Suction blister transplantation for leg ulcers.

Application of suction blister transplants to leg ulcers is an alternative symptomatic treatment to split-skin grafting, i.e. "pinch-grafting". Blisters are produced by the suction device Dermovac at a suction pressure of 250-300 mmHg for 1-2 hours. The blister-roofs are cut off at the periphery and placed on the granulation tissue of the ulcer. The healing time for leg ulcers was 10-14 days. Excellent epithelialization was seen in 10 out of 12 ulcers. The advantages of the method are, that it is easy to perform, no scarring is produced, and the procedure is painless.     

Treatment of leg ulcers with cryopreserved allogeneic cultured epithelium. A multicenter study.

BACKGROUND--In the past few years, several authors have described the usefulness of cultured allogeneic epidermal sheets in promoting wound healing of burns, leg ulcers, and donor sites. This study reports clinical results obtained by different departments in the treatment of chronic leg ulcers by cryopreserved cultured allogeneic epithelium. The freezing procedure and the assessment of viability of the cryopreserved epithelium are also described. A total of 30 ulcers were treated using 138 cryopreserved allografts. OBSERVATIONS--Twenty ulcers (66.6%) healed completely within 12 weeks. Four ulcers showed a 30% to 84.4% reduction in size by 3 weeks but did not heal completely; the remaining six ulcers did not show any improvement. A strong stimulation of granulation tissue formation and of reepithelialization from the wound edge were observed. RESULTS--The results indicate that frozen cultured epidermis, stored in a skin bank, is a valid and generally applicable alternative therapy for the treatment of chronic ulcers.     

Allogeneic cultured keratinocytes in the treatment of leg ulcers. A pilot study.

Forty-two patients (10 males and 32 females) with 52 chronic leg ulcers were treated with sheets of cultured allogeneic keratinocytes. Sixty-five % of the ulcers healed completely and the healing rate differed between various diagnostic groups. The best results were obtained in patients with venous ulcers and wounds with mixed etiology, whereas less improvement was observed with ischaemic ulcers. Rheumatic ulcers also responded well in combination with oral corticosteroids. The overall impression was that the grafting procedure markedly enhanced wound healing.     

A retrospective review of 20 hypertensive leg ulcers treated with mesh skin grafts

BACKGROUND: Few articles have been published about hypertensive leg ulcers and their surgical treatment. Since mid of the year 2000, it has been our policy to treat all hypertensive leg ulcers very early with mesh split-thickness skin grafts. The present series consists of 15 patients whose hypertensive leg ulcers, including five bilateral cases, were treated with 20 mesh grafts from 2000 to 2002. SUBJECTS AND METHODS: All patients, nine women and six men, had a long history of hypertension. The same surgical procedure was applied to all 15 patients: a complete mechanical debridement of all necrotic tissues, immediately followed by mesh skin grafting. RESULTS: Patients were discharged from the hospital after an average post-operative period of 16 days. Upon leaving the hospital, the patients had lesions completely healed in 14 of 20 cases. The graft take had been complete after an average period of 14 days. In six cases, one or two very small patches of skin graft had necrosed and complete healing required an additional period of 1 to 3 months. In all 20 cases, pain had disappeared within 1 week from surgery. DISCUSSION: All patients were on opioid therapy before surgery. With medical treatment only, hypertensive leg ulcers used to heal after a mean period of 15 months. After surgery, the average healing period was 2 weeks and opioids were stopped within 1 month after surgery. CONCLUSION: The review of the present series shows that early mesh grafting of hypertensive leg ulcers is beneficial, because healing is very quick and the pain will disappear quasi-instantly.     

Pinch grafting of chronic leg ulcers in primary care: fourteen years' experience

Pinch grafting for treatment of chronic leg ulcers has been evaluated mainly in hospitalized and immobilized patients. This study describes the results of 199 pinch graft operations of 126 chronic leg and foot ulcers in 85 patients in primary care between 1987 and 2001. The aetiology of the ulcers was venous insufficiency in 43% and multi-factorial in 25% (77% with venous insufficiency as the main determinant). The mean ulcer size was 13.5 cm2 and the mean ulcer duration was 15.9 months. The overall healing rate within 3 months was 33%, ranging from 19% for multi-factorial or combined venous and arterial ulcers to 48% for venous ulcers. Within 12 months the overall healing rate was 60%, with 67% healed venous ulcers. The results from our study suggest that pinch grafting is suitable for treating chronic leg ulcers, especially venous ulcers, in primary care.     

