As a model the mechanism of fibroplasia may be conceptualised as an analogous process to angiogenesis (see above) - only the cell type involved is fibroblasts rather than endothelial cells. Initially there is a latent phase where the wound undergoes plasma exudation, inflammatory decontamination and debridement. Oedema increases the wound histologic accessibility for later fibroplastic migration. Second, as inflammation nears completion, macrophage and mast cells release fibroblast growth and chemotactic factors to activate fibroblasts from adjacent tissue. Fibroblasts at this stage loosen themselves from surrounding cells and ECM. Phagocytes further release proteases that break down the ECM of neighbouring tissue, freeing the activated fibroblasts to proliferate and migrate towards the wound. The difference between vascular sprouting and fibroblast proliferation is that the former is enhanced by hypoxia, whilst the latter is inhibited by hypoxia. The deposited fibroblastic connective tissue matures by secreting ECM into the extracellular space, forming granulation tissue (see below). Lastly collagen is deposited into the ECM.


In the first two or three days after injury, fibroblasts mainly migrate and proliferate, while later, they are the main cells that lay down the collagen matrix in the wound site. [ 3 ]  Origins of these fibroblasts are thought to be from the adjacent uninjured cutaneous tissue (although new evidence suggests that some are derived from blood-borne, circulating adult stem cells/precursors). [ 39 ]  Initially fibroblasts utilize the fibrin cross-linking fibers (well-formed by the end of the inflammatory phase) to migrate across the wound, subsequently adhering to fibronectin. [ 37 ]    Fibroblasts then deposit  ground substance  into the wound bed, and later collagen, which they can adhere to for migration. [ 15 ]


Granulation tissue  functions as rudimentary tissue, and begins to appear in the wound already during the inflammatory phase, two to five days post wounding, and continues growing until the wound bed is covered.  Granulation tissue consists of new blood vessels, fibroblasts, inflammatory cells, endothelial cells, myofibroblasts, and the components of a new, provisional  extracellular matrix  (ECM). The provisional ECM is different in composition from the ECM in normal tissue and its components originate from fibroblasts. [ 28 ]  Such components include fibronectin, collagen,  glycosaminoglycans ,  elastin ,  glycoproteins  and  proteoglycans . [ 37 ]  Its main components are fibronectin and  hyaluronan , which create a very hydrated matrix and facilitate cell migration. [ 31 ]  Later this provisional matrix is replaced with an ECM that more closely resembles that found in non-injured tissue.


Growth factors ( PDGF ,  TGF-β ) and fibronectin encourage proliferation, migration to the wound bed, and production of ECM molecules by fibroblasts. Fibroblasts also secrete growth factors that attract epithelial cells to the wound site.  Hypoxia also contributes to fibroblast proliferation and excretion of growth factors, though too little oxygen will inhibit their growth and deposition of ECM components, and can lead to excessive, fibrotic  scarring .


One of fibroblasts' most important duties is the production of  collagen . [ 36 ]


Collagen deposition is important because it increases the strength of the wound; before it is laid down, the only thing holding the wound closed is the fibrin-fibronectin clot, which does not provide much resistance to  traumatic injury . [ 20 ]  Also, cells involved in inflammation, angiogenesis, and connective tissue construction attach to, grow and differentiate on the collagen matrix laid down by fibroblasts. [ 40 ]


Type III collagen  and  fibronectin  generally begin to be produced in appreciable amounts at somewhere between approximately 10 hours [ 41 ]  and 3 days, [ 37 ]  depending mainly on wound size. Their deposition peaks at one to three weeks. [ 28 ]  They are the predominating tensile substances until the later phase of maturation, in which they are replaced by the stronger  type I collagen .


Even as fibroblasts are producing new collagen, collagenases and other factors degrade it. Shortly after wounding, synthesis exceeds degradation so collagen levels in the wound rise, but later production and degradation become equal so there is no net collagen gain. [ 20 ]  This homeostasis signals the onset of the later maturation phase. Granulation gradually ceases and fibroblasts decrease in number in the wound once their work is done. [ 42 ]  At the end of the granulation phase, fibroblasts begin to commit apoptosis, converting granulation tissue from an environment rich in cells to one that consists mainly of collagen. [ 3 ]


