Clinical Surgery in General - part 6 doc

Principles of skin cover P. E. M. Butler, J. L. Atkins Objectives Understand the pathophysiological changes accompanying, and resulting from, different types of skin loss. Recognize the importance of pre-existing conditions in the skin and contiguous tissues before the skin loss. Differentiate between the special features of skin in different parts of the body. Identify circumstances in which primary closure is possible, better deferred, and contraindicated. Recognize the available methods of achieving closure and their indications. INTRODUCTION The skin is the largest organ of the body, forming just under a sixth of the total body weight. Skin function varies in different parts of the body and this is reflected in its qualities. Although the basic structure of skin is constant, thickness and elasticity, pigmentation, and the presence or absence of specialized skin appendages, such as exocrine glands, nails, hair and sensory apparatus, differ. Skin provides a number of diverse but vital functions to the body. Most obviously, it provides a physical barrier to the outside world, giving limited protection against mechanical, chemical and thermal damage as well as pre- venting invasion by microorganisms, including viruses. Its integrity is critical for homeostasis, maintaining the internal milieu by providing a relatively impermeable barrier to the passage of water, proteins or electrolytes in either direction. Similarly, a vital role in thermoregulation is manifest by the controlled release of sweat and variability of blood flow to the body surface, leading to heat loss or conservation as required. Melanin pigment within the dermis protects the skin by absorbing ultraviolet rays of long (UVA) and medium (UVB) wavelength. Sensory information received from sensory appendages located within the dermis is both vast and subtle, while the synthesis of vitamin D and deposition of fat in the subcutaneous layer are functions of metabolic importance. The appearance and feel of our skin is critical; abnormalities are readily visible to the world at large, can be socially stigmatizing and are a source of psychological distress as well as physical discomfort to the affected individual. Skin loss through disease or trauma exposes an individual to the risk of bacterial and viral infections, uncon- trolled loss of serous fluid, proteins and electrolytes, and loss of mechanical protection to vulnerable underlying tissue. When skin wounds are very extensive they can be painful, disabling and life threatening, as is seen in burn injuries. Smaller wounds also deserve careful attention as they provide a defect through which serious infections may enter and produce life threatening conditions such as gas gangrene, toxic shock syndrome and necrotizing fasciitis. Chronic skin wounds can undergo malignant transformation, as seen in Bowen's disease (intradermal precancerous skin lesion described by the Harvard der- matologist in 1912), which may progress to squamous cell carcinoma. Poorly managed wounds heal slowly, and form ugly, weak scars with a poor functional result. Your primary aims in restoring skin cover are to provide optimal function and form in a timely fashion. Understanding how certain injury types affect tissue viability and lead to skin loss is paramount. Undertake a systematic and thorough assessment of the patient in general, and the wound in particular, before instituting an appropriate course of treatment and rehabilitation. SKIN CHARACTERISTICS 1. You are not dealing with a homogeneous body covering but with a varied, dynamic, responsive complex surface overlying varying supportive tissues. 2. Skin varies in different parts of the body in thickness, vascularity, nerve supply, ability to tolerate trauma, 241 24 OPERATION mobility, and also in special attributes; for example, palmar skin of the hands, and especially of the fingertips of the index finger and thumb, are irreplaceable. Although it is tough and able to withstand and respond to hard usage, it is richly supplied with a variety of afferent nerve endings, enabling us to utilize our fingers as important sensory organs. 3. The elasticity of the skin varies with age and the individual, producing tension lines. These tend to run cir- cumferentially around joints and the trunk, at least in early life. They are often named Langer's lines after Carl von Langer, the Austrian anatomist. By puncturing cadaveric skin with round spikes, he observed, in 1832, how the circular defects deformed as a result of skin tension. Incisions orientated parallel to tension lines heal with superior scars. 4. Fetal skin heals without scar formation; at birth skin is extremely elastic but with increasing age it becomes less so. In old age, following loss of fat and muscle bulk, the inelastic skin hangs in folds, especially on the abdomen and neck. 5. Viability is reduced by defective nutrition (such as vitamin C, zinc, protein), ischaemia, denervation, vascular congestion, inflammation and infection. The skin is friable overlying an abscess and also in an area of celluli- tis or erysipelas (Greek erythros = red + pella = skin). 6. Pathological changes may develop as a result of exposure to solar or ionizing radiation, cancer chemotherapy and various drug treatments. A variety of drugs, such as sulphonamides, barbiturates and non-steroidal anti- inflammatory substances (NSAIDs), may induce toxic epidermal necrolysis (TEN or Lyell's syndrome), in which fluid-filled bullae develop, separating sheets of epithelium from the underlying dermis. WOUND ASSESSMENT Key point • The history is as important as the appearance when assessing wounds. 