Laparoscopic cholecystectomy versus percutaneous catheter drainage for acute cholecystitis in high risk patients (CHOCOLATE): multicentre randomised clinical trial
BMJ 2018; 363 doi: https://doi.org/10.1136/bmj.k3965 (Published 08 October 2018) Cite this as: BMJ 2018;363:k3965
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To the Editor
We read with interest the manuscript by Loozen et al [1] which sought to answer the dilemma of managing high risk patient with acute cholecystitis with percutaneous cholecystostomy or emergent laparoscopic cholecystostomy.
The results of the study advocate laparoscopic cholecystectomy rather than percutaneous cholecystostomy as the definitive mode of treatment in high risk patients presenting with acute cholecystitis. The study was concluded early after the planned interim analysis which demonstrated a much higher rate of major complications in the percutaneous cholecystostomy group (65%) compared to the cholecystectomy group (12%). Majority of the cases that accounted for this number came from the rate of reintervention as described by the study which saw a much higher rate (66% vs 12%) in the percutaneous cholecystostomy group given the lack of routine definitive cholecystectomy after percutaneous cholecystostomy.
The recurrent biliary complications after conservative methods of treatment of acute cholecystitis range from 12 to 29 percent in a study published by Mestral et al [2]. It is unlikely that the percutaneous cholecystostomy which is a temporizing measure would provide a long-term protection against recurrent biliary complications.
In addition, 43 patients (55%) in the cholecystectomy group and 41 patients (60%) in the percutaneous cholecystostomy group are in the ASA I And II categories as mentioned in this study. Under normal circumstances they would have qualified for definitive upfront cholecystectomy as per the Tokyo Guidelines 2018 [3].
In a meta-analysis by Elshaer et al [4] the rate of bile duct injury across 162464 cholecystectomies performed was noted to be 0.4%. Although common bile duct injury risk is known to be higher in the context of surgery in the setting of acute cholecystitis, in a study performed by Tornqvist et al [5] demonstrated that this was only seen in those with Grade II or Grade III cholecystitis based on the Tokyo Criteria for Severity with odds ratios of 2.41 and 8.43 respectively. For Grade I cases, there was no significant increased risk of injury (OR 0.96). We can see that the rate of biliary injury was 6 percent in this trial for those who were in the cholecystectomy arm, which although we do acknowledge is in the context of acute cholecystitis, this value is nevertheless not low.
A retrospective study published by our institution demonstrated that recurrent cholecystitis post percutaneous cholecystostomy was found to be 11.9% over a median follow up of 82 months [6]. 26 out of 71 patients (36%) underwent a planned interval cholecystectomy. Other studies such as those published by Horn et al [7] demonstrated a recurrence rate of 23.5% over a median period of 5 years. This closely mimics the results of the above-mentioned study which saw a recurrence rate of about 13% in the percutaneous group that represented with recurrent cholecystitis.
A Cochrane review published in 2013 [8] analysed randomised clinical trials (RCT) involving PC in acute calculous cholecystitis and included only two low quality studies with a total of 156 participants. It concluded that there was insufficient high-quality evidence to determine the role of PC in the management of high-risk surgical patients with AC.
The trial has ascertained that percutaneous cholecystostomy alone is insufficient in the context of acute cholecystitis but the opportunity to explore its role as an interim measure is lost.
