Acute appendicitis is an inflammatory process that involves part or all of the vermiform appendix, which is located at the base of the cecum (1). This process represents a spectrum of severity from simple appendicitis, involving acute intraluminal, mucosal and/or submucosal inflammation, to complicated appendicitis, which can be suppurative/phlegmonous, gangrenous, perforated, or periappendicitis (1,2). Acute negative outcomes encompass negative appendectomy rates, time to surgery (prolonged) and perforation/complication rates. Negative appendectomy refers to the surgical removal of a histologically normal appendix (1).
Historical Background of Appendicitis
One of the first descriptions of the appendix was by the 16th century physician and anatomist Berengario DaCarpi, while in 1492, anatomical sketches by Leonardo Da Vinci clearly illustrate the appendix (3). Evidence suggestive of acute appendicitis has been discovered in mummies as far back as ancient Egypt (3). Since its anatomical discovery, numerous accounts of gangrenous and perforated appendices have been described through autopsy evaluation. In 1886, Dr. Reginald Heber Fitz was one of the first to provide a comprehensive description of acute appendicitis and recommended early surgical intervention for its treatment (4). Although the first appendectomy was reported in 1735, the advent of ether and chloroform anesthetics around the mid-nineteenth century allowed surgical procedures to become safer and a more realistic option for treatment (3). This laid the foundation to current treatments of acute appendicitis.
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Appendicitis is the most common surgical emergency for acute abdominal pain and affects individuals of all ages (1). However, its incidence is highest in the 10-19 years of age group and affects about 40% more males than females (male:female, 1.4:1) (5,6). An epidemiological study in Ontario describes a significant seasonal effect with appendicitis being more prevalent in summer months (6). Appendicitis is approximately 50% more prevalent in whites than non-whites (5). It has been reported that the lifetime risk for appendicitis is 8.6% and 6.7% for males and females, respectively; however, lifetime risk for appendectomy is 12.0% and 23.1% for males and females, respectively (5).
The vermiform appendix is a blind-ended sac (a true diverticulum) located at the distal end of the cecum near the ileocecal valve where the three taeniae coli converge (Figure 1). The appendiceal wall in cross section contains the same tissue layers as the colonic wall. These include the mucosa, submucosa, circular muscle, intermuscular stroma, longitudinal muscle, subserous connective tissue and visceral peritoneum/serosa (7). Blood supply comes from the superior mesenteric artery, which branches to the ileocolic artery (ileal branch) and finally to the appendicular artery, which terminates at the distal portion of the appendix (7). Innervation to the appendix involves afferent nerve fibers at the level of T10-12 (7).
Originally, the vermiform appendix was thought to be a vestigial organ that served no meaningful function in humans; however, it is well recognized that the appendix serves an important immunologic function, primarily at an early age and particularly in secreting immunoglobulin A (8). This is due to the presence of B and T lymphocytes and lymphoid follicles in the mucosa and submucosa of the appendix (9).
Numerous anatomical variations of distal appendiceal positions exist. These positions include retrocecal, retrocolic, paracecal, preileal, postileal, pelvic and subcecal (Figure 2) (1,7). The clinical implication for these positions becomes important in predicting which physical examinations elicit irritation to the appendix.
Several theories exist concerning the etiology and development of acute appendicitis. However, it is generally accepted that without treatment, appendiceal wall inflammation ultimately leads to localized ischemia, perforation, abscess formation and generalized peritonitis (10). The most popular theory is that of appendiceal obstruction as the primary cause of acute appendicitis (2,10). Numerous culprits for obstruction exist including fecaliths, calcium appendicoliths (calculi), lymphoid hyperplasia, fibrous bands, infections and benign/malignant appendiceal tumors (2,10). It is believed that infections leading to lymphoid hyperplasia are more common in children and young adults due to the higher immunological function of the appendix at that age; in older persons, fecaliths, calculi, fibrous bands and tumors are believed to be the cause for obstruction (10). However, lymphoid hyperplasia, fecaliths and calculi are found in less than 30% of cases, implying obstruction may not be pathognomonic for developing acute appendicitis (2). Following obstruction, there is distension of the appendix from increased luminal and intraluminal pressure. Thereafter, it is believed that thrombosis, appendiceal small vessel occlusion and lymphatic flow obstruction ultimately result in wall ischemia, necrosis and subsequently perforation (10). However, measured intraluminal pressure during appendectomies have failed to show any increased pressure; it has therefore been suggested that inflammatory processes may lead to obstruction and increased pressure, as opposed to vice versa (2). Infectious organisms purported to be involved in the development/propagation of acute appendicitis include viruses (adenovirus, cytomegalovirus, rubeola virus), bacteria (E. coli, Yersinia spp, Actinomyces spp, Clostridium difficile) and parasites (Enterobius, Ascaris, Giardia) (11). Viral infections have been suspected in the development of mucosal ulceration with secondary bacterial infection (11). Fungal infections are rare; parasitic infections are more common in endemic areas with regards to acute appendicitis (11). Other theories and risk factors for acute appendicitis include colonic hygiene, diet, gut ischemia, trauma, and foreign bodies (2). However, limited studies and lack of supporting evidence limit their current acceptance.
