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

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

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.

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.

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

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.

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.

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.

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.

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

∗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)

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.

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)

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

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.

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.

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%).

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.

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

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

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

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 < 0.0001, OR . 0.07, 95% CI . 0.02e0.24; heterogeneity was found: P . 0.01, 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 < 0.0001, OR . 0.07, 95% CI . 0.02-0.24) Recurrence at 1 year follow-up was reported for a total of 142 patients in the AT group (22.5%)

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 . 0.02, RR . 5.29, 95% CI . 1.37e20.45; heterogeneity was found: P . 0.0008, 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 . 0.02, RR . 5.29, 95% CI . 1.37e20.45; heterogeneity was found: P . 0.0008, 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 . 0.02, RR . 5.29, 95% CI . 1.37-20.45)

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.

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.

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

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 0.12 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%

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.

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. 14.2 g/dL, p = 0.048).

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.

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.

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?