Risk factors for intra-abdominal abscess following laparoscopic appendectomy for acute appendicitis: a retrospective cohort study on 2,076 patients


 Background. Intra-abdominal abscesses (IAA) may develop after laparoscopic appendectomies (LA) for acute appendicitis. The identification of risk factors for postoperative IAA could lead to a decrease in the readmission rate and surgery redoes after LA for acute appendicitis.
Materials and methods. We reviewed 2,076 patients managed via a LA for acute appendicitis between 2001 and 2017. Male gender accounted for 53.5% of patients. Mean age was 29.5 (SD ± 18.47) years. Thirty-seven patients (1.8%) developed a postoperative IAA. Comparison between groups was made via univariate and multivariate analyses.
Results. Male gender (p<0.05), ASA score ≥ 2 (p<0.05), a gangrenous or perforated appendicitis (p<0.0001), abscess or pelvic peritonitis (p<0.0001), clipping the mesoappendix (p<0.0001), appendix division by mechanical stapler (p<0.05), and prolonged antibiotic therapy (p<0.01) were significantly more frequent in the group of patients with IAA. In terms of multivariate analysis, only pelvic peritonitis (p < 0.005), a perforated appendicitis (p <0.05), and clipping the mesoappendix (p < 0.0001) were independent predictive factors for postoperative IAA
Conclusion. Patients with peritonitis or a perforated appendicitis, and those who had their mesoappendix clipped showed a higher likelihood of developing an IAA. At-risk patients should be provided with careful follow-up for the early detection and management of this complication.

4 are suggestions that a large-volume intraoperative peritoneal lavage might increase the rate of postappendectomy IAA [5][6][7][8]. Unfortunately, most of the studies investigating the risk factors for IAA are relatively small-sized, retrospective, and often report conflicting results. The aim of the present study was to discover what factors that might contribute to the onset of IAA in patients undergoing LA.

Data collection
We reviewed the data of a prospectively collected database of patients who underwent laparoscopic appendectomy for acute appendicitis during the period 2001-2017 at the Department of Emergency Surgery of Pisa University Hospital. The diagnosis of acute appendicitis was based on the clinical presentation, laboratory parameters, and imaging studies. An ultrasound scan was performed for all of the patients with suspected acute appendicitis. Computed tomography was required in those cases for which a discordance was noted between the clinical presentation and the ultrasound. For all NC, USA). The base of the appendix was ligated with endoloops and divided or sectioned with a 45mm laparoscopic articulating stapler in the case of a large or gangrenous/perforated appendicular base. The appendix was then removed with a bag. After the complete evacuation of abdominal collections, a peritoneal lavage with warm saline solution, followed by suctioning, was performed in all patients until a satisfactory peritoneal clearance was achieved. Antibiotics (amoxicillin/clavulanic acid or ciprofloxacin) were continued after surgery in cases of complicated acute appendicitis. In cases of severe and diffuse contamination of the peritoneal cavity, a piperacillin/tazobactam regimen of antibiotic therapy was given.

Follow-up and IAA diagnosis
After discharge, a follow-up program of outpatient visits or phone calls was set up. IAA was suspected in the presence of fever, leukocytosis, and abdominal pain, and an abdominal imaging investigation confirmed the diagnosis (US and CT scan). Treatment consisted of therapy with broad-spectrum antibiotics for small-sized abscesses and percutaneous drainage for larger abscesses. Abscesses not amenable to percutaneous drainage or associated with peritonitis were best managed by surgical exploration.

Data analysis and statistics
The following parameters were the target of the analysis: gender, age, American Society of Anesthesiologists (ASA) score, intraoperative findings (abscess, gangrenous appendicitis, perforated appendix, pelvic peritonitis), method of management of the mesoappendix, type of technique adopted for the division of the inflamed appendix, and the use of postoperative antibiotics. The Lilliefors test was used to assess the normality of the distributions. A Mann-Whitney test was carried out to analyze quantitative variables. In addition, the Chi-squared test was performed to study categorical variables. Furthermore, stepwise forward multivariate logistic regression was used, and the Hosmer-Lemeshow test was carried out to evaluate the goodness of fit of the multivariate model.
The statistical analysis was performed using the IBM SPSS software package, version 17.0.1.

