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Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\nThis achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
\n\nWe are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
\n\nThank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
\n\n\n\n\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"6788",leadTitle:null,fullTitle:"In Vivo and Ex Vivo Gene Therapy for Inherited and Non-Inherited Disorders",title:"In Vivo and Ex Vivo Gene Therapy for Inherited and Non-Inherited Disorders",subtitle:null,reviewType:"peer-reviewed",abstract:"Ongoing advances in pharmaceutical biotechnology have paved the way to ground-breaking new biological therapeutic modalities, offering the possibility of a durable curative approach for a number of life-threatening diseases, for which the medical need is as yet unmet. Over the past decades, gene therapy has seen a massive transformation from a proof-of-concept approach to a clinical reality culminating in the regulatory approval of state-of-the-art products in the European Union and in the United States. This book captures some of the scientific progresses notably in gene transfer technologies and translational development of in vivo and ex vivo gene therapy interventions in the treatment of a broad range of complex and debilitating non-inherited and inherited disorders such as: human immunodeficiency virus 1 (HIV-1) infection, cancer, cystic fibrosis, hereditary retinopathies, haemophilia B, cardiac diseases, and chronic liver fibrosis.",isbn:"978-1-78985-718-4",printIsbn:"978-1-78985-717-7",pdfIsbn:"978-1-83962-082-9",doi:"10.5772/intechopen.72962",price:119,priceEur:129,priceUsd:155,slug:"in-vivo-and-ex-vivo-gene-therapy-for-inherited-and-non-inherited-disorders",numberOfPages:198,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"8cc5d9c7226ec72dfaf15a41133b3d46",bookSignature:"Houria Bachtarzi",publishedDate:"March 13th 2019",coverURL:"https://cdn.intechopen.com/books/images_new/6788.jpg",numberOfDownloads:10355,numberOfWosCitations:2,numberOfCrossrefCitations:5,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:8,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:15,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"January 9th 2018",dateEndSecondStepPublish:"January 30th 2018",dateEndThirdStepPublish:"March 31st 2018",dateEndFourthStepPublish:"June 19th 2018",dateEndFifthStepPublish:"August 18th 2018",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"178430",title:"Dr.",name:"Houria",middleName:null,surname:"Bachtarzi",slug:"houria-bachtarzi",fullName:"Houria Bachtarzi",profilePictureURL:"https://mts.intechopen.com/storage/users/178430/images/6356_n.jpg",biography:"Dr Houria Bachtarzi is a Senior Consultant, Regulatory Affairs - Gene and Cell Therapies, with a strong scientific and regulatory experience in the field of advanced biological therapies including virally vectored gene therapy, in vivo and ex vivo gene editing, cell-based immunotherapy, genetically modified cells for tissue regeneration, genetically engineered immune cells targeting cancer cells and stem cell-based therapies. \nShe was previously a Lecturer in Biopharmaceutics and Biotechnology within the Pharmacology and Therapeutics Division and Member of the Brighton Centre for Regenerative Medicine at the School of Pharmacy and Biomolecular Sciences, University of Brighton, UK. Houria completed her PhD in cancer gene therapy/viral gene delivery at the University of Oxford, Department of Oncology, followed by Post-Doctoral research work in AAV-based gene therapy and shRNA therapeutics for degenerative neuro-muscular disorders at the Centre for Biomedical Sciences, Royal Holloway-University of London, in joint collaboration with Benitec Biopharma. Houria holds a First Class Master of Pharmacy Degree (with honours) from the University of Bath, UK and is a Registered Pharmacist with the General Pharmaceutical Council in the UK. She is also a Member of the Royal Pharmaceutical Society of Great Britain (RPSGB) and a Member of the British Society for Gene and Cell Therapy (BSGCT). Houria has published a number of peer reviewed papers in gene therapy and has presented posters and platform presentations at many international and national scientific meetings. In 2014, she received a Rising Star Award from the University of Brighton.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"396",title:"Molecular Genetics",slug:"genomics-molecular-genetics"}],chapters:[{id:"63291",title:"Nucleic Acid-Based Therapy: Development of a Nonviral-Based Delivery Approach",doi:"10.5772/intechopen.80741",slug:"nucleic-acid-based-therapy-development-of-a-nonviral-based-delivery-approach",totalDownloads:1436,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Gene therapy returns to the center stage of medicine to treat patients with diseases that are unable to be cured with the conventional therapeutic strategies. This development is due to various reasons, including vector development and significant achievement in next-generation sequencing. Among the various methodologies of gene therapy, nucleic acid-based therapy has been considered to be promising in various diseases. The development of delivery methods to target cells in vivo, however, remains critical. These include viral vector-based and nonviral vector-based gene delivery methods as well as physical approaches such as hydrodynamic gene delivery (HGD). HGD is a simple and effective in vivo gene transfer method for the functional analysis of therapeutic genes and regulatory elements in small animals. Moreover, this chapter outlines the principle of HGD, gene expression studies in rodents, and recent advances in clinical application of HGD and provides future perspectives in developing a safe and efficient method for nucleic acid-based therapy.",signatures:"Takeshi Yokoo, Kenya Kamimura, Tsutomu Kanefuji, Takeshi Suda\nand Shuji Terai",downloadPdfUrl:"/chapter/pdf-download/63291",previewPdfUrl:"/chapter/pdf-preview/63291",authors:[{id:"51900",title:"Dr.",name:"Kenya",surname:"Kamimura",slug:"kenya-kamimura",fullName:"Kenya Kamimura"},{id:"248717",title:"Dr.",name:"Takeshi",surname:"Yokoo",slug:"takeshi-yokoo",fullName:"Takeshi Yokoo"},{id:"251820",title:"Prof.",name:"Shuji",surname:"Terai",slug:"shuji-terai",fullName:"Shuji Terai"},{id:"263141",title:"Dr.",name:"Tsutomu",surname:"Kanefuji",slug:"tsutomu-kanefuji",fullName:"Tsutomu Kanefuji"},{id:"263142",title:"Prof.",name:"Takeshi",surname:"Suda",slug:"takeshi-suda",fullName:"Takeshi Suda"}],corrections:null},{id:"62781",title:"Gene Therapy for Cystic Fibrosis: Hurdles to Overcome for Successful Clinical Translation",doi:"10.5772/intechopen.79719",slug:"gene-therapy-for-cystic-fibrosis-hurdles-to-overcome-for-successful-clinical-translation",totalDownloads:1250,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Cystic fibrosis (CF) is a genetic disease that hampers the lung function. Despite that the main defective gene has been deeply characterized, some relevant concerns still need to be resolved before considering gene therapy as a realistic medical choice. One of the major issues that need to be strongly considered in order to succeed in the search for an effective gene therapy approach for CF is the design of the appropriate genetic material to be delivered. Other relevant factors to take into consideration include the design of safe and effective gene delivery systems, the biological barriers that need