Digestive system disorders

Appendicitis
Search date November 2006 David Humes, William Speake, and John Simpson QUESTIONS What are the effects of treatments for acute appendicitis?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 INTERVENTIONS TREATMENTS Beneficial Surgery plus antibiotics . . . . . . . . . . . . . . . . . . . . . . 2 Likely to be beneficial Laparoscopic surgery versus open surgery (in children). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Trade off between benefits and harms Antibiotics versus surgery. . . . . . . . . . . . . . . . . . . . . 5 Laparoscopic surgery versus open surgery (in adults). . 3 Key Points The incidence of acute appendicitis is falling, although the reasons are unclear. The lifetime risk is approximately 79% in the USA, making appendicectomy the most common abdominal surgical emergency. Potential causes of appendicitis include faecoliths, lymphoid hyperplasia, and caecal carcinoma, all of which can lead to obstruction of the appendix lumen. Mortality from acute appendicitis is less than 0.3%, but rises to 1.7% after perforation. Spontaneous resolution of acute appendicitis has been reported in at least 8% of episodes. Very limited evidence suggests that conservative treatment of acute appendicitis with antibiotics may reduce pain and morphine consumption, but that a third of people are likely to be readmitted with acute appendicitis requiring surgery within 1 year. Standard treatment for acute appendicitis is appendicectomy. Clinical trials to compare surgery with no surgery would be considered unethical, and have not been done. There is some evidence that laparoscopic appendicectomy in adults reduces wound infections, postoperative pain, duration of hospital stay, and time off work compared with open surgery, but may increase the risk of intraabdominal abscesses. Limited evidence suggests that laparoscopic surgery in children may reduce wound infections and duration of hospital stay compared with open surgery, but it has not been shown to reduce other complications. The most common complication of appendicectomy is wound infection, with intra-abdominal abscess formation less common. Treatment with surgery plus antibiotics reduces wound infections and intra-abdominal abscesses compared with surgery alone in adults with simple or complicated appendicitis. However, in children, the benefit of antibiotics may be limited to those with complicated appendicitis. DEFINITION INCIDENCE/ PREVALENCE Acute appendicitis is acute inflammation of the vermiform appendix. The incidence of acute appendicitis is falling, although the reason is unclear. The reported lifetime [1] risk of appendicitis in the USA is 8.7% in men and 6.7% in women, and about 35,000 cases are [2] reported annually in England. Appendicitis is the most common abdominal surgical emergency requiring operation. 4 Unknown effectiveness Antibiotics (versus no treatment / placebo). . . . . . . . 6 Surgery (versus no treatment). . . . . . . . . . . . . . . . . . 6 Likely to be ineffective or harmful Stump inversion at open appendicectomy versus simple ligation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 To be covered in future updates Antibiotic regimens and dosages for appendicectomy

AETIOLOGY/ The cause of appendicitis is uncertain, although various theories exist. Most relate to luminal obRISK FACTORS struction, which prevents escape of secretions, and inevitably leads to a rise in intraluminal pressure within the appendix. This can lead to subsequent mucosal ischaemia, and the stasis provides an
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ideal environment for bacterial overgrowth. Potential causes of the obstruction are faecoliths (often [3] because of constipation), lymphoid hyperplasia, or caecal carcinoma. PROGNOSIS The prognosis of untreated appendicitis is unknown, although spontaneous resolution has been [4] reported in at least 1/13 (8%) episodes. The recurrence of appendicitis after conservative [4] [5] [6] management, and recurrent abdominal symptoms in certain people suggest that chronic [7] appendicitis and recurrent acute or subacute appendicitis may also exist. The standard treatment for acute appendicitis is appendicectomy. RCTs comparing treatment versus no treatment would be regarded as unethical. The mortality from acute appendicitis is less than 0.3%, rising to 1.7% [8] after perforation. The most common complication of appendicectomy is wound infection, occurring [9] in 533% of cases. Intra-abdominal abscess formation occurs less frequently, in 2% of appen[10] dicectomies. A perforated appendix in childhood does not seem to have subsequent negative [11] consequences for female fertility.

