Magnetic resonance imaging (MRI) for diagnosis of acute appendicitis

  • Protocol
  • Diagnostic

Authors


Abstract

This is the protocol for a review and there is no abstract. The objectives are as follows:

The primary objective is to determine the diagnostic accuracy of MRI for detecting appendicitis in all participants.

  • Investigate the accuracy of MRI in subgroups of pregnant women, children and adults.·

  • Investigate the potential influence of scanning variables such as sequences, slice thickness, or region of capture.

Background

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).

Index test(s)

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.

Clinical pathway

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.

Alternative test(s)

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.

Rationale

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.

Objectives

The primary objective is to determine the diagnostic accuracy of MRI for detecting appendicitis in all participants.

Secondary objectives

  • Investigate the accuracy of MRI in subgroups of pregnant women, children and adults.·

  • Investigate the potential influence of scanning variables such as sequences, slice thickness, or region of capture.

Methods

Criteria for considering studies for this review

Types of studies

We will include studies that compare the outcome of an MRI scan for appendicitis with a reference standard. Prospective or retrospective patient series (cross-sectional or diagnostic cohort) and randomised test accuracy studies will be eligible for inclusion. We will use data from randomised test accuracy studies (if available) to extract measures of diagnostic test accuracy for MRI, not to compare diagnostic accuracy of MRI with alternative tests. We will exclude studies with fewer than 10 participants or with a case-control design. There will be no language restrictions.

Participants

People with suspected appendicitis or people with abdominal pain in the right lower quadrant. We will exclude studies in people with abdominal pain in general.

Index tests

An abdominal MRI scan performed to assess for the presence of appendicitis.

Target conditions

The target condition is appendicitis. We will consider disease status as binary (dichotomous): appendicitis or not appendicitis.

Reference standards

The reference test to diagnose the presence of appendicitis is histological analysis of the appendix specimen following surgery. Mucosal ulceration and neutrophilic infiltration of the muscularis propria will be revealed upon microscopic analysis of simple appendicitis.

In a person with pain in the right iliac fossa, appendicitis can be said to be not present if one of several conditions are satisfied.

  • Firstly and most robustly, if the appendix histology is negative (i.e. not inflamed) following removal at surgery.

  • Secondly, if there is a normal appearance to the appendix at surgery, with or without alternate intra-operative findings that explain right iliac fossa pain, and clinical follow up that excludes a missed diagnosis of appendicitis.

  • Finally, if there is spontaneous resolution (i.e. without antibiotics) of symptoms and uneventful follow up in patients that do not have surgery.

Search methods for identification of studies

Electronic searches

We will search the following bibliographic databases:

  • The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library) (Latest issue and publication year) (Appendix 1)

  • MEDLINE (Ovid, 1946 to present) (Appendix 2)

  • EMBASE (Ovid, 1974 to present) (Appendix 3

Initially we will include studies in all languages and seek a translator for studies published in a foreign language not spoken by one of the review authors. We developed our search strategy in conjunction with a trials search coordinator and the Cochrane Diagnostic Test Accuracy editors.

Searching other resources

Reference lists: we will check the bibliographies of all included or relevant studies, for example existing reviews, for other eligible studies. We will also perform forward tracking of publications that cite included studies. We will revise the search terms if over half of the finally-included references originate from sources other than the electronic searches.

Grey literature: we will check published, citable reports and international conference proceedings from the last 10 years for eligible data or references.

Correspondence: if we cannot retrieve the full text of a study, we will personally contact all study authors to obtain a copy of the full text.

Data collection and analysis

Selection of studies

Two review authors (ND'S, AT) will independently screen titles and abstracts for potentially relevant studies. We will retrieve full-text articles of all potentially relevant studies and assess them for eligibility.

Two authors (ND'S, AT) will perform selection and data extraction processes in duplicate to ensure rigour and will resolve any discrepancies by discussion or referral to a third review author (BR) for arbitration.

