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Accepted Manuscript

Distinguishing fecal appendicular peritonitis from purulent


appendicular peritonitis

M. Mariage, C. Sabbagh, T. Yzet, H. Dupont, A. NTouba, J.M.


Regimbeau

PII: S0735-6757(18)30289-4
DOI: doi:10.1016/j.ajem.2018.04.014
Reference: YAJEM 57448
To appear in:
Received date: 10 December 2017
Revised date: 6 April 2018
Accepted date: 6 April 2018

Please cite this article as: M. Mariage, C. Sabbagh, T. Yzet, H. Dupont, A. NTouba,
J.M. Regimbeau , Distinguishing fecal appendicular peritonitis from purulent appendicular
peritonitis. The address for the corresponding author was captured as affiliation for all
authors. Please check if appropriate. Yajem(2017), doi:10.1016/j.ajem.2018.04.014

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Distinguishing fecal appendicular peritonitis from purulent appendicular peritonitis

M. Mariage 1,4, C. Sabbagh1,4,, T. Yzet2, H. Dupont3, A. NTouba3, J.M. Regimbeau1,4.

1. Department of Digestive Surgery, Amiens University Medical Center, Amiens, France

2. Department of Radiology, Amiens University Medical Center, Amiens, France

3. Intensive Care Unit, Amiens University Medical Center, Amiens, France

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4. Jules Verne University of Picardie, Amiens, France

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Correspondence:

Professor JM Regimbeau
Department of Digestive Surgery
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Amiens University Hospital


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Avenue Laennec
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F-80054 Amiens cedex 01


France
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Phone: +33 322 088 893; Fax: +33 322 089 683.
E-mail: regimbeau.jean-marc@chu-amiens.fr
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ABSTRACT

Introduction: Fecal appendicular peritonitis (FAP) is a poorly studied, rare form of acute

appendicitis, corresponding to peritoneal inflammation with the presence of feces secondary

to ruptured appendix. The purpose of this study was to describe FAP and to compare FAP

with purulent appendicular peritonitis (PAP).

Patients and methods: This single-center, retrospective study was conducted in consecutive

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patients to compare the FAP group and the PAP group. The primary endpoint was the 30-day

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postoperative morbidity and mortality according to the Clavien-Dindo classification. The

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secondary endpoints were description and comparison of intraoperative data (laparoscopy

rate, conversion rate, type of procedure and the mean operating time), and short-term
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outcomes (types of complications, length of stay, readmission rate, and reoperation rate),

comparison of intraoperative bacteriological samples of FAP and PAP as well as the rate of
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resistance to amoxicillin and clavulanic acid, used as routine postoperative antibiotic therapy.

Results: Between January 2006 and January 2016, 2.2% of appendectomies were performed
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for FAP. Patients of the FAP group reported a longer history of pain than patients of the PAP
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group (mean: 58 hours [range: 24-120] vs 24 hours [range: 6-504], p=0.0001) and
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hyperthermia was more frequent in the FAP group than in the PAP group (72% vs 26%,
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p=0.0001). Mean preoperative CRP was also higher in the FAP group than in the PAP group

(110 mg/L [range: 67-468] vs 37.5 mg/L [range: 3.1-560], p=0.007). Significantly less
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patients were operated by laparoscopy in the FAP group (89.7% vs 96.6%, p<0.0001). Mean

length of stay was significantly longer in the FAP group than in the PAP group (10 days

[range: 3-24] vs 5 days [range: 1-32], p=0.001). The overall 30-day complication rate was

significantly higher in the FAP group than in the PAP group (62.1% vs 24.7%, p= 0.0005).

The readmission rate was not significantly different between the two groups (14% vs 11.2%,

p=0.2), but the reoperation rate was higher in the FAP group than in the PAP group (31% vs

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11%, p=0.01). No significant difference was observed between the FAP and PAP groups in

terms of the positive culture rate (75.9% vs 65.6%, p=0.3). No significant difference was

observed between the two groups in terms of resistance to amoxicillin and clavulanic acid

(18.2% vs 20.5%, p=0.8).

Conclusion: FAP is associated with significantly more severe morbidity compared to PAP.

Clinicians must be familiar with this form of appendicitis in order to adequately inform their

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patients.

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Keywords: appendicitis, peritonitis, outcomes, morbidity, mortality
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INTRODUCTION

Acute appendicitis (AA) is one of the most frequent surgical emergencies with a lifetime risk

of 7 to 8% 1. Several studies have demonstrated the superiority of CT scan compared to

ultrasound for the diagnosis of AA with a sensitivity and specificity of 0.99 and 0.95,

respectively 2-4.

