literature review in article

What is a Literature Review? How to Write It (with Examples)

literature review

A literature review is a critical analysis and synthesis of existing research on a particular topic. It provides an overview of the current state of knowledge, identifies gaps, and highlights key findings in the literature. 1 The purpose of a literature review is to situate your own research within the context of existing scholarship, demonstrating your understanding of the topic and showing how your work contributes to the ongoing conversation in the field. Learning how to write a literature review is a critical tool for successful research. Your ability to summarize and synthesize prior research pertaining to a certain topic demonstrates your grasp on the topic of study, and assists in the learning process. 

Table of Contents

What is the purpose of literature review , a. habitat loss and species extinction: , b. range shifts and phenological changes: , c. ocean acidification and coral reefs: , d. adaptive strategies and conservation efforts: .

  • Choose a Topic and Define the Research Question: 
  • Decide on the Scope of Your Review: 
  • Select Databases for Searches: 
  • Conduct Searches and Keep Track: 
  • Review the Literature: 
  • Organize and Write Your Literature Review: 
  • How to write a literature review faster with Paperpal? 

Frequently asked questions 

What is a literature review .

A well-conducted literature review demonstrates the researcher’s familiarity with the existing literature, establishes the context for their own research, and contributes to scholarly conversations on the topic. One of the purposes of a literature review is also to help researchers avoid duplicating previous work and ensure that their research is informed by and builds upon the existing body of knowledge.

literature review in article

A literature review serves several important purposes within academic and research contexts. Here are some key objectives and functions of a literature review: 2  

1. Contextualizing the Research Problem: The literature review provides a background and context for the research problem under investigation. It helps to situate the study within the existing body of knowledge. 

2. Identifying Gaps in Knowledge: By identifying gaps, contradictions, or areas requiring further research, the researcher can shape the research question and justify the significance of the study. This is crucial for ensuring that the new research contributes something novel to the field.

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3. Understanding Theoretical and Conceptual Frameworks: Literature reviews help researchers gain an understanding of the theoretical and conceptual frameworks used in previous studies. This aids in the development of a theoretical framework for the current research. 

4. Providing Methodological Insights: Another purpose of literature reviews is that it allows researchers to learn about the methodologies employed in previous studies. This can help in choosing appropriate research methods for the current study and avoiding pitfalls that others may have encountered. 

5. Establishing Credibility: A well-conducted literature review demonstrates the researcher’s familiarity with existing scholarship, establishing their credibility and expertise in the field. It also helps in building a solid foundation for the new research. 

6. Informing Hypotheses or Research Questions: The literature review guides the formulation of hypotheses or research questions by highlighting relevant findings and areas of uncertainty in existing literature. 

Literature review example 

Let’s delve deeper with a literature review example: Let’s say your literature review is about the impact of climate change on biodiversity. You might format your literature review into sections such as the effects of climate change on habitat loss and species extinction, phenological changes, and marine biodiversity. Each section would then summarize and analyze relevant studies in those areas, highlighting key findings and identifying gaps in the research. The review would conclude by emphasizing the need for further research on specific aspects of the relationship between climate change and biodiversity. The following literature review template provides a glimpse into the recommended literature review structure and content, demonstrating how research findings are organized around specific themes within a broader topic. 

Literature Review on Climate Change Impacts on Biodiversity:  

Climate change is a global phenomenon with far-reaching consequences, including significant impacts on biodiversity. This literature review synthesizes key findings from various studies: 

Climate change-induced alterations in temperature and precipitation patterns contribute to habitat loss, affecting numerous species (Thomas et al., 2004). The review discusses how these changes increase the risk of extinction, particularly for species with specific habitat requirements. 

Observations of range shifts and changes in the timing of biological events (phenology) are documented in response to changing climatic conditions (Parmesan & Yohe, 2003). These shifts affect ecosystems and may lead to mismatches between species and their resources. 

The review explores the impact of climate change on marine biodiversity, emphasizing ocean acidification’s threat to coral reefs (Hoegh-Guldberg et al., 2007). Changes in pH levels negatively affect coral calcification, disrupting the delicate balance of marine ecosystems. 

Recognizing the urgency of the situation, the literature review discusses various adaptive strategies adopted by species and conservation efforts aimed at mitigating the impacts of climate change on biodiversity (Hannah et al., 2007). It emphasizes the importance of interdisciplinary approaches for effective conservation planning. 

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How to write a good literature review 

Writing a literature review involves summarizing and synthesizing existing research on a particular topic. A good literature review format should include the following elements. 

Introduction: The introduction sets the stage for your literature review, providing context and introducing the main focus of your review. 

  • Opening Statement: Begin with a general statement about the broader topic and its significance in the field. 
  • Scope and Purpose: Clearly define the scope of your literature review. Explain the specific research question or objective you aim to address. 
  • Organizational Framework: Briefly outline the structure of your literature review, indicating how you will categorize and discuss the existing research. 
  • Significance of the Study: Highlight why your literature review is important and how it contributes to the understanding of the chosen topic. 
  • Thesis Statement: Conclude the introduction with a concise thesis statement that outlines the main argument or perspective you will develop in the body of the literature review. 

Body: The body of the literature review is where you provide a comprehensive analysis of existing literature, grouping studies based on themes, methodologies, or other relevant criteria. 

  • Organize by Theme or Concept: Group studies that share common themes, concepts, or methodologies. Discuss each theme or concept in detail, summarizing key findings and identifying gaps or areas of disagreement. 
  • Critical Analysis: Evaluate the strengths and weaknesses of each study. Discuss the methodologies used, the quality of evidence, and the overall contribution of each work to the understanding of the topic. 
  • Synthesis of Findings: Synthesize the information from different studies to highlight trends, patterns, or areas of consensus in the literature. 
  • Identification of Gaps: Discuss any gaps or limitations in the existing research and explain how your review contributes to filling these gaps. 
  • Transition between Sections: Provide smooth transitions between different themes or concepts to maintain the flow of your literature review. 
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Conclusion: The conclusion of your literature review should summarize the main findings, highlight the contributions of the review, and suggest avenues for future research. 

  • Summary of Key Findings: Recap the main findings from the literature and restate how they contribute to your research question or objective. 
  • Contributions to the Field: Discuss the overall contribution of your literature review to the existing knowledge in the field. 
  • Implications and Applications: Explore the practical implications of the findings and suggest how they might impact future research or practice. 
  • Recommendations for Future Research: Identify areas that require further investigation and propose potential directions for future research in the field. 
  • Final Thoughts: Conclude with a final reflection on the importance of your literature review and its relevance to the broader academic community. 

what is a literature review

Conducting a literature review 

Conducting a literature review is an essential step in research that involves reviewing and analyzing existing literature on a specific topic. It’s important to know how to do a literature review effectively, so here are the steps to follow: 1  

Choose a Topic and Define the Research Question:  

  • Select a topic that is relevant to your field of study. 
  • Clearly define your research question or objective. Determine what specific aspect of the topic do you want to explore? 

Decide on the Scope of Your Review:  

  • Determine the timeframe for your literature review. Are you focusing on recent developments, or do you want a historical overview? 
  • Consider the geographical scope. Is your review global, or are you focusing on a specific region? 
  • Define the inclusion and exclusion criteria. What types of sources will you include? Are there specific types of studies or publications you will exclude? 

Select Databases for Searches:  

  • Identify relevant databases for your field. Examples include PubMed, IEEE Xplore, Scopus, Web of Science, and Google Scholar. 
  • Consider searching in library catalogs, institutional repositories, and specialized databases related to your topic. 

Conduct Searches and Keep Track:  

  • Develop a systematic search strategy using keywords, Boolean operators (AND, OR, NOT), and other search techniques. 
  • Record and document your search strategy for transparency and replicability. 
  • Keep track of the articles, including publication details, abstracts, and links. Use citation management tools like EndNote, Zotero, or Mendeley to organize your references. 

Review the Literature:  

  • Evaluate the relevance and quality of each source. Consider the methodology, sample size, and results of studies. 
  • Organize the literature by themes or key concepts. Identify patterns, trends, and gaps in the existing research. 
  • Summarize key findings and arguments from each source. Compare and contrast different perspectives. 
  • Identify areas where there is a consensus in the literature and where there are conflicting opinions. 
  • Provide critical analysis and synthesis of the literature. What are the strengths and weaknesses of existing research? 

Organize and Write Your Literature Review:  

  • Literature review outline should be based on themes, chronological order, or methodological approaches. 
  • Write a clear and coherent narrative that synthesizes the information gathered. 
  • Use proper citations for each source and ensure consistency in your citation style (APA, MLA, Chicago, etc.). 
  • Conclude your literature review by summarizing key findings, identifying gaps, and suggesting areas for future research. 

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literature review in article

The literature review sample and detailed advice on writing and conducting a review will help you produce a well-structured report. But remember that a good literature review is an ongoing process, and it may be necessary to revisit and update it as your research progresses. By combining effortless research with an easy citation process, Paperpal Research streamlines the literature review process and empowers you to write faster and with more confidence. Try Paperpal Research now and see for yourself.  

A literature review is a critical and comprehensive analysis of existing literature (published and unpublished works) on a specific topic or research question and provides a synthesis of the current state of knowledge in a particular field. A well-conducted literature review is crucial for researchers to build upon existing knowledge, avoid duplication of efforts, and contribute to the advancement of their field. It also helps researchers situate their work within a broader context and facilitates the development of a sound theoretical and conceptual framework for their studies.

Literature review is a crucial component of research writing, providing a solid background for a research paper’s investigation. The aim is to keep professionals up to date by providing an understanding of ongoing developments within a specific field, including research methods, and experimental techniques used in that field, and present that knowledge in the form of a written report. Also, the depth and breadth of the literature review emphasizes the credibility of the scholar in his or her field.  

Before writing a literature review, it’s essential to undertake several preparatory steps to ensure that your review is well-researched, organized, and focused. This includes choosing a topic of general interest to you and doing exploratory research on that topic, writing an annotated bibliography, and noting major points, especially those that relate to the position you have taken on the topic. 

Literature reviews and academic research papers are essential components of scholarly work but serve different purposes within the academic realm. 3 A literature review aims to provide a foundation for understanding the current state of research on a particular topic, identify gaps or controversies, and lay the groundwork for future research. Therefore, it draws heavily from existing academic sources, including books, journal articles, and other scholarly publications. In contrast, an academic research paper aims to present new knowledge, contribute to the academic discourse, and advance the understanding of a specific research question. Therefore, it involves a mix of existing literature (in the introduction and literature review sections) and original data or findings obtained through research methods. 

Literature reviews are essential components of academic and research papers, and various strategies can be employed to conduct them effectively. If you want to know how to write a literature review for a research paper, here are four common approaches that are often used by researchers.  Chronological Review: This strategy involves organizing the literature based on the chronological order of publication. It helps to trace the development of a topic over time, showing how ideas, theories, and research have evolved.  Thematic Review: Thematic reviews focus on identifying and analyzing themes or topics that cut across different studies. Instead of organizing the literature chronologically, it is grouped by key themes or concepts, allowing for a comprehensive exploration of various aspects of the topic.  Methodological Review: This strategy involves organizing the literature based on the research methods employed in different studies. It helps to highlight the strengths and weaknesses of various methodologies and allows the reader to evaluate the reliability and validity of the research findings.  Theoretical Review: A theoretical review examines the literature based on the theoretical frameworks used in different studies. This approach helps to identify the key theories that have been applied to the topic and assess their contributions to the understanding of the subject.  It’s important to note that these strategies are not mutually exclusive, and a literature review may combine elements of more than one approach. The choice of strategy depends on the research question, the nature of the literature available, and the goals of the review. Additionally, other strategies, such as integrative reviews or systematic reviews, may be employed depending on the specific requirements of the research.

The literature review format can vary depending on the specific publication guidelines. However, there are some common elements and structures that are often followed. Here is a general guideline for the format of a literature review:  Introduction:   Provide an overview of the topic.  Define the scope and purpose of the literature review.  State the research question or objective.  Body:   Organize the literature by themes, concepts, or chronology.  Critically analyze and evaluate each source.  Discuss the strengths and weaknesses of the studies.  Highlight any methodological limitations or biases.  Identify patterns, connections, or contradictions in the existing research.  Conclusion:   Summarize the key points discussed in the literature review.  Highlight the research gap.  Address the research question or objective stated in the introduction.  Highlight the contributions of the review and suggest directions for future research.

Both annotated bibliographies and literature reviews involve the examination of scholarly sources. While annotated bibliographies focus on individual sources with brief annotations, literature reviews provide a more in-depth, integrated, and comprehensive analysis of existing literature on a specific topic. The key differences are as follows: 

  Annotated Bibliography  Literature Review 
Purpose  List of citations of books, articles, and other sources with a brief description (annotation) of each source.  Comprehensive and critical analysis of existing literature on a specific topic. 
Focus  Summary and evaluation of each source, including its relevance, methodology, and key findings.  Provides an overview of the current state of knowledge on a particular subject and identifies gaps, trends, and patterns in existing literature. 
Structure  Each citation is followed by a concise paragraph (annotation) that describes the source’s content, methodology, and its contribution to the topic.  The literature review is organized thematically or chronologically and involves a synthesis of the findings from different sources to build a narrative or argument. 
Length  Typically 100-200 words  Length of literature review ranges from a few pages to several chapters 
Independence  Each source is treated separately, with less emphasis on synthesizing the information across sources.  The writer synthesizes information from multiple sources to present a cohesive overview of the topic. 

References 

  • Denney, A. S., & Tewksbury, R. (2013). How to write a literature review.  Journal of criminal justice education ,  24 (2), 218-234. 
  • Pan, M. L. (2016).  Preparing literature reviews: Qualitative and quantitative approaches . Taylor & Francis. 
  • Cantero, C. (2019). How to write a literature review.  San José State University Writing Center . 

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Writing a Literature Review

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A literature review is a document or section of a document that collects key sources on a topic and discusses those sources in conversation with each other (also called synthesis ). The lit review is an important genre in many disciplines, not just literature (i.e., the study of works of literature such as novels and plays). When we say “literature review” or refer to “the literature,” we are talking about the research ( scholarship ) in a given field. You will often see the terms “the research,” “the scholarship,” and “the literature” used mostly interchangeably.

Where, when, and why would I write a lit review?

There are a number of different situations where you might write a literature review, each with slightly different expectations; different disciplines, too, have field-specific expectations for what a literature review is and does. For instance, in the humanities, authors might include more overt argumentation and interpretation of source material in their literature reviews, whereas in the sciences, authors are more likely to report study designs and results in their literature reviews; these differences reflect these disciplines’ purposes and conventions in scholarship. You should always look at examples from your own discipline and talk to professors or mentors in your field to be sure you understand your discipline’s conventions, for literature reviews as well as for any other genre.

A literature review can be a part of a research paper or scholarly article, usually falling after the introduction and before the research methods sections. In these cases, the lit review just needs to cover scholarship that is important to the issue you are writing about; sometimes it will also cover key sources that informed your research methodology.

Lit reviews can also be standalone pieces, either as assignments in a class or as publications. In a class, a lit review may be assigned to help students familiarize themselves with a topic and with scholarship in their field, get an idea of the other researchers working on the topic they’re interested in, find gaps in existing research in order to propose new projects, and/or develop a theoretical framework and methodology for later research. As a publication, a lit review usually is meant to help make other scholars’ lives easier by collecting and summarizing, synthesizing, and analyzing existing research on a topic. This can be especially helpful for students or scholars getting into a new research area, or for directing an entire community of scholars toward questions that have not yet been answered.

What are the parts of a lit review?

Most lit reviews use a basic introduction-body-conclusion structure; if your lit review is part of a larger paper, the introduction and conclusion pieces may be just a few sentences while you focus most of your attention on the body. If your lit review is a standalone piece, the introduction and conclusion take up more space and give you a place to discuss your goals, research methods, and conclusions separately from where you discuss the literature itself.

Introduction:

  • An introductory paragraph that explains what your working topic and thesis is
  • A forecast of key topics or texts that will appear in the review
  • Potentially, a description of how you found sources and how you analyzed them for inclusion and discussion in the review (more often found in published, standalone literature reviews than in lit review sections in an article or research paper)
  • Summarize and synthesize: Give an overview of the main points of each source and combine them into a coherent whole
  • Analyze and interpret: Don’t just paraphrase other researchers – add your own interpretations where possible, discussing the significance of findings in relation to the literature as a whole
  • Critically Evaluate: Mention the strengths and weaknesses of your sources
  • Write in well-structured paragraphs: Use transition words and topic sentence to draw connections, comparisons, and contrasts.

Conclusion:

  • Summarize the key findings you have taken from the literature and emphasize their significance
  • Connect it back to your primary research question

How should I organize my lit review?

Lit reviews can take many different organizational patterns depending on what you are trying to accomplish with the review. Here are some examples:

  • Chronological : The simplest approach is to trace the development of the topic over time, which helps familiarize the audience with the topic (for instance if you are introducing something that is not commonly known in your field). If you choose this strategy, be careful to avoid simply listing and summarizing sources in order. Try to analyze the patterns, turning points, and key debates that have shaped the direction of the field. Give your interpretation of how and why certain developments occurred (as mentioned previously, this may not be appropriate in your discipline — check with a teacher or mentor if you’re unsure).
  • Thematic : If you have found some recurring central themes that you will continue working with throughout your piece, you can organize your literature review into subsections that address different aspects of the topic. For example, if you are reviewing literature about women and religion, key themes can include the role of women in churches and the religious attitude towards women.
  • Qualitative versus quantitative research
  • Empirical versus theoretical scholarship
  • Divide the research by sociological, historical, or cultural sources
  • Theoretical : In many humanities articles, the literature review is the foundation for the theoretical framework. You can use it to discuss various theories, models, and definitions of key concepts. You can argue for the relevance of a specific theoretical approach or combine various theorical concepts to create a framework for your research.

What are some strategies or tips I can use while writing my lit review?

Any lit review is only as good as the research it discusses; make sure your sources are well-chosen and your research is thorough. Don’t be afraid to do more research if you discover a new thread as you’re writing. More info on the research process is available in our "Conducting Research" resources .

As you’re doing your research, create an annotated bibliography ( see our page on the this type of document ). Much of the information used in an annotated bibliography can be used also in a literature review, so you’ll be not only partially drafting your lit review as you research, but also developing your sense of the larger conversation going on among scholars, professionals, and any other stakeholders in your topic.

