Support for the treatment of uncomplicated appendicitis with non-operative management rather than surgery has been increasing in the literature. We aimed to investigate whether treatment of uncomplicated appendicitis with antibiotics in children is inferior to appendicectomy by comparing failure rates for the two treatments.

In this pragmatic, multicentre, parallel-group, unmasked, randomised, non-inferiority trial, children aged 5-16 years with suspected non-perforated appendicitis (based on clinical diagnosis with or without radiological diagnosis) were recruited from 11 children's hospitals in Canada, the USA, Finland, Sweden, and Singapore. Patients were randomly assigned (1:1) to the antibiotic or the appendicectomy group with an online stratified randomisation tool, with stratification by sex, institution, and duration of symptoms (≥48 h vs <48 h). The primary outcome was treatment failure within 1 year of random assignment. In the antibiotic group, failure was defined as removal of the appendix, and in the appendicectomy group, failure was defined as a normal appendix based on pathology. In both groups, failure was also defined as additional procedures related to appendicitis requiring general anaesthesia. Interim analysis was done to determine whether inferiority was to be declared at the halfway point. We used a non-inferiority design with a margin of 20%. All outcomes were assessed in participants with 12-month follow-up data. The trial was registered at ClinicalTrials.gov (NCT02687464).

Between Jan 20, 2016, and Dec 3, 2021, 936 patients were enrolled and randomly assigned to appendicectomy (n=459) or antibiotics (n=477). At 12-month follow-up, primary outcome data were available for 846 (90%) patients. Treatment failure occurred in 153 (34%) of 452 patients in the antibiotic group, compared with 28 (7%) of 394 in the appendicectomy group (difference 26·7%, 90% CI 22·4-30·9). All but one patient meeting the definition for treatment failure with appendicectomy were those with negative appendicectomies. Of those who underwent appendicectomy in the antibiotic group, 13 (8%) had normal pathology. There were no deaths or serious adverse events in either group. The relative risk of having a mild-to-moderate adverse event in the antibiotic group compared with the appendicectomy group was 4·3 (95% CI 2·1-8·7; p<0·0001).

Based on cumulative failure rates and a 20% non-inferiority margin, antibiotic management of non-perforated appendicitis was inferior to appendicectomy.

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While patients with acute uncomplicated appendicitis may be treated conservatively, those who suffer from complicated appendicitis require surgery. We describe a logistic regression equation to calculate the likelihood of acute uncomplicated appendicitis and complicated appendicitis in patients presenting to the emergency department with suspected acute appendicitis.

A cohort of 895 patients who underwent appendicectomy were analysed retrospectively. Depending on the final histology, patients were divided into three groups; normal appendix, acute uncomplicated appendicitis and complicated appendicitis. Normal appendix was considered the reference category, while acute uncomplicated appendicitis and complicated appendicitis were the nominal categories. Multivariate and univariate regression models were undertaken to detect independent variables with significant odds ratio that can predict acute uncomplicated appendicitis and complicated appendicitis. Subsequently, a logistic regression equation was generated to produce the likelihood acute uncomplicated appendicitis and complicated appendicitis.

Pathological diagnosis of normal appendix, acute uncomplicated appendicitis and complicated appendicitis was identified in 188 (21%), 525 (59%) and 182 patients (20%), respectively. The odds ratio from a univariate analysis to predict complicated appendicitis for age, female gender, log2 white cell count, log2 C-reactive protein and log2 bilirubin were 1.02 (95% confidence interval, CI, 1.01, 1.04), 2.37 (95% CI 1.51, 3.70), 9.74 (95% CI 5.41, 17.5), 1.57 (95% CI 1.40, 1.74), 2.08 (95% CI 1.56, 2.76), respectively. For the same variable, similar odds ratios were demonstrated in a multivariate analysis to predict complicated appendicitis and univariate and multivariate analysis to predict acute uncomplicated appendicitis.

The likelihood of acute uncomplicated appendicitis and complicated appendicitis can be calculated by using the reported predictive equations integrated into a web application at www.appendistat.com. This will enable clinicians to determine the probability of appendicitis and the need for urgent surgery in case of complicated appendicitis.

Acute appendicitis (AA) develops in a progressive and irreversible manner, even if the clinical course of AA can be temporarily modified by intentional medications. Reliable and real-time diagnosis of AA can be made based on findings of the white blood cell count and enhanced computed tomography. Emergent laparoscopic appendectomy (LA) is considered as the first therapeutic choice for AA. Interval/delayed appendectomy at 6-12 wk after disease onset is considered as unsafe with a high recurrent rate during the waiting time. However, this technique may have some advantages for avoiding unnecessary extended resection in patients with an appendiceal mass. Non-operative management of AA may be tolerated only in children. Postoperative complications increase according to the patient's factors, and temporal avoidance of emergent general anesthesia may be beneficial for high-risk patients. The surgeon's skill and cooperation of the hospital are important for successful LA. Delaying appendectomy for less than 24 h from diagnosis is safe. Additionally, a semi-elective manner (i.e., LA within 24 h after onset of symptoms) may be paradoxically acceptable, according to the factors of the patient, physician, and institution. Prompt LA is mandatory for AA. Fortunately, the Japanese government uses a universal health insurance system, which covers LA.

