Venous Ulcers. A Little Basic Science. An Aggressive Prescription to Aid Healing. Why do venous ulcers occur? Ambulatory venous hypertension!

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1 UCSF Vascular Symposium April 26-28, 2012 San Francisco, California True statements about the management of venous ulcers include: An Aggressive Prescription to Aid Healing Anthony J. Comerota, MD, FACS, FACC Director, Jobst Vascular Institute A. All venous ulcers will heal if the foot is kept above heart level B. Micronized purified flavanoid fraction (Daflon-500) speeds ulcer healing C. Compression is the basis of care D. Pentoxifylline speeds ulcer healing E. All of the above F. A and C 23% 38% 38% Adjunct Professor of Surgery, University of Michigan 0% 0% 0% A. B. C. D. E. F. Post-thrombotic venous disease is associated with the highest risk of venous ulceration and is avoidable if venous thrombus is removed! A Little Basic Science Why do venous ulcers occur? Ambulatory venous hypertension! 1

2 Pathophysiology Ambulatory Venous Hypertension CVD Pathophysiology Normal 30 AVP of normal Low Pressure Long Refill Time (Normal Valve Fct.) 41 AVP of patients with CVD High Pressure Short Refill Time (Valve Incompetence) Ambulatory Venous Hypertension (Increased venous pressures) * * * * Cellular and molecular effects of increased venous pressure Venous Hypertension Causes Leukocyte Adhesion WBC Activation/Adhesion Normal Venous Pressure Venous Hypertension This initiates cellular infiltration and protease production ed MMPs, ed TIMP, ed TGFB No WBCs WBC Activation and Adhesion 2

3 Venous Hypertension Animal Model Sham (N Pressure) Ligated ( Pressure) p-value Pressure mmhg <0.05 Experimentally induced hind-limb venous MPO Activity hypertension causes WBC trapping in (leukocyte trapping) soft tissue (rodents) Venous Hypertension Human Study To Evaluate if Venous Hypertension causes: WBC activation (L-selectin) and Endothelial Cell adhesion (CD-11b integrin) L-Selectin - WBC adhesion molecule which allows rolling of WBC s along endothelium. Shed when WBC is activated ( s with WBC activation) CD-11b - Integrin that allows adhesion to endothelium ( s with WBC adhesion) Lalka S G et al J Surg Res 1998;74:59 Venous Hypertension Humans Increased Capillary Permeability Venous hypertension - Causes WBC activation and WBC adhesion to endothelial cells Blood Samples From Foot Vein Baseline Standing (30 min) p-value WBC adhesion and emigration results in: L-Selectin (activation) +20% 0.02 Protease production CD-11b -29% 0.02 (endothelial Capillary adhesion) permeability Saharay & Coleridge-Smith J Vasc Surg 1997;25:265 Schmid-Schönbein G N The Vein Book 2007 Academic Press 3

4 Majority of venous ulcers will heal with proper compression! Postthrombotic venous ulcer Present 4 years Referring MD states nothing works cannot get him healed! Venous Ulcer C-6 Compression x 2 weeks 4

5 C-5 Disease Venous Ulcer Compression x 6 months Goal of Treatment Top 10 Ways to Control Swelling The key to success Control Swelling! 1. Compression 2. Compression 3. Compression 4. Compression 5. Compression 6. Compression 7. Compression 8. Compression 9. Compression 10.Compression 5

6 Compression Pathophysiology Can the cellular and enzymatic abnormalities be improved by other mechanical and pharmacologic intervention? YES! Management What s New in Guidelines? Treatment Pathophysiology Based I. Hemodynamic Abnormalities Mechanical intervention Good compression is the foundation of care! II. Cellular/enzymatic Abnormalities Pharmacologic Therapy 6

7 What s New in Guidelines : Treatment What s New in Guidelines Sustained Compression Reduced edema Increased venous velocity Decreased venous reflux Improved calf muscle pump Improved arterial flow Increased lymphatic drainage Decreased WBC adhesion and cytokine production Sustained Compression Grade A Compliance is crucial! 2008 Nicolaides A N, Comerota A J et al Int l Angiol 2008; 27:1-59 What s New in Guidelines? What s New in Guidelines Compression Stockings Rx of Acute DVT 30-40mmHg Ankle Pressure Grade 1A (Reduces PTS by 50%) 2008 Kearon C et al CHEST 2008;133:4545 Intermittent Pneumatic Compression Increased venous velocity Increases endogenous fibrinolysis (Improved clearance of PAI-1) Improved tissue factor inhibitor Decreases intravascular coagulation Increases limb and skin blood flow Increased skin TcPO4 Randomized trials: Venous ulcers 7

8 : Treatment What s New in Guidelines Intermittent Pneumatic Compression Venous ulcers resistant to healing with wound care Grade 2B 2008 Surgical Management Ultimate goal reduce venous pressure On occasion, this is best accomplished by ligating the femoral vein! Suggested Approach Obstruction Identify underlying pathophysiology either reflux or obstruction! Eliminate iliocaval obstruction Correct infrainguinal superficial reflux so far so easy! We cannot reliably identify post-thrombotic venous obstruction! 8

9 S/P Iliofemoral DVT 10 Years Suggested Approach Total incompetence of a scarred, post-thrombotic femoral vein ligate! Any obstruction? Postthrombotic Syndrome - Multiple hospitalizations - Venous ulcers Venogram: no obstruction IPG - Normal Classic Linton Procedure X- Section Femoral Vein The Importance of Pelvic Venous Obstruction! 9

