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MRCP in the Assessment of Gallstone Disease
PROTOCOL VERSION 1.4
LAST UPDATED 13 JULY 2014
Contents
Key Contacts...................................................................................................................................1
Protocol Summary..........................................................................................................................3
Abstract................................................................................................................................................4
Introduction..........................................................................................................................................5
STUDY HYPOTHESIS...............................................................................................................................5
OBJECTIVES............................................................................................................................................6
DESIGN AND METHODS.........................................................................................................................7
Eligible Patients.................................................................................................................................7
Patient Identification.........................................................................................................................7
Study Period......................................................................................................................................8
Eligible Centres..................................................................................................................................8
Data Extraction..................................................................................................................................8
Trainees’ Roles...................................................................................................................................9
OUTCOME MEASURES AND STANDARDS..............................................................................................9
DATA COLLECTION...............................................................................................................................10
DEFINITIONS........................................................................................................................................10
STATISTICAL ANALYSIS.........................................................................................................................10
REFERENCES........................................................................................................................................11
APPENDIX............................................................................................................................................12
MAGD STEERING TEAM
List of Key Contacts
Miss Judith Ritchie
CRUK Clinical Research Fellow, Faculty of Medicine, University of Leeds, UK
Dr Emma Nofal
Core Surgical Trainee, Yorkshire and the Humber Deanery, Sheffield, UK
Jonathan R L Wild
Higher Surgical Trainee, Yorkshire and the Humber Deanery, Sheffield, UK
Raj Prasad
Consultant General Hepatobiliary and Transplant Surgeon
Leeds Teaching Hospitals NHS Trust
This protocol was developed on behalf of the committee members of the South Yorkshire Surgical Research Collaborative: Judith Ritchie, Emma Nofal, Matthew Lee, Jonathan Wild, Roxanna Zakeri, Victoria Proctor, Matthew Rigby, Thomas Drake, Tim O’ Connor, Charlotte Gunner, Sarah Daniels.
Protocol Summary
GENERAL INFORMATIONShort title MGD StudyFull title The Role of MRCP in Gallstone DiseaseSponsor South Yorkshire Surgical Research
CollaborativeChief Investigators Judith Ritchie, Emma Nofal, Jonathan WildWebsiteEmailCo-ordinating Centre
STUDY INFORMATIONAim of the study To look at current investigative practice for suspected
choledocholithiasis in order to investigate the role of MRCP in the assessment of patients presenting with suspected ductal stone disease and its impact on surgical management
Study Design Retrospective Observational Service EvaluationPrimary Outcomes Determining variation in investigative practice in patients
with suspected ductal stones Detection and miss rate of common bile duct stones for
different practices (MRCP, USS, CT, ERCP, EUS, OTC)Secondary Outcomes All-cause readmission rates
Post-operative (complications from retained common bile duct stones (pancreatitis, obstructive jaundice, pain, other complications)) within 6 months post-operation
Time from presentation to management (ERCP, LC ±OTC)
Time from presentation to investigation (USS; MRCP, EUS, OTC±ECBD, PTC)
Length of hospital stay, duration of surgery Pre-operative patient factors (demographics,
admission type, level of health/ASA grade and fitness for surgery, contraindications to MRCP)
Cost analysis of use of services (blood tests, USS, CT, EUS, MRCP, OTC)
STUDY TIMELINESPilot date May 2014 SYSuRGMain study period September 2013End of Study Definition November 2014Data submission (live process) November 2014Data analysis December 2014Results available January 2015Paper submission March 2015
Abstract
BACKGROUND
The benefit of MRCP in identifying ductal stones has been widely reported in case
series of patients with gallstone disease. Clinical assessment of patients with
gallstones varies widely across centres for a number of reasons.. This study aims to
look at use of MRCP in centres across the UK, to determine current practices and
their variations, and how these affect clinical outcome.
METHODS
The study consists of 2 parts: a retrospective multi-centric service evaluation and a
consultant surgeon questionnaire.