AIMS OF To reduce pain; prevent postoperative infection; shorten hospital stay; and hasten return to normal INTERVENTION activity. OUTCOMES Wound infection rates, intra-abdominal infection rates, postoperative pain, postoperative fever, length of operation, length of hospital stay, return of bowel function, time to return to normal activities, mortality. BMJ Clinical Evidence search and appraisal November 2006. The following databases were used to identify studies for this review: Medline 1966 to November 2006, Embase 1980 to November 2006, and The Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Clinical Trials 2006, Issue 4. Additional searches were carried out using these websites: NHS Centre for Reviews and Dissemination (CRD) for Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA), Turning Research into Practice (TRIP), and National Institute for Health and Clinical Excellence (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 predetermined criteria to identify relevant studies. Study design criteria for evaluation in this review were: published systematic reviews and RCTs in any language, at least single-blinded, and containing any number of individuals, of whom more than 80% were followed up. There was no minimum length of follow-up required to include studies. We excluded all studies described as open, open label, or not blinded unless blinding was impossible. We also did a search for cohort studies on specific harms of named interventions. 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 review as required. We have performed a GRADE evaluation of the quality of evidence for interventions included in this review ( see table, p 9 ). What are the effects of treatments for acute appendicitis? SURGERY PLUS ANTIBIOTICS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

METHODS

QUESTION OPTION

Wound infections Compared with surgery plus placebo or alone Surgery plus antibiotics may reduce wound infections in adults compared with surgery alone ( low-quality evidence ). Surgery plus antibiotics does not seem to reduce wound infections in children ( high-quality evidence ). Intra-abdominal abcesses Compared with surgery plus placebo or alone Surgery plus antibiotics may reduce intra-abdominla abcesses compared with surgery alone in adults (low-quality evidence). Adverse effects Antibiotics are associated with rash and Candida colitis. For GRADE evaluation of interventions for appendicitis, see table, p 9 . Benefits: Surgery plus antibiotics versus surgery plus placebo or surgery alone: [10] [12] We found one systematic review and one subsequent RCT comparing surgery plus antibiotics versus surgery plus placebo or surgery alone. The review did not distinguish between antibiotic regimens or between different antibiotic drugs.

