a b s t r a c t

Objective: The objective of the study is to assess the utility of Alvarado score in the diagnosis of acute appendicitis and the utility of computed tomographic (CT) scan for evaluation of acute appendicitis when stratified by Alvarado scores.

Materials and methods: Retrospective cohort study comprised adult patients who underwent abdominal CT for suspected acute appendicitis between January 2006 and December 2009. Two abdominal radiologists indepen- dently reviewed the CT scans; any discrepancies were resolved by a consensus review. Alvarado scores were cal- culated and categorized as low (0-3), equivocal (4-6), or high (7-10) probability for appendicitis. The Diagnostic utility of CT scans and Alvarado score for acute appendicitis were compared with the criterion standard of com- bined medical chart review and pathology findings.

Results: In a cohort of 158 subjects, 73 (46.2%) had clinical diagnoses of acute appendicitis. The accuracy, sensitiv- ity, specificity, positive predictive value, and negative predictive value of CT scan in the diagnosis of acute appen- dicitis were 97.5%, 98.6%, 96.5%, 96.0%, and 98.8%, respectively. The mean Alvarado score for subjects with complicated appendicitis was significantly higher (7.95) than subjects with uncomplicated appendicitis (6.67) and those with other diagnoses (5.95). Acute appendicitis was confirmed in 2 (13.3%) of 15 subjects with low probability Alvarado scores, 16 (30.8%) of 52 subjects with equivocal scores, and 55 (60.4%) of 91 subjects with high probability scores.

Conclusion: The CT scan had high diagnostic utility for acute appendicitis. The Alvarado score was not a reliable independent Predictive tool for acute appendicitis and could not replace CT scan.

(C) 2014

1. Introduction

Acute appendicitis is the most common reason for an acute surgical assessment of the abdomen, with an estimated 6% lifetime event risk in the general population [1,2]. The clinical diagnosis of acute appendicitis is principally based on symptoms, signs, and laboratory data. Together, these clinical and laboratory factors may be unreliable in up to 40% of premenopausal women [3]. The differential diagnosis includes colonic diverticulitis; Epiploic appendagitis; and gynecologic emergencies such as Pelvic inflammatory disease, ruptured ovarian cyst, ovarian tor- sion, and tubal pregnancy. This diagnostic problem has led to a high Negative appendectomy rate (NAR) of 12% among women of reproduc- tive age compared to 2% in the general population, even with CT scan imaging [4,5]. Appendiceal Perforation rates are higher in children

? Disclosure: AA was supported by the National Research University Project of the Thailand Office of Higher Education Commission.

* Corresponding author at: Division of Infectious Diseases, Thammasart University Hospital, Pratumthani 12120 Thailand. Tel.: +66 81 987 2030.

E-mail address: [email protected] (A. Apisarnthanarak).

(40%-57%) and the elderly (55%-70%), compared to the overall inci- dence of 16% to 39%, with additional diagnostic challenge attributed to the difficulty in obtaining a history and performing the physical exami- nation [6].

The utility of computed tomographic (CT) scan in acute appendicitis enables high accuracy in early diagnosis and reduction in morbidity at- tributed to perforation [6-9]. Unlike ultrasound, a true alternate diagno- sis for abdominal pain may be evident if the appendix appears normal [7,9]. Raman et al [7] showed that, in adult patients suspected of having appendicitis but confirmed later as not having acute appendicitis, CT scan suggested an alternative diagnosis in 65.4% of cases (266 in 407). Alternative diagnoses included colon-related causes (ie, colitis and di- verticulitis) in 34.6%, small bowel related causes (ie, small bowel ob- struction and inflammatory bowel diseases) in 27.4%, gynecologic causes (ie, ruptured ovarian cyst, ovarian mass, and tuboovarian ab- scess) in 10.2%, and other causes (ie, acute cholecystitis and acute pan- creatitis) in 27.8%. In general, CT scans perform uniformly high at diagnosing appendicitis with 99% sensitivity and 95% specificity [10], re- gardless of scanning techniques or combinations of oral, rectal, or intra- venous (IV) contrasts. There has been a consequent increase in the use

http://dx.doi.org/10.1016/j.ajem.2014.11.056

0735-6757/(C) 2014

of preoperative diagnostic CT scans to reduce the NAR for suspected acute appendicitis [4,8-11]. However, the routine use of CT scan for di- agnosis of acute appendicitis remains controversial, and overuse of CT scans may result in excess exposure to ionizing radiation, IV contrast, and related expenses [12-14].