Discussion
The severity of the appendix inflammation is believed to be the main risk factor associated with IAA.
The IAA rate after laparoscopic appendectomy reported in non-perforated appendicitis is 1-4%, but the incidence of postoperative IAA increases by up to 26% in patients with gangrenous perforated appendicitis [10][11][12][13]. We found perforated appendicitis in 45.9% of patients that developed a postoperative IAA but in only 8% of the patients who did not suffer this complication (Table 2).
According to Schlottmann et al. the higher the grade of intraperitoneal bacterial contamination, the higher the risk of postoperative IAA [14], and few doubts exist about the fact that perforation increases the grade of contamination of the peritoneum surrounding the appendix. Indeed, this study strongly supports the hypothesis that a perforated appendix should be regarded as a predictive factor for postoperative IAA (Table 3). Also, pelvic peritonitis was significantly more frequent in patients who developed postoperative IAAs (43.2% vs. 17.5%; p<0.0001) ( Table 2) and was recognized as a predictive factor for postoperative IAA via multivariate analysis (OR 2.9; p = 0.004) ( Table 3).
According to the WISS study, acute appendicitis is still the most frequent cause of intra-abdominal sepsis [15]. A delayed diagnosis, mostly occurring in patients who are unreliable or have an atypical clinical onset, may lead to severe, life-threatening complications such as gangrene, perforation, appendiceal mass, and peritonitis [16]. Overall, 17.5% of the patients enrolled in the study had a peritonitis localized to the pelvis or the paracolic gutter: this result is in line with rate reported in the literature (17.3%) [13].
The clipping of the mesoappendix is associated with a higher incidence of postoperative IAAs. In this study, the use of clips was left to the operating surgeon's discretion, but such use was always limited to the management of the mesoappendix. Compared to bipolar coagulation, we recorded a significantly higher occurrence of IAA when the mesoappendix was secured with polymeric clips (62.1% vs. 29.7%; p < 0.0001). Polymeric clips have been increasingly used for the closure of the appendiceal stump [17][18] significantly lower if the postoperative antibiotics regimen was prolonged for more than 24 hours compared to when antibiotics were withdrawn within 24 hours after surgery. Thus, they concluded that postoperative antibiotics might not provide an appreciable clinical benefit in terms of preventing intra-abdominal abscesses [21]. The postoperative use of antibiotics for complicated appendicitis has proven to be beneficial [22], but the optimal duration of treatment has not yet been established. In a recent retrospective study on 6,412 patients with complicated acute appendicitis, Anderson et al.
suggested that not all patients with complicated appendicitis should be discharged with antibiotics after surgery. Accordingly, only patients exhibiting SSI before discharge or those whose clinical progress requires a more extended in-hospital stay might benefit from extra-time antibiotic treatment. [23].
The present study suffers several limitations. Primarily, this is a retrospective study. Secondly, this series represents a vastly complex, heterogeneous patient population scattered over a considerable period. Thirdly, the lack of including other risks factor can affect the statistics of the multivariate analysis. Furthermore, the number of patients presenting a postoperative IAA constitutes a small cohort of cases. However, since the study was carried out at a tertiary referral center, the high volume of patients undergoing laparoscopy for acute appendicitis makes the statistical analysis credible and valuable. Lastly, we acknowledge that the patients were not routinely followed once symptoms resolved after the surgical intervention, making it possible that patients could have been lost during follow up.

Conclusions
Patients with localized peritonitis, a perforated appendicitis, and a clipped mesoappendix have a higher chance of developing postoperative IAA. The type of technique adopted for the division of the appendix (endostapler vs. endoloop) does not seem to be a risk factor for the development of postoperative IAA. The lack of postoperative antibiotic treatment was not identified as an independent risk factor for abscess formation.

Consent for publication: not applicable.
Availability of data and materials: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. All data generated or analysed during this study are included in this published article.