1. Antibiotics-first approach in uncomplicated acute appendicitis
Good morning senior and colleagues.
My topic for presentation is antibiotics first approach for uncomplicated acute appendicitis.
JOINT HOSPITAL SURGICAL GRAND ROUND
WONG YIM PING
TUEN MUN HOSPITAL
23rd April, 2016

2. Outline Background and introduction Definition
Literature review and appraisal
Summary

3. Acute appendicitis One of the commonest cause of acute abdomen
Lifetime incidence 7% in the US population [1]
In Hong Kong 2492 appendicectomies were performed in year [2]
[1] Addiss DG, Shaffer N, Fowler BS, Tauxe RV. The epidemiology of appendicitis and appendectomy in the United States. Am J Epidemiol. 1990;132:910–25.
[2] SOMIP reprt July 2014 –June 2015

4. Conventional teaching
Appendicectomy for uncomplicated appendicitis
Prevent progression to perforation and other complications
Appendicectomy is a surgery of low morbidity and mortality

6. Is antibiotic therapy as useful as surgery?

7. Antibiotics first approach
Antibiotic therapy
Supportive care
Careful observation
+/- appendicectomy

8. Uncomplicated acute appendicitis
No universal consensus
= Simple acute appendicitis

9. Sallinen, V. , Akl, E. A. , You, J. J. , Agarwal, A. , Shoucair, S
Sallinen, V., Akl, E. A., You, J. J., Agarwal, A., Shoucair, S., Vandvik, P. O., Agoritsas, T., Heels-Ansdell, D., Guyatt, G. H. and Tikkinen, K. A. O. (2016), Meta-analysis of antibiotics versus appendicectomy for non-perforated acute appendicitis. Br J Surg, 103: 656–667. doi:  /bjs.10147

10. Key points Five studies included, total 1116 adult patients
Single-center or multicenter randomized trials
All were conducted in the Europe
Participant: patients with suspected uncomplicated acute appendicitis ( clinical +/- radiological)

11. Key points Intervention :
3rd generation cephalosporin IV  fluoroquinolone and tinidazole PO
Carbopenem IV  fluoroquinolone + metronidazole PO
Amoxicillin plus clavunalic acid IV or PO
Duration of treatment 8-15 days
No pre-specified cross over criteria in most studies

12. Key points Control: open or laparoscopic appendicectomy
Outcomes measure:
Appendicectomy rate within index admission
Success of treatment
Post intervention complications
Recurrence
Length of stay
Length of sick leave
Pain( VAS or medications use)

13. Outcome measures Rate of appendicectomy within 1 month
Major complications
Minor complications
Recurrence of appendicitis
Length of hospital stay
Length of sick leave

14. Rate of appendicectomy within 1 month
Antibiotic group
Appendicectomy group
47/550 (8.5)
561/ 562 (99.8)
Open
434/561 (77.4)
Laparoscopic
127/561 (22.6)

15. Major complications Clavien- Dindo complications grade III or above
Appendiceal perforation
Deep infections
Incisional hernias
Adhesive bowel obstruction not requiring intervention
Clavien- Dindo complications grade III or above ( conditions requiring endoscopic, radiological or surgical intervention, or causing organ dysfunction or death), such as appendiceal perforation, deep infections, incisional hernias,adhesive bowel obstruction not requiring

16. Major complications 25/510 (4.9) 41/489 (8.4)
Appendiceal perforation (23)
Appendiceal perforation (32)
Adhesive bowel obstruction (1)
Deep infection (5)
Death (1)
Incisional hernia (2)
Laparoscopic adhesiolysis (1)

17. Major complications

18. Rate of perforation First author Antibiotic group Appendicectomy group
Eriksson (n=40)
1/20 (5)
Styrud (n=252)
7/128 (5)
6/124 (5)
Salminen (n=530)
5/257 (2)
2/273 (<1)

19. Minor complications Superficial wound infections Diarrhea
Abdominal discomfort

20. Minor complications 11/510 (2.2) 61/489 (12.5)
Superficial wound infections (3)
Superficial wound infection (38)
Abdominal or incisional discomfort (4)
Abdominal or incisional discomfort (22)
Not stated in detail (4)
Diarrhea (1)
All author fail to report complications of antibiotic such as diarrhoea and allergic reaction, and most failed to report appendicectomy complications in details in patients who initially received antibiotics, but who went on to have appendicectomy for recurrent appendicitis

21. Minor complications

22. Recurrence of appendicitis
Confirmed or suspected recurrence of appendicitis between 1 month and 1 year
Antibiotic group
Appendicectomy group
114/510 (22.6)
0/489 (0)

23. Length of hospital stay

24. Length of sick leave

25. Pain measure Not included as inconsistent measurement of pain
First author
Antibiotic group
Appendicectomy group
Eriksson (n=40) 6
>10
Hansson (n=369) 9
Vons (n=239)
1.63
1.7

26. Conclusion
Length of hospital stay is shorter in the appendicectomy group (p<0.001)

27. Limitation of current evidence
Poor study design
Low enrollment rate, ? Selection bias
Difficulty in establishment of diagnosis
Poor generalizability
High crossover rate

28. Cross over rate during index hospitalisation
First author
Crossover during index hospitalization
Eriksson (n=40)
1/20 (5)
Styrud (n=252)
15/128 (12)
Hansson (n=369)
96/202 (53)
Salminen (n=530)
15/257 (6)

29. Hansson J, Korner U, Khorram-Manesh A, Solberg A, Lundholm K
Hansson J, Korner U, Khorram-Manesh A, Solberg A, Lundholm K. Randomized clinical trial of antibiotic therapy versus appendicectomy as primary treatment of acute appendicitis in unselected patients. Br J Surg 2009; 96: 473–481.

