Abstract
Introduction
Of people admitted to hospital for biliary tract disease, 20% have acute cholecystitis. Up to the age of 50 years, acute calculous cholecystitis is three times more common in women than in men, and about 1.5 times more common in women than in men thereafter. About 95% of people with acute cholecystitis have gallstones. Optimal therapy for acute cholecystitis, based on timing and severity of presentation, remains controversial.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for acute cholecystitis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to December 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 12 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: early cholecystectomy, laparoscopic cholecystectomy, minilaparoscopic cholecystectomy, observation alone, and open cholecystectomy.
Key Points
Acute cholecystitis causes unremitting right upper quadrant pain, anorexia, nausea, vomiting, and fever, and if untreated can lead to perforations, abscess formation, or fistulae.
About 95% of people with acute cholecystitis have gallstones.
It is thought that blockage of the bile duct by a gallstone or local inflammation can lead to acute cholecystitis, but we don't know whether bacterial infection is also necessary.
Early cholecystectomy within 7 days of onset of symptoms is the treatment of choice for acute cholecystitis.
Early surgery reduces the duration of hospital admission compared with delayed surgery, but does not reduce mortality or complications.
Up to a quarter of people scheduled for delayed surgery may require urgent operations because of recurrent or worsening symptoms.
Laparoscopic cholecystectomy reduces the duration of admission and may improve intraoperative and postoperative outcomes compared with open cholecystectomy, but increases the risk of bile duct injury.
Up to a quarter of people having laparoscopic cholecystectomy may need conversion to open surgery because of risks of complications or uncontrolled bleeding.
We don't know whether minilaparoscopic surgery leads to further reductions in duration of admission or improved outcomes compared with laparoscopic surgery.
About this condition
Definition
Acute cholecystitis results from obstruction of the cystic duct, usually by a gallstone, followed by distension and subsequent chemical or bacterial inflammation of the gallbladder. People with acute cholecystitis usually have unremitting right upper quadrant pain, anorexia, nausea, vomiting, and fever. About 95% of people with acute cholecystitis have gallstones (calculous cholecystitis) and 5% lack gallstones (acalculous cholecystitis). Severe acute cholecystitis may lead to necrosis of the gallbladder wall, known as gangrenous cholecystitis. This review does not include people with acute cholangitis, which is a severe complication of gallstone disease and generally a result of bacterial infection.
Incidence/ Prevalence
The incidence of acute cholecystitis among people with gallstones is unknown. Of people admitted to hospital for biliary tract disease, 20% have acute cholecystitis. The number of cholecystectomies carried out for acute cholecystitis increased from the mid 1980s to the early 1990s, especially in elderly people. Acute calculous cholecystitis is three times more common in women than in men up to the age of 50 years, and is about 1.5 times more common in women than in men thereafter.
Aetiology/ Risk factors
Acute calculous cholecystitis seems to be caused by obstruction of the cystic duct by a gallstone, or local mucosal erosion and inflammation caused by a stone, but cystic duct ligation alone does not produce acute cholecystitis in animal studies. The role of bacteria in the pathogenesis of acute cholecystitis is not clear; positive cultures of bile or gallbladder wall are found in 50-75% of cases. The cause of acute acalculous cholecystitis is uncertain and may be multifactorial, including increased susceptibility to bacterial colonisation of static gallbladder bile.
Prognosis
Complications of acute cholecystitis include perforation of the gallbladder, pericholecystic abscess, and fistula caused by gallbladder wall ischaemia and infection. In the USA, the overall mortality from untreated complications is about 20%.
Aims of intervention
To reduce mortality and morbidity associated with acute cholecystitis, with minimal adverse effects of treatment.
Outcomes
Mortality, persistent pain, intolerance to food, recurrent attacks of cholecystitis, quality of life, and adverse effects of treatment. Some outcomes relate to surgery: duration of surgery, need for nasogastric tube, analgesic use, antibiotic requirement, rate of surgical complications (bile duct injuries, pancreatitis, other), and duration of hospital stay. Postoperative fall in haemoglobin and conversion of a planned laparoscopic cholecystectomy to an open cholecystectomy are surrogate outcomes.
Methods
Clinical Evidence search and appraisal December 2006. Two of the RCTs explicitly stated that participants had calculous cholecystitis. The remaining RCTs did not report whether participants had calculous or acalculous cholecystitis. The RCTs excluded people unable to have surgery because of comorbid conditions (recent MI, severe chronic obstructive pulmonary disease or respiratory insufficiency, end-stage metastatic disease, and multisystem organ failure) and contraindications for cholecystectomy (e.g. use of antiplatelet treatment that could not safely be discontinued during the perioperative period). The following databases were used to identify studies for this systematic review: Medline 1966 to December 2006, Embase 1980 to December 2006, and The Cochrane Library (all databases) 2006, Issue 4. Additional searches were carried out using these websites: NHS Centre for Reviews and Dissemination (CRD) (all databases), Turning Research into Practice (TRIP), and NICE. Abstracts of the studies retrieved from the initial search were assessed by an information specialist. Selected studies were then sent to the author for additional assessment, using pre-determined criteria to identify relevant studies. Study design criteria for inclusion in this review were: published systematic reviews and RCTs in any language with any level of blinding including ‘open’ studies. The maximum loss to follow-up allowed was 20%. There was no minimum number of participants or length of follow-up required to include studies. In addition, we use a regular surveillance protocol to capture harms alerts from organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA), which are added to the reviews as required. We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table ). To aid readability of the numerical data in our reviews, we round percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as RRs and ORs.
