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Colorectal Cancer Diagnosis and Therapeutic Updates Edited by Sankha Bhattacharya Department of Pharmaceutics School of Pharmacy & Technology Management SVKM'S NMIMS Deemed-to-be University India Amit Page Department of Pharma Science School of Pharmacy & Technology Management SVKM'S NMIMS Deemed-to-be University India Saurabh Maru Department of Pharmacology School of Pharmacy & Technology Management SVKM'S NMIMS Deemed-to-be University India & Shilpa Dawre Department of Pharmaceutics School of Pharmacy & Technology Management SVKM'S NMIMS Deemed-to-be University India Colorectal Cancer Diagnosis and Therapeutic Updates Editors: Sankha Bhattacharya, Amit Page, Saurabh Maru and Shilpa Dawre ISBN (Online): 978-981-5040-94-4 ISBN (Print): 978-981-5040-95-1 ISBN (Paperback): 978-981-5040-96-8 © 2022, Bentham Books imprint. Published by Bentham Science Publishers Pte. Ltd. Singapore. All Rights Reserved. First published in 2022 BENTHAM SCIENCE PUBLISHERS LTD. 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Ltd. 80 Robinson Road #02-00 Singapore 068898 Singapore Email: [email protected] CONTENTS FOREWORD ........................................................................................................................................... i PREFACE ................................................................................................................................................ ii ACKNOWLEDGEMENT ...................................................................................................................... iv LIST OF CONTRIBUTORS .................................................................................................................. v CHAPTER 1 COLORECTAL CANCER DIAGNOSIS .................................................................... 1 Sankha Bhattacharya, Amit Page, Kapil Gore and Amaiyya Agrawal INTRODUCTION .......................................................................................................................... 1 Invasive Examination .............................................................................................................. 2 NON-INVASIVE DIAGNOSIS METHODS ................................................................................ 3 Fecal Occult Blood Test .......................................................................................................... 3 Non-enzymatic Tumor Markers .............................................................................................. 4 Lysosomal Exoglycosidases as Potential CRC Markers ........................................................ 5 CONCLUSION ............................................................................................................................... 6 CONSENT FOR PUBLICATION ................................................................................................ 6 CONFLICT OF INTEREST ......................................................................................................... 6 ACKNOWLEDGEMENTS ........................................................................................................... 6 REFERENCES ............................................................................................................................... 6 CHAPTER 2 SCREENING FOR COLORECTAL CARCINOMA ................................................ 8 Sankha Bhattacharya, Saurabh Maru and Aseem Setia INTRODUCTION .......................................................................................................................... 8 DETECTION OF EARLY COLORECTAL CARCINOMA ..................................................... 9 EARLY DIAGNOSIS OF COLORECTAL CARCINOMA ...................................................... 9 WHAT IS SCREENING? .............................................................................................................. 9 WHO SHOULD BE SCREENED? ............................................................................................... 9 SCREENING PEOPLE AT AN AVERAGE RISK FOR COLORECTAL CARCINOMA ... 10 Fecal Occult Blood Test .......................................................................................................... 10 Flexible Sigmoidoscopy .......................................................................................................... 11 Combination of FOBT and Flexible Sigmoidoscopy ............................................................. 11 Colonoscopy ........................................................................................................................... 11 SCREENING PEOPLE AT INCREASED RISK FOR COLORECTAL CARCINOMA ...... 12 Genetic Syndromes ................................................................................................................. 12 NEW SCREENING TESTS ........................................................................................................... 13 CT Colonography .................................................................................................................... 13 Faecal Occult Blood Test ........................................................................................................ 13 CONCLUSION ............................................................................................................................... 13 CONSENT FOR PUBLICATION ................................................................................................ 13 CONFLICT OF INTEREST ......................................................................................................... 13 ACKNOWLEDGEMENTS ........................................................................................................... 13 REFERENCES ............................................................................................................................... 14 CHAPTER 3 HISTOPATHOLOGY ................................................................................................... 16 Sankha Bhattacharya, Shilpa Dawre and Dyanesh Saindane INTRODUCTION .......................................................................................................................... 16 NORMAL HISTOLOGY OF COLORECTAL AREA .............................................................. 16 GENERAL PRESENTATION IN COLORECTAL CANCER ................................................. 17 NEED FOR HISTOPATHOLOGICAL INSPECTION IN COLORECTAL CARCINOMA 18 FACTORS INVOLVED IN THE HISTOPATHOLOGICAL ANALYSIS OF COLORECTAL CARCINOMA ................................................................................................... 18 HISTOPATHOLOGIC DIAGNOSIS OF COLORECTAL CANCER ..................................... 19 HISTOLOGIC VARIANTS .......................................................................................................... 20 GRADING OF COLORECTAL CARCINOMA USING HISTOPATHOLOGICAL ANALYSIS ...................................................................................................................................... 20 Process of Grading the Cancers .............................................................................................. 21 Issues with PDC System and their Rectification ........................................................... 