A number of clinical scoring systems have been used to optimize the diagnosis of appendicitis. The Alvarado scoring system, first described in 1986, enables an early clinical diagnosis of acute appendicitis and has been associated with lower NAR [4,15,16]. The 10-point metric is com- posed of points for symptoms, clinical signs, and laboratory data. For symptoms, there is 1 point each for migration of pain to right lower quadrant, anorexia, and nausea/vomiting. For clinical signs, there are 2 points for tenderness in the right lower abdomen, 1 point for rebound tenderness, and 1 point for temperature greater than or equal to 37.3?C, and for the laboratory data, there are 2 points for leukocytosis and 1 point for neutrophils greater than or equal to 75% [1,17]. The com- posite Alvarado scores are categorized as low (0-3), equivocal (4-6), or high (7-10) probability for acute appendicitis. Historically, the Alvarado metric favors specificity over sensitivity, with high positive predictive value (PPV) and diagnostic accuracy for acute appendicitis [18,19].

The purpose of this retrospective study was to assess the utility of the Alvarado score and CT scan in the diagnosis of acute appendicitis. We postulated that CT scans were probably unnecessary in patients with low or high probability of acute appendicitis by Alvarado scores yet could be useful in patients with equivocal Alvarado scores and in adult female patients.

1. Materials and methods
   1. Study design and subjects

A retrospective, single-center study was performed at a 3000-bed university hospital in central Thailand. The study was approved by the institutional review board of our hospital, with waiver of written in- formed consent. Study inclusion criteria were hospitalized patients aged 16 to 60 years who underwent an abdominal CT scan for clinically suspected acute appendicitis from January 1, 2006 to December 31, 2009. Exclusion criteria were (1) age younger than 16 years and older than 60 years to minimize potential confounding bias associated with the obtainment of relevant history and physical examination in these age groups and (2) eligible patients without available CT scans or med- ical records.

Alvarado score

The medical charts were reviewed to calculate each subject’s Alvarado score and the probability for acute appendicitis [7]. The final clinical diagnosis for each subject was based on a combination of med- ical chart review and the Surgical pathology findings.

Computed tomographic techniques

Computed tomographic scans were retrospectively reviewed. There was a variety of oral, rectal, and IV contrast protocols. The standard oral contrast protocol was 1000-mL diluted iodine contrast ingestion before the scan. Patients who received rectal contrast underwent a diluted water soluble contrast enema as tolerated. Patients who received IV contrast obtained a Bolus injection of 100 mL of nonionic iodinated IV contrast agent. Intravenous contrast injection was withheld in patients with renal insufficiency.

Computed tomographic evaluation

The CT scans were blind reviewed by 2 fellowship trained gastroin- testinal radiologists (PA and AC), each with at least 12 years of experi- ence in abdominal CT scan evaluation. Radiologists were aware that

subjects had suspected acute appendicitis but were blinded to the clin- ical data and Alvarado scores. Each reviewer independently identified primary and secondary CT findings of acute appendicitis [20-22]. Primary findings of acute appendicitis were appendiceal dilatation, appendiceal wall thickening, periappendiceal fat stranding/fluid, and appendicolith. Additional signs indicating perforation included appendiceal wall disruption, extraluminal air, extraluminal appendicolith, phlegmon, or abscess formation. Secondary signs of acute appendicitis included adja- cent cecal or terminal ileal wall thickening, nearby lymphadenopathy, and vascular engorgement.

Subjects were partitioned by radiographic evidence of acute appen- dicitis, and those with radiographic evidence of acute appendicitis were further categorized as uncomplicated appendicitis vs complicated ap- pendicitis (Ruptured appendicitis with or without phlegmon/abscess formation). Among subjects without radiographic evidence of acute ap- pendicitis, an alternative CT-based diagnosis to explain the acute ab- dominal pain was sought. Any discrepancies were resolved by a consensus review of the 2 radiologists.

Statistical analysis

The accuracy, sensitivity, specificity, PPV, and negative predictive value (NPV), along with the 95% confidence intervals (CIs) of the CT scan at predicting acute appendicitis was compared to the criterion standard of combined medical chart review and surgical pathology findings. The criterion standard in subjects who underwent surgery was primarily based on the surgical pathology findings, along with the medical chart review. For the subjects without surgery, the criterion stan- dard was solely based on medical chart review. For the comparison of mean Alvarado scores in the categorical subject groups, a Kruskal-Wallis test was applied. All data analyses were performed by using PASW Statistic 18 (SPSS, Chicago, IL). A 2-sided P value of less than .05 was considered statistically significant.