30. Summary
Large multicenter high quality randomized trials are needed before the antibiotics-first approach could be considered comparable to appendicectomy

31. Summary
Appendicectomy remains the standard treatment for acute appendicitis
Non operative management reserves to selected group of patients

32. The appendectomy remains the treatment of choice for acute appendicitis. Antibiotic therapy is a safe means of primary treatment for patients with uncomplicated acute appendicitis, but this conservative approach is less effective in the long-term due to significant recurrence rates. (Recommendation 1A).

33. Reference
Sallinen, V., Akl, E. A., You, J. J., Agarwal, A., Shoucair, S., Vandvik, P. O., Agoritsas, T., Heels-Ansdell, D., Guyatt, G. H. and Tikkinen, K. A. O. (2016), Meta-analysis of antibiotics versus appendicectomy for non-perforated acute appendicitis. Br J Surg, 103: 656–667. doi:  /bjs.10147
Eriksson S, Granstrom L. Randomized controlled trial of appendicectomy versus antibiotic therapy for acute appendicitis. Br J Surg 1995; 82: 166–169.
Salminen P, Paajanen H, Rautio T, Nordstrom P, Aarnio M, Rantanen T et al. Antibiotic therapy vs appendectomy for treatment of uncomplicated acute appendicitis. JAMA 2015; 313: 2340–2349.
Styrud J,Eriksson S,Nilsson I, Ahlberg G, Haapaniemi S, Neovius G et al. Appendectomy versus antibiotic treatment in acute appendicitis. A prospective multicenter randomized controlled trial. World J Surg 2006; 30: 1033–1037.

34. Reference
Svensson JF, Patkova B, Almstrom M, Naji H, Hall NJ, Eaton S et al. Nonoperative treatment with antibiotics versus surgery for acute nonperforated appendicitis in children. Ann Surg 2015; 261: 67–71.
Vons C, Barry C, Maitre S, Pautrat K, Leconte M, Costaglioli B et al. Amoxicillin plus clavulanic acid versus appendicectomy for treatment of acute uncomplicated appendicitis: an open-label, non-inferiority, randomised controlled trial. Lancet 2011; 377: 1573–1579.
Hansson J, Korner U, Khorram-Manesh A, Solberg A, Lundholm K. Randomized clinical trial of antibiotic therapy versus appendicectomy as primary treatment of acute appendicitis in unselected patients. Br J Surg 2009; 96: 473–481.

37. Defining uncomplicated appendicitis
Simple appendicitis
Complicated appendicitis
‘’Early ‘’in time course
Mild periappendiceal inflammation
Nonperforated
‘’Late’’ in time course
Significant periappendiceal inflammation
Perforation
Mass
Abscess

38. Antibiotic
Common pathogens: Enteric gram- negative bacilli, anaerobes, enterococci
Mono therapy with a beta- lactam/ beta- lactamase inhibitor, i.e. Ampicillin- sulbactam, Piperacillin- tazobactam, Ticarcillin- clavulanate
Combination third generation cephalosporin plus metronidazole, i.e. Ceftriaxone plus metronidazole

39. Alternative empiric regimens
Combination fluoroquinolone plus metronidazole, i.e. Ciprofloxacin or levofloxacin plus metronidazole
Mono therapy with a carbapenem, i.e. Imipenem- cilastatin, meropenem, doripenem, ertapenem

40. Laparoscopic vs open Lap Open A lower rate of wound infection
Surg: 9
Abx: 6
Laparoscopic vs open
Lap
Open
A lower rate of wound infection
A higher rate of an intra-abdominal abscess
Less pain on postoperative day 1 by the VAS pain score
A longer operative time
Shorter duration of hospital stay
Higher operative and in-hospital costs
Shorter duration for return of bowel function

41. CT sensitivity For diagnosis
For differentiating complicated vs uncomplicated

42. Complicated acute appendicitis
Appendiceal maximal diameter (>10 mm), periappendiceal fat infiltration, and ascites on CT findings and CRP (>5 mg/dL) Min BW. Change in the Diagnosis of Appendicitis by Using a Computed Tomography Scan and the Necessity for a New Scoring System to Determine the Severity of the Appendicitis. Annals of Coloproctology. 2015;31(5): doi: /ac
Reference
Min BW. Change in the Diagnosis of Appendicitis by Using a Computed Tomography Scan and the Necessity for a New Scoring System to Determine the Severity of the Appendicitis. Annals of Coloproctology. 2015;31(5): doi: /ac

43. Risks factors of recurrent appendicitis
Male gender Lien WC1, Lee WC, Wang HP, Chen YC, Liu KL, Chen CJ. Male gender is a risk factor for recurrent appendicitis following nonoperative treatment. World J Surg Jul;35(7): doi: /s