The formation of granulation tissue into an open wound allows the reepithelialization phase to take place, as epithelial cells migrate across the new tissue to form a barrier between the wound and the environment. [ 37 ]   Basal   keratinocytes  from the wound edges and  dermal appendages  such as  hair follicles ,  sweat glands  and  sebaceous (oil) glands  are the main cells responsible for the epithelialization phase of wound healing. [ 42 ]  They advance in a sheet across the wound site and proliferate at its edges, ceasing movement when they meet in the middle. In healing that results in a scar, sweat glands, hair follicles [ 43 ] [ 44 ]  and nerves do not form. With the lack of hair follicles, nerves and sweat glands, the wound, and the resulting healing scar, provide a challenge to the body with regards to temperature control. [ 44 ]


Keratinocytes  migrate without first proliferating. [ 45 ]  Migration can begin as early as a few hours after wounding. However, epithelial cells require viable tissue to migrate across, so if the wound is deep it must first be filled with granulation tissue. [ 46 ]  Thus the time of onset of migration is variable and may occur about one day after wounding. [ 47 ]  Cells on the wound margins proliferate on the second and third day post-wounding in order to provide more cells for migration. [ 28 ]


If the  basement membrane  is not breached, epithelial cells are replaced within three days by division and upward migration of cells in the  stratum basale  in the same fashion that occurs in uninjured skin. [ 37 ]  However, if the basement membrane is ruined at the wound site, reepithelization must occur from the wound margins and from skin appendages such as hair follicles and sweat and oil glands that enter the  dermis  that are lined with viable keratinocytes. [ 28 ]  If the wound is very deep, skin appendages may also be ruined and migration can only occur from wound edges. [ 46 ]


Migration of keratinocytes over the wound site is stimulated by lack of  contact inhibition  and by chemicals such as  nitric oxide . [ 48 ]  Before they begin to migrate, cells must dissolve their  desmosomes  and  hemidesmosomes , which normally anchor the cells by  intermediate filaments  in their  cytoskeleton  to other cells and to the ECM. [ 23 ]   Transmembrane   receptor   proteins  called  integrins , which are made of  glycoproteins  and normally anchor the cell to the basement membrane by its  cytoskeleton , are released from the cell's intermediate filaments and relocate to  actin  filaments to serve as attachments to the ECM for  pseudopodia  during migration. [ 23 ]  Thus keratinocytes detach from the basement membrane and are able to enter the wound bed. [ 35 ]


Before they begin migrating, keratinocytes change shape, becoming longer and flatter and extending cellular processes like  lamellipodia  and wide processes that look like ruffles. [ 31 ]   Actin  filaments and  pseudopodia  form. [ 35 ]  During migration,  integrins  on the pseudopod attach to the ECM, and the actin filaments in the projection pull the cell along. [ 23 ]  The interaction with molecules in the ECM through integrins further promotes the formation of actin filaments, lamellipodia, and  filopodia . [ 23 ]


Epithelial cells climb over one another in order to migrate. [ 42 ]  This growing sheet of epithelial cells is often called the epithelial tongue. [ 45 ]  The first cells to attach to the  basement membrane  form the  stratum basale . These basal cells continue to migrate across the wound bed, and epithelial cells above them slide along as well. [ 45 ]  The more quickly this migration occurs, the less of a scar there will be. [ 49 ]


Fibrin , collagen, and fibronectin in the ECM may further signal cells to divide and migrate.  Like fibroblasts, migrating keratinocytes use the fibronectin cross-linked with fibrin that was deposited in inflammation as an attachment site to crawl across. [ 25 ] [ 31 ] [ 42 ]


As keratinocytes migrate, they move over granulation tissue but stay underneath the scab, thereby separating the scab from the underlying tissue. [ 42 ] [ 47 ]  Epithelial cells have the ability to phagocytize debris such as dead tissue and bacterial matter that would otherwise obstruct their path.  Because they must dissolve any scab that forms, keratinocyte migration is best enhanced by a moist environment, since a dry one leads to formation of a bigger, tougher scab. [ 25 ] [ 37 ] [ 42 ] [ 50 ]  To make their way along the tissue, keratinocytes must dissolve the clot, debris, and parts of the ECM in order to get through. [ 47 ] [ 51 ]  They secrete  plasminogen activator , which activates  plasminogen , turning it into  plasmin  to dissolve the scab.  Cells can only migrate over living tissue, [ 42 ]  so they must excrete collagenases and proteases like  matrix metalloproteinases  (MMPs) to dissolve damaged parts of the ECM in their way, particularly at the front of the migrating sheet. [ 47 ]  Keratinocytes also dissolve the basement membrane, using instead the new ECM laid down by fibroblasts to crawl across. [ 23 ]


