Treatment of appendiceal mass – a qualitative systematic review

Suspicion of acute appendicitis is one of the most common reasons for hospital admittance and emergency operations [1, 2]. In patients suffering from acute appendicitis, up to 7% will present with an appendiceal mass [3-5]. The pathological spectrum may range from discrete phlegmone to abscess formation [1, 2].

The optimal treatment of patients with an appendiceal mass is controversial and treatment strategies are based on sparse evidence [6, 7]. The different treatment strategies include conservative treatment with or without antibiotics, percutaneous, trans-rectal or trans-vaginal drainage and surgical treatment [1]. Conservative treatment may prolong hospital stay and convalescence, and surgical treatment carries a risk of intestinal resection and major complications. Drainage may carry a risk of both treatment failure and complications [2, 8].

This systematic review was undertaken to perform a critical analysis of outcome after conservative treatment with or without antibiotics, percutaneous drainage, and surgical treatment of appendiceal mass in children and adults. The primary outcome was treatment failure and complications, and the secondary outcome was duration of hospital stay. This review does not address treatment for recurrent appendicitis and interval appendectomy (“cold” appendicitis).

METHODS

The present analysis was based on the principles for qualitative systematic reviews as described by PRISMA [9, 10]. The search strategy and PICOS (Population, Interventions, Comparators, Outcomes, Study designs of interest) were made as described below. The heterogeneity of studies and the fact that the majority of the studies were uncontrolled retrospective series precluded a statistical meta-analysis.

Search strategy

The literature was searched through PubMed from 1966 to March 2014 using the following MeSH terms (and free text terms on a combination of these): “Appendicitis” [MeSH] AND (“abscess” [MeSH] OR “mass” [All Fields] OR “appendiceal” [All Fields] OR “conservative” [All Fields] OR “phlegmone” [All Fields] OR “interval” [All Fields]) AND (“humans” [MeSH Terms] AND English [lang]). A “free text term” search on combinations of the above terms was also performed in the Embase and Cochrane Library and included cross-reference to the referenced articles.

Study exclusion criteria

Only English language articles were included. Only original articles were included, thus reviews and meta-analysis were excluded. Papers on post-operative intra-abdominal abscesses/mass and abscesses of any cause other than appendicitis were excluded, as was papers including poorly defined subpopulations of patients with appendiceal mass. Furthermore, studies only describing recurrent appendicitis and/or interval appendectomy were excluded from the analysis. Finally, we excluded non-randomised studies including less than 20 patients (Figure 1).

Definitions and outcomes

We defined an appendiceal mass as an inflammatory mass consisting of an inflamed appendix and adjacent viscera, ranging from phlegmone to well-defined abscess [1-3, 11]. Diagnosis of appendiceal mass was based on clinical examination, computed tomography (CT), trans-abdominal ultrasound (US) or peroperative findings. Treatment failure with conservative treatment or percutaneous drainage was defined as unsuccessful in case of operation during the same hospital admission or shortly after discharge (less than one week). Surgical treatment was defined as attempted operative appendectomy either with laparotomy or laparoscopy. Treatment outcome for phlegmone and abscess was noted separately whenever possible. Complications after drainage and surgical treatment were divided into major and minor complications [12]. Major complications were defined as severe and potentially fatal complications comprising death and those requiring reoperation, except for wound opening due to infection [12]. All other complications were defined as minor complications. Both surgical and medical complications were included. As almost all included studies, rarely mentioned complications due to surgery after treatment failure, it was not possible to summarise these systematically. In several papers, it was not possible to distinguish between the total number of complications and complications per patient, and the analysis therefore included total numbers of complications. Clinical presentation and mean hospital stay were noted whenever these had been reported. Children ≤ 15 years and adult patients were analysed separately when possible. Studies reporting a mixture of paediatric and adult patients were classified as mixed.

Trial registration: not relevant.

RESULTS

If possible and for reasons of clarity (see methods above), we report results separately for children and adults. From a pool of 2,496 potentially relevant studies, we included 48 studies (three prospective randomised studies (RCT), four prospective non-randomised studies, and 41 retrospective studies) with a total of 3,772 patients (Figure 1). Results from the literature are summarised in Table 1. On the basis of the analysis, we have proposed a treatment algorithm for the management of the appendiceal mass (Figure 2), and evidence-based recommendations are summarised (Table 2). Finally, a brief overview of the overall incidence failure rate and complications after treatment with antibiotics, percutaneous drainage, and surgery is provided in Table 3.

