Target condition being diagnosed
Appendicitis is the most common abdominal emergency in general surgery. Over 42,000 and 270,000 appendicectomies are performed annually in the UK and USA respectively (Hall 2002; HES 2012). Appendicitis is diagnosed clinically with investigations that include blood tests and imaging studies, but no test exists that can reliably identify it with 100% accuracy. As a number of other medical conditions can mimic its symptoms and signs, appendicitis can be a very difficult disease to diagnose.
Although spontaneous resolution has been reported previously (Liu 2011), the potential complications of septicaemia, peritonitis or death from untreated appendicitis mean that treatment is mandated when appendicitis is provisionally diagnosed. A growing body of research has recently suggested that antibiotics may have a role in treatment of appendicitis, but this remains controversial as treatment with antibiotics may fail or lead to high recurrence rates (D'Souza 2014). Once a diagnosis of appendicitis is made, the traditional treatment is surgical excision of the appendix (appendicectomy) via open or laparoscopic approaches to the abdomen (Sauerland 2010).
An incorrect diagnosis of appendicitis may lead to unnecessary surgery if the underlying aetiology is self-limiting or requires medical treatment. Surgery will result in a negative appendicectomy (NA), where the appendix is excised but tissue analysis reveals no inflammation (a negative appendicectomy). The negative appendicectomy rate (NAR) in large-scale studies varies from 6.4% (Switzerland, Guller 2011), 11.8% (USA, Seetahal 2011), 18.2% (Hong Kong, Ma 2010) and 20.6% (UK, Bhangu 2013). More recent studies from Holland (Van Rossem 2015) and the USA (Florence 2008) have found a decreased NAR of 3.3% and 5.6% respectively with mandatory imaging. Surgical complications from NA occur in approximately 11% of patients (Bhangu 2013).
Interventions for appendicitis have been investigated by several Cochrane Reviews (Andersen 2005; Sauerland 2010; Rehman 2011; Wilms 2011; Cheng 2015). Ultrasonography (US) and Computed Tomography (CT) are the other commonly used imaging modalities for appendicitis, both of which are currently undergoing Cochrane Review, with two protocols published (Rud 2012; Wild 2013).
Magnetic Resonance Imaging (MRI) is an imaging modality that is increasingly used for the diagnosis of gastrointestinal (GI) disease. MRI uses magnetic fields to create images of the body, and is described as a safe imaging technology, with no exposure to radiation. Safety guidelines specify subgroups of patients that may be harmed during an MRI scan, for example patients with metallic implants or foreign bodies (Dill 2008). People with claustrophobiia and most young children or babies may also not tolerate the noise and closed space within an MRI scanner.
Magnetic Resonance Imaging can investigate pathology in multiple organ systems. It can detect early stroke and measure brain activity, assess cardiac function, perform angiography, and assess bone and soft tissue. MRI is frequently used to investigate gastrointestinal pathology (Martin 2005; Tkacz 2009), particularly Crohn's disease (Sempere 2005; Florie 2006). It can diagnose other groups of conditions that mimic appendicitis, such as gynaecological (Zanardi 2003; Birchard 2005; Sohaib 2007) or urinary tract pathology (Leyendecker 2008).
Historically, MRI has not been used as an imaging test for emergency abdominal conditions, where CT or ultrasound are the default modalities to image the appendix. Previous generations of MRI scanners would take up to 40 minutes to scan the abdomen, while a CT took less than five minutes. Furthermore, MRI scans of the abdomen require a subspecialist interest in GI radiology to interpret accurately.
Magnetic Resonance Imaging scanning technology was developed in the 1970s, and subsequent advances in MRI hardware (coil technology), software (protocols and sequences), and radiology expertise has led to an increase in its diagnostic capabilities and quicker scan times. As MRI accuracy has increased and scanning time has reduced, a growing number of primary research studies support the use of MRI to diagnose appendicitis in adults as well as women and children, where avoidance of radiation from CT scanning is highly desirable. A previous systematic review of eight studies on the diagnostic accuracy of MRI for appendicitis has calculated the summary sensitivity and specificity at 97% and 95% respectively (Barger 2010). This is comparable to the sensitivity and specificity of CT at 94% and 95% respectively (Terasawa 2004). No systematic review of MRI for the diagnosis of appendicitis has been conducted since 2010 (Barger 2010). If MRI is confirmed to be an accurate, radiation-free imaging test, then it could be a valid alternative or even first line imaging modality for appendicitis. This would be particularly true in children and pregnant women, to whom avoidance of radiation is especially desirable.
People admitted with a potential diagnosis of appendicitis should routinely undergo clinical assessment by history and examination by an emergency general surgical team. On that basis alone a diagnosis may be formed and the decision to operate, discharge, or perform further investigations may be made. Urinalysis and blood tests are commonly performed investigations, followed by imaging studies. Since the symptoms and signs of appendicitis are inconsistent, and investigations may be falsely positive or negative, the diagnosis of appendicitis is based on clinical judgement, weighing up relevant information from the patient's history and examination, and investigation results.
Ultrasonography and Computed Tomography are the two commonly used imaging tests. If US or CT is positive for appendicitis, the patient will proceed to surgery. If US is inconclusive, the person will either be admitted for observation, proceed to CT for further imaging, or proceed to diagnostic laparoscopy. If CT is inconclusive, the person will be admitted for observation, or proceed to diagnostic laparoscopy.