to be overcome in order to reach the nucleus of the target cells, and the problems related to the design of a drug formulation suitable for lung delivery purposes. Furthermore, some problems related to the commercialization of gene therapy products also need to be resolved. In this chapter, we discuss the up-to-date strategies to overcome such hurdles in order for gene therapy to become a routine treatment modality for CF.",signatures:"Myriam Sainz-Ramos, Nuseibah AL Qtaish, Idoia Gallego, Ilia Villate-\nBeitia, Tania López, Gustavo Puras and José Luis Pedraz",downloadPdfUrl:"/chapter/pdf-download/62781",previewPdfUrl:"/chapter/pdf-preview/62781",authors:[{id:"44050",title:"Dr.",name:"Jose Luis",surname:"Pedraz",slug:"jose-luis-pedraz",fullName:"Jose Luis Pedraz"},{id:"177087",title:"MSc.",name:"Ilia",surname:"Villate-Beitia",slug:"ilia-villate-beitia",fullName:"Ilia Villate-Beitia"},{id:"241258",title:"Dr.",name:"Gustavo",surname:"Puras",slug:"gustavo-puras",fullName:"Gustavo Puras"},{id:"241679",title:"Mrs.",name:"Nusaiba",surname:"Hasan",slug:"nusaiba-hasan",fullName:"Nusaiba Hasan"},{id:"241680",title:"Mrs.",name:"Miriam",surname:"Sainz",slug:"miriam-sainz",fullName:"Miriam Sainz"},{id:"241682",title:"Dr.",name:"Idoia",surname:"Gallego",slug:"idoia-gallego",fullName:"Idoia Gallego"},{id:"241683",title:"Mrs.",name:"Tania",surname:"López",slug:"tania-lopez",fullName:"Tania López"}],corrections:null},{id:"62765",title:"Mechanisms for Controlling HIV-1 Infection: A Gene Therapy Approach",doi:"10.5772/intechopen.79669",slug:"mechanisms-for-controlling-hiv-1-infection-a-gene-therapy-approach",totalDownloads:1421,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Current anti-retroviral treatment (ART) for HIV-1 is highly effectively at controlling the infection. However, during early infection the virus establishes a latent reservoir, which is not impacted by ART. Any treatment interruption rapidly results in virus rebound from the latent reservoir to pre-therapy levels and thus ART does not constitute an HIV-1 cure. Alternate treatments are currently being explored in the form of gene therapy, following the success of the Berlin patient who has had undetectable virus since 2007. This review will describe the contrasting cure approaches that are currently the focus of multiple studies to control HIV, then focus in on functional cure gene therapy strategies; specifically, epigenetic silencing of HIV-1 by various methods, including RNA-directed transcriptional gene silencing. The various delivery strategies for targeting cells of the latent reservoir will be reviewed and finally, the clinical status and current challenges for ex vivo versus in vivo gene therapy delivery approaches will be discussed.",signatures:"Katherine Ognenovska, Vera Klemm, Scott Ledger, Stuart Turville,\nGeoff Symonds, Anthony D. Kelleher and Chantelle L. Ahlenstiel",downloadPdfUrl:"/chapter/pdf-download/62765",previewPdfUrl:"/chapter/pdf-preview/62765",authors:[{id:"240943",title:"Ph.D.",name:"Chantelle",surname:"Ahlenstiel",slug:"chantelle-ahlenstiel",fullName:"Chantelle Ahlenstiel"},{id:"242163",title:"Ms.",name:"Vera",surname:"Klemm",slug:"vera-klemm",fullName:"Vera Klemm"},{id:"242164",title:"Ms.",name:"Katherine",surname:"Ognenovska",slug:"katherine-ognenovska",fullName:"Katherine Ognenovska"},{id:"255342",title:"Dr.",name:"Scott",surname:"Ledger",slug:"scott-ledger",fullName:"Scott Ledger"},{id:"255343",title:"Prof.",name:"Stuart",surname:"Turville",slug:"stuart-turville",fullName:"Stuart Turville"},{id:"255344",title:"Prof.",name:"Geoff",surname:"Symonds",slug:"geoff-symonds",fullName:"Geoff Symonds"},{id:"255345",title:"Prof.",name:"Anthony",surname:"Kelleher",slug:"anthony-kelleher",fullName:"Anthony Kelleher"}],corrections:null},{id:"62585",title:"Functional Activation of Autologous Human Diabetic Stem Cells for Cell Therapy",doi:"10.5772/intechopen.79650",slug:"functional-activation-of-autologous-human-diabetic-stem-cells-for-cell-therapy",totalDownloads:832,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Diabetic retinopathy (DR) is a common cause of vision loss and blindness. Healthy CD34+ stem cells are capable of homing to vascular lesions and facilitating vascular repair. However, many diabetic patients have dysfunctional CD34+ stem cells with no reparative potential. CD34+ dysfunction is corrected by transiently inhibiting endogenous transforming growth factor-β1 (TGF-β1) within the patient’s own dysfunctional CD34+ stem cells using phosphorodiamidate morpholino oligomers (PMOs). Antisense TGF-β1-treated dysfunctional CD34+ stem cells are now functional, no longer require growth factor stimulation to evade apoptosis, and are stable at 37°C ex vivo for >5 days. We identified three markers of restored stem cell function: (1) upregulation of CXCR4 expression necessary for stem cell homing and adhesion, (2) SDF-1-mediated nitric oxide (NO) production required for cell mobility, and (3) restoration of the ability of CD34+ cells to migrate and repair vascular lesions. The antisense targets autocrine TGF-β expression, whereas neutralizing antibodies do not. The PMO antisense triggers a cascade of hematopoietic proliferation and differentiation that paracrine TGF-β cannot alter. We describe optimal PMO manipulation of CD34+ stem cells ex vivo for transplantation, screening multiple gene targets leading to the identification of TGF-β1, and a lead TGF-β1 inhibitor evaluated in clinical studies.",signatures:"Patrick L. Iversen, Francis W. Ruscetti, Charles Garcia and Stephen H.\nBartelmez",downloadPdfUrl:"/chapter/pdf-download/62585",previewPdfUrl:"/chapter/pdf-preview/62585",authors:[{id:"241858",title:"Ph.D.",name:"Patrick",surname:"Iversen",slug:"patrick-iversen",fullName:"Patrick Iversen"},{id:"252583",title:"Dr.",name:"Stephen",surname:"Bartelmez",slug:"stephen-bartelmez",fullName:"Stephen Bartelmez"},{id:"252584",title:"Dr.",name:"Charles",surname:"Garcia",slug:"charles-garcia",fullName:"Charles Garcia"},{id:"252585",title:"Dr.",name:"Stephen",surname:"Bartelmez",slug:"stephen-bartelmez",fullName:"Stephen Bartelmez"}],corrections:null},{id:"63006",title:"Gene-based Interventions for Cancer Immunotherapy",doi:"10.5772/intechopen.80386",slug:"gene-based-interventions-for-cancer-immunotherapy",totalDownloads:983,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Immunotherapy of cancer has deservedly gained much attention in the past few years and is likely to continue to advance and become a fundamental cancer treatment. While vaccines, chimeric antigen receptor (CAR) T cells and checkpoint blockade have received the lion’s share of the attention, an important direct role for gene transfer as an immunotherapy is emerging. For example, oncolytic viruses induce immunogenic cell death, thus liberating both antigens and the signals that are necessary for the activation of antigen-presenting cells, ensuring stimulation of an adaptive response. In another example, transfer of prodrug converting enzymes, such as the herpes simplex virus-thymidine kinase (HSV-tk) gene or the cytosine deaminase gene, has been shown to promote an immune response, thus functioning as immunotherapies. Alternatively, our own work involves the use of nonreplicating viral vectors for the simultaneous delivery of gene combinations that promote both cell death and an immune response. In fact, our gene transfer approach has been applied as a vaccine, immunotherapy or in situ gene therapy, resulting in immunogenic