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Comparing the accuracy of Computed Tomography and Magnetic Resonance Imaging during the diagnosis of Pancreatic Adenocarcinoma

 

Table of Contents

Table of Contents. 2

Title. 3

Abstract 4

Introduction. 5

Background. 5

Research Question and Aims. 7

Perspective and Methodology. 8

Rationale for Undertaking a Systematic Literature Review.. 8

Alternative Research Methodologies. 9

Literature search strategy. 11

Research Protocol 12

Eligibility Criteria. 12

PICO.. 14

Quality Assessment (SIGN) and Data Extraction. 14

Conclusions. 16

Timetable. 17

Budget and likely funding sources. 17

Dissemination of Results and Conflict of Interests. 17

References. 18

Appendices. 21

 

 


Abstract

Pancreatic adenocarcinoma consists the most common form of pancreatic cancer, one of the most prevalent malignant diseases on a worldwide level. Its poor prognosis, even when in cases that it is diagnosed in the relatively early stages of the disease, and its dismal 5-year survival rate of less than 5 %, render this form of pancreatic cancer as a highly lethal malignancy. Therefore, it is of the utmost importance to investigate and compare the accuracy and the relative advantages or shortcoming of the existing imaging modalities for evaluating patients with suspected pancreatic adenocarcinoma. This essay intends to provide the basis for a systematic literature review that will compare two imaging modalities related to this field and, subsequently answer which one of them is more accurate and effective: Computed Tomography (CT) or Magnetic Resonance Imaging (MRI). We propose a distinct methodological design that will efficiently provide us with solid findings and answers this question with well-defined inclusion and elusion criteria, but also with a distinct research strategy. Furthermore, and with the critical assistance of tools and frameworks such as PICO, the SIGN checklist, and the PRISMA guidelines we intend to evaluate the pieces of evidence collected, and hence ensure that our finding not only will they be meaningful and accurate, but they will also identify existing gaps in literature and trigger novel directions on future research.

 

Introduction

The pancreas is an organ located behind the stomach which plays a fundamental role in digestion and in the regulation of sugar within the human body (Goodenough, Wallace and McGuire, 1998). The majority of the cells in the pancreas form the exocrine cells and glands that are, in turn, responsible for initiating the release of digesting enzymes in the stomach. However, and at the same time, the majority of pancreatic cancers begin in those cells. More specifically, approximately 95 % of exocrine pancreatic cancers are pancreatic adenocarcinomas, thus rendering this form the most common type of pancreatic cancer (Badashah, 2015; Sharma et al., 2011). Essentially, all types of pancreatic cancer affect approximately 1 to 10 individuals per 100,000, and their respective prevalence is much higher in developed countries and amongst men (Ryan, Hong and Bardeesy, 2014). In fact, this is now the third most common form of cancer in the United States, surpassing the respective incident rates of breast cancer (pancan.org, 2016). Yet, the most critical fact regarding this disease is that it typically has a dismal 5-year survival rate of less than 5 % (Klapman and Malafa, 2008). Therefore, it is of utmost importance to investigate and compare the accuracy and the relative advantages or shortcoming of the existing imaging modalities for evaluating patients with suspected pancreatic adenocarcinoma.

Background

First of all, and based on the devastating survival rates of patients suffering from pancreatic cancer, it comes as no surprise that there is a greater need to improve these rates by focusing on early and accurate detection imaging modalities that would, in turn, allow the provision of optimal treatment to patients (Lee and Lee, 2014). It should be mentioned that pancreatic cancer has an, overall, poor prognosis, even when it is diagnosed in relatively early stages of the disease, owing to the fact that most patients are asymptomatic till late or exhibit nonspecific symptoms (Tummala, Junaidi and Agarwal, 2011). Therefore, and according to Ryan, Hong and Bardeesy (2014) it is expected that 90 % of all patients diagnosed at some point with pancreatic cancer, they will eventually die. In other words, and as stated in the previous paragraph, pancreatic cancer is a highly lethal malignancy and a global health threat that needs to be anticipated in a much more effective manner.

