Mohs and Cutaneous Surgery

Maximizing Aesthetic Outcomes

Alexander Berlin, Alexander Berlin

• Publisher: CRC Press
• Year: 2014
• ISBN:
  9780429586637
• Edition: 1
• Topic: Medizin
• Subtopic: Medizinische Theorie, Praxis & Referenz

Achieving the best aesthetic results in Mohs and other cutaneous surgery requires proper patient selection, careful surgical technique, and meticulous postoperative care. Yet despite the best efforts of both surgeon and patient, complications may develop, sometimes resulting in suboptimal or objectionable scarring.Mohs and Cutaneous Surgery: Maximi

PART I

Preoperative, Intraoperative, and Immediate Postoperative Period: Optimizing Surgical Outcomes

Chapter 1

Wound Healing and Surgical Planning

Alexander L. Berlin, Sarah J. Felton, Christopher T. Burnett, and Divya Srivastava

INTRODUCTION

In 1938, Frederic E. Mohs revolutionized surgical treatment of skin cancer, allowing for the precise localization and removal of tumor cells. When the use of the original escharotic paste was replaced by the fresh-frozen technique, same-day removal of cancer and subsequent repair of the surgical defect became possible.

As a tissue-sparing technique, Mohs surgery offers the possibility of the least resulting scarring. In the United States, dermatologic surgeons perform the majority of head and neck cutaneous reconstructions in the Medicare population, including flaps, grafts, and primary closures.¹ Therefore, Mohs surgeons are uniquely positioned to provide the most aesthetic results following complete tumor resection.

The route to achieving the best aesthetic outcome starts before tumor extirpation is undertaken, with appropriate surgical planning and understanding of the cutaneous wound healing process, both in the general population and in pathological states. It is to these issues that this introductory chapter will be devoted.

WOUND HEALING

Since the result of any cutaneous injury, including Mohs surgery, is a wound, it is very important to understand the process of wound healing. Though the specific molecular events underlying this process are still being worked out, it has become clear that complex interactions take place between various cell types, the extracellular matrix (ECM), and numerous released chemical mediators. Though they often overlap, it is helpful to organize the individual events involved in cutaneous wound healing into three traditionally recognized phases: inflammatory, proliferative, and remodeling. Though initial wound hemostasis is occasionally separated into its own “coagulation” phase, it will be discussed here as part of the inflammatory phase.

Inflammatory Phase

The inflammatory phase is composed of the vascular response and the cellular response. The initial physiological response to injury is the achievement of hemostasis and the formation of a provisional wound matrix.

Vascular Response Immediately following injury to a blood vessel, platelets are activated by exposed collagen via glycoprotein Ia/IIa surface receptors.² Activated platelets release a variety of chemical mediators from their dense and alpha granules, including adenosine diphosphate (ADP), von Willebrand factor (vWF), thrombin, fibrinogen, transforming growth factor-β1 (TGF-β1), and several growth factors, such as platelet-derived growth factor (PDGF). vWF binds to collagen, as well as to vWF receptors on platelets, leading to platelet adhesion.^3,4 Both fibrinogen and vWF then bind to platelet glycoprotein IIb/IIIa receptors, resulting in platelet aggregation.^5,6 In addition, platelet activation induces membrane enzyme phospholipase A2. This results in the production of thromboxane A2 (TXA2), which causes vasoconstriction and further induces the expression of glycoprotein IIb/IIIa receptor.^7,8 Combined, these processes lead to the initial formation of a platelet plug, which may temporarily occlude a bleeding vessel.

Additionally, both the extrinsic and the intrinsic coagulation cascades are activated by contact with tissue factor in the injured skin and exposed fibrillar collagen, respectively. These ultimately lead to the formation of thrombin, a powerful platelet activator, which also converts fibrinogen to fibrin. Fibrin then acts as mortar between adherent platelets, leading to the formation of a fibrin clot. In addition to fibrin, the clot also contains fibronectin, thrombospondin, and other molecules, which form the initial scaffold for the influx of migrating cells.^9,10

Platelets synthesize or store a variety of vasoactive, chemotactic, and proliferative mediators. Histamine is released by platelets and other cells and causes vasodilation and vascular permeability, allowing for cellular infiltration into the wound. PDGF has been shown to be chemotactic for neutrophils, macrophages, fibroblasts, and smooth muscle cells.^11,12 TGF-β1 is also chemotactic for fibroblasts, macrophages, and other cell types but, in addition, stimulates new collagen production.^13,14,15 Furthermore, together with endothelial cell selectin (E-selectin), platelet selectin (P-selectin) facilitates neutrophil margination, rolling, and capture, stimulating neutrophil influx.¹⁶ Thus, platelet activation and aggregation directly contribute to the ensuing cellular response.