Conservative treatment with or without antibiotics

Children

We identified four uncontrolled retrospective studies (Table 1). Treatment failure was reported in 8/77, 65/411, 5/59 and 7/37 (8-19%) of cases [13-16] with a conservative regimen (with or without antibiotics). Unfortunately, the clinical presentation of the patients was only described sporadically.

Based on weak evidence, up to 19% of children presenting with appendiceal mass may experience treatment failure with conservative treatment.

Adults

Two uncontrolled retrospective studies were included (Table 1). One study (n = 67) found that 10/10 patients with phlegmone (no abscess on CT) responded on antibiotics alone [17]. Similar results were found in the other study (n = 40) where 9/9 of the patients with phlegmone responded to antibiotics [18].

Thus, weak evidence suggests that most adult patients with periappendicular phlegmone can be successfully treated using antibiotics alone.

Mixed

Two retrospective studies (Table 1) found that treatment failure with antibiotic treatment occurred in 23/193 and 9/40 (12-23%) [19, 20]. Treatment failure was defined as lack of clinical improvement, mechanical ileus, sepsis and persistent abscess. One patient died during hospitalisation, but the cause of death was not reported [19]. The clinical presentation of the patients was not described.

Conclusively, weak evidence from mixed patients with appendiceal mass suggests that treatment failure after using conservative treatment with antibiotics may reach 23%.

Percutaneous drainage

Children

Seven retrospective studies were included (Table 1). These studies reported data from patients treated with antibiotics and percutaneous drainage. Overall, treatment failure was seen in 19/73, 3/32, 0/36, 6/96, 1/42, 2/105 (0-26%) [21-26] of cases. In one small study, a high risk of treatment failure was observed in 10/23 (43%) in the subgroup of patients who underwent percutaneous drainage [21]. In another study, the risk of major complications related to drainage was 4/37 (11%) and in another study 0/42 [25, 27]. Drain-related complications were not reported in the remaining studies. In two studies, the clinical presentation was pain and fever and no clinical signs of generalised peritonitis [21, 22], whereas no information was provided in the remaining four studies.

In summary, percutaneous drainage may carry a risk of major complications of up to 11% and risk of treatment failure in up to 43% of cases.

Adults

Four retrospective studies were included (Table 1). One of the retrospective studies reported results for drainage after lack of clinical improvement with antibiotic treatment for at least 72 hours [17]. Clinical presentation was fever and leucocytosis. On this regimen, 30/66 patients (45%) had a drainage procedure performed and 4/30 (13%) underwent surgery after drainage due to lack of clinical improvement. No complications were reported in the patients who received antibiotics alone. One infection at a drain site was observed. The other three retrospective studies found treatment failure in 3/40, 5/94 and 4/41 (5-15%) for antibiotics and CT- or US-guided drainage, but not all included patients received a drainage procedure [18, 28, 29]. Complications to drainage in these studies were abscess perforation to the peritoneal cavity (1/17 patients) and small-bowel obstruction (1/41 and 1/94 patients) [18, 28, 29]. The clinical presentation of the patients was not described.

Thus, treatment failure with drainage may reach 15%. Major complications may appear in up to 6% of cases.

Mixed

We identified one RCT, one prospective non-randomised and one retrospective study (Table 1). The prospective randomised study (n = 50) compared intravenous antibiotics with a combination US-guided percutaneous drainage and antibiotics [30]. Treatment failure was significantly higher with 8/25 (32%) in the antibiotic group compared with 1/25 (4%) in the drainage group. Hospital stay was significantly longer for the drainage group than for the antibiotic group. Inclusion criteria were appendiceal abscess larger than 3 cm in diameter, and the clinical presentation was fever and leucocytosis. The prospective non-randomised study (n = 70) showed treatment failure in 4/32 (12.5%) on antibiotics alone [31]. Thirteen of 28 patients (46%) treated with drainage developed fistulas, and one patient underwent emergency operation due to diffuse peritonitis. The clinical presentation was fever, leucocytosis and pain in the right lower quadrant. In the retrospective study, no treatment failure was reported but two patients had an ileocecal resection performed due to entero-cutaneous fistulas (8%) [32]. The clinical presentation in this study included right lower quadrant pain, diffuse abdominal pain and/or fever and leucocytosis.

