Diyabetik Ayak Ülseri Hastalarında Major Amputasyonun Önlenmesi icin Bir Yöntem: Negatif Basınclı Yara Tedavisi ile Kombine İntralezyonel Epidermal Growth Faktör Kullanılması

Yıl 2019, Cilt: 16 Sayı: 2, 174 - 181, 29.08.2019

Bayram Çolak Atilla Orhan İlhan Ece Serdar Yormaz Hüseyin Yılmaz Mustafa Şahin

https://doi.org/10.35440/hutfd.462031

Cited By: 1

Öz

Amaç:
Diyabetik ayak ülserleri (DAÜ), diyabetik hastaların %15’ini etkileyen bir
sağlık problemidir. DAÜ, iş gücü kaybı, uzun süre hastanede yatış, maddi kayıp
ve ayrıca alt ekstremite amputasyonu gibi nedenlerle hastaların yaşam
kalitesinde düşüşe neden olmaktadır.

DAÜ’lerinin
tedavisinde birçok yöntem uygulanmış fakat amputasyonların önüne
geçilememiştir. Çalışmada major amputasyon (trans-metatarsal, tarsometatarsal,
intertarsal ve diz altı amputasyonlar) kararı alınmış DAÜ hastalarına
uyguladığımız tedavinin etkilerini sunmayı amaçladık.

Materyal ve Metod:
Çalışmada, çeşitli sağlık kurumlarından hastanemize yönlendirilen ve majör
amputasyon kararı alınmış fakat hastanemizde negatif basınçlı yara tedavisi
(NBYT) ile kombine intralezyonel epidermal growth faktör (EGF) uygulanarak
majör amputasyon yapılmadan tedavi edilen hastalar değerlendirildi. Hastalara
EGF (haftada 3 kez veya cilt dokusu ile tam kapanma oluşuncaya kadar) ile
kombine NBYT (haftada iki kez üç gün boyunca tam granulasyon dokusu oluşuncaya
kadar) tedavileri uygulandı. Yara kapanması ve amputasyonu önlemeye yönelik
tedavinin etkileri incelendi.

Bulgular: PEDİS
sınıflamasına göre 32 hastanın 27’si (%84.3) grade 3, 5’i (%15.6) grade 4
DAÜ’ine sahipti. Hastaların 24’ünde (%75) infeksiyon mevcuttu. 22 hastada
(%68.7) nekroz mevcuttu. Hastaların ortalama yara büyüklüğü 18 cm (10-25cm)
idi. Uygulanan tedavi ile hastaların 27’ sinde (%84.3) tam cilt kapanması, 5
hastada (%15.6) yara zemininin tamamının granülasyon dokusu ile
kapanmasısağlandı. Hastaların hiç birine major amputasyon yapılmadı. EGF
ortalama 10 injeksiyon (7-12 injeksiyon) ile kombine NBYT ortalama 11 seans
(8-13 seans) tedavisi ortalama 45 gün uygulandı. Yaklaşık bir yıllık takip
süresi içinde üç hastada enfeksiyon gelişti ve medikal tedavi uygulandı.

Sonuç:
Hastalarımız, major amputasyon önerilerek çeşitli hastanelerden yönlendirilen,
major amputasyon riski yüksek olan hastalardı. Çalışmanın sonucunda, NBYT ve
EGF’nin birlikte düzenli olarak uygulanması ile major

amputasyonların
önlenebileceği kanısındayız.

Anahtar Kelimeler

diyabetik ayak, amputasyon, epidermal büyüme faktörü

A Method for Preventing Major Amputation in Patients with Diabetic Foot Ulcer: Negative-Pressure Wound Therapy Combined with Intralesional Epidermal Growth Factor

Öz

Background:Diabetic foot ulcer (DFU) is a serious
health problem affecting 15% of patients with diabetes mellitus. Diabetic foot
ulcers cause a decrease in the quality of life of patients like job loss,
long-term hospital stay, financial burden and also lower extremity amputation.
Many methods have been applied to treat patients with DFU, but amputations have
not been prevented. In this study, we presented patients who had been referred
to us from various hospitals with a decision for major amputation, but treated
by us using intralesional epidermal growth factor therapy (EGF) combined with
negative-pressure wound therapy (NPWT) to prevent below-knee amputation.