cell death and the induction of a protective immune response. Here, we highlight the development of these approaches both in terms of technical advances and clinical experience.",signatures:"Otto L.D. Cerqueira, Gissele Rolemberg Oliveira Silva, Igor de Luna\nVieira, Marlous Vinícius Gomes Lana, Nadine Gimenez, Otavio\nAugusto Rodrigues, Paulo Roberto Del Valle, Samir Andrade\nMendonça and Bryan E. Strauss",downloadPdfUrl:"/chapter/pdf-download/63006",previewPdfUrl:"/chapter/pdf-preview/63006",authors:[{id:"32179",title:"Dr.",name:"Bryan",surname:"Strauss",slug:"bryan-strauss",fullName:"Bryan Strauss"},{id:"255568",title:"Dr.",name:"Otto",surname:"Cerqueira",slug:"otto-cerqueira",fullName:"Otto Cerqueira"},{id:"255569",title:"Dr.",name:"Gissele",surname:"Rolemberg",slug:"gissele-rolemberg",fullName:"Gissele Rolemberg"},{id:"255570",title:"M.Sc.",name:"Igor",surname:"Vieira",slug:"igor-vieira",fullName:"Igor Vieira"},{id:"255571",title:"M.Sc.",name:"Lana",surname:"Marlous",slug:"lana-marlous",fullName:"Lana Marlous"},{id:"255572",title:"Ms.",name:"Nadine",surname:"Gimenez",slug:"nadine-gimenez",fullName:"Nadine Gimenez"},{id:"255573",title:"Mr.",name:"Otavio",surname:"Rodrigues",slug:"otavio-rodrigues",fullName:"Otavio Rodrigues"},{id:"255574",title:"M.Sc.",name:"Paulo Roberto",surname:"Del Valle",slug:"paulo-roberto-del-valle",fullName:"Paulo Roberto Del Valle"},{id:"255575",title:"Mr.",name:"Samir",surname:"Andrade Mendonça",slug:"samir-andrade-mendonca",fullName:"Samir Andrade Mendonça"}],corrections:null},{id:"62432",title:"AAV-Mediated Gene Therapy for CRB1-Hereditary Retinopathies",doi:"10.5772/intechopen.79308",slug:"aav-mediated-gene-therapy-for-crb1-hereditary-retinopathies",totalDownloads:1202,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Variations in the Crumbs homolog-1 (CRB1) gene lead to autosomal recessive retinal dystrophies such as early-onset retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA). No treatment is yet available for these patients. Adeno-associated virus (AAV) mediated gene therapy for hereditary retinal diseases holds great promise proven by the large number of active clinical trials. We here summarized the knowledge about the localization and function of CRB1 in the retina and the main pathological features resulting from loss of CRB1 function in humans and in rodents. This know-how is being applied to design and develop AAV gene therapy vectors for the treatment of CRB1-Hereditary retinopathies. Knowing which cell types express the CRB proteins, the possible redundancy of function between CRB1 and CRB2, and the AAV tropism in the human retina, will allow us to rationalize about the AAV capsid, promoter and route of administration that should be used in the AAV vector in order to efficiently and specifically deliver CRB1 or CRB2 into the human retina.",signatures:"Celso Henrique Alves and Jan Wijnholds",downloadPdfUrl:"/chapter/pdf-download/62432",previewPdfUrl:"/chapter/pdf-preview/62432",authors:[{id:"243203",title:"Associate Prof.",name:"Jan",surname:"Wijnholds",slug:"jan-wijnholds",fullName:"Jan Wijnholds"},{id:"243206",title:"Dr.",name:"Henrique",surname:"Alves",slug:"henrique-alves",fullName:"Henrique Alves"}],corrections:null},{id:"62988",title:"Adeno-Associated Virus (AAV)-Mediated Gene Therapy for Disorders of Inherited and Non-Inherited Origin",doi:"10.5772/intechopen.80317",slug:"adeno-associated-virus-aav-mediated-gene-therapy-for-disorders-of-inherited-and-non-inherited-origin",totalDownloads:2152,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Gene therapy is a novel promising approach for treating a spectrum of inherited and non-inherited disorders by delivering therapeutic genes to specific organs or tissues. Of the viral vectors that have been used to date to deliver the genes of interest, the adeno-associated viral (AAV) vector appears to be the most safe and effective vehicle and has the ability to maintain long-term gene and protein expression following a single injection of the vector. Gene therapy studies using AAV vector have shown significant progress not only in animal models but also in human gene therapy with no known pathogenicity. While success has been achieved in gene therapy using AAV vector to deliver the target genes for inherited disorders, however, clinical trials are yet to begin to see whether gene therapy has promise for treatment of non-inherited diseases. This chapter describes AAV biology, viral structure, and cell entry mechanisms, with special emphasis on AAV tissue tropism achieved by manipulating different serotypes and capsid engineering. This chapter also discusses successful application of the AAV vector for non-inherited disorders in animal models with particular reference to liver fibrosis, outlining advantages, disadvantages, and future challenges that this therapy may face.",signatures:"Indu Rajapaksha, Peter Angus and Chandana Herath",downloadPdfUrl:"/chapter/pdf-download/62988",previewPdfUrl:"/chapter/pdf-preview/62988",authors:[{id:"245978",title:"Dr.",name:"Chandana",surname:"Herath",slug:"chandana-herath",fullName:"Chandana Herath"},{id:"248869",title:"Dr.",name:"Indu",surname:"Rajapaksha",slug:"indu-rajapaksha",fullName:"Indu Rajapaksha"},{id:"248870",title:"Prof.",name:"Peter",surname:"Angus",slug:"peter-angus",fullName:"Peter Angus"}],corrections:null},{id:"63153",title:"Gene Therapy for Cardiomyopathies",doi:"10.5772/intechopen.80478",slug:"gene-therapy-for-cardiomyopathies",totalDownloads:1083,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Heart disease remains the prevalent cause of premature death and accounts for a significant proportion of all hospital admissions. Molecular genetics was integrated quite late in cardiology, but introduced new concepts like sarcolemmopathies, cytoskeletalopathies, and channelopathies useful to better understand the pathophysiology of the development of inherited cardiomyopathies (CMs). As our understanding of the cellular and molecular processes involved in the development and progression of heart disease improved, new therapeutic targets were identified, as were novel approaches such as delivery of genes to replace defective or deficient components and thereby restore structure or function in a diseased heart. We discuss gene addition strategies in the context of monogenic disorders. Moreover, a broader nucleic acid-based modulation of cardiac gene expression for the treatment of cardiac diseases might have larger clinical indications. Inadequate gene delivery remains a potential cause of negative trials. However, progress in innovative formulations and clinically relevant ways of administration should lead to significant progress in the future. Cardiac gene therapy will be integrated into the therapeutic armamentarium for CM and heart failure.",signatures:"Yves Fromes and Caroline Roques",downloadPdfUrl:"/chapter/pdf-download/63153",previewPdfUrl:"/chapter/pdf-preview/63153",authors:[{id:"247560",title:"Dr.",name:"Yves",surname:"Fromes",slug:"yves-fromes",fullName:"Yves Fromes"},{id:"247561",title:"Prof.",name:"Caroline",surname:"Roques-Fromes",slug:"caroline-roques-fromes",fullName:"Caroline Roques-Fromes"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"1723",title:"DNA Methylation",subtitle:"From Genomics to Technology",isOpenForSubmission:!1,hash:"0b3809ec24719b565e1c788038b43870",slug:"dna-methylation-from-genomics-to-technology",bookSignature:"Tatiana Tatarinova and Owain