The treatment of appendicitis, especially in the case of complicated appendicitis, is

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appendectomy. Laparoscopic appendectomy, described for the first time in 1983 by Semm 5,

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6, 7
has become the gold standard in recent years . Several studies have demonstrated the non-

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inferiority of antibiotics versus surgery for uncomplicated acute appendicitis, but antibiotic
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therapy was associated with a high risk of recurrence . Other studies have also evaluated
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the feasibility of ambulatory care (less than 12 hours of inpatient hospitalization) for

uncomplicated acute appendicitis with a 90% success rate 11 12.


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This trend towards simplification of the management of appendicitis may suggest that

appendicitis is a benign disease and that treatment is associated with low morbidity. However,
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the mortality after appendectomy can range from 0.07% to 2.4%, depending on the severity of
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infection. The overall postoperative complication rate can be as high as 30% for complicated
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13, 14
acute appendicitis . Postoperative morbidity mainly consists of infectious complications
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(superficial wound abscess (3%) and deep abscess (5%)), which may require hospitalization,
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intravenous antibiotic therapy or invasive treatment . The distinction between simple and
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complicated forms of appendicitis remains difficult, even with the contribution of CT scan
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. The Saint Antoine group12 has therefore developed a score comprising 5 clinical,
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laboratory and morphological items to evaluate the probability of complicated appendicitis
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.

Fecal appendicular peritonitis (FAP) is a rare form of complicated appendicitis. It corresponds

to the presence of feces in one or more of the quadrants of the abdomen secondary to rupture
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of the appendix. To the best of our knowledge, no studies have specifically analyzed the

clinical presentation, operative and perioperative management, morbidity and mortality of

these patients. The aim of this study was to describe FAP and to compare FAP with purulent

appendicular peritonitis (PAP).

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PATIENTS AND METHODS

Population and study design

This single-center, retrospective study compared consecutive patients with FAP and PAP. All

adult patients operated for FAP between January 2006 and January 2016 at Amiens

University hospital were included in this study. Data were collected from a retrospective

database from January 2006 to January 2015, which has been prospectively maintained since

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January 2015 in the Appendambu protocol (NCT 01839435) 18. All data from January 2006 to

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January 2015 were extracted from medical software (DxCare, Medasys, France) in which all

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medical correspondence, hospitalizations, imaging, laboratory tests, and surgical or

radiological procedures were recorded. The PAP population (control group) was composed of
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consecutive patients with PAP (n=89) included in the Appendambu protocol from April 2013

to December 2015 (Figure 1). The differences in terms of inclusion period were due to the
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low frequency of FAP, requiring a long inclusion period. The inclusion period was

nevertheless limited by the use of medical software in our institution, in which all data were
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recorded (DxCare, Medasys, France). Very detailed research was possible due to the limited
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number of patients in the FAP group. We decided to use a prospective database as control to
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reduce missing data to a minimum.


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Endpoints
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Primary endpoint

The primary endpoint was the 30-day postoperative morbidity and mortality according to the

Clavien-Dindo classification 19.

Secondary endpoints

Secondary endpoints were:


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- Description and comparison of intraoperative data (laparoscopy rate, conversion rate,

type of procedure and mean operating time), and short-term outcomes (types of

complications, length of stay, readmission rate, and reoperation rate).

- Comparison of intraoperative bacteriological samples of FAP and PAP as well as the

rate of resistance to amoxicillin and clavulanic acid, used for routine postoperative

antibiotic therapy.

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Inclusion criteria

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All patients in whom feces was present in at least one abdominal quadrant during surgery

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were included in the FAP group. Patients with pus in at least one quadrant during surgery

were included in the PAP group.


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Exclusion criteria

Patients with uncomplicated appendicitis were not included in this study.


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Definitions

Uncomplicated appendicitis
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Uncomplicated appendicitis was an operative diagnosis defined by infection confined to the


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appendix without perforation or peritonitis. The presence of clear effusion without


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inflammation of the peritoneum was considered to be reactive and did not constitute
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complicated appendicitis (purulent appendicular peritonitis or fecal appendicular peritonitis).


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Purulent appendicular peritonitis and fecal appendicular peritonitis

Purulent appendicular peritonitis and fecal appendicular peritonitis are operative diagnoses,

defined by acute inflammation of the peritoneum secondary to infection of the appendix.

Purulent appendicular peritonitis was defined by the presence of purulent fluid in the

abdominal cavity and fecal appendicular peritonitis was defined by the presence of fecal fluid

in the abdominal cavity. Localized peritonitis was defined by the involvement of less than 3

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quadrants of the abdomen and generalized peritonitis was defined by the involvement of 3 or

more quadrants.