Dr James Lee Wai Kit, MBBS, MRCS (Ed)
Assistant Professor Alfred Kow Wei Chieh, MBBS, M Med (Surgery), MRCS (Ed), MRCS (Ire), FRCSEd (Gen Surgery)
Associate Professor Iyer Shridhar Ganpathi (MBBS, MS, FRCS, FAMS)
Division of Hepatobiliary Surgery, Department of Surgery, National University Health System, Singapore
References
1. Loozen CS, van Santvoort HC, van Duijvendijk P, et al. Laparoscopic cholecystectomy versus percutaneous catheter drainage for acute cholecystitis in high risk patients (CHOCOLATE): multicentre randomised clinical trial. Bmj. 2018:k3965. doi:10.1136/bmj.k3965
2. de Mestral C, Rotstein OD, Laupacis A, Hoch JS, Zagorski B, Nathens AB. A population-based analysis of the clinical course of 10,304 patients with acute cholecystitis, discharged without cholecystectomy. J Trauma Acute Care Surg. 2013;74(1):26-30; discussion 30-1. doi:10.1097/TA.0b013e3182788e4d
3. Okamoto K, Suzuki K, Takada T, et al. Tokyo Guidelines 2018: flowchart for the management of acute cholecystitis. J Hepatobiliary Pancreat Sci. 2018;25(1):55-72. doi:10.1002/jhbp.516
4. Elshaer M, Gravante G, Thomas K, Sorge R, Al-Hamali S, Ebdewi H. Subtotal cholecystectomy for “Difficult gallbladders”: Systematic review and meta-analysis. JAMA Surg. 2015;150(2):159-168. doi:10.1001/jamasurg.2014.1219
5. Törnqvist B, Waage A, Zheng Z, Ye W, Nilsson M. Severity of Acute Cholecystitis and Risk of Iatrogenic Bile Duct Injury During Cholecystectomy, a Population-Based Case–Control Study. World J Surg. 2016;40(5):1060-1067. doi:10.1007/s00268-015-3365-1
6. Pang KW, Tan CHN, Loh S, et al. Outcomes of Percutaneous Cholecystostomy for Acute Cholecystitis. World J Surg. 2016;40(11):2735-2744. doi:10.1007/s00268-016-3585-z
7. Horn T, Christensen SD, Kirkegård J, Larsen LP, Knudsen AR, Mortensen F V. Percutaneous cholecystostomy is an effective treatment option for acute calculous cholecystitis: a 10-year experience. HPB (Oxford). 2015;17(4):326-331. doi:10.1111/hpb.12360
8. Gurusamy KS, Rossi M, Davidson BR. Percutaneous cholecystostomy for high-risk surgical patients with acute calculous cholecystitis. Cochrane Database Syst Rev. 2013. doi:10.1002/14651858.CD007088.pub2
Competing interests: No competing interests
We read with interest the results of this multicentre randomised controlled trial comparing laparoscopic cholecystectomy to percutaneous drainage in moderate to severe acute calculous cholecystitis in patients with an APACHE score of 7-11. The authors found that there are an increased number of major complications following percutaneous drainage compared with acute cholecystectomy. They advise acute cholecystectomy for ‘virtually all patients with moderate to severe calculous cholecystitis’. However, there are a number of considerations in interpreting their findings.
Firstly, only 142 of 790 patients with acute calculous cholecystitis initially assessed were eligible for inclusion in the study based on inclusion and exclusion criteria. As such, the findings are drawn from 18 percent of patients with this presentation and are therefore open to considerable selection bias.
Secondly, significant differences were only found in the ‘major complications’ criteria related to recurrent gallstone disease including recurrent cholecystitis and an increased need for operation in the percutaneous drainage group; no other major complication demonstrated a statistically significant difference between the two groups. This finding seems inevitable when comparing cholecystectomy to non-cholecystectomy, although we do note that elective routine cholecystectomy is excluded from the re-operation statistics.
Finally, the median operation difficulty was classed as 8/10 and conversion to open occurred in 17 percent of cases; which seems surprisingly high. In contrast, the rate of acute cholecystectomy conversion to open or primary open procedure in the prospective multicentre CholeS study was 7.3 percent, it should be noted that this included all patients undergoing emergency cholecystectomy for any indication and with a range of co-morbidities1.
In summary, this study will certainly not change practice at our centre. We have not historically used percutaneous drainage unless patients have very severe co-morbidities or other complex disease which precludes cholecystectomy; patient groups which were not included in this trial. We will therefore continue to use NICE guidance as our gold standard for the treatment of acute cholecystitis.
References:
1. CholeS Study Group, British Journal of Surgery 2016; 103: 1704–1715
Competing interests: No competing interests
We read the manuscript entitled “Laparoscopic cholecystectomy versus percutaneous catheter drainage for acute cholecystitis in high risk patients (CHOCOLATE): multicentre randomised clinical trial” with great interest (1). Percutaneous cholecystostomy (PC) is an alternative treatment to open or laparoscopic cholecystectomy and it has been defined as a safe and effective treatment for acute cholecystitis (AC) in patients who are critically ill and/or have multiple comorbidities (2). This is the first well designed, well-attended, prospective randomized trial for comparing PC and cholecystectomy, however, we thought that there are some evincible points on this paper.
Patients with APACHE II score ≥7 have been included to the study. We thought that this criterion may examine the patients’ general condition and critical parameters but couldn’t show the gallbladder’s condition or severity of local inflammation. The presence of imaging findings such as pericholecystic fluid, increased wall thickness, pericholecystic abscess, and distended gallbladder can affect the clinical course of the patient. These findings have an important role in the Tokyo Guidelines 2018 and the AAST grading system (3, 4). When evaluating the high rate of biliary injury rate in both groups and major complication rate after PC, additional selection criteria may be considered for precise patient selection.
