Therapeutic Alternatives for Venous Ulcer

PROF Dr. FERNANDO VEGA RASGADO CLINICA DE VARICES Y ULCERAS DE MEXICO Therapeutic Alternatives for Venous Ulcer

EPIDEMIOLOGY: Recent epidemiological studies on chronic venous disease have been conducted in England, Sweden and Australia. They included between 12,000 and 434,699 individuals. The average prevalence for venous ulceration was 0.29%. Acta Phlebologica 2012 August;13(2):101-3 Apollonio et al

ETIOLOGY: A high rate of arterial hypertension s comorbidity (63.2%) The healing ratio ranging from 41% in the case of venous ulcers to 26% of those combined etiology Acta Phlebologica 2012 August;13(2):101-3 Epidemiology and healing of vascular ulcers in Italy Apollonio et al.

Differential diagnosis In 354 leg ulcers, Koerber found 75.25% venous leg ulcers, 3.66% arterial leg ulcers, 14.66% ulcers of mixed venous and arterial origin and 13.5% vasculitic ulcers Diabetic leg ulcer, the ulcers with an inflammatory border and skin necrosis are often associated to chronic inflammatory diseases like ulcerous colitis or rheumatoid arthtritis. F Pannier and E Rabe. Leg ulcers Differential diagnosis of leg ulcers Phlebology 2013;28 Suppl 1:55 60

Differential diagnosis Leg ulcers may also occur in patients with Klinefelter s syndrome, in these patients with hypogonadism and testosterone-deficit slow healing ulcers may occur with or without chronic venous disease. There is some evidence that abnormal platelet aggregability or fibrinolysis with an elevated activity of plasminogen activator inhibitor-1 may play an important role. Others Ulcers caused by infections. F Pannier and E Rabe. Leg ulcers Differential diagnosis of leg ulcers Phlebology 2013;28 Suppl 1:55 60

Differential diagnosis The most important differential diagnosis of leg ulcers are ulcerations caused by malignant or semimalignant diseases. Ulcerating tumours like basal cell carcinoma or melanoma may mimic venous ulcerations. F Pannier and E Rabe. Leg ulcers Differential diagnosis of leg ulcers Phlebology 2013;28 Suppl 1:55 60

DIAGNOSIS The single, most helpful confirmatory test is the duplex Doppler examination. In those with leg ulcers, determination of the ABI by Doppler ultrasonography can assess the presence and severity of arterial insufficiency. Phlebology 2014, Vol. 29(1S) 153 156 Dutch Venous Ulcer guideline update Maessen-Visch and de Roos

The most effective Tool Compression therapy is regarded as the basis of therapy in phlebology. The efficacy of compression therapy on venous leg ulcers can clearly be defined by explicit established endpoints: The rate time to complete healing. The reduction of wound surface in a defined period. Phlebology 2013;28 Suppl 1:68 72. M Stucker et al. Compression and venous ulcers

COMPRESSION Compression improves the healing of ulcers when compared with no compression 1. Multicomponent compression systems are more effective than single-component compression systems. 2. High compression is more effective than low compression. 3. Medical compression stockings are more effective than compression with short stretching bandages. Phlebology 2013;28 Suppl 1:68 72. M Stucker et al. Compression and venous ulcers

COMPRESSION It is possible that the effect of compression on neuronal function is an important mechanism that aids healing in venous leg ulcers. There was significant improvement in tcpo 2. Phlebology 2007; 22: No. 2. p49 55 Venous leg ulcers, four-layer compression and neurovascular changes. R Ogrin, P Darzins- and Z Khalil

COMPRESSION When correctly applied Inelastic bandage is significantly more effective than EB in improving the impaired hemodynamics and microcirculatory flow in patients with VLU and has been shown to be extremely effective in favouring the ulcer healing. With a reduced pressure within the range of 40mmHg it can be safely applied even in patients with arterial impairment. Phlebology 2014, Vol. 29(1S) 146 152 Compression in leg ulcer treatment: inelastic compression. Giovanni Mosti