Table.
GRADE evaluation of interventions for acute cholecystitis
| Important outcomes | Pain relief, recurrent attacks, mortality, duration of hospital stay, adverse effects | ||||||||
| Number of studies (participants) | Outcome | Comparison | Type of evidence | Quality | Consistency | Directness | Effect size | GRADE | Comment |
| What are the effects of treatments for acute cholecystitis? | |||||||||
| 16 (At least 1255) | Mortality | Early v delayed cholecystectomy | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for incomplete reporting of results. Directness point deducted for differences in surgeon expertise |
| 16 (At least 1255) | Morbidity | Early v delayed cholecystectomy | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for incomplete reporting of results. Directness point deducted for differences in surgeon expertise |
| 18 (At least 1255) | Duration of hospital stay | Early v delayed cholecystectomy | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for incomplete reporting of results. Directness point deducted for differences in surgeon expertise |
| 1 (145) | Quality of life | Early v delayed cholecystectomy | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| 1 (70) | Duration of hospital stay | Percutaneous cholecystostomy followed by early cholecystectomy v medical treatment followed by delayed cholecystectomy | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and no intention-to-treat analysis |
| 1 (70) | Symptom improvement | Percutaneous cholecystostomy followed by early cholecystectomy v medical treatment followed by delayed cholecystectomy | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and no intention-to-treat analysis |
| 4 (606) | Duration of hospital stay | Laparoscopic cholecystectomy v open cholecystectomy | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for incomplete reporting of results. Directness point deducted for population differences |
| 4 (606) | Duration of surgery | Laparoscopic cholecystectomy v open cholecystectomy | 4 | –1 | –1 | –2 | 0 | Very low | Quality point deducted for incomplete reporting of results. Consistency point deducted for conflicting results. Directness points deducted for population differences and differences in techniques |
| 4 (601) | Postoperative complications | Laparoscopic cholecystectomy v open cholecystectomy | 4 | –1 | –1 | –2 | 0 | Very low | Quality point deducted for incomplete reporting of results. Consistency point deducted for conflicting results. Directness points deducted for population differences and differences in techniques |
| 1 (69) | Duration of hospital stay | Conventional laparoscopic cholecystectomy v minilaparoscopic cholecystectomy | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| 1 (69) | Conversion rates | Minilaparoscopic cholecystectomy v conventional laparoscopic cholecystectomy | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| 1 (69) | Use of analgesia | Minilaparoscopic cholecystectomy v conventional laparoscopic cholecystectomy | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| 1 (69) | Duration of surgery | Minilaparoscopic cholecystectomy v conventional laparoscopic cholecystectomy | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| 1 (64) | Failure rates | Observation alone v laparoscopic cholecystectomy | 4 | -1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
| 1 (64) | Gallstone-related complications | Observation alone v laparoscopic cholecystectomy | 4 | -1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
Type of evidence: 4 = RCT; 2 = Observational; 1 = Non-analytical/expert opinion. Consistency: similarity of results across studies. Directness: generalisability of population or outcomes. Effect size: based on relative risk or odds ratio.
Glossary
- Laparoscopic cholecystectomy
Laparoscopic cholecystectomy involves removal of the gallbladder using a projection camera and 5–10 mm trocar ports. Conversion from laparoscopic to open cholecystectomy is needed if the laparoscopic procedure cannot be completed without risking injury to surrounding structures or when bleeding cannot be stopped. Open cholecystectomy is required in people who have a fistula from the gallbladder into the bile duct or intestine, and in some people who have perforation and abscess in the right upper quadrant.
- Low-quality evidence
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.
- Minilaparoscopic cholecystectomy
involves removal of the gallbladder using a projection camera and 2–3 mm trocar ports.
- Moderate-quality evidence
Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
- Open cholecystectomy
Open cholecystectomy involves removal of the gallbladder by laparotomy. Open cholecystectomy is required in people who have a fistula from the gallbladder into the bile duct or intestine, and in some people who have perforation and abscess in the right upper quadrant.
- Very low-quality evidence
Any estimate of effect is very uncertain.
Disclaimer
The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients.To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.
Contributor Information
Elizabeth Fialkowski, Washington University School of Medicine, Washington, USA.
Dr Valerie Halpin, Washington University School of Medicine, St Louis, MO, USA.
Dr Robb R Whinney, Washington University School of Medicine, St Louis, MO, USA.