1. Ascertain the timing, nature and force of the injury sustained. Accurately describe the appearance of a wound, and recognize how this changes over time; time elapsed since injury influences how you manage the wound. Ascertain exactly what tissue has been lost and what remains; are tendons, bones or neurovascular structures exposed? These may need urgent soft tissue cover to preserve function and prevent infection, and may require a more complex reconstruction. Wounds presenting early (<48 h) exhibit features of an acute inflammatory response. Following this acute phase, observe signs of healing in an untreated wound with some or all of the features of the acute inflammatory response having dispersed. Identify slough and granulation tissue in the wound base, with an advancing epithelial edge at the wound margin. Chronic inflammation occurs with continuing tissue damage; the wound exhibits features of ongoing tissue necrosis, acute inflammation, granulation tissue and fibrous scarring. 2. If you are inexperienced you may be distracted by the presence of an obvious or dramatic wound from other pathology. Carry out a full, careful examination of trauma- tized patients. Give priority to potentially life-threatening injuries; they require urgent treatment. 3. Different mechanisms of injury compromise tissue in different ways. Recognize and understand the effects of patterns of injury. The severity of the wound is affected by a number of factors. Elderly patients have thin, delicate skin, easily lost with relatively minor trauma compared with the skin of children or young adults. Take note of the anatomical area; pretibial skin is thin, vulnerable to trauma and slow to heal; skin on the back is thick and robust, while facial skin is delicate but heals quickly because it has a rich blood supply. Chronic systemic steroid use produces thin, atrophic skin, easily lost following minor trauma. Diabetics may develop peripheral neuropathy leading to chronic or recurrent ulceration of the lower limb; combined with microvascular disease and an impaired immune response, the ulcers heal reluctantly. SKIN LOSS Mechanical trauma 1. Contusion (Latin tundere = to bruise) results from blunt trauma. This is not usually a serious skin injury, but if it produces a haematoma, the swelling may cause pressure necrosis of the overlying skin. In elderly or anti- coagulated patients large haematomas may develop following a minor blow, leading to the formation of very large haematomas. Incise and evacuate these urgently to prevent loss of the overlying skin. Blood loss may be great enough to require transfusion. 2. Abrasion (Latin ab = from + radere = to scrape) is a superficial epidermal friction injury, often patchy. The epidermis regenerates by advancement of epithelium remaining within the skin appendages deep within the dermis. Healing is usually complete and can be encour- aged by gently and thoroughly cleaning the wound with a mild antiseptic to remove dirt or debris, and applying a moist, non-adherent occlusive dressing. Unless you 242 PRINCIPLES OF SKIN COVER 24 remove the dirt ground into the wound, permanent skin tattooing (Tahitian ta'tau) will develop. 3. Retraction (Latin re = back + trahere = to draw) of skin edges occurs when it is lacerated (Latin lacerare - to tear). Skin is innately elastic, the extent varying with age, race, familial trait, the use of systemic steroids, smoking and nutrition. If you are inexperienced you may mistake skin- edge retraction for skin loss, most commonly seen in children whose greater skin elasticity may lead to dramatic opening up of the wound. Avoid this mistake by carefully examining the wound and recognizing the pattern and markings of one edge that match those of the opposite edge if the skin has merely retracted. 4. Degloving results from severe shearing of the skin, for example, a pneumatic tyre running over a limb, detaching the skin from the underlying tissue. This separation may occur superficially, or beneath the layer of deep investing fascia, causing skin loss over a large area. The skin may tear, or remain intact initially, disguising the severity of this injury. Rupture of the vessels connecting the deeper tissues to the skin commonly produces ischaemic necrosis of the skin and other tissues superficial to the plane of separation. Prejudiced skin perfusion may be apparent from an absence of dermal bleeding at the skin edges, as may the absence of blanching followed by capillary refill, when you apply then release pressure. Subsequently the area of injury becomes more defined as the skin becomes mottled, then necrotic. You may be able to resurface the underlying tissue using a split thickness skin graft. 5. Avulsion (Latin ab = from + vellere - to pull) is the partial or complete tearing away of tissue and may involve skin, deeper structures such as bone, tendon, muscle and nerve, including digits, limbs or scalp. The force required to do this is considerable and creates a zone of injury around the point at which the tissue separates. Tissue is usually stretched, twisted and torn, leading to irreversible damage, in particular of neurovascular structures. It may be possible, when you have appropriate experience, to reattach or replant avulsed tissue using microvascular techniques. Completely avulsed tissue can be temporarily stored in moistened sterile gauze, sealed in a plastic bag and placed in ice, or stored in a refrigera- tor at 4°C. Vascular tissue such as muscle cannot be safely replanted if it has been ischaemic for more than 6 h. Tendon, skin and bone are more tolerant of ischaemia. Make every effort to salvage an avulsed or amputated upper limb, thumb, multiple lost digits, or digits in children. They are important for restoration of function, and especially in children they offer greater potential for recovery. Loss of individual digits is relatively less important in terms of benefit. An avulsed toe or foot is rarely suitable for microvascular replantation because sensory and functional recovery is poor and therefore unlikely to be satisfactory. If the patient has other significant life threatening injuries you may decide against attempting to reimplant divided tissues. Key point • Remember that even trivial skin loss may offer entry to strains of Staphylococcus aureus that may cause toxic shock syndrome, especially in vulnerable patients such as children, the elderly and the sick. Thermal injury 1. A scald (Latin ex = from + calidus = warm, hot) is caused by contact with hot liquids. A variety of agents may cause burns, such as flames, contact with hot objects, radiant heat and corrosive (Latin rodere = to gnaw) chemicals. 