As keratinocytes continue migrating, new epithelial cells must be formed at the wound edges to replace them and to provide more cells for the advancing sheet. [ 25 ]  Proliferation behind migrating keratinocytes normally begins a few days after wounding [ 46 ]  and occurs at a rate that is 17 times higher in this stage of epithelialization than in normal tissues. [ 25 ]  Until the entire wound area is resurfaced, the only epithelial cells to proliferate are at the wound edges. [ 45 ]


Growth factors, stimulated by integrins and MMPs, cause cells to proliferate at the wound edges.  Keratinocytes themselves also produce and secrete factors, including growth factors and basement membrane proteins, which aid both in epithelialization and in other phases of healing. [ 52 ]  Growth factors are also important for the innate immune defense of skin wounds by stimulation of the production of antimicrobial peptides and neutrophil chemotactic cytokines in keratinocytes.


Keratinocytes continue migrating across the wound bed until cells from either side meet in the middle, at which point  contact inhibition  causes them to stop migrating. [ 31 ]   When they have finished migrating, the keratinocytes secrete the proteins that form the new basement membrane. [ 31 ]   Cells reverse the morphological changes they underwent in order to begin migrating; they reestablish  desmosomes  and  hemidesmosomes  and become anchored once again to the basement membrane. [ 23 ]   Basal cells  begin to divide and differentiate in the same manner as they do in normal skin to reestablish the strata found in reepithelialized skin. [ 31 ]


Contraction is a key phase of wound healing with repair. If contraction continues for too long, it can lead to disfigurement and loss of function. [ 32 ]  Thus there is a great interest in understanding the biology of wound contraction, which can be modelled in vitro using the  collagen gel contraction assay  or the  dermal equivalent  model. [ 27 ] [ 53 ]


Contraction commences approximately a week after wounding, when fibroblasts have differentiated into  myofibroblasts . [ 54 ]   In  full thickness  wounds, contraction peaks at 5 to 15 days post wounding. [ 37 ]  Contraction can last for several weeks [ 46 ]  and continues even after the wound is completely reepithelialized. [ 3 ]  A large wound can become 40 to 80% smaller after contraction. [ 31 ] [ 42 ]   Wounds can contract at a speed of up to 0.75 mm per day, depending on how loose the tissue in the wounded area is. [ 37 ]   Contraction usually does not occur symmetrically; rather most wounds have an 'axis of contraction' which allows for greater organization and alignment of cells with collagen. [ 54 ]


At first, contraction occurs without myofibroblast involvement. [ 55 ]   Later, fibroblasts, stimulated by growth factors, differentiate into myofibroblasts.  Myofibroblasts, which are similar to smooth muscle cells, are responsible for contraction. [ 55 ]   Myofibroblasts contain the same kind of actin as that found in  smooth muscle  cells. [ 32 ]


Myofibroblasts are attracted by fibronectin and growth factors and they move along fibronectin linked to fibrin in the provisional ECM in order to reach the wound edges. [ 25 ]   They form connections to the ECM at the wound edges, and they attach to each other and to the wound edges by  desmosomes .  Also, at an adhesion called the  fibronexus , actin in the myofibroblast is linked across the cell membrane to molecules in the extracellular matrix like fibronectin and collagen. [ 55 ]   Myofibroblasts have many such adhesions, which allow them to pull the ECM when they contract, reducing the wound size. [ 32 ]   In this part of contraction, closure occurs more quickly than in the first, myofibroblast-independent part. [ 55 ]


As the actin in myofibroblasts contracts, the wound edges are pulled together.  Fibroblasts lay down collagen to reinforce the wound as myofibroblasts contract. [ 3 ]  The contraction stage in proliferation ends as myofibroblasts stop contracting and commit apoptosis. [ 32 ]   The breakdown of the provisional matrix leads to a decrease in hyaluronic acid and an increase in chondroitin sulfate, which gradually triggers fibroblasts to stop migrating and proliferating. [ 19 ]   These events signal the onset of the maturation stage of wound healing.


