Aspects of treatment of acute uncomplicated appendicitis in children and adults

<p dir="ltr">Acute appendicitis is a clinical term for inflammation of the vermiform appendix with a sudden onset. Symptoms depend both on the age of a patient and on the position of appendix intraabdominally. The aetiology remains unknown, although, there are multiple theories. The lifetime risk of acute appendicitis in Western countries has been established as 7-8%, with 8.6% for males and 6.7% for females. The standard treatment has been surgery for many decades, but non-operative treatment, in the form of antibiotics, has more recently come to light as a feasible alternative to appendectomies.</p><p dir="ltr">Aims: The aim of this thesis was to assess intermediate and long-term outcomes of non- operative treatment in both children and adults. This included assessing safety and feasibility of non-operative treatment and its complications. An additional aim was to ascertain the failure rate of non-operative treatment and recurrence of acute uncomplicated appendicitis in children and try to establish the reasons for the treatment failure.</p><p dir="ltr">Methods: Study I was a 5-year follow-up of all participants who underwent surgery or non- operative treatment with antibiotics in a previous randomised controlled pilot trial. Data was extracted from the hospital notes and telephone interviews.</p><p dir="ltr">Study II was a long-term follow-up of adults with acute appendicitis who were involved in two randomised controlled trials, which compared non-operative treatment with appendectomy. The first trial consisted of 40 patients (13 female) and second trial was a multicentre study with 252 male patients. National registers were used to retrieve data at follow up, including the Swedish National Patient Register, the Cancer Register, the Cause of Death Register and Statistics Sweden.</p><p dir="ltr">Study III was a systematic review that was registered in PROSPERO (CRD42024592607) and done according to PRISMA statement. We searched three databases (PubMed, Medline, Web of Science). Eligible studies were randomised controlled trials or prospective cohort studies with children aged <18 years that received non-operative treatment for uncomplicated appendicitis and reporting at least 30 days follow-up. We carried out a meta- analysis.</p><p dir="ltr">Results: In Study I, we followed up all 50 children (26 children in the appendectomy group, 24 children in the nonoperative group) for at least 5 years. The surgical group was without failures and in the nonoperative group there were 11 failures and recurrences. In the first year there were nine failures, two of them had an appendicitis on the histopathology. Another two recurrences, that were histopathologically confirmed appendicitis occurred one to five years after the initial trial. At the 5-year follow-up, 54% of children had been successfully treated nonoperatively with antibiotics alone.</p><p dir="ltr">In Study II, in total, we were able to trace down 259 patients in the Patient Register, 137 patients in the non-operative group and 122 in the surgical group. At the end of follow-up, 82 (60%) patients had had successful non-operative treatment without an appendectomy. In the non-operative group there were 21 (15%) failures during the first admission. Thirty-four recurrences happened after discharge, all with a diagnostic code of acute appendicitis. After successful initial treatment, 82/116 (71%) remained without appendectomy.</p><p dir="ltr">In Study III, through a systematic search we were able to identify 2343 abstracts. Thirty studies were eligible, 8 randomised controlled trials and 22 prospective cohort studies reporting 27 different patient cohorts. An early failure rate occurred in 10% (95% CI 7-14%) and the recurrence rate was 29% (95% CI 24-34%) at the end of follow-up. When analysing studies with faecalith, a failure rate was higher (17% versus 6.4%) with P-value <0.0001.</p><p dir="ltr">Conclusions: Studies I and II demonstrated intermediate- and long-term safety of non- operative treatment alone in children and adults. This treatment does not increase the risk of malignancy and other complications and patients avoid surgery. Study III demonstrated a low initial failure rate and the recurrence rate was 29%. Non-operative treatment was less successful in children with a faecalith, particularly during first admission. These results can be used for discussion about treatment options of uncomplicated appendicitis with child patients and their caregivers.</p><h3>List of scientific papers</h3><p dir="ltr">I. <b>Patkova B</b>, Svenningsson A, Almström M, Eaton S, Wester T, Svensson JF. Nonoperative Treatment Versus Appendectomy for Acute Nonperforated Appendicitis in Children: Five-year Follow Up of a Randomized Controlled Pilot Trial. Ann Surg. 2020 Jun;271(6):1030-1035. <a href="https://doi.org/10.1097/SLA.0000000000003646">https://doi.org/10.1097/SLA.0000000000003646</a></p><p dir="ltr">II. <b>Pátková B,</b> Svenningsson A, Almström M, Svensson JF, Eriksson S, Wester T, Eaton S. Long-Term Outcome of Nonoperative Treatment of Appendicitis. JAMA Surg. 2023 Oct 1;158(10):1105-1106. <a href="https://doi.org/10.1001/jamasurg.2023.2756">https://doi.org/10.1001/jamasurg.2023.2756</a></p><p dir="ltr">III. <b>Patková B</b>, Svenningsson A, Jumah S, Wester T, Eaton S. Failure and recurrence of non-operative treatment of uncomplicated appendicitis in children; a systematic review and meta-analysis. [Manuscript]</p>