2. Through and through electrical injuries differ from other burns in that the passage of the electrical current through the body causes injury to deep tissue that may not be immediately apparent. A small entrance and exit burn of the skin may be the only visible manifestation of the injury. The electrolyte-rich blood acts as a conduit for the current flow and the vascular endothelium is damaged so that the vessels subsequently undergo thrombosis. Deep-seated tissue necrosis becomes apparent as the patient becomes increasingly unwell over hours or days. High voltage injuries are the most destructive, and alternating current is more likely to cause myocardial fibrillation than direct current. Surgical diathermy heats the tissues as a result of intense vibration of the ions caused by the low amperage high frequency, high voltage, alternating current (see Ch. 17). Faulty equipment and inexpert use may result in skin burns. 3. Exposure to cold air may cause frostbite. Excessive exposure to cold causes peripheral vascular spasm, with ischaemia and anoxia of the extremities, affecting a local- ized area of soft tissue. The extent of the injury is affected by temperature, duration of contact and pre-existing hypoperfusion of tissues. Four phases of injury have been described. These are; a. Pre-freeze (3-10°C): increased vascular permeability b. Freeze-thaw (-6 to -14°C): formation of intra- and extracellular ice crystal. c. Vascular stasis: blood is shunted away from the damaged area d. Late ischaemic phase: cell death, gangrene. Thawing, with restoration of the circulation, liberates inflammatory mediators. Microemboli form on the damaged endothelium and these increase the ischaemia and tissue loss. Treatment includes rewarming by 243 24 OPERATION immersion of the affected part in circulating warm water, elevation and splinting. Ischaemic areas are allowed to demarcate prior to amputation of the necrotic parts. Cryosurgery (Greek kryon = frost) offers a method of destroying skin lesions almost painlessly (see Ch. 17). A lesser result of exposure to cold is chilblains (Old English blain = a boil or blister). Contact with very cold objects can result in adherence of the skin, which is pulled off on separation. 4. Assess burns, in terms of site, percentage of the body surface damaged and depth of damage, to determine the prognosis and as a guide to treatment. Depth is superficial (1st degree), partial skin thickness including the dermis (2nd degree) and full thickness of all the layers of the skin (3rd degree). Burn depth is difficult to assess. White, insensate areas are generally full thickness. Partial thickness burns usually blanch on pressure and refill when the pressure is released; it remains sensate and may be blistered. Superficial burns are often erythematous, perfused, painful and tender to touch. 5. Generally, full thickness burns are managed by excision and skin grafting of the underlying tissue bed; partial thickness burns may be suitable for conservative treatment, allowing epidermal regeneration from remaining epithelial elements within the skin appendages of the dermis. Ulceration 'Ulcer' (Greek elkos, Latin ulcus = sore) usually has a con- notation of chronicity. An acute loss of skin is not called an ulcer unless it fails to heal. 1. Pressure sores develop from unrelieved pressure on the tissues in a debilitated patient, especially if there is neurological impairment. Other factors include nutritional deficit, diabetes mellitus, immunosuppression, incontinence and an inappropriate physical environment. The commonest affected areas are on the lower body within tissue overlying bony prominences. The sore develops as the tissue becomes compressed and oedema- tous; the pressure within the tissue exceeds the capillary perfusion pressure, leading to ischaemia and tissue necrosis. The tissue adjacent to the bony prominence suffers the most extensive injury, with the least at the level of the skin; the visible skin wound belies the reality of a much more extensive tissue loss. Key point Treatment is predominantly conservative. Institute measures to relieve pressure, such as the use of specially adapted wheelchairs, beds and other padding, correct any nutritional deficiency, eliminate infection, control incontinence and apply appropriate dressings. A minority require surgical intervention, such as wound debridement, excision of the bony prominence to encourage closure, or covering the area with a soft tissue flap. Use flaps cautiously in the presence of chronic predisposing illness such as multiple sclerosis. 2. Other common causes of ulceration include diabetes, autoimmune disorders, infection, ischaemia, venous disease and neoplastic lesions. Identify the underlying cause, if necessary by obtaining an incisional or punch biopsy of the margin, and treat the underlying cause. Any chronic ulcer may undergo malignant change, with the formation of Bowen's disease prior to malignant invasion as squamous cell carcinoma. 3. Raynaud's disease, described by the Parisian physi- cian in 1862, is an excessive arteriolar sensitivity to cold of the extremities. In Raynaud's phenomenon the spasm is secondary to vascular or connective tissue disease, or occupations in which vibrating tools need to be used. The spasm causes necrosis and ulceration of the extremities. Key point Development of pressure sores represents a failure to protect skin at risk from continuing pressure or contact with damaging substances, including body secretions and excretions. Record the progress by keeping serial photographs of wound size, extent and healing. BIOLOGY OF SKIN HEALING (see also Ch. 33) 1. Wound healing is a multistep overlapping process involving an inflammatory response, granulation tissue formation, new blood vessel formation, wound closure and tissue remodelling. Tissue damage causes extra- vasation of blood and its constituents. Platelets and macrophages release a number of chemical mediators including transforming growth factors (TGF), fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), insulin- like growth factor (IGF) and keratinocyte growth factor (KGF). 