Usually you will need to synthesize research rather than just summarizing it. This means drawing connections between sources to create a picture of the scholarly conversation on a topic over time. Many student writers struggle to synthesize because they feel they don’t have anything to add to the scholars they are citing; here are some strategies to help you:

  • It often helps to remember that the point of these kinds of syntheses is to show your readers how you understand your research, to help them read the rest of your paper.
  • Writing teachers often say synthesis is like hosting a dinner party: imagine all your sources are together in a room, discussing your topic. What are they saying to each other?
  • Look at the in-text citations in each paragraph. Are you citing just one source for each paragraph? This usually indicates summary only. When you have multiple sources cited in a paragraph, you are more likely to be synthesizing them (not always, but often
  • Read more about synthesis here.

The most interesting literature reviews are often written as arguments (again, as mentioned at the beginning of the page, this is discipline-specific and doesn’t work for all situations). Often, the literature review is where you can establish your research as filling a particular gap or as relevant in a particular way. You have some chance to do this in your introduction in an article, but the literature review section gives a more extended opportunity to establish the conversation in the way you would like your readers to see it. You can choose the intellectual lineage you would like to be part of and whose definitions matter most to your thinking (mostly humanities-specific, but this goes for sciences as well). In addressing these points, you argue for your place in the conversation, which tends to make the lit review more compelling than a simple reporting of other sources.

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  • How to Write a Literature Review | Guide, Examples, & Templates

How to Write a Literature Review | Guide, Examples, & Templates

Published on January 2, 2023 by Shona McCombes . Revised on September 11, 2023.

What is a literature review? A literature review is a survey of scholarly sources on a specific topic. It provides an overview of current knowledge, allowing you to identify relevant theories, methods, and gaps in the existing research that you can later apply to your paper, thesis, or dissertation topic .

There are five key steps to writing a literature review:

  • Search for relevant literature
  • Evaluate sources
  • Identify themes, debates, and gaps
  • Outline the structure
  • Write your literature review

A good literature review doesn’t just summarize sources—it analyzes, synthesizes , and critically evaluates to give a clear picture of the state of knowledge on the subject.

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Table of contents

What is the purpose of a literature review, examples of literature reviews, step 1 – search for relevant literature, step 2 – evaluate and select sources, step 3 – identify themes, debates, and gaps, step 4 – outline your literature review’s structure, step 5 – write your literature review, free lecture slides, other interesting articles, frequently asked questions, introduction.

  • Quick Run-through
  • Step 1 & 2

When you write a thesis , dissertation , or research paper , you will likely have to conduct a literature review to situate your research within existing knowledge. The literature review gives you a chance to:

  • Demonstrate your familiarity with the topic and its scholarly context
  • Develop a theoretical framework and methodology for your research
  • Position your work in relation to other researchers and theorists
  • Show how your research addresses a gap or contributes to a debate
  • Evaluate the current state of research and demonstrate your knowledge of the scholarly debates around your topic.

Writing literature reviews is a particularly important skill if you want to apply for graduate school or pursue a career in research. We’ve written a step-by-step guide that you can follow below.

Literature review guide

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literature review in article

Writing literature reviews can be quite challenging! A good starting point could be to look at some examples, depending on what kind of literature review you’d like to write.

  • Example literature review #1: “Why Do People Migrate? A Review of the Theoretical Literature” ( Theoretical literature review about the development of economic migration theory from the 1950s to today.)
  • Example literature review #2: “Literature review as a research methodology: An overview and guidelines” ( Methodological literature review about interdisciplinary knowledge acquisition and production.)
  • Example literature review #3: “The Use of Technology in English Language Learning: A Literature Review” ( Thematic literature review about the effects of technology on language acquisition.)
  • Example literature review #4: “Learners’ Listening Comprehension Difficulties in English Language Learning: A Literature Review” ( Chronological literature review about how the concept of listening skills has changed over time.)

You can also check out our templates with literature review examples and sample outlines at the links below.

Download Word doc Download Google doc

Before you begin searching for literature, you need a clearly defined topic .

If you are writing the literature review section of a dissertation or research paper, you will search for literature related to your research problem and questions .

Make a list of keywords

Start by creating a list of keywords related to your research question. Include each of the key concepts or variables you’re interested in, and list any synonyms and related terms. You can add to this list as you discover new keywords in the process of your literature search.

  • Social media, Facebook, Instagram, Twitter, Snapchat, TikTok
  • Body image, self-perception, self-esteem, mental health
  • Generation Z, teenagers, adolescents, youth

Search for relevant sources

Use your keywords to begin searching for sources. Some useful databases to search for journals and articles include:

  • Your university’s library catalogue
  • Google Scholar
  • Project Muse (humanities and social sciences)
  • Medline (life sciences and biomedicine)
  • EconLit (economics)
  • Inspec (physics, engineering and computer science)

You can also use boolean operators to help narrow down your search.

Make sure to read the abstract to find out whether an article is relevant to your question. When you find a useful book or article, you can check the bibliography to find other relevant sources.

You likely won’t be able to read absolutely everything that has been written on your topic, so it will be necessary to evaluate which sources are most relevant to your research question.

For each publication, ask yourself:

  • What question or problem is the author addressing?
  • What are the key concepts and how are they defined?
  • What are the key theories, models, and methods?
  • Does the research use established frameworks or take an innovative approach?
  • What are the results and conclusions of the study?
  • How does the publication relate to other literature in the field? Does it confirm, add to, or challenge established knowledge?
  • What are the strengths and weaknesses of the research?

Make sure the sources you use are credible , and make sure you read any landmark studies and major theories in your field of research.

You can use our template to summarize and evaluate sources you’re thinking about using. Click on either button below to download.

Take notes and cite your sources

As you read, you should also begin the writing process. Take notes that you can later incorporate into the text of your literature review.

It is important to keep track of your sources with citations to avoid plagiarism . It can be helpful to make an annotated bibliography , where you compile full citation information and write a paragraph of summary and analysis for each source. This helps you remember what you read and saves time later in the process.

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To begin organizing your literature review’s argument and structure, be sure you understand the connections and relationships between the sources you’ve read. Based on your reading and notes, you can look for:

  • Trends and patterns (in theory, method or results): do certain approaches become more or less popular over time?
  • Themes: what questions or concepts recur across the literature?
  • Debates, conflicts and contradictions: where do sources disagree?
  • Pivotal publications: are there any influential theories or studies that changed the direction of the field?
  • Gaps: what is missing from the literature? Are there weaknesses that need to be addressed?

This step will help you work out the structure of your literature review and (if applicable) show how your own research will contribute to existing knowledge.

  • Most research has focused on young women.
  • There is an increasing interest in the visual aspects of social media.
  • But there is still a lack of robust research on highly visual platforms like Instagram and Snapchat—this is a gap that you could address in your own research.

There are various approaches to organizing the body of a literature review. Depending on the length of your literature review, you can combine several of these strategies (for example, your overall structure might be thematic, but each theme is discussed chronologically).

Chronological

The simplest approach is to trace the development of the topic over time. However, if you choose this strategy, be careful to avoid simply listing and summarizing sources in order.

Try to analyze patterns, turning points and key debates that have shaped the direction of the field. Give your interpretation of how and why certain developments occurred.

If you have found some recurring central themes, you can organize your literature review into subsections that address different aspects of the topic.

For example, if you are reviewing literature about inequalities in migrant health outcomes, key themes might include healthcare policy, language barriers, cultural attitudes, legal status, and economic access.

Methodological

If you draw your sources from different disciplines or fields that use a variety of research methods , you might want to compare the results and conclusions that emerge from different approaches. For example:

  • Look at what results have emerged in qualitative versus quantitative research
  • Discuss how the topic has been approached by empirical versus theoretical scholarship
  • Divide the literature into sociological, historical, and cultural sources

Theoretical

A literature review is often the foundation for a theoretical framework . You can use it to discuss various theories, models, and definitions of key concepts.

You might argue for the relevance of a specific theoretical approach, or combine various theoretical concepts to create a framework for your research.

Like any other academic text , your literature review should have an introduction , a main body, and a conclusion . What you include in each depends on the objective of your literature review.

The introduction should clearly establish the focus and purpose of the literature review.

Depending on the length of your literature review, you might want to divide the body into subsections. You can use a subheading for each theme, time period, or methodological approach.

As you write, you can follow these tips:

  • Summarize and synthesize: give an overview of the main points of each source and combine them into a coherent whole
  • Analyze and interpret: don’t just paraphrase other researchers — add your own interpretations where possible, discussing the significance of findings in relation to the literature as a whole
  • Critically evaluate: mention the strengths and weaknesses of your sources
  • Write in well-structured paragraphs: use transition words and topic sentences to draw connections, comparisons and contrasts

In the conclusion, you should summarize the key findings you have taken from the literature and emphasize their significance.

When you’ve finished writing and revising your literature review, don’t forget to proofread thoroughly before submitting. Not a language expert? Check out Scribbr’s professional proofreading services !

This article has been adapted into lecture slides that you can use to teach your students about writing a literature review.

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If you want to know more about the research process , methodology , research bias , or statistics , make sure to check out some of our other articles with explanations and examples.

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A literature review is a survey of scholarly sources (such as books, journal articles, and theses) related to a specific topic or research question .

It is often written as part of a thesis, dissertation , or research paper , in order to situate your work in relation to existing knowledge.

There are several reasons to conduct a literature review at the beginning of a research project:

  • To familiarize yourself with the current state of knowledge on your topic
  • To ensure that you’re not just repeating what others have already done
  • To identify gaps in knowledge and unresolved problems that your research can address
  • To develop your theoretical framework and methodology
  • To provide an overview of the key findings and debates on the topic

Writing the literature review shows your reader how your work relates to existing research and what new insights it will contribute.

The literature review usually comes near the beginning of your thesis or dissertation . After the introduction , it grounds your research in a scholarly field and leads directly to your theoretical framework or methodology .

A literature review is a survey of credible sources on a topic, often used in dissertations , theses, and research papers . Literature reviews give an overview of knowledge on a subject, helping you identify relevant theories and methods, as well as gaps in existing research. Literature reviews are set up similarly to other  academic texts , with an introduction , a main body, and a conclusion .

An  annotated bibliography is a list of  source references that has a short description (called an annotation ) for each of the sources. It is often assigned as part of the research process for a  paper .  

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Introduction

Literature reviews take time. here is some general information to know before you start.  .

  •  VIDEO -- This video is a great overview of the entire process.  (2020; North Carolina State University Libraries) --The transcript is included --This is for everyone; ignore the mention of "graduate students" --9.5 minutes, and every second is important  
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  • NOT A RESEARCH ARTICLE -- A literature review follows a different style, format, and structure from a research article.  
 
Reports on the work of others. Reports on original research.
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May include a short literature review to introduce the subject.

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How to Write a Literature Review

What is a literature review.

  • What Is the Literature
  • Writing the Review

A literature review is much more than an annotated bibliography or a list of separate reviews of articles and books. It is a critical, analytical summary and synthesis of the current knowledge of a topic. Thus it should compare and relate different theories, findings, etc, rather than just summarize them individually. In addition, it should have a particular focus or theme to organize the review. It does not have to be an exhaustive account of everything published on the topic, but it should discuss all the significant academic literature and other relevant sources important for that focus.

This is meant to be a general guide to writing a literature review: ways to structure one, what to include, how it supplements other research. For more specific help on writing a review, and especially for help on finding the literature to review, sign up for a Personal Research Session .

The specific organization of a literature review depends on the type and purpose of the review, as well as on the specific field or topic being reviewed. But in general, it is a relatively brief but thorough exploration of past and current work on a topic. Rather than a chronological listing of previous work, though, literature reviews are usually organized thematically, such as different theoretical approaches, methodologies, or specific issues or concepts involved in the topic. A thematic organization makes it much easier to examine contrasting perspectives, theoretical approaches, methodologies, findings, etc, and to analyze the strengths and weaknesses of, and point out any gaps in, previous research. And this is the heart of what a literature review is about. A literature review may offer new interpretations, theoretical approaches, or other ideas; if it is part of a research proposal or report it should demonstrate the relationship of the proposed or reported research to others' work; but whatever else it does, it must provide a critical overview of the current state of research efforts. 

Literature reviews are common and very important in the sciences and social sciences. They are less common and have a less important role in the humanities, but they do have a place, especially stand-alone reviews.

Types of Literature Reviews

There are different types of literature reviews, and different purposes for writing a review, but the most common are:

  • Stand-alone literature review articles . These provide an overview and analysis of the current state of research on a topic or question. The goal is to evaluate and compare previous research on a topic to provide an analysis of what is currently known, and also to reveal controversies, weaknesses, and gaps in current work, thus pointing to directions for future research. You can find examples published in any number of academic journals, but there is a series of Annual Reviews of *Subject* which are specifically devoted to literature review articles. Writing a stand-alone review is often an effective way to get a good handle on a topic and to develop ideas for your own research program. For example, contrasting theoretical approaches or conflicting interpretations of findings can be the basis of your research project: can you find evidence supporting one interpretation against another, or can you propose an alternative interpretation that overcomes their limitations?
  • Part of a research proposal . This could be a proposal for a PhD dissertation, a senior thesis, or a class project. It could also be a submission for a grant. The literature review, by pointing out the current issues and questions concerning a topic, is a crucial part of demonstrating how your proposed research will contribute to the field, and thus of convincing your thesis committee to allow you to pursue the topic of your interest or a funding agency to pay for your research efforts.
  • Part of a research report . When you finish your research and write your thesis or paper to present your findings, it should include a literature review to provide the context to which your work is a contribution. Your report, in addition to detailing the methods, results, etc. of your research, should show how your work relates to others' work.

A literature review for a research report is often a revision of the review for a research proposal, which can be a revision of a stand-alone review. Each revision should be a fairly extensive revision. With the increased knowledge of and experience in the topic as you proceed, your understanding of the topic will increase. Thus, you will be in a better position to analyze and critique the literature. In addition, your focus will change as you proceed in your research. Some areas of the literature you initially reviewed will be marginal or irrelevant for your eventual research, and you will need to explore other areas more thoroughly. 

Examples of Literature Reviews

See the series of Annual Reviews of *Subject* which are specifically devoted to literature review articles to find many examples of stand-alone literature reviews in the biomedical, physical, and social sciences. 

Research report articles vary in how they are organized, but a common general structure is to have sections such as:

  • Abstract - Brief summary of the contents of the article
  • Introduction - A explanation of the purpose of the study, a statement of the research question(s) the study intends to address
  • Literature review - A critical assessment of the work done so far on this topic, to show how the current study relates to what has already been done
  • Methods - How the study was carried out (e.g. instruments or equipment, procedures, methods to gather and analyze data)
  • Results - What was found in the course of the study
  • Discussion - What do the results mean
  • Conclusion - State the conclusions and implications of the results, and discuss how it relates to the work reviewed in the literature review; also, point to directions for further work in the area

Here are some articles that illustrate variations on this theme. There is no need to read the entire articles (unless the contents interest you); just quickly browse through to see the sections, and see how each section is introduced and what is contained in them.

The Determinants of Undergraduate Grade Point Average: The Relative Importance of Family Background, High School Resources, and Peer Group Effects , in The Journal of Human Resources , v. 34 no. 2 (Spring 1999), p. 268-293.

This article has a standard breakdown of sections:

  • Introduction
  • Literature Review
  • Some discussion sections

First Encounters of the Bureaucratic Kind: Early Freshman Experiences with a Campus Bureaucracy , in The Journal of Higher Education , v. 67 no. 6 (Nov-Dec 1996), p. 660-691.

This one does not have a section specifically labeled as a "literature review" or "review of the literature," but the first few sections cite a long list of other sources discussing previous research in the area before the authors present their own study they are reporting.

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  • Literature Review: The What, Why and How-to Guide
  • Introduction

Literature Review: The What, Why and How-to Guide — Introduction

  • Getting Started
  • How to Pick a Topic
  • Strategies to Find Sources
  • Evaluating Sources & Lit. Reviews
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What are Literature Reviews?

So, what is a literature review? "A literature review is an account of what has been published on a topic by accredited scholars and researchers. In writing the literature review, your purpose is to convey to your reader what knowledge and ideas have been established on a topic, and what their strengths and weaknesses are. As a piece of writing, the literature review must be defined by a guiding concept (e.g., your research objective, the problem or issue you are discussing, or your argumentative thesis). It is not just a descriptive list of the material available, or a set of summaries." Taylor, D.  The literature review: A few tips on conducting it . University of Toronto Health Sciences Writing Centre.

Goals of Literature Reviews

What are the goals of creating a Literature Review?  A literature could be written to accomplish different aims:

  • To develop a theory or evaluate an existing theory
  • To summarize the historical or existing state of a research topic
  • Identify a problem in a field of research 

Baumeister, R. F., & Leary, M. R. (1997). Writing narrative literature reviews .  Review of General Psychology , 1 (3), 311-320.

What kinds of sources require a Literature Review?

  • A research paper assigned in a course
  • A thesis or dissertation
  • A grant proposal
  • An article intended for publication in a journal

All these instances require you to collect what has been written about your research topic so that you can demonstrate how your own research sheds new light on the topic.

Types of Literature Reviews

What kinds of literature reviews are written?

Narrative review: The purpose of this type of review is to describe the current state of the research on a specific topic/research and to offer a critical analysis of the literature reviewed. Studies are grouped by research/theoretical categories, and themes and trends, strengths and weakness, and gaps are identified. The review ends with a conclusion section which summarizes the findings regarding the state of the research of the specific study, the gaps identify and if applicable, explains how the author's research will address gaps identify in the review and expand the knowledge on the topic reviewed.

  • Example : Predictors and Outcomes of U.S. Quality Maternity Leave: A Review and Conceptual Framework:  10.1177/08948453211037398  

Systematic review : "The authors of a systematic review use a specific procedure to search the research literature, select the studies to include in their review, and critically evaluate the studies they find." (p. 139). Nelson, L. K. (2013). Research in Communication Sciences and Disorders . Plural Publishing.

  • Example : The effect of leave policies on increasing fertility: a systematic review:  10.1057/s41599-022-01270-w

Meta-analysis : "Meta-analysis is a method of reviewing research findings in a quantitative fashion by transforming the data from individual studies into what is called an effect size and then pooling and analyzing this information. The basic goal in meta-analysis is to explain why different outcomes have occurred in different studies." (p. 197). Roberts, M. C., & Ilardi, S. S. (2003). Handbook of Research Methods in Clinical Psychology . Blackwell Publishing.

  • Example : Employment Instability and Fertility in Europe: A Meta-Analysis:  10.1215/00703370-9164737

Meta-synthesis : "Qualitative meta-synthesis is a type of qualitative study that uses as data the findings from other qualitative studies linked by the same or related topic." (p.312). Zimmer, L. (2006). Qualitative meta-synthesis: A question of dialoguing with texts .  Journal of Advanced Nursing , 53 (3), 311-318.