1. Results
   1. Study population

The study population was composed of all consecutive subjects eval- uated by CT scan for potential appendicitis. By review of the radiology logs, all subjects were included. We were not able to ascertain informa- tion on patients who presented with abdominal pain and did not under- go CT imaging studies. The final study cohort comprised 158 adult hospitalized patients who underwent CT scan for evaluation of appen- dicitis. There were 92 women (58.2%), and the mean age was 38.7 (range, 16-60) years. The majority of cases (n = 146, 92.4%) received IV contrast. A combination of oral, rectal, and IV contrasts was adminis- tered to 89 (56.3%). Oral and IV contrasts were given in 11 (7.0%), rectal and IV contrasts were given in 23 (14.6%), and IV contrast alone was given in 23 (14.6%). Oral and rectal contrasts were given in 4 (2.5%),

oral alone in 1 (0.6%), rectal alone in 2 (1.3%), and 5 (3.2%) received no contrast.

Review of medical charts and pathology records

The medical charts were available for all 158 subjects, and the surgi- cal pathology reports were available for 64 (40.5%). The distribution of the study participants is shown in Fig. 1. Among 73 subjects (46.2%) with acute appendicitis, 18 were uncomplicated cases, and 55 were complicated cases (19 had ruptured appendicitis, 13 had ruptured ap- pendicitis with phlegmon, and 23 had ruptured appendicitis with ab- scess). Among 73 subjects with appendicitis, 51 (69.9%) underwent surgery with confirmatory surgical pathology of acute appendicitis. The other 22 subjects (30.1%) received conservative treatment with IV antibiotics with or without percutaneous drainage. The reasons for non- surgical management included complicated appendicitis, inappropriate

Fig. 1. The categorical distribution of the 158 study subjects based on the final clinical diagnosis of appendicitis.

general health status for surgery, and underlying immunodeficiency conditions. The 85 subjects (53.8%) with nonappendiceal conditions in- cluded 29 gastrointestinal abnormalities, 22 gynecologic abnormalities, 7 urologic abnormalities, 5 miscellaneous cases, and 22 inconclusive cases. Of these 85 cases, 13 (15.3%) underwent surgery and had no evi- dence of acute appendicitis. The remaining 72 subjects (84.7%) without acute appendicitis were treated conservatively and had no further evi- dence to support a diagnosis of appendicitis during the hospital stay. Overall, the NAR was 1.9% (1 of 52 appendiceal specimens).

Alvarado scores

The subset of subjects with complicated appendicitis had a signifi- cantly higher mean Alvarado score than subjects with uncomplicated appendicitis and those with other diagnoses (P b .001) (Table 1). Fifteen cases (9.5%) had low probability Alvarado scores, 52 cases (32.9%) had equivocal scores, and 91 cases (57.6%) had high probability scores (Table 2). The mean (range) Alvarado scores were 2.87 (1-3) in the low probability group, 4.94 (4-6) in the equivocal group, and 8.38 (7- 10) in the high probability group.

Acute appendicitis was confirmed in 13.3% of cases in the low prob- ability Alvarado group, 30.8% in the equivocal group, and 60.4% in the high probability group (Table 2). Based on Alvarado score alone, 2 (13.3%) of 15 subjects in the low probability group and 16 (30.8%) of 52 subjects in the equivocal group were not identified for acute appen- dicitis. Furthermore, 36 subjects (39.6%) in the high probability group were diagnosed with other nonappendiceal conditions (Table 3). More men (65.9%) than women (55.3%) in the high probability group had confirmed acute appendicitis (P = .39) (Table 4).

Computed tomographic evaluation

All 158 Abdominal CT scans were deemed technically adequate for review. Compared to the criterion standard, the accuracy of CT scans for acute appendicitis was 97.5% (95% CI, 93.7-99.3), with sensitivity of 98.6% (95% CI, 92.6-100.0), specificity of 96.5% (95% CI, 90.0-99.3),

PPV of 96.0% (95% CI, 88.8-99.2), and NPV of 98.8% (95% CI, 93.5-

100.0). There were 1 false-negative and 3 false-positive CT studies for the diagnosis of acute appendicitis; each of these subjects’ scans was performed with 64-detector CT scanners with a slice collimation of

1.25 to 1.5 mm. Three cases received oral, rectal, and IV contrasts. The fourth case received rectal and IV contrasts. The false-negative case was a 19-year-old man with the final diagnosis of acute eosinophilic appendicitis confirmed by the surgical pathology specimen. Acute eosinophilic appendicitis was characterized by a grossly inflamed appendix with the infiltration of eosinophils (not neutrophils) in the muscularis propria [23]. This case presented with 3 hours of abdominal pain before the CT scan and had an Alvarado score of 7, and the CT images showed a normal air-filled appendix with no appendiceal wall thickening or adjacent fat stranding.