Compression The Coban 2 bandage, induced the ulcer healing in all the patients within three months of observation period. The effect was not different from Unna boot so far considered as the gold standard bandage in compression therapy of venous ulcers. Acta Vulnologica 2010 September;8(3):119-27 A prospective multicenter randomized controlled trial comparing the new 2-component bandage system Coban 2 with a zinc oxide bandage Mosti G. 1, Crespi A. 2, Mattaliano V. 1

Impregnated bandage with coumarine and zinc oxide Patients show a healing of 75% in 8 weeks of treatment, the use of an impregnated bandage with coumarine and zinc oxide is a good choice as treatment for venolymphatic ulcers. Tratamiento de la úlcera veno-linfática con sistema de compresión de óxido de zinc-cumarina Fernando Vega R. et al. Revista Española de Inv. Quirúrgicas, Vol10:3,2007. págs. 161-165

SEQUENTIAL GRADIENT INTERMITTENT COMPRESSION Using sequential gradient intermittent pneumatic compression for just a few hours daily to supplement graduated elastic compression heals venous ulcers at least as well as the Unna Boot, without its disadvantages. Phlebology (1996) 11:111-116 Treatment of Chronic Venous Ulcers Using Sequential Gradient Intermittent Pneumatic Compression J. J. Schuler et al.

Truncal solution The guidelines recommend radiofrequency ablation and endovenous laser treatment as first-line treatment for confirmed symptomatic varicose veins and truncal reflux, and foam sclerotherapy if these treatments are unsuitable. Phlebology 0(0) 1 8 Grover et al. Chronic venous leg ulcers

VEINS ABLATION (SURGERY) Endovenous ablation of incompetent superficial veins improves the healing of chronic primary venous ulcers and decreases the recurrence rates (6-12 m, healing time with RF or L). Phlebology 2011;26:301 306 Sufian et al. Superficial vein ablation of primary chronic venous ulcers The use of EVLA in the local management of refractory ulcers following venous surgery appears to be an attractive option that needs to be explored. Phlebology 2008;23:193 195 A A Kambal et al. EVLA for persistent and recurrent VU

VEINS ABLATION With surgical intervention a significant proportion of ulcers are currently managed, and can be conservatively healed. Ulcer healing occurred in 85% (44 of 52 limbs) of which 52% (27) limbs were no longer confined to compression. Clinical improvement was achieved in 98% of limbs. Phlebology 2013;28:132 139 C A Thomas et al. Healing rates of venous leg ulcers

AVP The ulcer-free period for the whole group was 76% (3 years). There was a significant (p<o.05) difference in the ulcer-free period in limbs with an AVP below 60 mmhg (89%) compared with limbs with a higher AVP (70%). Conclusion: Failure to normalize AVP with surgery results in persistent high venous pressure and an increased risk of venous ulceration recurrences. Phlebology (1993) 8:12S-131 Does Reduction of Venous Hypertension Reduce Ulcer Recurrences? H. Akesson

INFRAGENICULATE GREAT SAPHENOUS VEIN ABLATION Retrograde below knee mechanic-chemical endovenous ablation (MOCA) treating from the knee down to the ankle saphenous vein insufficiency is the opposite way that this treatment is routinely done. However, if subsequent larger studies confirm our results, this will prove to be one more weapon in our armamentarium to combat venous ulcers. Phlebology 2014, Vol. 29(10) 654 657 Sullivan et al. Retrograde mechanico-chemical endovenous ablation of infrageniculate great saphenous vein forvpersistent venous stasis ulcers

