Research
Laparoscopic cholecystectomy versus percutaneous catheter drainage for acute cholecystitis in high risk patients (CHOCOLATE): multicentre randomised clinical trial
Charlotte S Loozen, Hjalmar C van Santvoort, Peter van Duijvendijk, et al
BMJ 2018; 363 doi: https://doi.org/10.1136/bmj.k3965
(Published 08 October 2018)Cite this as: BMJ 2018;363:k3965
Abstract
Objective 目的
To assess whether laparoscopic cholecystectomy is superior to percutaneous catheter drainage in high risk patients with acute calculous cholecystitis.
对于高危急性结石性胆囊炎患者，评估腹腔镜胆囊切除术是否优于经皮导管引流。
Design 设计
Multicentre, randomised controlled, superiority trial.
多中心随机对照优效试验
Setting 场景
11 hospitals in the Netherlands, February 2011 to January 2016.
荷兰11家医院，2011年2月至2016年1月
Participants 研究人群
142 high risk patients with acute calculous cholecystitis were randomly allocated to laparoscopic cholecystectomy (n=66) or to percutaneous catheter drainage (n=68). High risk was defined as an acute physiological assessment and chronic health evaluation II (APACHE II) score of 7 or more.
142名高危急性结石性胆囊炎患者被随机分为腹腔镜胆囊切除术组(n = 66)或经皮导管引流组(n = 68)。高危定义为APACHE II评分大于等于7分。
Main outcome measures 主要预后指标
The primary endpoints were death within one year and the occurrence of major complications, defined as infectious and cardiopulmonary complications within one month, need for reintervention (surgical, radiological, or endoscopic that had to be related to acute cholecystitis) within one year, or recurrent biliary disease within one year.
主要预后终点为一年内死亡及严重并发症（定义为一个月内感染或心肺并发症，一年内需要再次干预[与急性胆囊炎相关的手术，影像或内镜治疗]，或一年内胆道疾病复发）发生率。
Results 结果
The trial was concluded early after a planned interim analysis. The rate of death did not differ between the laparoscopic cholecystectomy and percutaneous catheter drainage group (3% v 9%, P=0.27), but major complications occurred in eight of 66 patients (12%) assigned to cholecystectomy and in 44 of 68 patients (65%) assigned to percutaneous drainage (risk ratio 0.19, 95% confidence interval 0.10 to 0.37; P<0.001). In the drainage group 45 patients (66%) required a reintervention compared with eight patients (12%) in the cholecystectomy group (P<0.001). Recurrent biliary disease occurred more often in the percutaneous drainage group (53% v 5%, P<0.001), and the median length of hospital stay was longer (9 days v 5 days, P<0.001).
在计划中的中期分析后试验提早终止。腹腔镜胆囊切除术组与经皮导管引流组患者病死率五显著差异 (3% v 9%, P=0.27)，但胆囊切除术组66名患者中8名 (12%) 及经皮引流组68名患者中44名(65%)出现严重并发症（风险比0.19，95% 可信区间 0.10 to 0.37；P<0.001）。引流组中45名(66%)患者需要再次干预治疗，胆囊切除术组仅有8名(12%)(P<0.001)。经皮引流组患者胆道疾病复发率更高(53% v 5%, P<0.001)，中位住院日更长（9 天 v 5 天，P<0.001）。
Table 1 Definitions of primary endpoints
| Endpoint | Definition | Comment |
|---|---|---|
| Death | Within one year after randomisation | |
| Major complications: | ||
| Intra-abdominal abscess | Fever or increased C reactive protein level/white blood cell count, or both, and intra-abdominal fluid collection on computed tomography or ultrasonography | Within 30 days after randomisation |
| Pneumonia | Coughing or dyspnoea, radiography with infiltrative abnormalities, increased infection variable, and positive sputum culture result | Within 30 days after randomisation |
| Myocardial infarction | Symptomatic increased cardiac enzyme levels and abnormalities on electrocardiography or cardiac ultrasonography | Within 30 days after randomisation |
| Pulmonary embolism | Radiologically proven pulmonary embolism | Within 30 days after randomisation |