Appendectomy is considered the gold standard treatment for acute appendicitis. Recently the need for surgery has been challenged in both adults and children. In children there is growing clinician, patient and parental interest in non-operative treatment of acute appendicitis with antibiotics as opposed to surgery. To date no multicentre randomised controlled trials that are appropriately powered to determine efficacy of non-operative treatment (antibiotics) for acute appendicitis in children compared with surgery (appendectomy) have been performed.

Multicentre, international, randomised controlled trial with a non-inferiority design. Children (age 5-16 years) with a clinical and/or radiological diagnosis of acute uncomplicated appendicitis will be randomised (1:1 ratio) to receive either laparoscopic appendectomy or treatment with intravenous (minimum 12 hours) followed by oral antibiotics (total course 10 days). Allocation to groups will be stratified by gender, duration of symptoms (> or <48 hours) and centre. Children in both treatment groups will follow a standardised treatment pathway. Primary outcome is treatment failure defined as additional intervention related to appendicitis requiring general anaesthesia within 1 year of randomisation (including recurrent appendicitis) or negative appendectomy. Important secondary outcomes will be reported and a cost-effectiveness analysis will be performed. The primary outcome will be analysed on a non-inferiority basis using a 20% non-inferiority margin. Planned sample size is 978 children.

The APPY trial will be the first multicentre randomised trial comparing non-operative treatment with appendectomy for acute uncomplicated appendicitis in children. The results of this trial have the potential to revolutionise the treatment of this common gastrointestinal emergency. The randomised design will limit the effect of bias on outcomes seen in other studies.

clinicaltrials.gov: NCT02687464. Registered on Jan 13th 2016.

Randomized trials suggest that nonoperative treatment of uncomplicated appendicitis with antibiotics-first is safe. No trial has evaluated outpatient treatment and no US randomized trial has been conducted, to our knowledge. This pilot study assessed feasibility of a multicenter US study comparing antibiotics-first, including outpatient management, with appendectomy.

Patients aged 5 years or older with uncomplicated appendicitis at 1 US hospital were randomized to appendectomy or intravenous ertapenem greater than or equal to 48 hours and oral cefdinir and metronidazole. Stable antibiotics-first-treated participants older than 13 years could be discharged after greater than or equal to 6-hour emergency department (ED) observation with next-day follow-up. Outcomes included 1-month major complication rate (primary) and hospital duration, pain, disability, quality of life, and hospital charges, and antibiotics-first appendectomy rate.

Of 48 eligible patients, 30 (62.5%) consented, of whom 16 (53.3%) were randomized to antibiotics-first and 14 (46.7%) to appendectomy. Median age was 33 years (range 9 to 73 years), median WBC count was 15,000/μL (range 6,200 to 23,100/μL), and median computed tomography appendiceal diameter was 10 mm (range 7 to 18 mm). Of 15 antibiotic-treated adults, 14 (93.3%) were discharged from the ED and all had symptom resolution. At 1 month, major complications occurred in 2 appendectomy participants (14.3%; 95% confidence interval [CI] 1.8% to 42.8%) and 1 antibiotics-first participant (6.3%; 95% CI 0.2% to 30.2%). Antibiotics-first participants had less total hospital time than appendectomy participants, 16.2 versus 42.1 hours, respectively. Antibiotics-first-treated participants had less pain and disability. During median 12-month follow-up, 2 of 15 antibiotics-first-treated participants (13.3%; 95% CI 3.7% to 37.9%) developed appendicitis and 1 was treated successfully with antibiotics; 1 had appendectomy. No more major complications occurred in either group.

A multicenter US trial comparing antibiotics-first to appendectomy, including outpatient management, is feasible to evaluate efficacy and safety.

A man in his early thirties presented to our clinic with right lower abdominal pain. Computed tomography (CT) and ultrasonography (US) revealed a swollen appendix and an appendicolith. Abscess formation was not observed but ongoing appendiceal rupture was not ruled out. Three months after successful conservative therapy, the lumen of the apical portion was kept dilated and laparoscopic interval appendectomy was performed. No tumorous findings were observed macroscopically. However, histology revealed many tiny nests infiltrating the submucosa, muscular layer, and subserosa at the root of the appendix. An appendiceal neuroendocrine tumor G1 (NET G1; carcinoid) was diagnosed immunohistologically. Neither CT nor US visualized the tumor because of its non-tumor-forming but infiltrative growth. In conclusion, after successful conservative treatment, interval appendectomy should be considered to uncover a possible appendiceal NET G1 (carcinoid), particularly when dilatation of the distal lumen is kept under observation.

