What is the main problem in conservative management for complicated appendicitis? A systematic review

Background: As a classification of appendicitis, complicated appendicitis has no standardized treatment for adults. Method: According to the related literature systematically searched on PubMed, Embase, Cochrane and Web of Science, we evaluated the efficacy of surgical treatment and conservative treatment for complicated appendicitis, especially focused on the outcomes about the length of stay, operation time, postoperative complications and unplanned additional intervention, in the literature. Result: A total of 14 studies were involved in the meta-analysis, including 845 patients in the immediate operation group (IO) and 756 patients in the conservative management group (CM). Compared with conservative treatment, the total hospitalization time was reduced by 1 day (WMD=-1.29, 95%CI [-2.42, -0.16], P=0.03<0.05). The incidence of unplanned additional intervention in patients undergoing emergency surgery is lower than that of conservative treatment (OR=0.18, 95%CI [0.11, 0.30], P<0.00001). Surgical patients are more likely to have complications such as wound infection (OR=2.41, 95%CI [1.08, 5.38], P=0.03<0.05) and intestinal obstruction (OR=4.14, 95%CI [2.21, 7.75], P<0.00001) than conservative patients. The incidence of abdominal abscess was lower than that of conservative treatment, and the difference was not statistically significant (OR=0.9, 95%CI [0.54, 1.47], P=0.66>0.05). Conclusion: Compared with conservative management patients, immediately operated patients have shorter hospitalization time and less unplanned intervention, which can significantly reduce the readmission opportunity of patients with complicated appendicitis and lighten the burden of follow-up and medical resource consumption.

Appendicitis is the most common form of acute abdomen, affecting about 7-8% percent of adults 1 . It can be divided into uncomplicated appendicitis and complicated appendicitis, between which complicated appendicitis is often related to the rapid development of acute appendicitis or the improper and untimely treatment 2 , the incidence of which is about 3.8-5.0% of acute appendicitis 1 . When the appendix appears to exudate, necrosis and perforation, the inflammatory factors spread into the surrounding tissues of the appendix, causing the retina and the nearby small intestine to form an appendiceal wrapping. After successful formation, an inflammatory mass or localized abscess containing pus, small intestine and retina is formed 3 .
For uncomplicated appendicitis, a number of studies have shown that conservative treatment with antibiotics and emergency surgery can achieve relatively good results in the adults 4,5 . But so far, there is still a big controversy on the treatment of complicated appendicitis. Some studies have shown that immediate operation (IO) for complicated appendicitis has the advantages of short hospitalization time and low recurrence rate compared with the early conservative treatment of anti-infection and the interval surgical resection 6,7 . At the same time, recently published meta-analyses indicate that the postoperative complications of early surgery were significantly higher than that of conservative surgery 6,8 .
However, most studies have no research on the short-term recurrence after early treatment and abdominal abscess appendicitis. With the improvement of level of antibiotics and medical technology, laparoscopic and percutaneous puncture drainage has gradually become a new operation for complicated appendicitis, and the treatment of complicated appendicitis has changed 9,10 , the cure rate and complication of complicated appendicitis has been changed 11 . The main purpose of this study is to include recent related studies and compare the complicated appendicitis treated by surgical treatment with conservative treatment through meta-analysis. year, research purpose, sample size and relevant effect indexes selected for the study were sorted out respectively. The collected data were reviewed and discussed by the study organizer (Peng Gao), and the controversial documents were selected or excluded by the study organizer.

Research selection and exclusion criteria
Only studies comparing surgical methods (laparoscopic or open) and conservative methods (anti-infection or including early drainage and selective appendectomy) could be included in the analysis.
According to NOS 13 score, for eligible studies, the scores higher than 6 were defined as high-quality studies. For randomized controlled studies, evidence quality was evaluated using the method recommended by Cochrane Handbook 12 . The selected study should include the following elements Considering the differences in children's development at different ages 14,15 , only patients with complicated appendicitis over 12 could be selected as the study subjects.
Outcome indicators should include at least one kind of hospitalization time, postoperative complications or the total number of complications.
The intervention and control measures should be surgical (laparoscopic or open surgery) and conservative (antibiotics, drainage or no drainage).
Describe the surgical treatment and conservative treatment of the treatment process and results in details.
Report the comparative analysis with other studies or similar studies by the same author.
Randomized controlled study or retrospective study should be including.

exclusion criteria
The study that does not meet the selection criteria.
Important outcome data is incomplete, and there is no report on the results of the two treatments.
The study samples include patients with uncomplicated appendicitis.
The research cannot obtain the required data for meta-analysis through public channels.
The study cannot accurately deduce the outcome.

Interested ending and definition
The immediate operation group (IO) includes patients with complicated appendicitis who underwent emergency surgical treatment and/or exploration. The conservative management group (CM) included patients with complicated appendicitis who failed early conservative treatment, had emergency surgical treatment after early conservative treatment, had elective surgery after early conservative treatment, and did not undergo surgery at all. The outcomes used to contrast the differences between the immediate appendectomy group and the conservative management group were as follows The length of hospital stay includes the first time of hospital stay, the average length of hospital stay, the length of hospital stay after the operation and the total length of hospital stay with the readmission time.
The length of antibiotics includes the time of intravenous antibiotics in the first hospitalization and the time of intravenous antibiotics after recurrent appendicitis and other complications.
Overall complications refer to the number of complications caused by complicated appendicitis during the whole (including follow-up period). Wound infection occurs on the surface or deep layer of the skin after the wound is closed, eliminating the formation of an abscess. Abdominal abscess and ileus obstruction were defined during the whole treatment process diagnosis by imaging diagnosis or emergency surgery or interval appendectomy.
Unplanned additional intervention refers to the unplanned medical intervention (repeated surgery, emergency surgery, puncture drainage, etc.) for recurrent appendicitis, abdominal abscess, etc. that occurs during the treatment and follow-up period.