The retrospective study will capture data over a 4 week period across teaching and
district general hospitals that have an adult acute surgical take, an ERCP facility and
resident consultant surgeons that routinely do cholecystectomies. A cohort of
patients presenting with gallstone disease with suspected ductal stones will be
identified from operative and ERCP lists. Clinical information will be collected
including past medical history and ASA grade, presence of sepsis, blood work,
imaging, previous biliary history and previous interventions. Outcome data will
include length of acute admission stay, timescale and details of investigations,
operative details (cholangiogram, CBD exploration, post-operative ERCP) and post-
operative complications (readmission, identification of retained stones). A
rudimentary cost analysis shall be performed. This study will also include a
questionnaire sent to UK surgeons performing cholecystectomies regarding their
management of these patients and the use of MRCP in their practice.
OUTPUT
This study shall generate a large and informative dataset regarding current clinical
practice for suspected choledocholithiasis. The results of this study will be presented
at ASGBI, AUGIS and BSG conference and will be prepared for publication.
Introduction
Gallstone related disease is a significant cause of morbidity with a major impact on modern
day healthcare. The prevalence of common bile duct stones in symptomatic gallstone
disease has been estimated to be between 10-20% of cases(Tazuma 2006). Ductal stones
can present with pain and deranged liver function tests, or occasionally may be an incidental
finding in asymptomatic patients. Detection and removal of choledocholithiasis is important
as they can result in stone-related complications such as obstructive jaundice, ascending
cholangitis, liver abscess and gallstone pancreatitis. Therefore, clinical judgement is
paramount, and it should guide appropriate use of diagnostic modalities as much as
management.
Diagnostic imaging of the biliary tree can technically be achieved using both invasive and
non-invasive measures. Non-invasive imaging includes ultrasound, CT and MRI. More
invasive measures include cholangiogram of the biliary system, which can be performed
endoscopically through cannulation of the ampulla at endoscopy (ERCP) and
percutaneously through cannulation of the intrahepatic biliary system (PTC), or
intraoperatively at time of cholecystectomy.
Ultrasound imaging is the first line recommended imaging technique in clinically suspected
gallstone disease and also for suspected choledocholithiasis (Williams 2008), and can
reliably detect stones within the gallbladder. However, ultrasound is not a reliable diagnostic
test to justify the use of more invasive measures such as common bile duct exploration. It
has a high sensitivity and specificity for detecting intrahepatic duct dilatation (Stott, Farrands
et al. 1991), but a poor sensitivity but a high specificity for detecting ductal stones (Stott,
Farrands et al. 1991; Varghese, Liddell et al. 1999; Varghese, Liddell et al. 2000).
Furthermore, the presence of intrahepatic duct dilatation on ultrasound does not correlate
reliably with the presence of ductal stones at intraoperative cholangiogram (Stott, Farrands
et al. 1991). Magnetic cholangiopancreatography is a non-invasive imaging technique that
gives three dimensional images of diagnostic clarity of the biliary system similar to those
achieved by endoscopic cholangiogram. MRCP has been shown to give comparable
diagnostic results to ERCP (Adamek, Albert et al. 1998; Shanmugam, Beattie et al. 2005)
with a high sensitivity and specificity for choledocholithiasis (Taylor, Little et al. 2002; Topal,
Van de Moortel et al. 2003; Shanmugam, Beattie et al. 2005) without the associated
morbidity. The ability to detect choledocholithiasis by CT depends upon the constitution of
the gallstones. Calcified stones will be readily visible whereas pure cholesterol stones
hypoattenuate against bile (Brakel 1990)which can make them impossible to detect,
particularly by non-contrast CT. CT imaging has a low sensitivity relative to MRCP and
cholangiography, but this is significantly improved with contrast enhancement versus
non/contrast enhancement (Soto, Alvarez et al. 2000). MRCP has a similar diagnostic
capacity as cholangiography for choledocholithiasis (Varghese, Liddell et al. 2000), biliary
structures and malignant pancreatic pathology (Rösch, Meining et al. ; Hekimoglu, Ustundag
et al. 2008) and has become the preferred non-invasive test for detecting ductal stones
(Paul 2006; Williams 2008). However there are technical contraindications to MRI, in
particular indwelling metallic implants such as pacemakers, aneurysm coils and nerve
stimulators, and it may not be tolerated by patients with claustrophobia(Kaltenthaler E 2004).