2. The injured cells and other cells and platelets generate vasoactive and chemotactic (Arabic al kimiea, Greek chemeia + tassein = to arrange; cell movement in response to a chemical stimulus) substances that attract inflammatory neutrophils. Monocytes are also attracted and convert to macrophages. These phagocytes remove 244 PRINCIPLES OF SKIN COVER 24 dead tissue and foreign material, including bacteria. As inflammatory exudate accumulates, there is a cascade of events leading to oedema, erythema, pain, heat and impaired function. Macrophages and factors derived from them are essential in stimulating repair (Singer & Clark 1999). 3. Epidermal cells from skin appendages break desmosomal contact with each other and also with the basement membrane; they migrate in the plane between the viable and necrotic tissues by producing collagenase, which degrades the intercellular substance (matrix) reinforced by matrix metalloproteinase. Epithelial cells behind the migrating ones proliferate after 1 or 2 days, probably from the release of growth factors. As re- epithelialization proceeds, the epithelial cells reattach themselves to the basement membrane and underlying dermis. 4. As a result of hypoxia, growth and angiogenesis factors are released by macrophages and activated epithelial cells. The wound is invaded by blood capillaries, macrophages, fibroblasts after 3-4 days, bringing nutrients and oxygen. The crests of the capillary loops appear like small cobblestones, hence the name of 'granulation' tissue. Blood capillaries require the presence of perivascular fibronectins (Latin nectere = to bind, tie) in order to move into the wound. Vascular growth is a delicate balance of positive regulators such as VEGF and PDGF, and negative regulators such as angiopoietin-2, endostatin and angiostatin. Once the wound is covered with granulation tissue angiogenesis stops. The fibroblasts synthesize extracellular matrix, which is later replaced with acellular collagen, when cells in the wound undergo apoptosis (Greek apo = from + piptein = to fall; programmed cell death). During the second week following injury, fibroblasts become myofibroblasts, acquiring actin-containing microfilaments (Greek aktinos = ray) and cell-to-cell and cell-to-matrix linkages. Probably under the influence of TGF and PDGF, the fibroblasts attach to the collagen matrix through integrin receptors and form cross-links. Myofibroblast contraction draws together the attachments at each end of the cell. However, in animal experiments the evidence for the role of myofibroblasts has been questioned (Berry et al 1998). 5. The contribution of epithelial migration and wound contraction to healing is not fully resolved. There are also differences in the factors involved between humans and in animal experiments. One suggestion is that wound contraction in granulation tissue results from the com- paction of collagen fibres influenced by cellular forces, not directly from contraction of cells pulling on the surrounding tissues. 6. When closure of large raw areas has failed or is unavailable, healing and scar formation continues for weeks, months or years. This is often termed scar con- tracture. Powerful forces draw in skin and scar tissue is laid down, often causing severe limitation of function. A classical example is that of a young child who pulls over a pan of scalding water, burning the face, neck, shoulder, chest, axilla and upper arm. The head is permanently drawn to the side of the burn, the neck is webbed, the shoulder is drawn upwards and fixed; the shoulder cannot be abducted and the deltoid muscle atrophies, while the anterior axillary fold and skin over the chest circumference is tight, restricting inspiration. 7. Collagen degradation proceeds in step with wound contraction. The wound gains only 20% of its final strength in the first 3 weeks, and the maximum strength it achieves is only 70% of that of normal skin. 8. Healing is prejudiced in diabetes, especially in the presence of neuropathy and ischaemia. Wounds are prone to infection because of impaired granulocyte function and chemotaxis. 9. Abnormal accumulation of collagen causes hypertrophic scarring and keloid formation. Normal mature scars and keloids display no scar contraction and they do not contain any myofibroblasts. Increased levels of TGFB, PDGF, interleukin 1 (IL-1) and IGF-I are present in both, with TGFB appearing to predominate. 10. Growth factors have proved disappointing in accelerating wound healing, possibly because they need to be administered in carefully graded doses and sequence. 11. Fetal skin wounds heal rapidly without scarring; the epithelial cells are drawn across the wound by contraction of actin fibres. Scarring does not occur because there is a reduced level of TGFB1. PRX-2, a member of the Paired Related Homeobox gene family, is upregu- lated in dermal fibroblasts during scarless fetal wound healing. DEBRIDEMENT 1. Debris, foreign material, devitalized tissue, slough, pus or heavy contamination with pathological bacteria form a focus for infection, irritate the wound, prevent the formation of granulation tissue and obstruct epithelial migration. 2. Excise all non-viable skin under anaesthesia and, if you are in doubt regarding viability, return the patient to the operating theatre for a second inspection and debridement after 24-48 h. Debridement (French de = from + bridle; unbridle = release from constriction) was origi- nally used for releasing tension but has been extended to mean the removal of dead tissue. 3. It can often be achieved non-surgically using saline irrigation, topical agents to lift slough or with dressings 245 24 OPERATION or sharp dissection under anaesthesia. Debride areas with specialized and precious tissue, such as the fingertips, palm and face, adequately but minimally. If there is uncertainty at the time of surgery as to the viability of tissue or adequacy of debridement, be willing to redress the wound with an occlusive non-adherent dressing and return the patient to the operating theatre for a second inspection after 24-48 h. ACHIEVING WOUND CLOSURE AND SKIN COVER No skin loss 1. Clean incised wounds vary, depending on where and how the wound is made. If it is made parallel to the lines of tension the edges remain closely apposed, if made across the tension lines they gape. There is virtually no damage to contiguous tissues so that, apart from the almost singular layer of cells along the line of division, the remainder of the tissues are viable. Such a wound, once closed, is said to heal by primary intention, and should heal with a fine linear scar. 2. If the incision is only partial thickness the deeper intact parts maintain the edges in good apposition. If the wound extends through the full thickness this support is partially lost, depending on the strength and attachment of the deeper tissues. 