Currently, the initial diagnosis of pancreatic masses is performed with cross-sectional imaging techniques such as endoscopic ultrasound (EUS), multi-detector computed tomography (MDCT), magnetic resonance imaging (MRI), or even with a combination of Positron Emission Tomography and CT (PET/CT) (Pietuga and Morgan, 2015; Shrikhande et al., 2012). In fact, there have been several research studies that have already examined the role and the effectiveness of each of these imaging modalities in the early diagnosis of pancreatic cancers – and more specifically of pancreatic adenocarcinomas. However, the majority of them are not recent; hence they do not include novel research studies, and they also suffer from distinct limitations. For instance, Tummala, Junaidi and Agarwal (2011), performed a literature review by summarising current literature – peer reviewed articles –  in order to state the novelties and developments made in each imaging modality and, subsequently define their advantages or/and disadvantages. The authors concluded that MDCT is the preferred imaging method for patients with clinical suspicion of suffering from pancreatic cancers. The respective methodology is adequate, however a more beneficial approach would be the implementation of a systematic literature review (Uman, 2011). Moreover, the authors are stating that the role of MRI in the diagnosis of this disease is rapidly evolving – and is currently used interchangeably with MDCT for this purpose -, yet they are not using sufficient amount of recent articles to demonstrate its critical use – not to mention that this review was performed more than five years ago, hence the authors have unavoidably omitted innovative recent studies. Furthermore, an additional example demonstrating the current gap in literature is the study performed by Lee and Lee and which was published in 2014. The authors efficiently summarise current evidence, including a comparison of the existing imaging modalities in the diagnosis of pancreatic cancer, yet they fail – when it comes to MRI – to include related innovative studies or new developments. Finally, it should be mentioned that Pietryga and Morgan, in their 2015 published research study, are also focusing on the role of CT in the diagnosis of this disease, yet, once again, they fail to report new studies that emphasise on the accuracy and the role of MRI in the detection of pancreatic adenocarcinoma in adult patients.

Nevertheless, and despite the fact that the ability to diagnose pancreatic carcinomas has substantially improved over the last 20 or so years, the respective prognosis still remains very obscure. Therefore, there is a direct need to firstly summarise the existing on literature, thus relating imaging modalities with their respective accuracy and efficiency, and, subsequently, to emphasise on their disadvantages to further optimise their success – and, hence improve the respective survival rates. This is exactly the reason that has propelled the implementation of our research study that firstly suggests the implementation of a distinct systematic literature review. This review intends to examine the latest trends, results and investigations regarding the accuracy and the efficiency of the two most important imaging modalities in the early detection of pancreatic adenocarcinoma in adult patients.

Research Question and Aims

The principal aim of this study is to demonstrate the abilities needed in order to perform a structured literature review on a given research question. Our topic revolves around the efficiency and the accuracy of both CT and MRI with respect to the diagnosis of pancreatic adenocarcinoma. Therefore, the fundamental objective of this essay is to compare both imaging modalities, evaluate their respective advantages and disadvantages, and to, ultimately, critically state which imaging technique is more accurate and appropriate for the detection of pancreatic adenocarcinoma in adult patients.

Research question:

  • Which imaging modality is most accurate and efficient in the detection and diagnosis of pancreatic adenocarcinoma in adult patient: Computed Tomography (CT) or Magnetic Imaging Resonance (MRI)?

In spite of the fact that there is a substantial amount of evidence that can be found in existing literature, there is a solid need for the provision of more updated evidence regarding the efficiency of current imaging modalities. Hence, this comparison that will be performed is bound to allow researchers to extract far more solid conclusions and, of course, focus on and improve the respective disadvantages of each technique – by simultaneously suggest new directions in future research.

Perspective and Methodology

This next chapter intends to provide a thorough understanding of the means that will be used for the implementation of this research study. There will be a distinct justification why a structured (systematic) literature review is chosen by additionally mentioning the disadvantages of qualitative and quantitative research studies.

Rationale for Undertaking a Systematic Literature Review

First of all, and according to Kitchenham (2004) a systematic literature review can be defined as the ‘means of identifying, evaluating and interpreting all available research relevant to a particular research question, or topic area, or phenomenon of interest’ (p. 1). Consequently, the principal reason for undertaking and implementing such a research methodology on a predefined research question is because they are, by default, extremely powerful tools that allow researchers and readers to either prove or a disprove a given research question or hypothesis (Sousa, Driessnack, & Mendes, 2007). In other words, the acquired results allow for objective conclusions that are far from biased and which allow researchers to critically assess and answer their initial research question (Creswell, 2003). It should also be mentioned that systematic literature reviews are practically a method of secondary study, as opposed to the collection of primary data (Booth, Sutton and Papaioannou, 2016). In other words, this suggests that these reviews rely exclusively on the collection of data from primary – or meta-analysis – studies that are based on the employment of far more rigorous and well-defined methods in terms of reviewing current literature in specific subject areas (Cronin, Ryan and Coughlan, 2008). Furthermore, one of the major advantages of this methodology is that they tend to identify existing gaps in literature, thus allowing for the formation – or inception, if you will – of appropriate frameworks that, in turn, dictate novel directions on a given issue (Mickenausch, 2012). Conclusively, the employment of a systematic literature approach will provide us with all means necessary in order to distinctly answer our research question. This should be performed by setting a specific and well-defined research design and protocol, by emphasising on the respective eligibility criteria for the inclusion of research studies and the respective data extraction.