Efficacy of erbium YAG laser-assisted autologous epidermal grafting in vitiligo

BACKGROUND: Of the various modalities of therapy available for the treatment of vitiligo, a combination of psoralen + ultraviolet A (PUVA) with autologous epidermal grafting appears to offer the best results. The erbium YAG laser can be used to prepare the recipient site in both punch grafting and suction blister grafting. METHODS: In this study 29 subjects, 26 with localized and three with generalized stable vitiligo, had received pregrafting PUVA and underwent further PUVA starting 2 weeks after surgery until maximal pigmentation was achieved. The erbium YAG laser was used on 16 subjects; the recipient site for punch grafting was prepared with laser and minigrafts harvested by manual punch were placed into the prepared sites. For suction blister grafting, the site was dermabraded with a laser and the harvested blister roof (created using suction apparatus) was transplanted on to the site. RESULTS: More than two-thirds (68.75%) of the subjects who were punch grafted using a laser showed repigmentation of more than 75%, but only one-half of those who underwent conventional punch grafting showed a similar response. All subjects with laser-assisted suction blister grafting showed a good response, compared with only 60% of those who underwent conventional suction blister grafting. CONCLUSIONS: The results obtained with laser-assisted grafting are more satisfactory than those achieved with conventional grafting techniques. We found that the repigmentation zones are larger (up to 9 mm in the former vs. 3 mm in the latter) and cobblestoning does not occur with laser-assisted grafting. Also, the procedure is precise, relatively atraumatic and can be performed rapidly even when covering vast areas.     

Recombinant human granulocyte-macrophage colony-stimulating factor applied locally in low doses enhances healing and prevents recurrence of chronic venous ulcers

BACKGROUND: Chronic venous leg ulcers have a major medical and economic impact on the elderly worldwide. Healing of the large ulcers (>10 cm2) occurs only in two-thirds of the patients and reulceration of healed ulcers recurs in one-third within 1 year. Because both healing and relapse rate influence greatly a patient's quality of life and the overall cost of treatment, every effort should be made to improve these two parameters. OBJECTIVE: To determine the safety and efficacy of topical low-dose recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) for the treatment of venous ulcers, and to document any improvement in healing rates. METHODS: Thirty-eight patients (29 women, 9 men; median age, 74 years) with chronic venous insufficiency were treated with topical rhu GM-CSF (5 microg/mL 0.9% sodium chloride solution), followed by application of a compression dressing. All subjects were treated as outpatients. RESULTS: Complete healing was observed in 47 of the 52 ulcers (90.4%). The average healing time was 19 weeks. No systemic or local side-effects from the therapy were observed. Nine chronic ulcers, previously refractory to conventional treatment (pretreatment for more than 46 weeks), showed the same response rate (9/8, or 88.9%) and healing time (mean, 19 weeks). After 40 months, no reulceration of the healed ulcers was observed, but two patients developed new ulcers on the same leg. Healing remained stable, with excellent cosmetic results. CONCLUSIONS: In this first study, topically applied low-dose rhu GM-CSF was a safe treatment for chronic venous leg ulcers. Healing rates were significantly increased and relapse rates were minimal.     

A multicentre study of percentage change in venous leg ulcer area as a prognostic index of healing at 24 weeks

Venous leg ulcers, which may take months to heal, account for 40-70% of all lower extremity chronic wounds. New treatment options for venous leg ulcers have recently been proposed, and therefore deciding which patients are candidates for these novel-and often expensive-treatments is an important task. Moreover, researchers conducting clinical trials often wish to enroll patients who are unlikely to heal in order to minimize sample sizes needed and research costs. Our purpose was to assess the use of percentage change in venous leg ulcer area over the first few weeks of treatment as a prognostic indicator of healing or non-healing at 24 weeks. We conducted a cohort study based on an existing data set from a multicentre randomized clinical trial that enrolled 104 patients. Wounds were measured using digital planimetry for 4 consecutive weeks following the inception of good wound care. Utilizing the Wilcoxon rank sum (Mann-Whitney) test, we found that percentage change in area over time distinguished between those who healed and those who failed to heal after 24 weeks of good wound care (P < 0.05). The rate of healing, or area healed per week, did not differentiate between those who healed at 24 weeks and those who did not, as all patients had similar rates of healing over the first 4 weeks of treatment. Percentage change in area from baseline to week 4 provided the best combination of positive and negative predictive values (68.2%, 74.7%) and the largest area under the receiver operating characteristic curve (0.75). Thus, percentage change in area over the first 4 weeks of treatment represents a practical and predictive measure of complete wound healing by 24 weeks.     