  • Example : Women’s perspectives on career successes and barriers: A qualitative meta-synthesis:  10.1177/05390184221113735

Literature Reviews in the Health Sciences

  • UConn Health subject guide on systematic reviews Explanation of the different review types used in health sciences literature as well as tools to help you find the right review type
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What is a Literature Review?

A literature or narrative review is a comprehensive review and analysis of the published literature on a specific topic or research question. The literature that is reviewed contains: books, articles, academic articles, conference proceedings, association papers, and dissertations. It contains the most pertinent studies and points to important past and current research and practices. It provides background and context, and shows how your research will contribute to the field. 

A literature review should: 

  • Provide a comprehensive and updated review of the literature;
  • Explain why this review has taken place;
  • Articulate a position or hypothesis;
  • Acknowledge and account for conflicting and corroborating points of view

From  S age Research Methods

Purpose of a Literature Review

A literature review can be written as an introduction to a study to:

  • Demonstrate how a study fills a gap in research
  • Compare a study with other research that's been done

Or it can be a separate work (a research article on its own) which:

  • Organizes or describes a topic
  • Describes variables within a particular issue/problem

Limitations of a Literature Review

Some of the limitations of a literature review are:

  • It's a snapshot in time. Unlike other reviews, this one has beginning, a middle and an end. There may be future developments that could make your work less relevant.
  • It may be too focused. Some niche studies may miss the bigger picture.
  • It can be difficult to be comprehensive. There is no way to make sure all the literature on a topic was considered.
  • It is easy to be biased if you stick to top tier journals. There may be other places where people are publishing exemplary research. Look to open access publications and conferences to reflect a more inclusive collection. Also, make sure to include opposing views (and not just supporting evidence).

Source: Grant, Maria J., and Andrew Booth. “A Typology of Reviews: An Analysis of 14 Review Types and Associated Methodologies.” Health Information & Libraries Journal, vol. 26, no. 2, June 2009, pp. 91–108. Wiley Online Library, doi:10.1111/j.1471-1842.2009.00848.x.

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A literature review is a review and synthesis of existing research on a topic or research question. A literature review is meant to analyze the scholarly literature, make connections across writings and identify strengths, weaknesses, trends, and missing conversations. A literature review should address different aspects of a topic as it relates to your research question. A literature review goes beyond a description or summary of the literature you have read. 

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How To Write A Literature Review - A Complete Guide

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Table of Contents

A literature review is much more than just another section in your research paper. It forms the very foundation of your research. It is a formal piece of writing where you analyze the existing theoretical framework, principles, and assumptions and use that as a base to shape your approach to the research question.

Curating and drafting a solid literature review section not only lends more credibility to your research paper but also makes your research tighter and better focused. But, writing literature reviews is a difficult task. It requires extensive reading, plus you have to consider market trends and technological and political changes, which tend to change in the blink of an eye.

Now streamline your literature review process with the help of SciSpace Copilot. With this AI research assistant, you can efficiently synthesize and analyze a vast amount of information, identify key themes and trends, and uncover gaps in the existing research. Get real-time explanations, summaries, and answers to your questions for the paper you're reviewing, making navigating and understanding the complex literature landscape easier.

Perform Literature reviews using SciSpace Copilot

In this comprehensive guide, we will explore everything from the definition of a literature review, its appropriate length, various types of literature reviews, and how to write one.

What is a literature review?

A literature review is a collation of survey, research, critical evaluation, and assessment of the existing literature in a preferred domain.

Eminent researcher and academic Arlene Fink, in her book Conducting Research Literature Reviews , defines it as the following:

“A literature review surveys books, scholarly articles, and any other sources relevant to a particular issue, area of research, or theory, and by so doing, provides a description, summary, and critical evaluation of these works in relation to the research problem being investigated.

Literature reviews are designed to provide an overview of sources you have explored while researching a particular topic, and to demonstrate to your readers how your research fits within a larger field of study.”

Simply put, a literature review can be defined as a critical discussion of relevant pre-existing research around your research question and carving out a definitive place for your study in the existing body of knowledge. Literature reviews can be presented in multiple ways: a section of an article, the whole research paper itself, or a chapter of your thesis.

A literature review paper

A literature review does function as a summary of sources, but it also allows you to analyze further, interpret, and examine the stated theories, methods, viewpoints, and, of course, the gaps in the existing content.

As an author, you can discuss and interpret the research question and its various aspects and debate your adopted methods to support the claim.

What is the purpose of a literature review?

A literature review is meant to help your readers understand the relevance of your research question and where it fits within the existing body of knowledge. As a researcher, you should use it to set the context, build your argument, and establish the need for your study.

What is the importance of a literature review?

The literature review is a critical part of research papers because it helps you:

  • Gain an in-depth understanding of your research question and the surrounding area
  • Convey that you have a thorough understanding of your research area and are up-to-date with the latest changes and advancements
  • Establish how your research is connected or builds on the existing body of knowledge and how it could contribute to further research
  • Elaborate on the validity and suitability of your theoretical framework and research methodology
  • Identify and highlight gaps and shortcomings in the existing body of knowledge and how things need to change
  • Convey to readers how your study is different or how it contributes to the research area

How long should a literature review be?

Ideally, the literature review should take up 15%-40% of the total length of your manuscript. So, if you have a 10,000-word research paper, the minimum word count could be 1500.

Your literature review format depends heavily on the kind of manuscript you are writing — an entire chapter in case of doctoral theses, a part of the introductory section in a research article, to a full-fledged review article that examines the previously published research on a topic.

Another determining factor is the type of research you are doing. The literature review section tends to be longer for secondary research projects than primary research projects.

What are the different types of literature reviews?

All literature reviews are not the same. There are a variety of possible approaches that you can take. It all depends on the type of research you are pursuing.

Here are the different types of literature reviews:

Argumentative review

It is called an argumentative review when you carefully present literature that only supports or counters a specific argument or premise to establish a viewpoint.

Integrative review

It is a type of literature review focused on building a comprehensive understanding of a topic by combining available theoretical frameworks and empirical evidence.

Methodological review

This approach delves into the ''how'' and the ''what" of the research question —  you cannot look at the outcome in isolation; you should also review the methodology used.

Systematic review

This form consists of an overview of existing evidence pertinent to a clearly formulated research question, which uses pre-specified and standardized methods to identify and critically appraise relevant research and collect, report, and analyze data from the studies included in the review.

Meta-analysis review

Meta-analysis uses statistical methods to summarize the results of independent studies. By combining information from all relevant studies, meta-analysis can provide more precise estimates of the effects than those derived from the individual studies included within a review.

Historical review

Historical literature reviews focus on examining research throughout a period, often starting with the first time an issue, concept, theory, or phenomenon emerged in the literature, then tracing its evolution within the scholarship of a discipline. The purpose is to place research in a historical context to show familiarity with state-of-the-art developments and identify future research's likely directions.

Theoretical Review

This form aims to examine the corpus of theory accumulated regarding an issue, concept, theory, and phenomenon. The theoretical literature review helps to establish what theories exist, the relationships between them, the degree the existing approaches have been investigated, and to develop new hypotheses to be tested.

Scoping Review

The Scoping Review is often used at the beginning of an article, dissertation, or research proposal. It is conducted before the research to highlight gaps in the existing body of knowledge and explains why the project should be greenlit.

State-of-the-Art Review

The State-of-the-Art review is conducted periodically, focusing on the most recent research. It describes what is currently known, understood, or agreed upon regarding the research topic and highlights where there are still disagreements.

Can you use the first person in a literature review?

When writing literature reviews, you should avoid the usage of first-person pronouns. It means that instead of "I argue that" or "we argue that," the appropriate expression would be "this research paper argues that."

Do you need an abstract for a literature review?

Ideally, yes. It is always good to have a condensed summary that is self-contained and independent of the rest of your review. As for how to draft one, you can follow the same fundamental idea when preparing an abstract for a literature review. It should also include:

  • The research topic and your motivation behind selecting it
  • A one-sentence thesis statement
  • An explanation of the kinds of literature featured in the review
  • Summary of what you've learned
  • Conclusions you drew from the literature you reviewed
  • Potential implications and future scope for research

Here's an example of the abstract of a literature review

Abstract-of-a-literature-review

Is a literature review written in the past tense?

Yes, the literature review should ideally be written in the past tense. You should not use the present or future tense when writing one. The exceptions are when you have statements describing events that happened earlier than the literature you are reviewing or events that are currently occurring; then, you can use the past perfect or present perfect tenses.

How many sources for a literature review?

There are multiple approaches to deciding how many sources to include in a literature review section. The first approach would be to look level you are at as a researcher. For instance, a doctoral thesis might need 60+ sources. In contrast, you might only need to refer to 5-15 sources at the undergraduate level.

The second approach is based on the kind of literature review you are doing — whether it is merely a chapter of your paper or if it is a self-contained paper in itself. When it is just a chapter, sources should equal the total number of pages in your article's body. In the second scenario, you need at least three times as many sources as there are pages in your work.

Quick tips on how to write a literature review

To know how to write a literature review, you must clearly understand its impact and role in establishing your work as substantive research material.

You need to follow the below-mentioned steps, to write a literature review:

  • Outline the purpose behind the literature review
  • Search relevant literature
  • Examine and assess the relevant resources
  • Discover connections by drawing deep insights from the resources
  • Structure planning to write a good literature review

1. Outline and identify the purpose of  a literature review

As a first step on how to write a literature review, you must know what the research question or topic is and what shape you want your literature review to take. Ensure you understand the research topic inside out, or else seek clarifications. You must be able to the answer below questions before you start:

  • How many sources do I need to include?
  • What kind of sources should I analyze?
  • How much should I critically evaluate each source?
  • Should I summarize, synthesize or offer a critique of the sources?
  • Do I need to include any background information or definitions?

Additionally, you should know that the narrower your research topic is, the swifter it will be for you to restrict the number of sources to be analyzed.

2. Search relevant literature

Dig deeper into search engines to discover what has already been published around your chosen topic. Make sure you thoroughly go through appropriate reference sources like books, reports, journal articles, government docs, and web-based resources.

You must prepare a list of keywords and their different variations. You can start your search from any library’s catalog, provided you are an active member of that institution. The exact keywords can be extended to widen your research over other databases and academic search engines like:

  • Google Scholar
  • Microsoft Academic
  • Science.gov

Besides, it is not advisable to go through every resource word by word. Alternatively, what you can do is you can start by reading the abstract and then decide whether that source is relevant to your research or not.

Additionally, you must spend surplus time assessing the quality and relevance of resources. It would help if you tried preparing a list of citations to ensure that there lies no repetition of authors, publications, or articles in the literature review.

3. Examine and assess the sources

It is nearly impossible for you to go through every detail in the research article. So rather than trying to fetch every detail, you have to analyze and decide which research sources resemble closest and appear relevant to your chosen domain.

While analyzing the sources, you should look to find out answers to questions like:

  • What question or problem has the author been describing and debating?
  • What is the definition of critical aspects?
  • How well the theories, approach, and methodology have been explained?
  • Whether the research theory used some conventional or new innovative approach?
  • How relevant are the key findings of the work?
  • In what ways does it relate to other sources on the same topic?
  • What challenges does this research paper pose to the existing theory
  • What are the possible contributions or benefits it adds to the subject domain?

Be always mindful that you refer only to credible and authentic resources. It would be best if you always take references from different publications to validate your theory.

Always keep track of important information or data you can present in your literature review right from the beginning. It will help steer your path from any threats of plagiarism and also make it easier to curate an annotated bibliography or reference section.

4. Discover connections

At this stage, you must start deciding on the argument and structure of your literature review. To accomplish this, you must discover and identify the relations and connections between various resources while drafting your abstract.

A few aspects that you should be aware of while writing a literature review include:

  • Rise to prominence: Theories and methods that have gained reputation and supporters over time.
  • Constant scrutiny: Concepts or theories that repeatedly went under examination.
  • Contradictions and conflicts: Theories, both the supporting and the contradictory ones, for the research topic.
  • Knowledge gaps: What exactly does it fail to address, and how to bridge them with further research?
  • Influential resources: Significant research projects available that have been upheld as milestones or perhaps, something that can modify the current trends

Once you join the dots between various past research works, it will be easier for you to draw a conclusion and identify your contribution to the existing knowledge base.

5. Structure planning to write a good literature review

There exist different ways towards planning and executing the structure of a literature review. The format of a literature review varies and depends upon the length of the research.

Like any other research paper, the literature review format must contain three sections: introduction, body, and conclusion. The goals and objectives of the research question determine what goes inside these three sections.

Nevertheless, a good literature review can be structured according to the chronological, thematic, methodological, or theoretical framework approach.

Literature review samples

1. Standalone

Standalone-Literature-Review

2. As a section of a research paper

Literature-review-as-a-section-of-a-research-paper

How SciSpace Discover makes literature review a breeze?

SciSpace Discover is a one-stop solution to do an effective literature search and get barrier-free access to scientific knowledge. It is an excellent repository where you can find millions of only peer-reviewed articles and full-text PDF files. Here’s more on how you can use it:

Find the right information

Find-the-right-information-using-SciSpace

Find what you want quickly and easily with comprehensive search filters that let you narrow down papers according to PDF availability, year of publishing, document type, and affiliated institution. Moreover, you can sort the results based on the publishing date, citation count, and relevance.

Assess credibility of papers quickly

Assess-credibility-of-papers-quickly-using-SciSpace

When doing the literature review, it is critical to establish the quality of your sources. They form the foundation of your research. SciSpace Discover helps you assess the quality of a source by providing an overview of its references, citations, and performance metrics.

Get the complete picture in no time

SciSpace's-personalized-informtion-engine

SciSpace Discover’s personalized suggestion engine helps you stay on course and get the complete picture of the topic from one place. Every time you visit an article page, it provides you links to related papers. Besides that, it helps you understand what’s trending, who are the top authors, and who are the leading publishers on a topic.

Make referring sources super easy

Make-referring-pages-super-easy-with-SciSpace

To ensure you don't lose track of your sources, you must start noting down your references when doing the literature review. SciSpace Discover makes this step effortless. Click the 'cite' button on an article page, and you will receive preloaded citation text in multiple styles — all you've to do is copy-paste it into your manuscript.

Final tips on how to write a literature review

A massive chunk of time and effort is required to write a good literature review. But, if you go about it systematically, you'll be able to save a ton of time and build a solid foundation for your research.

We hope this guide has helped you answer several key questions you have about writing literature reviews.

Would you like to explore SciSpace Discover and kick off your literature search right away? You can get started here .

Frequently Asked Questions (FAQs)

1. how to start a literature review.

• What questions do you want to answer?

• What sources do you need to answer these questions?

• What information do these sources contain?

• How can you use this information to answer your questions?

2. What to include in a literature review?

• A brief background of the problem or issue

• What has previously been done to address the problem or issue

• A description of what you will do in your project

• How this study will contribute to research on the subject

3. Why literature review is important?

The literature review is an important part of any research project because it allows the writer to look at previous studies on a topic and determine existing gaps in the literature, as well as what has already been done. It will also help them to choose the most appropriate method for their own study.

4. How to cite a literature review in APA format?

To cite a literature review in APA style, you need to provide the author's name, the title of the article, and the year of publication. For example: Patel, A. B., & Stokes, G. S. (2012). The relationship between personality and intelligence: A meta-analysis of longitudinal research. Personality and Individual Differences, 53(1), 16-21

5. What are the components of a literature review?

• A brief introduction to the topic, including its background and context. The introduction should also include a rationale for why the study is being conducted and what it will accomplish.

• A description of the methodologies used in the study. This can include information about data collection methods, sample size, and statistical analyses.

• A presentation of the findings in an organized format that helps readers follow along with the author's conclusions.

6. What are common errors in writing literature review?

• Not spending enough time to critically evaluate the relevance of resources, observations and conclusions.

• Totally relying on secondary data while ignoring primary data.

• Letting your personal bias seep into your interpretation of existing literature.

• No detailed explanation of the procedure to discover and identify an appropriate literature review.

7. What are the 5 C's of writing literature review?

• Cite - the sources you utilized and referenced in your research.

• Compare - existing arguments, hypotheses, methodologies, and conclusions found in the knowledge base.

• Contrast - the arguments, topics, methodologies, approaches, and disputes that may be found in the literature.

• Critique - the literature and describe the ideas and opinions you find more convincing and why.

• Connect - the various studies you reviewed in your research.

8. How many sources should a literature review have?

When it is just a chapter, sources should equal the total number of pages in your article's body. if it is a self-contained paper in itself, you need at least three times as many sources as there are pages in your work.

9. Can literature review have diagrams?

• To represent an abstract idea or concept

• To explain the steps of a process or procedure

• To help readers understand the relationships between different concepts

10. How old should sources be in a literature review?

Sources for a literature review should be as current as possible or not older than ten years. The only exception to this rule is if you are reviewing a historical topic and need to use older sources.

11. What are the types of literature review?

• Argumentative review

• Integrative review

• Methodological review

• Systematic review

• Meta-analysis review

• Historical review

• Theoretical review

• Scoping review

• State-of-the-Art review

12. Is a literature review mandatory?

Yes. Literature review is a mandatory part of any research project. It is a critical step in the process that allows you to establish the scope of your research, and provide a background for the rest of your work.

But before you go,

  • Six Online Tools for Easy Literature Review
  • Evaluating literature review: systematic vs. scoping reviews
  • Systematic Approaches to a Successful Literature Review
  • Writing Integrative Literature Reviews: Guidelines and Examples

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What is a review article?

Learn how to write a review article.

What is a review article? A review article can also be called a literature review, or a review of literature. It is a survey of previously published research on a topic. It should give an overview of current thinking on the topic. And, unlike an original research article, it will not present new experimental results.

Writing a review of literature is to provide a critical evaluation of the data available from existing studies. Review articles can identify potential research areas to explore next, and sometimes they will draw new conclusions from the existing data.

Why write a review article?

To provide a comprehensive foundation on a topic.

To explain the current state of knowledge.

To identify gaps in existing studies for potential future research.

To highlight the main methodologies and research techniques.

Did you know? 

There are some journals that only publish review articles, and others that do not accept them.

Make sure you check the  aims and scope  of the journal you’d like to publish in to find out if it’s the right place for your review article.

How to write a review article

Below are 8 key items to consider when you begin writing your review article.

Check the journal’s aims and scope

Make sure you have read the aims and scope for the journal you are submitting to and follow them closely. Different journals accept different types of articles and not all will accept review articles, so it’s important to check this before you start writing.

Define your scope

Define the scope of your review article and the research question you’ll be answering, making sure your article contributes something new to the field. 

As award-winning author Angus Crake told us, you’ll also need to “define the scope of your review so that it is manageable, not too large or small; it may be necessary to focus on recent advances if the field is well established.” 

