1. General Surgery, Group C
Journal Club
March 13, 2017
General Surgery, Group C
HUSVF

2. PICO QUESTION Patients: adult population with acute appendicitis
Intervention: medical management – antibiotic therapy
Control: surgical management
Outcome: recurrence, complications, malignancy

4. British Medical Journal Open
Annals of Surgery Volume 260, Number 1, July 2014
British Medical Journal Open
This is a single-cohort, prospective, observational study.

5. Objectives
To evaluate the safety and efficacy of antibiotics treatment for suspected acute uncomplicated appendicitis and to monitor the long term follow- up of non-operated patients.

6. Background
Right lower quadrant abdominal pain is a common cause of emergency department admission.
The natural history of acute appendicitis nonoperatively treated with antibiotics remains unclear

7. Background As surgery carries various risks.
Conservative non-surgical treatment with antibiotics for suspected appendix inflammation may avoid needless surgery.
The appendix is found to be free of disease in 15-30% of appendectomies.

8. Methods
In 2010, a total of 159 patients with suspected appendicitis were enrolled nonoperative management (NOM) with amoxicillin/clavulanate.
The follow-up period was 2 years.

9. How did they do this?
Patients presented to the Emergency Department with right iliac fossa pain:
Complete blood cell count with differential and C- reactive protein.
Rule out acute appendicitis and need for operation.
Absence of a definite alternative diagnosis
Eventually patients were underwent additional abdominal US and abdominal CT scan.

10. Alvarado score: sum 0–4 = not likely appendicitis; sum 5–6 = equivocal; sum 7–8 = probably appendicitis; sum 9–10 = highly likely appendicitis. Acute appendicitis response score (AIR): sum 0–4 = low probability; sum 5–8 = indeterminate; sum 9–12 = high probability.

11. Patients were selected applying inclusion criteria
Follow up
. ED indicates emergency department. outpatients
Patients were selected applying inclusion criteria
Who didn´t undergo surgery was physically examined 5 days later.
If their condition didn´t improve, they were admitted for surgical appendectomy.
emergency department

13. ∗US positive for at least one of the following: enlarged appendix >6 mm, fluid-filled appendix, loculated pericecal fluid, free intraperitoneal fluid, appendicolith, increased periappendiceal echogenicity, hypoechoic appendix, echogenic submucosa, lack of compressibility, inflamed periappendiceal fat.
†Nonperforated appendicitis with CT findings consistent with inflamed but not perforated appendix.
‡Mean value (days)

14. Results Short-term (7 days) NOM failure rate was 11.9%.
All patients with initial failure were operated within 7 days.
At 15 days, no recurrences were recorded.
After 2 years, the overall recurrence rate was 13.8% (22/159)
14 of 22 patients were successfully treated with further cycle of amoxicillin/clavulanate.
No major side effects occurred.
Abdominal pain evaluated by the Numeric Rating Scale and the visual analog scale; median Numeric Rating Scale score was 3 at 5 days and 2 after 7 days.
Mean sick leave period was 5.8 days.

15. Long-term efficacy of NOM treatment was 83%
14 of 22 patients were successfully treated with further cycle of amoxicillin/clavulanate
Long-term efficacy of NOM treatment was 83%
∗68.5% had an Alvarado score of 7–8 (probably appendicitis) and 31.5% had Alvarado score of 5–6 (equivocal for acute appendicitis).
†All patients with initial failures underwent surgery within 7 days.
O.R., indicates operating room.
Long-term efficacy of NOM treatment was 83% (118 patients recurrence free and 14 patients with recurrence nonoperatively managed)
(118 patients recurrence free and 14 patients with recurrence nonoperatively managed)

16. Predictive factors of NOM failure, but both did not correlate with recurrences
None of the single factors forming the Alvarado or AIR score were independent predictors of failure of NOM or long-term recurrence.
Alvarado and AIR scores were the only independent predictive factors of NOM failure after multivariate analysis, but both did not correlate with recurrences
None of the single factors forming the Alvarado or AIR score were independent predictors of failure of NOM or long-term recurrence

17. Conclusions
Antibiotics for suspected acute appendicitis are safe and effective and may avoid unnecessary appendectomy, reducing operation rate, surgical risks, and overall costs.
After 2 years of follow-up, recurrences of nonoperatively treated right lower quadrant abdominal pain are less than 14% and may be safely and effectively treated with further antibiotics.

19. METHODS
Systematic literature search: PubMed, EMBASE, Medline, Google Scholar and Cochrane Central Register of Controlled Trials databases
Randomized controlled trials comparing antibiotic therapy (AT) and surgical therapy appendectomy (ST) for uncomplicated AA.

20. HISTORY
1886: Fitz reported that many autopsy specimens were showing pathologic signs consistent with AA  in some patients the disease could resolve without any surgery
1953: Harrison reported 42 of 47 cases of AA being successfully treated using antibiotics
1956: Coldrey published the data on 471 patients with AA treated conservatively, with low morbidity, mortality (0.2%), and recurrence rates (14.4%).

21. OUTCOMES PRIMARY OUTCOMES:
1. Treatment efficacy based on 1 year follow-up.
Efficacy was defined:
Achieving a definitive improvement without requiring surgery within a median follow-up of 1 year
AA confirmed at the time of the surgical operation and resolution of symptoms after surgical treatment.
2. Recurrence at 1 year follow-up.
Episode of appendicitis being diagnosed again after the initial antibiotic treatment was completed and the patient had been discharged home.