| Need for reintervention | Surgical, endoscopic, or radiological reintervention | Within one year after randomisation. Before analysis, the adjudication committee decided to only report reinterventions directly or indirectly related to acute cholecystitis. A routine elective cholecystectomy after percutaneous catheter drainage was not included in the primary endpoint (ie, only cholecystectomies for recurrent gallstone related complications were included) |
| Recurrent biliary disease | Within one year after randomisation. Before analysis, the adjudication committee decided to only report recurrent biliary disease when readmission was required |
Table 2 Baseline characteristics of participants. Values are numbers (percentages) unless stated otherwise
| Characteristics | Laparoscopic cholecystectomy (n=66) | Percutaneous catheter drainage (n=68) |
|---|---|---|
| Mean (SD) age (years) | 71.4 (10.6) | 74.9 (8.6) |
| Men | 41 (62) | 44 (65) |
| Mean (SD) body mass index* | 28.7 (5.3) | 29.0 (5.5) |
| Coexisting conditions: | ||
| Cardiovascular disease | 38 (58) | 53 (78) |
| Pulmonary disease | 13 (20) | 14 (21) |
| Chronic renal insufficiency | 3 (5) | 5 (7) |
| Diabetes | 13 (20) | 16 (24) |
| Previous abdominal surgery | 16 (24) | 10 (15) |
| ERCP before randomisation | 3 (5) | 4 (6) |
| ASA classification on admission: | ||
| I: healthy status | 10 (15) | 4 (6) |
| II: mild systemic disease | 33 (50) | 37 (54) |
| III: severe systemic disease | 23 (35) | 24 (35) |
| IV: severe systemic disease that is a constant threat to life | 0 | 3 (4) |
| Disease severity: | ||
| Mean (SD) APACHE II score† | 9.5 (1.9) | 9.4 (2.0) |
| Mean (SD) C reactive protein level (mg/L) | 218.5 (117.2) | 214.7 (123.8) |
| Mean (SD) white blood cell count (×109/L)‡ | 17.0 (5.1) | 17.2 (5.2) |
| Mean (SD) body temperature (°C)§ | 37.7 (1.1) | 37.8 (0.9) |
| Median (interquartile range) time since onset of symptoms (days)¶ | 3 (2 to 3) | 2 (1 to 4) |
ERCP=endoscopic retrograde cholangiopancreatography; ASA=American Society of Anaesthesiologists; APACHE II=acute physiology and chronic health evaluation II.
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* Data missing for 12 patients in cholecystectomy group and nine in drainage group.
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† Scores on acute physiological and chronic health evaluation II (APACHE II) scale range from 0 to 71, with higher scores indicating more severe disease.
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‡ Data missing for one patient in drainage group.
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§ Data missing for five patients in cholecystectomy group and two in drainage group.
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¶ In all patients, time since onset of symptoms was seven days or less. Data on exact number of days were missing for five patients in drainage group but were reported to be less than 7.
Table 3 Primary and secondary endpoints for participants allocated to laparoscopic cholecystectomy or percutaneous catheter drainage. Values are numbers (percentages) unless stated otherwise
| Outcomes | Cholecystectomy group (n=66) | Drainage group (n=68) | Risk ratio (95% CI) | P value |
|---|---|---|---|---|
| Primary endpoints* | ||||
| Death | 2 (3) | 6 (9) | 0.34 (0.07 to 1.64) | 0.27 |
| Major complications† | 8 (12) | 44 (65) | 0.19 (0.10 to 0.37) | <0.001 |
| Secondary endpoints* | ||||
| Death: | 2 (3) | 6 (9) | 0.34 (0.07 to 1.64) | 0.27 |
| Directly/indirectly related to acute cholecystitis | 0 | 3 (4) | ||
| Unrelated to acute cholecystitis | 2 (3) | 2 (3) | ||
| Unknown cause | 0 | 1 (2) | ||
| Infectious and cardiopulmonary complication‡: | 5 (8) | 3 (4) | 0.97 (0.89 to 1.05) | 0.49 |
| Intra-abdominal abscess | 4 (6) | 2 (3) | ||
| Pneumonia | 2 (3) | 1 (2) | ||