ERCP has been shown to have a high sensitivity and specificity for detecting ductal stones
(Varghese, Liddell et al. 1999). Its associated rates of morbidity and mortality (Andriulli 2007;
Williams, Taylor et al. 2007) such as perforation and post-ERCP pancreatitis do not make
this an acceptable diagnostic test, and ERCP should be used solely for therapeutic purposes
(Williams 2008; Royal College of Surgeons of England 2013). EUS generates good images
of the biliary system, on which stones are visualised as hyperechoic foci. It has been
demonstrated to be as sensitive and specific for choledocholithiasis to MRCP (Verma,
Kapadia et al. 2006).
Management options for choledocholithiasis include endoscopic via therapeutic ERCP to
remove stones plus/minus sphincterotomy where there is a high likelihood of recurrent
stones or biliary stenting to bypass impacted stones and restore biliary flow. Surgical
management includes exploration of the common bile duct and stone extraction at time of
cholecystectomy, with pre- or postoperative ERCP where stones are suspected. Service
provision for ERCP requires dedicated endoscopy services and experienced endoscopists
trained in ERCP which can make ready accessibility to its service difficult. Similarly, common
bile duct exploration requires a considerable level of expertise that will not be available
across the cohort of surgeons performing cholecystectomies. There is very little robust
evidence regarding the efficacy of endoscopic versus surgical common bile duct exploration.
Existing evidence suggests there is less chance of missed stones following open CBD
exploration but no difference between laparoscopic CBD exploration and ERCP (Dasari, Tan
et al. 2013), with comparable morbidity and mortality.
Current guidelines on management of common bile duct stones recommend abdominal
ultrasound as a first line investigation along with blood tests including liver function (Williams
2008). EUS or MRCP is recommended for further investigation where choledocholithiasis is
suspected, depending on patient suitability, accessibility to resources and expertise
(Williams 2008). Clinical practice in investigating and managing suspected common bile duct
stones varies between centres, influenced by surgeons' practice and local expertise
(Poulose, Phillips et al. 2011), access and availability of resources (Williams, Taylor et al.
2007) and individual patient factors. This study aims to explore this variation in clinical
practice, and more specifically determine whether it has any impact on patient outcomes.
STUDY HYPOTHESES
MRCP has made a significant impact on the detection of ductal stones or other ductal pathology in the surgical patient cohort.
Use of non-invasive diagnostic modalities is associated with less morbidity.
MRCP is associated with lower morbidity, a lower incidence of missed CBD stones and better patient outcomes.
Variations in clinical practice may affect influence patient outcomes.
Investigation and treatment of ductal stones in clinical practice is affected by local access and availability of resources.
OBJECTIVES
The aim is to gain insight into the practices used in the surgical assessment of the biliary system in general surgery units across the country and whether this has any impact on surgical outcomes. In particular, this study wants to determine the impact that the non-invasive imaging modality MRCP has had on patient care.
The primary objective is to determine the detection rate and miss rate of ductal stones according to the approach taken to investigation and management.
The secondary objectives are:
To determine time from presentation to each imaging modality (USS, CT, EUS, MRCP) and the time from presentation to definitive treatment (ERCP, surgery and OTC± CBD exploration), or non-surgical interventions in those unfit for surgery e.g. ERCP and stent, PTC and stent)
To determine the effect of other surgical outcomes including length of operation, length of hospital stay (for surgery taking place during the presentation episode)
To determine the all-cause 30 day complication and readmission rate following surgery and determine how these rates correlate to preoperative assessment.
To determine the cost of investigations.
DESIGN AND METHODS
This study is comprised of two parts.
The first part is a retrospective multi-centric service evaluation.
The second part is a postal questionnaire for UK consultant surgeons who performed the cholecystectomies included in the study period. The questionnaire aims to explore each consultant’s practice in assessment and management of these patients and the reasons behind this.