Unterschiedliche Abheilungsdauer und Häufigkeit der Hospitalisation bei Ulcus cruris verschiedener Ursachen

Background

Leg ulcers are a symptom of a heterogeneous group of diseases. Their treatment causes substantial costs due to the long healing times and extensive wound care measures. There is a paucity of information about healing times and the necessity of hospital treatment for leg ulcers of different etiologies.

Materials and methods

In this retrospective study, healing times and the frequency of in-hospital treatment of 355 patients with leg ulcers attending a wound care clinic of a university hospital were examined.

Results

The proportion of healed ulcers was 32.0?% after 3 months and 54.3?% after 6 months with an average treatment duration of 6.1 months for all ulcers. This proportion of healed ulcers was higher for venous ulcers with 45.5?% after 3 months and 63.0?% after 6 months, whereas only 30.0?% of mixed arterial-venous ulcers and 35.0?% of hypertensive ischemic leg ulcers (HYTILU) were healed after 6 months. Of the latter group, 71?% of patients were hospitalized at least once during the observation period as compared to 47?% of patients with a venous ulcer. The duration of the hospital stay was longer for mixed ulcers and HYTILU with an average of 30 days vs. 23 days for venous ulcers.

Conclusions

These data indicate that the healing times of ulcers of different etiologies differ substantially and that especially ulcers with arteriosclerosis as a causative factor have longer healing times. The fact that they require in-hospital treatment more frequently and for longer periods has significant socio-economic consequences.     

Grafting of skin ulcers with cultured autologous epidermal cells

We treated five adult individuals with six full-thickness chronic ulcerations in the skin caused by venous insufficiency, sickle cell anemia, or surgical wounds. Each patient received applications to the ulcerations of sheets of autologous epidermal cells grown in culture. All patients experienced relief of pain after grafting. Four of the six ulcers healed completely in 21 to 35 days, and three of the four remained healed for up to 2 years. One ulceration recurred within 2 months. Our experience suggests that cultured autologous epidermal grafts can provide continuous covering, relief from pain, and rapid healing of chronic debilitating ulcerations of the skin.     

Topical prostaglandin E2 in the treatment of chronic leg ulcers—a pilot study

The results of treatment with topical PGE2 dispersed in hydrocolloid granules, in nine patients with chronic leg ulcers is reported. The healing process was evaluated by stereophotogrammetry, which enables objective measurements of ulcer area and volume. Ulcers in eight patients healed completely and that in the ninth, almost completely. These results suggest that topical PGE2 has a beneficial effect in the treatment of leg ulcers.     

Autologous full-thickness skin substitute for healing chronic wounds

BACKGROUND: Chronic wounds represent a major problem to our society. Therefore, advanced wound-healing strategies for the treatment of these wounds are expanding into the field of tissue engineering. OBJECTIVES: To develop a novel tissue-engineered, autologous, full-thickness skin substitute of entirely human origin and to determine its ability to heal chronic wounds. METHODS: Skin substitutes (fully differentiated epidermis on fibroblast-populated human dermis) were constructed from 3-mm punch biopsies isolated from patients to be treated. Acellular allodermis was used as a dermal matrix. After a prior 5-day vacuum-assisted closure therapy to prepare the wound bed, skin substitutes were applied in a simple one-step surgical procedure to 19 long-standing recalcitrant leg ulcers (14 patients; ulcer duration 0.5-50 years). RESULTS: The success rate in culturing biopsies was 97%. The skin substitute visibly resembled an autograft. Eleven of the 19 ulcers (size 1-10 cm2) healed within 8 weeks after a single application of the skin substitute. The other eight larger (60-150 cm2) and/or complicated ulcers healed completely (n = 5) or continued to decrease substantially in size (n = 3) after the 8-week follow-up period. Wound healing occurred by direct take of the skin substitute (n = 12) and/or stimulation of granulation tissue/epithelialization (n = 7). Skin substitutes were very well tolerated and pain relief was immediate after application. CONCLUSIONS: Application of this novel skin substitute provides a promising new therapy for healing chronic wounds resistant to conventional therapies.     