We will document the selection process and present this in a PRISMA flow chart (Liberati 2009).

Data extraction and management

We will collect data using a standard data extraction form and analyse the collected data using Review Manager software (RevMan 2014). We will extract data in duplicate to ensure quality assurance. We will resolve any discrepancies by discussion or refer them to a third review author for arbitration.

The data collection form may require several iterations to ensure that we capture all relevant data variables.
The data collection form will include the following key variables:

  • patient demographics,

  • selection criteria,

  • recruitment procedure,

  • clinical setting,

  • MRI scanner generation,

  • region scanned,

  • MRI sequence,

  • MRI scan time,

  • contrast,

  • radiologist experience or specialisation,

  • MRI tolerability,

  • MRI criteria for appendicitis,

  • technique for diagnosis of appendicitis,

  • prevalence of appendicitis,

  • type of appendicitis present (simple or complicated (gangrenous, perforated, abscess)).

Assessment of methodological quality

Two reviewers (ND'S, AT) will utilise the QUADAS-2 tool (Whiting 2011) to assess methodological quality. A rating guideline has been developed, and included in Appendix 4. This tool may require further revision during the study. We will resolve any discrepancies by discussion or by arbitration by a third reviewer (BR). We will present outcomes of methodological quality assessment in table format. We will use heterogeneity analysis to investigate the influence of bias risk on accuracy.

Statistical analysis and data synthesis

We will present primary study estimates of sensitivity and specificity in forest plots and in a receiver-operating characteristics plot.

We anticipate little variation between studies in MRI-criteria for appendicitis. We will use the bivariate random-effects method to determine summary estimates of sensitivity and specificity with 95% confidence intervals (CI) and prediction regions (Reitsma 2005). Regardless of MRI-protocol, we will include all studies in one overall meta-analysis. We will calculate post-test probabilities of appendicitis following positive and negative MRI scans from summary estimates of sensitivity and specificity for the median, upper and lower quartiles of encountered pretest probabilities.

We will use the metandi command in Stata to perform the meta-analyses (Takwoingi 2013; Stata 2015) and follow the guidelines in chapter 10 of the DTA handbook to handle (Macaskill 2010)convergence issues.

If included studies report estimates of accuracy for several MRI-criteria, we will focus on the criterion that confers the highest degree of clinical homogeneity with the other studies. If sensitivity and specificity are reported for several observers in studies with a paired design, we will calculate mean counts for true positives, false positives, false negatives and true negatives and round them to integers when mean results across observers are not available.

Investigations of heterogeneity

We will perform subgroup analyses to explore the impact of the following potential sources of heterogeneity on summary estimates of sensitivity and specificity.

  • Patient population including

    • pregnant women

    • children

    • adults

  • MRI protocol variables including

    • field of view (e.g. whole abdomen versus limited area)

    • slice thickness (3 mm versus >3 mm)

    • sequence (e.g. T2 weighted images only versus T2 and T1 weighted images)

    • total scan time (less than five minutes, between five and 20 minutes, more than 20 minutes).

    • contrast (iv (e.g, gadolinium), oral (e.g. barium)) versus no contrast.

We will use the xtmelogit command in STATA to perform the subgroup analyses (Takwoingi 2013).

Sensitivity analyses

We will explore the impact of methodological quality on summary estimates of sensitivity and specificity. We will perform sensitivity analyses that compare summary estimates of sensitivity and specificity with 95% confidence intervals after excluding studies rated with high or unclear risk of bias in each of the four QUADAS-2 domains.

Assessment of reporting bias

Reporting bias will not be assessed.

Acknowledgements

We would like to thank Sys Johnsen (trials search co-ordinator for Cochrane Colorectal Cancer) for her help devising the search terms. Drs Scott Steele and Henning Keinke Andersen for peer reviewing; we used their many excellent comments to edit this manuscript. The Cochrane DTA Editorial team in Birmingham also made helpful comments on the methodological part of the protocol. Finally we are also grateful to Denise Mitchell for her excellent work as copy editor.