Kerton",coverURL:"https://cdn.intechopen.com/books/images_new/1723.jpg",editedByType:"Edited by",editors:[{id:"95992",title:"Dr.",name:"Tatiana",surname:"Tatarinova",slug:"tatiana-tatarinova",fullName:"Tatiana Tatarinova"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6987",title:"Antisense Therapy",subtitle:null,isOpenForSubmission:!1,hash:"5d60550dc1e3afbb083fe61925b33caa",slug:"antisense-therapy",bookSignature:"Shashwat Sharad and Suman Kapur",coverURL:"https://cdn.intechopen.com/books/images_new/6987.jpg",editedByType:"Edited by",editors:[{id:"80113",title:"Dr.",name:"Shashwat",surname:"Sharad",slug:"shashwat-sharad",fullName:"Shashwat Sharad"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1719",title:"Genetic Manipulation of DNA and Protein",subtitle:"Examples from Current 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Pumo",reviewType:"peer-reviewed",authors:[{id:"99589",title:"Dr.",name:"Maria Letizia",middleName:null,surname:"Pumo",fullName:"Maria Letizia Pumo",slug:"maria-letizia-pumo"}]},{id:"34260",type:"chapter",title:"The r-Process of Nucleosynthesis: The Puzzle Is Still with Us",slug:"the-r-process-of-nucleosynthesis-the-puzzle-is-still-with-us",totalDownloads:2248,totalCrossrefCites:0,signatures:"Marcel Arnould and Stephane Goriely",reviewType:"peer-reviewed",authors:[{id:"108278",title:"Prof.",name:"Marcel",middleName:null,surname:"Arnould",fullName:"Marcel Arnould",slug:"marcel-arnould"},{id:"108283",title:"Dr.",name:"Stephane",middleName:null,surname:"Goriely",fullName:"Stephane Goriely",slug:"stephane-goriely"}]},{id:"34261",type:"chapter",title:"Diffuse Emission of 26Al and 60Fe in the Galaxy",slug:"diffuse-emission-of-26al-and-60fe-in-the-galaxy",totalDownloads:2151,totalCrossrefCites:0,signatures:"Wei Wang",reviewType:"peer-reviewed",authors:[{id:"104833",title:"Dr.",name:"Wei",middleName:null,surname:"Wang",fullName:"Wei Wang",slug:"wei-wang"}]},{id:"34262",type:"chapter",title:"Energy Generation Mechanisms in Stellar Interiors",slug:"energy-generation-mechanisms-in-stellar-interiors",totalDownloads:2386,totalCrossrefCites:0,signatures:"İbrahim Küçük",reviewType:"peer-reviewed",authors:[{id:"102957",title:"Prof.",name:"İbrahim",middleName:null,surname:"Küçük",fullName:"İbrahim Küçük",slug:"ibrahim-kucuk"}]},{id:"34263",type:"chapter",title:"The Lane-Emden-Fowler Equation and Its Generalizations - Lie Symmetry Analysis",slug:"the-lane-emden-equation-and-its-generalizations",totalDownloads:3902,totalCrossrefCites:2,signatures:"Chaudry Masood Khalique",reviewType:"peer-reviewed",authors:[{id:"94177",title:"Dr.",name:"Chaudry",middleName:"Masood",surname:"Khalique",fullName:"Chaudry Khalique",slug:"chaudry-khalique"}]},{id:"34264",type:"chapter",title:"The Missing Matter Problem: From the Dark Matter Search to Alternative Hypotheses",slug:"the-missing-matter-problem-from-dark-matter-to-alternative-hypotheses",totalDownloads:2002,totalCrossrefCites:1,signatures:"S. Capozziello, L. Consiglio, M. De Laurentis, G. De Rosa and C. 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Aleksandrov, N.G. Polukhina and N.I. Starkov",reviewType:"peer-reviewed",authors:[{id:"90408",title:"Prof.",name:"Natalia",middleName:null,surname:"Polukhina",fullName:"Natalia Polukhina",slug:"natalia-polukhina"},{id:"100258",title:"Prof.",name:"Nikolai",middleName:null,surname:"Starkov",fullName:"Nikolai Starkov",slug:"nikolai-starkov"},{id:"100259",title:"Dr.",name:"Andrey",middleName:null,surname:"Aleksandrov",fullName:"Andrey Aleksandrov",slug:"andrey-aleksandrov"}]},{id:"34267",type:"chapter",title:"Implementation of Dynamic Logic Algorithm for Detection of EM Fields Scattered by Langmuir Soliton",slug:"implementation-of-dynamic-logic-algorithm-for-detection-of-em-fields-scattered-by-langmuir-soliton",totalDownloads:1694,totalCrossrefCites:0,signatures:"V.I. Sotnikov, R.W. Deming and L. Perlovsky",reviewType:"peer-reviewed",authors:[{id:"97711",title:"Dr.",name:"Vladimir I.",middleName:null,surname:"Sotnikov",fullName:"Vladimir I. Sotnikov",slug:"vladimir-i.-sotnikov"}]},{id:"34268",type:"chapter",title:"Visualization Methods for Numerical Astrophysics",slug:"visualization-methods-for-numerical-astrophysics",totalDownloads:2509,totalCrossrefCites:1,signatures:"Werner Benger, Markus Haider, Harald Höller, Dominik Steinhauser, Josef Stöckl, Biagio Cosenza and Marcel Ritter",reviewType:"peer-reviewed",authors:[{id:"90557",title:"Dr.",name:"Werner",middleName:null,surname:"Benger",fullName:"Werner Benger",slug:"werner-benger"},{id:"112252",title:"MSc.",name:"Markus",middleName:null,surname:"Haider",fullName:"Markus Haider",slug:"markus-haider"},{id:"112253",title:"Dr.",name:"Josef",middleName:null,surname:"Stoeckl",fullName:"Josef Stoeckl",slug:"josef-stoeckl"},{id:"112254",title:"Dr.",name:"Biagio",middleName:null,surname:"Cosenza",fullName:"Biagio Cosenza",slug:"biagio-cosenza"},{id:"112257",title:"MSc.",name:"Marcel",middleName:null,surname:"Ritter",fullName:"Marcel Ritter",slug:"marcel-ritter"},{id:"112258",title:"MSc.",name:"Dominik",middleName:null,surname:"Steinhauser",fullName:"Dominik Steinhauser",slug:"dominik-steinhauser"},{id:"128849",title:"MSc.",name:"Harald",middleName:null,surname:"Hoeller",fullName:"Harald Hoeller",slug:"harald-hoeller"}]},{id:"34269",type:"chapter",title:"Asteroseismology of Vibration Powered Neutron Stars",slug:"asteroseismology-of-vibration-powered-neutron-stars",totalDownloads:2482,totalCrossrefCites:0,signatures:"Sergey Bastrukov, Renxin Xu, Junwei Yu, Irina Molodtsova and Hsiang-Kuang Chang",reviewType:"peer-reviewed",authors:[{id:"92999",title:"Dr.",name:"Sergey",middleName:null,surname:"Bastrukov",fullName:"Sergey Bastrukov",slug:"sergey-bastrukov"},{id:"93004",title:"Dr.",name:"Irina",middleName:null,surname:"Molodtsova",fullName:"Irina Molodtsova",slug:"irina-molodtsova"},{id:"94322",title:"MSc.",name:"Junwei",middleName:null,surname:"Yu",fullName:"Junwei Yu",slug:"junwei-yu"},{id:"94323",title:"Prof.",name:"Renxin",middleName:null,surname:"Xu",fullName:"Renxin Xu",slug:"renxin-xu"},{id:"106311",title:"Prof.",name:"Hsiang-Kuang",middleName:null,surname:"Chang",fullName:"Hsiang-Kuang Chang",slug:"hsiang-kuang-chang"}]},{id:"34270",type:"chapter",title:"Energetic Charged Particles in the Heliosphere from 1-120 AU Measured by the Voyager Spacecraft",slug:"charged-particle-intensities-in-the-heliosphere-as-measured-by-voyagers-1-and-2",totalDownloads:1670,totalCrossrefCites:0,signatures:"W.R. Webber",reviewType:"peer-reviewed",authors:[{id:"114311",title:"Prof.",name:"William R",middleName:null,surname:"Webber",fullName:"William R Webber",slug:"william-r-webber"}]},{id:"34271",type:"chapter",title:"A Comparison of Non Negative Blind Source Separation Methods for Identifying Astrophysical Ice Compounds",slug:"a-comparison-of-non-negative-blind-source-separation-methods-for-identifying-astrophysical-ice-compo",totalDownloads:2042,totalCrossrefCites:0,signatures:"Jorge Igual and Raul llinares",reviewType:"peer-reviewed",authors:[{id:"2290",title:"Dr.",name:"Raul",middleName:null,surname:"Llinares",fullName:"Raul Llinares",slug:"raul-llinares"},{id:"90804",title:"Dr.",name:"Jorge",middleName:null,surname:"Igual",fullName:"Jorge Igual",slug:"jorge-igual"}]},{id:"34272",type:"chapter",title:"Graviton Emission in the Bulk and Nucleosynthesis in a Model with Extra Dimension",slug:"graviton-emission-in-the-bulk-and-nucleosynthesis-in-a-model-with-extra-dimension-",totalDownloads:1628,totalCrossrefCites:0,signatures:"Mikhail