Magnetic Resonance Imaging is not commonly used in clinical practice, but could replace US or CT as a first or second line imaging test.
Blood tests for appendicitis are used to check whether inflammatory markers (white blood cell count (WBC) or C-reactive protein (CRP)) are elevated, with a clinical suspicion (based on history and examination) for appendicitis. In this clinical context, normal WBC and CRP values mean that appendicitis is unlikely (Gronroos 1999; Sengupta 2009). Other markers have also emerged such as bilirubin (D'Souza 2013; Giordano 2013) and procalcitonin (Yu 2013), although their exact role in the diagnosis of appendicitis is not established.
Ultrasound is a commonly used investigation in the UK (Jaunoo 2012), particularly in young women to exclude gynaecological abnormalities. It is cheaper than CT with no radiation burden to the person, but as its diagnostic accuracy depends directly on the expertise of the operator, its sensitivity and specificity is frequently inferior to CT (Terasawa 2004; D'Souza 2015).
Computed Tomography has excellent sensitivity and specificity of 94% and 95% respectively (Terasawa 2004), is widely available and quick to perform. It is still not commonly used in the UK and other countries due to its expense and radiation dose. An abdominal CT exposes the recipient to as much radiation as 2.7 years of background radiation (U.S. 2015). It is estimated that 0.4% of all cancers diagnosed in the United States will be due to radiation exposure from CT scans (Brenner 2007). However, new low-dose CT protocols (2mSv vs 16mSv for standard CT abdo-pelvis protocols) are also effective to diagnose appendicitis (Kim 2012).
Diagnostic laparoscopy is an invasive, intra-operative diagnostic modality to confirm appendicitis by direct visualisation or other intra-abdominal pathologies during keyhole surgery. The diagnostic capability of laparoscopy in cases of uncertainty has probably lowered the threshold for surgery. However, as intra-operative laparoscopic diagnosis of appendicitis can be difficult, diagnostic laparoscopy can paradoxically increase the negative appendicectomy rate. In some studies over 30% of appendices that look normal at laparoscopy are inflamed on histological analysis (Roberts 2008; Phillips 2009; Slotboom 2014). If no other significant pathology is seen inside the abdomen, some intra-operative protocols will mandate the appendix is removed, even if it looks normal, to ensure that microscopic appendicitis is not missed. The negative appendicectomy rate (NAR) has therefore gone up in some centres since the advent of laparoscopy (Akbar 2010; Jones 2012). Other centres advocate leaving a normal appendix in situ, consequently decreasing the NAR rate (Teh 2000), but still having subjected a patient to surgery.
Many conditions mimic the symptoms and signs of appendicitis. Up to one third of all women of child-bearing age with right iliac fossa pain (Rothrock 1995) are incorrectly diagnosed with appendicitis due to similar symptoms caused by a wide range of common gynaecological conditions. Women have a higher negative appendicectomy rate (NAR) in most studies compared to men (28.6% vs 12.8% respectively, Bhangu 2013).
Children, adults and elderly people also have alternate diagnoses that may mimic appendicitis. Some of these conditions may be self-limiting (e.g. mesenteric adenitis or gastroenteritis) and will resolve without any treatment, or may require medical treatment only. Other conditions that require surgical treatment may leave patients and surgeons unprepared for the extent of the operation required, and its potential complications (e.g. perforated diverticulitis requiring bowel resection and stoma formation).
When appendicitis is diagnosed incorrectly, the decision to operate may lead to unnecessary surgery and subject a patient to an avoidable operation with the risk of complications. It additionally incurs costs to the hospital (costs of inpatient stay, surgery, treatment of complications), to the wider healthcare setting (costs of community follow up by a general practitioner or family doctor), and to the economy (costs of time off work for the patient and their caregiver).
A lack of access to imaging resources can contribute to a higher negative appendicectomy rate. CT has excellent diagnostic accuracy for appendicitis, and evidence exists from previous studies that routine CT scanning can decrease the negative appendicectomy rate (Krajewski 2011; Drake 2012) by excluding appendicitis or finding alternate diagnoses. CT may not be used routinely due to its cost, but studies from the USA have confirmed that the cost of surgery and inpatient stay in hospitals with a high NAR can outweigh the cost of routine CT scanning in all patients (Rao 1998; Pena 1999). However concerns still exist over the radiation exposure from CT which can increase the scanned patient's lifetime risk of cancer.
Magnetic Resonance Imaging is not commonly used to diagnose appendicitis. However, there is a growing body of evidence from single centre studies that MRI can diagnose appendicitis with a similar diagnostic accuracy to CT, but without exposing scanned patients to radiation. If this meta-analysis confirms that MRI has equivalent sensitivity and specificity to CT, then it would challenge current clinical management to replace CT with MRI in the routine assessment of patients with suspected appendicitis. Routine MRI scanning could replace CT to reduce the NAR and save costs, without radiation exposure.
Other questions exist that could be answered by this systematic review. Shortened MRI protocols exist, so that people may be scanned expeditiously. However, it is unclear if people with abdominal pain can tolerate 15 minutes to 30 minutes in an MRI scanner. It is also unclear whether these abbreviated scans can still diagnose intra-abdominal pathologies other than appendicitis. Answers to these questions are necessary to demonstrate evidence that MRI scanning should be embedded in clinical pathways.