Thus, drainage may lower the risk of treatment failure compared with conservative treatment. However, drainage may be associated with a moderate risk of complications.

Surgical treatment

Children

One RCT, two prospective non-randomised studies and four retrospective studies were included (Table 1). In the prospective randomised study (n = 40) comparing surgical treatment and percutaneous drainage, 4/20 patients (20%) had treatment failure after drainage and subsequently underwent surgical intervention [33]. There was no significant difference in number of complications between drainage and surgery. Clinical presentation included fever and leucocytosis. In one of the prospective non-randomised studies (n = 22), no complications were reported after laparoscopic surgery [34]. In another non-randomised prospective study (n = 82) and in the four retrospective studies comparing conservative treatment or drainage with surgery, there were treatment failure in 10/48, 0/32, 6/29, 3/31 and 0/21 (0-21%) [35-39]. Minor complications were reported in 4/34, 6/60, 12/36, 9/16 and 2/19 (10-56%) [35–39] and major complications in 4/36, 3/16 and 2/19 (10.5-19%) [37-39]. The clinical presentation in these studies was pain, fever vomiting and for some patients rebound and guarding.

In conclusion, surgical treatment in children proably carries a high risk of minor complications in up to 56% of cases and a risk of major complications in up to 19% of cases.

Adults

A total of 13 retrospective studies were included (Table 1). Ten of these studies compared a conservative regimen or drainage with surgery. Thus minor and major complications were found in 12/21, 30/36, 34/67, 0/13, 10/40, 27/43, 6/15, 34/104, 22/78 and 30/95 (0-57%) [4, 40-48]. Three uncontrolled retrospective studies assessed complications after surgical intervention without comparison with other treatment modalities and found overall complications in 10/34, 12/114 and 18/47 (10.5-38%) [49–51]. Complications were mostly minor, but in five studies the frequency of major complications was 4/68, 13/67, 2/40, 7/43, 7/78, 5/95 and 4/47 (5-19%) [40, 41, 43, 44, 47, 48, 51]. Ileocecal resections were performed in 1/21, 2/13, 10/40, 5/43, 6/95 and 5/47 (5-25%) [4, 42-44, 48, 51]. Complication rates in patients receiving additional antibiotic treatment and/or drainage were found in 7/68, 15/88, 0/16, 0/43 0/15 (0-17%) with major complications in 1/68, 5/88 [40, 41, 43-45]. The rate of treatment failure was 3/68, 0/16, 1/43 and 0/15 (0-5%) for the regimes with antibiotics and drainage [40, 43-45], whereas treatment failure was 6/27, 3/30, 0/17, 6/69 and 3/101 (0-22%) in the groups treated with antibiotics alone [4, 42, 46-48]. In two of the studies, patients with signs of generalised peritonitis and severe sepsis were excluded [41, 45]. The clinical presentation in four of the studies was right lower quadrant pain, fever, raised c-reactive protein and leucocytosis [40, 44, 46, 47], whereas there was no information on clinical presentation in the other studies [4, 42, 43].

In conclusion, surgical treatment in adults carries a risk of complications in up to 57% and major complications in up to 19% of cases. In adult patients, the risk of intestinal resection may be 5-25%.

Mixed

We found one RCT, three prospective non-randomised studies and four retrospective studies (Table 1). In the prospective randomised study (n = 60) 6/20 minor complications were reported after surgical intervention compared with 0/40 after conservative treatment [52]. The clinical presentation was right lower quadrant pain, whereas the exclusion criteria were free air or pus collection in the pelvis on x-ray/US. The three non-randomised prospective studies and three of the retrospective studies found the complication rates due to surgery in 5/30, 10/19, 19/88, 5/15, 15/42 and 15/46 (17-52%) of cases, most of these were minor [53-58], whereas treatment failure was 4/29, 0/28 and 13/88 (0-15%) in the conservative regime/drainage groups [53-55]. The clinical presentation was only reported in two studies (right lower quadrant pain, fever and leucocytosis) [57, 58]. The last retrospective study (n = 92) reported outcomes from ileocecal resections as the primary treatment modality of appendiceal mass [59]. A total of 59% had a primary anastomosis. Complications were seen in 25/92 (27%) of which 5/92 (5%) were major complications.

In summary, the risk of minor complications in mixed patients after surgical treatment may be up to 52%, and the risk of major complications may reach 5%.