Z. Iofa",reviewType:"peer-reviewed",authors:[{id:"100559",title:"Dr.",name:"Iofa",middleName:null,surname:"Mikhail",fullName:"Iofa Mikhail",slug:"iofa-mikhail"}]},{id:"34273",type:"chapter",title:"Putting Einstein to Test - Astrometric Experiments from Space, Fundamental Physics and Local Cosmology",slug:"putting-einstein-to-test-astrometric-experiments-from-space-fundamental-physics-and-local-cosmology",totalDownloads:1960,totalCrossrefCites:0,signatures:"Alberto Vecchiato",reviewType:"peer-reviewed",authors:[{id:"97352",title:"Dr.",name:"Alberto",middleName:null,surname:"Vecchiato",fullName:"Alberto Vecchiato",slug:"alberto-vecchiato"}]},{id:"34274",type:"chapter",title:"BBN as Probe of Fundamental Physics",slug:"bbn-as-probe-of-fundamental-physics",totalDownloads:2039,totalCrossrefCites:0,signatures:"L. A. Popa and A. Caramete",reviewType:"peer-reviewed",authors:[{id:"99744",title:"Prof.",name:"Lucia",middleName:null,surname:"Popa",fullName:"Lucia Popa",slug:"lucia-popa"},{id:"152277",title:"Dr.",name:"Ana",middleName:null,surname:"Caramete",fullName:"Ana Caramete",slug:"ana-caramete"}]}]},relatedBooks:[{type:"book",id:"8444",title:"Lunar Science",subtitle:null,isOpenForSubmission:!1,hash:"f1dcf511a174e8ec89d97ca8c0c6146a",slug:"lunar-science",bookSignature:"Yann H. Chemin",coverURL:"https://cdn.intechopen.com/books/images_new/8444.jpg",editedByType:"Edited by",editors:[{id:"270578",title:"Dr.",name:"Yann",surname:"Chemin",slug:"yann-chemin",fullName:"Yann Chemin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"},chapters:[{id:"67064",title:"Introductory Chapter: A Tipping Point for a Return to the Moon",slug:"introductory-chapter-a-tipping-point-for-a-return-to-the-moon",signatures:"Yann H. Chemin",authors:[{id:"270578",title:"Dr.",name:"Yann",middleName:"H.",surname:"Chemin",fullName:"Yann Chemin",slug:"yann-chemin"}]},{id:"65612",title:"Initial Evolution of the Moon",slug:"initial-evolution-of-the-moon",signatures:"Khachay Yuriy",authors:[{id:"225379",title:"Prof.",name:"Yuriy",middleName:null,surname:"Khachay",fullName:"Yuriy Khachay",slug:"yuriy-khachay"}]},{id:"65725",title:"On the Deviation of the Lunar Center of Mass to the East: Two Possible Mechanisms Based on Evolution of the Orbit and Rounding Off the Shape of the Moon",slug:"on-the-deviation-of-the-lunar-center-of-mass-to-the-east-two-possible-mechanisms-based-on-evolution-",signatures:"Boris P. Kondratyev",authors:[{id:"277909",title:"Prof.",name:"Boris",middleName:"Petrovich",surname:"Kondratyev",fullName:"Boris Kondratyev",slug:"boris-kondratyev"}]},{id:"65508",title:"New Principles of Monitoring Seismological and Deformation Processes Occurring in the Moon Rock Massive",slug:"new-principles-of-monitoring-seismological-and-deformation-processes-occurring-in-the-moon-rock-mass",signatures:"Olga Hachay and Oleg Khachay",authors:[{id:"150801",title:"Prof.",name:"Olga",middleName:"Alexandrovna",surname:"Hachay",fullName:"Olga Hachay",slug:"olga-hachay"},{id:"263300",title:"Dr.",name:"Oleg",middleName:null,surname:"Khachay",fullName:"Oleg Khachay",slug:"oleg-khachay"}]},{id:"66992",title:"Lunar Occultation",slug:"lunar-occultation",signatures:"Abdulrahman Malawi",authors:[{id:"282963",title:"Dr.",name:"Abdulrahman",middleName:"Ali",surname:"Malawi",fullName:"Abdulrahman Malawi",slug:"abdulrahman-malawi"}]},{id:"65534",title:"Solar System Exploration Augmented by In Situ Resource Utilization: Lunar Base Issues",slug:"solar-system-exploration-augmented-by-in-situ-resource-utilization-lunar-base-issues",signatures:"Bryan Palaszewski",authors:[{id:"279275",title:"M.Sc.",name:"Bryan",middleName:null,surname:"Palaszewski",fullName:"Bryan Palaszewski",slug:"bryan-palaszewski"}]},{id:"65461",title:"Human Health in the Lunar Environment",slug:"human-health-in-the-lunar-environment",signatures:"Robert J. Reynolds",authors:[{id:"220737",title:"Dr.",name:"Robert",middleName:null,surname:"J. Reynolds",fullName:"Robert J. Reynolds",slug:"robert-j.-reynolds"}]}]}],publishedBooks:[{type:"book",id:"1629",title:"Astrophysics",subtitle:null,isOpenForSubmission:!1,hash:"95209a68cff9bc045b51611c513b63bd",slug:"astrophysics",bookSignature:"Ibrahim Kucuk",coverURL:"https://cdn.intechopen.com/books/images_new/1629.jpg",editedByType:"Edited by",editors:[{id:"102957",title:"Prof.",name:"İbrahim",surname:"Küçük",slug:"ibrahim-kucuk",fullName:"İbrahim Küçük"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8444",title:"Lunar Science",subtitle:null,isOpenForSubmission:!1,hash:"f1dcf511a174e8ec89d97ca8c0c6146a",slug:"lunar-science",bookSignature:"Yann H. Chemin",coverURL:"https://cdn.intechopen.com/books/images_new/8444.jpg",editedByType:"Edited by",editors:[{id:"270578",title:"Dr.",name:"Yann",surname:"Chemin",slug:"yann-chemin",fullName:"Yann Chemin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7338",title:"Planetology",subtitle:"Future Explorations",isOpenForSubmission:!1,hash:"d52566a2f61bb3d7021ed630a149e1e6",slug:"planetology-future-explorations",bookSignature:"Bryan Palaszewski",coverURL:"https://cdn.intechopen.com/books/images_new/7338.jpg",editedByType:"Edited by",editors:[{id:"279275",title:"M.Sc.",name:"Bryan",surname:"Palaszewski",slug:"bryan-palaszewski",fullName:"Bryan Palaszewski"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],publishedBooksByAuthor:[{type:"book",id:"1629",title:"Astrophysics",subtitle:null,isOpenForSubmission:!1,hash:"95209a68cff9bc045b51611c513b63bd",slug:"astrophysics",bookSignature:"Ibrahim Kucuk",coverURL:"https://cdn.intechopen.com/books/images_new/1629.jpg",editedByType:"Edited by",editors:[{id:"102957",title:"Prof.",name:"İbrahim",surname:"Küçük",slug:"ibrahim-kucuk",fullName:"İbrahim Küçük"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6768",title:"Cosmic Rays",subtitle:null,isOpenForSubmission:!1,hash:"1578350f18d0bc3abfbcf62278630739",slug:"cosmic-rays",bookSignature:"Zbigniew Szadkowski",coverURL:"https://cdn.intechopen.com/books/images_new/6768.jpg",editedByType:"Edited by",editors:[{id:"67836",title:"Prof.",name:"Zbigniew Piotr",surname:"Szadkowski",slug:"zbigniew-piotr-szadkowski",fullName:"Zbigniew Piotr Szadkowski"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},onlineFirst:{chapter:{type:"chapter",id:"78676",title:"Pelvic Anatomy for Distal Rectal Cancer Surgery",doi:"10.5772/intechopen.99120",slug:"pelvic-anatomy-for-distal-rectal-cancer-surgery",body:'Colorectal cancer is the third most common cancer and the fourth leading cause of cancer-related deaths worldwide [1]. Especially, rectal cancer accounts for 30–40% of colorectal cancer, and the treatment strategy is different and more complicated compared to colon cancer because of its anatomical features. Although the treatment outcome of rectal cancer has greatly improved with the development of multimodality treatment including neoadjuvant radiotherapy, cytotoxic chemotherapy, and target agents, surgery remains the mainstay of therapy. Since the concept of total mesorectal excision (TME) was first described by Richard Heald in 1979, this procedure became the gold standard technique for rectal cancer surgery until now [2]. The fundamental principle of TME is en bloc resection of the rectum with its surrounding fatty tissue complex which contains the blood vessels and lymphatics down to the pelvic floor. To achieve complete TME and sphincter preserving surgery in low-lying rectal cancer, knowledge for regarding the pelvic fascia (mesorectal, parietal) and autonomic nerves, a thorough understanding of the pelvic floor anatomy is essential.