Eligible Patients
Adult patients presenting to general surgical units across the country with a diagnosis of gallstone disease with suspected ductal stones who have undergone cholecystectomy or ERCP during the study period (4 week period in February-March 2013), namely:
Symptomatic gallstones with deranged liver function tests Obstructive jaundice with low suspicion of cancer (painful/painless) Gallstone pancreatitis
Patient IdentificationEligible
Patients who have undergone cholecystectomy or ERCP during the study period will be included. These patients will be identified by scrutiny of the operative management systems (cholecystectomy codes) and endoscopy data management systems that are in use at each participating hospital
Not Eligible
Patients under the age of 18
Data extraction forms comprise an eligibility form which would determine whether further data extraction and follow-up is warranted.
Study Period
Pilot
The study shall be piloted within Sheffield over a one week period in July 2014. This pilot period will allow the feasibility and applicability of the study protocol and data extraction. The study shall be registered with the clinical effectiveness and audit units in each centre prior to carrying out the pilot. Any alterations to the study protocol or data extraction process will be made following evaluation of this pilot period.
Main Study
The main study will recruit over 4 weeks. The study is projected to start from September 2014.
Eligible Centres
Surgical centres across the country will be invited to take part. Eligible centres include:
Centres with an acute surgical admissions unit. Centres with consultant surgeons routinely performing elective and
emergency cholecystectomies. Centres with endoscopy units that run regular ERCP lists.
Data Extraction
The data extraction form will capture important demographic and clinical details from these patients including:
Nature of presentation (elective, emergency) General health with ASA grade. Drug history. Previous biliary history, investigation and intervention Contraindications to imaging (pacemaker/metalwork, claustrophobia etc).
The study will also capture information regarding the surgical workup
Clinical parameters (signs of biliary sepsis) Blood work (deranged LFTs (new/not new/no previous to compare) Imaging (USS, CT, MRCP, EUS, other) Preoperative interventions (ERCP, PTC)
Details regarding the surgical outcome shall be sought:
Cholecystectomy (index, scheduled/hot list, elective, delayed) On table cholangiogram ± bile duct exploration Grade of surgeon Consultant name Length of surgery Definitive treatment if no surgery (and reason)
Finally details regarding the post-operative outcomes shall be gathered, namely:
Perioperative complications Postoperative complications during surgical episode Length of acute admission stay Length of surgical stay Readmission with post-operative complications following discharge from
surgical episode Further investigations and interventions
Trainees’ RolesInterested trainees at each centre should nominate one trainee as the lead investigator, and identify an appropriate consultant surgeon at their unit who is happy to be the consultant lead for their centre. The lead investigator must take responsibility for registering the study through their hospital’s clinical audit and effectiveness unit according to their local policy. Proof of consultant lead and registration with the audit office will need to be provided to SYSuRG before the study begins. Ongoing support will be available from SYSuRG for trainees taking part in the study.
DATA COLLECTION
Data should be collated for each centre electronically. Leeds University is hosting an online encrypted secure database. An account shall be made for a contact at each participating centre into which to input data.
All data should be recorded according to the policy of their hospital’s clinical audit unit policy. Hospitals should fill out the relevant Data Protection forms that are available from Information Governance.
All data should be anonymised at point of entry into electronic database. No patient identifiable information should be entered into the database. Each centre is asked to therefore generate a study number for each eligible patient.
SYSURG MAGD team can help, advise or answer any questions regarding any aspect of the above on request.
AUTHORSHIP
All those coordinating and contributing in data collection will be listed as authors in any publications arising from this work, after the relevant members of the project steering committee. Therefore all those actively contributing to the project would be listed in Pubmed as an author to the paper in a Pubmed linked journal.
DEFINITIONS
MRCP: Magnetic resonance cholangiopancreaticogram
ERCP: Endoscopic retrograde cholangiopancreaticogram
EUS: Endoscopic ultrasound
Deranged liver function tests: Bilirubin aboveAlkaline phosphatase above
GGT above
ALT above
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Verma, D., A. Kapadia, et al. (2006). "EUS vs MRCP for detection of choledocholithiasis." Gastrointestinal Endoscopy 64(2): 248-254.
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