Appendicitis

Abstract

Introduction

Appendicitis is an inflammation of the appendix that may lead to an abscess, ileus, peritonitis, or death if untreated. Appendicitis is the most common abdominal surgical emergency. The current standard treatment of uncomplicated appendicitis is usually surgery, but there has been increasing evidence published on the use of antibiotics.

Methods and outcomes

We conducted a systematic review and aimed to answer the following clinical question: What are the effects of surgery compared with antibiotics for acute appendicitis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2014 (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 four 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 surgery (including laparoscopic and open appendicectomy) compared with antibiotics.

Key Points

Appendicitis is inflammation of the appendix that may lead to an abscess, ileus, peritonitis, or death, if untreated.

Appendicitis is the most common abdominal surgical emergency.

The current standard treatment for uncomplicated appendicitis is usually surgical removal of the appendix (appendicectomy), but there has been increasing evidence published on the use of antibiotics.

The evidence comparing surgery with antibiotics is weak and confounded by factors such as inconsistencies with results and outcomes measured, which makes it difficult to compare these interventions.

Appendicectomy may be associated with reduced overall treatment failure (including recurrence requiring surgery within 1 year) in the treatment of adults with acute appendicitis, but may also be associated with an increase in complications and sick days compared with antibiotics.

• We don’t know whether appendicectomy and antibiotics differ with regard to hospital stay, or in improving quality of life scores.

• We found no studies reporting outcomes beyond 1 year, which is a major limitation of the available evidence.

• All of the evidence we found was in adults; we found no RCTs in children.

At present, the weight of evidence does not suggest that antibiotics are superior to surgery for treating appendicitis.

There is a lack of high-quality RCTs comparing what might be termed optimal current surgical techniques with optimal current antibiotic regimens. Further trials are currently under way, which may provide further information on how current surgical techniques compare with current antibiotic regimens when both treatment approaches are optimised.

About this condition

Definition

Appendicitis is inflammation of the vermiform appendix. Progression of the inflammatory process can lead to abscess, ileus, peritonitis, or death if untreated. The term 'complicated' appendicitis refers to the presence of gangrene or perforation of the appendix. Free perforation into the peritoneal cavity can lead to purulent or faeculent peritonitis. A contained perforation can lead to appendix abscess or phlegmon (inflammatory mass).

Incidence/ Prevalence

Appendicitis is the most common abdominal surgical emergency. The reported lifetime risk of appendicitis in the US is 8.6% in men and 6.7% in women, with an annual incidence of 9.38 per 100,000. In the US, it is estimated that around 326,000 operations for appendicitis were performed in 2007. In the UK, around 42,000 to 47,000 operations for appendicitis were performed yearly between 2007 and 2012. Large studies from the UK and US have shown that complicated appendicitis is found at surgery in around 16.5% to 24.4% of cases.

Aetiology/ Risk factors

The cause of appendicitis is uncertain, although various theories exist. The predominant theories centre on luminal obstruction of the blind-ending appendix as the primary pathology. When goblet cell secretions are blocked from escaping by the luminal obstruction, the intra-luminal pressure within the appendix increases and leads to ischaemia of the appendix wall. The translocation of bacteria from the lumen across the compromised mucosa causes transmural inflammation. Ongoing tissue ischaemia and inflammation can then lead to infarction and perforation of the appendix (complicated appendicitis). Free perforation will lead to soiling of the intra-peritoneal cavity with pus or faeces. A perforation can also be enclosed by the surrounding soft tissues (omentum, mesentery, or bowel), thus leading to the development of an inflammatory mass. This inflammatory mass may contain pus (abscess) or it may not (phlegmon). There is some debate as to whether perforated appendicitis is a disease process distinct from uncomplicated appendicitis. Hyperplasia of the lymphoid tissue in the mucosa or submucosa has been posited as the most common mechanism causing obstruction of the appendix lumen. This may present with acute catarrhal appendicitis, with a gradual onset of symptoms. Lymphoid hyperplasia may be caused by infections (bacterial, viral, fungal, parasitic) or by inflammation, such as in inflammatory bowel disease. Other, rarer causes of obstruction may include parasites (more common in developing countries), fibrous bands, foreign bodies, or carcinoid and caecal carcinoma. A more abrupt course of symptoms has been described in acute obstructive appendicitis from faecoliths.

Prognosis

The prognosis of untreated appendicitis is unknown, since RCTs comparing treatment with no treatment would be unethical. Spontaneous resolution rate of radiologically confirmed appendicitis has been reported to range from around 4% to 20%. However, spontaneous resolution and recurrence of appendicitis (the 'grumbling appendix') remains a contentious issue among surgeons. The current standard treatment for uncomplicated appendicitis is usually surgical removal of the appendix (appendicectomy) to prevent potential complications from untreated appendicitis. There has been increasing evidence published on the use of antibiotics. Surgical treatment is performed either through an incision (open appendicectomy) or using keyhole surgery (laparoscopic appendicectomy). One systematic review found that wound infection was less likely with laparoscopic appendicectomy compared with open appendicectomy (OR 0.43, CI 0.34 to 0.54), but intra-abdominal abscess formation was more likely with laparoscopic appendicectomy (OR 1.87, CI 1.19 to 2.93). The incidences of both wound infection and abscess formation appear to be higher in complicated appendicitis. A perforated appendix in childhood does not seem to have subsequent negative consequences for female fertility.