The rectum is the most distal part of the large intestine that exists from the sacral promontory level to the anorectal ring. The anterior and lateral portion of the upper one-third of the rectum is covered with peritoneum, and the middle one-third of the rectum is covered with peritoneum on its anterior portion. The lower one-third cannot be observed in the intraperitoneal space because it is located in the extraperitoneal space. The taenia coli disappears in the rectum, forming one longitudinal muscle layer surrounding the rectum. The length of the rectum is approximately 12-15 cm and has three curvatures, which is related to Houston’s valves. The upper and lower part are convex to the right, and the middle portion is convex to the left. The middle valve is the most prominent and is located approximately equal to the level of peritoneal reflection [3].
The rectum is surrounded by a fatty tissue complex called the mesorectum, which corresponds to the mesentery of the rectum. Mesorectum contains abundant blood vessels, lymphatics, and lymph nodes, and it is enveloped by thin visceral pelvic fascia [4]. It is developed thickest in the posterolateral side and the anterior part is formed relatively thin. In addition, the volume of the mesorectum decreases as it approaches the pelvic floor, and disappears approximately 2 cm above the levator ani muscle (Figure 1). A number of studies have revealed that the mesorectum is an important structure for tumor spreading, and en bloc resection through sharp dissection of mesorectum is very important in improving treatment outcomes [2, 5, 6].
Anatomy of the rectum and mesorectum. (a) Structures around the rectum. The rectum is surrounded by mesorectum, and the rectum and mesorectum are enveloped by the fascia propria of the rectum. (b) Total mesorectal excision (TME). En bloc resection of mesorectum is important.
Dissecting the correct anatomical plane can lead to good oncological outcomes and preserve the autonomic nerves to prevent postoperative urinary, sexual, and defecatory dysfunction. If pelvic dissection is performed along the exact embryologic fascial plane, the operation can be done without bleeding. To perform precise total mesorectal excision, a thorough understanding of the fascia around the rectum and pelvic cavity is essential. Figure 2 shows the anatomical relationship of the fascia around the rectum.
Anatomy of fascia around the rectum. The fascia propria of the rectum covers the rectum and mesorectum. The presacral fascia covers the anterior surface of the sacrum. It combines with the fascia propria of the rectum at the S4 level (recto-sacral fascia = Waldeyer’s fascia). Denonvilliers’ fascia is a dense membrane between the rectum and seminal vesicles.
The rectum and mesorectum are enveloped by the fascia propria of the rectum, also called as mesorectal fascia. The mesorectal fascia corresponds to the visceral fascia of the rectum. Caudally, it ends at the internal sphincter and laterally ends at the internal iliac artery, and is connected to the parietal pelvic fascia [7]. A magnetic resonance image scan (MRI) can clearly show the boundaries of these mesorectum and mesorectal fascia (Figure 3). During total mesorectal excision, it is important to completely excise this mesorectal fascia without damage to obtain optimal oncologic outcome [6, 8, 9].
Magnetic resonance image scan. Magnetic resonance image scan (MRI) can clearly show the boundaries of these mesorectum and mesorectal fascia. (a) T2 weighted image on MRI. Axial view. The rectum and mesorectum are enveloped by the fascia propria of the rectum (mesorectal fascia). (b) T2 weighted image on MRI. Coronal view. Mesorectum, mesorectal fascia, and puborectalis muscle.
The presacral fascia, also called as parietal pelvic fascia, covers the anterior surface of the sacrum and encloses the sacral vessels and nerves. It combines with the mesorectal fascia at the S4 level and became part of the anococcygeal ligament at the level of anorectal junction. The presacral venous plexus is formed by the two lateral sacral veins, the middle sacral vein, and the communicating veins, and it runs underneath the presacral fascia. If the dissection plane is too deep to damage the presacral fascia during the posterior dissection, life-threatening massive bleeding can occur and it often is difficult to control. Therefore, dissection should be done along with the space between the mesorectal fascia and the presacral fascia until the recto-sacral fascia is encountered [10, 11].
Recto-sacral fascia, also known as Waldeyer’s fascia, is a dense connective tissue linking the presacral fascia to the mesorectal fascia at the S4 level. As the posterior dissection proceeds down along the plane between the mesorectal fascia and the presacral fascia, a dense, tough recto-sacral fascia is identified. To enter the retro-rectal space and reach the pelvic floor, this fascia must be incised and dissected further caudally. This fascia has a different thickness from individuals, it is not visible when it is too thin. Because the presacral artery and venous plexus and autonomic nerves pass behind this fascia, it is important to perform sharp division to avoid excessive bleeding due to presacral vein injury (Figure 4) [8, 12].
Recto-sacral fascia (Waldeyer’s fascia). Recto-sacral fascia (Waldeyer’s fascia) is a dense connective tissue linking the presacral fascia to the mesorectal fascia at the S4 level. It is important to perform sharp dissection [
During the anterior dissection of the rectum, a thin, dense connective tissue layer known as the Denonvilliers’ fascia presents between the seminal vesicles and rectum [13]. The rectum can be separated from the seminal vesicles and prostate by opening this membrane at the level of anterior peritoneal reflection. After incising the fascia and entering the embryologic plane between the rectum and the seminal vesicles, the dissection should be performed below the Denonvilliers’ fascia [14]. It is because there were neurovascular bundles running from the pelvic plexus to the ventral side of the Denonvilliers’ fascia, especially in the directions of 10 and 2 o’clock, and these neurovascular bundles were related to urogenital function (Figure 5) [15]. However, if the deeply infiltrative tumor is located on the anterior wall of the rectum, the dissection should be performed in front of the Denonvilliers’ fascia for curative resection. In females, there is a thin membranous structure that separates the rectum and vagina, which is called the rectovaginal septum. Although Denonvilliers reported that the Denonvilliers’ fascia was not present in females, many researchers considered that the rectovaginal septum was consistent with the Denonvilliers’ fascia in males (Figure 6) [16, 17, 18, 19]. During the anterior dissection of the rectum in female, care must be taken not to perforate the vagina since this septum is very thin.
Denonvilliers’ fascia. During anterior dissection of the rectum. The dense connective tissue between rectum and seminal vesicles can be seen. The dissection should be performed below the Denonvilliers’ fascia.
Rectovaginal septum. In female, the rectovaginal septum was consistent with the denonvilliers’ fascia in male.
The rectum enters the pelvic floor and becomes the anus. The anal canal is defined as from the dentate line to the anal verge by anatomists, but most surgeons consider the anal canal from the anorectal ring to the anal verge [20]. The anorectal ring is where the rectum enters the pelvic floor and is angled by the puborectalis muscle. This ring can be palpated by a meticulous digital rectal exam. The dentate line, which divides the upper two-thirds and lower third of the anal canal, is an anatomically important landmark of the anal canal, and there are 6–14 longitudinal folds on the dentate line known as columns of Morgagni (Figure 7). The upper and lower part of the anal canal differs in venous and lymphatic drainage, innervation, and the epithelial surface based on the dentate line. Above the dentate line, the blood drains into the portal venous system, and lymphatics drains to the superior rectal and iliac lymphatic chains. Below the dentate line, the blood drains into the caval system, and lymphatics drain into the inguinal lymph nodes.
Anal canal and anal sphincter complex. (a) The dentate line divides the upper two thirds and lower third of the anal canal, and there are longitudinal folds known as columns of Morgagni. The external sphincter consists of three separate parts: Subcutaneous, superficial, and deep part [
There are two sphincter muscles surrounding the anus, the internal sphincter and the external sphincter. The internal sphincter is connected from the inner circular smooth muscle of the rectum and descends to 1–1.5 cm below the dentate line. Its length is about 2.5–4 cm and the mean thickness is about 0.5 cm. It is an involuntary smooth muscle and plays an important role in the maintenance of fecal incontinence because it contributes a majority of the resting pressure of the anal canal. The outer longitudinal muscle of the rectum conjoins the fibers from the puborectalis muscle and is located between the external and internal sphincter. The external sphincter muscle is a striated muscle surrounding the internal sphincter in the shape of a cylinder, and it extends slightly below the internal sphincter. The external sphincter consists of three separate parts: subcutaneous, superficial, and deep part. The subcutaneous external sphincter attaches to the perianal skin encircling the anus. The external anal sphincter is innervated by the rectal branch of the pudendal nerve and is under voluntary control [20, 22, 23]. The intersphincteric groove between the internal and external sphincter is an important landmark in surgery for patients with distal rectal cancer such as intersphincteric resection (ISR) [24].