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In adults: The systematic review (search date 2005, 40 RCTs and 5 CCTs) found that surgery plus perioperative systemic antibiotics significantly reduced wound infections and intra-abdominal abscesses compared with surgery alone (wound infections: 35 RCTs, 8812 adults having an appendicectomy with either simple appendicitis or complicated appendicitis , 287/4417 [6%] with surgery plus antibiotics v 632/4395 [14%] with surgery alone; intra-abdominal abscesses: 10 RCTs/CCTs, 4468 adults having an appendicectomy with either simple appendicitis or complicated appendicitis, 16/2211 [0.72%] with surgery plus antibiotics v 39/2257 [1.72%] with surgery alone, OR 0.35, 95% CI 0.13 to 0.91). Subgroup analysis found that, in adults with simple appendicitis, adding antibiotics to surgery significantly reduced wound infections and intra-abdominal abscesses compared with surgery alone (wound infections: 26 RCTs/CCTs, 5317 adults having an appendicectomy with simple appendicitis, 113/2610 [4%] with surgery plus antibiotics v 286/2707 [11%] with surgery alone, OR 0.37, 95% CI 0.30 to 0.46; intra-abdominal abscesses: 8 RCTs/CCTs, 2968 adults having an appendicectomy with simple appendicitis, 9/1433 [0.63%] with surgery plus antibiotics v 22/1535 [1.43%] with surgery alone, OR 0.46, 95% CI 0.23 to 0.94). A subgroup analysis in adults with complicated appendicitis found that antibiotic prophylaxis significantly reduced wound infections, but found no significant difference in intra-abdominal abscesses (wound infections: 24 RCTs/CCTs, 1152 adults having an appendicectomy with complicated appendicitis, 121/645 [19%] with surgery plus antibiotics v 175/507 [35%] with surgery alone, OR 0.28, 95% CI 0.21 to 0.38; intra-abdominal abscesses: 3 RCTs/CCTs, 467 adults having an appendicectomy with complicated appendicitis, 3/262 [1%] with surgery plus antibiotics v 4/205 [2%] with surgery alone, OR 0.54, 95% CI 0.12 to 2.43). The analysis on intra-abdominal abscesses was based on a small number of events. The review also found no significant difference in wound infections with surgery plus topical antibiotics compared with surgery plus placebo (52/339 [15%] with surgery plus topical antibiotics v 61/340 [18%] surgery plus placebo; OR 0.77, 95% CI 0.49 to 1.23). Of the 40 RCTs identified by the review, 23 did not state the method of randomisation. In children: The systematic review found no significant difference in wound infections or intra-abdominal abscess between surgery plus perioperative systemic antibiotics versus surgery alone (wound infections: 6 RCTs, 1090 children aged 015 years with either simple or complicated appendicitis, 23/548 [4%] with surgery plus antibiotics v 34/542 [6%] with surgery alone, OR 0.64, 95% CI 0.37 to 1.10; intra-abdominal abscesses: 6 RCTs, 1003 children with either simple or complicated appendicitis, 3/510 [0.6%] with surgery plus antibiotics v 11/493 [2.2%] with surgery alone, OR 0.25, 95% CI [10] 0.05 to 1.26). Subgroup analysis in children with simple appendicitis found no significant difference between treatments in wound infections, although surgery plus antibiotics in children with complicated appendicitis significantly reduced wound infections (simple appendicitis: 3 RCTs/CCTs, 704 children aged 015 years, 7/347 [2.0%] with surgery plus antibiotics v 8/357 [2.2%] with surgery alone, OR 0.92, 95% CI 0.33 to 2.57; complicated appendicitis: 3 RCTs/CCTs, 253 children aged 015 years, 5/134 [4%] with surgery plus antibiotics v 15/119 [13%] with surgery alone, OR 0.31, 95% CI 0.12 to 0.77). The review found insufficient data to provide subgroup analysis for numbers of intra-abdominal abscesses in children with either simple or complicated appendicitis. It should be noted that there were limited numbers of children in the systematic review, and that the results [10] may therefore lack statistical power. The subsequent RCT compared surgery alone versus surgery plus a single antibiotic dose (1 g ceftriaxone) versus surgery plus 5 days of regular antibiotics [12] (1 g/day ceftriaxone). The RCT reported that only one wound infection occurred, in a child who received surgery alone (108 children with simple appendicitis; other numerical data not provided). Harms: We have reported on the occurrence of wound infections and intra-abdominal abscesses in the benefits section above. The systematic review gave no information on adverse effects of antibiotics. [10] The subsequent RCT reported that adverse effects of antibiotics included rash (2/77 [2.6%]) and colitis with massive Candida infection (1/41 [2.4%]), all occurring after a single dose of antibi[12] otics. The review did not report on preoperative imaging studies. for simple appendicitis in children is unclear.
[10]

Comment:

The benefit of adjuvant antibiotics

OPTION

LAPAROSCOPIC SURGERY VERSUS OPEN SURGERY IN ADULTS. . . . . . . . . . . . . . . . . . . .