When the levels of collagen production and degradation equalize, the maturation phase of tissue repair is said to have begun. [ 20 ]  During maturation,  type III collagen , which is prevalent during proliferation, is replaced by type I collagen. [ 17 ]  Originally disorganized collagen fibers are rearranged, cross-linked, and aligned along  tension lines . [ 31 ]  The onset of the maturation phase may vary extensively, depending on the size of the wound and whether it was initially closed or left open, [ 28 ]  ranging from approximately three days [ 41 ]  to three weeks. [ 56 ]  The maturation phase can last for a year or longer, similarly depending on wound type. [ 28 ]


As the phase progresses, the  tensile strength  of the wound increases. [ 28 ]  Collagen will reach approximately 20% of its tensile strength after three weeks, increasing to 80% after 12 months. The maximum scar strength is 80% of that of unwounded skin. [ 57 ]  Since activity at the wound site is reduced, the scar loses its red appearance as  blood vessels  that are no longer needed are removed by  apoptosis . [ 20 ]


The phases of wound healing normally progress in a predictable, timely manner; if they do not, healing may progress inappropriately to either a  chronic wound [ 7 ]  such as a  venous ulcer  or pathological scarring such as a  keloid scar . [ 58 ] [ 59 ]


Many factors controlling the efficacy, speed, and manner of wound healing fall under two types: local and systemic factors. [ 2 ]


In the 2000s there arose the first Mathematical models of the healing process, based on simplified assumptions and on a  system of differential equations  solved through  MATLAB . The models show that the "rate of the healing process" appears to be "highly influenced by the activity and size of the injury itself as well as the activity of the healing agent." [ 69 ]


Up until about 2000, the classic paradigm of wound healing, involving  stem cells  restricted to organ-specific lineages, had never been seriously challenged. Since then, the notion of  adult stem cells  having cellular  plasticity  or the ability to  differentiate  into non-lineage cells has emerged as an alternative explanation. [ 1 ]  To be more specific,  hematopoietic   progenitor cells  (that give rise to mature cells in the blood) may have the ability  de-differentiate   back into hematopoietic stem cells and/or  transdifferentiate  into non-lineage cells, such as fibroblasts. [ 39 ]


Multipotent adult stem cells have the capacity to be self-renewing and give rise to different cell types. Stem cells give rise to progenitor cells, which are cells that are not self-renewing, but can generate several types of cells. The extent of stem cell involvement in cutaneous (skin) wound healing is complex and not fully understood. [ citation needed ]  Stem cell injection leads to wound healing primarily through stimulation of angiogenesis. [ 70 ]


It is thought that the epidermis and dermis are reconstituted by mitotically active stem cells that reside at the apex of  rete ridges  (basal stem cells or BSC), the bulge of  hair follicles  (hair follicular stem cell or HFSC), and the papillary dermis (dermal stem cells). [ 1 ]  Moreover, bone marrow may also contain stem cells that play a major role in cutaneous wound healing. [ 39 ]


In rare circumstances, such as extensive cutaneous injury, self-renewal subpopulations in the bone marrow are induced to participate in the healing process, whereby they give rise to collagen-secreting cells that seem to play a role during wound repair. [ 1 ]  These two self-renewal subpopulations are (1) bone marrow-derived  mesenchymal stem cells  (MSC) and (2)  hematopoietic stem cells  (HSC). Bone marrow also harbors a progenitor subpopulation ( endothelial  progenitor cells or EPC) that, in the same type of setting, are mobilized to aid in the reconstruction of blood vessels. [ 39 ]  Moreover, it is thought that extensive injury to skin also promotes the early trafficking of a unique subclass of  leukocytes  (circulating  fibrocytes ) to the injured region, where they perform various functions related to wound healing. [ 1 ]


An injury is an interruption of morphology and/or functionality of a given tissue. After injury, structural tissue heals with incomplete or complete regeneration. [ 71 ] [ 72 ]  Tissue without an interruption to the morphology almost always completely regenerates. An example of complete regeneration without an interruption of the morphology is non-injured tissue, such as skin. [ 73 ]  Non-injured skin has a continued replacement and regeneration of cells which always results in complete regeneration. [ 73 ]