Cellular Response In the early phase of the cellular response, neutrophils are recruited to the site of injury and typically persist for 2–5 days. As mentioned above, they are induced to infiltrate into the wound through the action of various chemotactic molecules, some of which are derived from platelets and other cells, while others may be released as a result of tissue damage (e.g., bradykinin and fibrin degradation products) or bacterial activation of the complement system (e.g., complement protein 5a). Through subsequent interactions between adhesion molecules on their surfaces and those on endothelial cells, neutrophils migrate out of blood vessels in the process of diapedesis.^17,18 Once in the wound, neutrophils phagocytose and kill bacteria through oxidative burst; additionally, they help to degrade matrix proteins and clear necrotic tissue.

In the late phase of the cellular response, monocytes are recruited from the circulation to enter the injury zone, thus becoming tissue macrophages. This typically begins around 3 days after cutaneous injury. Various chemotactic mediators of this influx have been identified; they may include PDGF, thrombin, TGF-β, and monocyte chemoattractant protein-1 (MCP-1).^19,20,21,22

Macrophages are antigen-presenting cells critical to the wound healing process, and their dysfunction can lead to abnormal healing, including chronic wounds, ulcers, and hypertrophic scarring.²³ Similar to neutrophils, they also phagocytose and kill bacteria and eliminate debris. In addition, they clear residual neutrophils and other apoptotic cells; support fibroblast migration, proliferation, and differentiation; induce neovascularization; and promote ECM synthesis.²⁴ These functions are mediated through numerous potent growth factors synthesized and secreted by macrophages, including PDGF, basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), TGF-α, and TGF-β.²⁵

Animal models have demonstrated that selective ablation or deactivation of macrophages leads to decreased collagen deposition, angiogenesis, and cellular proliferation; loss of myofibroblast differentiation and wound contraction; and delayed reepithelialization.^26,27 In this way, macrophages provide a critical link to the next phase of the wound healing process, the proliferative phase.

Proliferative Phase

In the proliferative phase, cellular migration and proliferation predominate. The goal of this phase is to achieve the restoration of epidermal integrity through reepithelialization and that of dermal support through angiogenesis, fibroplasia, and ECM synthesis.

Reepithelialization The process of reestablishment of the epidermis starts with keratinocyte migration from the wound edges and, in partial-thickness wounds, from skin appendages, such as the bulge region of the hair follicle.^28,29 This migration may be stimulated by the loss of contact inhibition, as well as through the release of numerous cytokines and growth factors, such as TGF-β, epidermal growth factor (EGF), and keratinocyte growth factor (KGF), and by macrophages, fibroblasts, and other cells.^30,31 Previously described hypotheses on keratinocyte migration include the “leapfrog” and the “train,” or epidermal tongue extension, methods, though a recent three-dimensional in vitro model revealed a novel mechanism of reepithelialization: an extending shield.³²

Keratinocytes near the wound edge develop pseudopod-like projections, lose their desmosomal and hemidesmosomal attachments, and reorganize their intracellular cytoskeletons, including actin filaments, in the direction of movement. This process is likely regulated by RhoGTPases, a family of small GTPases that include Rho, Rac, and Cdc42.³³ Activated keratinocytes also express collagenase-1, also known as matrix metalloproteinase-1 (MMP-1), which severs adhesions to collagen in the underlying dermal matrix, allowing migration until complete epidermal merging and reappearance of the basement membrane have been achieved.^34,35

While migrating cells do not actively proliferate, trailing keratinocytes do, contributing to complete reepithelialization. This difference in behavior appears to be influenced by a number of growth factors and cytokines, such as EGF and TGF-β1.^36,37 Subsequently, keratinocyte differentiation leads to the restoration of epidermal barrier function. Expression of various mediators, such as KGF in fibroblasts and activin in basal keratinocytes, may affect epidermal redifferentiation.^38,39

Angiogenesis Angiogenesis, or neovascularization, in a healing wound is a complex process aimed at reestablishment of tissue perfusion in response to low-oxygen conditions. A vascu...