3. Abraded skin has intact deeper layers and will heal spontaneously. Torn skin dragged as a flap may initially appear viable; a triangular flap attached distally over the subcutaneous face of the tibia notoriously fails to survive. 4. In wounds with very irregular margins, it is helpful to close the most obvious matching points first and then to close the other points in between. Do not be afraid to remove and reposition sutures until the edges are per- fectly matched. Small bridges of skin separating lacera- tions are best excised to achieve a cosmetic result. Skin loss 1. When a skin or other superficial lesion has been excised, the surviving edges and the base are normally left healthy, dry and free of bacterial contamination, foreign material or dead tissue. 2. Closure can usually be performed immediately (primary closure); indeed the excision is usually planned with this in mind, except in the presence of malignant disease, when total clearance of the rumour is paramount. Primary closure allows more rapid healing and an earlier return to normal function. 3. In elective surgical procedures, the closure can be planned before operation and discussed with the patient. It may be possible to close the defect directly, reconstruct or resurface it. 4. As far as possible, replace large defects with skin and tissue giving the closest possible match to the surrounding tissues with regard to colour, thickness and texture. 5. To achieve the best results the wound edges must be accurately opposed. If the wound is irregular, perfect apposition can be aided by first identifying and apposing landmarks with key sutures before inserting intervening sutures. 6. Perfect closure is prejudiced by unevenness, inver- sion of the edges and tension, as inevitable postoperative oedema increases the tension. 7. Many small wounds of 1 cm in diameter or less, including many fingertip injuries, usually heal with a satisfactory result by secondary intention within 2-3 weeks. Treat larger wounds conservatively in ill, frail patients, and those likely to heal within a reasonable time. This may include pressure sores. Key point Assess the nature of the skin at the margins of the defect that you intend to close. Complicating factors 1. The skin may be atrophic or stretched, especially in elderly people, or affected by eczema, solar or ionizing radiation, hypertrophy or the scar of a previous operation. Neonatal and infant skin usually heals well. 2. Inflammation, neoplasm, ischaemia, oedema, infection, congestion or injury - possibly with the presence of foreign material - of contiguous tissues such as bones, muscles, tendons, nerves or vessels may force a change of strategy. 3. Repair is prejudiced if the patient is very old, undernourished, immunosuppressed is undergoing chemotherapy, or has general infection, neoplasia or organ failure. 4. The wound may be too large to close. Achieving closure 1. Grafting (Greek graphein = to write; from the Roman use of tree grafting using shoots sharpened like a pencil), may allow transfer of completely detached partial or full thickness skin from a donor site to a 246 PRINCIPLES OF SKIN COVER 24 wound that cannot be closed directly. The graft adheres by fibrinous bonds, initially gaining nourishment by serum imbibition - metabolites diffusing through the thin film of intervening serum. Capillaries connect from the recipient site and are functioning by the second day, but the connection is fragile and susceptible to shear stress for 2-3 weeks. The best recipient sites for skin grafts are clean, granulating and well vascularized; unsuitable sites include bone lacking periosteum, tendons stripped of paratenon, denuded cartilage, irra- diated or avascular wounds and those covered in blood clot. Gross contamination with microorganisms preju- dice graft survival and Streptococcus pyogenes is an abso- lute contraindication because it produces fibrinolysin, destroying the fibrin bond between the bed and the graft. The likelihood of graft movement can be reduced by applying moderate pressure with a conforming, tie- over dressing, which will also inhibit the development of a seroma or haematoma. 2. A split thickness skin graft consists of epidermis and a variable proportion of dermis, harvested in sheets using a handheld knife or electronic dermatome. Retained epidermal components, such as pilosebaceous follicles, provide foci for epidermal regeneration. The thinner the graft harvested, the more epidermal elements left behind, the quicker the epidermis regenerates. If the volume of donor skin is inadequate, split skin grafts can be expanded by the use of a meshing machine; this creates fenestrations throughout the graft, allowing it to expand and cover a larger area, with a net-like appearance. Split skin grafts can be harvested, wrapped in sterile saline-soaked gauze and stored in a refriger- ator at 4 Q C, with up to 3 weeks viability. The commonest donor site for these grafts is the thigh or buttock area. The donor site often heals with altered pigmentation, and occasionally with a hypertrophic scar. Split thickness grafts, especially thin ones, tend to contract during the healing process, limiting movement across flexor surfaces. The application of compression garments when the graft is healed improves the appearance, flattens the scar and minimizes contraction, aided by daily massage with moisturizing cream. 