Finding sources to evaluate

When finding sources to evaluate, Angus Crake says it’s critical that you “use multiple search engines/databases so you don’t miss any important ones.” 

For finding studies for a systematic review in medical sciences,  read advice from NCBI . 

Writing your title, abstract and keywords

Spend time writing an effective title, abstract and keywords. This will help maximize the visibility of your article online, making sure the right readers find your research. Your title and abstract should be clear, concise, accurate, and informative. 

For more information and guidance on getting these right, read our guide to writing a good abstract and title  and our  researcher’s guide to search engine optimization . 

Introduce the topic

Does a literature review need an introduction? Yes, always start with an overview of the topic and give some context, explaining why a review of the topic is necessary. Gather research to inform your introduction and make it broad enough to reach out to a large audience of non-specialists. This will help maximize its wider relevance and impact. 

Don’t make your introduction too long. Divide the review into sections of a suitable length to allow key points to be identified more easily.

Include critical discussion

Make sure you present a critical discussion, not just a descriptive summary of the topic. If there is contradictory research in your area of focus, make sure to include an element of debate and present both sides of the argument. You can also use your review paper to resolve conflict between contradictory studies.

What researchers say

Angus Crake, researcher

As part of your conclusion, include making suggestions for future research on the topic. Focus on the goal to communicate what you understood and what unknowns still remains.

Use a critical friend

Always perform a final spell and grammar check of your article before submission. 

You may want to ask a critical friend or colleague to give their feedback before you submit. If English is not your first language, think about using a language-polishing service.

Find out more about how  Taylor & Francis Editing Services can help improve your manuscript before you submit.

What is the difference between a research article and a review article?

Differences in...
Presents the viewpoint of the author Critiques the viewpoint of other authors on a particular topic
New content Assessing already published content
Depends on the word limit provided by the journal you submit to Tends to be shorter than a research article, but will still need to adhere to words limit

Before you submit your review article…

Complete this checklist before you submit your review article:

Have you checked the journal’s aims and scope?

Have you defined the scope of your article?

Did you use multiple search engines to find sources to evaluate?

Have you written a descriptive title and abstract using keywords?

Did you start with an overview of the topic?

Have you presented a critical discussion?

Have you included future suggestions for research in your conclusion?

Have you asked a friend to do a final spell and grammar check?

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Open Access

Ten Simple Rules for Writing a Literature Review

* E-mail: [email protected]

Affiliations Centre for Functional and Evolutionary Ecology (CEFE), CNRS, Montpellier, France, Centre for Biodiversity Synthesis and Analysis (CESAB), FRB, Aix-en-Provence, France

  • Marco Pautasso

PLOS

Published: July 18, 2013

  • https://doi.org/10.1371/journal.pcbi.1003149
  • Reader Comments

Figure 1

Citation: Pautasso M (2013) Ten Simple Rules for Writing a Literature Review. PLoS Comput Biol 9(7): e1003149. https://doi.org/10.1371/journal.pcbi.1003149

Editor: Philip E. Bourne, University of California San Diego, United States of America

Copyright: © 2013 Marco Pautasso. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This work was funded by the French Foundation for Research on Biodiversity (FRB) through its Centre for Synthesis and Analysis of Biodiversity data (CESAB), as part of the NETSEED research project. The funders had no role in the preparation of the manuscript.

Competing interests: The author has declared that no competing interests exist.

Literature reviews are in great demand in most scientific fields. Their need stems from the ever-increasing output of scientific publications [1] . For example, compared to 1991, in 2008 three, eight, and forty times more papers were indexed in Web of Science on malaria, obesity, and biodiversity, respectively [2] . Given such mountains of papers, scientists cannot be expected to examine in detail every single new paper relevant to their interests [3] . Thus, it is both advantageous and necessary to rely on regular summaries of the recent literature. Although recognition for scientists mainly comes from primary research, timely literature reviews can lead to new synthetic insights and are often widely read [4] . For such summaries to be useful, however, they need to be compiled in a professional way [5] .

When starting from scratch, reviewing the literature can require a titanic amount of work. That is why researchers who have spent their career working on a certain research issue are in a perfect position to review that literature. Some graduate schools are now offering courses in reviewing the literature, given that most research students start their project by producing an overview of what has already been done on their research issue [6] . However, it is likely that most scientists have not thought in detail about how to approach and carry out a literature review.

Reviewing the literature requires the ability to juggle multiple tasks, from finding and evaluating relevant material to synthesising information from various sources, from critical thinking to paraphrasing, evaluating, and citation skills [7] . In this contribution, I share ten simple rules I learned working on about 25 literature reviews as a PhD and postdoctoral student. Ideas and insights also come from discussions with coauthors and colleagues, as well as feedback from reviewers and editors.

Rule 1: Define a Topic and Audience

How to choose which topic to review? There are so many issues in contemporary science that you could spend a lifetime of attending conferences and reading the literature just pondering what to review. On the one hand, if you take several years to choose, several other people may have had the same idea in the meantime. On the other hand, only a well-considered topic is likely to lead to a brilliant literature review [8] . The topic must at least be:

  • interesting to you (ideally, you should have come across a series of recent papers related to your line of work that call for a critical summary),
  • an important aspect of the field (so that many readers will be interested in the review and there will be enough material to write it), and
  • a well-defined issue (otherwise you could potentially include thousands of publications, which would make the review unhelpful).

Ideas for potential reviews may come from papers providing lists of key research questions to be answered [9] , but also from serendipitous moments during desultory reading and discussions. In addition to choosing your topic, you should also select a target audience. In many cases, the topic (e.g., web services in computational biology) will automatically define an audience (e.g., computational biologists), but that same topic may also be of interest to neighbouring fields (e.g., computer science, biology, etc.).

Rule 2: Search and Re-search the Literature

After having chosen your topic and audience, start by checking the literature and downloading relevant papers. Five pieces of advice here:

  • keep track of the search items you use (so that your search can be replicated [10] ),
  • keep a list of papers whose pdfs you cannot access immediately (so as to retrieve them later with alternative strategies),
  • use a paper management system (e.g., Mendeley, Papers, Qiqqa, Sente),
  • define early in the process some criteria for exclusion of irrelevant papers (these criteria can then be described in the review to help define its scope), and
  • do not just look for research papers in the area you wish to review, but also seek previous reviews.

The chances are high that someone will already have published a literature review ( Figure 1 ), if not exactly on the issue you are planning to tackle, at least on a related topic. If there are already a few or several reviews of the literature on your issue, my advice is not to give up, but to carry on with your own literature review,

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The bottom-right situation (many literature reviews but few research papers) is not just a theoretical situation; it applies, for example, to the study of the impacts of climate change on plant diseases, where there appear to be more literature reviews than research studies [33] .

https://doi.org/10.1371/journal.pcbi.1003149.g001

  • discussing in your review the approaches, limitations, and conclusions of past reviews,
  • trying to find a new angle that has not been covered adequately in the previous reviews, and
  • incorporating new material that has inevitably accumulated since their appearance.

When searching the literature for pertinent papers and reviews, the usual rules apply:

  • be thorough,
  • use different keywords and database sources (e.g., DBLP, Google Scholar, ISI Proceedings, JSTOR Search, Medline, Scopus, Web of Science), and
  • look at who has cited past relevant papers and book chapters.

Rule 3: Take Notes While Reading

If you read the papers first, and only afterwards start writing the review, you will need a very good memory to remember who wrote what, and what your impressions and associations were while reading each single paper. My advice is, while reading, to start writing down interesting pieces of information, insights about how to organize the review, and thoughts on what to write. This way, by the time you have read the literature you selected, you will already have a rough draft of the review.

Of course, this draft will still need much rewriting, restructuring, and rethinking to obtain a text with a coherent argument [11] , but you will have avoided the danger posed by staring at a blank document. Be careful when taking notes to use quotation marks if you are provisionally copying verbatim from the literature. It is advisable then to reformulate such quotes with your own words in the final draft. It is important to be careful in noting the references already at this stage, so as to avoid misattributions. Using referencing software from the very beginning of your endeavour will save you time.

Rule 4: Choose the Type of Review You Wish to Write

After having taken notes while reading the literature, you will have a rough idea of the amount of material available for the review. This is probably a good time to decide whether to go for a mini- or a full review. Some journals are now favouring the publication of rather short reviews focusing on the last few years, with a limit on the number of words and citations. A mini-review is not necessarily a minor review: it may well attract more attention from busy readers, although it will inevitably simplify some issues and leave out some relevant material due to space limitations. A full review will have the advantage of more freedom to cover in detail the complexities of a particular scientific development, but may then be left in the pile of the very important papers “to be read” by readers with little time to spare for major monographs.

There is probably a continuum between mini- and full reviews. The same point applies to the dichotomy of descriptive vs. integrative reviews. While descriptive reviews focus on the methodology, findings, and interpretation of each reviewed study, integrative reviews attempt to find common ideas and concepts from the reviewed material [12] . A similar distinction exists between narrative and systematic reviews: while narrative reviews are qualitative, systematic reviews attempt to test a hypothesis based on the published evidence, which is gathered using a predefined protocol to reduce bias [13] , [14] . When systematic reviews analyse quantitative results in a quantitative way, they become meta-analyses. The choice between different review types will have to be made on a case-by-case basis, depending not just on the nature of the material found and the preferences of the target journal(s), but also on the time available to write the review and the number of coauthors [15] .

Rule 5: Keep the Review Focused, but Make It of Broad Interest

Whether your plan is to write a mini- or a full review, it is good advice to keep it focused 16 , 17 . Including material just for the sake of it can easily lead to reviews that are trying to do too many things at once. The need to keep a review focused can be problematic for interdisciplinary reviews, where the aim is to bridge the gap between fields [18] . If you are writing a review on, for example, how epidemiological approaches are used in modelling the spread of ideas, you may be inclined to include material from both parent fields, epidemiology and the study of cultural diffusion. This may be necessary to some extent, but in this case a focused review would only deal in detail with those studies at the interface between epidemiology and the spread of ideas.

While focus is an important feature of a successful review, this requirement has to be balanced with the need to make the review relevant to a broad audience. This square may be circled by discussing the wider implications of the reviewed topic for other disciplines.

Rule 6: Be Critical and Consistent

Reviewing the literature is not stamp collecting. A good review does not just summarize the literature, but discusses it critically, identifies methodological problems, and points out research gaps [19] . After having read a review of the literature, a reader should have a rough idea of:

  • the major achievements in the reviewed field,
  • the main areas of debate, and
  • the outstanding research questions.

It is challenging to achieve a successful review on all these fronts. A solution can be to involve a set of complementary coauthors: some people are excellent at mapping what has been achieved, some others are very good at identifying dark clouds on the horizon, and some have instead a knack at predicting where solutions are going to come from. If your journal club has exactly this sort of team, then you should definitely write a review of the literature! In addition to critical thinking, a literature review needs consistency, for example in the choice of passive vs. active voice and present vs. past tense.

Rule 7: Find a Logical Structure

Like a well-baked cake, a good review has a number of telling features: it is worth the reader's time, timely, systematic, well written, focused, and critical. It also needs a good structure. With reviews, the usual subdivision of research papers into introduction, methods, results, and discussion does not work or is rarely used. However, a general introduction of the context and, toward the end, a recapitulation of the main points covered and take-home messages make sense also in the case of reviews. For systematic reviews, there is a trend towards including information about how the literature was searched (database, keywords, time limits) [20] .

How can you organize the flow of the main body of the review so that the reader will be drawn into and guided through it? It is generally helpful to draw a conceptual scheme of the review, e.g., with mind-mapping techniques. Such diagrams can help recognize a logical way to order and link the various sections of a review [21] . This is the case not just at the writing stage, but also for readers if the diagram is included in the review as a figure. A careful selection of diagrams and figures relevant to the reviewed topic can be very helpful to structure the text too [22] .

Rule 8: Make Use of Feedback

Reviews of the literature are normally peer-reviewed in the same way as research papers, and rightly so [23] . As a rule, incorporating feedback from reviewers greatly helps improve a review draft. Having read the review with a fresh mind, reviewers may spot inaccuracies, inconsistencies, and ambiguities that had not been noticed by the writers due to rereading the typescript too many times. It is however advisable to reread the draft one more time before submission, as a last-minute correction of typos, leaps, and muddled sentences may enable the reviewers to focus on providing advice on the content rather than the form.

Feedback is vital to writing a good review, and should be sought from a variety of colleagues, so as to obtain a diversity of views on the draft. This may lead in some cases to conflicting views on the merits of the paper, and on how to improve it, but such a situation is better than the absence of feedback. A diversity of feedback perspectives on a literature review can help identify where the consensus view stands in the landscape of the current scientific understanding of an issue [24] .

Rule 9: Include Your Own Relevant Research, but Be Objective

In many cases, reviewers of the literature will have published studies relevant to the review they are writing. This could create a conflict of interest: how can reviewers report objectively on their own work [25] ? Some scientists may be overly enthusiastic about what they have published, and thus risk giving too much importance to their own findings in the review. However, bias could also occur in the other direction: some scientists may be unduly dismissive of their own achievements, so that they will tend to downplay their contribution (if any) to a field when reviewing it.

In general, a review of the literature should neither be a public relations brochure nor an exercise in competitive self-denial. If a reviewer is up to the job of producing a well-organized and methodical review, which flows well and provides a service to the readership, then it should be possible to be objective in reviewing one's own relevant findings. In reviews written by multiple authors, this may be achieved by assigning the review of the results of a coauthor to different coauthors.

Rule 10: Be Up-to-Date, but Do Not Forget Older Studies

Given the progressive acceleration in the publication of scientific papers, today's reviews of the literature need awareness not just of the overall direction and achievements of a field of inquiry, but also of the latest studies, so as not to become out-of-date before they have been published. Ideally, a literature review should not identify as a major research gap an issue that has just been addressed in a series of papers in press (the same applies, of course, to older, overlooked studies (“sleeping beauties” [26] )). This implies that literature reviewers would do well to keep an eye on electronic lists of papers in press, given that it can take months before these appear in scientific databases. Some reviews declare that they have scanned the literature up to a certain point in time, but given that peer review can be a rather lengthy process, a full search for newly appeared literature at the revision stage may be worthwhile. Assessing the contribution of papers that have just appeared is particularly challenging, because there is little perspective with which to gauge their significance and impact on further research and society.

Inevitably, new papers on the reviewed topic (including independently written literature reviews) will appear from all quarters after the review has been published, so that there may soon be the need for an updated review. But this is the nature of science [27] – [32] . I wish everybody good luck with writing a review of the literature.

Acknowledgments

Many thanks to M. Barbosa, K. Dehnen-Schmutz, T. Döring, D. Fontaneto, M. Garbelotto, O. Holdenrieder, M. Jeger, D. Lonsdale, A. MacLeod, P. Mills, M. Moslonka-Lefebvre, G. Stancanelli, P. Weisberg, and X. Xu for insights and discussions, and to P. Bourne, T. Matoni, and D. Smith for helpful comments on a previous draft.

  • 1. Rapple C (2011) The role of the critical review article in alleviating information overload. Annual Reviews White Paper. Available: http://www.annualreviews.org/userimages/ContentEditor/1300384004941/Annual_Reviews_WhitePaper_Web_2011.pdf . Accessed May 2013.
  • View Article
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  • 7. Budgen D, Brereton P (2006) Performing systematic literature reviews in software engineering. Proc 28th Int Conf Software Engineering, ACM New York, NY, USA, pp. 1051–1052. doi: https://doi.org/10.1145/1134285.1134500 .
  • 16. Eco U (1977) Come si fa una tesi di laurea. Milan: Bompiani.
  • 17. Hart C (1998) Doing a literature review: releasing the social science research imagination. London: SAGE.
  • 21. Ridley D (2008) The literature review: a step-by-step guide for students. London: SAGE.
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Scholarly Articles: How can I tell?

  • Journal Information

Literature Review

  • Author and affiliation
  • Introduction
  • Specialized Vocabulary
  • Methodology
  • Research sponsors
  • Peer-review

The literature review section of an article is a summary or analysis of all the research the author read before doing his/her own research. This section may be part of the introduction or in a section called Background. It provides the background on who has done related research, what that research has or has not uncovered and how the current research contributes to the conversation on the topic. When you read the lit review ask:

  • Does the review of the literature logically lead up to the research questions?
  • Do the authors review articles relevant to their research study?
  • Do the authors show where there are gaps in the literature?

The lit review is also a good place to find other sources you may want to read on this topic to help you get the bigger picture.

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  • Last Updated: Apr 15, 2024 3:26 PM
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Literature Reviews

  • What is a Literature Review?
  • Steps for Creating a Literature Review
  • Providing Evidence / Critical Analysis
  • Challenges when writing a Literature Review
  • Systematic Literature Reviews

Developing a Literature Review

1. Purpose and Scope

To help you develop a literature review, gather information on existing research, sub-topics, relevant research, and overlaps. Note initial thoughts on the topic - a mind map or list might be helpful - and avoid unfocused reading, collecting irrelevant content.  A literature review serves to place your research within the context of existing knowledge. It demonstrates your understanding of the field and identifies gaps that your research aims to fill. This helps in justifying the relevance and necessity of your study.

To avoid over-reading, set a target word count for each section and limit reading time. Plan backwards from the deadline and move on to other parts of the investigation. Read major texts and explore up-to-date research. Check reference lists and citation indexes for common standard texts. Be guided by research questions and refocus on your topic when needed. Stop reading if you find similar viewpoints or if you're going off topic.

You can use a "Synthesis Matrix" to keep track of your reading notes. This concept map helps you to provide a summary of the literature and its connections is produced as a result of this study. Utilizing referencing software like RefWorks to obtain citations, you can construct the framework for composing your literature evaluation.

2. Source Selection

Focus on searching for academically authoritative texts such as academic books, journals, research reports, and government publications. These sources are critical for ensuring the credibility and reliability of your review. 

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Each work's critical assessment should take into account:

Provenance:  What qualifications does the author have? Are the author's claims backed up by proof, such as first-hand accounts from history, case studies, stories, statistics, and current scientific discoveries? Methodology:  Were the strategies employed to locate, collect, and evaluate the data suitable for tackling the study question? Was the sample size suitable? Were the findings properly reported and interpreted? Objectivity : Is the author's viewpoint impartial or biased? Does the author's thesis get supported by evidence that refutes it, or does it ignore certain important facts? Persuasiveness:  Which of the author's arguments is the strongest or weakest in terms of persuasiveness? Value:  Are the author's claims and deductions believable? Does the study ultimately advance our understanding of the issue in any meaningful way?

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Practical Tips

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Brown University Library (2024) Organizing and Creating Information. Available at: https://libguides.brown.edu/organize/litreview (Accessed: 30 July 2024).

