Wooshin Cho Knee Joint Arthroplasty 123 Knee Joint Arthroplasty Wooshin Cho Knee Joint Arthroplasty Wooshin Cho Department of Orthopedic Surgery ASAN Medical Center University of Ulsan College of Medicine Seoul Korea, Republic of South Korea ISBN 978-3-642-39388-4 ISBN 978-3-642-39389-1 (eBook) DOI 10.1007/978-3-642-39389-1 Springer Heidelberg New York Dordrecht London Library of Congress Control Number: 2013950313 © Springer-Verlag Berlin Heidelberg 2014 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifi cally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfi lms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifi cally for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher's location, in its current version, and permission for use must always be obtained from Springer. Permissions for use may be obtained through RightsLink at the Copyright Clearance Center. Violations are liable to prosecution under the respective Copyright Law. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specifi c statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein. Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com) Pref ace When I fi rst ventured the fi eld of arthroplasty, I was under the impression that the operation can be performed by simply following the manuals provided by the manufacturers. However, as my apprehension regarding the knee joint arthroplasty increased, I realized that I cannot always only follow the manuals in order to achieve good results and that the entire process starting from patient selection to postoperative treatment is not easy. After an experience of more than 6,000 cases of knee arthroplasty in the last 20 years, I came to believe that arthroplasty is an interesting and highly gratifying operation that requires deep contemplation. During this time, I wandered a lot academically. I was unsure of my own beliefs whenever others shared their opinion with me. There must have been some truth in their opinion, but I always felt that the actual truth was hidden somewhere which I must explore. Of course, there could be more than one truth and numerous academic theories. Even then, I was surprised to see that the relatively widely accepted theories did not stand true practically. I am certain that many other surgeons must have experienced these problems which I was confronted with. I am well aware that my arguments must have evidence-based academic background. However, it was sometimes diffi cult to prove certain theories due to the numerous variables and I was also confronted with several obstacles to present my opinion which was different from the preexisting theory. Nevertheless, I could not keep everything to myself. I just wanted to share my opinion with the other surgeons. This was the fi rst motivational factor for writing this book. As my experience increased, I realized that I should always keep thinking about the operative procedures, I should not overlook any of the operation fi ndings, and I should be able to feel even the smallest difference during the operation in order to achieve better results. However, this was not described in any other book as it was not easy to express this in words. Also, I have devel- oped a few surgical tips throughout these years and I thought that it would be valuable to share them with the other surgeons. This was the second motivational factor for writing this book. For a carpenter to build a good house, a good design and good materials are needed, and it should be built using good tools. In arthroplasty, the tools used for the operation should ensure convenience, accuracy, and reproducibility, but many surgical instruments lack these proper- ties. I have modifi ed the existing surgical instruments and have also invented some new surgi- cal instruments. Although these surgical instruments have undergone many trials and errors, some of the surgical instruments that I have invented are still very useful. I wanted to share the information regarding these surgical tools with the other surgeons. This was the third motiva- tional factor for writing this book. These motivational factors gave me the energy to write this book. I have reviewed about 1,500 articles and 5–6 textbooks in about 3 years and have exerted my opinion to publish the Korean version of “Knee Joint Arthroplasty” in 2004. Seeing the enthusiasm of my readers, I felt that it was my responsibility to revise the fi rst edition, and I published the second edition in 2007. With encouragement from the Korean readers and a few colleagues, I planned to publish the English version and I have also added new concepts and theories in the second edition of the Korean version. v vi Preface It is not easy for a person to write a book all by himself, and there may be some shortcom- ings. First, there may be a lack of in-depth knowledge. Since my knowledge is limited, I have tried to read and refer to as many articles as possible. Second, my perspectives on the contents may be biased. I believe that this part has improved to a great extent in comparison with the fi rst and second editions of the Korean version. Third, some of the descriptions may be inac- curate. I promise to keep making corrections. On the other hand, there are some benefi ts as well. The descriptions are well organized and consistent, making it easier for the readers to read and comprehend. Since English is not my native language, some of the expressions may sound awkward for the English readers. This was the biggest obstacle for me in writing the English version. I have tried to use the appropriate expressions at most places, but I do agree that some of the expres- sions are still strange. I hope that my readers will point out these mistakes so that I can publish a much better written book next time. This book consists of ten chapters that are arranged in the order of management of the patients. Each chapter provides theoretical information as well as