Aims of intervention

To resolve acute symptoms (e.g., pain) with minimal adverse effects; to prevent the need for surgery (after antibiotics); to prevent postoperative complications, such as wound infection (after surgery); to shorten hospital stay; and to hasten return to normal activity.

Outcomes

Treatment success discharge from hospital without surgery (for antibiotics), post-treatment complications (e.g., wound infection from surgery; and perforation and peritonitis from antibiotics), treatment failure; mortality from appendicitis; length of hospital stay; return to normal activities (including sick leave days); quality of life; and adverse effects (including recurrence).

Methods

Clinical Evidence search and appraisal May 2014. The following databases were used to identify studies for this systematic review: Medline 1966 to May 2014, Embase 1980 to May 2014, and The Cochrane Database of Systematic Reviews 2014, issue 4 (1966 to date of issue). Additional searches were carried out in the Database of Abstracts of Reviews of Effects (DARE) and the Health Technology Assessment (HTA) database. We also searched for retractions of studies included in the review. Titles and abstracts identified by the initial search, run by an information specialist, were first assessed against predefined criteria by an evidence scanner. Full texts for potentially relevant studies were then assessed against predefined criteria by an evidence analyst. Studies selected for inclusion were discussed with an expert contributor. All data relevant to the review were then extracted by an evidence analyst. Study design criteria for inclusion in this review were: published RCTs and systematic reviews of RCTs in the English language, at least single-blinded (where possible), and containing 20 or more people (10 or more in each arm) with uncomplicated acute appendicitis or appendix abscess (excluding perforated appendicitis), of whom more than 80% were followed up. There was no minimum length of follow-up. We excluded all studies described as 'open', 'open label', or not blinded unless blinding was impossible. We included RCTs and systematic reviews of RCTs where harms of an included intervention were assessed, applying the same study design criteria for inclusion as we did for benefits. All serious adverse effects or those adverse effects that are reported as statistically significant were data extracted for inclusion in the harms table of the review. Pre-specified adverse effects identified as being clinically important were reported, even if the results were not statistically significant. In addition, we use a regular surveillance protocol to capture harms alerts from organisations such as the FDA and the MHRA that are added to the reviews as required. To aid readability of the numerical data in our reviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as RRs and ORs. We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).

Table.

GRADE Evaluation of interventions for Appendicitis.

Important outcomes	Length of hospital stay, Mortality (from appendicitis), Quality of life, Return to normal activities, Treatment success
Studies (Participants)	Outcome	Comparison	Type of evidence	Quality	Consistency	Directness	Effect size	GRADE	Comment
What are the effects of surgery compared with antibiotics for acute appendicitis?
at least 4 (at least 900)	Treatment success	Surgery versus antibiotics	4	–3	–1	–2	0	Very low	Quality points deducted for weak methods (unclear allocation concealment, blinding, and randomisation), uncertainty of diagnosis, and incomplete reporting of results; consistency point deducted for significant heterogeneity and different outcome measures; directness points deducted for unclear clinical generalisability (unclear if antibiotics used with surgery, no comparison of optimal therapies, no outcomes beyond 1 year, predominantly males, adults only)
5 (at least 900)	Mortality (from appendicitis)	Surgery versus antibiotics	4	–3	0	–2	0	Very low	Quality points deducted for weak methods (unclear allocation concealment, blinding, and randomisation), uncertainty of diagnosis, and incomplete reporting of results; directness points deducted for unclear clinical generalisability (unclear if antibiotics used with surgery, no comparison of optimal therapies, no outcomes beyond 1 year, predominantly males, adults only)
at least 4 (at least 821)	Length of hospital stay	Surgery versus antibiotics	4	–3	0	–2	0	Very low	Quality points deducted for weak methods (unclear allocation concealment, blinding, and randomisation), and uncertainty of diagnosis; directness points deducted for unclear exclusion of trial, and unclear clinical generalisability (unclear if antibiotics used with surgery, no comparison of optimal therapies, no outcomes beyond 1 year, predominantly males, adults only)
at least 3 (at least 491)	Return to normal activities	Surgery versus antibiotics	4	–3	0	–2	0	Very low	Quality points deducted for weak methods (unclear allocation concealment, blinding, and randomisation) and uncertainty of diagnosis; directness points deducted for unclear clinical generalisability (unclear if antibiotics used with surgery, no comparison of optimal therapies, no outcomes beyond 1 year, predominantly males, adults only)

We initially allocate 4 points to evidence from RCTs, and 2 points to evidence from observational studies. To attain the final GRADE score for a given comparison, points are deducted or added from this initial score based on preset criteria relating to the categories of quality, directness, consistency, and effect size. Quality: based on issues affecting methodological rigour (e.g., incomplete reporting of results, quasi-randomisation, sparse data [<200 people in the analysis]). Consistency: based on similarity of results across studies. Directness: based on generalisability of population or outcomes. Effect size: based on magnitude of effect as measured by statistics such as relative risk, odds ratio, or hazard ratio.

Glossary

Negative appendix at histology

Term used to describe an appendix that has been surgically removed as a result of suspected appendicitis, but is then found to be normal on histological evaluation.

Phlegmon

Inflammatory, soft tissue mass (often palpable) enclosing an inflamed appendix with no drainable pus.

Uncomplicated appendicitis

Inflamed appendix without necrosis, gangrene, perforation, or abscess, and with no peritoneal contamination.

Very low-quality evidence

Any estimate of effect is very uncertain.

Disclaimer

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