Pacheco-Vega, R. (2016) Synthesizing different bodies of work in your literature review: The Conceptual Synthesis Excel Dump (CSED) technique . Available at: http://www.raulpacheco.org/2016/06/synthesizing-different-bodies-of-work-in-your-literature-review-the-conceptual-synthesis-excel-dump-technique/ (Accessed: 30 July 2024).

Study Advice at the University of Reading (2024) Literature reviews . Available at: https://libguides.reading.ac.uk/literaturereview/developing (Accessed: 31 July 2024).

Further Reading

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  • Review Article
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  • Published: 04 September 2024

Biopsy strategies in the era of mpMRI: a comprehensive review

  • Olivier Windisch   ORCID: orcid.org/0000-0002-8963-5445 1 , 2 ,
  • Massimo Valerio 1 , 2 ,
  • Chi-Hang Yee   ORCID: orcid.org/0000-0001-6557-3107 3 ,
  • Paolo Gontero 4 ,
  • Baris Bakir   ORCID: orcid.org/0000-0002-6587-9787 5 ,
  • Christof Kastner 6 ,
  • Hashim U. Ahmed   ORCID: orcid.org/0000-0003-1674-6723 7 , 8 ,
  • Cosimo De Nunzio   ORCID: orcid.org/0000-0002-2190-512X 9 &
  • Jean de la Rosette   ORCID: orcid.org/0000-0002-6308-1763 10  

Prostate Cancer and Prostatic Diseases ( 2024 ) Cite this article

Metrics details

  • Cancer screening
  • Prostate cancer

Since its initial description the prostate biopsy technique for detection of prostate cancer (PCA) has constantly evolved. Multiparametric magnetic resonance imaging (mpMRI) has been proven to have a sensitivity exceeding 90% to detect the index lesion. This narrative review discusses the evidence around several biopsy strategies, especially in the context of patients that might be eligible for focal therapy.

A non-systematic literature research was performed on February 15th 2024 using the Medical Literature Analysis and Retrieval System Online (Medline), Web of Science and Google Scholar.

The transrectal (TR) route is associated with an increased postoperative sepsis rate, even with adequate antibiotic prophylaxis. The transperineal (TP) route is now recommended by international guidelines, firstly for its decreased rate of urosepsis. Recent evidence shows a non-inferiority of TP compared to TR route, and even a higher detection rate of clinically significant PCA (csPCA) in the anterior and apical region, that are usually difficult to target using the TR route. Several targeting techniques (cognitive, software-fusion or in-bore) enhance our ability to provide an accurate risk assessment of prostate cancer aggressiveness and burden, while reducing the number of cores and reducing the number of clinically insignificant prostate cancer (ciPCA). While MRI-TB have proven their role, the role of systematic biopsies (SB) is still important because it detects 5–16% of csPCA that would have been missed by MRI-TB alone. The strategies of SB depend mainly on the route used (TR vs. TP) and the number of cores to be collected (10–12 cores vs. saturation biopsies vs. trans-perineal template mapping-biopsies or Ginsburg Protocol vs. regional biopsies).

Several biopsy strategies have been described and should be known when assessing patients for focal therapy. Because MRI systematically under evaluates the lesion size, systematic biopsies, and especially perilesional biopsies, can help to increase sensitivity at the cost of an increased number of cores.

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Introduction.

Since its first description in the early 1920s, by transperineal open surgery, prostate biopsy techniques have evolved fast towards less invasive, less morbid, and more accurate sampling. The first description of the transrectal approach using the sextant transrectal biopsy with ultrasound guidance was reported by Hodge in 1989 [ 1 ]. After this first description, the 10–12 cores became the standard method because of the acceptable balance of increased detection rate and acceptable side-effect rate compared to high core numbers [ 2 ]. The prostate biopsy evolution timeline is displayed in Fig.  1 . A randomized-controlled trial (RCT) published in 1990 initially showed no benefit of prostate MRI over transrectal ultrasound, both modalities significantly underestimating prostate cancer risk, limiting at that moment its adoption. Since then, prostate multiparametric magnetic resonance imaging (mpMRI) gained significant attention after reports showing improved cancer detection. A 30-fold increase in the use of mpMRI before biopsy was observed in the US from 2009 to 2015 (from 0.2% to 6.5%) even before formal recommendation was formulated [ 3 ]. Since then, growing evidence supports the routine use of mpMRI; the PROMIS trial showed a sensitivity to detect clinically significant prostate cancer (csPCA) exceeding 90%, while the PRECISION trial showed the ability of mpMRI targeted biopsy (MRI-TB) to increase the detection of csPCA while decreasing the detection of clinically insignificant prostate cancer (ciPCA) and at the same time avoiding the need for biopsies in 28% of the patients [ 4 , 5 ]. The European Association of Urology (EAU) recommends mpMRI as an upfront tool to guide biopsies in biopsy-naïve patients and for patients with previous negative systematic biopsies with persistent cancer suspicion [ 6 ].

figure 1

Figure 1 provides a timeline of the different biopsy techniques described in the procedure. Name in parenthesis correspond to the first author of the technique first description [ 1 , 49 , 51 , 52 , 77 , 78 , 79 , 80 , 81 , 82 ].

The advance of mpMRI has changed the prostate cancer diagnostic pathway. Prior to MR-imaging, the debate around prostate biopsy concerned density and location. The 10–12 cores transrectal ultrasound guided biopsy became the pragmatic response to sample the area of the prostate more likely to harbor PCA, namely the peripheral zone, in a systematic fashion from the base to the apex. A prostate MRI prior to biopsy offers clinicians an imaging phenotype which prompts different questions to be addressed. First, after the identification of a MR-visible lesion, the need for a precise targeting is required to realize targeted biopsies (TB). The distribution and density of targeted biopsies in and around a lesion are still matters of debate, which are particularly important in the context of focal therapy. Second, the value of additional systematic biopsy as well as the intensity and the route of sampling are key questions to be answered.

This manuscript aims to provide a comprehensive review of the most commonly used biopsy strategies reported in literature. While some are now considered obsolete by many, they will be included to provide a wide overview and to better assess the comparative diagnostic performance against technological evolutions. The manuscript will first focus on targeted biopsies, perilesional biopsies and the several types of guidance that the MRI information offers (cognitive, TRUS-MRI fusion or MRI in-bore), then discuss the role of systematic biopsies and combined biopsies. Safety aspects will be then discussed. The performance of these strategies in adequately identifying patients for FT concludes the discussion. Pros and conns of each technique are summarized in Table  1 .

mpMRI targeted biopsies

Key concepts.

The European Association of Urology (EAU) and the American Urology Association (AUA) both integrate the use of mpMRI in their diagnostic pathway. The EAU 2024 update recommends the use of MRI-TB and perilesional prostate biopsy for patients presenting a positive mpMRI [ 7 ]. The AUA considers mpMRI as an optional exam before initial prostate biopsy, and if positive, recommend targeted biopsies (at least 2 cores) ± systematic biopsies [ 8 ].

The PI-RADS latest version (2.1) was published in 2019 to standardize image acquisition and quality to increase and spread diagnostic performance beyond reference centers [ 9 ]. The PI-QUAL score has been described as a tool to help assess mpMRI quality underlining the need for good quality images [ 10 , 11 ]. Current guidelines recommend MRI-TB in the presence of equivocal or more suspicious lesions (PI-RADS ≥ 3), defined as a positive mpMRI. Because of the relatively low proportion of csPCA in the PI-RADS 3 (around 12%), current recommendation suggest using PSA-density cut-offs to decide whether to biopsy or not [ 12 ]. This is a more recent practice since most studies reported in this manuscript regarding MRI-TB usually considered PI-RADS3 as a positive mpMRI and prompted subsequent MRI-TB.

mpMRI has a 92% sensitivity to identify the index lesion, also called region of interest (ROI). The index lesion has been defined as the largest, highest grade or lesion with extraprostatic extension (EPE). The index lesion is thought to be the lesion containing the most aggressive cancer cells, and therefore the clone with metastasis potential. Treating this lesion in patients in whom it can be identified is therefore the aim of focal therapy [ 13 , 14 ]. While mpMRI is a central tool in the MRI-TB pathway, it tends to underestimate the actual burden of prostate cancer, as well as its borders, that are usually irregular and not as circumscribed as the mpMRI lesion [ 15 , 16 ].

Fusion biopsies : techniques, accuracy and comparison

The benefits of MRI-based diagnostics heavily depend on image quality and reading quality [ 17 , 18 ]. The region of interest (ROI) on MRI has to be identified and marked by the specialist reader and then be transferred onto the live prostate during the biopsy. The ROI information can be used with cognitive transfer, software-driven US-MRI fusion and in-bore targeting. Cognitive targeted biopsy (COG-TB) describes a term where the operator uses his brain only to register MRI-derived targets to a transrectal ultrasound. No additional equipment to standard transrectal ultrasound is required, hence it is the easiest form with no cost implication of fusion [ 19 ]. However, it inevitably carries a risk of operator-dependent transfer error. MRI-US fusion targeted biopsy (FUS-TB) consists of a fusion of previously acquired mpMRI images with pre-marked ROI with real-time TRUS imaging, allowing for a potentially more precise targeting. Several platforms have been successfully developed, with no clear superior diagnostic ability reported of one over the others [ 20 ]. In-bore MRI targeted biopsy (IB-TB) implies to proceed to the biopsy directly in the bore of an MRI scanner, requiring specific compatible equipment. It usually requires the previous acquisition of mpMRI images to identify lesions, and a reacquisition at the moment of biopsy. Usually, a sedation or general anesthesia is performed, while only targeted-biopsies are acquired because of the lengthy time and difficulty to perform systematic biopsies at the same time [ 21 ].

When comparing the three different techniques of targeting techniques in a systematic review, Wegelin et al. could show no difference in 2019 between FUS-TB and COG-TB (sensitivity of 81% vs. 72%, p  = 0.11), while IB-TB significantly outperformed COG-TB (sensitivity 89% vs. 72%, p  = 0.02) for PCA detection. For csPCA, COG-TB had an 86% sensitivity similar to FUS-TB (89%, p  = 0.62) and MRI-TB (92%, p  = 0.42). In this meta-analysis encompassing records utill 2015, 43 studies were included, 39.5% (17/43) using FUS-TB, 25.6% (11/43) using IB-TB, and 25.6% (11/43) using COG-TB. In 2022, Bass et al. reported an updated systematic review and showed that FUS-TB was the most represented technique (76.7%; 33/43 studies) while COG-TB (18.6%; 8/43) came second and IB-TB came last (4.6%; 2/43), possibly suggesting a decreased used of IB-TB with the larger implantation of FUS-TB [ 22 ]. This meta-analysis confirmed similar sensitivities of IB-TB (87%), COG-TB (81%) and FUS-TB (81%) for the detection of csPCA ( p  = 0.55), as well as similar ciPCA yield of IB-TB (10%), COG-TB (5%) and FUS-TB (8%, p  = 0.46). Wegelin et al. afterwards reported the results of the FUTURE trial, a multicenter randomized control trial that confirmed the absence of difference regarding csPCA between the different MRI-TB techniques. They however stated as an important limitation the lack of power of the study, that would have required the inclusion of 9886 additional patients [ 23 ].

When comparing MRI-TB to transrectal ultrasound guided systematic biopsy (TRUS-SB), both meta-analyses agreed ; Wegelin reported an increased detection of csPCA using MRI-TB (RR : 1.16) corresponding to an MRI-TB sensitivity of 90% compared to TRUS-SB sensitivity of 79%, as well as a decreased detection of ciPCA (RR = 0.47). Bass confirmed these findings, with an increased detection of csPCA seen with MRI-TB (RR : 1.24, p  = 0.02) compared to TRUS-SB corresponding to an MRI-TB sensitivity of 83% compared to TRUS sensitivity of 63%, as well as a decreased detection of ciPCA (RR = 0.58, p  < 0.01). Overall, data on fusion biopsies can be biased by differences in urologist expertise. However, trained residents ( > 50 cases) tend to perform similar as consultant urologists, suggesting an acceptable learning curve [ 24 ]. Microultrasound, is a novel technology using a high-frequency 29-Mhz transrectal probe, that allows real-time recognition and targeting of lesions during biopsy. The diagnostic value of this technology seems to be comparable to MRI, at least in expert centers [ 25 ]. In addition, MRI and microultrasound seem to be complementary technologies that might enhance the risk stratification, especially in case of focal therapy [ 26 ]. An explanatory RCT evaluating microultrasound against MRI in ongoing, and will further clarify the role of this technology [ 27 ]. Another promising technology is the multiparametric ultrasound (mpUS). Recently, a high-quality diagnostic study (CADMUS) has compared mpUS to mpMRI and showed a 73% agreement between both modalities. Each test alone resulted in a 26% vs. 30% csPCA detection rate respectively for patient that underwent modality diagnosed and guided biopsies. While mpUS detected slighty less csPCA (−4%), it also increased the number of patients referred for biopsies, still being inferior to mpMRI [ 28 ]. Further studies are required to precise its future perspectives in prostate cancer diagnosis, but it could already play an interesting role for patient that cannot benefit from mpMRI.

Role of perilesional sampling

Several authors reported on the importance of perilesional sampling [ 29 , 30 ]. Brisbane et al. accounted for the phenomenon of invisible cancer around the index lesion, under the concept of “penumbra” ; a distance starting at the border of the ROI and containing the 90% of all csPCA in the gland. They showed that only 50% of the csPCA was contained within the ROI for patients presenting with PI-RADS 3, compared to 60% for PI-RADS 4 and 74% for PI-RADS 5. The radius of the penumbra depended on the PI-RADS score, with an additional perimeter of 16 mm, 12 mm and 5 mm for PI-RADS 3, 4 and 5 respectively [ 29 ]. This concept is important in focal therapy since margins of treatment have to been assessed [ 31 , 32 ].

Meanwhile, Hansen et al. established in 2020 that a targeted saturation biopsy on the same side as the ROI is highly effective for diagnosing cancer, although the exact size of the “penumbra” relative to the PIRADS score of the ROI remains a subject of discussion [ 32 ]. More recently, Noujeim et al. conducted a thorough analysis to assess the distance between systematic cores containing clinically significant prostate cancer (csPCa) and the region of interest (ROI). The authors demonstrated that sampling around the lesion combined with TB was as effective as SB + TB for detecting csPCa (35% vs. 37%, p  = 0.2). By employing a machine learning algorithm and categorizing three risk groups based on PIRADS score and PSA density, they found the risk of missing csPCa beyond the 10 mm penumbra was 2%, 8%, and 29% for low, intermediate, and high-risk groups, respectively [ 33 ]. Furthermore, the cumulative distribution rate for csPCa reached 86% within a 10 mm margin. It was concluded that for men with PIRADS 3–5 lesions and a PSA density below 0.15 ng/ml 2 , biopsies beyond the 10 mm penumbra might be unnecessary. This goes in the same direction as the 2019 PIRADS committee recommendation to conduct template biopsies (TB) of the region of interest (ROI) in addition with a 5-mm penumbra for lesions rated as PIRADS 4 and 5 [ 34 ]. Tafuri et al. also noted that for PIRADS 5 lesions with a PSA density greater than 0.15 ng/ml 2 , systematic samples offered only a marginal increase in csPCA detection [ 35 ]. Standard biopsy seems to remain important, especially in the perilesional area, especially for PI-RADS 4/5 lesions and a PSA density above 0.15 ng/ml. If confirmed in wider studies, these findings suggest the need for a risk-group based approach, based on PI-RADS score and PSA density to potentially avoid systematic or contralateral biopsies [ 36 , 37 , 38 ].

Systematic biopsies

While systematic transrectal biopsies were a long-lasting standard, their role has been superseded by mpMRI targeted as seen in the previous section. Delongchamps et al. reported the result of a per-patient analysis comparing TRUS-SB (10–12 cores) to TRUS-TB (3 cores). They reported a reduced overall PCA rate but a similar csPCA rate (46.2% vs. 48.1%, p  = 0.69) [ 39 ]. Later, the PRECISION trial showed a higher detection of csPCA in biopsy-naïve patients benefitting from transrectal (TR) MRI-TB (38% vs. 26%) compared to TRUS-SB alone, while 28% of the randomized men in the MRI group could avoid biopsies [ 4 ]. Despite this best performance, allowing for a precise staging with less cores, about between 0 to 16% csPCA would be missed if concomitant systematic biopsies were not performed [ 39 , 40 , 41 , 42 ].

Systematic samples of the prostate might be performed in different ways. These techniques are summarized as well in Fig.  2 .

figure 2

Figure 2 displays the most frequently employed biopsy techniques, differentiated by the biopsy route, type of systematic biopsies and use of targeted biopsies. It displays a coronal cut of the prostate and the relative positive of the biopsies. Transperineal biopsies are perpendicular to the coronal plane and shown as dots, whereas transrectal are parallel and appear as traits. Ginsburg protocol uses anterior, mid-sector and posterior biopsies (as displayed) and depends on the size of the gland (this template is valid for glands up to 30 ml). For glands larger than 30 ml, 8 additional biopsies (not displayed on this figure) are obtained from the basal sector, in the extension of the mid-sector (total 32 cores). For glands larger than 50 ml, the number of cores per sector (anterior, mid and posterior) and per side is 5 (total 38 cores). TTPM uses a brachytherapy grid to obtain biopsies at regular interval of 5 mm. Created with Biorender.com. TP transperineal, TR transrectal, TB targeted biopsy, TTPM transperineal template prostate-mapping.

TRUS 10–12 systematic cores (TRUS-SB)

10 or 12-TRUS cores was considered the standard TRUS-guided technique and its technique has been largely reported [ 43 ]. The main problem that arose from 10–12 TRUS cores pattern is the random and systematic errors. Random errors are due to the absence of targeting ; it promotes the detection of ciPCA while missing csPCA. Systematic errors happen when a zone (such as the anterior zone, anterior zones and midline under the urethra) is hard to target and will systematically be missed or inadequately sampled [ 44 ]. Therefore, the TRUS-SB present with a high risk of false negative (30–45%) and an accuracy of only around 59% [ 41 , 44 ]. Valerio et al. compared the efficiency (number of cores required to detect one significant cancer) and showed that 37 cores vs. 9 cores were required respectively for TRUS-SB compared to MRI-TB (median difference of 32.1 cores). When assessing utility (number of men with PCA that have been detected with a sampling strategy that would have been missed using the other strategy), they reported an 9% additional csPCA detection using MRI-TB, compared to 2% when using TRUS-SB alone [ 45 ].