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As previously stated, acute appendicitis encompasses a spectrum of severity. Acute inflammation of the lumen, mucosal and submucosal wall present with generally no gross abnormalities and histologically show only neutrophil infiltration (2). Acute suppurative/phlegmonous appendicitis may range from grossly normal upon examination to enlarged with dilated/congested surface vessels or with purulent serous exudates; histologically, there is neutrophilic infiltration throughout all layers, ulceration and abscess formation with or without vascular thrombosis (2). Acute gangrenous appendicitis will show a friable purple/green/black appendiceal wall with histological transmural inflammation and areas of mucosal ulceration and necrosis (2). Lastly, periappendicitis may appear grossly normal or dull, congested with exudate, and with histological evidence of serosal and subserosal inflammation only, whose etiology is believed to have started outside the appendix (2).
Clinical Evaluation in Diagnosis of Acute Appendicitis
The diagnosis of acute appendicitis begins with a thorough and accurate clinical evaluation. Typically, in classic presentations, clinical evaluation alone may suffice for diagnosis. However, diagnostic signs, symptoms and labs can be obscured by the variation of appendix anatomical positions and if the patient is female or of an extreme age (1). The overall result for diagnosis best incorporates all of the features of clinical evaluation.
The classic triad of acute appendicitis includes colicky periumbilical pain migrating to the right lower quadrant, nausea with or without vomiting and decreased or loss of appetite (1). The greatest predictor of acute appendicitis is migratory pain (12). However, this is only present in less than half of patients and its likelihood increases after 24 hours of symptoms (1). In addition, retrocecal and retrocolic positioning may be described as a dull ache as opposed to a sharp pain (1). Nausea and loss of appetite are less likely predictors of acute appendicitis (12). However, vomiting is more indicative of advanced appendicitis, especially when profuse, which may implicate possible perforation (1,12). Patients with subcecal/pelvic appendicitis may experience urinary symptoms and diarrhea due to bladder and rectum irritation, respectively; rectal irritation leading to diarrhea can also occur in preileal/postileal appendicitis (1). Lastly, duration of symptoms is not very predictive, while history of fever is only moderately predictive of acute appendicitis (12).
It is difficult to evaluate physical exam findings due to examiner subjectivity of positive/negative findings. However, there are several findings that present more consistently. The greatest predictors of acute appendicitis include direct and indirect tenderness, psoas sign, rigidity, guarding, and rebound tenderness (1,12). Point of maximal tenderness over McBurney's point, which is one-third the distance from the anterior superior iliac spine of the hip to the umbilicus, is highly suggestive of appendiceal irritation (1) with high sensitivity (50-94%) and specificity (75-86%) (10). Again, anatomical consideration is important in interpreting various physical exam findings. In patients with retrocecal/retrocolic appendicitis, there may be more right loin pain and tenderness compared to McBurney's point tenderness (1). Also, in these patients, proximity of the psoas muscle may lead to its irritation and a positive psoas sign is commonly found with moderate sensitivity (13-42%) but high specificity (79-97%) (1,10). Patients with subcecal/pelvic appendicitis may have suprapubic and/or rectal tenderness (1). Other physical exam findings include Rovsing's sign, indicative of right-sided peritoneal irritation, and obturator sign, both of which have poor sensitivity and moderate to high specificity (10). Body temperature over 37.7Â°C is moderately predictive, with higher fevers more suggestive of perforation (12).