Appendices

Appendix 1. CENTRAL, search strategy

1. “Appendicitis”

2. (Right near/2 (iliac fossa* or quadrant pain)):ti,ab,kw

3. “Appendix”

4. “Appendectomy”

5. (appendec* or appendicec* or appendicit*):ti,ab,kw

6. ((operat* or resect* or remov* or suger* or surgical or laparoscop* or acute) near/5 appendi*):ti,ab,kw

7. #1 or #2 or #3 or #4 or #5 or #6

8. “magnetic resonance” or “magnetic resonance imaging”

9. (MRI or MRIs):ti,ab,kw

10. (MR near/3 (imag* or scan*)):ti,ab,kw

11. #8 or #9 or #10

12. #7 and #11

Appendix 2. MEDLINE, search strategy

1. Appendicitis/

2. Appendicitis.tw,kf.

3. (right adj2 (iliac fossa* or quadrant pain)).kw,kf.

4. Appendix/su

5. Appendectomy/

6. (appendec* or appendicec* or appendicit*).kw,kf.

7. ((operat* or resect* or remov* or suger* or surgical or laparoscop* or acute) adj5 appendi*).kw,kf.

8. Or/1-7

9. Magnetic resonance/ or magnetic resonance imaging/

10. (MRI or MRIs).kw,kf.

11. (MR adj3 (imag* or scan*)).kw,kf.

12. Or/9-11

13. 8 and 12

14. Exp animals/ not humans.sh.

15. 13 not 14

Appendix 3. EMBASE, search strategy

1. appendicitis/ or acute appendicitis/ or appendix perforation/

2. ((right adj2 (iliac fossa* or quadrant pain)).tw,kw.

3. Appendix/su

4. Appendectomy/

5. (appendec* or appendicec* or appendicit*).tw,kw.

6. ((operat* or resect* or remov* or suger* or surgical or laparoscop* or acute) adj5 appendi*).tw,kw.

7. Or/1-6

8. Nuclear magnetic resonance/ or nuclear magnetic resonance imagning/

9. (MRI or MRI’s).tw,kw.

10. (MR adj3 (imag* or scan*)).tw,kw.

11. Or/8-10

12. 7 and 11

13. (exp animal/ or exp invertebrate/ or animal.hw. or nonhuman/) not (exp human/ or human cell/ or (human or humans or man or men or wom?n).ti.)

14. 12 not 13

Appendix 4. QUADAS 2 guideline

QUADAS-2 Assessment for MRI in Appendicitis Meta-Analysis

Review question

What is the diagnostic accuracy of MRI for appendicitis?

Patients

All patients presenting to ED or the acute surgical team with suspected appendicitis (based on history and examination, or blood tests and urinalysis, or both).

Index Test

MRI scan of the abdomen.

Reference Standard

Appendicitis present: positive appendix histology.

Appendicitis not present: surgery resulting in negative appendix histology, or a normal appendix appearance intra-operatively with clinical follow up. If no surgery, spontaneous resolution of symptoms with clinical follow up.

Domain 1: Patient Selection

Risk of bias: Could the selection of patients have introduced bias?

Signalling question 1: Was a consecutive or random sample of patients enrolled?

  • Yes: explicitly stated that enrolment was consecutive or random.

  • No: above condition not met.

  • Unclear: insufficient information available to answer yes or no.

Signalling question 2: Did the study describe explicit eligibility criteria for patients with suspected appendicitis?

  • Yes: specific eligibility criteria on history, examination, observations and baseline investigations described.

  • No: no eligibility criteria described.

  • Unclear: insufficient information available to answer yes or no.

Signalling question 3: Did the study avoid inappropriate exclusions?

  • Yes if only following patients were excluded.

    • Patients with very low clinical probability of appendicitis.