Wound infections Compared with open surgery in adults Laparoscopic surgery reduces wound infection compared with open surgery ( high-quality evidence ). Intra-abdominal abcesses Compared with open surgery in adults Laparascopic surgery increases intra-abdominal abcesses compared with open surgery (high-quality evidence).
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Pain Compared with open surgery in adults We don't know how effective laparoscopic surgery is compared with open surgery (very low-quality evidence ). For GRADE evaluation of interventions for appendicitis, see table, p 9 . Benefits: We found one systematic review and one subsequent RCT comparing laparoscopic surgery versus open surgery. The systematic review (search date 2004) found that laparoscopic surgery significantly reduced the number of wound infections compared with open surgery, but significantly increased the number of postoperative intra-abdominal abscesses (wound infections: 40 RCTs, 4904 adults, 89/2481 [4%] with laparoscopic surgery v 178/2423 [7%] with open surgery, OR 0.45, 95% CI 0.35 to 0.58; abscesses: 40 RCTs, 4953 adults, 41/2507 [2%] with laparoscopic surgery [13] v 15/2446 [0.61%] with open surgery, OR 2.48, 95% CI 1.45 to 4.21). The review also found that, compared with open surgery, laparoscopic surgery significantly reduced pain on the first postoperative day (weighted mean difference [pain measured using a 100 mm visual analogue scale]: 9 mm, 95% CI 5 mm to 13 mm), reduced the length of hospital stay (weighted mean difference length of hospital stay: 1.1 days, 95% CI 0.6 days to 1.5 days), and reduced time taken to return to normal activity (weighted mean difference: 6 days, 95% CI 4 days to 8 days). The subsequent RCT (268 men) found that operating time was significantly longer with laparoscopic surgery than with open surgery (median length of operation: 80 minutes with laparoscopic v 60 minutes with [14] open; P = 0.000). It found no significant difference between groups in the number of doses of pain relief medication required (median number of parenteral narcotic doses: 2 with laparoscopic v 2 with open, P = 0.716; median number of oral analgesic doses: 2 v 2, P = 0.502) or length of hospital stay (2 days with laparoscopic v 3 days with open, P = 0.66). The RCT found similar levels of pain or activity between laparoscopic and open surgery, but did not report whether these results were significant (pain distress score [measured using a visual assessment scale from 0 = no pain to 100 = most intense pain imaginable] at 1 day: 63.5 with laparoscopic v 57.5 with open; at 2 days: 34 v 40.5; at 3 days: 29 v 26; at 14 days: 5 v 6, P values not reported; pain activity score [measured on a visual assessment scale from 0 = no pain to 100 = most intense pain imaginable during rest, normal activities, and exercise, to give a total score between 0300]: at 1 day: 96 with laparoscopic v 77 with open; at 2 days: 73 v 67; at 3 days: 41.5 v 41; at 14 days: 16.5 v 14, P values not reported; activity assessment [13 activities rated 1 [no difficulty at all] to 5 [not able to do it], to give a total score between 1365: day 1: 50 with laparoscopic v 48 with open; day 2: 51 v 54; day 3: 56 v 55; [14] day 14: 36 v 36, P values not reported). The review did not give any further information on harms. The subsequent RCT (268 people) found no significant difference between laparoscopic and open surgery in complication rates (overall postoperative complications: 21/113 [18.5%] with laparoscopic v 23/134 [17.1%] with open, P = 1.00; wound infections: 7/113 [6.2%] v 9/134 [6.7%], P = 1.00; intra-abdominal abscesses: [14] 6/113 [5%] v 4/134 [3%], P = 0.51). The systematic review included people with a clinical diagnosis of acute appendicitis, and provided [13] no information on preoperative imaging, or on the use of perioperative antibiotics. Analyses were performed on an intention-to-treat basis. Studies reporting a negative appendicectomy rate of more than 50% were excluded. The number of trials looking specifically at paediatric practice is small and, as in the adult studies, not all outcomes were assessed in all trials. Most trials were unblinded and, in addition, heterogeneity was present in most analyses, although not for wound infections or intra-abdominal abscesses. The definition and reporting of additional operative or postoperative complications was inconsistent. In the subsequent RCT there was a similar frequency of overall complications in both groups, although there was a higher proportion of major complications [14] in the laparoscopic group compared with the open surgery group. LAPAROSCOPIC SURGERY VERSUS OPEN SURGERY IN CHILDREN. . . . . . . . . . . . . . . . . .
[13] [13] [14]

Harms:

Comment:

OPTION

Wound infections Compared with open surgery in children Laparoscopic surgery may reduce wound infections compared with open surgery ( moderate-quality evidence ). Intra-abdominal abcesses Compared with open surgery in children Intra-abdominal abcesses are similar for laparoscopic surgery and open surgery ( high-quality evidence ). For GRADE evaluation of interventions for appendicitis, see table, p 9 . Benefits: We found two systematic reviews that compared laparoscopic versus open surgery. The first review (search date 2004) excluded RCTs that allocated interventions depending on the availability of staff or instruments, randomised alternately by the day of admission, or that had no BMJ Publishing Group Ltd 2007 ...................................................................... 4
[13] [15]