22 CONCLUSION ............................................................................................................................... 22 CONSENT FOR PUBLICATION ................................................................................................ 22 CONFLICT OF INTEREST ......................................................................................................... 22 ACKNOWLEDGEMENTS ........................................................................................................... 22 REFERENCES ............................................................................................................................... 22 CHAPTER 4 CHEMOTHERAPY AND COLORECTAL CANCER ............................................. 24 Kapil Gore, Dnyanesh Saindane and Sankha Bhattacharya INTRODUCTION .......................................................................................................................... 24 CHEMOTHERAPY AND COLORECTAL CANCER .............................................................. 24 Administration of Chemotherapeutic Agents ........................................................................ 24 CHEMOTHERAPY IN DIFFERENT STAGES OF COLORECTAL CANCER ................... 25 COMPONENTS OF CHEMOTHERAPY ................................................................................... 26 5-Fluorouracil (5-FU) ............................................................................................................. 26 Irinotecan ................................................................................................................................ 27 Oxaliplatin ............................................................................................................................... 27 NOVEL THERAPIES FOR COLORECTAL CARCINOMA .................................................. 27 Agarose Microbeads ............................................................................................................... 27 Anti-inflammatory Agents ...................................................................................................... 28 Probiotics ................................................................................................................................ 28 Functional Foods ..................................................................................................................... 28 TARGETED THERAPIES ............................................................................................................ 29 Targeting EGFR ...................................................................................................................... 29 Cetuximab and Panitumumab ................................................................................................. 29 BRAF Inhibitors ...................................................................................................................... 30 HER-2 Inhibitors ..................................................................................................................... 30 Targeting VEGF ...................................................................................................................... 30 Bevacizumab ........................................................................................................................... 30 Novel anti-VEGFR Agents ..................................................................................................... 31 HGF/C-MET Pathway ............................................................................................................ 31 HGF Inhibitors ........................................................................................................................ 32 MET Antagonists .................................................................................................................... 32 TKIs ........................................................................................................................................ 32 IMMUNE CHECKPOINT BLOCKADE ..................................................................................... 32 ADJUVANT AND NEOADJUVANT THERAPY USING TARGETED MEDICINE ........... 33 CONCLUSION ............................................................................................................................... 34 CONSENT FOR PUBLICATION ................................................................................................ 34 CONFLICT OF INTEREST ......................................................................................................... 34 ACKNOWLEDGEMENTS ........................................................................................................... 34 REFERENCES ............................................................................................................................... 34 CHAPTER 5 ROBOTICS FOR RECTAL CANCER ....................................................................... 37 Dnyanesh Saindane, Ajay Madrewar and Sankha Bhattacharya INTRODUCTION .......................................................................................................................... 37 TOTAL MESORECTAL EXCISION .......................................................................................... 37 Techniques Abdominoperineal Resection .............................................................................. 38 Coloanal Anastomosis ............................................................................................................ 38 LOCAL EXCISION ....................................................................................................................... 38 Transanal Excision .................................................................................................................. 38 Transcoccygeal Excision ........................................................................................................ 39 Transsphincteric Excision ....................................................................................................... 39 Transanal Endoscopic Microsurgery ...................................................................................... 39 DISADVANTAGES OF SURGICAL TREATMENT FOR RECTAL CANCER ................... 40 Short Term Effects of Surgery ................................................................................................ 40 Long Term Effects .................................................................................................................. 40 LAPAROSCOPIC SURGERY ...................................................................................................... 40 ADVANTAGES OVER CONVENTIONAL SURGICAL METHODS .................................... 40 Short Term Advantages Are: .................................................................................................. 40 Long Term Advantages ........................................................................................................... 41 Limitations of Laparoscopic Surgery ...................................................................................... 41 ROBOTIC SURGERY FOR COLORECTAL CANCER .......................................................... 42 Components of the da Vinci surgical System ......................................................................... 