I. General concept of ulcers
Ulcers are one of the common diseases,as clinicians often encounter the treatment of ulcers. The definition of ulcers seems to be self-explanatory, however, the difference between wounds and ulcers is not very clear to many people. According to Dermatology [1], “a deep dermal or subcutaneous tissue defect is called an ulcer, in which a deep, round-hole-shaped purulent ulcer is called an abscess, and a small, deeply located ulcer is called a fistula.” Lever’s [2] defines an ulcer as “a partial defect of the epidermis and dermis that leaves a scar after healing.” On the other hand, Anderson’s [3] pathology considers that “inflammation occurs near the surface of tissues or organs, and strong inflammatory irritation causes necrosis of tissues, which become ulcers after exfoliation.” The above shows that dermatology in histomorphology, the partial defect of epithelium and dermis is called ulcer, not necessarily with inflammatory symptoms as a condition. In pathology, the surface of the organ is first inflamed and the necrotic tissue is shed to form an ulcer. That is, wounds are classified as ulcers in dermatology, but not in pathology.
The relationship between wounds and ulcers, according to Siemens [4], is that “wounds that cannot be cured at once usually develop a secondary infection, and granulation tissue grows and covers the bottom of the wound, at which point the wound is called an ulcer.” . It is worth noting that this part of the wound is sometimes referred to as an open wound in China, and the author classified this part of the wound as a traumatic ulcer.
Refractory ulcers are commonly found in the extremities, especially in the lower extremities of the anterior tibia and the foot where there are few soft tissue reserves, and are often difficult to treat once skin defects and ulcers are formed because of the venous stasis easily caused by standing and walking, and the poor local blood supply compared with other parts of the body.
II. Reasons for refractory ulcers
In the process of treatment of chronic ulcers, we must first find out the causes and triggers of ulcer formation, as well as the disturbing factors that prevent trauma healing, and on this basis choose the appropriate treatment method. There are various causes of refractory ulcers of the extremities, which can be divided into 3 major categories [5-7], one is exogenous ulcers caused by skin damage due to extra-skin factors, the other is endogenous ulcers caused by internal factors of the organism, and the third is compound ulcers caused by both internal and external compounding factors (Table 1). Most refractory ulcers are caused by trauma, vascular disorders, diabetes mellitus and radiation damage, but for some ulcers that do not heal, other rare causes should be considered, such as atypical anaerobic bacteria, fungal infections, VitC, zinc deficiency and the possibility of malignancy.
The pathological state of refractory ulcers
From a surgical point of view, most of the reasons that prevent refractory ulcers from healing are insufficient tissue volume and impaired blood circulation. Most of the post-traumatic refractory ulcers have a deficiency of absolute tissue volume, occlusive arteriosclerosis, venous stasis of the lower extremities, connective tissue disease and radiologically induced ulcers are associated with impaired blood supply. As symptomatic treatment, tissue transplantation or improvement of the blood supply can be performed by replacing the cover with tissue of good blood supply. The stage of development of the decubitus wound, in the necrotic phase, the infected exudative phase, the granulomatous phase or the healing phase of growth, should be judged and treated differently. Recently, the development of skin grafting and flap grafting techniques has provided an effective treatment for refractory ulcers [7].
IV. Treatment
First of all, it is necessary to explore the causes, triggers and influencing factors that prevent healing of refractory ulcers, and to choose appropriate surgical treatment if systemic treatment and local conservative treatment fail to heal. Indefinite conservative treatment and rash amputation of limbs should be avoided.
(1) Preoperative examination
Bacteriological examination: Bacterial culture and drug sensitivity test should be performed on the ulcer exudate to select the appropriate antimicrobial agent. Preoperative asepsis is ideal, but sometimes difficult to achieve. Pseudomonas aeruginosa is not an absolute surgical contraindication, and wound healing can be achieved through debridement and tissue coverage.
Blood tests: anemia, hypoproteinemia is one of the causes of refractory ulcers and sometimes may be the result of chronic ulcers.
X-rays: To determine the presence of osteomyelitis, calcification of vascular tissue and foot deformities.
Biopsy: The possibility of malignant ulcers should be considered for long-term chronic ulcers that do not heal. The more typical ones are those that occur in scars and repeatedly break down, mostly over 10 years, with a high chance of malignant transformation (Majolin Ulcer). Other carcinomas such as basal cell carcinoma and squamous carcinoma may also manifest as skin ulcers.