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concealment of allocation. The systematic review found that laparoscopic surgery significantly reduced the number of wound infections and the length of hospital stay compared with open surgery (wound infections: 5 RCTs, 462 children aged 116 years, 2/233 [1%] with laparoscopic v 15/229 [7%] with open, OR 0.20, 95% CI 0.08 to 0.54; difference in hospital stay: 1 RCT, difference of [13] 0.7 days, 95% CI 1.1 days to 0.3 days). The review found no significant difference between laparoscopic surgery and open surgery in intra-abdominal abscesses (5 RCTs, 462 children aged 116 years: 2/220 [0.91%] with laparoscopic v 1/229 [0.44%] with open; OR 1.97, 95% CI 0.20 to [13] 19.13). The analysis on intra-abdominal abscesses was based on a small number of events. [15] The second systematic review (search date 2004, 23 studies) also pooled data. However, its main analysis also included data from retrospective and non-randomised studies (see comment below). It included 7 RCTs and reported a subgroup analysis on these. Of the seven included RCTs, three were included in the first review, and three had been excluded from the first review for methodological reasons (1 RCT with no allocation concealment or intention-to-treat analysis; 1 RCT with allocation based on availability of staff; 1 RCT which included children with peritonitis). On subgroup analysis of the included RCTs, the review found no significant difference between laparoscopic and open surgery for wound infection, although infection rates were lower with laparoscopic surgery (4 RCTs, 5/262 [2%] with laparoscopic v 24/512 [5%] with open; OR 0.47, 95% CI [15] 0.16 to 1.35). It found no significant difference between groups in intra-abdominal abscess or in postoperative ileus (intra-abdominal abscess: 6 RCTs, 1174 children, OR 1.7, 95% CI 1 to 2.87; [15] postoperative ileus: 3 RCTs, 799 children, OR 0.48, 95% CI 0.21 to 1.10). Harms: Comment: See harms of laparoscopic surgery versus open surgery in adults, p 4 . The first systematic review included people with a clinical diagnosis of acute appendicitis, and [13] provided no information on preoperative imaging, or on the use of perioperative antibiotics. See comment on laparoscopic surgery versus open surgery in adults, p 4 . One RCT included in the review subsequently presented results from a subset of 25 children aged 415 years with [16] complicated appendicitis . It found no significant difference between laparoscopic and open surgery in length of hospital stay or time to return to normal activities. It found two major complications (one pelvic abscess and one enterocutaneous fistula) in 13 children receiving laparoscopic surgery, compared with no major complications in 12 children receiving open surgery. In the analysis which also included data from non-randomised and retrospective studies, the second review found that laparoscopic appendicectomy significantly reduced wound infection, hospital stay, and ileus compared with open surgery, and found no significant difference between groups in intra[15] abdominal abscess formation. However, these results included data from non-randomised studies, and should be interpreted with caution. ANTIBIOTICS VERSUS SURGERY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
[13]

OPTION

Pain Compared with surgery Antibiotics reduce pain at 1224 hours compared with surgery ( very low-quality evidence ). T ime to recovery Compared with surgery Antibiotics may lead to similar recovery times compared with surgery (very low-quality evidence). Adverse effects Up to 12% of people given antibiotics may need urgery surgery, and up to 35% have surgery in the following year. For GRADE evaluation of interventions for appendicitis, see table, p 9 . Benefits: We found two RCTs which compared antibiotics versus surgery. The first RCT compared antibiotic treatment (iv cefotaxime 2 g twice daily plus tinidazole 800 mg/day for 2 days, followed by oral ofloxacin 200 mg twice daily plus tinidazole 500 mg twice daily for 8 days) versus open [5] appendicectomy. It found that, compared with appendicectomy, antibiotics significantly reduced patients' subjective pain scores (recorded on a visual analogue scale) at between 12 and 42 hours after start of treatment (40 adults with suspected appendicitis; P < 0.001; other data presented graphically), and surgeon assessed pain scores (recorded on a visual analogue scale) at between 1 day and 10 days after start of treatment (P < 0.01; other data presented graphically), and significantly reduced morphine consumption (mean morphine dose: 0.9 mg with antibiotics v 17.8 mg with surgery; P < 0.001). The inclusion criteria for the RCT included typical symptoms and signs of acute appendicitis, such as positive findings on ultrasound and raised neutrophil/C reactive protein levels on blood assays. The second RCT (252 men aged 1850 years [men with suspected perforation of the appendix excluded] all with raised C reactive protein) compared antibiotic treatment BMJ Publishing Group Ltd 2007 ...................................................................... 5
[5] [17]