The first case with a false-positive CT scan was a 50-year-old woman with advanced cholangiocarcinoma. She had an Alvarado score of 6 (equivocal), and the CT scan showed slight thickening of the appendiceal wall with adjacent fat stranding and minimal fluid. Hepatomegaly was noted with a large liver mass that occupied almost the entire left hepatic lobe with evidence of intrahepatic biliary dilatation. The subject’s clinical condition improved after IV antibiotics, and the clinical diagnosis was acute cholangitis. The second case was a 36-year-old woman with an Alvarado score of 9 (high), slight thickening of the appendiceal wall on CT scan, clinical improvement without Antimicrobial treatment, and a

Table 1

The Alvarado score of 158 study participants categorized by the final clinical diagno- sis of appendicitis

Table 2

The final clinical diagnosis of appendicitis in 158 participants, categorized by the Alvarado score

Final clinical diagnosis of appendicitis^b

Alvarado score

Alvarado scorea

Yes, n (%) No, n (%)

Total, n (%)

Final clinical diagnosis of appendicitis	n (%)	Mean (SD)	Range			Low (0-3)	2 (13.3)	13 (86.7)	15 (9.5)
Nonappendicitis	85 (53.8)	5.95 (2.27)	1-10			Equivocal (4-6)	16 (30.8)	36 (69.2)	52 (32.9)
Uncomplicated appendicitis	18 (11.4)	6.67 (1.97)	3-10			High (7-10)	55 (60.4)	36 (39.6)	91 (57.6)
Complicated appendicitis	55 (34.8)	7.95 (1.73)	3-10			Total	73 (46.2)	85 (53.8)	158 (100)
Total 158 (100) 6.73 (2.25) 1-10 a Probability of acute appendicitis

P b .001 ^b Clinical criterion standard based on medical chart review and surgical pathology findings.

Table 3

The final clinical diagnosis of 36 participants with high probability for acute appendicitis by Alvarado score who were diagnosed with other conditions

Final clinical diagnosis n

Gastrointestinal abnormalities

Acute pancreatitis with fluid collection 2

acute gastroenteritis 2

Spontaneous bacterial peritonitis 2

Others (one each): appendiceal tumor, cecal diverticulitis, ileal metastasis 8

with perforation, sigmoid perforation, colitis, tuberculous peritonitis, mesenteric hematoma, Liver abscess

Gynecologic abnormalities

Pelvic inflammatory disease/tuboovarian abscess 7

Endometriosis/ruptured endometriotic cyst 4

Ruptured corpus luteal cyst 1

Urologic abnormalities

Right Ureteral stones 2

Renal abscess/lobar nephronia 2

Urinary tract infection with septic shock 1

Cystitis 1

Inconclusive 4

Total 36

Table 4 The final clinical diagnosis of appendicitis in 158 participants, categorized by the Alvarado scores, subclassified by sex

Final clinical diagnosis of appendicitis^b

treatment and had full resolution of clinical conditions. Seven months later, she had repeated Right lower quadrant abdominal pain with clinical suspicion of recurrent appendicitis. The CT scan showed a large appendiceal mass with histopathology confirmed of a primary appendiceal mesenchy- mal (spindle cell) tumor.

The CT scan showed appendicoliths in 5 (5.9%) of 85 cases without appendicitis, 3 (16.7%) of 18 cases with uncomplicated appendicitis, and 31 (56.4%) of 55 cases with complicated appendicitis (P b .001).

1. Discussion

The major finding of this study was that the preoperative abdominal CT scan had significant diagnostic utility for acute appendicitis, especial- ly when compared with the Alvarado Clinical scores. These results were consistent with prior studies that evaluated the CT performance for acute appendicitis [22,24-27]. We propose an algorithm (Fig. 2) to guide physicians for the utilization of multimodalities approaches (Alvarado score, CT scan, and clinical observation) in the diagnosis of acute appendicitis.