The pelvic floor is a structure that forms the bottom of the pelvis, and plays an important role in supporting the pelvic organs. In the past, pelvic floor muscles could not be visualized clearly, however, the development of magnetic resonance imaging assessments and improvements in minimally invasive surgery techniques such as laparoscopy and robotic surgery can clearly show the anatomy of this region It is mainly composed of the levator ani muscle complex: pubococcygeus, iliococcygeus, and puborectalis muscle. The levator ani muscle received direct innervation from sacral nerve roots (S3-S5) and play an important role in cooperative action through coordinated contraction and relaxation during defecation [25]. The pubococcygeus is located in the most anterior portion of the levator ani muscles, and from both pubic bone to the coccyx. The iliococcygeus is the posterior part of the levator ani muscle and extends from the ischial spine to the anococcygeal raphe and coccyx. The puborectalis muscle, which is located below the pubococcygeus, forms a U-shaped ring around the rectum and makes an anorectal angle to prevent fecal incontinence. The coccygeus muscle, which is also a part of the pelvic floor, is located posterior portion of the levator ani muscle and reinforces the posterior pelvic floor (Figure 8) [20]. The pelvic floor has two hiatuses: the urogenital hiatus and the rectal hiatus. The rectal hiatus is located in the posterior of the pelvic floor through which the anal canal passes. The perineal body, a pyramidal fibromuscular mass, is located between the urogenital hiatus and the anal canal, strengthens the pelvic floor [26]. During distal rectal cancer surgery for sphincter preservation such as ISR, the intersphincteric space between the puborectalis muscle and the rectal wall should be identified, and the dissection continues down to the deep part of the anal canal through the intersphincteric space (Figure 9) [24]. On the other hand, during an abdominoperineal resection, the levator ani muscles must be cut [27].
Anatomy of the pelvic floor. (a) Inferior view. The levator ani muscle consists of pubococcygeus, iliococcygeus, and puborectalis muscle [
Levator ani muscles and intersphincteric space. (a) Puborectalis and pubococcygeus muscle. (b) Intersphincteric space between rectum and puborectalis muscle.
The anococcygeal ligament is a fibrous membrane, which extends between the coccyx and the margin of the anal canal. In an anatomical study, the anococcygeal ligament was divided into two layers. The ventral layer of the ligament was loose and rich in small and fragile vessels and extended from the presacral fascia to the conjoint longitudinal muscle layer of the anal canal. The dorsal layer of the ligament was thin and dense and extended between the coccyx and external anal sphincter (Figure 10) [28]. To fully mobilize the rectum from the pelvic floor at the final stage of total mesorectal excision, the anococcygeal ligament must be divided. If the anococcygeal ligament cannot be seen in the final step, it can be visualized after the mesorectum is completely mobilized from the pelvic floor.
Anococcygeal ligament. (a) Anococcygeal ligament and pelvic floor. During posterior dissection of the rectum. (b) Anococcygeal ligament during cadeveric dissection. Lt. hemipelvis.
In case of very low-lying rectal cancer, several surgical options can be considered (Figure 11). If the tumor did not invade the anal sphincter complex, the ultra-low anterior resection with coloanal anastomosis could be considered. If the tumors are located close to the dentate line, the intersphincteric resection (ISR) could be considered. The ISR is the partial or complete resection of the internal anal sphincter along the intersphincteric plane. However, if the tumor invades the external sphincter complex, the abdominoperineal resection (APR) should be performed. For invasive low rectal cancer which invades the levator ani muscle, extralevator APR (ELAPE) should be considered to achieve adequate resection margin. The ELAPE is the cylindrical anorectal excision and removes more tissue around the tumor including levator ani muscle (Figure 12). This procedure has the advantage of reducing the risk of tumor perforation during operation and acquiring sufficient safety resection margin, but there is still controversy about the long-term oncologic outcome [29]. In addition, the postoperative complications can be increased due to the wide resection range.
Low-lying rectal cancer. (a) T2 weighted image on MRI. Coronal view. The low-lying rectal cancer invades internal anal sphincter. (b) T2 weighted image on MRI. Sagittal view.
Sugical plane for low-lying rectal cancer. (a) Low anterior resection (LAR). (b) Intersphincteric resection (ISR). (c) Abdominoperineal resection (APR). (d) Extralevator APR.
In terms of quality of life, the importance of not only oncological outcomes but also functional outcomes such as urinary function, sexual function, and defecatory function after rectal cancer surgery have been emphasized. Urinary dysfunction after rectal surgery occurs in approximately 27%, and it includes difficulty emptying the bladder and incontinence [30, 31]. Sexual dysfunction for males consists of erectile dysfunction, absence of ejaculation, or retrograde ejaculation. For females, it causes sexual dysfunction such as impaired ability to achieve orgasm, decreased vaginal secretion, or dyspareunia [15]. The major cause of postoperative urogenital dysfunction is autonomic nerve damage that occurs during surgery. As minimally invasive surgery such as laparoscopy and robotic approach develops, meticulous nerve preserving surgery became possible with good visualization of the pelvic autonomic nerves [32, 33, 34]. To preserve the postoperative urogenital function, a thorough understanding of the anatomy of the pelvic autonomic nerve is crucial.
The superior hypogastric plexus, which is a collection of sympathetic nerve bundles arising from T10-L3, forms a dense nerve plexus at the anterior area to the body of L5 and bifurcates into hypogastric nerves at the level of the sacral promontory (Figure 13). The superior hypogastric plexus runs around the inferior mesenteric artery. Therefore, this nerve can be damaged during dissection around the origin of the inferior mesenteric artery, and it results in retrograde ejaculation, urinary incontinence [35]. The hypogastric nerve crosses the left common iliac artery at the level of the first sacrum and descends to the pelvic cavity along the lateral pelvic wall.
Hypogastric nerves. The hypogastric nerves run from the superior hypogastric plexus and descend to the pelvic cavity and meet the pelvic splanchnic nerves.
The pelvic splanchnic nerves are considered to be parasympathetic nerves that arise from the second to fourth sacral spinal nerves. These nerves enter the pelvis through the sacral foramen, posterior to the parietal fascia that covers the piriformis muscle and crosses the retrorectal space, to enter the visceral compartment through the visceral fascia about 4 cm from the midline. Small branches of the pelvic splanchnic nerves run medially and enter the mesorectum (Figure 14). These nerves regulate the emptying of the urinary bladder and influence erectile functions and motility of the rectum. Therefore, damage to these nerves causes erectile dysfunction and decreased blood flow to the vagina and vulva, which can reduce vaginal lubrication.
Pelvic splanchnic nerves. The pelvic splanchnic nerves arise from the S2 to S4 spinal nerves. Small branches of the pelvic splanchnic nerves run medially and enter the mesorectum.
The pelvic splanchnic nerves meet the hypogastric nerves and form the inferior hypogastric plexus at the lateral pelvic wall. It lies outside the fascia propria in the superficial layer of the parietal fascia. The inferior hypogastric plexus can be observed as a mesh-like structure at the posterolateral pelvic wall close to the prostate and seminal vesicles. Because the inferior hypogastric plexus consists of both sympathetic and parasympathetic efferent fibers, any damage to this plexus may cause severe disturbances in urogenital and sexual function including erection and ejaculation. It extends forward to form neurovascular bundles running down the seminal vesicle at 2 o’clock and 10 o’clock direction (Figure 15). These neurovascular bundles run through the posterolateral border of the prostate and continue to the periprostatic plexus, which supplies to the prostate, seminal vesicles, corpi cavernosi, and the vas deferens [15, 36]. Injury to the neurovascular bundles during anterior dissection may cause urinary and sexual dysfunction. Meticulous dissection is required because nerve damage may occur when surgery is performed along the wrong plane or excessive traction is performed.
