Target condition being diagnosed
Appendicitis results from inflammation of the vermiform appendix and is the most common abdominal condition requiring emergency surgery. Typically appendicitis presents with a 24 hour history of vague central abdominal pain that migrates to the right iliac fossa. This is often accompanied by anorexia, nausea and constipation. A tachycardia and pyrexia are common. Abdominal examination may reveal localised tenderness in the right iliac fossa with guarding, rigidity and percussion or rebound tenderness. Often the site of maximum tenderness is located at McBurney’s point, which lies two-thirds along a line from the umbilicus to the anterior superior iliac spine (Grover 2011). Pain may be exacerbated by movement, and by asking the patient to cough which will often localise the pain to the right iliac fossa.
The incidence of appendicitis is approximately 1 per 1,000 per year (Hall 2010) with a male to female ratio of1.1:1 and an overall lifetime risk of 8.6% for males and 6.7% for females (Addiss 1990). It is the most common abdominal emergency and accounts for more than 40 000 hospital admissions in England every year (approximately 1 per 1500 population) (Lewis 2011). Appendicitis is a progressive inflammatory process which may result in perforation, abscess formation, generalised peritonitis, bowel obstruction and rarely death with a mortality rate of 0.08%, rising to 0.5% in the event of a perforated appendix (Blomqvist 2001). The incidence of perforation rises with the duration of symptoms (Bickell 2006) therefore, prompt diagnosis and treatment are essential for reducing the morbidity and mortality associated with advanced inflammation.
The treatment of choice for appendicitis is appropriate resuscitation followed by expedient appendicectomy. Traditionally appendicectomy has been performed by laparotomy via a right iliac fossa incision, however in recent decades appendicectomy has been performed laparoscopically via multiple incisions (Swank 2011), with advances in technology also spurring an interest in single incision laparoscopic surgery (SILS) (Feinberg 2011) and Natural Orifice Transluminal Endoscopic Surgery (NOTES) (Roberts 2011) in more recent years. All patients with appendicitis should receive broad spectrum perioperative antibiotics as this decreases the incidence of postoperative wound infections and abscess formation (Andersen 2005). Antibiotics have also been proposed as the primary treatment for uncomplicated appendicitis (Varadhan 2010), however appendicectomy remains the gold standard.
In the Cochrane Library, there are five intervention reviews published relating to appendicitis; antibiotics versus placebo for prevention of postoperative infection after appendicectomy (Andersen 2005), laparoscopic versus open surgery for suspected appendicitis (Sauerland 2010), laparoscopy for the management of acute lower abdominal pain in women of childbearing age (Gaitan 2011), single incision versus conventional multi-incision appendicectomy for suspected appendicitis (Rehman 2011) and appendicectomy versus antibiotic treatment for acute appendicitis (Wilms 2011). In addition two protocols have been published, one intervention review protocol on appendix stump closure during laparoscopic appendectomy (Sauerland 2010), and one diagnostic test accuracy review protocol of computed tomography for appendicitis in adults (Rud 2012).
Ultrasound (US) has been an important tool used in the diagnosis of appendicitis since the 1980s.The pulse-echo principle, in which sound waves are transmitted through a medium and reflected back, forms the basic principle of conventional ultrasound (US) (Case 1998). US machines consist of a transducer that contains piezoelectric crystals that convert electrical energy into ultrasonic sound waves, above the frequency of human hearing of 20 kHz or 20,000 cycles per second. The transducer then simultaneously detects the echo sound waves, reversing the conversion from ultrasonic sound waves into an electrical signal (Case 1998). This echo signal, having reflected off any structures that lying in its path, is then analysed and displayed as a cross-sectional tomographic image. Hyperechoic structures appear brighter and hypoechoic structures are darker, with the brightness of each pixel corresponding to the amplitude of the echo (Hangiandreou 2003). The echo strength is determined by the differential acoustic impedance between adjacent structures. US images can be made clearer by increasing the size of the transducer crystals, altering the US frequency, changing the angle of the transducer or focusing the sound beam (Hangiandreou 2003). Modern US technology has enabled multiple areas of beam focusing on the same image (Smith 2004).
