Faculty of Medicine University of Helsinki ISCHAEMIC DIABETIC FOOT PERSPECTIVES ON LONG-TERM OUTCOME Milla Kallio DOCTORAL DISSERTATION To be presented for public discussion, with the permission of the Faculty of Medicine of the University of Helsinki, in Auditorium 1, Metsätalo, on the 14th of August, 2020 at 12 noon. Helsinki 2020 Supervised by: Professor Maarit Venermo University of Helsinki Department of Vascular Surgery Helsinki University Hospital, Helsinki, Finland Professor Erkki Tukiainen University of Helsinki Department of Plastic Surgery Helsinki University Hospital, Helsinki, Finland Professor emeritus Mauri Lepäntalo Helsinki University Hospital, Helsinki, Finland Reviewed by: Docent Eva Saarinen Centre for Vascular Surgery and Interventional Radiology Tampere University Hospital, Tampere, Finland Docent Ilkka Kaartinen Department of Plastic Surgery Tampere University Hospital, Tampere, Finland Discussed with: Professor Mauro Gargiulo Head of the Department of Experimental, Diagnostic and Speciality Medicine (DIMES), University of Bologna, Bologna, Italy The Faculty of Medicine uses the Urkund system (plagiarism recognition) to examine all doctoral dissertations. ISBN978-951-51-6295-3(nid.) ISBN 978-951-51-6296-0 (PDF) Unigrafia Helsinki 2020 To individuals who live or work with chronic ulcers CONTENTS ORIGINAL PUBLICATIONS ........................................................................................................ 6 ABBREVIATIONS AND DEFINITIONS ......................................................................................... 7 ABSTRACT ................................................................................................................................ 9 1 INTRODUCTION .................................................................................................................. 11 2 REVIEW OF THE LITERATURE .............................................................................................. 12 2.1 DIABETES MELLITUS (DM) ............................................................................................12 2.1.1 Definition ...............................................................................................................12 2.1.2 Aetiology ................................................................................................................12 2.1.3 Epidemiology .........................................................................................................13 2.1.4 Diabetic complications ...........................................................................................14 2.2 LOWER EXTREMITY ARTERIAL DISEASE (LEAD) .............................................................20 2.2.1 Clinical manifestations ...........................................................................................20 2.2.2 Epidemiology in diabetes .......................................................................................23 2.2.3 DM as a risk factor for LEAD and the progression of the disease..........................25 2.2.4 Angiosomes ............................................................................................................26 2.2.5 Classification ..........................................................................................................28 2.2.6 Diagnosis of LEAD in diabetic patients ...................................................................29 2.3 DIABETIC FOOT ULCERS ................................................................................................31 2.3.1 Epidemiology .........................................................................................................31 2.3.2 Aetiology ................................................................................................................32 2.3.3 Classification ..........................................................................................................33 2.3.4 Ulcers and infection ...............................................................................................38 2.4 TREATMENT OF SEVERE TISSUE DEFECTS .....................................................................42 2.4.1 Revisions and minor amputations .........................................................................42 2.4.2 Split thickness skin graft ........................................................................................44 2.4.3 Local flaps ..............................................................................................................44 2.4.4 Other treatments ...................................................................................................45 2.5 MAJOR AMPUTATIONS .................................................................................................46 2.5.1 Epidemiology .........................................................................................................46 2.5.2 Reamputation ........................................................................................................47 2.5.3 Mortality after amputation ....................................................................................47 2.5.4 Ambulation after major amputation .....................................................................48 2.6 REVASCULARISATION FOR CRITICAL LIMB THREATENING ISCHAEMIA (CLTI) ..............51 2.6.1 Surgical revascularisation ......................................................................................52 2.6.2 Endovascular treatment ....................................................................................... 53 2.6.3 Hybrid procedures ................................................................................................ 55 2.6.4 Selection of revascularisation modality ................................................................ 55 2.6.5 Timing of revascularisation ................................................................................... 59 2.6.6 Increasing revascularisation rate – decreasing amputation rate ......................... 59 2.6.7 Patency ................................................................................................................. 60 2.6.8 Complications ....................................................................................................... 63 2.6.9 No Revascularisation............................................................................................. 63 2.7 FREE TISSUE TRANSFER (FTT) IN THE DIABETIC FOOT ................................................. 66 2.7.1 History ................................................................................................................... 66 2.7.2 Indications ............................................................................................................. 66 2.7.3 FTT and CLTI .......................................................................................................... 69 2.7.4 Flaps ...................................................................................................................... 70 2.7.5 FTT technique in the ischaemic diabetic foot ....................................................... 71 2.7.6 Postoperative surveillance and ambulation ......................................................... 72 2.8 OUTCOME .................................................................................................................... 73 2.8.1 Ulcer healing ......................................................................................................... 73 2.8.2 Limb salvage .......................................................................................................... 81 2.8.3 Amputation free survival ...................................................................................... 85 2.8.4 Survival .................................................................................................................. 85 2.8.5 Clinical/functional outcome .................................................................................. 86 2.8.6 Outcome of free tissue transfer............................................................................ 87 3 AIMS OF THE PRESENT STUDY ............................................................................................ 91 4 MATERIAL AND METHODS ................................................................................................. 92 4.1 STUDY I......................................................................................................................... 93 4.1.1 Patients and study design ..................................................................................... 93 4.1.2 Outcome measures ............................................................................................... 93 4.1.3 Statistical analysis ................................................................................................. 93 4.2 STUDY II........................................................................................................................ 94 4.2.1 Patients and study design ..................................................................................... 94 4.2.2 Outcome measures ............................................................................................... 95 4.2.3 Statistical analysis ................................................................................................. 95 4.3 STUDY III....................................................................................................................... 96 4.3.1 Patients