Although non-operative treatment is known to be effective for the treatment of uncomplicated acute appendicitis in children, randomised trial data comparing important outcomes of non-operative treatment with those of appendicectomy are lacking. The objectives were to ascertain the feasibility of conducting a multicentre randomised controlled trial comparing the clinical effectiveness and cost-effectiveness of a non-operative treatment pathway with appendicectomy for the treatment of uncomplicated acute appendicitis in children. This was a mixed-methods study, which included a feasibility randomised controlled trial, embedded and parallel qualitative and survey studies, a parallel health economic feasibility study and the development of a core outcome set. This study was set in three specialist NHS paediatric surgical units in England. Children (aged 4-15 years) clinically diagnosed with uncomplicated acute appendicitis participated in the feasibility randomised controlled trial. Children, their families, recruiting clinicians and other health-care professionals involved in caring for children with appendicitis took part in the qualitative study. UK specialist paediatric surgeons took part in the survey. Specialist paediatric surgeons, adult general surgeons who treat children, and children and young people who previously had appendicitis, along with their families, took part in the development of the core outcome set. Participants in the feasibility randomised controlled trial were randomised to a non-operative treatment pathway (broad-spectrum antibiotics and active observation) or appendicectomy. The primary outcome measure was the proportion of eligible patients recruited to the feasibility trial. Data were sourced from NHS case notes, questionnaire responses, transcribed audio-recordings of recruitment discussions and qualitative interviews. Overall, 50% (95% confidence interval 40% to 59%) of 115 eligible patients approached about the trial agreed to participate and were randomised. There was high acceptance of randomisation and good adherence to trial procedures and follow-up (follow-up rates of 89%, 85% and 85% at 6 weeks, 3 months and 6 months, respectively). More participants had perforated appendicitis than had been anticipated. Qualitative work enabled us to communicate about the trial effectively with patients and families, to design and deliver bespoke training to optimise recruitment and to understand how to optimise the design and delivery of a future trial. The health economic study indicated that the main cost drivers are the ward stay cost and the cost of the operation; it has also informed quality-of-life assessment methods for future work. A core outcome set for the treatment of uncomplicated acute appendicitis in children and young people was developed, containing 14 outcomes. There is adequate surgeon interest to justify proceeding to an effectiveness trial, with 51% of those surveyed expressing a willingness to recruit with an unchanged trial protocol. Because the feasibility randomised controlled trial was performed in only three centres, successful recruitment across a larger number of sites cannot be guaranteed. However, the qualitative work has informed a bespoke training package to facilitate this. Although survey results suggest adequate clinician interest to make a larger trial possible, actual participation may differ, and equipoise may have changed over time. A future effectiveness trial is feasible, following limited additional preparation, to establish appropriate outcome measures and case identification. It is recommended to include a limited package of qualitative work to optimise recruitment, in particular at new centres. Prior to proceeding to an effectiveness trial, there is a need to develop a robust method for distinguishing children with uncomplicated acute appendicitis from those with more advanced appendicitis, and to reach agreement on a primary outcome measure and effect size that is acceptable to all stakeholder groups involved. Current Controlled Trials ISRCTN15830435. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 10. See the NIHR Journals Library website for further project information.

Systematic review of nonoperative versus operative treatment of uncomplicated appendicitis

BackgroundAppendectomy 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...