Complications
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Complications were classified according to the Clavien-Dindo classification . Clavien I

and II complications were considered to be minor complications and Clavien III, IV and V

complications were considered to be major complications.

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Statistical analysis

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Chi-square test or Fisher’s exact test was used to compare categorical variables and Student’s

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t test or Mann-Whitney test was used to compare quantitative variables. ROC curve analysis

was performed to evaluate the best cutoff to determine impending cecal perforation. A p value
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<0.05 was considered to be statistically significant. All variables with a p value <0.05 were

included in the multivariate model. All statistical analyses were performed using SPSS for
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Macintosh® software (version 22.0, SPSS Inc., Chicago, IL, USA).


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RESULTS

Population

Between January 2006 and January 2016, 1,343 appendectomies were performed at Amiens

University Hospital, 29 (2.2%) of which were performed for FAP. The FAP group comprised

14 men (48.3%) with a mean age of 53 years (18-87) and a mean BMI of 27 kg/m2 (range:

16.6- 41.9). Thirteen patients (44.8%) presented associated comorbidities (Table 1). No

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significant differences were observed between the FAP group and the group of 89 patients

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with purulent appendicular peritonitis (PAP) in terms of the distribution of demographic data

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except for mean age (53 years vs 40 years, p=0.0002) and history of digestive surgery (0% vs

8.7%, p=0.03) (Table 1).


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Patients of the FAP group reported a longer history of pain than patients of the PAP group (58

hours (range: 24-120) vs 24 hours (range: 6-504), p=0.0001) and higher rates of
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hyperthermia than patients of the PAP group (72% vs 26%, p=0.0001). The mean

preoperative CRP was also higher in the FAP group than in the PAP group (110 mg/L (range:
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67-468) vs 37.5 mg/L (range (3.1-560), p=0.007). The best CRP cutoff value to predict FAP
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was 65 mg/L (AUC=0.8, LR+=3.02, LR-= 0.3, p<0.0001) (Table 1, Figure 2).
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Primary endpoint
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The overall 30-day complication rate was significantly higher in the FAP group than in the

PAP group (62.1% vs 24.7%, p= 0.0005), with no significant difference for the minor
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complication rate (17.4% vs 12.4%, p=0.3). The major complication rate was significantly

higher in the FAP group (44.7% vs 12.3%, p = 0.0001). No significant difference in mortality

was observed between the two groups (0% vs 1.1%, p=0.9). An 85-year-old patient in the

PAP group died of proximal pulmonary embolism.

Secondary endpoints

Intraoperative data
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Significantly fewer patients were operated by laparoscopy in the FAP group compared to the

PAP group (89.7% vs 96.6%, p<0.0001), wile the conversion rate was not significantly

different between the two groups (11.5% vs 12.7%, p= 0.9). In the FAP group, appendectomy

was performed in 17 patients (58.6%), cecectomy was performed in 10 patients (34.5%) and

ileocolic resection with stoma was performed in 2 patients (6.9%). In the PAP group,

appendectomy was performed in 67 patients (75%) and cecectomy was performed in 22

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patients (25%) (p=0.04). The mean operating time was significantly longer in the FAP group

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(81 min (range: 50-240) vs 60 min (range: 30-120), p=0.02).

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Short-term outcomes

The mean length of stay was significantly longer in the FAP group than in the PAP group (10
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days (range: 3-24) vs 5 days (range: 1-32), p=0.001). The readmission rate was not

significantly different between the groups (14% vs 11.2%, p=0.2), but the reoperation rate
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was higher in the FAP group than in the PAP group (31% vs 11%, p=0.01).

Bacteriology
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The positive culture rate was not significantly different between the FAP group and the PAP
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group (75.9% vs 65.6%, p=0.3). Escherichia coli was isolated significantly more frequently in
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the FAP group than in the PAP group (95.5% vs 61.3%, p=0.03). The two groups were not
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significantly different in terms of the rates of resistance to amoxicillin and clavulanic acid

(18.2% vs 20.5%, p=0.8). The mean duration of antibiotic therapy was 9 days in the FAP
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group (range: 5-21) vs 5.4 days in the PAP group (2-15) (p=0.04).