Alternative Research Methodologies

Qualitative (Narrative) Literature Reviews

Nevertheless, and for the purposes of this research study, it would be also valuable to provide distinct reasoning for not employing different research methodologies. For instance, a qualitative research design – or narrative review, if you will – essentially summarises various primary research studies out of which the researchers can export holistic conclusions (Kirkevold, 1997).  However, this is performed by subjective interpretations, including the researchers’ individual experience, theories and/or models. In fact, narrative reviews are practically a descriptive way of investigating a given research topic and with no, whatsoever, systematic or substantial approach. Therefore, and while being informative, they tend to include a distinct element of selection bias (Pau, 2015). Furthermore, such studies usually tend to overlook small research studies whose size (sample), regardless of their sound methodology, does not possess the ability to induce a statistical change to the overall result (Sargeant et al., 2006). Despite their profound disadvantages which receive a great deal of criticism, they are still a very popular means of performing literature reviews, especially in issues related to science and medicine. However, they are not described as efficient and they are not the optimal method of performing an in-depth analysis. Therefore, and for the purposes of this research study, a narrative literature review would highly diminish the important conclusions and results we want to extract, especially owing to the, unavoidable, selection bias induced.

Quantitative Literature Reviews

On the other hand, quantitative literature reviews offer an additional research tool that makes use of quantitative methodologies. In principle, and much like in this research study, they are usually employed when there is a pre-defined and specific research question that needs to be either proved or disproved by implementing conventional statistical analysis to the acquired data (Guthrie, 2010). Therefore, quantitative research studies have a primary target of searching for various differentiating features, fundamental properties and experimental limits by simultaneously trying to quantify “how much” or “how often” (Jones, 1997). In other words, systematic literature reviews are based on a deductive scheme in which the primary ideas or concepts are converted to mere variables – that are, in turn tested and compared for the acquisition of meaningful results and conclusions. However, and regardless of the usefulness of such research designs, they tend to lose their importance and significance when several parameters affecting their results cannot be fully elucidated. Moreover, they are usually characterised by temporal limitations as they tend to provide a mere snapshot of the research question within a given moment in time (Chiapelli et al., 2010). Consequently, and taking into consideration the pros and cons for each of the previous methodologies, it is evident that a systematic literature approach is the optimal research design that we need to implement. Hence, the following paragraphs intend to present the process that we are proposing to implement by emphasising on the respective search strategy, the data selection process, our inclusion – and exclusion – criteria and data extraction.

Literature search strategy

In principle, a systematic literature review strategy is distinguished into five steps (Khan, Kunz, Kleijnen and Antes, 2003).

  • The initial formulation of a well-defined research framework. This is extremely important because it will allow for the unambiguous definition of our research questions.
  • The investigation and, subsequent identification of relevant research studies in literature.
  • The subsequent evaluation of the importance or significance of the identified studies. This is extremely essential because not all collected evidence and data will prove to be of assistance to our study.
  • Effective and suffice summary of the collected research studies. This is an extremely important step because it will allow for the efficient data extraction and synthesis by taking into serious consideration the potential heterogeneity – or conflicting evidence – that some research studies are bound to present (Gartlehner et al., 2012).
  • Finally, we must then successfully interpret the respective findings, hence verifying the validity of all previous steps in our methodology.

