Can surgery be avoided in patients with symptomatic gallstone disease and no complications?BMJ 2019; 367 doi: https://doi.org/10.1136/bmj.l5709 (Published 11 October 2019) Cite this as: BMJ 2019;367:l5709
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As a practising surgeon I have found this commissioned paper intriguing in terms of evidence of uncertainty and embarked in reviewing the relevant original papers of the two Norwegian trials (reference 15 and 16 in the BMJ article). These two trials published in two different journals reported on patients recruited in the same interval of time (late 1991 (ref 15) /October 1991 (ref 16) for starting and mid 1994 (ref15) /May 1994 (ref 16) for end of recruitment) thus unclear if these were two completely different study populations.
The first paper (15) reported on 64 patients recruited over 3 years between 1991 and 1994 with a diagnosis of acute cholecystitis with one third of patients randomised to observation being operated within 3 years (only one patient from the observation group operated beyond 5 years).The study was underpowered by authors own admission and they stated: “We conclude that conservative management is an option in the elderly and frail. However, for the younger patients, for example, below 65 years of age, cholecystectomy will prevent further unwanted episodes of acute cholecystitis that may be medically compromising and consequently seems a reasonable choice in these patients”.
The second larger study (16) from the same group covers the same period 1991 -1994 expanding the number of recruited patients to 137 and the paper does not make clear if the 64 patients with acute cholecystitis reported in the first article (15) were excluded from this second one. In the observation group 50.7% underwent cholecystectomy all within 5 years with the authors concluding “Cholecystectomy was the preferred treatment after extended long-term follow-up, but conservative management for symptomatic gallstone disease is an alternative to surgery in the elderly”.
This is a very common sense conclusion for any practising surgeon managing patients with gallstone disease. We should also not forget that 1990s’ were the beginning of the laparoscopic cholecystectomy and since then this procedure has been standardised and perfected, albeit still carries risk of complications.
The authors of the BMJ paper use these two underpowered and possibly double reported studies to introduce the concept of uncertainty of management options and to introduce the C-Gall trial (looking at laparoscopic cholecystectomy versus pain relief and generic life-style in 430 UK patients with the aim to identify those who may benefit from non-surgical approach).
While a well conceived RCT is the best way to answer a question, in gallstone disease there is evidence from a large cohort study (1) which offers the answers needed in day to day practice, both for primary and secondary care.
In this Danish cohort 664 patients diagnosed on ultrasound with incidental gallstone disease were observed for a median of 17.4 years without being informed of the diagnosis. More than 4 out of 5 participants with gallstones remained uneventful during the 20-year follow-up period with a cumulative incidence of uncomplicated events (biliary colic) of 11% and complicated events (cholecystitis, pancreatitis and common bile duct stones) of 8%. The study demonstrated that patients in age group 30-40 and 40-50 had significantly more events when compared with the oldest group (60-70).
Determinants of clinical events over a 10-year period were female sex, young age, awareness of gallstones, and large, multiple and older stones (over 5 years old). In a prediction score derived from this study the person who had the highest risk for an event was the female with multiple and large stones and she had an 11 times greater relative risk of cholecystectomy or complications over 10 years when compared with a male with a single gallstone of no more than 10 mm in size.
The authors of the BMJ paper mix together in the same group patients with symptomatic uncomplicated gallstones (i.e. biliary colic) and patient with acute cholecystitis in terms of management uncertainty and this is a controversial concept. The vast majority of studies regard acute cholecystitis as a complication or a significant gallstone related event as requires active intervention with admission and antibiotic treatment and surgery in fit patients. This paper is rather singular in mixing acute cholecystitis with symptomatic uncomplicated gallstones for purpose of discussing management options.
The quoted UK run C-Gall trial competes to some extent with SECURE – a Dutch trial including patient with biliary colic only (acute cholecystitis excluded) and with a follow up of 12 months 2, both trials with a shorter follow-up compared to studies already reported.
If observation with pain relief plus anti-inflammatory in acute cholecystitis is considered a treatment arm versus laparoscopic cholecystectomy, one may raise the ethical question of offering a treatment option with a predicted failure rate of 45% at 5 years (45% of patients randomised to observation required surgery, almost all within 5 years, in the combined analysis undertaken in the BMJ article).
The economic reference is rather crude as the quoted NHS cost for a laparoscopic cholecystectomy of £2700 is for the standard simple day case/overnight stay. A hospital cost per day in the NHS was £222 in 2018 and in acute cholecystitis the length of stay averages 7 days in UK. In the CholeS study quoted by authors (ref 12 in original paper) 37% of the patients who underwent cholecystectomy had at least one previous admission with gallstone related events, adding to the total cost of definitive treatment. In addition, gallstones related sick leave in the working age population is difficult if not impossible to capture accurately and this introduces bias in cost-effectiveness analysis.
At a time when the Royal College of Surgeons has launched the quality improvement project CholeQuIC-ER aiming to streamline the treatment of acute cholecystitis across England, it is likely that the majority of surgical units will look at its recommendations for adoption in daily practice.
I would suggest that we already know what to tell our patients: if one is 30-60 years old with a previous episode of acute cholecystitis, the chance of readmission and surgery within 5 years is almost 50%, making it a very common event according to C-Gall trial own definition. As it is very common to be readmitted and operated for recurrent significant gallstone related events, it is common sense to consider removal of gallbladder after the first episode of cholecystitis in a patient fit for surgery. It is unlikely that current research will make us any wiser or patients will make different choices in such a scenario in the future.
1 Shabanzadeh DM, Sorensen LT, Jorgensen T. A Prediction Rule for Risk Stratification of Incidentally Discovered Gallstones: Results from a Large Cohort Study. Gastroenterology, 2016; 150:156-167.
2 de Reuver RR, van Dijk AH, Wennmacker SZ etal. A randomized controlled trial to compare a restrictive strategy to usual care for the effectiveness of cholecystectomy in patients with symptomatic gallstones (SECURE trial protocol). BMC Surg. 2016; 16: 46.
Competing interests: No competing interests
Brazzelli et al rightly state some patients continue to experience symptoms after cholecystectomy. This is important and needs to be factored into how we approach the problem and advise our patients. There are a number of scenarios:
1) Gallstones found with no typical symptoms - an incidentaloma
2) Gallstones not found despite highly suggestive symptoms - a wide differential diagnosis for other causes.
3) Gallstones found with highly suggestive symptoms which are due to the gallstones - might benefit from surgery - the focus of the article.
4) Gallstones with highly suggestive symptoms which are not due to the gallstones - surgery will not help but will carry the predictable associated risks and harms.
I have seen many patients with Scenario 4) - a miserable and frustrated lot usually; whilst I had a Scenario 2) experience many years ago when many colleagues and friends all insisted I get an ultrasound scan - which was negative. I am now sure my differential was cramp in the anterior abdominal muscles.
Better history taking, clinical examination and diagnostic tests might be the answer to the uncertainties described.
Competing interests: No competing interests
This article raises some interesting uncertainties and is well presented. However why does my heart sink when I read it?
Firstly, because no patient perspective was sought in its production.
Secondly, because, although the figure of 55% of patients not needing surgery is quoted, the authors do downplay the fact that a significant number continue to have biliary pain. (Ask a few patients what that is like.)
But, thirdly, and more worryingly, I can see rogue clinical commissioning groups selectively quoting the data to justify adding cholecystectomy to their lists of “procedures of limited clinical value”. The law of unintended consequences, I suggest.
Competing interests: No competing interests