Laboratory evaluation is considered an adjunct exam that should not be used independently in diagnosing appendicitis (10). A white blood cell (WBC) count over 10,000 X 109/L with polymorphonuclear leukocytes over 75% (left shift) increases the likelihood of acute appendicitis and is present in 80-90% of cases (1,12). A WBC count over 15,000 X 109/L is more predictive of advanced appendicitis with or without perforation (1). Lastly, an abnormal urinalysis may be found in up to 40% of cases, which may be more prominent in subcecal/pelvic appendicitis (1).
Computed Tomography in Diagnosis of Acute Appendicitis
The use of imaging modalities is commonly employed in assessing the diagnosis of acute appendicitis, especially in atypical presentations (13). Numerous studies have been performed comparing various imaging modalities. However, computed tomography (CT) has been demonstrated to have the highest sensitivity and specificity (10,13). Since the attachment of the appendix to the cecum remains relatively constant in relation to the ileocecal valve, it is therefore readily identified on CT (13). Various CT protocols exist for imaging the appendix. These include unenhanced (no contrast) and enhanced with various combinations of intravenous, oral and rectal contrast (13). The normal appendix on CT has variable length but averages about 8 cm in length, between 0.5-1cm in width and wall thickness approximately 1.5mm (13). It is readily visible on unenhanced CT but its pick-up rate is up to 90-100% with oral and/or rectal contrast (13).
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Characteristic findings of acute appendicitis on CT include appendiceal wall thickening and enhancement, widened appendix and stranding of the periappendiceal fat (10,13). In up to 25-30% of cases, a calcified deposit within the appendix known as an appendicolith may be seen (10,13). There is no opacification of the appendicular lumen with rectal contrast in appendicitis (13). As such, air or contrast found within the appendix lumen effectively eliminates appendicitis (10). A thickened cecal wall may point to the opening of the appendix and is known as an "arrowhead sign" (13). In perforated appendicitis, the most specific findings include abscess, extraluminal air, and ileus, although they are less sensitive; in addition, the appendix is larger compared with non-perforated appendicitis (13).
In adult patients with suspected acute appendicitis, how does the use of enhanced abdominal/pelvic computed tomography compare to clinical evaluation alone with regards to negative clinical outcomes of false positive appendectomies, time to surgery, and perforation/complication rates?
A review of scientific literature was performed to address the clinical question on the use of abdominal/pelvic CT scanning in possible acute appendicitis with regards to the above negative clinical outcomes. This literature search was done using PubMed, Scopus and The Cochrane Reviews as databases. No dating limitations were applied. Search terms used in these databases included "acute appendicitis", "appendicitis", "computer tomography", "computed tomography" and "CT" with Boolean operators "AND" and "OR" in appropriate combinations. The search terms were used as text words in all fields and as MeSH terms in PubMed in the advanced search tool. Search parameters were expanded by using the "related citations" function in PubMed, searching for meta-analyses on CT in appendicitis, and using references within these articles.
From the obtained results, certain criteria were used to assess the suitability of the research article in addressing the clinical question. To be considered, the research article must have studied adults who presented with possible acute appendicitis. These patients must have been assessed by clinical evaluation and compared with abdominal/pelvic CT scanning with contrast at the same time point. As such, studies that compared outcomes from pre-CT era to CT era, as well as other CT imaging techniques (ie: appendiceal CT) were ignored. The outcomes of the research must have included either negative appendectomy rates, time from presentation to surgery or complication/perforation rates. Further screening included the use of an appropriate reference standard (a gold standard). Consideration was only given to randomized controlled trials and prospective/retrospective cohort studies.
From the literature search and respective criteria, five articles were chosen to address the clinical question and were critically evaluated for validity, importance of findings and applicability of results (14-18). A summary description for critical appraisal can be found for each article in Tables 1-5 of the appendix.
Although randomized controlled trials are the ideal studies for evaluating clinical data, the literature search yielded only two prospective randomized controlled trials (14,15). Only Lee et al (2007) describes a randomization process for his randomized controlled trial using a computerized random numbers program (15). Hong et al (2003) fail to state how they randomized their patients and not all patients were randomized in their study (14). The remaining studies (16-18) were retrospective cohort studies using chart reviews, which introduce elements of selection bias, and study elements were not blinded to evaluators. Only Lee et al (2007) describe blinding where outcomes were assessed by evaluators blinded to diagnostic strategy and radiologists masked to study groups (15). Hong et al (2003) fail to mention any blinding in their study and four studies did not mention blinding of clinical assessment results in the use of CT scanning (14,16-18).