3. Full thickness skin grafts comprise the epidermis and full thickness of the dermis. It is harvested using a template to plan the size and shape, and subcutaneous fat is removed. The donor site, such as post- or preauricular, supraclavicular or groin, is closed directly. It generally provides good colour match on the face and contracts minimally. Such grafts are inevitably limited in size and must be placed on a healthy, vascular base. 4. Flaps are detached tissue, containing a network of arterial, venous and capillary vessels, transferred from one site to another. They can retain their intact circulation on the original vascular pedicle. Random pattern flaps do not have an anatomically recognized vascular supply and as a general rule the length of the flap should not exceed twice the length of the attached base. Some flaps have identified vessels supplying them - axial pattern flaps, including the forehead, groin and deltopectoral region; these may be raised on a narrow pedicle and discon- nected completely, for the vessels to be joined to vessels at the recipient site - a free flap. This is achievable as a result of microsurgical techniques. They may include other tissues, including deep fascia, muscle or bone. Useful sites include the forehead, groin and deltopectoral region. 5. Myocutaneous flaps provide a robust vascularized wound cover over exposed bone, tendon or areas sub- jected to high mechanical demands. Skin in many areas is supplied by perforating vessels from the underlying muscle and an island of skin can be transferred with the muscle to provide simultaneous skin cover. The muscle is isolated onto its vascular pedicle alone and rotated into the defect. Commonly used myocutaneous flaps include the latissimus dorsi, rectus abdominis, pectoralis major and gastrocnemius. 6. Deep fascia included with overlying layers of skin improves vascularity and safety; they can also be transferred as vascularized free flaps. 7. Tissue expansion allows the skin and subcutaneous tissue to be stretched in order to fill a defect nearby. An expandable silicone (Silastic) bag is inserted beneath the skin and subcutaneous fat. When the wound is healed, the sac can be filled percutaneously with increasing volumes of saline though a special subcutaneous port. Once the overlying skin is sufficiently stretched, the implant is removed and the stretched excess skin can be advanced into the defect. SKIN SUBSTITUTES Wound coverage is vitally important. If sufficient skin is not available it may be possible to apply a substitute. The main need for these substitutes is in the management of extensive burns. 1. Autologous (derived from the same individual) cultured epidermal cells provide permanent coverage but they require 3 weeks in order to grow sufficient cells. 2. Allografts (Greek allos = other; from another individual) cultured epidermal cells from living persons or cadavers do not appear to be rejected, possibly because they do not express major histocompatability complex 247 24 OPERATION class II antigens and are not contaminated with Langerhans cells, which are the antigen-presenting cells of the epidermis. They are eventually replaced by host cells, so they offer temporary coverage. 3. Neonatal epidermal cells, for example from excised foreskins, release growth factors. Cultured cells accelerate healing and relieve painful chronic ulcers. 4. A composite collagen-based dermal lattice in a silicone covering may be valuable in the treatment of burns. The dermal cells are gradually degraded but after 3 weeks the Silastic sheet cover can be removed and replaced by cultured autologous cells. Human epidermal cells and viable fibroblasts may be included in the composite. Viable fibroblasts may also be included in a nylon net cover overlaid with Silastic to reduce evaporation. 5. In order to provide substitute dermal as well as epidermal cells, bovine collagen and allogeneic human cells may be combined. Summary • Are you aware of the multiplicity of factors to which the skin is exposed? • Do you recognize the varied causes of skin damage and loss? • Do you understand the complex biology of skin healing? • Can you discuss the methods of skin closure? References Berry DP, Harding K, Stanton MR, Tasani B, Ehrlich HP 1998. Human wound contraction: collagen organization, fibroblasts and myofibroblasts. Plastic and Reconstructive Surgery 102: 124-131 Singer AJ, Clark RA 1999. Mechanisms of disease: cutaneous wound healing. New England Journal of Medicine 341: 738-746 Further reading Brough M 2000. Plastic surgery in general surgical operations, 4th edn. Churchill Livingstone Edinburgh, pp 727-773 Kirk RM 2002 Basic surgical techniques, 5th edn. Churchill Livingstone, Edinburgh McGregor IA, McGregor AD 1995 Fundamental techniques in plastic surgery and their surgical applications. Churchill Livingstone, Edinburgh Nedelec B, Ghahary A, Scott PG, Tredget EE 2000. Control of wound contraction. Basic and clinical features. Hand Clinics 16: 289-302 Richard R, DerSarkisian D, Miller SF, Johnson RM, Staley M 1999. Directional variance in skin movement. Journal of Burn Care and Rehabilitation 20: 259-264 Saba AA, Freedman BM, Gaffield JW, Mackay DR, Ehrlich HP 2002. Topical platelet-derived growth factor enhances wound closure in the absence of wound contraction: an experimental study. Annals of Plastic Surgery 49: 62-66 Witte MB, Barbul A 2002. Role of nitric oxide in wound repair. American Journal of Surgery 183: 406-412 Younai S, Venters G, Vu G, Nichter L, Nimni E, Tuan TL 1996. Role of growth factors in scar contraction: an in vitro analysis. Annals of Plastic Surgery 36: 495-501 248 Transplantation P. McMaster, L. J. Buist Objectives Appreciate the causes of organ rejection. Understand the principles of transplantation and immunosuppression. Be aware of the source of transplanted organs, and the associated ethical and legal considerations. BASIC PRINCIPLES Early Christian legends attest to the attempts to replace diseased or destroyed organs or tissues by the transfer from another individual. The father of modern surgery, John Hunter, carried out extensive experiments on the transposition of tissues and concluded what he thought were successful experiments on the transposition of teeth! However, it was not until the