TRUS saturation biopsies (TRUS-SatB)

The term “saturation biopsies” (SatB) has been reported several times in the literature, but no clear and accepted definition defines it. Most authors agree that it is a higher density biopsy protocol, that usually includes at least 20 cores. It has mainly been advocated for re-biopsy after one or several previous negative TRUS-SB, before MRI-TB was recommended, since it allowed the detection of previously missed csPCA [ 46 , 47 ]. Despite initial promising results, a randomized control trial showed no benefit when comparing 20-cores to the standard 12-cores biopsies, therefore limiting its widespread adoption afterwards [ 2 , 47 , 48 ].

Transperineal systematic biopsies

The first description of the technique of transperineal, ultrasound guided biopsies was reported in 1981 by Holm and Gammelgard [ 49 ]. Based on the transrectal techniques, several templates were reported. The most known and standardized techniques are the Transperineal Template Prostate Mapping (TTPM), and Ginsburg protocol. Other techniques have been reported, such as the 10-sector template, 12-core template and the MUSIC template [ 50 ]. These techniques, using a reduced number of cores, are possible to perform under local anesthesia. Figure  3 provides an illustration of the local anesthesia for TP-Bx.

figure 3

Figure 3 displays one of the frequently used and reported technique (Emiliozzi). The orange line illustrate the para-sagital axis where the puncture will be made. This axis is found using a 45 degree angle from the anus in the lithotomy position, at a 1.5 cm distance on each side (left and right). Using a linear transrectal ultrasound probe, the sagittal (more precisely the para-sagital axis) is obtained. A needle (22 G) is inserted between the Denonviliers fascia and the apex of the prostate. Slow injection will lift the prostate upwards and be visible. The technique requires a bilateral injection of 10 ml of rapid acting anesthetic [ 83 ]. Created with Biorender.com.

The concept of TTPM was first described by Barzell and Whitmore in 2003 and later standardized in 2007 [ 51 ]. TTPM uses a brachytherapy grid to exhaustively biopsy the prostate, with cores taken every 5 mm, with at least one biopsy from each hole of the grid [ 52 ]. On a 3-dimensional virtually created model, this strategy yields a > 95% correct risk stratification of all clinically significant cancers (defined as lesions of 0.5 ml or greater) [ 53 ]. This strategy results in a high biopsy density, and high number of cores per patient (mean of 63 cores, ranges described as high as 160 for very large glands) [ 53 ]. Valerio et al. reported that reducing the number of biopsies has a negative impact on its ability to exclude clinically significant disease and is therefore inferior [ 54 ]. TTPM served as a the gold-standard for the PROMIS study that was the first level 1b evidence-study to prove the increased sensitivity of MRI-TB compared to TRUS-SB [ 5 ].

The Ginsburg protocol is based on a multidisciplinary panel agreement (Ginsburg Study Group for Enhanced Prostate Diagnostics) to provide a reproducible dataset to standardize reporting among future studies. The number of cores is directly dependent on the prostate size ; it involves a minimum of 24 cores for prostate ≤ 30 ml (as displayed in Fig.  2 ), 32 cores for prostate >30–50 ml and length >4 cm, and up to 38 cores for larger prostate [ 52 ]. After its original description, it was tested on 534 patients with a median number of biopsy cores of 26 (IQR 24–28) and a mean procedure length between 25 to 60 min. It allowed the detection of csPCA in 39% biopsy-naïve patients, 27% of patients that previously had previous negative biopsies, and 45% of patients on active surveillance for low-risk cancers [ 55 ].

Combined targeted and systematic biopsies

Combined MRI-TB and TRUS-SB or TP systematic biopsies (TP-SB) is recommended as the upfront strategy for biopsy-naïve men by the European Association of Urology [ 6 ]. In general, MRI-TB consist of 3–4 cores/target, but more variations exist regarding SB, also depending on the route used. In general, ipsilateral and contralateral biopsies to MRI-TB are collected. 10–12 cores (TR or TP), Ginsburg protocol, TTPM or RB have been described in addition to MRI-TB.

Hagens et al. conducted a recent meta-analysis comparing the performance of MRI-TB alone compared to MRI-TB + RB or MRI-TB + SB. The median number of cores was 9.5 in the MRI-TB + RB group compared to 16.5 in the MRI-TB + SB, while no difference in csPCA detection was seen (RR = 0.95, p  = 0.09). Interestingly, the RB strategy avoided contralateral SB. As awaited, MRI-TB + SBx overperformed when compared to MRI-TB only (RR:1.24, p  < 0.001), but at a cost of increasing the median number of cores from 3.5 to 16.5. Interestingly, when adding RB to MRI-TB, only 6 cores were necessary to increase substantially the detection compared to MRI-TB alone (RR:1.18, p  < 0.001) [ 56 ]. The risk of such strategy is however a grade inflation and grade shift that may overestimate the cancer burden [ 57 ]. This grade shift may compromise the use of nomograms, frequently used for lymph node invasion or EPE prediction. Another recent prospective RCT compared MRI-TB and regional saturation biopsies (RSB) using 9 cores, for men with PSA 4–20 ng/ml, and found a similar performance of MRI + RSB compared to MRI-TB + SB (csPCA detection rate in 44.1% vs. 40.7%, p  = 0.3) while requiring less cores. It significantly overperformed TB alone (csPCA detection rate 44.1% vs. 31.8, p  = 0.01). When comparing their biopsy results with whole mount histology (WMH) analysis, 97% of the significant cancer were identified using RSB. They could also determine that the average underestimation of size comparing WMH and mpMRI was 0.76 cm confirming previously reported mpMRI cancer burden underestimation of 0.9 cm suggested by Le Nobin et al. [ 15 , 31 ]. Tschirdewahn et al. reported a per-patient detection of 99% of csPCA using the RB-saturation technique compared to 87% ( p  = 0.001) for MRI-TB (4 cores) and 81% ( p  < 0.001) for extended systematic biopsies (24 cores), suggesting increased diagnostic performance of the RB-saturation technique [ 58 ]. However, the same team conducted afterwards a RCT comparing 4 cores MRI-TB to MRI-TB + RB (9 cores total) where they could not show a statistical difference regarding per-patient csPCA detection (91.6% vs. 100%, p  = 0.058) [ 59 ]. Although these results did not show a statistical difference, they raise the question whether the Ginsburg protocol should still be adopted, or if MRI-TB + RB may be accurate enough to supersede it [ 32 ].

Transrectal vs. transperineal route

Some factors have been limiting the widespread adoption of TP. The need for general anesthesia at the beginning of the experience, and the need to switch equipment for a generation of urologists naïve to the TP approach have limited initial widespread adoption. Also, the biopsy strategy needs to take into account external factors as well, such as the time of the procedure, cost and access to the operating theater, since TP are usually more expensive, lengthy and less frequently performed under local anesthesia [ 39 , 60 , 61 ]. For example, Altok et al. reported in a cost-efficacy analysis a 2.5x times increase of the price of general anesthesia for TTPM (3554$) compared to local anesthesia TRUS-SB (1405$), with a cost even superior to in-bore MRI biopsy (2.2x times increase – 3158 $) [ 61 ]. Also, until recently, there was no certainty regarding the staging accuracy of TP route compared to TR route.

Ber et al. reported a non-inferiority within-person study comparing TP and TR, that proved non-inferiority and actually suggested that TP route was superior for csPCA detection rate (42% vs. 27%, p  = 0.03) [ 62 ]. Loy et al. found a comparable sensitivity and specificity (81% vs. 80%, 99% vs. 95%, for TR and TP respectively) in a recent systematic analysis and meta-analysis [ 63 ]. A large recent multicenter retrospective cohort including 5200 patients compared TR and TP route for patients benefitting of MRI-TB for lesions PI-RADS ≥ 3 and showed a higher rate of PCA and csPCA detection using TP route (64% vs. 50%, 49% vs. 35%, p  < 0.01 respectively) [ 64 ]. TP route was an independent predictor of PCA (OR:1.37) and especially csPCA (OR:1.19), with higher performance in the apex (OR:4.81), transition/central zone (OR:2.67) and anterior zone (OR:5.62). Those finding were confirmed by Uleri et al. in a 2023 systematic review and meta-analysis including 8662 patients, showing that TP significantly outperformed TR for anterior lesions (OR : 2.17, p  < 0.001) and apical lesions (OR : 1.86, p  = 0.01) with a similar overall csPCA rate (OR = 1.11, p  = 0.1). TP significantly outperformed TR for PI-RADS 4 lesions (OR : 1.57, p  = 0.02), possibly hinting at a more precise targeting with TP since PI-RADS 4 lesions are usually smaller [ 65 ]. Wu et al. also showed a higher csPCA detection rate of TP compared to TR (RR 1.33, p  = 0.005) on a per-patient analysis and comparing two cohorts (RR:1.37, p  = 0.0002) as well. They also reported an increased csPCA detection in the anterior region on a per patient analysis (RR:2.55) as well as per-lesion analysis (RR:1.52), but did not provide information regarding apical lesions [ 66 ]. These findings confirm that TP is an adequate and safe substitute to transrectal mpMRI targeted lesions, and possibly provides a higher diagnostic accuracy when focusing on apical and anterior lesions that are subject to systematic sampling error using the TR route.

Safety aspects

Another important aspect to discuss is the possible complications related to transperineal and transrectal route. Overall, some trials have assessed the complications of the TP + antibiotics, TP alone and TR + antibiotics strategies. A systematic review (SR) including 165 studies with 162,577 patients reported sepsis rates of 0.1% for TP and 0.9% for TR biopsies [ 67 ]. Additionally, a population-based study from the UK involving 73,630 patients demonstrated lower re-admission rates for sepsis in those who underwent TP biopsies (1.0%) compared to those who underwent transrectal biopsies (1.4%) [ 68 ]. These results collectively indicate a lower risk of infectious complications with transperineal biopsies compared to transrectal methods. However, a recent randomized controlled trial by Mian et al. of 840 men challenges the abovementioned results. In terms of complications both routes showed similar results with a 2,6% and 2,7% of infectious complications and a 1,7% and 2,2% rate of other complications [ 69 ]. The present study with such large numbers clearly challenges the results of the Cochrane review. Regarding the u antibiotic prophylaxis, a multicenter, randomized trial compared TP biopsy without antibiotic prophylaxis to TR biopsy with targeted prophylaxis based on rectal culture screening. No infections were reported in the TP group, whereas the TR group experienced a 1.4% infection rate (difference –1.4%; p  = 0.059). Participants undergoing TP biopsies reported higher levels of periprocedural pain, with a small adjusted difference of 0.6 on a 0–10 scale, but this discomfort resolved within 7 days [ 70 ]. A systematic review (SR) and meta-analysis of eight non-randomized controlled trials (non-RCTs) evaluated the impact of antibiotic prophylaxis on infection outcomes for patients undergoing TP biopsies. The analysis found no significant differences between patients who received antibiotic prophylaxis and those who did not in terms of post-biopsy infection rates (0.11% vs. 0.31%) and sepsis rates (0.13% vs. 0.09%) [ 71 ]. These results suggest that antibiotic prophylaxis may not significantly affect the incidence of infections or sepsis following TP biopsies, which might be another reason to choose TP over TR route.

Focal therapy : adaptation of the biopsy strategy

After having described several prostate biopsy strategies, the question is ; is there a recognized “best strategy” for focal therapy? The Ginsburg Protocol and TTPM have been advocated as a reference for focal therapy, but required to be performed under general anesthesia which is a non-deliverable expensive strategy across the board. Also, minimizing the toxicity is also important, since higher core number is associated with increased adverse events [ 72 ]. To answer this question, several authors have compared the sensitivity of several biopsy strategy to WMH to identify whether preoperative biopsy were accurate enough to detect all csPCA.

Nassiri et al. investigated FT eligibility of men that underwent MRI-TB using FUS-TB and 12-cores TRUS-SB. On a cohort of 454 men with biopsy proven region of interest, 175 were candidates after biopsies. When compared with WHM, this biopsy strategy showed a 80% sensitivity, 73.5% specificity, 75% accuracy for FT eligibility [ 73 ]. Johnson et al. investigated the reliability of MRI-TB using TR route. They included 665 patients of a prospectively maintained database and identified 92 as candidates after the biopsies. Among them, 44 (48%) were inadequately considered as candidate when studying the WMH. Reason for exclusion was the tumor crossing the midline (21 patients), contralateral csPCA (20 patients) and ipsilateral high-risk tumor (3 patients). Interestingly, men with anterior index tumor where 2.4 times more likely to present undetected contralateral csPCA when compared to men with posterior tumor. Unfortunately, the number of targeted cores and the total number of cores were not reported [ 74 ]. Choi reported in 2023 a study on 120 men that underwent TTPM + MRI-TB and RP. On the 120 studied men, 52 were deemed eligible. Forty-two (80.7%) of them were correctly eligible based on WMH, while only 10 (19.2%) would have been contra-indicated (6 had bilateral disease, 4 had small ISUP2 volume priorly undetected), suggesting a more accurate staging. Their biopsy strategy used a median 29 cores on mean prostatic volume of 36 ml and required general anesthesia [ 75 ]. Lee recently reported a retrospective analysis of 398 patients that underwent TP-SatB (around 24 cores) combined with TP MRI-TB. They studied the impact of the reduction of number of systematic cores on the eligibility for focal therapy, using 4 different strategies (2/3 cores, ½ cores, 1/3 cores, ¼ cores), using a computer algorithm to evenly and artificially suppress biopsies and erase any systematic biopsy that overlapped MRI-TB. Patients had a treatment plan based on the biopsy finding, that could either consist of single quadrant ablation, hemi-ablation (anterior or lateral), three-quadrant ablation or whole-gland ablation. They reported a median number of 33 cores per patient [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ], with a median of 9 targeted cores. When compared to the plan that would have been realized on the basis of MRI-TB alone, adding the full systematic biopsy set resulted in a treatment plan change in 44% of the patients, with 10% of them becoming unsuitable for FT. Reducing the number of systematic cores had an important impact on FT treatment plan, with a modification in 12% of the patient (2/3 cores), 19% (1/2 cores), 24% (1/3 cores), and 29% (1/4 cores), showing that inadequate systematic sampling would probably result in suboptimal focal therapy planning [ 40 ].

Several consensus statement have been published for preoperative biopsy strategy as well as follow-up. Ong et al. studied all consensuses statement published regarding focal therapy up to 2023. All these consensuses agreed that mpMRI was the imaging modality of choice, and that MRI-TB + SB were required. While some authors agreed that in absence of mpMRI the TTPM can be sufficient, other agreed that systematic TRUS biopsies were sufficient, underlining the ongoing heterogeneity of practice and lack of identified “best biopsy strategy” yet [ 76 ]. The heterogeneity in csPCa definition as well as what we can accept as a community in the untreated area of men undergoing focal therapy are matters of debate which widely explain the ongoing controversy. This is beyond the purpose of this study. Follow-up after focal therapy is needed since as high as 20–30% patients will require re-treatment after the 1 st treatment. While no consensus was reached, most consensuses recommend a first mpMRI at 6 month with follow-up prostate biopsy at 6–12 months (targeted on the treated region, and SB) [ 76 ].

A large heterogeneity of practice exists regarding prostate biopsies, in term of access (transrectal versus transperineal), type of targeting used for MRI-targeted biopsies (cognitive, software-based, in-bore), and template of systematic biopsies. Transrectal access is easier to perform under local anesthesia and is still widely perform. Transperineal has been advocated as a safer route because of a reduced risk of postoperative urosepsis, possibility to perform without antibiotic prophylaxis, and increasing evidence show increased diagnostic performance especially in the apex and anterior zone, that are difficult zones to biopsy using transrectal biopsy. Biopsy protocols have emerged to standardize study reporting concerning transperineal biopsies, especially for focal therapy but have not seen widespread adoption yet. Systematic biopsies are subject to random and systematic errors and often misclassify patient (overdetection of ciPCA, underdetection of csPCA) and have been progressively abandoned as an alone procedure. MRI-TB alone reduces the detection of ciPCA but misses csPCA when compared to combined biopsy techniques, therefore asking for adequate combination strategy. Among the combinations and systematic strategies, the TTPM and Ginsburg protocol have shown to be have the highest negative predictive value, but require a high number of cores, exposing patients to potential combinations and the need for general anesthesia that limit this widespread implantation. Regional biopsies are gaining a lot of interest recently, since they have an overall sensitivity of about 90%, while importantly reducing the number of cores and avoiding the detection of ciPCA and are easily performed under local anesthesia. PSA density, and PI-RADS score as important markers to guide the biopsy strategy (only ipsilateral biopsies (regional)) or addition of contralateral biopsies. Finally, the accuracy of staging has a direct impact on focal therapy eligibility, with the need to define the borders of the index lesion to target as well as to minimize the likelihood of missed csPCA that may expose the patient to undertreatment. All these aspects have to be taken into consideration when planning biopsy for patients who might be eligible and considering focal therapy.

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Progressive trend, conceptual terminology, and future directions of green façade research: A review of literature in 2010–2023

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  • Y. Cui 1 , 2 ,
  • J. Tang 3 &
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Climate change and urbanization have caused environmental problems to cities, making it critical to build a low-carbon, resilient, and sustainable urban environment. Green façade (GFA) is an important nature-based solution for implementation by exploring urban vertical space. GFA is often expected to meet versatile needs across different fields, but existing literature has not well documented the evolution of green façade research and future directions. Accordingly, this study examined GFA studies in 2010–2023 through a review to identify progressive trends, conceptual terminology, knowledge gaps, and future research directions. Overall, the GFA could be described by 46 additional terms given structure, vegetation, and technique properties. GFA research has evolved into transdisciplinary research, but mainly includes four clusters: (1) urban greening and sustainability; (2) energy saving mechanism and associated factors; (3) green infrastructure and cooling benefits; and (4) modelling and simulation for heat island mitigation and microclimate regulation. However, the ecological properties, lighting, and acoustic performance of GFA have scarcely been analyzed. Europe and China were key contributors of relevant literature, and there was strong co-authorship among authors from an organization, region, or country. Future efforts should focus on (1) verification and quantification of GFA environmental, ecological, and health benefits, (2) technical needs, economic benefits, social acceptance and support, and policy formation for promotion, (3) development of efficient and tangible numerical models and GFA typology for parametric analysis, and (4) promotion of inter-department, inter-organization, and inter-regional collaboration. Overall, this study enhances GFA understanding to enable the transformation from research to practice.

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Acknowledgements

Authors would like to appreciate the valuable comments from sessional chairs of 4th International Conference on Urban Climate and Urban Design in Xi’an, China.

This study is supported by the National Natural Science Foundation of China (No. 42301339), the Fundamental Research Funds for the Central Universities (Grant No. 2024CDJXY014), the China Meteorological Administration “Research on value realization of climate ecological products” Youth Innovation Team Project (No. CMA2024QN15), and Chongqing Natural Science Foundation Project (No. CSTB2024NSCQ-MSX0670).