10 Ascending Phlebogram Pelvic Phlebogram Post Stent 10

11 Femoral Vein Translocation Managing Valvular Incompetence Venous Transposition Results (Poor Follow-Up) Descending Phlebogram: Incompetent Values # Series Ulcer Healing Ulcer Recur Improved Hemdyn 6 35% 36% 35% Technique no longer recommended! O Donnell TF Handbook of Venous Disorders 2 nd Ed,

12 Deep Venous Insufficiency: Primary Open Valvuloplasty Deep Venous Insufficiency: Primary Primary Valve Repair: Incompetent Valve insertion lines must be identified anterior Courtesy: P. Neglén, MD, PhD River Oaks Hospital posterior Deep Venous Insufficiency: Primary External Valvuloplasty Deep Venous Insufficiency: Primary External Valvuloplasty 12

13 External Valvuloplasty: Strip Test Competent Valve Axillary Vein-Valve Transplant In patients without a repairable valve Avoid obstructed femoral vein! Deep Venous Insufficiency Axillary Vein Transplant: Axillary Exposure Deep Venous Insufficiency Competent Valve 13

14 Deep Venous Insufficiency Popliteal Anastomosis Deep Venous Insufficiency Transplanted Axillary Vein: Competent Valve Deep Venous Insufficiency Fenestrated Dacron Wrap Percutaneous Vein-Valve The Solution! or so we thought! 14

15 Percutaneous Venous Valve Venous Ulcer X15 Years Percutaneous Venous Valve D.B. 44 yo woman, Wt. 327# Biopsy of wound to r/o malignancy Normal arterial perfusion Descending phlebography of Femoral Vein Severe primary venous valvular incompetence! Percutaneous Venous Valve Deployment Via Internal Jugular Vein Percutaneous Venous Valve Post-deployment descending phlebography showing valve competence 15

16 Percutaneous Venous Valve Percutaneous Venous Valve Before After 1 year follow-up Patent vein Functional valve 360 msec closure Could not find valve at 2 year study! Percutaneous Venous Valve Incompetent Perforators Ultrasound-guided perforator vein ablation Patient continues to do well! 16

17 US-Guided Perforator Ablation Surgical Procedures US-Guided Perforator Ablation Surgical Procedures US-Guided Perforator Ablation Surgical Procedures US-Guided Perforator Ablation Surgical Procedures Phlebectomy hook engaging IPV 17

18 On occasion, ulcer excision and skin grafting is required Extensive Obstruction: Postthrombotic Deep Vein and Perforator Incompetence - Principles - 1. Exercise ulcer (with fascia) to muscle 2. Don t put skin graft on granulation tissue, ulcers will recur Plus: - Inflammatory bowel disease - Antiphospholipid ab. Extensive Obstruction: Postthrombotic Deep Vein and Perforator Incompetence Extensive Femoral Iliac Obstruction 18

19 Extensive Leg Ulcer Extensive Obstruction: Postthrombotic Resected to Muscle: Perforators Ligated Extensive Leg Ulcer Resected to Muscle Extensive Obstruction: Postthrombotic Resected: Skin-Fascia Sutured Ulcer with surrounding skin Fascia 19

20 Extensive Leg Ulcer Resected with STSG Extensive Leg Ulcer 3 Months Postop Extensive Leg Ulcer 1Year Postop Superficial Venous Insufficiency What is the role of saphenous ablation on ulcer healing and recurrence? 20

21 Purpose Brit Med J 2007;335:83 Evaluate whether recurrence of venous leg ulcers could be prevented by surgical ablation of superficial venous reflux in addition to compression Gohel M S et al BMJ 2007;335:83 Venous Ulcer (N=500) Healing at 3 Years Ligation/Stripping plus Compression Compression Time to complete healing Recurrence at 3 years Gohel M S et al BMJ 2007;335:83 No difference in healing between groups! Gohel M S et al BMJ 2007;335:83 21

22 Ulcer Recurrence at 4 Years Ulcer Recurrence at 4 Years - Degree of Deep Reflux - None Segmental Total p<0.001 p<0.044 p<0.331 Ulcer free time longer in surgery group p=0.007 Gohel M S et al BMJ 2007;335:83 Gohel M S et al BMJ 2007;335:83 : Treatment What s New in Guidelines? Pentoxifylline Nonoperative and Pharmacologic Management Hemorheologic Agent Improves microcirculatory blood flow Improves tissue oxygenation Decreases whole blood viscosity Decreases inflammation 22

23 : Treatment What s New in Guidelines Treatment: Micro Pure Flavonoid Fraction Mechanism of Benefit Pentoxifylline Venous leg ulcers Grade 2B Reduced capillary filtration 2. Increased venous tone 3. Improved T c P Increased lymphatic flows 5. Decreased leukocyte activation/adhesion (Decreased inflammatory response) 6. Decreased capillary protein leak 7. Decreased VEGF : Treatment What s New in Guidelines? Micronized purified flavonoid fraction Healing of venous leg ulcers (Only venotonic agent mentioned) Grade 1A 2008 : Prescription 1. Compression! Conclusions 2. Understand pathology! 3. Obstruction if often more important than we realize! 4. Always correct pelvic venous obstruction! 5. Judicious reconstructive procedures below the inguinal ligament! 6. Maximize pharmacologic support 23

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