 Methods:Patients who had been referred to us
from various hospitals with a decision for major amputation, but treated by us
using combined therapy to prevent below-knee amputation. The efficacy of
treatment was assessed according to wound closure and amputation prevention.

 Results:According to Wagner's classification, 17
(51.6%) out of 33 patients were the grade 3, and 16 (48.4%) were the grade 4
patients. Major amputation was performed in one patient. Infection was present
in 24 (75%) of the patients. Necrosis was present in 12 (37.5%) of these
patients. The average wound size was 18 cm (10-25 cm). Complete skin closure
was achieved in 27 patients (84.3%), and closure with 100% granulation was
achieved in 5 patients (15.6%). None of the patients underwent major
amputation. EGF+NPWT treatment were administered for 45 days on average. Infections
were developed in three patients during one-year of follow-up approximately,
and medical treatment was administered.

Conclusions: Our patients were in the high risk group
for major amputation, which were referred from various hospitals with the
recommendation of major amputation. We believe that the regular application of
NPWT combined with EGF can prevent major amputations.

Anahtar Kelimeler

Diabetic foot, amputation, epidermal growth factor

Kaynakça

• 1) Frykberg RG, Zgonis T, Armstrong DG, Driver VR, Giurini JM, Kravitz SR, Landsman AS, Lavery LA, Moore JC, Schuberth JM,Wukich DK, Andersen C, Vanore JV. American College of Foot and Ankle Surgeons. Diabetic foot disorders. A clinical practice guideline (2006 revision). J Foot Ankle Surg 2006; 45(5 Suppl): S1–S66.
• 2) Reiber GE, Bowker JH, Pfefier MA. Epidemiology of foot ulcers and amputation in the diabetic foot. In: The diabetic foot. 6th ed. St Louis, Mo Inc 2001;p.1332.
• 3) Ragnarson-Tennvall G, Apelgvist J. Health-economic consequences of diabetic foot lesions. Clin. Infect Dis 2004; 39(2):132-139.
• 4) Levin MH. Preventing amputation in the patient wıth diabetes. Diabetes Care 1995;18 (10): 1383-1394.
• 5) Frykberg RG. An evidence-based approach to diabetic foot infections. Am J Surg 2003; 186 (5A): 44-54.
• 6) Tsang MW, Wong WK, Hung CS, Lai KM, Tang W, Cheung EY, et al. Human epidermal growth factor enhances healing of diabetic foot ulcers. Diabetes Care 2003; 26: 1856-61.
• 7) Ertugrul BM, Buke C, Ersoy OS, Ay B, Demirez DS, Savk O. Intralesional epidermal growth factor for diabetic foot wounds: the first cases in Turkey. Diabetic Foot & Ankle 2015, 6: 28419
• 8) Berlanga-Acosta J. Diabetic lower extremity wounds: the rationale for growth factors-based infiltration treatment. Int Wound J 2011; 8: 612_20.
• 9) Lone AM, Zaroo MI, Laway BA, Pala NA, Bashir SA, Rasool A, Vacuum-assisted closure versus conventional dressings in the management of diabetic foot ulcers: a prospective casecontrol study. Diabetic Foot & Ankle 2014, 5: 23345.
• 10) Morykwas MJ, Argenta LC, Shelton B, McGuirt W. Vacuumassisted closure: a new method for wound control and treatment: animal studies and basic foundation. Ann Plast Surg 1997; 38: 553-62.
• 11) Dumantepe M, Fazliogullari O, Seren M, Uyar I, Basar F. Efficacy of intralesional recombinant human epidermal growth factor in chronic diabetic foot ulcers. Growth Factors, 2015; 33(2): 128–132.
• 12) Ravari H, Modaghegh MHS, Kazemzadeh GH, Johari HG, et al. Comparision of Vacuum-Asisted Closure and Moist Wound dressing in the Treatment of Diabetic Foot Ulcers. Journal of Cutaneous and Aesthetic Surg 2013; 6(1): 17-20.