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(iv cefotaxime 2 g twice daily plus tinidazole 800 mg daily for 2 days, followed by ofloxacin 200 mg twice daily and tinidazole 500 mg twice daily for 10 days) versus either laparoscopic or open ap[17] pendicectomy. The study found similar lengths of sick leave and time off work between the two groups (mean sick leave: 5.3 days with antibiotics v 6.0 days with surgery; mean time off work: 8.0 [17] days with antibiotics v 10.1 days with surgery; between group P values not reported). Harms: The first RCT found that all people treated conservatively with antibiotics were discharged from hospital within 48 hours, except for one who had surgery for generalised peritonitis after a perforation [5] of the appendix 12 hours after randomisation to receive antibiotic treatment. It found that 7/20 (35%) people who received conservative treatment with antibiotics were readmitted with acute appendicitis and underwent appendicectomy within 1 year (mean 7 months, range 312 months). The RCT found one wound infection in the surgically treated group, and no deaths occurred with either treatment.The second RCT found that 15/128 (12%) of people treated with antibiotics required [17] open surgery within 24 hours and, of these, seven had a perforated appendix. The RCT reported that their outcomes in terms of sick leave or hospital stay did not vary compared with the six people [17] with perforation found at surgery (no further numerical data reported). The RCT also found that 16 people (15%) in the antibiotic group required an appendicectomy during the first year (range 110 months after antibiotic treatment). There was a complication rate of 17/124 (14%) in the surgery group which were said to be mainly wound infections, but no further details were given.
[17]

Comment:

The second RCT made no mention of a power calculation, and did not report results using an in[17] [17] tention-to-treat analysis. This RCT was done by a similar group to that which had done the [5] first, smaller RCT. ANTIBIOTICS VERSUS NO TREATMENT / PLACEBO. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

OPTION

We found no clinically important results about antibiotics compared with no treatment or placebo in people with appendicitis. Because of ethical concerns, such RCTs are unlikely to be conducted. For GRADE evaluation of interventions for appendicitis, see table, p 9 . Benefits: Harms: Comment: We found no systematic review and no RCTs comparing antibiotics versus placebo or no treatment. We found no systematic review and no RCTs. RCTs comparing antibiotics versus no treatment or placebo are unlikely to be done, because of ethical concerns. SURGERY VERSUS NO TREATMENT. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

OPTION

We found no clinically important results about surgery compared with no treatment in people with appendicitis. Because of ethical concerns, such RCTs are unlikely to be conducted. For GRADE evaluation of interventions for appendicitis, see table, p 9 . Benefits: Surgery versus no treatment: We found no systematic review or RCTs comparing surgery versus no treatment. Surgery versus no treatment: We found no systematic review or RCTs comparing open surgery versus no treatment. Surgery is now a well-established treatment. No RCTs comparing surgery versus no treatment are likely to be conducted, because of to ethical concerns. STUMP INVERSION AT OPEN APPENDICECTOMY VERSUS SIMPLE LIGATION . . . . . . . . . .

Harms:

Comment:

OPTION

Wound infection Compared with simple ligation We don't know how effective stump inversion at open appendicectomy is compared with simple ligation ( low-quality evidence ). Intra-abdominal abcesses Compared with simple ligation Intra-abdominal abcesses are similar for stump inversion at open appendicectomy and simple ligation ( moderate-quality evidence ). Postoperative ileus
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Compared with simple ligation Stump inversion may increase the postoperative ileus rate compared with simple ligation. For GRADE evaluation of interventions for appendicitis, see table, p 9 . Benefits: Stump inversion versus simple ligation: [18] [19] We found no systematic review, but found two RCTs. The first RCT compared double invagination (purse string with Z stitch, 374 people) versus simple ligation of the stump (361 people). [18] The RCT found no significant difference in wound infection, length of hospital stay, postoperative fever, or intra-abdominal abscesses between double invagination and simple ligation (735 people aged 1491 years with complicated or simple appendicitis ; wound infection: 33/374 [8.8%] with double invagination v 30/361 [8.3%] with simple ligation, reported as not significant; length of hospital stay: 4.6 days with double invagination v 4.9 days with simple ligation, reported as not significant; postoperative fever: 16.3% with double invagination v 16.1% with simple ligation, absolute numbers not reported, reported as not significant; intra-abdominal abscesses: 6/374 [1.6%] with double invagination v 2/361 [0.55%] with simple ligation, reported as not significant). The second [19] RCT also compared double invagination versus simple ligation. The RCT found a significantly higher incidence of wound infection with double invagination compared with simple ligation, but found no significant difference in intra-abdominal abscesses or length of hospital stay (134 people aged 490 years; wound infection: 4/55 [7.3%] with double invagination v 0/79 [0%] with simple ligation, P = 0.017; abscesses: 1 in each group; length of hospital stay: median 5 days for both groups). In the two RCTs, postoperative adhesive ileus was more frequently seen in the double invagination [18] groups (6/374 [1.6%] with double invagination v 1/361 [0.28%] with simple ligation, P < 0.05; 1/55 [1.88%] with double invagination v 0/79 [0%] with simple ligation, reported as not significant [19] ). No other specific complications were documented. Increased complications after invagination are believed to be caused by longer operative time. Both trials commented on potential caecal distortion after invagination of the appendix stump, which has mimicked caecal cancer on subsequent contrast imaging a further potential hazard of stump [17] [18] invagination. Clinical guide: Although the evidence suggests increased complications with appendiceal stump inversion compared with simple ligation, invagination of the stump is unavoidable during some appendicectomies. It may, for example, be necessary in order to achieve adequate closure if the appendix is perforated at the base.