The use of histopathology is typically the "gold standard" in the definitive diagnosis of acute appendicitis (12). However, this is impractical in the control groups where there is no surgery and there is no general consensus on diagnosis criteria, where various degrees of inflammation and infiltration exist in acute appendicitis (12). All studies except Mathis et al (2005) describe the use of pathology reports in diagnosing acute appendicitis in their studies (14-18). However, the reference standard could not be assessed in all patients, for reasons stated above. In those patients who did not undergo surgery, follow-up by phone at various time points post-discharge was described in three studies (14-16). Mathis et al (2005) failed to describe a follow-up method in their non-surgical patients (17), while Petrosyan et al (2008) excluded non-surgical patients in their study (18). CT scanning in all studies was used in an appropriate spectrum of adult patients (14-18).
Most studies had small sample sizes (n=143-224) (14-17), with the exception of Petrosyan et al (2008) (n=1,422 adults) (18). Inadequate sample size introduces limitations in detecting statistical significance due to poor power. Significant age difference between study groups was found in two studies, where patients in the CT group were older (16,17). There were also significant gender differences in all but two studies (15,17), where more females were in the CT group compared to the clinical evaluation group (14,16,18).
Lastly, only two studies describe the breakdown of their clinical assessment and CT diagnostic criteria (14,18). The remaining studies were either vague or did not discuss them at all, making extrapolation and comparison of their findings difficult.
The negative clinical outcomes of acute appendicitis, which include negative appendectomy rate, perforation or complication rate and time to surgery, were assessed. In the three studies that discussed negative appendectomy rates, no significant differences were found in overall rates between CT and clinical evaluation alone (15,16,18). However, two studies (15,16) showed a trend of decreased negative appendectomy rates with CT scanning, while the study of Petrosyan et al (2008) showed equal rates (18). Lastly, Fuchs et al (2002) did show a significantly lower negative appendectomy rate in females with CT scanning (16).
Time to surgery was discussed in all but one study (14-17). No significant difference was found between groups in two studies, which show approximately equal times (15,17). However, CT scanning was shown to approximately double patient's time to surgery in suspected acute appendicitis in the remaining two studies (14,16).
Perforation/complication rates were discussed in all but one study (14-17). Again, there were no significant differences in overall rates. There is, however, a split in the trends between the various studies: two studies show CT scanning decreases overall perforation/complication rates (15,17), while rates are increased in the other two studies (14,16). However, Mathis et al (2005) identified complication rates significantly more often in females 15-50 years with clinical evaluation alone (17).
The use of CT in assisting the diagnosis of acute appendicitis is readily available and applicable, especially in emergency departments that have CT scanning capability. This is true here in Manitoba, where nine regions have CT scanners: Thompson, The Pas, Dauphin, Brandon, Portage la Prairie, Winkler, Winnipeg, Selkirk and Steinbach (Figure 3). CT scanning has been shown to be extremely sensitive, specific and accurate in the diagnosis of acute appendicitis (13). Patients with classic presentation of acute appendicitis generally have high pre-test probability for the disease. However, atypical presentations tend to have lower pre-test probability. In the study of Fuchs et al (2002), the authors state that CT scanning made a significant difference in the management plan in 79% of patients with atypical presentations (16). Therefore, CT scanning can be considered to increase the post-test probability in certain populations with atypical presentations in the emergency room setting.
To date, there is no general consensus on the use of CT scanning in patients with suspected acute appendicitis, especially in those who present atypically. Currently, there are two general schools of thought regarding the use of CT in the diagnosis of acute appendicitis: 1) the routine use of CT on all patients and 2) selective CT scanning, especially in atypical presentations and certain populations such as older adults and females of childbearing age (18). A large number of studies evaluating clinical outcomes assessed patients in the last decade that received CT versus patients from an earlier era who did not receive CT, as it was not a common diagnostic tool at the time. This retrospective design has numerous flaws, most notably comparing data from past and present populations and investigator cohorts. It was therefore imperative to search studies that used current populations in comparing CT and clinical evaluation together at the same time point for negative clinical outcomes.