Transumbilical laparoscopic-assisted appendectomy (TULAA) is increasingly being performed worldwide. The authors report their experience in the treatment of acute uncomplicated appendicitis in children with TULAA. From January 2008 to December 2012 all types of acute appendicitis were divided, according to the clinical and ultrasonographic findings, into complicated (appendiceal mass/abscess, diffuse peritonitis) and uncomplicated. Complicated appendicitis was treated by open appendectomy (OA). All patients with the suspicion of uncomplicated appendicitis were offered TULAA by all surgeons of the team. Conversion to open or laparoscopic appendectomy (LA) was performed in case of impossibility to complete TULAA, depending on the choice of surgeon. The histopathologic examination of appendix was always performed. 444 children (252 males) with acute appendicitis were treated. The mean age was 9.2 years (range, 2 to 14 years). Primary OA was performed in 144 cases. In 300 patients a transumbilical laparoscopic-assisted approach was performed. TULAA was completed in 252 patients. Conversion to OA was performed in 45 patients and to LA in 3. Conversion was related to the impossibility to adequately expose the appendix in 47 patients and bleeding in 1. The mean operative time for TULAA was 42 minutes. Histopathologic examination of the appendix removed by TULAA showed a phlegmonous/gangrenous type in 92.8% of cases. Among the 252 TULAA there were 11 cases of umbilical wound infection. TULAA is a feasible and effective procedure for uncomplicated appendicitis in children. It combines the advantages of open and laparoscopic technique (low operative time, low complications rate, and excellent cosmetic results).

BackgroundCurrently, the routine treatment for acute appendicitis in the United Kingdom is an appendicectomy. However, there is increasing scientific interest and research into non-operative treatment of appendicitis in adults and children. While a number of studies have investigated non-operative treatment of appendicitis in adults, this research cannot be applied to the paediatric population. Ultimately, we aim to perform a UK-based multicentre randomised controlled trial (RCT) to test the clinical and cost effectiveness of non-operative treatment of acute uncomplicated appendicitis in children, as compared with appendicectomy. First, we will undertake a feasibility study to assess the feasibility of performing such a trial.Methods/designThe study involves a feasibility RCT with a nested qualitative research to optimise recruitment as well as a health economic substudy. Children (aged 4–15 years inclusive) diagnosed with acute uncomplicated appendicitis that would normally be treated with an appendicectomy are eligible for the RCT. Exclusion criteria include clinical/radiological suspicion of perforated appendicitis, appendix mass or previous non-operative treatment of appendicitis. Participants will be randomised into one of two arms. Participants in the intervention arm are treated with antibiotics and regular clinical assessment to ensure clinical improvement. Participants in the control arm will receive appendicectomy. Randomisation will be minimised by age, sex, duration of symptoms and centre. Children and families who are approached for the RCT will be invited to participate in the embedded qualitative substudy, which includes recording of recruitment consultants and subsequent interviews with participants and non-participants and their families and recruiters. Analyses of these will inform interventions to optimise recruitment. The main study outcomes include recruitment rate (primary outcome), identification of strategies to optimise recruitment, performance of trial treatment pathways, clinical outcomes and safety of non-operative treatment. We have involved children, young people and parents in study design and delivery.DiscussionIn this study we will explore the feasibility of performing a full efficacy RCT comparing non-operative treatment with appendicectomy in children with acute uncomplicated appendicitis. Factors determining success of the present study include recruitment rate, safety of non-operative treatment and adequate interest in the future RCT. Ultimately this feasibility study will form the foundation of the main RCT and reinforce its design.Trial registrationISRCTN15830435. Registered on 8 February 2017.

Currently, the most frequently used treatment for acute appendicitis in children in the United Kingdom (UK) is an appendicectomy. However, there is increasing scientific and patient interest and research into non-operative treatment of appendicitis. Despite a number of non-randomised studies in children and randomised studies in adults, comparative outcomes of non-operative treatment and appendicectomy in comparable groups of children remain unknown. Following the successful completion of a feasibility study, we now aim to perform a UK-based multi-centre open-label randomised controlled trial (RCT) to investigate the clinical and cost-effectiveness of non-operative treatment pathway of acute uncomplicated appendicitis in children compared with appendicectomy. Non-inferiority RCT with internal pilot, health economic evaluation and qualitative communication sub-study. The study is conducted in England, Northern Ireland, Scotland and Wales at both specialist children's hospitals and district general hospitals. Children (aged 4-15years inclusive) diagnosed with acute uncomplicated appendicitis that would normally be treated with an appendicectomy are eligible for the RCT. Exclusion criteria include clinical/radiological suspicion of perforated appendicitis, appendix mass or previous non-operative treatment of appendicitis. Sample size is 376 participants, recruited by surgeons and supported by research staff and randomised with a 1:1 allocation ratio to either non-operative treatment pathway (intervention) or appendicectomy (control). Participants in the intervention arm are treated with antibiotics, analgesia and regular clinical assessment to ensure clinical improvement. Participants in the control arm receive appendicectomy. Randomisation is minimised by age, sex, duration of symptoms and centre. The primary end-point is a composite outcome of treatment success at 1year following randomisation. Secondary outcomes include: duration of hospital stay, measures of recovery from acute appendicitis, complications, need for further treatment, persistent symptoms, health care resource use, quality of life and costs. Adverse events, serious adverse events and suspected unexpected serious adverse events are collected directly on the database and by paper form up to 12-month visit. Primary outcome will be analysed on a non-inferiority basis using a 20% non-inferiority margin to test the hypothesis that non-operative treatment pathway is non-inferior to appendicectomy. Children and families who are approached for the RCT will be invited to participate in the embedded qualitative sub-study. This will include recording of recruitment consultations, which will inform future interventions to optimise recruitment. We have involved children, young people and parents in study design and delivery. This RCT will allow determination of the comparative clinical and cost-effectiveness of non-operative treatment pathway compared to appendicectomy for children with uncomplicated acute appendicitis in the UK. First planned enrolment-December 2022, first actual recruit-March 2022, current status of trial-open to recruitment. ISRCTN16720026 . Registered on July 28, 2021.