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Yi Cui: Conceptualization, Formal analysis, Investigation, Methodology, Visualization, Writing – original draft. Junqing Tang: Conceptualization, Investigation, Methodology, Resources, and Writing – review and editing. Bao-Jie He: Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Supervision, Writing – original draft, and writing – review and editing.

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Cui, Y., Tang, J. & He, BJ. Progressive trend, conceptual terminology, and future directions of green façade research: A review of literature in 2010–2023. Int. J. Environ. Sci. Technol. (2024). https://doi.org/10.1007/s13762-024-06030-8

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A case of resected anaplastic carcinoma of the pancreas producing granulocyte-colony stimulating factor with literature review

  • Norio Kubo   ORCID: orcid.org/0000-0003-2624-2529 1 ,
  • Shigemasa Suzuki 1 ,
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Granulocyte colony-stimulating factor (G-CSF)-producing tumors have been reported in various organs, and the prognosis of patients with G-CSF-producing pancreatic cancers is particularly dismal. In this report, we present a case of G-CSF-producing anaplastic carcinoma of the pancreas (ACP), characterized by early postoperative recurrence and rapid, uncontrolled growth.

Case presentation

A 74-year-old man presented to our hospital with complaints of abdominal fullness and pain after eating. On admission, it was observed that the peripheral leukocyte counts and serum G-CSF levels were significantly elevated (23,770/µL and 251 pg/mL, respectively). Computed tomography of the abdomen revealed a pancreatic head tumor involving the superior mesenteric vein. Pathologically, ultrasound-guided fine-needle aspiration confirmed ACP. Subsequently, we performed a subtotal stomach-preserving pancreaticoduodenectomy with portal vein reconstruction and partial transverse colon resection. On postoperative day (POD) 7, the leukocyte count decreased from 21,180/μL to 8490/μL; moreover, computed tomography revealed liver metastasis. Therefore, mFOLFILINOX chemotherapy was initiated on POD 30. However, the tumor exhibited rapid progression, and the patient died on POD 45.

Conclusions

G-CSF-producing ACP is rare, and the prognosis of patients is extremely poor. Basic research is required to develop effective drugs against G-CSF-producing tumors, and large-scale studies using national databases are needed to develop multidisciplinary treatment methods.

Anaplastic carcinoma of the pancreas (ACP) is a rare undifferentiated variant of pancreatic carcinoma with a poor prognosis and an average overall survival of 12.8 months [ 1 ]. Granulocyte colony-stimulating factor (G-CSF)-producing tumors have been reported in various organs since its initial discovery in 1977 in patients with lung cancer, with markedly increased leukocyte counts [ 2 ]. Lung cancer is the most frequently reported G-CSF-producing tumor; however, such cases of gastrointestinal and pancreatic cancers are rarely reported. The prognosis of patients with G-CSF-producing pancreatic cancers is very poor [ 3 , 4 ]. Here, we report a case of G-CSF-producing ACP that displayed early postoperative recurrence, and grew rapidly and uncontrollably.

A 74-year-old Japanese man was referred to our hospital with an elevated white blood cell (WBC) count and a pancreatic head tumor measuring 42 mm on computed tomography (CT). He complained of abdominal fullness and pain after eating; however, no jaundice or fever was observed. The patient had a medical history of hyperlipidemia and diabetes mellitus and received the required treatment. After admission, laboratory examination findings were as follows: WBC count, 23,770/μL (90.9% neutrophils, 5.6% lymphocytes, 2.8% monocytes, 0.3% eosinophils, and 0.4% basophils); hemoglobin, 13.6 g/dL; platelet count, 34.7 × 10 4 /mm 3 ; C-reactive protein, 7.19 mg/dL). Tumor marker levels were normal: carcinoembryonic antigen, 0.9 ng/mL; carbohydrate antigen 19–9, 17.3 U/mL; duke pancreatic monoclonal antigen type 2, 25 U/mL; and s-pancreas-1 antigen, 5.1 U/mL. The patient exhibited an increased inflammatory response without clinical signs, such as fever; however, antibiotics were administered owing to the possibility of cholangitis. A few days later, a blood test showed a persistently high inflammatory reaction level (WBC: 22,480/μL). G-CSF showed a high value of 251 pg/mL (normal < 39.0 pg/mL). Dynamic enhanced CT, conducted 2 weeks after the previous hospital CT scan, revealed a well-demarcated low-density mass measuring 60 mm in diameter with an enhancement of the peripheral portion of the lesion in the pancreatic head. The tumor involved the superior mesenteric vein (SMV) and gastroduodenal artery (Fig.  1 A), but did not invade the nerve of the superior mesenteric artery, and there were no enlarged lymph nodes or distant metastases. Dynamic magnetic resonance imaging (MRI) with Gd-EOB-DPTA enhancement revealed a tumor in the pancreatic head with low intensity on T1-weighted images and slightly high intensity on T2-weighted images. MRI showed clear tumor borders and invasion within the SMV in the portal phase of dynamic enhancement (Fig.  1 B). Diffusion-weighted imaging revealed the hyperintensity of the pancreatic head tumor (Fig.  1 C). No liver metastases were observed in the hepatobiliary phase. Endoscopic ultrasonography revealed a low-echoic mass with a round shape and capsular-like structures (Fig.  1 D). The pathological diagnosis based on ultrasound-guided fine-needle aspiration was anaplastic carcinoma. As there are no reports of effective chemotherapy for anaplastic pancreatic cancer and no clear distant metastasis or non-resectable factors, we decided to perform surgery for pancreatic head cancer without preoperative chemotherapy. Intraoperative findings showed that the tumor had invaded the SMV and transverse mesocolon. Intraoperative Sonazoid contrast-enhanced ultrasonography revealed no obvious liver metastases. Peritoneal dissemination was not observed. We performed a subtotal stomach-preserving pancreaticoduodenectomy (PD) with portal vein reconstruction, partial transverse colon resection, and the modified Child method. The operation time was 406 min, and the blood loss was 650 g. The resected specimen showed a gray and dark reddish brown solid mass with hemorrhage and necrosis measuring 65 mm in diameter in the pancreatic head (Fig.  2 A). Histologically, the tumor showed a diffused proliferation with necrosis (Fig.  2 B). The tumor comprised poorly cohesive, large, pleomorphic cells with abundant eosinophilic cytoplasm and a neutrophilic infiltration (Fig.  2 C). The tumor showed venous invasion (Fig.  2 D). Immunohistochemical analysis of the resected specimen revealed G-CSF expression on the plasma membrane of tumor cells (Fig.  2 E). Pathological diagnosis was Ph, TS4 (65 mm), nodular type, anaplastic carcinoma, pleomorphic type, int, INFb, Ly1, V2, Pn2, mpd0, pT3, pCH0, pDU1, pS1, pRP0, pPV1 (PVsm), pA0, pPL0, pOO0, pPCM0, pBCM0, pDPM0, R0, pN1a (1/16) M0 pStage IIB, according to the JPS 8th classification. It was classified as T3, N1, M0, Stage IIB according to the UICC 8th TNM staging system. We finally diagnosed the case as G-CSF-producing pleomorphic ACP based on these pathological findings. The WBC level decreased from 21,180/μL on the day before the surgery to 8490/μL on the postoperative day (POD) 7. Dynamic CT on POD 7 showed no obvious intra-abdominal complications, but did reveal liver metastasis in hepatic segment IV, measuring 8 mm in diameter. The patient required rehabilitation to improve the quality of daily life before discharge. The patient progressed without any postoperative complications and was discharged on POD 21.

figure 1

Preoperative images. A Abdominal CT in the coronal section revealed a well-demarcated cystic tumor with slight enhancement of the peripheral portion of the pancreatic head. B MRI revealed a pancreatic head tumor with SMV invasion. C Diffusion-weighted magnetic resonance imaging showing reduced tumor diffusion. D Diffusion-weighted images showing a pancreatic head mass with a high signal intensity

figure 2

Macroscopic and microscopic findings of the tumor. A Macroscopic appearance of the resected specimen. A gray and dark reddish mass measuring 65 mm in diameter with hemorrhage and necrosis was found in the pancreatic head. B Histological findings of the tumor showed a diffuse proliferation with necrosis. C Tumor cells were poorly cohesive, large, pleomorphic with abundant eosinophilic cytoplasm. The tumor showed a neutrophilic infiltration. D Tumor showed a vascular invasion. E Immunohistochemical staining for anti-G-CSF antibody in formalin-fixed paraffin-embedded resected specimen. Anaplastic cancer cells were positive for G-CSF

A blood test on POD 29 showed a high WBC count of 33,010/μL; however, no fever or other inflammatory reactions were observed. Modified FOLFILINOX was initiated on POD 30 as chemotherapy for recurrence. On POD 39, the patient was admitted to the hospital with a loss of appetite and fatigue. On POD 41, the patient had impaired consciousness, and a head CT scan showed multiple cerebral infarcts, leading to a diagnosis of Trousseau’s syndrome. Abdominal CT revealed that the metastatic liver tumor had spread rapidly (Fig.  3 A, B ). Treatment was set as the best supportive care; however, the patient died on POD 45.

figure 3

Postoperative enhanced abdominal computed tomography findings. A CT showing an 8 mm nodule on the hepatic segment 4 on POD 7. B Tumor in liver segment 4 increased to 85 mm on POD 41. Multiple intrahepatic liver metastases were also observed

This report describes a rare case of G-CSF-producing ACP. The frequency of ACP is reported to be 0.1–5.7% [ 3 ]. The median overall survival of patients with ACP is poor (< 1 year), except for surgical cases [ 4 ]. A recent report highlighted an aggressive resection of a huge ACP, including other invaded organs, with an improved prognosis [ 5 ]. G-CSF-producing ACP is extremely rare, with only a few case reports, and the prognosis is very poor in all the reports [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. Of the 345 pancreatic cancer cases operated on in our hospital over the past 10 years, 8 (2.3%) were ACP cases, of which only 1 (0.3%), the present case, was G-CSF-producing. The following four characteristics of G-CSF-producing tumors were presented by Asano et al. [ 2 ]. (i) extreme leukocytosis, (ii) elevated G-CSF activity, (iii) decreased WBC count after tumor resection, and (iv) detection of G-CSF production in the tumor [ 2 ]. They have also been described as the diagnostic criteria in previous reports [ 11 ]. In one case from Table  1 , G-CSF was not measured, but immunostaining results showed G-CSF production along with other features, and it was diagnosed as a G-CSF-producing tumor [ 14 ]. In another case, the WBC count did not improve postoperatively; however, in one case of R1 resection, the postoperative WBC count remained high and displayed early recurrence, and it was thus diagnosed as a G-CSF-producing tumor [ 8 ]. Currently, tumors are diagnosed as G-CSF-producing tumors even if all the four diagnostic criteria are not fulfilled. In the present case, all diagnostic criteria were met. There have been reports of G-CSF production in other types of pancreatic cancers, such as poorly differentiated adenocarcinomas [ 15 ] and adenosquamous carcinomas [ 16 ]. Mucinous cystic neoplasms [ 17 ] and solid pseudopapillary tumors [ 18 ] that produce G-CSF have also been reported.

Reports on other organs also suggest poor prognosis of G-CSF-producing tumors [ 19 , 20 ]. KRAS mutant allele-specific imbalance correlates with the progression to ACP [ 21 ], and G-CSF expression correlates with KRAS mutations in pancreatic tumors [ 22 ]. G-CSF enhances pancreatic cancer cell proliferation via autocrine signaling by increasing inflammatory cytokines, adversely affecting cancer progression [ 23 ]. In this case, two preoperative and two postoperative CT scans were performed, which confirmed tumor growth within a short period. Pre-operatively, the tumor doubling time was 8 days, whereas the postoperative liver metastatic lesion showed faster tumor growth, with a doubling time of 3 days. The inflammatory response to surgical invasion possibly stimulates tumor growth. Epithelial–mesenchymal transition (EMT) is associated with poor prognosis in ACP [ 4 ]. Decreased E-cadherin and increased N-cadherin expression have previously been associated with EMT, which mediates cancer progression [ 24 ]. Immunohistochemical staining showed that E-cadherin expression was absent in seven out of eight cases of anaplastic carcinoma [ 25 ].

A search of the PubMed database using the keywords ‘ACP or undifferentiated carcinoma’ and ‘G-CSF’ was performed. Nine cases of surgical resection of this rare high-grade tumor have been reported, with the present case being the tenth; however, there may be additional cases. The prognosis has been consistently poor (Table  1 ) [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. The possibility that only cases with extremely poor outcomes have been reported, cannot be denied. Among these, there were eight male patients, with many cases involving large tumors, averaging 91 mm (55–154 mm) in diameter. In two cases, G-CSF levels were low or not measured, but the diagnosis was based on the criteria for G-CSF-producing tumors. PD was performed for lesions in the pancreatic head only in this case and in one other case. Complicated resection of other organs was performed in 6 of the 10 cases, probably because of the large tumor size and invasion. Patients with pleomorphic pathologies tend to have high G-CSF levels. A patient with reduced accumulation of fluorodeoxyglucose with TS-1 treatment survived for only 88 days [ 26 ]. Inoue et al. reported that radiotherapy temporarily reduced the size of recurrent lesions after surgery, suggesting that radiotherapy might be effective [ 10 ]. However, while there are a few case reports suggesting potential effectiveness, no clear treatment strategy has been established. All patients died within 8 months, and most cases recurred early in the immediate postoperative period. The median survival time for ACP patients with G-CSF production was only 58 days by survival curves using the Kaplan–Meier method (Fig.  4 ). The postoperative prognosis for G-CSF-producing ACP was very poor. This rare and highly malignant tumor has been treated by surgical resection only 10 times, with consistently poor outcomes. We expect that a multidisciplinary treatment approach, including surgery, chemotherapy, and radiotherapy, will improve prognosis. Additionally, further basic research can contribute to the development of effective treatment methods for G-CSF-producing tumors. There has been no large-scale analysis of the prognosis for G-CSF-producing ACP using national databases, making it necessary to further investigate this rare cancer to develop potential treatment strategies.

figure 4

Kaplan–Meier curve for G-CSF producing ACP cases. Survival curve for previous resected cases of G-CSF producing ACP are shown. Median survival time was only 58 days

A very rare case of G-CSF-producing ACP was reported. Extended surgical resection was performed; however, early recurrence and rapid proliferation led to unfortunate outcomes. No case has been reported of a prolonged prognosis, and the disease urgently requires the development of new treatment strategies.

Availability of data and materials

Data sharing was not applicable to this article as no datasets were generated or analyzed during the current study.

Abbreviations

Anaplastic carcinoma of the pancreas

  • Granulocyte-colony stimulating factor

White blood cell

Computed tomography

Superior mesenteric vein

Magnetic resonance imaging

Pancreaticoduodenectomy

Postoperative day

Epithelial–mesenchymal transition

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Acknowledgements

We would like to thank Chika Obata and Keiko Kitazume for their work on data management.

The authors received no financial support.

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Department of Surgery, Gunma Prefecture Saiseikai Maebashi Hospital, 564-1 Kamishinden, Maebashi, Gunma, 371-0821, Japan

Norio Kubo, Shigemasa Suzuki, Takahiro Seki, Shunsaku Furuke, Naoki Yagi, Takashi Ooki, Ryusuke Aihara, Akira Mogi & Yasuo Hosouchi

Department of Pathology, Gunma Saiseikai Maebashi Hospital, Maebashi, Japan

Yuka Yoshida & Kenji Kashiwabara

Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Japan

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Norio Kubo participated in research design, data collection, and the writing of the paper; Shigemasa Suzuki and Ken Shirabe contributed to the discussion and reviewed the manuscript; Takahiro Seki, Shunsaku Furuke, Naoki Yagi, Takashi Ooki, Ryusuke Aihara, Akira Mogi and Yasuo Hosouchi participated in data collection; Yuka Yoshida and Kenji Kashiwabara contributed to pathological diagnosis.

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Kubo, N., Suzuki, S., Seki, T. et al. A case of resected anaplastic carcinoma of the pancreas producing granulocyte-colony stimulating factor with literature review. surg case rep 10 , 205 (2024). https://doi.org/10.1186/s40792-024-02008-3

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How to write a review article?

In the medical sciences, the importance of review articles is rising. When clinicians want to update their knowledge and generate guidelines about a topic, they frequently use reviews as a starting point. The value of a review is associated with what has been done, what has been found and how these findings are presented. Before asking ‘how,’ the question of ‘why’ is more important when starting to write a review. The main and fundamental purpose of writing a review is to create a readable synthesis of the best resources available in the literature for an important research question or a current area of research. Although the idea of writing a review is attractive, it is important to spend time identifying the important questions. Good review methods are critical because they provide an unbiased point of view for the reader regarding the current literature. There is a consensus that a review should be written in a systematic fashion, a notion that is usually followed. In a systematic review with a focused question, the research methods must be clearly described. A ‘methodological filter’ is the best method for identifying the best working style for a research question, and this method reduces the workload when surveying the literature. An essential part of the review process is differentiating good research from bad and leaning on the results of the better studies. The ideal way to synthesize studies is to perform a meta-analysis. In conclusion, when writing a review, it is best to clearly focus on fixed ideas, to use a procedural and critical approach to the literature and to express your findings in an attractive way.

The importance of review articles in health sciences is increasing day by day. Clinicians frequently benefit from review articles to update their knowledge in their field of specialization, and use these articles as a starting point for formulating guidelines. [ 1 , 2 ] The institutions which provide financial support for further investigations resort to these reviews to reveal the need for these researches. [ 3 ] As is the case with all other researches, the value of a review article is related to what is achieved, what is found, and the way of communicating this information. A few studies have evaluated the quality of review articles. Murlow evaluated 50 review articles published in 1985, and 1986, and revealed that none of them had complied with clear-cut scientific criteria. [ 4 ] In 1996 an international group that analyzed articles, demonstrated the aspects of review articles, and meta-analyses that had not complied with scientific criteria, and elaborated QUOROM (QUality Of Reporting Of Meta-analyses) statement which focused on meta-analyses of randomized controlled studies. [ 5 ] Later on this guideline was updated, and named as PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). [ 6 ]

Review articles are divided into 2 categories as narrative, and systematic reviews. Narrative reviews are written in an easily readable format, and allow consideration of the subject matter within a large spectrum. However in a systematic review, a very detailed, and comprehensive literature surveying is performed on the selected topic. [ 7 , 8 ] Since it is a result of a more detailed literature surveying with relatively lesser involvement of author’s bias, systematic reviews are considered as gold standard articles. Systematic reviews can be diivded into qualitative, and quantitative reviews. In both of them detailed literature surveying is performed. However in quantitative reviews, study data are collected, and statistically evaluated (ie. meta-analysis). [ 8 ]

Before inquring for the method of preparation of a review article, it is more logical to investigate the motivation behind writing the review article in question. The fundamental rationale of writing a review article is to make a readable synthesis of the best literature sources on an important research inquiry or a topic. This simple definition of a review article contains the following key elements:

  • The question(s) to be dealt with
  • Methods used to find out, and select the best quality researches so as to respond to these questions.
  • To synthetize available, but quite different researches

For the specification of important questions to be answered, number of literature references to be consulted should be more or less determined. Discussions should be conducted with colleagues in the same area of interest, and time should be reserved for the solution of the problem(s). Though starting to write the review article promptly seems to be very alluring, the time you spend for the determination of important issues won’t be a waste of time. [ 9 ]

The PRISMA statement [ 6 ] elaborated to write a well-designed review articles contains a 27-item checklist ( Table 1 ). It will be reasonable to fulfill the requirements of these items during preparation of a review article or a meta-analysis. Thus preparation of a comprehensible article with a high-quality scientific content can be feasible.