References
- 1.Indar AA, Beckingham IJ. Acute cholecystitis. BMJ 2002;325:639–643. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Diettrick NA, Cacioppo JC, Davis RP. The vanishing elective cholecystectomy. Arch Surg 1988;810:123–126. [DOI] [PubMed] [Google Scholar]
- 3.Fukunaga FH. Gallbladder bacteriology, histology and gallstones: study of unselected cholecystectomy specimens in Honolulu. Arch Surg 1973;169:106–110. [DOI] [PubMed] [Google Scholar]
- 4.Lou MA, Mandal AK, Alexander JL, et al. Bacteriology of the human biliary tract and the duodenum. Arch Surg 1997;965:112–116. [DOI] [PubMed] [Google Scholar]
- 5.Isch JH, Finnernan JC, Nahrwold DL. Perforation of the gallbladder. Am J Gastroenterol 1971;55:451–458. [PubMed] [Google Scholar]
- 6.Johansson M, Thune A, Nelvin L, et al. Randomized clinical trial of open versus laparoscopic cholecystectomy in the treatment of acute cholecystitis. Br J Surg 2005;92:44–49. [DOI] [PubMed] [Google Scholar]
- 7.Akyurek N, Salman B, Yuksel O, et al. Management of acute calculous cholecystitis in high-risk patients: percutaneous cholecystotomy followed by early laparoscopic cholecystectomy. Surg Laparosc Endosc Percutan Tech 2005;15:315–320. [DOI] [PubMed] [Google Scholar]
- 8.Papi C, Catarci M, D'Ambrosio L, et al. Timing of cholecystectomy for acute calculous cholecystitis: a meta-analysis. Am J Gastroenterol 2004;99:147–155. Search date 2001; primary sources Medline, Embase, CancerLit, Healthstar, Cochrane Library, and hand searches of reference lists. [DOI] [PubMed] [Google Scholar]
- 9.Shikata S, Noguchi Y, Fukui T. Early versus delayed cholecystectomy for acute cholecystitis: a meta-analysis of randomized controlled trials. Surg Today 2005;35:553–560. Search date 2003; primary sources Cochrane Register of Controlled Trials, Medline, and refence lists of papers and reviews. [DOI] [PubMed] [Google Scholar]
- 10.Gurusamy KS, Samraj K. Early versus delayed laparoscopic cholecystectomy for acute cholecystitis. In: The Cochrane Library, Issue 4, 2006. Chichester, UK: John Wiley & Sons, Ltd. Search date November 2005. [DOI] [PubMed] [Google Scholar]
- 11.Johansson M, Thune A, Blomqvist A, et al. Impact of choice on therapeutic strategy on patient's health-related quality of life. Results of a randomized, controlled clinical trial. Dig Surg 2004;21:359–362. [DOI] [PubMed] [Google Scholar]
- 12.Jarvinen HJ, Hastbacka J. Early cholecystectomy for acute cholecystitis. Ann Surg 1980;191:501–505. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Norrby S, Herlin P, Holmin T, et al. Early or delayed cholecystectomy in acute cholecystitis? A clinical trial. Br J Surg 1983;70:163–165. [DOI] [PubMed] [Google Scholar]
- 14.Lai BS, Kwong KH, Leung KL, et al. Randomized trial of early versus delayed laparoscopic cholecystectomy for acute cholecystitis. Br J Surg 1998;85:764–767. [DOI] [PubMed] [Google Scholar]
- 15.Lo CM, Liu CL, Fan ST, et al. Prospective randomized study of early versus delayed laparoscopic cholecystectomy for acute cholecystitis. Ann Surg 1998;227:461–467. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Eldar S, Sabo E, Nash E, et al. Laparoscopic versus open cholecystectomy in acute cholecystitis. Surg Laparosc Endosc 1997;7:407–414. [PubMed] [Google Scholar]
- 17.Kiviluoto T, Siren J, Luukkonen P, et al. Randomised trial of laparoscopic versus open cholecystectomy for acute and gangrenous cholecystitis. Lancet 1998;351:321–325. [DOI] [PubMed] [Google Scholar]
- 18.Schiedeck THK, Schulte T, Gunarsson R, et al. Laparoscopic cholecystectomy in acute cholecystitis. Minim Invasive Chirurg 1997;6:48–51. [Google Scholar]
- 19.Hsieh CH. Early minilaparoscopic cholecystectomy in patients with acute cholecystitis. Am J Surg 2003;185:344–348. [DOI] [PubMed] [Google Scholar]
- 20.Shea JA, Healey MJ, Berlin JA, et al. Mortality and complications associated with laparoscopic cholecystectomy: a meta-analysis. Ann Surg 1996;224:609–620. Search date 1995; primary sources Medline and hand searches of bibliographies. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Vetrhus M, Berhane T, Soreide O, et al. Pain persists in many patients five years after removal of the gallbladder: observations from two randomized controlled trials of symptomatic, noncomplicated gallstone disease and acute cholecystitis. J Gastrointest Surg 2005;9:826–831. [DOI] [PubMed] [Google Scholar]
- 22.Vetrhus M, Soreide O, Nesvik I, et al. Acute cholecystitis: delayed surgery or observation. A randomized clinical trial. Scand J Gastroenterol 2003;38:985–990. [DOI] [PubMed] [Google Scholar]