Harms:

Comment:

GLOSSARY
Complicated appendicitis Perforated or gangrenous appendicitis, or the presence of a periappendicular abscess. Negative appendicectomy Term used for an operation performed for suspected appendicitis, in which the appendix is found to be normal on histological evaluation. Simple appendicitis Clinically normal or inflamed appendix, in the absence of gangrene, perforation, or abscess around the appendix. High-quality evidence Further research is very unlikely to change our confidence in the estimate of effect 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 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 Very low-quality evidence Any estimate of effect is very uncertain

SUBSTANTIVE CHANGES
Antibiotics versus surgery One RCT added; categorisation unchanged (Trade-off between benefits and harms). [15] Laparoscopic surgery versus open surgery in children One systematic review added; benefits data enhanced, categorisation unchanged (Likely to be beneficial).
[17]

REFERENCES
1. 2. Addiss DG, Shaffer N, Fowler BS, et al. The epidemiology of appendicitis and appendectomy in the United States. Am J Epidemiol 1990;132:910925. [PubMed] Department of Health. Hospital episode statistics; England: financial year 200405. http://www.hesonline.nhs.uk/Ease/servlet/ContentServer?siteID=1937&categoryID=202 (last accessed 29 June 2006). Larner AJ. The aetiology of appendicitis. Br J Hosp Med 1988;39:540542. [PubMed] Cobben LP, de van Otterloo AM, Puylaert JB. Spontaneously resolving acute appendicitis: frequency and natural history in 60 patients. Radiology 2000;215:349352. [PubMed] 5. 6. 7. 8. Eriksson S, Granstrom L. Randomized controlled trial of appendicectomy versus antibiotic therapy for acute appendicitis. Br J Surg 1995;82:166169. [PubMed] Barber MD, McLaren J, Rainey JB. Recurrent appendicitis. Br J Surg 1997;84:110112. [PubMed] Mattei P, Sola JE, Yeo CJ. Chronic and recurrent appendicitis are uncommon entities often misdiagnosed. J Am Coll Surg 1994;178:385389. [PubMed] Velanovich V, Satava R. Balancing the normal appendectomy rate with the perforated appendicitis rate: implications for quality assurance. Am Surg 1992;58:264269. [PubMed] Krukowski ZH, Irwin ST, Denholm S, et al. Preventing wound infection after appendicectomy: a review. Br J Surg 1988;75:10231033. [PubMed]

3. 4.

9.