Covid-19 Pandemic Strategy for Treatment of Acute Uncomplicated Appendicitis with Antibiotics- Risk Categorization and Shared Decision-Making

Background: Pediatric healthcare is evolving, with acute appendicitis being a common issue. Traditionally, appendectomy has been the standard treatment. However, recent literature suggests that conservative antibiotic treatment could be a viable option, particularly for uncomplicated cases in children. Aim of the study: The aim of the study was to evaluate the outcomes of conservative treatment for uncomplicated acute appendicitis in children. Methods: From July 2017 to March 2019, a prospective observational study was conducted at Dhaka Medical College Hospital, Bangladesh, involving 62 children with uncomplicated acute appendicitis. They received conservative treatment, including supportive care, for five days. Patients who responded positively within 24 hours continued for at least five days before discharge and underwent a 6-month follow-up. Results: The study encompassed 62 patients, with a mean age of 8.95 years, and a slight male predominance (61.3% male, 38.7% female). Clinical findings revealed a notable decrease in pain intensity (9.42 to 0.77), temperature (101.02º to 98.90º), and inflammatory markers (CRP: 28.13 ± 11.56 mg/L to 9.78 ± 7.50 mg/L) from admission to day 5. The mean duration of hospital stay was 5.26 ± 0.63 days. Remarkably, 95.1% of patients successfully recovered with conservative treatment, while 4.9% required surgery as part of their treatment course. Conclusion: This study found some potential benefits of conservative treatment for uncomplicated acute appendicitis in children. Significant improvements in clinical parameters and a high success rate emphasize its potential as a viable alternative to surgery in select cases, warranting further exploration in pediatric healthcare practices.

Nonoperative management in children with early acute appendicitis: A systematic review

Background: Acute appendicitis is one of the commonest cause of acute abdomen. For more than 100 years, surgeons have been successfully performing appendectomy to treat acute appendicitis. However, there is a recent trend to shift towards a more conservative approach. There has been a wide discussion and controversy on the surgical and non-surgical treatment of acute uncomplicated appendicitis. This work aimed to assess the effectiveness of non-operative conservative management in the treatment of acute uncomplicated appendicitis. Method: This was a single tertiary care level hospital based study done within the duration from 1st September 2016 to 31st January 2018. 180 patients with clinical and radiological features of acute appendicitis presenting within 48 hrs of onset of the symptoms were enrolled. The patients received a broad spectrum antibiotic and symptomatic treatment. The patients were followed up for 6 months. Results: Total 180 patients were enrolled. 108 (60%) of patients were female and 72 (40%) patients were males with mean age of 36 years. 144 (80%) patients successfully responded with the conservative treatment with antibiotics while 36 (20%) patients failed. No mortality was recorded in our study. Out of 36 patients who failed, 13 patients developed appendicular abscess, 12 patients had perforation of appendix while 11 patients had appendicular lump. Conclusions: Conservative management can be established as the first line of management for uncomplicated acute appendicitis patients having first attack successfully, but it should be followed with close monitoring of patients.

