1. BMJ. 2018 Oct 8;363:k3965. doi: 10.1136/bmj.k3965.

Laparoscopic cholecystectomy versus percutaneous catheter drainage for acute
cholecystitis in high risk patients (CHOCOLATE): multicentre randomised clinical 
trial.

Loozen CS(1), van Santvoort HC(1)(2), van Duijvendijk P(3), Besselink MG(4),
Gouma DJ(4), Nieuwenhuijzen GA(5), Kelder JC(6), Donkervoort SC(7), van Geloven
AA(8), Kruyt PM(9), Roos D(10), Kortram K(1), Kornmann VN(1), Pronk A(11), van
der Peet DL(12), Crolla RM(13), van Ramshorst B(1), Bollen TL(14), Boerma D(15).

Author information: 
(1)Department of Surgery, St Antonius Hospital, 3435CM, PO box 2500, Nieuwegein, 
Netherlands.
(2)Department of Surgery, University Medical Centre Utrecht, Utrecht,
Netherlands.
(3)Department of Surgery, Gelre Hospital, Apeldoorn, Netherlands.
(4)Department of Surgery, Academic Medical Centre, Amsterdam, Netherlands.
(5)Department of Surgery, Catharina Hospital, Eindhoven, Netherlands.
(6)Department of Clinical Epidemiology, St Antonius Hospital, Nieuwegein,
Netherlands.
(7)Department of Surgery, Onze Lieve Vrouwe Gasthuis, Amsterdam, Netherlands.
(8)Department of Surgery, Tergooi Hospital, Hilversum, Netherlands.
(9)Department of Surgery, Gelderse Vallei Hospital, Amsterdam, Netherlands.
(10)Department of Surgery, Reinier de Graaff Hospital, Delft, Netherlands.
(11)Department of Surgery, Diakonessenhuis, Utrecht, Netherlands.
(12)Department of Surgery, VU University Medical Centre, Amsterdam, Netherlands.
(13)Department of Surgery, Amphia Hospital, Breda, Netherlands.
(14)Department of Radiology, St Antonius Hospital, Nieuwegein, Netherlands.
(15)Department of Surgery, St Antonius Hospital, 3435CM, PO box 2500, Nieuwegein,
Netherlands d.boerma@antoniusziekenhuis.nl.

OBJECTIVE: To assess whether laparoscopic cholecystectomy is superior to
percutaneous catheter drainage in high risk patients with acute calculous
cholecystitis.
DESIGN: Multicentre, randomised controlled, superiority trial.
SETTING: 11 hospitals in the Netherlands, February 2011 to January 2016.
PARTICIPANTS: 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.
MAIN OUTCOME MEASURES: 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.
RESULTS: 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).
CONCLUSION: Laparoscopic cholecystectomy compared with percutaneous catheter
drainage reduced the rate of major complications in high risk patients with acute
cholecystitis.
TRIAL REGISTRATION: Dutch Trial Register NTR2666.

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DOI: 10.1136/bmj.k3965 
PMCID: PMC6174331
PMID: 30297544  [Indexed for MEDLINE]

Conflict of interest statement: Competing interests: All authors have completed
the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf declare no 
support from any organisation for the submitted work, no financial relationships 
with any organizations that might have an interest in the submitted work, and no 
other relationships or activities that could appear to have influenced the
submitted work.