There is a subtle distinction between 'repair' and 'regeneration'. [ 1 ] [ 71 ] [ 72 ]   Repair  means  incomplete regeneration . [ 71 ]  Repair or incomplete regeneration, refers to the physiologic adaptation of an organ after injury in an effort to re-establish continuity without regards to exact replacement of lost/damaged tissue. [ 71 ]
 True tissue regeneration  or  complete regeneration , [ 72 ]  refers to the replacement of lost/damaged tissue with an 'exact' copy, such that both morphology and functionality are completely restored. [ 72 ]   Though after injury mammals can completely regenerate spontaneously, they usually do not completely regenerate. An example of a tissue regenerating completely after an interruption of morphology is the  endometrium ; the endometrium after the process of breakdown via the menstruation cycle heals with complete regeneration. [ 73 ]


In some instances, after a tissue breakdown, such as in skin, a regeneration closer to complete regeneration may be induced by the use of biodegradable ( collagen - glycoaminoglycan ) scaffolds. These scaffolds are structurally analogous to  extracellular matrix  (ECM) found in normal/un-injured dermis. [ 74 ]  Fundamental conditions required for tissue regeneration often oppose conditions that favor efficient wound repair, including inhibition of (1) platelet activation, (2) inflammatory response, and (3) wound contraction. [ 1 ]  In addition to providing support for fibroblast and endothelial cell attachment, biodegradable scaffolds inhibit wound contraction, thereby allowing the healing process to proceed towards a more-regenerative/less-scarring pathway. Pharmaceutical agents have been investigated which may be able to turn off  myofibroblast  differentiation. [ 75 ]


A new way of thinking derived from the notion that  heparan sulfates  are key player in tissue homeostasis:  the process that makes the tissue replace dead cells by identical cells. In wound areas, tissue homeostasis is lost as the heparan sulfates are degraded preventing the replacement of dead cells by identical cells.  Heparan sulfate analogues  cannot be degraded by all known heparanases and glycanases and bind to the free heparin sulfate binding spots on the ECM, therefore preserving the normal tissue homeostasis and preventing scarring. [ 76 ] [ 77 ] [ 78 ]


Repair or regeneration with regards to hypoxia-inducible factor 1-alpha (HIF-1a). In normal circumstances after injury  HIF-1a  is degraded by prolyl hydroxylases (PHDs). Scientists found that the simple up-regulation of HIF-1a via PHD inhibitors regenerates lost or damaged tissue in mammals that have a repair response; and the continued down-regulation of Hif-1a results in healing with a scarring response in mammals with a previous regenerative response to the loss of tissue. The act of regulating HIF-1a can either turn off, or turn on the key process of mammalian regeneration. [ 79 ] [ 80 ]


Scarless wound healing  is a concept based on the healing or repair of the skin (or other tissue/organs) after injury with the aim of healing with subjectively and relatively  less   scar  tissue than normally expected. Scarless healing is sometimes mixed up with the concept of  scar free healing ,  which is wound healing which results in absolutely no scar ( free  of scarring). However they are different concepts.


A reverse to scarless wound healing is  scarification  (wound healing to scar more). Historically, certain cultures consider scarification attractive; [ 81 ]  however, this is generally not the case in the modern western society, in which many patients are turning to  plastic surgery  clinics with unrealistic expectations. Depending on  scar  type, treatment may be  invasive  (intralesional steroid injections, surgery) and/or conservative ( compression therapy , topical  silicone gel ,  brachytherapy ,  photodynamic therapy ). [ 82 ]  Clinical judgment is necessary to successfully balance the potential benefits of the various treatments available against the likelihood of a poor response and possible complications resulting from these treatments. Many of these treatments may only have a  placebo effect , and the evidence base for the use of many current treatments is poor. [ 83 ]


Since the 1960s, comprehension of the basic biologic processes involved in wound repair and  tissue regeneration  have expanded due to advances in cellular and  molecular biology . [ 84 ]  Currently, the principal goals in wound management are to achieve rapid wound closure with a functional tissue that has minimal aesthetic scarring. [ 85 ]  However, the ultimate goal of wound healing biology is to induce a more perfect reconstruction of the wound area. Scarless wound healing only occurs in mammalian foetal tissues [ 86 ]  and complete  regeneration  is limited to lower vertebrates, such as  salamanders , and  invertebrates . [ 87 ]  In adult humans, injured tissue are repaired by  collagen  deposition, collagen remodelling and eventual scar formation, where fetal wound healing is believed to be more of a regenerative process with minimal or no scar formation. [ 86 ]  Therefore, foetal wound healing can be used to provide an accessible mammalian model of an optimal healing response in adult human tissues. Clues as to how this might be achieved come from studies of wound healing in embryos, where repair is fast and efficient and results in essentially perfect regeneration of any lost tissue.