Advances in US technology and the graded compression technique have improved the visualisation of the appendix (Birnbaum 2000). A standard contemporary US performed in suspected appendicitis will first examine the right hypochondrium and pelvis (typically using a 3-5 MHz transducer) in order to exclude alternative pathology relating to the liver, gallbladder, pancreas, kidney or pelvic organs and assess for the presence of free peritoneal fluid. Graded compression and colour Doppler sonography is then performed in the right iliac fossa. The ascending colon is identified and followed proximally, with the iliac vessels identified by the Doppler sonogram (Gaitini 2008). The graded compression technique involves applying steady, gradual pressure to the right iliac fossa, with emphasis over the site of maximal tenderness, in order to collapse the normal small bowel by dispelling bowel gas, and to differentiate between an incompressible inflamed appendix and compressible and displaceable normal small bowel (Puylaert 1986). A normal appendix appears as a blind ended, aperistaltic tubular structure with a wall thickness of 2mm or less that originates from the base of the caecum (Yabunaka 2007). An incompressible, blind-ended, fluid-filled, tubular structure with hyperemic walls with a thickness of greater than 6mm are often used as a criterium for sonographic appendicitis (Prystowsky 2005). Other positive findings suggesting appendicitis are the presence of a faecolith, hyperechoic periappendicular fat, peritoneal fluid or a collection (Gaitini 2008). To improve visualisation of a retrocaecal appendix, lumbar manual compression can also be performed (Lee 2002). A combined transabdominal and transvaginal approach has been suggested to improve the diagnostic accuracy of ultrasound in females with suspected appendicitis (Bondi 2012). Reports from US performed for suspected appendicitis often conclude as being positive, negative or inconclusive for appendicitis. US is operator dependent and as a result the reported sensitivity, between 76%-90% and specificity, between 83%-100% can vary (Keyzer 2005, Parks 2011). With increasing technical expertise and experience the diagnostic accuracy of US is improving, especially in high volume centres.
The main advantages of US over other modalities is that it is noninvasive, quick to perform, relatively cheap (Wan 2009), can be used to identify other alternative causes of abdominal pain and has real-time capability, mobility and lack of ionizing radiation making US safer for patients and operators (Cogbill 2011). With concerns over childhood and foetal exposure to ionizing radiation, US has been particularly useful in the diagnosis of appendicitis in children (Doria 2009) and in pregnant women, with a variable sensitivity ranging from 66% to 100% and a specificity of 95% to 96% reported (Patel 2007). Disadvantages of US include operator dependency and inconclusive results in the event of the appendix not being visible (Parks 2011). A false negative US result may lead to a delayed diagnosis, increased risk of perforation and increased sepsis-related morbidity and rarely mortality. A false positive US results in unnecessary surgery, and risk of unnecessary surgical complications.
The traditional approach of diagnosing appendicitis is based on careful history taking and physical examination, with assessment of the intensity and sequence of symptoms, clinical signs and basic laboratory tests. However, the classical sequence of vague abdominal pain followed by vomiting with migration of the pain to the right iliac fossa may only be present in as few as 6% of patients with suspected appendicitis (Lameris 2009) and the presence or absence of any particular individual symptom or sign cannot be relied upon to diagnose or exclude appendicitis. Each single element of the history and of clinical and laboratory examination are of weak discriminatory and predictive capacity. However, higher discriminatory and predictive power can be achieved by using the variables in combination with repeated patient evaluations over a period of close observation also increases the discriminatory power of clinical assessment (Andersson 2004). Although good clinical acumen remains the mainstay of the correct diagnosis of appendicitis, clinical presentation is, however, often equivocal and diagnostic errors are common (Wagner 1996). Presentation may be influenced by the anatomical position of the appendix, for example displacement of the appendix by the gravid uterus often results in atypical presentations of appendicitis in pregnancy (Ito 2011), and an accurate history may be difficult to obtain in young children or the elderly with delirium. There are also many conditions that can cause right iliac fossa pain and may therefore mimic appendicitis, sometimes making the early diagnosis of acute appendicitis a challenge. Therefore, initially, in order to reduce diagnostic uncertainty, clinicians utilise blood tests, such as white cell count and C-reactive protein, and diagnostic scoring systems.
Scoring systems have been developed to aid diagnosis by estimating the probability of appendicitis occurring in the individual patient. The best known is the Alvarado scale (Alvarado 1986), although alternatives have been proposed (Enochsson 2004; Andersson 2008; Chong 2010). The Alvarado scoring system comprises of eight weighted clinical indicators - three symptoms, three signs and two laboratory findings; migratory pain, anorexia, nausea and/or vomiting, right lower quadrant tenderness, rebound tenderness, pyrexia, leucocytosis (>10 X 109/L) and a neutrophilic shift to the left >75. Patients with an intermediate score require serial reassessment of physical findings and often complementary diagnostic imaging. The diagnostic accuracy of the Alvarado score has been reported as 90.9% for a score of 7-10 and 100% for a score of 0-4 (Jang 2008).