22. OUTCOMES
3. Complicated appendicitis with peritonitis identified at the time of surgical operation.
In the AT group the analysis was carried out within the cohort of patients who underwent appendectomy after the failure of the AT.
4. Overall post-intervention complications.
Abscesses, postoperative peritonitis, surgical site infections, incisional hernias, incisional pain or obstructive symptoms

23. OUTCOMES SECONDARY OUTCOMES Length of primary hospital stay.
Period of sick leave, intended as “absence from work”.

24. 1.351 patients included: 632 in AT group and 719 in ST group

26. RESULTS
The meta-analysis of studies comparing treatment efficacy based on one year follow-up after AT (75.9%) and ST (98.3%) was
conducted on five RCTs. A higher rate of efficacy was found in the ST group (P < , OR , 95% CI e0.24; heterogeneity
was found: P , I2 . 70%) (Table 3, Fig. 2).
Data on the outcomes of interest were reported by four authors. When analyzing the cases of complicated AA reported in the AT group, we found that peritonitis were reported in 23 cases of persistency (patients were operated on within the first 48 h of antibiotic treatment) and 14 cases were reported as recurrence. However, a lack of data was found regarding the modality of treatment used for the recurrences.
A higher rate of efficacy was found in the ST group (P < , OR , 95% CI )
Recurrence at 1 year follow-up was reported for a total of 142 patients in the AT group (22.5%)

27. RESULTS
Recurrence at 1 year follow-up was reported for a total of 142 patients in the AT group (22.5%). The forest plot of comparison for risk of complicated
appendicitis with peritonitis identified at the time of surgical operation showed a statistically significant difference between antibiotic treatment and appendectomy groups: 34 cases of
peritonitis up to 171 patients who underwent appendectomy (19.9%) were reported in the AT group and 61 cases up to 719 (8.5%) were reported in the ST group (P , RR , 95%
CI e20.45; heterogeneity was found: P , I2 . 82%) (Table 3, Fig. 3).
The forest plot of comparison for risk of complicated
appendicitis with peritonitis identified at the time of surgical operation
showed a statistically significant difference between
antibiotic treatment and appendectomy groups: 34 cases of
peritonitis up to 171 patients who underwent appendectomy
(19.9%) were reported in the AT group and 61 cases up to 719
(8.5%) were reported in the ST group (P , RR , 95%
CI e20.45; heterogeneity was found: P , I2 . 82%)
(Table 3, Fig. 3). Data on the outcomes of interest were reported
by four authors. When analyzing the cases of complicated
AA reported in the AT group, we found that peritonitis
were reported in 23 cases of persistency (patients were operated
on within the first 48 h of antibiotic treatment) and 14
cases were reported as recurrence. However, a lack of data
was found regarding the modality of treatment used for the
recurrences.
Statistically significant difference between antibiotic treatment and appendectomy groups:
34 cases of peritonitis up to 171 patients who underwent appendectomy (19.9%) were reported in the AT group
61 cases up to 719 (8.5%) were reported in the ST group (P , RR , 95% CI )

28. Patients who underwent appendectomy within the first 48 h of antibiotic therapy were 42 (6.6%), and 142 patients (22.5%)
presented with a recurrence of AA within the first year of follow-up. The mean length of time for recurrence was 4.65 ± 1.60 months.

29. DISCUSSION
Shorter length of hospital stay and early return to daily normal activity are two cited advantages of the antibiotic management, especially in terms of costeffectiveness
Although CT scan is used in many centers due to its high sensitivity and specificity for the diagnosis of perforated appendicitis and abscess, only three studies included in this meta-analysis used CT scan to rule out perforated appendicitis.

30. CONCLUSION
With its high efficacy and low complication rates, appendectomy remains undoubtedly the most effective treatment for patients with uncomplicated AA.
Similar complication rates have been reported when comparing appendectomy and AT, even among patients who underwent surgery after failure of the AT.
Higher rates of peritonitis  this suggests that a close clinical surveillance must be carried out if non-operative treatment strategy is chosen

32. INTRODUCTION
As non-operative management of appendicitis gains popularity identification of patients who are at increased risk for appendiceal tumors becomes increasingly important.
The age-adjusted incidence of appendix cancer was only cases per 1 million people per year, accounting for less than 0.5% of all gastrointestinal malignancies
Appendiceal tumors are commonly found incidentally on appendectomy specimens
Incidence of appendiceal tumor on appendectomy specimens 0.9%-1.7%

33. METHODS
Retrospective cohort analysis of 677 consecutive adult patients (age ≥ 18 years) who underwent appendectomy for acute appendicitis during a 4-year period ending 7/1/2016.
Seventeen patients (2.5%) had an appendiceal tumor.
14 underwent immediate appendectomy
2 initially had non-operative management but failed to improve on antibiotics
1 had successful non-operative management and elective appendectomy 19 days after discharge
Conditions present on admission that were significantly different (p < 0.05) between groups were assessed for the ability to predict the presence of an appendiceal tumor on univariate logistic regression.

34. On subgroup analysis, admission hemoglobin was significantly lower among patients with tumor stage II or greater (n=10) compared to all other patients (13.6 vs g/dL, p = 0.048).

36. PATHOLOGY On final pathology reports,:
7 pre-malignant tumors (four carcinoids and three goblet cell carcinoids)
10 malignant tumors (five adenocarcinomas, two mucinous adenocarcinomas, one signet ring adenocarcinoma, one adenosquamous carcinoma, and one B- cell lymphoma)
Stages : stage I: n = 7, stage II: n = 3, stage III: n = 5, stage IV: n = 2.

37. RESULTS
Patients with these risk factors should be advised to undergo appendectomy at the index admission or at earliest convenience if non- operative management is necessary.

38. QUESTION If you arrived today to the ER with suspected appendicitis…
Would you call a nurse for an IV line?
Would you call a surgeon?