Research Protocol

For the purposes of our review, a distinct investigation will be performed in various electronic databases such as PubMed, EMBASE, Science Direct, PLOS, BioMed Central, SpringerLink WHO, etc. It is of utmost importance to make use of specific text and keywords, define alternative synonyms, and, of course, to consider both UK and US spellings. In our case, keywords used included ‘pancreatic adenocarcinoma’, ‘pancreatic cancer’, ‘MRI’, Computed Tomography’, Diagnostic Tools’, etc. Furthermore, issues such as the journal on which this specific study was published, the year of its publication, and its content are additionally very essential (Pautasso, 2013). This is due to the fact that these factors can affect the quality of the information conveyed e.g. publications need to be up-to-date (older ones are bound to present findings that are not innovative and can practically negatively affect our subsequent conclusions), the higher the impact factor of a journal the more accurate and well-designed or established is the research study, etc. Furthermore, we additionally need to define a distinct and well-defined time frame within which studies will be selected (Parahoo, 2006). In this review, this frame will involve the inclusion of studies that were published not before 2006 (ten years interval).

Eligibility Criteria

In accordance to the PRISMA guidelines, this section will unfold the eligibility criteria that we implemented for the purposes of this systematic literature review (Liberati, Altman and Moher, 2009).

In our case the inclusion criteria will involve the selection of studies that satisfy the following:

  • Studies that present either primary or secondary research data and follow an accurate research methodology e.g. cohort studies, meta-analysis, systematic literature reviews. Such efficient and well-designed research studies can, subsequently, and effectively, assist us to compare – and evaluate – the accuracy with which CT and MRI can detect pancreatic adenocarcinomas in adult patients by, simultaneously allowing us to perform a distinct comparison between these two imaging modalities.
  • Studies that are published in English.
  • Studies that can be found online and which their content is available as full text. Keep in mind that published research studies will practically never report any limitations to their methodology in e.g. their abstract. However, and as a result of the impact factor in which they are published, they tend to have a section in which all limitations are broadly discussed and analysed.
  • Studies performed not earlier than 2006 (a span of decade). This is important because the field of diagnostic imaging is a rapidly evolving science where innovation and novel imaging approaches can render older articles as not useful or informative (Hruby, 2013).

Consequently, we must also define the respective criteria for the exclusion of research studies from our review.

  • Studies will be excluded from this systematic literature review if their reported data or conclusions do not have any precise scientific validity for the purposes of this review.
  • Studies will be excluded from this systematic literature review in case they are found to violate any of the inclusion criteria that were previously unfolded

PICO

A very efficient technique that is used in evidence based practise and which is a highly efficient means of answering clinical questions, is PICO – Population Index test Comparator test Outcomes (usc.edu, 2016). PICO involves the following steps:

  • Formulate the question by defining your target group.
  • Define the interventions or tools that are involved in this question.
  • Comparison or conflict of interest
  • Evaluate the usefulness and quality of the outcomes.

This framework is a very essential method for guiding our research strategy. More specifically, each and every article that will be included in this systematic literature review must satisfy both our inclusive criteria and the steps of the PICO framework.

Quality Assessment (SIGN) and Data Extraction

It was previously mentioned that our inclusion and exclusion criteria are meant to distinguish between useful or appropriate and meaningless or uninformative research studies. Despite the fact that we have already defined an additional framework with which each and every study selected will be assessed – and, subsequently either included or excluded – we also need a qualitative assessment tool in order to ensure that the respective methodology and research design that we follow are both sound and effective. In principle, quality assessment is a very important aspect of a systematic literature review because it provides the necessary methodological quality assessment of the primary research studies included (Wells and Littell, 2009). In fact, and according to Guyatt et al. (2008) ‘In the context of systematic reviews, the quality of evidence reflects the extent of confidence that an estimate of effect is correct’. For the purposes of this research design, we plan to employ the SIGN guidelines, a methodology checklist tool that provides an explicit and well-defined framework with which our methodology needs to comply. In principle, the SIGN checklist is distinguished into three core principles (sign.ac.uk, 2014). The first one dictates that the respective methodology development should be performed by multidisciplinary, nationally representative groups. The second principle defines that the systematic literature review will be performed in order to critically evaluate the related evidence. Finally, any potential recommendations must be connected to distinct supportive evidence. Owing to the fact that these three principle have long been defined and introduced – yet, their respective application is of utmost importance – they need to be adjusted according to the given systematic literature review. Hence, a checklist of 12 distinct questions (see table I, in appendix), as dictated by this quality assessment tool, need to be completed in order for each and every study included to fulfil all necessary criteria and methodologies.

Nevertheless, the process of data extraction focuses on research studies and peer-published articles that effectively provide an answer to our primary research question:

Which imaging modality is most accurate and efficient in the detection and diagnosis of pancreatic adenocarcinoma in adult patient: Computed Tomography (CT) or Magnetic Imaging Resonance (MRI)?