Data analysis and processing
Statistical analysis was performed using the Revman 5.3 software provided by the The effect of publication bias on the robustness of meta-analysis was evaluated by the metatrim method 19 Result A total of 148 articles were retrieved and 14 studies were eventually included (see Fig. 1 for the procedure of literature selection), of which 845 patients were treated surgically (group IO) and 756 patients were treated conservatively (group CM). A total of 4 randomized controlled studies (RCT) [20][21][22][23] were included, and 10 retrospective studies (RS) [24][25][26][27][28][29][30][31][32][33] were included. The literature information of major concern is shown in the following

Abdominal Abscess
There were 11 studies 20,22,23,26− 32 reported the occurrence of abdominal abscess (Fig. 2. B), of which Brown 25 classified the patients with diffuse peritonitis as abdominal abscess in the study, which did not meet the requirements of this study and was not included in the meta-analysis. The remaining 10 studies showed homogeneity (P > 0.05; I²<50%), Combined with the statistical amount OR, the results showed that the incidence of abdominal abscess was lower in surgical treatment than in conservative treatment, but the difference was not statistically significant (OR = 0.9, 95%CI [0.54, 1.47], P = 0.66 > 0.05).

Post-operate Stay
Four studies 26,28,32,33 reported the length of postoperative stay (Fig. 4. F), with interstudy heterogeneity(P < 0.05; I²>50%), and the Egger method was used to analyze the postoperative hospitalization time, and no significant publication bias was found (P = 0.859 > 0.1). Meta-analysis results showed that the postoperative hospitalization time of patients undergoing surgical treatment was longer than that after interval operate, and the difference was statistically significant (SMD = 0.66, 95%CI [0.42, 0.91], P < 0.00001).

Intestinal Obstruction
Six studies 25,26,29− 32 reported the presence of intestinal obstruction in the surgery group and the conservative group (Fig. 4. G), and each study showed homogeneity (P > 0.05; I²=0%). The results showed that the incidence of intestinal obstruction was higher in surgical treatment than in conservative treatment (OR = 4.14, 95%CI [2.21, 7.75], P < 0.00001).

Post-operate complication
In the analysis of postoperative complications (Fig. 4. H

Discussion
We've found that the total time of admission decrease by about 1 day compared with conservative treatment. Despite the high heterogeneity, the outcome of the event was not reversed after the estimation by the metatrim method, indicating the robustness of this meta-analysis. At the same time, the incidence of unplanned additional intervention in patients undergoing emergency surgery is lower than that of conservative treatment, which means that patients undergoing conservative treatment were more likely to have emergency surgery or repeated admission due to failure of conservative treatment, recurrent appendicitis, abdominal abscess, and potential malignancy. This was the same as Mentula's 22 conclusion.
However, patients undergoing IO are more prone to complications such as wound infections and intestinal obstructions than conservative management patients. This may be related to the dirtier abdominal environment in the emergency surgery, and the conservative treatment group has a selective drain of the abdominal abscess to improve the environment.
Notably, the meta-analysis of abdominal abscess shows that the incidence of abdominal abscess is lower with surgery than with conservative treatment. Although there is no statistically significant difference between the two, the results indicated that surgical treatment is more effective than conservative treatment in emptying the pus.
Unfortunately, due to the lack of rigorous RCT researches, and the variety of patients, it is difficult to accurately determine the merits of surgical versus percutaneous drainage for abdominal abscess.
To date, there is no standard treatment for complicated appendicitis with localized perforation, abscess, or mass formation. In some areas, IO for complicated appendicitis remains the preferred treatment for many surgeons. In recent years, the evidence that conservative treatment is a superior way of the complicated appendicitis has been questioned 26 . Some patients with conservative treatment finally have worse symptoms and lead to more surgical treatment. Not only that, the patient has to show a response for this anti-infective treatment to continue. These patients with the conservative management failure are eventually excluded from the analysis, this situation may cause data analysis more inclined to non-surgical treatment.
As the follow-up of patients after discharge became more detailed, opponents of the strategy raised some issues caused by conservative treatment, such as recurrent appendicitis, missed potential malignancies, and unconsolidated appendicitis progressing to appendiceal mass. This study clearly explained that conservative treatment caused more additional operations to patients through the summary of studies in recent 20 years.

Consent for publication
Not applicable

Availability of data and materials
All data in this article are derived from published articles, and the data generated or analysed during this study are included in this article.

Competing interests
The authors declare that they have no competing interests.

Funding
All financial support in this study came from corresponding author sponsorship

Authors' contributions
Each author is responsible for the design of the study, the analysis of the data and the drafting and revision of the article, and ensure that questions related to the accuracy or integrity of any part of the work The Corresponding authors Peng Gao ensure that all listed authors have approved the manuscript before submission, including the names and order of authors, make it certain that no author on earlier versions have been removed or new authors added, and all data comply with the transparency and reproducibility standards of both the field and journal.
university, who is engaged in emergency surgery. He has come into contact with many patients with acute appendicitis in his work, and has great interest in the treatment of acute appendicitis.
appendicitis: a randomized controlled trial to prove safety.