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DISCUSSION

Fecal peritonitis of appendicular origin is a rare but not exceptional form of acute

appendicitis, accounting for 2.2% of all cases of AA. The present study illustrates the severity

of this form of peritonitis, with a very high morbidity rate of 62.1%, significantly higher that

that observed with other forms of acute appendicitis (24.7%, p = 0.0005 for PAP). This

morbidity was characterized by a high major complication rate (44.7%), requiring invasive

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management with either radiological drainage or surgical reoperation. This complication rate

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was higher than those reported in the literature, as, in a national prospective observational
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study of more than 1,300 appendectomies, all forms combined, Van Rossem et al reported

an overall complication rate of 13.4%. Radiological drainage and reoperation rates were 1.3%
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and 2.0%, respectively. However, complication rates are difficult to compare, as no published

studies are specially devoted to FAP, but report the overall morbidity of complicated forms,
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and morbidity is probably underestimated because of other complicated forms of AA.

Analysis of demographic data revealed a significant difference in terms of the mean age of the
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patients (53.3 years for FAP versus 39.8 years for PAP). Several published studies of
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appendicitis in patients over 60 years of age have reported a relationship between age and the
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rate of complicated forms. The complication rate was between 30% and 60% in this
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population . The clinical presentation was nonspecific, with differences between the two

groups in terms of a significantly longer history of pain, and higher rates of hyperthermia, but
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these features are not specific compared to other forms of acute appendicitis.

Elevated serum CRP was the only laboratory parameter significantly predictive of FAP. ROC

curve analysis showed a diagnostic cutoff of 65 mg/L in favor of fecal peritonitis with a

sensitivity of 77.8% and a specificity of 74.2%. Several studies have evaluated laboratory
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markers predictive of complicated forms of appendicitis: in a prospective study, Cikot et al
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demonstrated a relationship between CRP and complicated forms with a CRP cutoff of 162
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mg/L. Yu et al. published a meta-analysis in 2013 confirming the value of CRP to identify

complicated forms and also demonstrating the value of procalcitonin (sensitivity of 62% and

specificity of 94%). Unfortunately, procalcitonin was not assessed in the present study, as this

parameter is not routinely assayed in the emergency room.

The bacteriology results in this study were similar to those reported in the literature in terms

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of the types of pathogens. However, a high proportion (about 20%) of bacteria were resistant

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to AUGMENTIN® (amoxicillin + clavulanic acid), with no significant difference between the

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two groups (p = 0.8). This rate of resistance is higher than that reported in the literature; in a

multicenter observational study, Coccolini et al reported a resistance rate of 6.8% 24.


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One of the limitations of this study is the retrospective nature of data collection in the FAP

group from January 2006 to January 2015. This bias is limited by: i) the limited number of
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patients in this group, allowing detailed research for each patient, ii) the use of medical

software in our institution in which all data for each patient are recorded.
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CONCLUSION
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FAP is associated with significantly more severe morbidity compared to PAP. Clinicians must
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be familiar with this form of appendicitis in order to adequately inform their patients.
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Table 1. Epidemiological data of the FAP and PAP populations

FAP PAP p
(n= 29) (n=89)
Epidemiology
Mean age (years) 53.3 (18-87) 39.8 (18-94)
Gender (M/W) 14/15 49/40
Mean BMI (Kg/m2) 27 (16.6-41.9) 25.6 (16.2-40.7)
ASA, n
I-II 23 80
III-IV 6 9
Comorbidity, n (%)

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Cardio-vascular 7 (24) 15 (17)
Smoking 8 (28) 25 (28)
Pulmonary 2 (7) 18 (10)
Renal 1 (3) 8 (5)

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Diabetes 2 (7) 7 (4)
HIV 1 (3) 0 (0)
Digestive surgery 0 (0) 15 (9)

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Clinical diagnosis
Duration of pain (hours (range)) 58 (24-120) 24 (6-504) 0.0001
Hyperthermia, n (%) 21 (72) 27 (26) 0.0001
Tenderness in RIF, n (%) 25 (86) 71 (81) 0.3
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Mean leucocyte count (103/mm3 (range)) 14,000 (10,000-22,900) 15,500 (6,800-26,900) 0.2
Mean CRP (mg/L (range)) 110 (67-468) 37.5 (3.1-560) 0.007
Radiological diagnosis 0.4
CT scan performed 26 (90) 77 (86)
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Signs of peritonitis 20 (77) 37 (48)


Saint Antoine score 2 (0-4) 2 (0-5) 0.5
Location of peritonitis, n (%) 0.3
Localized 20 (69) 60 (67)
Generalized 9 (31) 29 (33)
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RIF= right iliac fossa


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Figure 1. Study synopsis

From January 2006 to January 2016


1343 appendectomies

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Fecal appendicular peritonitis April 2013- D ecember 2015
Appendambu study
29 patients (2.2%) Control group

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(89 Purulent appendicular peritonitis)

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Figure 2. ROC curve analysis for CRP as a predictive factor of FAP

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