Role of sulphydryl-containing agents in the management of venous (varicose) ulceration. A new approach

This randomized double-blind controlled study examined whether sulphydryl-containing agents influence the healing of venous ulceration occurring for the first time on the medial side of the leg. Graduated compression bandaging, which exerted a mean ankle pressure of 40.6 +/- 0.4 mmHg, and a mean below-knee pressure of 17.1 +/- 0.2 mmHg, healed 70% of ulcers within 12 weeks (n = 46). The addition of the sulphydryl-containing agents DL-cysteine (n = 46) or DL-methionine-methyl sulphonium chloride (n = 45) to the compression bandaging (daily application of the powder for 7 days, followed by once weekly applications until the end of the study 3 months later) significantly (P < 0.01) stimulated healing of venous ulceration relative to control values when studied 4, 8 and 12 weeks after commencing treatment. After 3 months of treatment, both sulphydryl-containing compounds healed 93% of the ulcers. The results show that sulphydryls stimulate healing of venous ulceration.     

Arterial hypertension causing leg ulcers

We report clinical and histological features of 16 consecutive patients with hypertensive leg ulcers. The lumen/wall ratio in arterioles at the edges of these hypertensive leg ulcers was compared with that in other types of chronic leg ulcers and was found to be significantly reduced (P < 0.001). Additional conditions such as venous hypertension or main vessel arterial disease contributed. Nineteen of 22 ulcers were completely healed after a mean of 4.9 months. Recognition of this condition enables correct treatment choice, which usually involves excision and grafting, and early healing. The classical hypertensive leg ulcer was initially described by Martorell in 1945¹ and subsequently by others.^2–8 As described, it is situated on the lateral aspect of the lower leg above the ankle, is painful, often severely so, and has necrotic edges. Patients have a history of arterial hypertension, although the blood pressure may be normal at presentation. There is usually no surrounding oedema or stasis pigmentation and peripheral vascular disease is absent. The ulcers are often resistant to conservative treatments and most reported cases eventually require excision and grafting or lumbar sympathectomy before healing occurs. Martorell¹ emphasized that usually there is no evidence of main vessel arterial disease or a disturbance in the venous circulation. Milder or atypical cases may be misdiagnosed. We studied patients with leg ulcers in which hypertension was considered the main aetiological factor to document features.     

Cryopreserved and lyophilized cultured epidermal allografts in the treatment of leg ulcers: a pilot study

BACKGROUND: In the conservative therapy of venous leg ulcers modern types of dressings are used most frequently. In the past 20 years 'active wound dressings' - cultured epidermal keratinocytes as autografts and allografts - were also introduced in the management of leg ulcers. METHODS: The aim of our study was to compare the effect of cryopreserved and lyophilized cultured epidermal allografts in the treatment of venous leg ulcers. Evaluation of the therapy was documented as photodocumentation, planimetry, healing time and evaluation of pain relief over a 3-month period after application. Fifty patients with venous leg ulcers were selected. Twenty-five patients (group I) were treated with cryopreserved keratinocytes and 25 (group II) with lyophilized keratinocytes. RESULTS: The final evaluation 3 months after the application of allografts showed 84% of healed ulcers in group I and 80% in group II. The number of healed ulcers and the healing rate both showed no statistically significant differences. The size of the ulcer was reduced by half during the first week in both groups. The size differences during the first week are statistically significant in both groups and they are comparable (P < 0.001). The intensity of the pain was statistically significantly reduced during the first week after application in both groups (P < 0.001). CONCLUSIONS: The cryopreserved and lyophilized cultured allografts are comparable in healing rate, course of healing and relief of pain, and also in planimetric changes during the healing of venous leg ulcers. Lyophilized allografts are more convenient for routine use than cryopreserved allografts as they can be stored at room temperature. These results could give rise to the more frequent use of lyophilized allografts in slow-healing venous leg ulcers.     

Fibrin Glue Fixation for Suction Blister Epidermal Grafting in Two Patients with Stable Vitiligo