(2) Conservative treatment
Systemic treatment: Diabetes mellitus, connective tissue disease, etc. should be treated first with appropriate systemic treatment to control the development of the disease. Surgical treatment should be carried out after the condition is stabilized. Long-term high-dose application of steroid corticosteroids can delay the healing of ulcers, and should be slowly reduced and discontinued when the condition permits.
Local treatment: including necrotic tissue debridement, infection control, improvement of blood supply, maintenance of moist environment, promotion of granulation tissue growth and wound contraction, and promotion of epithelialization. Except for surgical removal of necrotic tissues, topical ointments or dressings are used for this purpose. There are many kinds of ointments, some of which are commercially available and some are prepared by the hospitals themselves, and they are applied according to the focus of the treatment stage.
The removal of necrotic tissues and surrounding scars mainly depends on surgical excision, and a small amount of necrotic tissues can be treated with drugs such as Chinese medicine Jiu Yi Dan, medicated thread buried in the main decay effect, hydrogen peroxide, in addition to inhibiting the growth of anaerobic bacteria, has a good effect on cleaning wounds and dissolving decayed tissues.
Trauma wet dressing (wet to dry dressing) is an effective way to control infection, you can use saline wet dressing, sensitive antimicrobial wet dressing, or Uzo (mainly bleaching powder) wet dressing.
Improved circulation can be achieved by infrared light, helium-neon laser irradiation, or ointments containing vasodilators such as PGE1, and elevation of the affected limb.
Maintaining a moist environment has been shown to promote wound healing and is more effective than dry therapy. A large number of ointments, such as silver sulfadiazine (SD-Ag) cream, aureomycin ointment, wet wound dressing or application of a biologic dressing such as ampoule, can be applied. However, maintaining a moist environment is only indicated for traumatic wounds, relatively clean wounds such as donor areas, and for chronic ulcers for wounds with well-controlled infection and in the granulation growth phase.
Promoting the growth of granulation and epithelial tissues can be done by wet compresses with 10% glucose solution containing a little insulin, which can promote the absorption and utilization of sugar by local tissues. Oriental 1 (herbal compounded topical preparation), SD-Ag cream, Skin Care (cumecoside), and various long skin creams are also available. Recently notable is the application of bioactive growth factors, TGF-beta, bFGF as well as the neurotransmitter CGRP (calcintonin-gene related peptide) [8] and vasoactive intestinal polypeptide have been shown to promote granulation and Among them, bFGF-containing agents are commercially available and have been clinically tested with good results. It is worth noting that bFGF should be stored in the refrigerator and purchased at any time to prevent inactivation of active factors.
A misconception worth noting in the treatment of refractory ulcers is that many people do not bathe for a long time for fear of getting water into the wound. Bathing cleans the wound, improves blood circulation and promotes the growth of granulation and epithelium. Moreover, it is important that the patient’s mental changes after showering. Patients should be encouraged to take a shower during the treatment of refractory ulcers, and the wound can be rinsed off with water.
(3) Surgical treatment
Skin grafting: In order to ensure the survival of the transplanted skin pieces, thin bladed thick mesh skin grafting needs to be chosen. You can also choose methods such as dotted implant or intra-sarcomeric epidermal embedding.
Dermal and musculocutaneous flaps: Refractory ulcers are often associated with blood supply problems, and sufficient attention should be paid to the design of local flaps. If the recipient area is well vascularized, free flap grafting is an effective method for large scale ulcers.
(4) Postoperative management
Refractory ulcers often have recurrence, and postoperative care is important after wound healing. Quietness and elevation of the affected limb, selection of protective elastic stockings, soft-soled shoes, etc. are used as needed.
V. Classification and treatment of refractory ulcers
1. Traumatic refractory ulcers
There are mainly three kinds of chronic refractory ulcers caused by trauma. One is a skin defect of medium degree or above, which cannot be healed for a long time by conservative treatment and becomes a refractory ulcer. Second, ulcers formed within highly scarred tissues, which repeatedly ulcerate and sometimes malignantly become scar cancer. Third, chronic ulcers or fistulas with osteomyelitis, which are difficult to be cured if the osteomyelitis is not controlled.
Treatment of intra-scar ulcers should include excision of the scar together followed by skin grafting (Figure 1). Especially in the anterior tibia, local ulcers can recur without excision of the scar that is healed together with the tibia and covered with a skin flap. In ulcers with joint scar contracture, local skin grafting or flap grafting is performed after the ulcer is excised and the scar adhesions are sufficiently loosened. In addition, multiple biopsies should be performed when repeated ulcers within the scar are suspected of being malignant. Ulcers with osteomyelitis are given priority for treatment of osteomyelitis, and the lesion can be scratched, bone grafted, covered with skin flap or filled with myocutaneous flap.