Inferior hypogastric (pelvic) plexus. The inferior hypogastric (pelvic) plexus is a network of sympathetic and parasympathetic fibers arising from the hypogastric nerves and the pelvic splanchnic nerves. It can be observed as a mesh-like structure at the posterolateral pelvic wall. It extends forward to form neurovascular bundles running down the seminal vesicle on both sides.
The rectum is surrounded by a fatty tissue complex called the mesorectum, which contains abundant blood vessels, lymphatics, and lymph nodes. The rectum and mesorectum are enveloped by the mesorectal fascia. During total mesorectal excision, it is important to completely excise this mesorectal fascia without damage. The mesorectal fascia conjoins with the recto-sacral fascia, which extends forward from the presacral fascia at the level of S4, and descends to the pelvic floor. To enter the retro-rectal space and reach the pelvic floor, this fascia must be incised and sharp dissection should be performed to prevent severe bleeding due to injury to the presacral plexus. During the anterior dissection of the rectum, it is important to recognize Denonvillers’ fascia located between the rectum and seminal vesicles, and dissection should be performed below the Denonvilliers’ fascia. The pelvic floor is a structure that forms the bottom of the pelvis and is mainly composed of the levator ani muscle complex: pubococcygeus, iliococcygeus, and puborectalis muscle. The levator ani muscle received direct innervation from sacral nerve roots (S3-S5) and play an important role in cooperative action during defecation. To reach the deep part of the anal canal, the dissection should be performed between the puborectalis muscle and the rectal wall. During the whole process of TME, surgeons should take care to identify and preserve the autonomic nerve in order to avoid postoperative urogenital dysfunction. Care should be taken not to damage the superior hypogastric nerve during IMA ligation, and not to damage the pelvic plexus during posterolateral pelvic dissection. In addition, during anterior dissection of the rectum, it is important to perform meticulous dissection so as not to injure small numerous neurovascular bundles running in the 2 o’clock and 10 o’clock directions of the seminal vesicle. Based on a sufficient understanding of pelvic anatomy, precise surgical techniques using advanced surgical tools will give favorable oncologic and functional outcomes for rectal cancer patients.
The authors declare no conflict of interest.
None.
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He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. Her research interests include immunity against influenza and COVID-19 and the development of immunization schemes for high-risk individuals.",institutionString:'Federal State Budgetary Scientific Institution "Institute of Experimental Medicine"',institution:null},{id:"238958",title:"Mr.",name:"Atamjit",middleName:null,surname:"Singh",slug:"atamjit-singh",fullName:"Atamjit Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/238958/images/6575_n.jpg",biography:null,institutionString:null,institution:null},{id:"252058",title:"M.Sc.",name:"Juan",middleName:null,surname:"Sulca",slug:"juan-sulca",fullName:"Juan Sulca",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252058/images/12834_n.jpg",biography:null,institutionString:null,institution:null},{id:"191392",title:"Dr.",name:"Marimuthu",middleName:null,surname:"Govindarajan",slug:"marimuthu-govindarajan",fullName:"Marimuthu Govindarajan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/191392/images/5828_n.jpg",biography:"Dr. M. Govindarajan completed his BSc degree in Zoology at Government Arts College (Autonomous), Kumbakonam, and MSc, MPhil, and PhD degrees at Annamalai University, Annamalai Nagar, Tamil Nadu, India. He is serving as an assistant professor at the Department of Zoology, Annamalai University. His research interests include isolation, identification, and characterization of biologically active molecules from plants and microbes. He has identified more than 20 pure compounds with high mosquitocidal activity and also conducted high-quality research on photochemistry and nanosynthesis. He has published more than 150 studies in journals with impact factor and 2 books in Lambert Academic Publishing, Germany. He serves as an editorial board member in various national and international scientific journals.",institutionString:null,institution:null},{id:"274660",title:"Dr.",name:"Damodar",middleName:null,surname:"Paudel",slug:"damodar-paudel",fullName:"Damodar Paudel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274660/images/8176_n.jpg",biography:"I am DrDamodar Paudel,currently working as consultant Physician in Nepal police Hospital.",institutionString:null,institution:null},{id:"241562",title:"Dr.",name:"Melvin",middleName:null,surname:"Sanicas",slug:"melvin-sanicas",fullName:"Melvin Sanicas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241562/images/6699_n.jpg",biography:null,institutionString:null,institution:null},{id:"322007",title:"Dr.",name:"Maria Elizbeth",middleName:null,surname:"Alvarez-Sánchez",slug:"maria-elizbeth-alvarez-sanchez",fullName:"Maria Elizbeth Alvarez-Sánchez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",country:{name:"Mexico"}}},{id:"337443",title:"Dr.",name:"Juan",middleName:null,surname:"A. Gonzalez-Sanchez",slug:"juan-a.-gonzalez-sanchez",fullName:"Juan A. Gonzalez-Sanchez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico System",country:{name:"United States of America"}}},{id:"337446",title:"Dr.",name:"Maria",middleName:null,surname:"Zavala-Colon",slug:"maria-zavala-colon",fullName:"Maria Zavala-Colon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico, Medical Sciences Campus",country:{name:"United States of America"}}},{id:"338856",title:"Mrs.",name:"Nur Alvira",middleName:null,surname:"Pascawati",slug:"nur-alvira-pascawati",fullName:"Nur Alvira Pascawati",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universitas Respati Yogyakarta",country:{name:"Indonesia"}}}]}},subseries:{item:{id:"8",type:"subseries",title:"Bioinspired Technology and Biomechanics",keywords:"Bioinspired Systems, Biomechanics, Assistive Technology, Rehabilitation",scope:'Bioinspired technologies take advantage of understanding the actual biological system to provide solutions to problems in several areas. Recently, bioinspired systems have been successfully employing biomechanics to develop and improve assistive technology and rehabilitation devices. The research topic "Bioinspired Technology and Biomechanics" welcomes studies reporting recent advances in bioinspired technologies that contribute to individuals\' health, inclusion, and rehabilitation. Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",hasOnlineFirst:!1,hasPublishedBooks:!0,annualVolume:11404,editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",slug:"adriano-andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",biography:"Dr. Adriano de Oliveira Andrade graduated in Electrical Engineering at the Federal University of Goiás (Brazil) in 1997. He received his MSc and PhD in Biomedical Engineering respectively from the Federal University of Uberlândia (UFU, Brazil) in 2000 and from the University of Reading (UK) in 2005. He completed a one-year Post-Doctoral Fellowship awarded by the DFAIT (Foreign Affairs and International Trade Canada) at the Institute of Biomedical Engineering of the University of New Brunswick (Canada) in 2010. Currently, he is Professor in the Faculty of Electrical Engineering (UFU). He has authored and co-authored more than 200 peer-reviewed publications in Biomedical Engineering. He has been a researcher of The National Council for Scientific and Technological Development (CNPq-Brazil) since 2009. He has served as an ad-hoc consultant for CNPq, CAPES (Coordination for the Improvement of Higher Education Personnel), FINEP (Brazilian Innovation Agency), and other funding bodies on several occasions. He was the Secretary of the Brazilian Society of Biomedical Engineering (SBEB) from 2015 to 2016, President of SBEB (2017-2018) and Vice-President of SBEB (2019-2020). He was the head of the undergraduate program in Biomedical Engineering of the Federal University of Uberlândia (2015 - June/2019) and the head of the Centre for Innovation and Technology Assessment in Health (NIATS/UFU) since 2010. He is the head of the Postgraduate Program in Biomedical Engineering (UFU, July/2019 - to date). He was the secretary of the Parkinson's Disease Association of Uberlândia (2018-2019). Dr. Andrade's primary area of research is focused towards getting information from the neuromuscular system to understand its strategies of organization, adaptation and controlling in the context of motor neuron diseases. 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We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. 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