The etymology of the term scarless wound healing has a long history. [ 88 ] [ 89 ] [ 90 ]  In print the antiquated concept of scarless healing was brought up in the early 20th century and appeared in a paper published in the London Lancet. This process involved cutting at a surgical slant to the skin surface, rather than at a right angle it; the process was described in various Newspapers. [ 88 ] [ 89 ] [ 90 ]


After inflammation, restoration of normal tissue integrity and function is preserved by feedback interactions between diverse cell types mediated by adhesion molecules and secreted cytokines. Disruption of normal feedback mechanisms in cancer threatens tissue integrity and enables a malignant tumor to escape the immune system. [ 91 ] [ 92 ]  An example of the importance of the wound healing response within tumors is illustrated in work by  Howard Chang  and colleagues at  Stanford University  studying breast cancers. [ 8 ]


Preliminary results are promising for the  short and long-term use of oral collagen supplements for wound healing  and skin aging. Oral collagen supplements also increase skin elasticity, hydration, and dermal collagen density. Collagen supplementation is generally safe with no reported adverse events. Further studies are needed to elucidate medical use in skin barrier diseases such as atopic dermatitis and to determine optimal dosing regimens. [ 93 ]


Modern wound dressing to aid in wound repair has undergone considerable research and development in recent years. Scientists aim to develop wound dressings which have the following characteristics: [ 94 ]


Cotton gauze dressings have been the standard of care, despite their dry properties that can adhere to wound surfaces and cause discomfort upon removal. Recent research has set out to improve cotton gauze dressings to bring them closer in line to achieve modern wound dressing properties, by coating cotton gauze wound dressing with a  chitosan / Ag / ZnO   nanocomposite . These updated dressing provide increase water absorbency and improved antibacterial  efficacy . [ 94 ]


Dirt or dust on the surface of the wound, bacteria, tissue that has died, and fluid from the wound may be cleaned. The evidence supporting the most effective technique is not clear and there is insufficient evidence to conclude whether cleaning wounds is beneficial for promoting healing or whether wound cleaning solutions ( polyhexamethylene biguanide ,  aqueous   hydrogen peroxide , etc.) are better than  sterile water  or  saline solutions  to help venous leg ulcers heal. [ 95 ]  It is uncertain whether the choice of cleaning solution or method of application makes any difference to  venous leg ulcer  healing. [ 95 ]


Considerable effort has been devoted to understanding the physical relationships governing wound healing and subsequent scarring, with mathematical models and simulations developed to elucidate these relationships. [ 96 ]   The growth of tissue around the wound site is a result of the migration of cells and collagen deposition by these cells.  The alignment of collagen describes the degree of scarring; basket-weave orientation of collagen is characteristic of normal skin, whereas aligned collagen fibers lead to significant scarring. [ 97 ]   It has been shown that the growth of tissue and extent of scar formation can be controlled by modulating the stress at a wound site. [ 98 ]


The growth of tissue can be simulated using the aforementioned relationships from a biochemical and biomechanical point of view.  The biologically active chemicals that play an important role in wound healing are modeled with Fickian diffusion to generate concentration profiles.  The balance equation for open systems when modeling wound healing incorporates mass growth due to cell migration and proliferation.  Here the following equation is used:


D t ρ 0  = Div (R) + R 0 ,


where  ρ  represents mass density,  R  represents a mass flux (from cell migration), and  R 0  represents a mass source (from cell proliferation, division, or enlargement). [ 99 ]  Relationships like these can be incorporated into an  agent-based models , where the sensitivity to single parameters such as initial collagen alignment, cytokine properties, and cell proliferation rates can be tested. [ 100 ]


Successful wound healing is dependent on various cell types, molecular mediators and structural elements. [ 101 ]


Primary intention is the healing of a clean wound without tissue loss. [ 101 ]  In this process, wound edges are brought together, so that they are adjacent to each other (re-approximated). Wound closure is performed with sutures (stitches), staples, or adhesive tape or glue.