PRISMA statement: A 27-item checklist

Title
Title1 Identify the article as a systematic review, meta-analysis, or both
Summary
Structured summary2 Write a structured summary including, as applicable, background; objectives; data sources; study eligibility criteria, participants, treatments, study appraisal and synthesis methods; results; limitations; conclusions and implications of key findings; and systematic review registration number
Introduction
Rationale3 Explain the rationale for the review in the context of what is already known
Objectives4 Provide an explicit statement of questions being addressed with reference to participants, interventions, comparisons, outcomes, and study design (PICOS)
Methods
Protocol and registration5 Indicate if a review protocol exists, if and where it can be accessed (such as a web address), and, if available, provide registration information including the registration number
Eligibility criteria6 Specify study characteristics (such as PICOS, length of follow-up) and report characteristics (such as years considered, language, publication status) used as criteria for eligibility, giving rationale
Sources of Information7 Describe all information sources in the survey (such as databases with dates of coverage, contact with study authors to identify additional studies) and date last searched
Survey8 Present the full electronic search strategy for at least one major database, including any limits used, such that it could be repeated
Study selection9 State the process for selecting studies (that is, for screening, for determining eligibility, for inclusion in the systematic review, and, if applicable, for inclusion in the meta-analysis)
Data collection process10 Describe the method of data extraction from reports (such as piloted forms, independently by two reviewers) and any processes for obtaining and confirming data from investigators
Data items11 List and define all variables for which data were sought (such as PICOS, funding sources) and any assumptions and simplifications made
Risk of bias in individual studies12 Describe methods used for assessing risk of bias in individual studies (including specification of whether this was done at the study or outcome level, or both), and how this information is to be used in any data synthesis
Summary measures13 State the principal summary measures (such as risk ratio, difference in means)
Synthesis of outcomes14 For each meta-analysis, explain methods of data use, and combination methods of study outcomes, and if done consistency measurements should be indicated (ie P test)
Risk of bias across studies15 Specify any assessment of risk of bias that may affect the cumulative evidence (such as publication bias, selective reporting within studies).
Additional analyses16 Describe methods of additional analyses (such as sensitivity or subgroup analyses, meta-regression), if done, indicating which were pre-specified.
Results
Study selection17 Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally with a flow diagram.
Study characteristics18 For each study, present characteristics for which data were extracted (such as study size, PICOS, follow-up period) and provide the citation.
Risk of bias within studies19 Present data on risk of bias of each study and, if available, any outcome-level assessment (see item 12)
Results of individual studies20 For all outcomes considered (benefits and harms), present, for each study, simple summary data for each intervention group and effect estimates and confidence intervals, ideally with a forest plot (a type of graph used in meta-analyses which demonstrates relat, ve success rates of treatment outcomes of multiple scientific studies analyzing the same topic)
Syntheses of resxults21 Present the results of each meta-analyses including confidence intervals and measures of consistency
Risk of bias across studies22 Present results of any assessment of risk of bias across studies (see item 15).
Additional analyses23 Give results of additional analyses, if done such as sensitivity or subgroup analyses, meta-regression (see item 16)
Discussion
Summary of evidence24 Summarize the main findings, including the strength of evidence for each main outcome; consider their relevance to key groups (such as healthcare providers, users, and policy makers)
Limitations25 Discuss limitations at study and outcome level (such as risk of bias), and at review level such as incomplete retrieval of identified research, reporting bias
Conclusions26 Provide a general interpretation of the results in the context of other evidence, and implications for future research
Funding
Funding27 Indicate sources of funding or other support (such as supply of data) for the systematic review, and the role of funders for the systematic review

Contents and format

Important differences exist between systematic, and non-systematic reviews which especially arise from methodologies used in the description of the literature sources. A non-systematic review means use of articles collected for years with the recommendations of your colleagues, while systematic review is based on struggles to search for, and find the best possible researches which will respond to the questions predetermined at the start of the review.

Though a consensus has been reached about the systematic design of the review articles, studies revealed that most of them had not been written in a systematic format. McAlister et al. analyzed review articles in 6 medical journals, and disclosed that in less than one fourth of the review articles, methods of description, evaluation or synthesis of evidence had been provided, one third of them had focused on a clinical topic, and only half of them had provided quantitative data about the extend of the potential benefits. [ 10 ]

Use of proper methodologies in review articles is important in that readers assume an objective attitude towards updated information. We can confront two problems while we are using data from researches in order to answer certain questions. Firstly, we can be prejudiced during selection of research articles or these articles might be biased. To minimize this risk, methodologies used in our reviews should allow us to define, and use researches with minimal degree of bias. The second problem is that, most of the researches have been performed with small sample sizes. In statistical methods in meta-analyses, available researches are combined to increase the statistical power of the study. The problematic aspect of a non-systematic review is that our tendency to give biased responses to the questions, in other words we apt to select the studies with known or favourite results, rather than the best quality investigations among them.

As is the case with many research articles, general format of a systematic review on a single subject includes sections of Introduction, Methods, Results, and Discussion ( Table 2 ).

Structure of a systematic review

IntroductionPresents the problem and certain issues dealt in the review article
MethodsDescribes research, and evaluation process
Specifies the number of studies evaluated orselected
ResultsDescribes the quality, and outcomes of the selected studies
DiscussionSummarizes results, limitations, and outcomes of the procedure and research

Preparation of the review article

Steps, and targets of constructing a good review article are listed in Table 3 . To write a good review article the items in Table 3 should be implemented step by step. [ 11 – 13 ]

Steps of a systematic review

Formulation of researchable questionsSelect answerable questions
Disclosure of studiesDatabases, and key words
Evaluation of its qualityQuality criteria during selection of studies
SynthesisMethods interpretation, and synthesis of outcomes

The research question

It might be helpful to divide the research question into components. The most prevalently used format for questions related to the treatment is PICO (P - Patient, Problem or Population; I-Intervention; C-appropriate Comparisons, and O-Outcome measures) procedure. For example In female patients (P) with stress urinary incontinence, comparisons (C) between transobturator, and retropubic midurethral tension-free band surgery (I) as for patients’ satisfaction (O).

Finding Studies

In a systematic review on a focused question, methods of investigation used should be clearly specified.

Ideally, research methods, investigated databases, and key words should be described in the final report. Different databases are used dependent on the topic analyzed. In most of the clinical topics, Medline should be surveyed. However searching through Embase and CINAHL can be also appropriate.

While determining appropriate terms for surveying, PICO elements of the issue to be sought may guide the process. Since in general we are interested in more than one outcome, P, and I can be key elements. In this case we should think about synonyms of P, and I elements, and combine them with a conjunction AND.

One method which might alleviate the workload of surveying process is “methodological filter” which aims to find the best investigation method for each research question. A good example of this method can be found in PubMed interface of Medline. The Clinical Queries tool offers empirically developed filters for five different inquiries as guidelines for etiology, diagnosis, treatment, prognosis or clinical prediction.

Evaluation of the Quality of the Study

As an indispensable component of the review process is to discriminate good, and bad quality researches from each other, and the outcomes should be based on better qualified researches, as far as possible. To achieve this goal you should know the best possible evidence for each type of question The first component of the quality is its general planning/design of the study. General planning/design of a cohort study, a case series or normal study demonstrates variations.

A hierarchy of evidence for different research questions is presented in Table 4 . However this hierarchy is only a first step. After you find good quality research articles, you won’t need to read all the rest of other articles which saves you tons of time. [ 14 ]

Determination of levels of evidence based on the type of the research question

ISystematic review of Level II studiesSystematic review of Level II studiesSystematic review of Level II studiesSystematic review of Level II studies
IIRandomized controlled studyCrross-sectional study in consecutive patientsInitial cohort studyProspective cohort study
IIIOne of the following: Non-randomized experimental study (ie. controlled pre-, and post-test intervention study) Comparative studies with concurrent control groups (observational study) (ie. cohort study, case-control study)One of the following: Cross-sectional study in non-consecutive case series; diagnostic case-control studyOne of the following: Untreated control group patients in a randomized controlled study, integrated cohort studyOne of the following: Retrospective cohort study, case-control study (Note: these are most prevalently used types of etiological studies; for other alternatives, and interventional studies see Level III
IVCase seriesCase seriesCase series or cohort studies with patients at different stages of their disease states

Formulating a Synthesis

Rarely all researches arrive at the same conclusion. In this case a solution should be found. However it is risky to make a decision based on the votes of absolute majority. Indeed, a well-performed large scale study, and a weakly designed one are weighed on the same scale. Therefore, ideally a meta-analysis should be performed to solve apparent differences. Ideally, first of all, one should be focused on the largest, and higher quality study, then other studies should be compared with this basic study.

Conclusions

In conclusion, during writing process of a review article, the procedures to be achieved can be indicated as follows: 1) Get rid of fixed ideas, and obsessions from your head, and view the subject from a large perspective. 2) Research articles in the literature should be approached with a methodological, and critical attitude and 3) finally data should be explained in an attractive way.

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Cyclodextrin complexes for the treatment of chagas disease: a literature review.

literature review in article

1. Introduction

2. flowchart of this study.

YearReferenceTitleGoalsConclusions
2023[ ]New drug encapsulated incyclodextrin with promising anti-Trypanosoma cruzi activity.Production and Characterization of a host–guest complex (Anti-Chagas Drug-Modified Chalcone (CHC) in 2-Hydroxypropyl-Beta-Cyclodextrin).HPβCD/CHC showed promising activity against Trypanosoma cruzi. This complex offers improved water solubility and requires a lower amount of CHC to be effective.
2023[ ]Elucidating the complexation of nifurtimox (NIF) with cyclodextrins.Evaluate whether the formation of complexes with β-cyclodextrin and sulfobutyl ether-β-cyclodextrin would improve the solubility and dissolution rate of the drug.β-CD/NIF and SBE-β-CD/NIF improved drug solubility and dissolution rate, showing significant stability in dissolution and crystallinity over 6 months at 25 °C and 40 °C.
2023[ ]O-allyl-lawsone inclusion complex with 2-hydroxypropyl-β-cyclodextrin: Preparation, physical characterization, antiparasitic and antifunga activity.Evaluate the antiparasitic and antifungal activity of O-allyl-lawsone (OAL) free and encapsulated in 2-hydroxypropyl-β-cyclodextrin (OAL MKN) against Trypanosoma cruzi.HPβCD/OAL increased antiparasitic activity compared with the free form (OAL) while reducing cytotoxicity and enhancing selectivity for the trypomastigote form of T. cruzi.
2021[ ]Characterization and trypanocidal activity of a drug carrier containing β-lapachone.Investigate the in vitro action of anti-T. cruzi, effects of β-Lap encapsulated in 2-hydroxypropyl-β-cyclodextrin (2HP-β-CD), and its potential toxicity to mammalian cells.The trypanocidal activity was increased by encapsulation of HP-β-CD/β-Lap compared with free naphthoquinone (β-Lap).
2020[ ]Synthesis and biological evaluation of β-lapachone and nor-β-lapachone complexes with 2-hydroxypropyl-β-cyclodextrin as trypanocidal agents.Study βLAP and its derivative complexes nor-β-Lapachone (NβL) with 2-hydroxypropyl-β-cyclodextrin to increase solubility and bioavailability.HP-β-CD/βLAP and HP-β-CD/NβL increased the drug solubility and, additionally, vectorization was observed, resulting in higher biological activity against the epimastigote and trypomastigote forms of T. cruzi.
2022[ ]Synthesis and study of the trypanocidal activity of catechol-containing 3-arylcoumarins, inclusion in β-cyclodextrin complexes and combination with benznidazole.Evaluate trypanocidal activity and cytotoxicity of a series of catechol-containing 3-arylcoumarins, their combination with BZN, and inclusion in β-cyclodextrins (β-CDs).Catechol-containing 3-arylcoumarins showed moderate trypanocidal activity against Trypanosoma cruzi, and their inclusion in β-cyclodextrins improved solubility. Combining these coumarins with benznidazole (BZN) further enhanced their effectiveness.
2018[ ]Technological innovation strategies for the specific treatment of Chagas disease based on Benznidazole.Conduct a literature review to identify current pharmaceutical technologies used in conjunction with BNZ to improve therapy for Chagas disease.Uma menor concentração de BNZ foi necessária para eliminar 50% das formas tripomastigotas de T. cruzi. Isso foi alcançado através da formação de complexos BNZ/CD e da modulação e vetorização do tratamento anti-Chagas utilizando estruturas metal-orgânicas.
2017[ ]Benznidazole nanoformulates: A chance to improve therapeutics for Chagas disease.Describe the characterization of several encapsulated formulations of benznidazole, currently a first-line medication for the treatment of Chagas disease.The in vitro cytotoxicity of BZN/CDs was significantly lower than that of free benznidazole, while their trypanocidal activity was not impaired.
2011[ ]Activity of a metronidazole analogue and its β-cyclodextrin complex against Trypanosoma cruzi.Prepare an inclusion complex between a metronidazole iodide analog (MTZ-I) and cyclodextrin (CD) to develop a safer and more effective method of treating Trypanosoma cruzi infections.MTZ-I and MTZ-I/β-CD were 10 times more active than MTZ, indicating that the presence of an iodine atom in the side chain increased trypanocidal activity while maintaining its cytotoxicity.
2011[ ]Modulated dissolution rate of the antichagasic benznidazole inclusion complex and cyclodextrin using hydrophilic polymer.Investigate the utility of hydroxypropylmethylcellulose (HPMC) polymer in controlling the release of BNZ from solid inclusion complexes with cyclodextrin to overcome the problem of its bioavailability.The addition of HPMC to BZN/CD inclusion complexes significantly improved the dissolution rate and controlled drug release, showing promising potential for Chagas disease therapy.
2012[ ]Benznidazole drug delivery by binary and multicomponent inclusion complexes using cyclodextrins and polymers.Develop and characterize inclusion complexes in binary systems with BNZ and randomly methylated β-cyclodextrin (RMβCD), and in ternary systems with BNZ, RMβCD, and hydrophilic polymers.Cyclodextrin-based inclusion complexes with benznidazole (BNZ) and hydrophilic polymers demonstrated effective, standardized, and safe drug delivery.
2008[ ]Study of the interaction between hydroxymethyl nitrofurazone and 2-hydroxypropyl-β-cyclodextrin.Characterize an NFOH inclusion complex in 2-hydroxypropyl-β-cyclodextrin (HP-β-CD).HP-β-CD/NFOH significantly reduced the toxic effects of NFOH, according to preliminary toxicity studies and cell viability tests.
2007[ ]Hydroxymethylnitrofurazone inclusion complex: dimethyl-β-cyclodextrin: a physicochemical characterization.Characterize inclusion complexes formed between NFOH and dimethyl-β-cyclodextrin (DM-β-CD) through complexation/release kinetics and solubility isotherm experiments using ultraviolet (UV)–visible spectrophotometry and dynamics measurement.NFOH/DM-β-CD showed improved solubility and favorable complexation, as demonstrated by solubility isotherm studies.

3. Brief Review

3.1. cyclodextrin, 3.2. industrial applications, 3.3. complexation mechanism, 3.4. chagas disease, 3.5. biological cycle, 3.6. nifurtimox and benznidazole, 3.7. studies conducted on the treatment of t. cruzi, 4. impact of cyclodextrins on the optimization of drug solubility and efficacy, 5. impact of cyclodextrins with benznidazole in the treatment of chagas disease, 6. impact of cyclodextrins with natural products in the treatment of chagas disease, 7. discussion, 8. final considerations, 9. conclusions, author contributions, conflicts of interest.

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Click here to enlarge figure

CyclodextrinGlucose Unit NumberMolecular WeightCavity Diameter (Å)Cavity Volume (Å )Aqueous Solubility at 25° C
(% m/v)
α-CD69724.5–5.317414.5
β-CD711356.0–6.52621.85
γ-CD812977.5–8.342723.2
Symptom/SignBenznidazolNifurtimox
Anorexia+++++
Headache+++
Dermatopathy++++
Psychic excitement-+++
Gastralgia++++
Insomnia+++
Nausea+++++
Weight loss++++
Polyneuropathy++++
Vomiting+++++
Type of CyclodextrinReferenceCyclodextrin Structure
β-cyclodextrin
(β-CD)
[ ]
2-Hydroxypropyl-β-cyclodextrin
(HP-β-CD)
[ ]
Dimethyl-β-cyclodextrin
(DM-β-CD)
[ ]
Ether sulfobutílico-β-cyclodextrin
(SBE-β-CD)
[ ]
Molecule NameReferenceMolecular Structure
HidroximetilNitrofurazone
(NFOH)
[ ]
Chalcones
(CHC)
[ ]
O-allyl-lawsone
(OAL)
[ ]
Nifurtimox
(NF)
[ ]
Benznidazole
(BNZ)
[ ]
Metronidazole
(MTZ)
[ ]
β-lapachone
(β-Lap)
[ ]
Nor-β-lapachone
(NβL)
[ ]
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Share and Cite

Taio, F.; Converti, A.; Lima, Á.A.N.d. Cyclodextrin Complexes for the Treatment of Chagas Disease: A Literature Review. Int. J. Mol. Sci. 2024 , 25 , 9511. https://doi.org/10.3390/ijms25179511

Taio F, Converti A, Lima ÁANd. Cyclodextrin Complexes for the Treatment of Chagas Disease: A Literature Review. International Journal of Molecular Sciences . 2024; 25(17):9511. https://doi.org/10.3390/ijms25179511

Taio, Fabrice, Attilio Converti, and Ádley Antonini Neves de Lima. 2024. "Cyclodextrin Complexes for the Treatment of Chagas Disease: A Literature Review" International Journal of Molecular Sciences 25, no. 17: 9511. https://doi.org/10.3390/ijms25179511

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