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10. Andersen BR, Kallehave FL, Andersen HK. Antibiotics versus placebo for prevention of postoperative infection after appendectomy. In: The Cochrane Library: Issue 4, 2006. Chichester, UK: John Wiley & Sons, Ltd. Search date 2005; primary sources Cochrane Controlled Trials Register, Medline, Embase, Cochrane Colorectal Cancer Group Specialised Register, and hand searches of reference lists of identified trials. Andersson R, Lambe M, Bergstrom R. Fertility patterns after appendicectomy: historical cohort study. BMJ 1999;318:963967. [PubMed] Gorecki WJ, Grochowski JA. Are antibiotics necessary in nonperforated appendicitis in children? A double blind randomised controlled trial. Med Sci Monit 2001;7:289292. [PubMed] Sauerland SR, Lefering R, Neugebauer EAM. Laparoscopic versus open surgery for suspected appendicitis. In: The Cochrane Library: Issue 4, 2006. Chichester, UK: John Wiley & Sons, Ltd. Search date 2004; primary sources The Cochrane Library, Medline, Embase, Scisearch, and Biosis. 14. Katkhouda N, Mason RJ, Towfigh S, et al. Laparoscopic versus open appendicectomy. A prospective randomised double-blind study. Ann Surg 2005;242:439448. [PubMed] Aziz O, Athanasiou T, Tekkis PP, et al. Laparoscopic versus open appendectomy in children: a meta-analysis. Ann Surg 2006;243:1727. [PubMed] Lintula H, Kokki H, Vanamo K, et al. Laparoscopy in children with complicated appendicitis. J Pediatr Surg 2002;37:13171320. [PubMed] Stryud J, Eriksson S, Nilsson I, et al. Appendectomy versus antibiotic treatment in acute appendicitis. A prospective multicenter randomized controlled trial. World J Surg 2006;30:10331037. [PubMed] Engstrom L, Fenyo G. Appendicectomy: assessment of stump invagination versus simple ligation: a prospective, randomized trial. Br J Surg 1985;72:971972. [PubMed] Jacobs PP, Koeyers GF, Bruyninckx CM. Simple ligation superior to inversion of the appendiceal stump; a prospective randomized study. Ned Tijdschr Geneeskd 1992;136:10201023. [in Dutch] [PubMed] 15. 16. 17.

11. 12.

13.

18.

19.

David Humes Research Fellow General Surgery University of Nottingham Nottingham UK William James Speake Consultant Colorectal Surgeon Derby City General Hospital Nottingham UK John Simpson Lecturer in Surgery University of Nottingham Nottingham UK
Competing interests: JS, WS, and DH declare that they have no competing interests.

BMJ Publishing Group Ltd 2007

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Digestive system disorders

Appendicitis
TABLE 1
Important outcomes Number of studies (participants)

Appendicitis
Infections, pain, time to recovery, mortality, adverse effects Outcome Comparison Type of evidence Quality Consistency Directness Effect size GRADE Comment

What are the effects of treatments for acute appendicitis? 35 (at least 8812 people)
[10]

Wound infections

Surgery plus antibiotics v surgery plus placebo or surgery alone in adults Surgery plus antibiotics v surgery plus placebo or surgery alone in adults Surgery plus antibiotics v surgery plus placebo or surgery alone in children Laparoscopic surgery v open surgery in adults Laparoscopic surgery v open surgery in adults Laparoscopic surgery v open surgery in adults

Low

Quality points deducted for inclusion of CCTs and randomisation flaws Quality points deducted for inclusion of CCTs and randomisation flaws

10 (at least 4468 people)

[10]

Intra-abodiminal abcesses

Low

7 (1898)

[10]

Wound infections

High

40 (4904)

[13]

Wound infections Intra-abdominal abcesses Pain on VAS

High

40 (4953)

[13]

+1

High

Effect size point added for OR greater than 2 Consistency point deduced for conflicting results. Directness points deduced for narrow inclusion criteria and uncertainty about intervention Consistency point deducted for conflicting results between studies

41 (at least 5172 people)

[13]

Very low

9 (1236)

[13]

Wound infections Intra-abdominal abcesses Pain (VAS)

Laparoscopic surgery v open surgery in children Laparoscopic surgery v open surgery in children Antibiotics v surgery

Moderate High

11 (1636)

[13]

1 (40)

[5]

Very low

Quality points deducted for sparse data and incomplete reporting of results. Directness point deducted for specific antibiotics and surgery Quality point deducted for analysis flaw. Directness points deducted for narrow inclusion criteria and intervention Consistency point deducted for lack of agreement between studies. Quality point deducted for incomplete reporting of results Quality point deducted for incomplete reporting of results

1 (252)

[17]

Time to recovery

Antibiotics v surgery

Very low

2 (869)
[19]

[18]

Wound infection

Stump inversion at open appendicectomy v simple ligation

Low

2 (869)
[19]

[18]

Intra-abdominal abcesses Postoperative ileus

Stump inversion at open appendicectomy v simple ligation Stump inversion at open appendicectomy v simple ligation

Moderate Low

2 (869)
[19]

[18]

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.

BMJ Publishing Group Ltd 2007

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