Complicated intra-abdominal infections such as acute appendicitis and complicated diverticulitis represent both diagnostic and therapeutic challenges. Both diseases, although different in many ways, are caused by the obstruction of a blind pouch leading to inflammation, abscesses, and perforation of surrounding tissues. For many decades, acute appendicitis was managed through a conventional surgical incision in the right iliac fossa. As for other diseases, there is a significant tendency to propose less invasive treatments. For many teams, laparoscopy, which leads to less postoperative pain, a shorter hospital stay, and a quicker recovery, represents the standard of care for appendectomy. For selected cases, a medical approach can be proposed with satisfactory outcomes. Additionally, the management of complicated diverticulitis is also quickly moving towards less invasive procedures than the deleterious '3-phase surgery', which is Hartmann's procedure, followed by reversal protected with a stoma, and finally stoma closure. Benefiting from the evolution of antimicrobial therapy and interventional radiology, many complicated cases classified as Hinchey stage I and Hinchey stage II complicated diverticulitis are now treated medically. CT images allow the identification of patients requiring radiological drainage of localized abscesses or collections over 5 cm in size. Patients with Hinchey stage III sigmoiditis may benefit from an initial laparoscopic exploration allowing, in some cases, a conservative nonresective approach that will prevent laparotomy and stoma. Major resection leading to temporary or definitive stoma is usually indicated for stage IV complications and is required only in exceptional cases. Although a surgical intervention can be the definitive treatment for complicated intra-abdominal infections, multidisciplinary management including radiology, medical treatment, and laparoscopic surgery may limit the severe consequences of an acute surgical approach in patients suffering from complicated appendicitis and diverticulitis. Today, the ultimate goal of acutely infected abdomen management is to reduce hospital stay, disability, and numerous operations for these patients.

Neoplasms are an uncommon finding after appendectomy, with malignant tumors occurring in less than 1% of the surgical specimens, and carcinoid being the most frequent malignancy. A negative or inconclusive ultrasound is not adequate to rule out appendicitis and should be followed by CT scan. For pregnant patients, MRI is a reasonable alternative to CT scan. Nonoperative treatment with antibiotics is safe as an initial treatment of uncomplicated appendicitis, with a significant decrease in complications but a high failure rate. Open and laparoscopic appendectomies for appendicitis provide similar results overall, although the laparoscopic technique may be advantageous for obese and elderly patients but may be associated with a higher incidence of intraabdominal abscess. Preoperative diagnostic accuracy is of utmost importance during pregnancy because a negative appendectomy is associated with a significant incidence of fetal loss. The increased morbidity associated with appendectomy delay suggests that prompt surgical intervention remains the safest approach. Routine incidental appendectomy should not be performed except in selected cases. Interval appendectomy is not indicated because of considerable risks of complications and lack of any clinical benefit. Patients older than 40 years with an appendiceal mass or abscess treated nonoperatively should routinely have a colonoscopy as part of their follow-up to rule out cancer or alternative diagnosis.

The objective was to conduct a meta-analysis of randomized controlled trials evaluating the efficacy and morbidity of the management of acute uncomplicated (no abscess or phlegmon) appendicitis by antibiotics versus appendectomy.

Appropriate trials were identified. The seven outcome variables were overall complication rate, treatment failure rate for index hospital admission, overall treatment failure rate, length of stay (LOS), utilization of pain medication, duration of pain, and sick leave. Both fixed and random effects meta-analyses were performed using odds ratios (ORs) and weighted or standardized mean differences (WMDs or SMDs, respectively).

Five trials totaling 980 patients (antibiotics=510, appendectomy=470) were analyzed. In three of the seven outcome analyses, the summary point estimates favored antibiotics over appendectomy, with a 46% reduction in the relative odds of complications (OR 0.54; 95% confidence interval [CI] 0.37, 0.78; p=0.001); a reduction in sick leave/disability (SMD -0.19; CI -0.33, -0.06; p=0.005), and decreased pain medication utilization (SMD -1.55; CI -1.96, -1.14; p<0.0001). For overall treatment failure, the summary point estimate favored appendectomy, with a 40.2% failure rate for antibiotics versus 8.5% for appendectomy (OR 6.72; CI 0.08, 12.99; p<0.001). Initial treatment failure, LOS, and pain duration were similar in the two groups.

Non-operative management of uncomplicated appendicitis with antibiotics was associated with significantly fewer complications, better pain control, and shorter sick leave, but overall had inferior efficacy because of the high rate of recurrence in comparison with appendectomy.