Objective: To compare the efficacy of non-surgical conservative management with surgical management in cases of uncomplicated acute appendicitis in children.
 Study design: Prospective comparative study.
 Settings: Pediatric surgery Department, Ghulam Muhammad Mahar Medical College Sukkur.
 Study duration: 1st February 2020 to 31st May 2021.
 Materials and Methods: Ninety patients of either gender with age range from 5-12 years, diagnosed as uncomplicated acute appendicitis, were divided in two groups. Group C patients were managed conservatively with antibiotics (ceftriaxone 100 mg/kg/day, amikacin 10mg/kg/day and metronidazole 22.5 mg/kg/day) and maintenance fluids were started. Patients were observed for improvement or any signs of deterioration. Those who deteriorated within 24 hours were managed with surgical management immediately. Follow-ups were carried out after discharge on the 7th day, 1 month, and six months. Patients reporting a recurrence of symptoms were managed with appendicectomy. Group S patients were managed with appendicectomy with the open technique. Patients were observed for post-operative complications.
 Results: Demographic data of both groups was comparable. In group C, 34 (75.56%) patients were successfully treated with conservative management, whereas in group S, 39 (86.67%) were successfully treated with surgical management. The difference was insignificant with a p-value of 0.114. In group C, 5 (11.11%) patients did not respond to conservative management and they were managed with appendicectomy and recurrence of symptoms was seen in 6 (13.33%) patients in group C, they were also managed with appendicectomy. In group S, 6 (13.33%) patients suffered post-operative complications. Mean length of stay in hospital was 4.31±1.20 and 4.09±1.12 days in group C and S respectively. This difference was statistically insignificant with a p-value of 0.368.
 Conclusion: It is concluded in our study that uncomplicated acute appendicitis in children can be successfully managed with non-surgical conservative management.

More than a century after its introduction, appendectomy has remained the gold standard treatment for acute appendicitis. In adults with acute uncomplicated appendicitis, nonoperative management (NOM) has been shown to be a viable treatment option. To date, there has been relatively limited data on the nonoperative management of acute appendicitis in the pediatric population. The primary objective of this study was to systematically review the available literature in the pediatric population and compare the efficacy and recurrence between initial nonoperative treatment strategy and appendectomy in children with uncomplicated appendicitis. In July 2021, we conducted systematic searches of the PubMed and Google Scholar databases. We only included full-text comparative original studies published within the last decade, and we excluded articles that solely examined NOM without comparing it to appendectomy. Two writers worked independently on the data collection and analysis. It was found that NOM had a high initial success rate and a low rate of recurrent appendicitis. After months of follow-up, the vast majority of patients with uncomplicated acute appendicitis who received initial nonoperative treatment did not require surgical intervention. Furthermore, the rate of complication was comparable in both treatment groups, and NOM did not appear to be associated with an increased risk of complications. The most significant drawback stemmed from the fact that the included articles in this study had a wide range of study designs and inclusion criteria. According to current evidence, NOM is feasible and cost-effective. Antibiotic therapy can be given safely in a small subset of individuals with uncomplicated appendicitis. To optimize outcomes, physicians should evaluate the clinical presentation and the patient's desire when selecting those to be managed nonoperatively. Again, more research, preferably large randomized trials, is required to compare the long-term clinical efficacy of NOM with appendicectomy. Finally, additional research is required to establish the characteristics of patients who are the best candidates for nonoperative treatment.

2412 Cost effectiveness analysis of operative Versus antibiotic management for uncomplicated appendicitis

The aim of this study was to evaluate the feasibility and safety of nonoperative treatment of acute nonperforated appendicitis with antibiotics in children. A pilot randomized controlled trial was performed comparing nonoperative treatment with antibiotics versus surgery for acute appendicitis in children. Patients with imaging-confirmed acute nonperforated appendicitis who would normally have had emergency appendectomy were randomized either to treatment with antibiotics or to surgery. Follow-up was for 1 year. Fifty patients were enrolled; 26 were randomized to surgery and 24 to nonoperative treatment with antibiotics. All children in the surgery group had histopathologically confirmed acute appendicitis, and there were no significant complications in this group. Two of 24 patients in the nonoperative treatment group had appendectomy within the time of primary antibiotic treatment and 1 patient after 9 months for recurrent acute appendicitis. Another 6 patients have had an appendectomy due to recurrent abdominal pain (n = 5) or parental wish (n = 1) during the follow-up period; none of these 6 patients had evidence of appendicitis on histopathological examination. Twenty-two of 24 patients (92%) treated with antibiotics had initial resolution of symptoms. Of these 22, only 1 patient (5%) had recurrence of acute appendicitis during follow-up. Overall, 62% of patients have not had an appendectomy during the follow-up period. This pilot trial suggests that nonoperative treatment of acute appendicitis in children is feasible and safe and that further investigation of nonoperative treatment is warranted.