• 13) Cohen S. Isolation of a mouse submaxillary gland protein accelerating incisor eruption and eyelid opening in the new-born animal. J Biol Chem 1962; 237: 1555_62.
• 14) Stein MD, Salkin LM, Freedman AL, Glushko V. Collagen sponge as a topical hemostatic agent in mucogingival surgery. J Periodontol. 1985; 56:35–8.
• 15) Heldin CH, Westermark B. Mechanism of action and in vivo role of platelet derived growth factor. Physiol Rev 1999; 79: 1283 1316
• 16) Jin Q, Wei G, Lin Z, Sugai JV, Lynch SE, Ma PX, Giannobile WV. Nanofibrous scaffolds incorporating PDGF BB microspheres induce chemokine expression and tissue neogenesis in vivo. PLoS One 2008; 3: 1729.
• 17) Shiraha H, Glading A, Gupta K and Wells A: IP 10 inhibits epidermal growth factor induced motility by decreasing epidermal growth factor receptor mediated calpain activity. J Cell Biol 1999; 146: 243 254.
• 18) Brown GL, Curtsinger L III, Brightwell JR, et al: Enhancement of epidermal regeneration by biosynthetic epidermal growth factor. J Exp Med 1986; 163: 1319 1324.
• 19) Erba P, Adini A, Demcheva M, Valeri CR and Orgill DP: Poly N acetyl glucosamine fibers are synergistic with vacuum assisted closure in augmenting the healing response of diabetic mice. J Trauma 2011; 71: 187 193
• 20) Goldberg AC, Goldberg Eliaschewitz F, Sogayar MC, Genre J and Rizzo LV: Leptin and the immune response: an active player or an innocent bystander? Ann NY Acad Sci 2009; 1153: 184 192.
• 21) Murad A, Nath AK, Cha ST, Demir E, Flores-Riveros J, Sierra-Honigmann MR. Leptin is an autocrine/paracrine regulator of wound healing. FASEB J 2003; 17: 1895 1897.
• 22) Cheng Yan Xıa, Aı xı Yu, Baıwen Qı, Mın Zhou, Zong Huan Lı, Weı Yang Wang. Analysis of blood flow and local expression of angiogenesis associated growth factors in infected wounds treated with negative pressure wound therapy. Molecular Medicine Reports 2014; 9: 1749-1754
• 23) Jacobs S, Simhaee DA, Marsano A, Fomovsky GM, Niedt G and Wu JK: Efficacy and mechanisms of vacuum assisted closure (VAC) therapy in promoting wound healing: a rodent model. J Plast Reconstr Aesthet Surg 2009; 62: 1331 1338.
• 24) Ferrara N: Molecular and biological properties of vascular endo¬thelial growth factor. J Mol Med (Berl) 1999; 77: 527 543
• 25) Labler L, Rancan M, Mica L, Härter L, Mihic Probst D and Keel M: Vacuum assisted closure therapy increases local interleukin 8 and vascular endothelial growth factor levels in traumatic wounds. J Trauma 2009; 3: 749 757.
• 26) Akcay S, Satoglu IS, Harman E, Kurtulmuş A, Kazımoglu C. A Retrospective Analysis of Amputation Rates and Comorbidity in Patients with Diabetic Foot Ulcer. Medicine Science 2012;1(4):331-340
• 27) Yesil S, Akıncı B, Yener S, Bayraktar F, Karabay O, Havitcioglu H , Yapar N, Atabey A, Kucukyavas Y, Comlekci A, Eraslan S. Predictors of amputation in diabetics with foot ulcer: Single center exprience in a large Turkish kohort. Hormones 2009, 8(4): 286-295.
• 28) Aziz Z, Lİn WK, Nather A, Huak CY. Predictive factors for lower extremity amputatioons in diabetic foot infecions. Diabetic Foot and Ankle 2011; 2:7463.
• 29) Eneroth M, Apelqvist J, Stenstrom A. Clinical characteristics and outcome in 223 diabetic patients with deep foot infections. Foot Ankle Int 1997; 18: 716-722.