    • Peritonitic or septic patients too unwell for MRI.

    • Patients unable to undergo MRI due to

      • Unwillingness or inability to give consent (patient or guardian) or

      • Inability to tolerate MRI (infants requiring intubation, claustrophobia).

  • No: patients not meeting the above criteria were excluded.

  • Unclear: insufficient information available to answer yes or no, or if consecutive or random sampling was stated, but was inconsistent with other information in the study report

No signalling question re case-control design will be included as these studies will be excluded from the review.

Risk of selection bias assessment

  • High risk of bias: signalling questions 1, 2 and 3 are answered “no”.

  • Low risk of bias: signalling questions 1, 2 and 3 are answered “yes”.

  • Unclear risk of bias: insufficient information is reported to answer signalling questions 1, 2 and 3.

Applicability

Are there concerns that the included patients and setting do not match the review question?

  • No concern

    • If patients are seen in the acute setting with a clinical history (migratory right iliac fossa pain, nausea, fevers, anorexia) and examination (rebound tenderness, tachycardia, low grade pyrexia) consistent with appendicitis, with or without baseline investigations (blood tests and urinalysis) prior to MRI.

  • High concern

    • Patients as above are not included, including stable patients with a high risk of appendicitis.

    • Patients from other settings (eg elective outpatient investigation) are included.

  • Unclear

    • Insufficient information available.

Domain 2: Index Test

Risk of bias: Could the conduct or interpretation of the index test have introduced bias?

Signalling question 1: Were the index test results interpreted without knowledge of the results of the reference standard?

MRI scans will routinely be performed prior to surgery. Reporting bias will only be present if the scan is reported after surgery and the radiologist is aware of the operative findings.

  • Yes if one the two conditions are met

    • MRI scan reported prior to surgery or

    • MRI scan reported:

      • Following surgery with the radiologist blinded to the patient’s operative findings or

      • Following conservative management with the radiologist blinded to the patient’s clinical outcome

  • No

    • Neither condition met

  • Unclear

    • Insufficient information available to answer yes or no

    • Insufficient information available to answer yes or no

Signalling question 2: If a threshold was used, was it pre-specified?

  • Yes if pre-set criteria for MRI diagnosis of appendicitis are stated in the methodology.

  • No if the above condition not met.

  • Unclear: insufficient information available to answer yes or no

Risk of index test bias assessment

  • High risk of bias: signalling questions 1 or 2 are answered “no”.

  • Low risk of bias: signalling questions 1 or 2 are answered “yes”.

  • Unclear risk of bias: insufficient information is reported to answer signalling questions 1 or 2.

Applicability

Are there concerns that the index test, its conduct, or interpretation differ from the review question?

The reproducibility of the index tests depends on several variables in its conduct and interpretation.

  • Conduct

    • Sequences (eg T2 fast spin echo vs T1 GRE)

    • Region included in the scan (pelvis only vs abdomen and pelvis)

    • Slice thickness

    • Contrast (IV, oral, rectal)

    • Magnet strength

  • Interpretation

    • Radiologist expertise and seniority

Domain 3: Reference Standard

Risk of Bias: Could the reference standard, its conduct, or its interpretation have introduced bias?

Signalling question 1: Is the reference standard likely to correctly classify the target condition?

  • Yes if one the following conditions are met

    • The diagnosis of appendicitis is based on histological analysis of the appendix specimen (all cases of macroscopic appendicitis at surgery should lead to appendicectomy).

    • A diagnosis excluding appendicitis not present is based on

      • Negative appendix histology

      • A normal appearance to the appendix at surgery, with or without alternate pathology consistent with pre-operative signs and symptoms

        • This should be confirmed with treatment and symptom resolution or clinical follow up for 31 days without recurrent symptoms or consequent appendicectomy

    • Spontaneous resolution (ie without antibiotics) of symptoms and uneventful follow up in patients that do not have surgery.