In the study, interval cholecystectomy rate was low (15%) (5). We thought this may be associated with high major complication rate after PC.
In the management of AC, conversion to open surgery, subtotal cholecystectomy, top-down cholecystectomy should always be thought for reducing biliary injury rate and operation time especially in difficult cases.
In conclusion, we think prospective randomized trials have indisputably benefits to clinical approach but it may not answer all the questions in our minds (6).
Sabri Özden, M.D.
Sadettin Er, M.D.
Mesut Tez, M.D., Assoc. Prof.
Ankara Numune Training and Research Hospital, Department of General Surgey,
Talatpasa blvd, n: 44, 06100, Altindag, ANKARA/TURKEY
References:
1. Loozen CS, van Santvoort HC, van Duijvendijk P, Besselink MG, Gouma DJ, Nieuwenhuijzen GA, et al. Laparoscopic cholecystectomy versus percutaneous catheter drainage for acute cholecystitis in high risk patients (CHOCOLATE): multicentre randomised clinical trial. BMJ. 2018;363:k3965.
2. Sartelli M, Chichom-Mefire A, Labricciosa FM, Hardcastle T, Abu-Zidan FM, Adesunkanmi AK, et al. The management of intra-abdominal infections from a global perspective: 2017 WSES guidelines for management of intra-abdominal infections. World J Emerg Surg. 2017;12:29.
3. Hernandez M, Murphy B, Aho JM, Haddad NN, Saleem H, Zeb M, et al. Validation of the AAST EGS acute cholecystitis grade and comparison with the Tokyo guidelines. Surgery. 2018;163(4):739-46.
4. Miura F, Okamoto K, Takada T, Strasberg SM, Asbun HJ, Pitt HA, et al. Tokyo Guidelines 2018: initial management of acute biliary infection and flowchart for acute cholangitis. J Hepatobiliary Pancreat Sci. 2018;25(1):31-40.
5. Yeo CS, Tay VW, Low JK, Woon WW, Punamiya SJ, Shelat VG. Outcomes of percutaneous cholecystostomy and predictors of eventual cholecystectomy. J Hepatobiliary Pancreat Sci. 2016;23(1):65-73.
6. Smith GC, Pell JP. Parachute use to prevent death and major trauma related to gravitational challenge: systematic review of randomised controlled trials. Bmj. 2003;327(7429):1459-61.
Competing interests: No competing interests
Re: Laparoscopic cholecystectomy versus percutaneous catheter drainage for acute cholecystitis in high risk patients (CHOCOLATE): multicentre randomised clinical trial
It was interesting to read the results of the CHOCOLATE trial by Loozen et al(1) where they report their experience of comparing laparoscopic cholecystectomy with percutaneous catheter drainage as treatment for acute cholecystitis. Whilst their efforts in this regard are commendable, I feel comparison of these two techniques is flawed if seen as a treatment choice of acute cholecystitis. Percutaneous drainage is not the gold standard treatment of acute cholecystitis and is usually only employed when a cholecystectomy is not considered appropriate or possible be it for delayed presentation, extensive co morbidities, frailty or severe systemic illness. In such circumstances It is used in the acute setting where drainage & attention to organ support gets the patient over the acute episode. It is almost always used to buy time as a “bridge” to surgery or “survival” in cases where patient recovers from the acute episode and no definitive surgery is being considered.
This is supported by the data presented in this study(1) where 29% patients were “bridged to surgery” and had an elective cholecystectomy after an initial drainage procedure while another 91% were successfully bridged to “survival”.
This study also did not include patients having an APACHE2 score of 15 or more as explained by the authors as this group was deemed very high risk and a cholecystectomy was considered strongly contraindicated. Precisely this is the group who would perhaps benefit from a drainage procedure. If these 10 patients were also included in the analysis results would possibly be different.
Of the 790 patients assessed for eligibility only 142 were randomised and 134 (17%) were analysed. 71 (9%) patients declined and 174(22%) were not asked to participate, but no reason given as to why such a significant proportion was not invited or did not want to participate.
In conclusion, percutaneous drainage is not expected to cure stone disease and hence is not comparable to laparoscopic cholecystectomy, it may still have a limited but useful role as a bridging technique. It would be perhaps more appropriate to compare it with conservative or non-operative treatment.
1. Loozen CS, van Santvoort HC, van Duijvendijk P, Besselink MG, Gouma DJ, Nieuwenhuijzen GA, et al. Laparoscopic cholecystectomy versus percutaneous catheter drainage for acute cholecystitis in high risk patients (CHOCOLATE): multicentre randomised clinical trial. BMJ. 2018;363:k3965.
Competing interests: No competing interests