy 2013), there was no statistically significant difference in the conversion rate between the two groups. However, it is likely that the difference in the hospital stay becomes even higher when the participants who were excluded post-randomisation were included.

Overall completeness and applicability of evidence

The mean waiting time for operation was 4.2 months in the delayed laparoscopic cholecystectomy group. The result of the comparison between early versus delayed laparoscopic cholecystectomy is very likely to change if one has more or less waiting time in the delayed group. So, this review is applicable only when the waiting time for elective surgery is approximately four months.

Quality of the evidence

The overall quality of the evidence was very low, as shown in the Summary of findings for the main comparison. While it is difficult or even unethical to blind the participants to the groups, it is possible to blind the personnel and outcome assessors to the groups. It is also possible to perform a strict intention-to-treat analysis by including all the trial participants in the analysis.

Potential biases in the review process

We performed a thorough search of the literature and identified two trials (Salman 2005; Macafee 2009). However, only one trial provided information for this review (Salman 2005). Our attempts to obtain further information on the participants in the other trial were futile (Macafee 2009).

Agreements and disagreements with other studies or reviews

This is the only systematic review on this topic. The conclusions are broadly the same as in our previous version in spite of the search update and alteration in the methods (Gurusamy 2008).

Authors' conclusions

Implications for practice

Based on evidence from one trial, it appears that early laparoscopic cholecystectomy decreases the morbidity during the waiting period for elective laparoscopic cholecystectomy, conversion to open cholecystectomy, operating time, and hospital stay compared to delayed laparoscopic cholecystectomy, with a waiting period of approximately four months.

Implications for research

Further randomised clinical trials are urgently needed. Future trials need to be conducted and reported according to the SPIRIT (SPIRIT 2013) and CONSORT Statement (www.consort-statement.org) (Moher 2001).

Acknowledgements

To the Cochrane Hepato-Biliary Group for the support that they have provided.

K Samraj who independently assessed the trials for inclusion and extracted data on the included trials for the first version.

Peer reviewers: Karl Sondenaa, Norway; Malte Schmidt, Norway; Giuseppe Borzellino, Italy.
Contact Editor: Christian Gluud, Denmark.

This project was funded by the National Institute for Health Research.
Disclaimer of the Department of Health: 'The views and opinions expressed in the review are those of the authors and do not necessarily reflect those of the National Institute for Health Research (NIHR), National Health Services (NHS), or the Department of Health'.

Data and analyses

Download statistical data

Comparison 1. Early or delayed laparoscopic cholecystectomy for biliary colic
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Mortality175Risk Ratio (M-H, Fixed, 95% CI)0.38 [0.02, 9.03]
2 Serious adverse events1 Risk Ratio (M-H, Fixed, 95% CI)Subtotals only
3 Conversion to open cholecystectomy163Risk Ratio (M-H, Fixed, 95% CI)0.10 [0.01, 1.63]
4 Hospital stay (days)163Mean Difference (IV, Fixed, 95% CI)-1.25 [-2.05, -0.45]
5 Operating time (minutes)163Mean Difference (IV, Fixed, 95% CI)-14.80 [-18.02, -11.58]
Analysis 1.1.

Comparison 1 Early or delayed laparoscopic cholecystectomy for biliary colic, Outcome 1 Mortality.

Analysis 1.2.

Comparison 1 Early or delayed laparoscopic cholecystectomy for biliary colic, Outcome 2 Serious adverse events.

Analysis 1.3.

Comparison 1 Early or delayed laparoscopic cholecystectomy for biliary colic, Outcome 3 Conversion to open cholecystectomy.

Analysis 1.4.

Comparison 1 Early or delayed laparoscopic cholecystectomy for biliary colic, Outcome 4 Hospital stay (days).

Analysis 1.5.

Comparison 1 Early or delayed laparoscopic cholecystectomy for biliary colic, Outcome 5 Operating time (minutes).