surgical tips, and the main points have been emphasized in italics. I have described my thoughts and have given tips in the boxes of “Author’s Opinion” and “Author’s Method” after describing certain theories or tech- niques. Although some of the readers may not agree with my thoughts, my comments would help my readers summarize and apprehend the concepts and techniques of the knee joint arthroplasty. I hope to interact with many more surgeons through this book and contribute to the aca- demic foundation and surgical advancement of knee joint arthroplasty. Finally, many people have helped me publish this book. First, I would like to give my appreciation to my wife and my three daughters who have supported me throughout. Second, I would like to thank the prior Dean and Professor Key Yong, Kim who guided me to become an orthopedic surgeon. Third, I would like to thank Professor Yoon Seok Yeom, who will succeed this book after me, and Doctor Young Sun Yoon, Seongeun Byun, and Kunal Dhurve who have helped me arrange the contents of this book. Finally, I would also like to thank the offi cials at the Department of Orthopedic Surgery, Asan Medical Center and offi cials of Springer Korea. Seoul , South Korea Wooshin Cho Contents 1 Patient Selection. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1.1 Social Conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1.2 Economic Conditions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1.3 Psychological Conditions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1.4 Indication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 1.4.1 Age. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 1.4.2 Physical Conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 1.4.3 Knee Joint Conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 1.4.4 Surgeon’s Experience. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 1.5 Contraindications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 2 Implant Selection. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 2.1 Material. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 2.1.1 Metal. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 2.1.2 Ceramic. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 2.1.3 Polyethylene (Ultrahigh Molecular Weight Polyethylene: UHMWPE, PE) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 2.1.4 Bone Cement (Polymethylmethacrylate, PMMA). . . . . . . . . . . . . . . 19 2.2 Design. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 2.2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 2.2.2 Anatomy and Biomechanics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 2.2.3 Factors to Be Considered in Implant Design . . . . . . . . . . . . . . . . . . . 24 2.3 Design of Each Component . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 2.3.1 Femur . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 2.3.2 Tibia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41 2.3.3 Spacer (Polyethylene). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 2.3.4 Patella. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 2.3.5 Size Matching. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 2.3.6 Options. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 2.3.7 Design to Increase Knee Flexion . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 2.4 Surgical Instruments. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 2.4.1 Surgical Instruments for Use in TKA. . . . . . . . . . . . . . . . . . . . . . . . . 53 2.4.2 Implant-Specifi c Surgical Instruments. . . . . . . . . . . . . . . . . . . . . . . . 59 Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60 3 Preparation for the Operation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 3.1 Admission Checkup . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 3.1.1 History Taking . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 3.1.2 Physical Examination. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68 3.1.3 Preoperative Evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68 vii viii Contents 3.2 Final Decision. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68 3.3 Outcome Study. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71 3.3.1 HSS Score. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71 3.3.2 Knee Society Score. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73 3.3.3 Knee Society Total Knee Arthroplasty Roentgenographic Evaluation System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74 3.3.4 WOMAC Score (The Western Ontario and McMaster Universities Osteoarthritis Index Score). . . . . . . . . . . . . . . . . . . . . . . 76 3.3.5 SF-36 (36-Item Short-Form Health Survey) or MOS (Medical Outcomes Study). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77 3.3.6 Patellofemoral Scoring System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78 3.3.7 Miscellaneous Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78 3.4 Patient Education . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 3.5 Final Checkup for the Operation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 3.5.1 Consent Form. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 3.5.2 Medical Preparation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80 3.5.3 Preparation for Anesthesia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80 3.5.4 Knee Joint Preparation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 4 Surgical Techniques. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 4.1 Drape . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 4.2 Surgical Approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 4.2.1 Skin Incision. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84 4.2.2 Arthrotomy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86 4.2.3 Ancillary Procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89 4.3 Soft Tissue Procedure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92 4.3.1 Cruciate Ligament Treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92 4.3.2 Meniscectomy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92 4.3.3 Soft Tissue Release. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93 4.3.4 Fat Pad Removal. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94 4.3.5 Removal of Posterior Soft Tissues . . . . . . . . . . . . . . . . . . . . . . . . . . . 94 4.4 Osteotomy and Bone Preparation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95 4.4.1 Osteotomy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95 4.4.2 Osteotomy of Each Bone and Preparation for Fixation . . . . . . . . . . . 100 4.5 Balancing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117 4.5.1 Flexion and Extension Gap Balancing. . . . . . . . . . . . . . . . . . . . . . . . 117 4.5.2 Mediolateral Balancing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120 4.5.3 Patellofemoral Balancing. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126 4.6 Fixation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129 4.6.1 Fixation Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129 4.6.2 Cementing Techniques. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129 4.7 Closure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132 4.7.1 Hemostasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132 4.7.2 Hemovac Insertion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132 4.7.3 Suturing Technique. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132 4.8 Miscellaneous Techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132 4.8.1 Methods for Increasing the ROM. . . . . . . . . . . . . . . . . . . . . . . . . . . . 133 4.8.2 Techniques for the Mobile-Bearing Joint. . . . . . . . . . . . . . . . . . . . . . 135 4.8.3 Techniques for the Posterior Cruciate- Substituting Type. . . . . . . . . . 136 Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137 Contents ix 5 TKA in Specifi c Conditions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143 5.1 Bone Defects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143 5.1.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143 5.1.2 Classifi cation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143 5.1.3 Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144 5.1.4 Principles and Methods of Treatment. . . . . . . . . . . . . . . . . . . . . . . . . 145 5.1.5 Surgical Methods of Each Bone. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 152 5.2 Deformity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159 5.2.1 Intra-articular Deformity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 160 5.2.2 Extra-articular Deformity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 168 5.3 Ankylosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 172 5.3.1 Indication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173 5.3.2 Prognostic Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173 5.3.3 Surgical Techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 174 5.4 Miscellaneous Conditions and Diseases. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 176 5.4.1 Osteopenia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 176 5.4.2 Previous Knee Operation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178 5.4.3 Ankylotic Hip. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 182 5.4.4 Miscellaneous Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183 5.5 Tumor Prosthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 186 5.5.1 Indication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 186 5.5.2 Type and Composition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 187 5.5.3 Surgical Techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 187 5.5.4 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189 Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191 6 Unicompartmental Knee Arthroplasty . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195 6.1 Unicompartmental Knee Arthroplasty. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195 6.1.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195 6.1.2 Implant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 196 6.1.3 Indications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 198 6.1.4 Surgical Technique. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200 6.1.5 Postoperative Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205 6.1.6 Complications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205 6.1.7 Prognosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 207 6.2 Patellofemoral Arthroplasty. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 208 6.2.1 Overview. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 208 6.2.2 Design. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209 6.2.3 Indication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209 6.2.4 Surgical Technique. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 210 6.2.5 Postoperative Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 210 6.2.6 Complications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211 6.2.7 Prognosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211 6.3 Bicompartmental Knee Arthroplasty . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211 Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 212 7 Postoperative Management. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215 7.1 Postoperative Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215 7.1.1 Early Stage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 216 7.1.2 Midterm Stage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 218 7.1.3 Late Stage. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223 7.2 Education . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223 7.3 Follow-Up. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 224 Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 225