The diagnosis of acute appendicitis is classically a clinical one. Typical negative appendectomy rates have been as high as 20%, and even double in women, as to avoid the adverse outcomes of a missed appendicitis (5). However, negative appendectomies also carry risks including abdominal adhesions, anesthetic complications and other complications from unnecessary surgery (13). This review did not identify a significant difference in overall negative appendectomy rates. However, the general trend was of decreased rates with CT scanning. This was most significant in females of childbearing age. The lack of statistical significance, however, is most likely due to relatively small sample sizes, although the Petrosyan et al (2008) study included over 1,422 adult participants and had equal rates (18).
Increasing use of imaging, especially CT, has become more widespread in the last decade to increase the certainty of diagnosis (13). Although unenhanced CT scans are faster and more readily available, enhanced CT scanning has a higher pick-up rate for acute appendicitis and allows for better visualization of other abdominal organs when there might be an alternative diagnosis (10,13). In this review, alternative diagnoses when acute appendicitis was not found mostly included colitis, ovarian cyst, diverticular disease, pelvic inflammatory disease, endometriosis, renal colic and uterine fibroids (15,16). These diagnoses were predominantly made with the aid of CT scanning which significantly affected medical management. Most of the populations involved in these cases were females of childbearing age and the elderly. As such, the use of other CT techniques, such as unenhanced and appendiceal CT, would limit the ability to identify these abnormalities.
Enhanced CT may take up to two hours due to contrast administration (10). Any delay in definitive diagnosis increases the time to appendectomy. In Manitoba, CT coverage is limited to only certain areas (Figure 3), where travel time must be incorporated, especially from the north. Prolonged delay risks major complications such as perforation, which may lead to sepsis and infertility in women (13). There was a divide on the time to surgery in this review, with either no difference or a double in time to surgery with CT scanning. It would, however, seem logical that CT scanning would increase a patient's time to surgery, especially if contrast is involved. Regarding complications due to prolonged time to surgery, this review found no significant difference in overall complication rates, including perforation, between CT and clinical evaluation alone. Mathis et al (2005) showed significantly more females had complications in the clinical evaluation group. However, the authors of that study describe those women as being more acutely ill and CT scanning was not possible due to time constraints in those emergent situations requiring immediate surgery (17).
The limitations to acquiring statistical significance in the studies reviewed may be in part due to small sample sizes. Additional limitations to this research through critical appraisal make interpretation and application of the results difficult (Tables 1-5). However, more research would be needed to better address this clinical question.
Certain gaps in the current literature need to be addressed to better answer this clinical question. There need to be more studies that are blinded, that make use of prospective randomized controlled trials of sufficient size for appropriate statistical significance and have no significant differences in age and gender between the CT and clinical evaluation groups. This however presents certain realistic dilemmas. For instance, surgeons will generally not blindly operate on patients. Most important, however, is further evaluation in certain subgroups, including older adults and women of childbearing age, where CT may have its most important application. There also needs to be a general consensus on the histopathalogical diagnosis of acute appendicitis, as there is a wide spectrum of results. Some experts argue that mild inflammation is sufficient while others require more extensive inflammation. Although beyond the scope of this paper, routine use of CT exposes patients to increased levels of radiation, perhaps unnecessarily, and contrast can lead to allergic reactions and/or impairment of kidney function (15). This provides another element of a negative clinical outcome that can be studied, which this review does not address.
This review found that CT scanning is most common in women of childbearing age and older adults who present to the emergency department with suspected acute appendicitis. Clinical assessment appears to be sufficient in identifying most cases in adult males and others with classic presentations, such as Alvarado scores over seven. A trend of decreasing negative appendectomies appears to occur with CT scanning, which is most significant in women of childbearing age. CT scanning increases a patient's time to surgery (up to double the time versus clinical assessment alone), but this does not appear to correlate with a significant increase in perforation or other complication rates. As such, routine use of CT scanning does not appear to be necessary in all patients. Therefore, the use of selective CT scanning appears to be most important in patients with atypical presentations, especially in women of childbearing age. In cases where CT is to be utilized, the use of contrast (when not contraindicated) and abdominal/pelvic scanning best helps to identify acute appendicitis and alternative diagnoses. Ultimately, the diagnosis and management plan of suspected acute appendicitis requires clinical judgment, skill, and responsible use of available resources.
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