Primary intention can only be implemented when the wound is precise and there is minimal disruption to the local tissue and the epithelial basement membrane, e.g. surgical incisions. [ 102 ]


This process is faster than healing by secondary intention. [ 101 ]  There is also less scarring associated with primary intention, as there are no large tissue losses to be filled with granulation tissue, though some granulation tissue will form. [ 101 ]


(Delayed primary closure):


If the wound edges are not reapproximated immediately, delayed primary wound healing transpires. This type of healing may be desired in the case of contaminated wounds. By the fourth day, phagocytosis of contaminated tissues is well underway, and the processes of epithelization, collagen deposition, and maturation are occurring. Foreign materials are walled off by macrophages that may metamorphose into epithelioid cells, which are encircled by mononuclear leukocytes, forming granulomas. Usually the wound is closed surgically at this juncture, or the scab is eaten, and if the "cleansing" of the wound is incomplete, chronic inflammation can ensue, resulting in prominent scarring.


Following are the main  growth factors  involved in wound healing:


The major complications are many:


Other complications can include infection and  Marjolin's ulcer .


Advancements in the clinical understanding of wounds and their  pathophysiology  have commanded significant biomedical innovations in the treatment of acute, chronic, and other types of wounds. Many biologics,  skin substitutes ,  biomembranes  and scaffolds have been developed to facilitate wound healing through various mechanisms. [ 108 ]  This includes a number of products under the trade names such as  Epicel ,  Laserskin ,  Transcyte, Dermagraft, AlloDerm/Strattice, Biobrane, Integra, Apligraf, OrCel, GraftJacket and PermaDerm. [ 109 ]


Railway surgery  was a branch of medical practice that flourished in the 19th and early 20th centuries.  It concerned itself with the medical requirements of railway companies.  Depending on country, it included some or all of:  general practice  for railway staff,  trauma surgery  as a result of accidents on the railways,  occupational health and safety ,  medico-legal  activities regarding compensation claims against the company, and occupational testing.


Railway surgery was especially well-developed in the US with formal professional organisations and scholarly journals.  One of the reasons for this was that US railways were particularly dangerous with a high number of casualties from crashes and an even higher number of workers hurt in  industrial accidents .  Another reason was that many US routes passed through areas with little or no existing medical infrastructure.  In Europe the railways were safer and infrastructure was generally already in place.  The duties of railway surgeons in Europe mostly involved investigations into accidents and the resulting claims arising from passengers.  In India the railways also faced a lack of existing medical infrastructure and, like the US, had to build it from scratch.  Indian Railways  still maintains a network of hospitals.


By the middle of the 20th century railway surgery had lost its separate identity.  The growth of other industries and improving rail safety meant that the railways no longer stood out as a leading cause of injuries.  Likewise, industrial medicine and health and safety became a concern for all industries.  There was no longer a need for an industry-specific branch of medicine.


The primary purpose of railway surgeons was to attend to the many injuries of staff and passengers on the railways.  Railway surgeons were also responsible for assessing medical claims against their companies and providing routine medical examinations of employees and applicants. [ 1 ]   Railway surgeons were keen to establish their profession as a separate discipline with unique problems.  For instance, the textbook  Railway Surgery , published in 1899, spends a whole chapter on the claim that crushing injuries from the heavy moving equipment on railways are of a kind not found in other industries. [ 2 ]


Railway surgeons were generally not well paid.  While a chief surgeon or consultant surgeon might attract a good salary, the ordinary doctors working out on the lines were not well rewarded. [ 3 ]


Rail crashes were common in the 19th century with many deaths and broken bones. [ 5 ]   In Europe, the majority of injuries were due to collisions, hence passengers rather than employees formed the bulk of the injured.  For instance, in Britain, accidents on the line such as crushing between  wagons  and being struck by trains (accidents suffered mostly by railway staff) were far fewer than passenger injuries through collisions in 1887. [ 6 ]   In the US, the railways were significantly more dangerous. [ 7 ]   Counterintuitively, this led to staff injuries being by far the greatest proportion. In 1892, US railroads reported 28,000 injuries to workers compared to 3,200 for passengers.  The most dangerous role was  brakeman , whose job included coupling and uncoupling wagons.  The most frequent injury was the brakeman being crushed between wagons while carrying out this task. [ 8 ]   One third of all railway injuries to staff were crushed hands or fingers. [ 9 ]