42 Operation of the System .......................................................................................................... 42 OUTCOMES OF DA VINCI SURGICAL SYSTEM ................................................................. 43 Short Term Outcomes ............................................................................................................. 43 Long Term Outcomes ............................................................................................................. 43 CONCLUSION ............................................................................................................................... 44 CONSENT FOR PUBLICATION ................................................................................................ 44 CONFLICT OF INTEREST ......................................................................................................... 44 ACKNOWLEDGEMENTS ........................................................................................................... 44 REFERENCES ............................................................................................................................... 44 CHAPTER 6 LNCRNA NLIPMT INHIBITORS IN COLORECTAL CANCER MANAGEMENT ..................................................................................................................................... 46 Aseem Setia, Sankha Bhattacharya and Amaiyya Agrawal INTRODUCTION .......................................................................................................................... 46 LNCRNA IN COLORECTAL CANCER .................................................................................... 49 HOTAIR .......................................................................................................................................... 50 H19 .......................................................................................................................................... 52 MALAT 1 ............................................................................................................................... 54 INVOLVEMENT OF LNCRNAS IN CRC PATHOGENESIS ................................................. 55 Wnt/β-Catenin Pathway .......................................................................................................... 56 EGFR/IGF-IR SIGNALING (PI3K AND KRAS PATHWAYS) ............................................... 59 TGF-Β SIGNALING PATHWAY ................................................................................................ 60 P53. PATHWAY ............................................................................................................................. 60 EMT PROGRAM ........................................................................................................................... 61 DETAIL DISCUSSION OF EXPERIMENTAL DATA CONDUCTED FOR COLORECTAL CANCER (CRC) ............................................................................................... 61 lncRNA Overexpression TGF-β1 Downregulation by NLIPMT Inhibits Colorectal Cancer Cell Migration and Invasion ................................................................................................... 61 The Activation of KPNA3 by LncRNA DLEU1 Leads to the Advancement of Colorectal Cancer ..................................................................................................................................... 62 CONCLUSION ............................................................................................................................... 63 ABBREVIATIONS ......................................................................................................................... 63 CONSENT FOR PUBLICATION ................................................................................................ 64 CONFLICT OF INTEREST ......................................................................................................... 64 ACKNOWLEDGEMENTS ........................................................................................................... 64 REFERENCES ............................................................................................................................... 64 CHAPTER 7 PATHWAYS IN COLORECTAL CANCER ............................................................. 71 Ajay Madrewar, Kapil Gore and Sankha Bhattacharya INTRODUCTION .......................................................................................................................... 71 CHROMOSOMAL INSTABILITY PATHWAY ........................................................................ 71 Adenomatous Polyposis Coli gene and wnt Signaling Pathway ............................................ 72 TP-53 Mutation ....................................................................................................................... 72 18q Loss of Heterozygosity (LOH) ........................................................................................ 72 MICROSATELLITE INSTABILITY PATHWAY .................................................................... 73 EPIGENETIC INSTABILITY AND CPG METHYLATION ................................................... 73 PI3K/AKT PATHWAY, PTEN, AND TGFΒR2 ......................................................................... 74 SIGNALLING PATHWAYS IN COLORECTAL CANCER .................................................... 75 EGFR/MAPK Signaling Pathway ........................................................................................... 75 Notch Signaling Pathway ........................................................................................................ 75 PI3K Signaling Pathway ......................................................................................................... 76 TGF-βsignalling Pathway ....................................................................................................... 77 Wnt Pathway ........................................................................................................................... 78 CONCLUSION ............................................................................................................................... 79 CONSENT FOR PUBLICATION ................................................................................................ 79 CONFLICT OF INTEREST ......................................................................................................... 79 ACKNOWLEDGEMENTS ........................................................................................................... 79 REFERENCES ............................................................................................................................... 79 CHAPTER 8 RADIOTHERAPY IN COLORECTAL CANCER .................................................... 81 Amit Page, Dnyanesh Saindane and Sankha Bhattacharya INTRODUCTION .......................................................................................................................... 81 TYPES OF RADIATION THERAPY .......................................................................................... 82 CLINICAL TRIALS OR RESEARCH STUDIES OF RADIATION AND CHEMO- RADIATION THERAPY IN COLORECTAL CANCER ......................................................... 