There are many reasons for false-negative CT scans in the setting of true appendicitis. Appendiceal nonidentification is a particular problem in thin individuals, whereas no radiological evidence of appendicitis oc- curs when the CT scan is performed at the early onset of symptoms [28]. In our study, there was 1 false-negative case (0.6%) of appendicitis, a relatively low estimate compared to reports as high as 7% in the litera-

Sex Male
Low (0-3)	1 (25.0)	3 (75.0)	4 (6.1)
Equivocal (4-6)	8 (44.4)	10 (55.6)	18 (27.3)
High (7-10)	29 (65.9)	15 (34.1)	44 (66.7)
Total	38 (57.6)	28 (42.4)	66 (100)
Female Low (0-3)	1 (9.1)	10 (90.9)	11 (12.0)
Equivocal (4-6)	8 (23.5)	26 (76.5)	34 (37.0)
High (7-10)	26 (55.3)	21 (44.7)	47 (51.1)
Total	35 (38.0)	57 (62.0)	92 (100)

Alvarado scorea

Yes, n (%) No, n (%)

Total, n (%)

ture [29]. In the single false-negative case, the CT scan was performed within 3 hours of the onset of abdominal pain, and it was possible that the classic radiographic evidence of acute appendicitis had not yet evolved. In addition, there were 3 false-positive cases (1.9%) in this study, 2 of whom had no pathologic evidence of the final diagnoses. In the minority of cases, symptoms of appendicitis spontaneously re- solved with or without antimicrobial treatment. This phenomenon, la- beled spontaneously resolving appendicitis, is hypothesized to occur by the relief of appendiceal obstruction within 24 to 48 hours of clinical onset [6,30,31]. The final false-positive case had a surgical specimen with an appendiceal spindle cell tumor identified 7 months after the

^a Probability of acute appendicitis.

^b Clinical criterion standard based on medical chart review and surgical pathology findings.

discharge diagnosis of acute gastroenteritis. The last case was a 37-year- old immunocompromised woman with an Alvarado score of 8 (high); the CT scan suggested acute appendicitis. She received IV antimicrobial

index CT scan for this study. Notably, primary neoplasms of the appen-

dix have been reported in 0.5% to 1.0% of appendiceal specimens [32,33]. In such cases, up to 50% of cases have presented with clinical signs and symptoms of acute appendicitis, most often due to the occlu- sion of the appendiceal lumen by tumor [32]. Although CT was a sensi- tive technique for detection of underlying appendiceal neoplasm, there was no evidence of appendiceal tumor identified in this subject’s initial CT scan.

Fig. 2. The algorithm for assisting the physician for utilization of multimodalities approaches for the diagnosis of acute appendicitis.

In our study, an appendicolith was more commonly identified in cases with complicated appendicitis than in cases with uncomplicated appendicitis and cases without appendicitis. However, the significance, size, and specificity of an appendicolith, as a marker of acute appendici- tis or its severity on CT scan, are still debated [6,22,34,35].

As with all retrospective studies, we acknowledged several limita- tions. First, our sample size was small and restricted to hospitalized adults with a clinical presentation consistent with acute appendicitis and procurement of a diagnostic abdominal CT scan. We did not have the information on the patients who were suspected of acute appendi- citis and underwent surgery without CT scans. Second, most cases were evaluated by surgical residents as part of routine care before the order of CT scans. Hence, the ascertainment of diagnostic CT scans may have been biased toward the less definitive cases with equivocal clinical presentations or to advanced cases with suspected complica- tions. We were unable to ascertain the number of simple cases with straightforward symptoms and signs of appendicitis for which the CT scan was not requested. Thus, the true performance of Alvarado score is likely to be underestimated, especially in the low probability group. Third, children younger than 16 years and elderly older than 60 years were excluded from the study cohort to minimize ascertainment biases attributed to History taking and physical examinations, in an effort to achieve an accurate Alvarado score. Lastly, there was variation in the CT Imaging techniques (eg, CT machines, collimation thickness, and contrast administration) for the study subjects, but this most likely had minimal effect due to excellent performance being reported for all generations of CT scanners in the diagnosis of acute appendicitis.

In conclusion, the preoperative abdominal CT scan had significant di- agnostic utility for acute appendicitis relative to the Alvarado clinical scoring metric in this study. Our study provides supportive evidence for the inclusion of CT scans in the clinical evaluation of acute appendi- citis, as consistent with prior studies. Utilization of multimodalities ap- proaches (Alvarado score, CT scan, and clinical observation) as suggested in Fig. 2 will help physicians selecting the suitable patients for CT scans and avoiding missed diagnosis of acute appendicitis in pa- tients who had vague clinical signs and symptoms.

Acknowledgment

The authors thank Linda M. Mundy for critical manuscript review.

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