FOAM SCLEROTHERAPY The healing and recurrence rates in the present study were similar to the surgery group of the ESCHAR trial and compared well with the compression alone group of the ESCHAR trial and other published studies using compression alone. The present study demonstrated that UGFS was effective in the abolition of superficial venous reflux with favourable ulcer healing and long-term recurrence rates with a low complication rate. Foam sclerotherapy is an attractive alternative to surgery in this group of patients. Phlebology 2013;28:140 146 Foam sclerotherapy reduces venous ulcer recurrence S R Kulkarni et al

FOAM SCLEROTHERAPY Venous ulcers in patients with severe venous insufficiency responded quickly to UGFS. Long-term follow-up will be important to determine the sustainability of these results. Our preliminary observations have shown that large ulcers present for many years respond quickly to this simple therapy. P A Hertzman and R Owens. Ultrasound-guided foam sclerotherapy Phlebology Vol 22 No. 1 2007

FOAM SCLEROTHERAPY After three months, no additional ulcers were healed leaving nine non-healed ulcers, 29% (9/31 limbs). Six of these nine ulcers decreased in size. Two previously healed ulcers recurred within 12 months. This gives a total ulcer healing rate of 71% (22/31) of the studied limbs or 70% (21/30) of the patients. In one year, 65% (20/31) limbs did not have active ulcers. Phlebology 2014, Vol. 29(10) 688 693 Catheter-directed foam sclerotherapy for chronic venous leg ulcers. Williamsson et al.

DRESSINGS A Cochrane review failed to find advantages for any dressing type compared with lowadherent dressings applied beneath compression. Surgical debridement and grafting of wounds, negative wound pressure treatment: surgical and hydrosurgical debridement are indicated in large, necrotic and infected wounds. Mosti. Wound care in venous ulcers Phlebology 2013;28 Suppl 1:79 85

NEGATIVE WOUND PRESSURE Negative wound pressure treatment creating a negative pressure on ulcer bed is able to favour granulation tissue and shorten healing time. Mosti. Wound care in venous ulcers Phlebology 2013;28 Suppl 1:79 85

Lower Molecular Weigth Heparins Nadroparin plays an important adjuvant role in venous ulcer treatment because it favours pain relief and improves quality of life. Not improve the healing, only the pain. Acta Phlebologica 2010 April;11(1):17-21 Guarnera G. Treatment of venous ulcers with LMWH: effects on healing rate, pain and quality of life

Therapeutic ultrasound Ultrasound is an efficient and useful method only in conservatively treated venous leg ulcers. There are no special reasons for application of the ultrasound in surgically treated patients. A well-conducted surgical operation is much more effective for a healing process than conservative pharmacological procedures. Phlebology 2008;23:178 183 J Taradaj et al. Use of therapeutic ultrasound in venous leg ulcers

LEG ULCERS AND OEDEMA Oedema was present in 55% of patients, but its prevalence in the community-treated group was much greater than in the hospital-treated group. Lymphatic insufficiency was present in 22% of patients, the presence of oedema was associated with a longer duration of ulcer whereas the use of diuretics was associated with a shorter duration. Phlebology (1990) S, 181-187 Leg ulcers and oedema Prasad et ai.

VENOUS ULCERS CIRCANNUAL FLUCTUATIONS Venous ulcers exhibit circannual fluctuations in their onset and healing rates. Healing rates after one, two or three months for ulcers that developed in a given month. Data smoothed with a moving average are marked with thinner lines. Phlebology 2010;25:29 34 M Simka. Chronobiology of venous ulcers

VENOUS ULCERS EXHIBIT CIRCANNUAL FLUCTUATIONS

FASCIOTOMY This follow-up study suggests that eradication of superficial reflux with additional subcutaneous fasciotomy as therapy for resistant and recurrent venous ulcer in patients with severe chronic venous insufficiency improves ulcer healing or skin graft survival. Phlebology 2011;26:197 202 J T Christenson et al. Subcutaneous fasciotomy and eradication of superficial venous reflux

Ankle motility The 24-week healing rate was significantly reduced in patients with poor ankle motility: 13%, in legs with an ankle motility <35 compared with 60% in legs with an ankle motility >35. Ankle motility was an independent risk factor for chronic venous ulcer healing rate when adjusted for age, ulcer chronicity and popliteal vein reflux (p = 0.001). Phlebology (2001) 16:38-40 Ankle Mortility Is a Risk Factor for Healing of Leg Ulcers 1. R. Barwell et al.