83 Neoadjuvant Radiation Therapy ............................................................................................. 86 Probable Side Effects of Radiotherapy ................................................................................... 86 CONCLUSION ............................................................................................................................... 87 CONSENT FOR PUBLICATION ................................................................................................ 87 CONFLICT OF INTEREST ......................................................................................................... 87 ACKNOWLEDGEMENTS ........................................................................................................... 87 REFERENCES ............................................................................................................................... 87 CHAPTER 9 SURVEILLANCE FOR COLORECTAL CANCER ................................................. 90 Saurabh Maru, Kapil Gore and Sankha Bhattacharya INTRODUCTION .......................................................................................................................... 90 COLONOSCOPY ........................................................................................................................... 91 FLEXIBLE SIGMOIDOSCOPY .................................................................................................. 92 CONCLUSIONS ............................................................................................................................. 93 CONSENT FOR PUBLICATION ................................................................................................ 93 CONFLICT OF INTEREST ......................................................................................................... 93 ACKNOWLEDGEMENTS ........................................................................................................... 93 REFERENCES ............................................................................................................................... 93 CHAPTER 10 RECENT THERANOSTICS IN TREATMENT OF COLORECTAL CANCER 95 Shilpa Dawre, Ajay Madrewar and Sankha Bhattacharya INTRODUCTION .......................................................................................................................... 95 NANOFLATFORMS FOR DRUG DELIVERY AND THERANOSTICS ............................... 96 NANOLIPOSOMAL BASED THERANOSTIC NANOPARTICLES ...................................... 97 Prodrug Approach ................................................................................................................... 98 SUPER MAGNETIC IRON-OXIDE NANOPARTICLES (SPIONS) ...................................... 99 CONCLUSION ............................................................................................................................... 100 CONSENT FOR PUBLICATION ................................................................................................ 100 CONFLICT OF INTEREST ......................................................................................................... 100 ACKNOWLEDGEMENTS ........................................................................................................... 101 REFERENCES ............................................................................................................................... 101 CHAPTER 11 MANAGEMENT OF COLORECTAL CANCER ................................................... 103 Sankha Bhattacharya, Amit Page, Saurabh Maru and Shilpa Dawre MANAGEMENT OF COLORECTAL CANCER ...................................................................... 103 HOW CAN YOU PREPARE PATIENTS FOR SURGERY? .................................................... 104 Enhanced Recovery After Surgery (ERAS) ........................................................................... 104 Stomal Therapy ....................................................................................................................... 104 Bowel Preparation ................................................................................................................... 104 Nutritional Interventions ......................................................................................................... 105 LOCAL RECTAL TREATMENT OF RECTAL CANCER (CLINICS IN THE COLON A RECTAL) ........................................................................................................................................ 105 Tumor Evaluation ................................................................................................................... 105 Electrocoagulation .................................................................................................................. 106 Contract Radiotherapy ............................................................................................................ 107 Local Excision ........................................................................................................................ 107 ENDOSCOPIC TREATMENT ..................................................................................................... 108 Snare Polypectomy ................................................................................................................. 108 Endoscopic Mucosal Resection (EMR) .................................................................................. 108 Endoscopic Submucosal Dissection ....................................................................................... 109 WHAT IS THE SURGICAL OPTION FOR COLORECTAL CANCER? .............................. 109 Open Surgery .......................................................................................................................... 109 Laparoscopic Surgery ............................................................................................................. 110 WHAT ARE POSSIBLE COMPLICATIONS? .......................................................................... 110 Immediate ............................................................................................................................... 110 Long Term .............................................................................................................................. 110 WHAT IS THE ROLE OF ADJUVANT CHEMOTHERAPY IN COLORECTAL CANCER TREATMENT? ............................................................................................................ 111 CONCLUSION ............................................................................................................................... 111 CONSENT FOR PUBLICATION ................................................................................................ 112 CONFLICT OF INTEREST ......................................................................................................... 112 ACKNOWLEDGEMENTS ........................................................................................................... 112 REFERENCES ............................................................................................................................... 112 SUBJECT INDEX .................................................................................................................................... 115