2.Diabetic ulcers
With the increase in the incidence of diabetes, the number of patients with diabetic foot ulcers is also increasing. The causes of ulcers can be divided into two categories: neurological dysfunction and blood circulation disorders. Diabetic ulcers rely excessively on conservative medical treatment, which takes a long time to treat, forms unstable scars after healing, and is easy to repeatedly ulcerate. If the wound does not heal after a certain time of medication change, surgical treatment such as blood supply reconstruction or skin grafting should be considered.
Treatment guidelines vary depending on the presence or absence of arterial occlusion. In the presence of arterial occlusion, blood supply reconstruction should be considered, or limb dissection and early rehabilitation should be performed in a site with good blood supply. In the case of palpable dorsalis pedis artery pulsation, conservative treatment should be performed first (Figure 2) to keep the affected limb quiet and control infection, and skin grafting later. Early removal of necrotic tissue, especially necrotic tendon tissue, is proven to be the key to promote early healing of ulcers. Diabetic ulcers are often associated with autonomic nerve disorders, and the opening of arteriovenous anastomosis causes the phenomenon of blood theft (stealing phenomenon), and the pressure of small arteries decreases, so the design of local flaps should be carefully considered, and the pressure resistance of flaps is also significantly reduced, which should be paid sufficient attention to prevent recurrence.
3.Venous ulcers
Venous ulcers have the highest incidence of intractable ulcers in the extremities. Due to deep vein obstruction or regurgitation caused by venous valve insufficiency, the venous pressure rises, resulting in extravascular leakage of serum proteins and red blood cells, leading to subcutaneous tissue fibrosis, skin pigmentation and ulcer formation. The fibrin cuff theory (FCT) has attracted more attention [9]. This theory suggests that elevated venous pressure causes fibrinogen to leak out of the blood vessels and transform into fibrin in the interstitium, which accumulates around the capillaries and forms a fibrin cuff, causing impaired supply of oxygen and other nutrients, tissue necrosis, and preventing wound healing. Venous ulcers tend to occur in the lower 1/3 of the inner calf. Deep vein obstruction tests as well as venography are useful for diagnosis. Treatment includes elevation of the affected limb, wearing elastic socks, applying TGF-beta and CGRP, etc. If conservative treatment is ineffective, superficial vein stripping of the lower limb and ligation of subfascial traffic branches are chosen; if chronic failure to heal, skin grafting or flap grafting is performed.
4.Arterial ulcers
Arterial ulcers are different from venous ulcers in that they are associated with severe pain and are commonly associated with arteriosclerotic occlusive disease. Arteriography can help clinical diagnosis, and vasodilating drugs such as low right, salvia, pulsatilla, pansentin and PGE1 can be applied. In patients with reconstructed arterial blood supply, ulcers can be cured outside, reconstruction of microvascular lesions is more difficult, and limb dissection is often the only option.
5.Radioactive ulcers
The treatment of radioactive ulcers is sometimes very difficult. After irradiation, skin fibrosis, tissue atrophy and hardening, vascular regeneration is impaired, and the wound does not heal easily. Sometimes the wound seems to grow back, but it is still difficult to heal due to impaired wound contraction and poor epithelial proliferation. Therefore, early surgery and covering with tissues with good blood supply is an effective way to treat radioactive ulcers as long as the systemic condition allows. Conservative treatment can be done with Beflex (Figure 3), anti-oxidant free radical drug SOD, etc., all of which require attention to prevent inactivation of active factors.
6.Leakage ulcers
Ulcers caused by leaking intravenous drips vary in treatment depending on the nature of the leaking drug. One type is the leakage of electrolytes or hypertonic sugar in large quantities, which can cause skin ulcers, but since the electrolyte solution itself is not cytotoxic, the ulcers are usually not very deep and can be healed by drug exchange or skin implantation. The other category is anticancer drugs, especially mitomycin and adriamycin, which have high cytotoxicity, deeper ulcers, local cell division disorder, and wounds that do not heal easily. It often requires excision of necrotic tissue followed by skin graft or flap graft (Figure 4).
7.Werner syndrome
Werner syndrome is a relatively rare systemic disease, which is associated with premature appearance, cataract and skin sclerosis, in addition to refractory ulcers. Conservative treatment is ineffective and requires skin grafting or flap grafting. When local flaps are used, attention needs to be paid to arteriosclerosis and skin sclerosis.