PLATELET-RICH GEL Application of autologous platelet-rich gel (PRP) to non healing vascular ulcers. This treatment is effective in the majority of cases, without side effects. The easy application, the almost complete absence of side effects and the low cost of platelet gel make this approach very interesting to treat chronic non-healing ulcers. Italian Journal of Vascular and Endovascular Surgery 2011 March;18(1):31-8 Villa V. 1, Froio A. 1, Cova M. 1, Ariano F. 1, Perseghin P. 2, Incontri A. 2, Casarotto E. 2, Pozzi M. 2, Biasi G. M. 1

MINOCYCLINE: Administration of oral doses of minocycline 50 mg, in addition to basic treatment (compression therapy followed or not by vein surgery) showed a beneficial therapeutic effect on wound healing of chronic venous ulcers. This through the inhibition of MMPs and its immunomodulatory and anti-inflammatory actions in extracellular matrix. Acta Phlebologica 2013 December;14(3):99-107 The effects of minocycline on extracellular matrix in patients with chronic venous leg ulcers Serra R. 1, 2, Grande R. 1, Buffone G. 1, Gallelli L. 3, De Franciscis S.

SULODEXIDE: The use of sulodexide in patients with chronic venous leg ulcers accelerates the healing process. The speed of decreasing of ulcers in group I varied from 0.029 to 0.171 cm2/d while in group II it equalled 0.200 to 0.343 cm2/d. Phlebologie 2003; 32: 115 20 Treatment of venous leg ulcers with sulodexide M. Kucharzewski1, A. Franek2, H. Koziol/ ek1

GROWTH HORMONE The study failed to demonstrate a statistically significant stimulation of healing whereas a dose-dependent stimulation of collagen synthesis by growth hormone was revealed. Growth Hormone Treatment of Venous Leg Ulcers L. H. Rasmussen et al. Phlebology (1994) 9:92-98

CONNEXIN43-BASED PEPTIDE Targeting Cx43 with ACT1, a peptide mimetic of the carboxyl-terminus of Cx43, accelerates fibroblast migration and proliferation, as well as wound reepithelialization. Evaluation indicated a reduced median time to 50 and 100% ulcer reepithelialization for ACT1-treated ulcers. Journal of Investigative Dermatology (2015), Volume 135 ACT1 in the Healing of Venous Leg Ulcers G Ghatnekar et al.

ELECTROTHERAPY Electrical Muscle Stimulation demonstrated high efficacy and good tolerability and provided significant reduction in pain severity, VCSS score and ankle edema, as well as a 3-fold increase in the number of healed venous ulcers. Electrical muscle stimulation with Veinoplus device in the treatment of venous ulcers Bogachev V. Y. 1, Lobanov V. N. 2, Golovanova O. V. 1, Kuznetsov A. N. 1, Yershov P. V. 1 International Angiology 2015 June;34(3):257-62

CONCLUSIONS: The compression remains the most useful and effective method. The multi-layer is more effective, Unna Boot remains the Gold standard. Axial disconnection is very important.

CONCLUSIONS: Some drugs may contribute to healing. Special dressings are expensive. New methods and considerations should be evaluated, specially for poorly healing ulcers also differential diagnosis. The Electrical Muscle Estimulation will be Very usefull in non ambulatory patients.

See you in September 26-28, 2016 at the Panamerican Congress of Phlebology and Lymphology. Mexico City www.flebologiamexico.org THANK YOU PROF. DR. FERNANDO VEGA R