dawn of the 20th century that the practical technical realities of organ transfer were combined with sufficient understanding of the immunological mechanisms involved to allow transplantation to become a practical reality. While it had long been recognized that successful blood transfusion was in large measure dependent on matching donor and recipient cells, it was only in the 1950s that Mitchison (1953) demonstrated that, while cell-mediated immunity was responsible for early destruction and rejection, it was the humeral mechanism with cytotoxic antibodies that was primarily involved in the host response to foreign tissue. It became increasingly recognized that all tissue and fluid transfer was governed by basic immunomechanisms (Table 25.1). The need in the Second World War to find improved ways of treating badly burned pilots led Gibson & Medawar (1943) to carry out a series of classic experiments on skin transplantation. They were able to con- clude that the transfer of skin from one part of the body to another in the same individual (an autograft), survived indefinitely, whereas the transfer of skin from another Table 25.1 Forms of tissue transfer Transfer of tissue Blood Bone marrow Transfer of solid organ Skin Cornea Kidney Heart Liver Pancreas individual (an allogmft) was in due course destroyed and that the recipient retained memory of the donor tissue and further transfers or allografts were destroyed in an accelerated mechanism. Thus the wider recognition of the universal acceptance of autografts became realized, whereas the failure of an allograft was recognized as part of an immune response. An alternative source of organs is, of course, the animal world, and the transfer from another species is known as a xenograft. FIRST CLINICAL PROGRAMMES The recognition that an autograft would be universally acceptable led to the first successful attempts at organ grafting in humans. In the early 1950s, Murray et al (1955) at the Peter Bent Brigham Hospital in Boston, were able to demonstrate the successful transfer of a kidney graft from an identical twin, with acceptance and successful function, and to develop a programme of renal transplantation between monozygotic twins. Some of the recipients of kidney transplants from identical twins remain well more than 40 years after grafting; however, grafts between unrelated living individuals performed by this same group invariably failed, although not as quickly as experimental studies might have suggested. 249 25 25 OPERATION RESPONSE The other major human source of organs, other than from living relatives, is from individuals who have died as a result of road traffic accidents or cerebral injuries. Cadaveric organ grafting from non-related individuals is now the major source of organs. Within Europe, more than 80% of all organs transplanted are from brain-dead donors. Thus, although technical considerations presented the initial formidable barrier to organ transfer, it was increasingly the understanding of the immune response causing organ destruction by rejection, which led to clinical schedules permitting practical transplantation services to be established. The body's immune response to destroy the invading organ we now recognize as rejection. REJECTION Early experimental studies involving tissue transfer suggested genetic regulation of the rejection process. It was suggested in the 1930s that rejection was a response to specific foreign antigens (alloantigens) and that they were similar to blood groups of other species. The development of inbred lines of experimental animal models allowed the demonstration of antigens present on red blood cells and the concept of histocompatibility. This suggestion of an immunological theory of tissue transplantation stimu- lated Medawar's (1944) work in rabbits and later in mice, and led to similar studies in humans, with the discovery of the human leucocyte antigen (HLA) system. Further experimental studies defined the concept of rejection into three primary categories: hyperacute rejection, which can occur in a matter of hours due to preformed antibodies in a sensitized recipient; acute rejection, which takes place in a few days or weeks and is usually caused by cellular mechanisms; and chronic rejection, which occurs over months or years and remains largely undefined, but involves primarily humeral antibodies. A detailed review of experimental and modern transplantation biology is quite beyond the scope of this chapter, but increasing understanding of this area will allow more refined changes in rejection management and increasingly successful organ grafting. AVOIDING REJECTION The degree of disparity between donor and recipient is an important key element in the severity of the immune rejection response. In xenografting (transfer between species) the presence of preformed antibodies leads to rapid endothelial damage, causing vascular thrombosis, gross interstitial swelling and necrosis of the graft, all within a matter, usually, of hours. Similarly, when transfer occurs between human beings, the degree of compatibility between donor and recipient is important to the success, or otherwise, of the graft. As indicated earlier, transfer between identical twins is associated with universal success, without the need to modulate the immune mechanism. However, transfer between non-identical relatives or using cadaveric organs produces the recognition of non-self by the recipient and the mounting of an immune response. It is the avoidance or modification of this immune response that has been the main target over the last 25 years, and the avoidance of overwhelming rejection has been a prime goal. Two approaches have been taken to the problem: tissue typing and reduction of immune response. Tissue typing In the attempt to match the donor and recipient more closely, the concept of typing has become widely devel- oped. Early work demonstrating that blood transfusion was dependent on matching between donor and recipient was extended into experimental and then clinical transplantation studies in the 1960s and 1970s. The human chromosome 6 contains the genetically deter- mined major histocompatibility complex (MHC), i.e. the HLA-A, HLA-B, HLA-C (class I) and HLA-DR (D-related; class II) loci. A whole series of additional genetic regions have been linked to the HLA complex, although in clinical terms these are probably less significant. Thus it has become increasingly possible, using serological studies, to map genetically an individual on the basis of the HLA region of this chromosome. Since one chromosome is inherited from each parent and each individual has two HLA haplotypes, there is a 25% chance that two siblings will share both haplotypes (i.e. identical) and, by standard and mendelian inheritance, a 50% chance that they will share one haplotype. Thus in first- degree relatives when the donor and recipient are matched for HLA-A and -B antigens there is an excellent likelihood of graft success, whereas because of the com- plexity of the MHC allele, the wide divergence of antigens and random cadaveric donors, even if matched for one or two antigens, there may still be very substantial disparity. Thus, in order to avoid rejection, the concept of tissue typing trying to match more accurately the donor and the recipient has gained wide acceptance. Serological methods allow class I HLA antigens to be defined using typed serum obtained from nulliparous women. Using a microcytotoxicity assay, multiple antisera against HLA-A, -B, -C and -DR antigens are provided on Terasaki trays 250 [...]... receptor-ligand binding induces a change of form in the receptor This in turn activates an enzyme, for example a tyrosine kinase Tyrosine kinases function within cells to attach phosphate groups to the amino acid tyrosine phosphorylation This triggers an intracellular signalling cascade, mediated via protein-protein interactions, inducing enzyme activity The result is a change in gene expression, producing... Medawar PB 1943 The fate of skin homografts in man Journal of Anatomy 77: 29 9-3 09 Hitchings GH, Elion GB 1959 Activity of heterocyclic derivatives of 6- mercaptopurine and 6- thioguanine in adenocarcinoma 755 Proceedings of the American Association for Cancer Research 3: 27 Medawar PB 1944 Behaviour and fate of skin autografts and skin homografts in rabbits Journal of Anatomy 78: 17 6- 1 99 Mitchison NA 1953 Passive... antilymphocytic globulin by sensitization in animals was also demonstrated to inhibit the immune response, although variability and efficacy limited its clinical use Ciclosporin Clearly the ultimate goal of selectively inhibiting the recipient's immune response remains a long way off, and in clinical practice non-specific agents continue to be used In 19 76, Borel and colleagues working in Sandoz laboratories... transfer of transplantation immunity Nature 171: 26 7-2 68 Murray JE, Merrill JP, Harrison JH 1955 Renal homotransplantation in identical twins Surgery Forum 6: 42 3-4 26 Schwartz R, Dameschek W 1959 Drug induced immunological tolerance Nature 183: 168 2-1 68 3 255 This page intentionally left blank SECTION 5 MALIGNANT DISEASE 257 This page intentionally left blank 26 Pathogenesis of cancer P D Nathan, D Hochhauser... lympho- nor myelotoxic and had no influence on the viability of the mature T cells or the antibody-producing B cells Further agents have recently been introduced to clinical practice, perhaps resulting in less rejection still (FK5 06 or tacrolimus, mycofenolate and monoclonal antibodies) CURRENT CLINICAL IMMUNOSUPPRESSIVE USE For nearly 30 years the mainstay of clinical immunosuppression was the combined... expression, producing an increased cellular proliferation Tyrosine phosphorylation is thus an early event in a complex signalling system Depending upon the incoming information, the cell may respond in a variety of ways If the ligand is a growth factor, the cell enters into the S phase of the cell cycle (Fig 26. 1) 6 Once a resting cell is in G0 it can remain quiescent and viable, yet it can reinitiate growth... one example in which grade is a part of the staging system and therefore has an influence on treatment protocols 4 Initial assessment using combined imaging modalities such as CT, MRI and scintigraphic bone scanning allow accurate assessment of local and distal spread This is essential in the planning of surgical intervention The 269 27 MALIGNANT DISEASE degree of surrounding soft tissue involvement,... (Latin col = together + linea = a line; to make parallel: beam defining devices allowing irregular shaping of fields), which can vary during treatment administration, and 'inverse planning' where the radiotherapist determines what he or she wishes to achieve and the computer determines optimum field size, shape, direction and weighting, are likely to lead to further sophistication in treatment administration,... to surgery Better results than anoperineal resection T2/3 34 T1/2 80 60 75 Salvage cystectomy for local relapse Surgery only 28% 5 year survival Equivalent to surgery Lung Conventional Gastrointestinal tract Oesophagus Anal canal Urology Bladder Prostate Penile Gynaecology Cervix T3 All All 8 5-9 0 6 1-8 5 6 0 -6 5 Stage 1 75 1B 2A/B Endometrium Vagina 2 76 Over 90% cure for stage 1 tumours Equivalent to surgery. .. normal genes require two somatic mutations, resulting in sporadic disease occurring at a later age Large adenoma Pre-malignant changes — E-cadherin Colorectal >• carcinoma *- Invasion Fig 26. 5 The multi-step pathway to colorectal cancer The accumulation of 5-1 0 mutations in several tumour suppressor genes or oncogenes over a lifetime results in cancer 263 t Summary • Do you understand the genetic damage . damage as well as pre- venting invasion by microorganisms, including viruses. Its integrity is critical for homeostasis, maintaining the internal milieu by providing a relatively impermeable barrier . investing fascia, causing skin loss over a large area. The skin may tear, or remain intact initially, disguising the severity of this injury. Rupture of the vessels connecting . become myofibroblasts, acquiring actin-containing microfilaments (Greek aktinos = ray) and cell-to-cell and cell-to-matrix linkages. Probably under the influence of TGF and PDGF, the fibroblasts

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