  • No if none of the above conditions are met.

  • Unclear: Insufficient information available to answer yes or no

Signalling question 2: Were the reference standard results interpreted without knowledge of the results of the index test?

  • Yes if the following conditions are met

    • If the appendix is removed, the histopathologist is blinded to results of MRI scan.

    • If the appendix not removed, the clinician performing follow up is blinded to the results of the MRI scan.

  • No if neither of the above conditions met.

  • Unclear: insufficient information available to answer yes or no

Risk of reference test bias assessment

  • High risk of bias: signalling questions 1 or 2 are answered “no”

  • Low risk of bias: signalling questions 1 or 2 are answered “yes”

  • Unclear risk of bias: insufficient information is reported to answer signalling questions 1 or 2

Domain 4: Flow and tIming

Risk of Bias: Could the patient flow have introduced bias?

Signalling question 1: Did all patients receive a reference standard?

  • Yes if the following conditions are met

    • At least 95% of included patients had histological assessment (if appendicectomy performed) or clinical follow up (if appendicectomy not performed).

  • No if the above condition is not met.

  • Unclear: insufficient information available to answer yes or no

Signalling question 2: Did all patients receive the same reference standard?

Patients are unlikely to have all received the same reference standard as patients with high risk of appendicitis would not undergo conservative management and clinical follow up. Additionally, patients with low risk of appendicitis may not proceed to surgery. Nonetheless, different reference tests may introduce bias, since histological analysis is the reference standard.

  • Yes if the following conditions are met

    • All patients had surgery with histological analysis of the appendix specimen.

  • No if the above conditions is not met.

  • Unclear: insufficient information available to answer yes or no.

Signalling question 3: Did all patients with a positive MRI scan undergo surgery?

  • Yes if the following condition is met

    • o All patients with a positive MRI scan underwent surgery or clinical follow up.

  • No if the above condition was not met.

  • Unclear: insufficient information available to answer yes or no.

Signalling question 4: Did all patients with a negative MRI scan undergo surgery or clinical followup?

  • Yes if the following condition is met

    • All patients with a negative MRI scan underwent surgery or clinical follow up.

  • No if the above condition was not met.

  • Unclear: insufficient information available to answer yes or no.

Signalling question 5: Was the choice of reference standard independent of the index test result

  • Yes if surgeons decided on surgery or clinical follow up were unaware of the MRI result.

  • No if the above condition was not met.

  • Unclear: insufficient information available to answer yes or no.

Signalling question 6: Were all patients included in the analysis?

  • Yes if the following condition is met

    • At least 95% patients underwent surgery or clinical follow up, or both.

  • No if the above condition was not met.

  • Unclear: insufficient information available to answer yes or no.

Risk of reference test bias assessment

  • High risk of bias: signalling questions 1, 2 or 6 are answered “no”.

  • Low risk of bias: signalling questions 1, 2 or 6 are answered “yes”.

  • Unclear risk of bias: insufficient information is reported to answer signalling questions 1, 2 or 6.

What's new

DateEventDescription
2 February 2016Amendedtitle updated to preferred standard

History

Protocol first published: Issue 1, 2016

DateEventDescription
20 November 2015Feedback has been incorporatedProtocol revised according to editor's comments
8 July 2015AmendedFinal version of protocol for editorial approval
30 June 2015AmendedFinal draft of protocol prepared for editorial approval
31 January 2015AmendedStarted first draft of protocol

Contributions of authors

Nigel D'Souza conceived and co-ordinated the review, and is the guarantor.

Nigel D'Souza, Anthony Thavenirathan and Bo Rud drafted the protocol.

Richard Beable and Anthony Higginson reviewed and contributed to the protocol.

Nigel D'Souza and Bo Rud designed the search strategies.

Declarations of interest

Nigel D'Souza: none
Anthony Thaventhiran: none
Richard Beable: none
Antony Higginson: none
Bo Rud: none

Ancillary