Appendices

Appendix 1. Search strategies

DatabasePeriodofSearchSearch Strategy
Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Wiley)Issue 1 of 12, 2013.#1 MeSH descriptor Biliary Tract Diseases explode all trees
#2 MeSH descriptor Biliary Tract explode all trees
#3 MeSH descriptor Gallbladder explode all trees
#4 MeSH descriptor Gallbladder Diseases explode all trees
#5 biliary OR gallbladder OR gall-bladder OR "gall bladder"
#6 (#1 OR #2 OR #3 OR #4 OR #5)
#7 MeSH descriptor Colic explode all trees
#8 MeSH descriptor Pain explode all trees
#9 colic* OR pain OR pains OR cramp* OR ache OR aches
#10 (#7 OR #8 OR #9)
#11 MeSH descriptor Cholecystectomy explode all trees
#12 cholecystecto* OR colecystecto*
#13 (#11 OR #12)
#14 (#6 AND #10 AND #13)
MEDLINE (PubMed)1987 to March 2013.(biliary OR "Biliary Tract Diseases"[MeSH] OR "Biliary Tract"[MeSH] OR gallbladder OR gall-bladder OR "gall bladder" OR "Gallbladder"[MeSH] OR "Gallbladder Diseases"[MeSH]) AND (colic* OR pain OR pains OR cramp* OR ache OR aches OR "Colic"[MeSH] OR "Pain"[MeSH]) AND (cholecystecto* OR colecystecto* OR "cholecystectomy"[MeSH]) AND (((randomized controlled trial [pt] OR controlled clinical trial [pt] OR randomized controlled trials [mh] OR random allocation [mh] OR double-blind method [mh] OR single-blind method [mh] OR clinical trial [pt] OR clinical trials [mh] OR ("clinical trial" [tw]) OR ((singl* [tw] OR doubl* [tw] OR trebl* [tw] OR tripl* [tw]) AND (mask* [tw] OR blind* [tw])) OR (placebos [mh] OR placebo* [tw] OR random* [tw] OR research design [mh:noexp]) NOT (animals [mh] NOT human [mh]))))
EMBASE (OvidSP)1987 to March 2013.

1. exp BILIARY COLIC/

2. ((biliary or gallbladder or gall bladder or gall bladder) and (colic* or pain or pains or cramp* or ache or aches)).af.

3. 1 or 2

4. exp CHOLECYSTECTOMY/ or (cholecystecto* or colecystecto*).af.

5. exp laparoscopic surgery/ or (laparoscop* or coelioscop* or celioscop* or peritoneoscop*).af.

6. 3 and 4 and 5

7. exp RANDOMIZED CONTROLLED TRIAL/ or exp RANDOMIZATION/ or exp CONTROLLED STUDY/ or exp MULTICENTER STUDY/ or exp PHASE 3 CLINICAL TRIAL/ or exp PHASE 4 CLINICAL TRIAL/ or exp DOUBLE BLIND PROCEDURE/ or exp SINGLE BLIND PROCEDURE/

8. (RANDOM* or CROSSOVER* or CROSS OVER or FACTORIAL* or PLACEBO* or VOLUNTEER*).af.

9. ((SINGLE or DOUBLE or TREBLE or TRIPLE) and (BLIND or MASK)).af.

10. 7 or 8 or 9

11. 6 and 10

Science Citation Index Expanded (Web of Knowledge)1987 to March 2013.#1 TS=(biliary OR gallbladder OR gall-bladder OR gall bladder)
#2 TS=(colic* OR pain OR pains OR cramp* OR ache OR aches)
#3 TS=(cholecystecto* OR colecystecto*)
#4 TS=(random* OR blind* OR placebo* OR meta-analysis)
#5 #4 AND #3 AND #2 AND #1

What's new

DateEventDescription
24 March 2013New citation required and conclusions have changedThe methods were revised and, because of better interpretation of evidence, modifications to the conclusions have been made: from "Based on evidence from only one high-bias risk trial, it appears that early laparoscopic cholecystectomy (< 24 hours of diagnosis of biliary colic) decreases the morbidity during the waiting period for elective laparoscopic cholecystectomy, decreases the rate of conversion to open cholecystectomy, decreases operating time, and decreases hospital stay. Further randomised clinical trials are necessary to confirm or refute this finding", to "Based on evidence from only one high-bias risk trial, it appears that early laparoscopic cholecystectomy (< 24 hours after diagnosis of biliary colic) decreases the morbidity during the waiting period for elective laparoscopic cholecystectomy (mean waiting time 4.2 months) and decreases the hospital stay and operating time. Further randomised clinical trials are necessary to confirm or refute this finding and to determine if early laparoscopic cholecystectomy is better than delayed laparoscopic cholecystectomy with a shorter waiting time".
24 March 2013AmendedAuthor list: Kurinchi Selvan Gurusamy, Rahul Koti, Giuseppe Fusai, Brian R Davidson.
14 March 2013New search has been performedSearches were updated. One new trial was identified (Macafee 2009). However, this trial did not provide any information for this review (Macafee 2009).

History

Protocol first published: Issue 2, 2008
Review first published: Issue 4, 2008

DateEventDescription
16 March 2008AmendedConverted to new review format.

Contributions of authors

KS Gurusamy wrote the review and assessed the trials for inclusion and extracted data on included trials. R Koti independently assessed the trials for inclusion and extracted data on included trials for the update. BR Davidson and G Fusai critically commented on the review and provided advice for improving the review.

Declarations of interest

None known.

Sources of support

Internal sources

  • None, Not specified.