If the diagnosis of acute appendicitis appear highly likely, especially in male patients where alternative diagnoses are less common, it is currently accepted practice to proceed directly to exploratory surgery, which will be either an open or laparoscopic approach. However, with increasing evidence demonstrating that preoperative imaging improves diagnostic accuracy in appendicitis, there has been an increase in use of radiological investigations in order to confirm diagnosis prior to invasive surgical intervention.
Role of index test(s)
Following clinical assessment, US is often used as the primary imaging modality, especially in the paediatric and obstetric setting.
If the US is negative or equivoval, a computed tomography (CT) scan is often the next imaging modality of choice. CT has been used in the diagnosis of appendicitis for around twenty years, with modern multi-slice CT scanners now capable of acquiring an image in a few seconds with the ability to reformat axial images into coronal and sagittal cross-sectional images that facilitate identification of the appendix (Paulson 2005). Attempts to improve the accuracy of CT with enhancement by intravenous (IV), oral or rectal contrast agents are controversial. The use of IV-contrast may cause allergic reactions, using enteric contrast is time consuming and some argue that enhancement may not be necessary (Neville 2009). Although CT has been shown to have a high diagnostic accuracy, with a sensitivity of 90%-100% and specificity of 90%-100% (Parks 2011), the major limitation of CT is the use of ionising radiation. The estimated lifetime risk of cancer due to the radiation exposure resulting from a CT scan is 0.14 - 0.02%, the lower the age at the time of the CT scan - the higher the estimates (Brenner 2007). It is for this reason that CT should be reserved for those cases of possible appendicitis with equivocal presentations (Hernanz-Schulman 2010). Diagnositic laparoscopy may often be used instead of CT, especially in young female patients, in order to prevent unnecessary radiation exposure with the added benefit of offering definitive treatment at the same setting as the investigation.Although diagnostic laparoscopy enables direct visualisation of the appendix and other intra-abdominal viscera, a recent study estimates the positive predictive value of laparoscopy to be 93%, with a negative predictive value of 71% (Hussain 2009). Laparoscopy is also associated with increased morbidity and expense (Golash 2005). Magnetic resonance imaging (MRI) has been shown to be an accurate test for diagnosing appendicitis, with a prospective study in 138 patients reporting a 100% sensitivity and 98% specificity (Cobben 2009). Although MRI has had a limited role in the evaluation of the acute abdomen due to low availability, high cost and long study duration, MRI is an attractive option in diagnosing appendicitis in pregnancy following an inconclusive ultrasound scan due to its high accuracy and that it does not involve the use of ionising radiation (Basaran 2009). Due to the above limitations, however, MRI is not currently routinely used in clinical practice for the diagnosis of acute appendicitis.
It has been estimated that a third of patients with appendicitis have atypical presentations, with one study suggesting as few as 6% present with the classical sequence of vague abdominal pain followed by vomiting with migration of the pain to the right iliac fossa (Lameris 2009). A delay in diagnosis can result in increased perforation rates and increased morbidity and mortality therefore surgeons have been more inclined to operate when the diagnosis is probable rather than to wait until it is certain. An early decision to perform surgery may reduce potential morbidity and mortality, however can also lead to the unnecessary removal of a normal appendix. In the Western world, the life-time risk of acute appendicitis is 6.7% for females and 8.6% for males (Addiss 1990), yet the life-time chance of an appendicectomy is higher, with some reports of a negative appendicectomy rate as high as 20% (Parks 2011). In acute appendicitis, the diagnostic accuracy based on clinical examination alone is 80% (Old 2005). Recent studies advocate the use of medical imaging to reduce the rate of negative appendicectomies. US may be especially useful where there are equivocal clinical signs or an indeterminate diagnostic score. In these situations US may improve diagnostic accuracy by reducing the number of false negatives and therefore prevent unnecessary surgery. There are, however, there are no clear guidelines regarding the optimal use of US in the diagnosis of acute appendicitis. Practice varies across the world and reported sensitivity (76%-90%) and specificity (83%-100%) can vary (Keyzer 2005; Parks 2011). Although CT has been shown to have a high sensitivity and specificity, a prospective trial revealed similar diagnostic performance of US and CT (Keyzer 2005). When compared to CT, US is inexpensive, more readily available and does not expose the patient to ionising radiation, making US more preferable in the paediatric and pregnant patients.
A contemporary review of the diagnostic accuracy of US for acute appendicitis is therefore required which incorporates formal assessment of methodological quality while also exploring clinically relevant sources of heterogeneity and implementing appropriate statistical methods therefore providing the reader with a quantitative summary of the available evidence in this field. We believe that a systematic assessment comparing the diagnostic performances of US and CT merits a review of its own and we plan to carry out this comparison in a separate Cochrane review in the future.