Vitiligo is a chronic disorder characterized by depigmented macules which can slowly enlarge with the concurrent development of new lesions. Although autologous suction blister epidermal grafting is an established technique for the treatment of recalcitrant, stable vitiligo, the donor tissue graft is not easy to fix at the recipient site, especially in areas such as the joints, face, cutaneous folds, hands, feet, and hair-bearing areas. Therefore, various methods of donor tissue fixation have been attempted. We report two cases of vitiligo treated with suction blister epidermal grafting, with fibrin tissue adhesion. The first case is that of 16-year-old female patient presented with hypopigmented patches on the forehead and frontal scalp area. The other case is that of 32-year-old female patient presented with hypopigmented patches on the chin. We treated them with phototherapy for 1~4 years; however, the lesions were recalcitrant. Therefore, we tried treatment with a suction blister epidermal graft. Because graft fixation is difficult at the recipient sites, fibrin glue was sprayed on the grafts. Thereafter, we applied a porous silicone wound contact layer over the graft area and applied sterile gauze dressing that was left for a week. One week after the procedure, firm fixation of the donor tissue was observed in both cases. Fibrin glue seemed to improve the graft fixation, providng protection against infection and an optimal environment for wound healing. This report suggests that the application of an epidermal graft with fibrin glufixation, can provide the best result in the surgical treatment of stable vitiligo.     

Allogeneic cultured epidermal grafts heal chronic ulcers although they do not remain as proved by DNA analysis

To investigate whether allogeneic cultured keratinocytes are rejected or not, and to find out how beneficial their effect on wound healing could be, patients with chronic ulcers were grafted with allogeneic cultured human keratinocytes. In order to examine the epidermal origin of the healed wound, DNA analysis was performed and compared to donor and recipient blood-cell DNA. Healing was observed in 84% of the grafted ulcers by granulation tissue stimulation and would edge effect. In little time 60% of the grafted chronic ulcers healed completely. Although no rejection was observed, DNA analysis revealed that the grafted allogeneic keratinocytes were finally replaced by the patient's own epidermis. This study confirmed that cultured allogeneic keratinocytes that have been grafted on ulcers, play an important role in the wound healing process.     

Organotypic cultures of autologous hair follicle keratinocytes for the treatment of recurrent leg ulcers

Our purpose was to evaluate, in an open study, the efficacy of epidermal equivalents (EEs), a tissue-engineered epidermis prepared from autologous hair follicle keratinocytes, for the treatment of recurrent leg ulcers (n = 50). To generate EEs, keratinocytes expanded from the outer root sheaths of plucked anagen hair follicles were seeded on cell culture inserts at air-liquid interface. The total culture time was 5 to 6 weeks. Three days after the procedure, 95% of EEs adhered to the wound bed. After 8 weeks, 70% of the total wound surface was re-epithelialized and 32% of the ulcers were healed. After applying the EEs, a major relief of wound pain was noticed by the patients. EEs were applied in ambulatory patients without surgical facilities. Because 92% of the cases included in this study presented a recurrence of their ulcers after a split-thickness skin graft, we consider these ulcers as difficult to treat and propose the EEs as an alternative effective treatment of recurrent leg ulcers.     

Grafting of venous leg ulcers. An intraindividual comparison between cultured skin equivalents and full-thickness skin punch grafts

Skin equivalents that consisted of a noncontracted collagen gel populated with allogeneic fibroblasts and covered with autologous cultured keratinocytes were used for grafting venous leg ulcers. The results were compared in the same patient with those obtained with a routinely used standard method of grafting with autologous full-thickness punch grafts. The skin equivalents and the punch grafts were grafted successfully in four of five patients. The median healing time of ulcers grafted with skin equivalents was 18 days whereas that of ulcers covered with punch grafts was 15 days. The cosmetic appearance of the skin equivalent-grafted ulcers was better than that of the punch-grafted ulcers.     

Epidermal grafting for depigmentation due to discoid lupus erythematosus.

BACKGROUND: Longstanding lesions of discoid lupus erythematosus (DLE) may heal with thin, depigmented scar(s). The depigmentation may fail to respond to medical therapies. OBJECTIVE: To evaluate the efficacy of suction blister epidermal grafting in longstanding, quiescent, depigmented scar(s) of DLE. METHODS: The suction blisters were raised on the lateral aspect of the upper third of the thigh in 4 patients (3 males, 1 female) with depigmented scars of DLE on the face. The roofs of the blisters were transferred to the dermabraded recipient area. Both donor and recipient sites were dressed with nonadherent tulle. RESULTS: The dressings were removed after 7 days. The graft take was complete. The pigmentation achieved was more than 100% of the grafted area due to peripheral spread of the pigmentation and more than 75% of the depigmented area. The color match was good. There was no loss of pigment or recurrence/relapse of the disease during the follow-up of 6 months to 1 year. CONCLUSIONS: Our preliminary results suggest that leukodermic scars of healed inactive DLE lesions can be successfully treated with epidermal grafting.