• 30) Bridges RM, Deitch EA. Diabetic foot infections. Pathophysiology and treatment. Surg Clin North Am. 1994; 74(3): 537-555
• 31) Rooh-UI-Muqim, Ahmed M, Griffin S. Evaluation and management of diabetic foot according to Wagner’s classification. A study of 100 cases. J Ayub Med Coll Abbottabad 2003; 15(3): 39-42
• 32) Boutin RD, Brossmann J, Sartoris DJ, et al. Update on imaging of orthopaedic infection. Orthop Clin North Am, 1998; 29: 41-66.
• 33) Grayson ML. Diabetic foot infections: Antimicrobial therapy. Infect Dis Clin North Am, 1995; 9: 143-161.
• 34) Pecoraro RE, Reiber GE, Burgess EM. Pathways to diabetic limb amputation: basis for prevention. Diabetes Care. 1990;13: 513-521
• 35) Mutluoglu M, Sivrioglu AK, Eroglu M, et al. The implications of the presence of osteomyelitis on outcomes of infected diabetic foot wounds. Scand J Infect Dis. 2013;45: 497-503.
• 36) Lee YJ, Sadigh S, Mankad K, Kapse N, Rajeswaran G. The imaging of osteomyelitis. Quant Imaging Med Surg. 2016; 6: 184-198.
• 37) Schaper NC. Lessons from Eurodiale. Diabetes Metab Res Rev 2012; 28(1) :21–6.
• 38) Baktıroğlu S, Yanar F, Özata IH. Vascular problems in diabetic foot. TOTBİD Dergisi 2015; 14: 387–391
• 39) Colwell JA, Nesto RW. The platelet in diabetes: focus on prevention of ischemic events. Diabetes Care 2003; 26: 2181-2188.
• 40) American Diabetes Association. Clinical practice recommendations. Diabetes Care 1997; 20 : 1–70
• 41) Ueno H, Koyama H, Mima Y, Fukumoto S, Tanaka S, Shoji T, Emoto M, Shoji T, Nishizawa Y, Inaba M. Comparison of the effect of cilostazol with aspirin on circulating endothelial progenitor cells and small-dense LDL cholesterol in diabetic patients with cerebral ischemia: a randomized controlled pilot trial. J Atheroscler Thromb. 2011;18(10):883-90.
• 42) Huang Y, Cheng Y, Wu J, Li Y, Xu E, Hong Z, Li Z, Zhang W, Ding M, Gao X, Fan D, Zeng J, Wong K, Lu C, Xiao J, Yao C; Cilostazol as an alternative to aspirin after ischaemic stroke: a randomised, double-blind, pilot study. Lancet Neurol 2008 Jun; 7(6):494-9.
• 43) Jose´ I Ferna´ ndez-Montequı´n, Blas Y Betancourt, Gisselle Leyva-Gonzalez, Ernesto L Mola, Katia Gala´ n-Naranjo, et al. Intralesional administration of epidermal growth factor-based formulation (Heberprot-P) in chronic diabetic foot ulcer: treatment up to complete wound closure. International Wound Journal 2009; 6(1): 67-72
• 44) Acosta JB, Savigne W, Valdez C, Franco N, Alba JS, del Rio A, et al. Epidermal growth factor intralesional infiltrations can prevent amputation in patients with advanced diabetic foot wounds. Int Wound J 2006; 3: 232–239.
• 45) Velazquez W, Valles A, Curbelo W. Impact of epidermal growth factor on the treatment of diabetic foot ulcer. Biotecnologia Aplicada 2010; 27: 136–141.
• 46) Nather A, Chionh SB, Audrey YY Han, Pauline PL Chan, Nambiar A. Effectiveness of Vacuum-assisted Closure (VAC) Therapy in the Healing of Chronic Diabetic Foot Ulcers. Ann Acad Med Singapore 2010; 39: 353-358
• 47) Armstrong DG, Lavery LA, Abu-Rumman P, Espensen EH, Vazquez JR, Nixon BP, et al. Outcomes of subatmospheric pressure dressing therapy on wounds of the diabetic foot. Ostomy Wound Manage 2002; 48: 64-68.
• 48) Clare MP, Fitzgibbons TC, McMullen ST, Stice RC, Hayes DF, Henkel L. Experience with the vacuum assisted closure negative pressure technique in the treatment of non-healing diabetic and dysvascular wounds. Foot Ankle Int 2002; 23: 896-901.