There are several tools that are available and which can assist us in the extraction and the management of the respective data. However, their selection is dictated by several parameters such as the number of the location of the reviewers, data needs, and even the complexity of the project – including, of course, the time available to successfully complete the given research study (Elamin et al., 2009). Moreover, the available funding and accessibility are two elements that can practically define the overall extraction process (Benyagoub, Flynn, and Bassler, 2009). Nevertheless, and for the purposes of this research design, we will select the PRISMA guidelines, as we selected to do in our eligibility criteria. The primary objectives of the PRISMA guidelines are to ensure the transparency, the efficiency, the optimal collection, and successful extraction of the reported data from a given systematic review (Atkins, Fink and Slutsky, 2005). Figure 1 exhibits the flow of information throughout the various phases of a systematic literature review as dictated by the PRISMA guidelines.

Figure 1. The flow of information throughout the various phases of a systematic literature review. Image taken from Liberati  et al. (2009).

 

Conclusions

All things considered, this essay intended to provide the scaffold upon which our prospective dissertation study will be performed, thus investigating the research question forming the core of this proposal: to compare the accuracy and efficiency of computed tomography and magnetic Resonance Imaging in detection of pancreatic adenocarcinoma in adult patients. The previous sections presented our distinct research methodology and perspective by emphasising on the importance of performing a systematic literature review. Consequently, we unfolded the respective search strategy by presenting a distinct research protocol with well-defined eligibility criteria. On the other hand, and in order to ensure the quality and the relevance of extracted research studies and data, we have additionally suggested the employment of distinct frameworks and tools such as the PICO, the SIGN checklist guidelines and the PRISMA framework, that will, undoubtedly, evaluate and ensure the validity and transparency of both our results and our methodology. Therefore, and conclusively, the proposed systematic literature review, is bound to provide solid findings and results that will evaluate both imaging modalities, and hence identify any potential gaps for future directions with respect to research.

Timetable

Review activities weeks 1 2 3 4 5 6 7 8 9 10 11 12-13
Literature overview and  refinement of the research question
Literature searches
Eligibility screening by applying inclusion & exclusion criteria
Methodological quality appraisal
Data extraction
Data synthesis, review report write-up

 

Budget and likely funding sources

Structured literature reviews will not induce any costs – or seek any related funding mechanism. All sources are freely available from most bibliographic databases that access is allowed. However, and in case the research strategy identifies essential sources that are not accessible then these journal articles will be purchased by the library. Furthermore, data management and data extraction solely require the use a personal computer, same as with any printing or binding required throughout the implementation of this research study.

Dissemination of Results and Conflict of Interests

This dissertation proposal has no conflicts of interests that are of legal, ethical, moral, financial, or personal nature. The sole reason for collecting data and performing this systematic literature review is the acquisition of meaningful results and conclusions that will be used for future publications on Academic Journals. Moreover, the respective results stemming from this process will be used in conference presentations or in any other academic activity revolving around this issue. A free copy will be stored in the library to allow other students to study and critique the respective findings.

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Appendices

Table I. Methodology Checklist for Systematic Reviews

Section 1:  Internal validity
In a well conducted systematic review: Does this study do it?
1.1 The research question is clearly defined and the                                      inclusion/ exclusion criteria must be listed in the paper.  Yes  If no reject No  
1.2 A comprehensive literature search is carried out.  Yes  Not applicable

If no reject

No  

 

1.3 At least two people should have selected studies.  Yes    No Can’t say
1.4 At least two people should have extracted data. Yes  No Can’t say
1.5 The status of publication was not used as an inclusion criterion. Yes  No  
1.6 The excluded studies are listed. Yes    No  
1.7 The relevant characteristics of the included studies are provided.  Yes    No  
1.8 The scientific quality of the included studies was assessed and reported. Yes  No
1.9 Was the scientific quality of the included studies used appropriately? Yes  No
1.10 Appropriate methods are used to combine the individual study findings. Yes  Can’t say

 

No Not applicable
1.11 The likelihood of publication bias was assessed appropriately.  Yes  Not applicable

 

No  
1.12 Conflicts of interest are declared.  Yes  No  
Section 2:   OVERALL ASSESSMENT OF THE STUDY
2.1 What is your overall assessment of the methodological quality of this review? High quality (++) Acceptable (+)

Low quality (-)

Unacceptable – reject 0

2.2 Are the results of this study directly applicable to the patient group targeted by this guideline? Yes  No