External sources

  • NIHR, UK.

    Kurinchi Gurusamy is part funded by NIHR, UK.

Differences between protocol and review

Following a peer reviewer's request, severe morbidity (all causes) was added as an outcome.

Differences between first version and second version of the review

The methods were revised according to Version 5.1.0 of Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). This included revision of the outcomes and bias risk in the trials.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Macafee 2009

MethodsRandomised clinical trial
ParticipantsCountry: United Kingdom.
Number randomised: not stated.
Post-randomisation drop-outs: not stated.
Revised sample size: not stated.
Average age: not stated.
Females: not stated.
Inclusion criteria
1. Patients aged 18 to 80 years.
2. Presenting for the first time with biliary colic or acute cholecystitis.
3. Admitted as an emergency.
Exclusion criteria
1. Patients with medical co-morbidity deeming them unfit for laparoscopic cholecystectomy.
2. Previously diagnosed with gallstone disease.
3. Deranged liver function test results.
4. Acute pancreatitis.
5. Ascending cholangitis.
6. Unable to understand the implications of the trial or give informed consent. 
Interventions

Participants were randomly assigned to two groups.
Group 1: early laparoscopic cholecystectomy (n = not stated).

Further details: surgery within 72 hours of recruitment.
Group 2: delayed laparoscopic cholecystectomy (n = not stated).
Further details: surgery delayed by three months of discharge after conservative treatment.
Peroperative cholangiogram: when necessary. 

OutcomesNone of the outcomes were reported separately for participants with acute cholecystitis and biliary colic.
Notes

Although the authors measured the quality of life, this was measured at specific intervals after the surgery, rather than from the time of randomisation. As a result, this information was not used.

Attempts were made to contact the authors in March 2013. The authors have not replied yet.

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskQuote: "The randomization sequence was determined using a web-based random number generator (http://www.randomizer.org)".
Allocation concealment (selection bias)Low riskQuote: "Patients were randomized to early laparoscopic cholecystectomy or conventional management using sequentially numbered, sealed, opaque envelopes by someone not involved with the trial"
Blinding of participants and personnel (performance bias)
All outcomes
High riskComment: Neither the investigators nor the participants were blinded to the allocation groups.
Blinding of outcome assessment (detection bias)
All outcomes
High riskComment: Neither the investigators nor the participants were blinded to the allocation groups.
Incomplete outcome data (attrition bias)
All outcomes
Low riskComment: There were no post-randomisation dropouts.
Selective reporting (reporting bias)High riskComment: None of the outcomes were reported separately for participants with acute cholecystitis and biliary colic separately.
For-profit biasLow riskQuote: This study was funded by UK NHS Culyer Funding.

Salman 2005

MethodsRandomised clinical trial
ParticipantsCountry: Turkey.
Number randomised: 75.
Post-randomisation drop-outs: 12 (16%).
Revised sample size: 63.
Average age: 43 years.
Females: 41 (65.1%).
Inclusion criteria
Patients presenting to the emergency room or clinic office with an initial biliary colic diagnosis.
Exclusion criteria
Patients with other biliary complications such as acute cholecystitis, obstructive jaundice, cholangitis, or pancreatitis.
Interventions

Participants were randomly assigned to two groups.
Group 1: early laparoscopic cholecystectomy (n = 28).
Further details: surgery within 24 hours of admission

Group 2: delayed laparoscopic cholecystectomy (n = 35).
Further details: elective laparoscopic cholecystectomy (interval between presentation and surgery: average of 4.2 months).

OutcomesThe outcomes reported were mortality, serious adverse events, hospital stay, and operating time.
Notes

Of the 75 participants, seven participants in group 1 and five participants in group 2 were excluded after randomisation.

In group 1, the participants were excluded because of intra-operative acute cholecystitis.

In group 2, the participants were excluded because of acute severe pancreatitis and death (1); empyema of gallbladder (1); gallbladder perforation (1); and acute cholecystitis (2). Wherever possible, these participants have been included as we performed the analysis by an 'intention-to-treat' analysis.

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskQuote: "After informed consent was obtained, patients were randomly assigned by simple random sampling using a random table number to one of the treatment arms".
Allocation concealment (selection bias)Unclear riskComment: This information was not available.
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskComment: This information was not available.
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskComment: This information was not available.
Incomplete outcome data (attrition bias)
All outcomes
High riskComment: There were post-randomisation drop-outs.
Selective reporting (reporting bias)Low riskComment: Important outcomes such as mortality and morbidity were reported
For-profit biasUnclear riskComment: This information was not available.

Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion
Vetrhus 2002This trial compared delayed laparoscopic cholecystectomy and deferred cholecystectomy (wait-and-watch policy).

Ancillary