| Myocardial infarction | 0 | 0 | ||
| Pulmonary embolism | 0 | 0 | ||
| Need for reintervention‡: | 8 (12) | 45 (66) | 0.18 (0.09 to 0.36) | <0.001 |
| Surgical intervention | 3 (5) | 32 (47) | 0.10 (0.03 to 0.30) | <0.001 |
| Emergency cholecystectomy | NA | 11 (16) | ||
| Clinical deterioration | NA | 2 (3) | ||
| Recurrent cholecystitis | NA | 9 (13) | ||
| Elective cholecystectomy§ | 2 (2) | 20 (29) | ||
| Recurrent gallstone related disease | NA | 15 (22) | ||
| Dysfunctional drain¶ | NA | 1 (2) | ||
| Absence of duodenal backflow revealed by cholangiography¶ | NA | 4 (6) | ||
| Cholecystectomy not performed during index admission¶ | 2 (2) | NA | ||
| Diagnostic laparoscopy | 1 (2) | 1 (2) | ||
| Endoscopic intervention | 6 (9) | 11 (16) | 0.56 (0.22 to 1.43) | 0.22 |
| ERCP | 6 (9) | 11 (16) | ||
| Choledocholithiasis | 2 (3) | 9 (13) | ||
| Biliary injury | 4 (6) | 2 (3) | ||
| Removal of biliary stent | 1 (2) | 0 | ||
| Radiological intervention | 4 (6) | 15 (22) | 0.28 (0.10 to 0.79) | 0.008 |
| Percutaneous catheter drainage | NA | 8 (12) | ||
| Recurrent cholecystitis | NA | 6 (9) | ||
| Dysfunctional drain | NA | 2 (3) | ||
| Drainage abscess | 3 (5) | 4 (6) | ||
| Drainage biloma | 2 (3) | 0 | ||
| Drainage ascites | 0 | 1 (2) | ||
| Antegrade cholangiography | NA | 4 (6) | ||
| Contrast image PTC tube | 1 (2) | 0 | ||
| Recurrent biliary disease‡: | 3 (5) | 36 (53) | 0.09 (0.03 to 0.27) | <0.001 |
| Requiring emergency readmission | 3 (5) | 28 (41) | ||
| Requiring planned readmission | 2 (3) | 16 (24) | ||
| Elective cholecystectomy | NA | 15 (22) | ||
| ERCP | 2 (3) | 3 (4) | ||
| Minor complication: | 0 | 4 (6) | 0.12 | |
| Wound infection | 0 | 2 (3) | ||
| Bleeding | 0 | 0 | ||
| Urinary tract infection | 0 | 2 (3) | ||
| Healthcare utilisation: | ||||
| Median (interquartile range) length of stay after randomisation (days) | 4 (3-6) | 6 (4-8) | 0.01 | |
| Median (interquartile range) total length of hospital stay (days) | 5 (4-8) | 9 (6-19) | <0.001 | |
| Median (interquartile range) total length of stay in ICU (days) | 0 (0-0) | 0 (0-0) | 0.16 | |
| Total No (range per patient) of ER visits per study group | 7 (0-1) | 56 (0-5) | <0.001 | |
| Total No (range per patient) of reinterventions per study group | 21 (0-6) | 64 (0-4) | <0.001 | |
| Total No (range per patient) of readmissions per study group | 9 (0-2) | 67 (0-5) | <0.001 | |
ERCP=endoscopic retrograde cholangiopancreatography; PTC=percutaneous transhepatic cholangiography; ICU=intensive care unit; ER=emergency department; NA=not applicable.
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* Multiple events in same patient were considered as one endpoint.
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† For example, infectious and cardiopulmonary complications within one month, need for reintervention within one year, or recurrent biliary disease within one year.
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‡ Included in primary endpoint of major complications.
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§ Elective cholecystectomies were not included in primary endpoint, unless performed for recurrent gallstone related disease.
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¶ These procedures were not included in primary endpoint because the adjudication committee judged the indication debatable.
Conclusion 结论
Laparoscopic cholecystectomy compared with percutaneous catheter drainage reduced the rate of major complications in high risk patients with acute cholecystitis.
对于高危急性胆囊炎患者，与经皮导管引流相比，腹腔镜胆囊切除术减少严重并发症发生率。
Trial registration 试验注册
Dutch Trial Register NTR2666.