The number of deaths and injuries grew rapidly as the century progressed.  In the US, the first death occurred in 1831. There were 234 deaths in 1853, the year in which there were eleven major crashes. [ 10 ]   In 1890, there were 6,335 deaths and 35,362 injuries, [ 11 ]  and by 1907 it had reached its peak at nearly 12,000 deaths. [ 12 ]   In England, an early railway death was  William Huskisson ,  Member of Parliament  for  Liverpool , killed during the  opening of the Liverpool and Manchester Railway  in 1830. [ 13 ]   In the UK as a whole, deaths and injuries grew much less dramatically than the US.  There were 338 passenger deaths and injuries in 1855 and 435 in 1863, but at the same time passenger numbers were increasing.  From about the middle of this period the  rate  of injury started to go down with improving safety—2.85 per million passengers in 1855 to 2.12 in 1863. [ 14 ]   A similar picture of low rates pertained in other European countries such as France, Prussia, Belgium and Germany. [ 15 ]


Many injuries required amputation.  For instance, in 1880 the  Baltimore and Ohio Railroad  reported 184 crushed limbs, including 85 fractures and fifteen amputations. [ 16 ]   The need to perform amputations and other surgery may be why railway surgeons were named  surgeon  rather than  doctor  or  physician .  While traumatic injuries were not the most frequent ailment they had to deal with (that was infectious diseases) it did distinguish them from typical  general practitioners .  Other influences may have been the comparison to  ship's surgeons  in the age of sail, and the greater status and pay of surgeons. [ 17 ]


First aid kits  and training were introduced at the instigation of Charles Dickson of the  Canadian St. John Ambulance Association  and backed by many railway surgeons.  One railway surgeon reported that his fatality rate following amputation more than halved after first aid was introduced.  There was some opposition to first aid through fear that it eroded the professional status of doctors and that local contract railway surgeons would lose the fees they would otherwise have accrued for the work. [ 18 ]   However, by  World War I  first aid kits on trains had become widespread. [ 19 ]


As the twentieth century progressed, rail safety improved dramatically.  So much so that by 1956 the president of the Association of Surgeons of the  Chesapeake and Ohio Railway , when asked if he saw a lot of accident cases at the company hospital, could reply "yes, I see a lot of accidents from the highway" and "[t]he primary purpose of our group has all but passed out of the picture." [ 20 ]   The discipline of railway surgery had been folded into the more general discipline of  trauma surgery . [ 21 ]


An important function of railway surgeons was to control the costs of claims against their companies, leading to conflicts of interest regarding treatment of their patients.  For instance, the chief surgeon of the  Missouri Pacific Railroad  proudly boasted that he kept claims in the region of 14–35 dollars whereas claims against another railroad were nearly 600 dollars on average.  Company medical staff were also expected to help achieve political aims with expert evidence. In some cases chief surgeons were appointed purely on the basis of their relationship to important politicians. [ 22 ]


Fraudulent claims were a big concern for railway companies.  Sometimes, these were entirely contrived "accidents" by confidence tricksters; more commonly, however, they were exaggerations of the results of a genuine accident.  In 1906, railway surgeon Willis King claimed that 96% of claimants were actually  malingering . [ 23 ]   One common claim that was hotly debated [ 24 ]  by railway surgeons was the condition known as  railway spine .  Over a hundred papers were published on the subject in the medical literature for the period 1866–1890. [ 25 ]   In this condition, the patient reports cerebral symptoms such as headache or loss of memory, but there is no visible damage to the spine.  It was first described by Danish-British surgeon  John Eric Erichsen .  Erichsen believed the condition was  physiological , due to inflammation of the spinal cord.  He compared it to  meningitis  which had similar symptoms and a similar cause.  Others, such as  Herbert W. Page  (surgeon to the  London and North Western Railway ), argued that it was  psychological , or else, like  Arthur Dean Bevan  (1918 president of the  American Medical Association ), outright faked.  Railway surgeons were generally skeptical of the condition and disliked the implication that there was an injury peculiar to railways.  British surgeon Edwin Morris described the term as "most reprehensible". [ 26 ]   Bevan claimed to have cured one patient in ten minutes by standing him up and speaking to him forcefully. [ 27 ]


In Britain, a number of major train crashes led to parliament passing an  act  which compelled rail companies to pay compensation to victims of accidents.  A large proportion of the thousands of resulting claims were for railway spine.  In a five-year period in the 1870s English railway companies paid  £2.2 million ($11 million) in claims for railway spine. [ 28 ]   Following a similar law in Germany, 78% of claims in the period 1871–1879 were for back injury.  Claims for railway spine had subsided by 1900.  From 1890 there were more claims for  psychosomatic  conditions such as  hysteria  and the  neurasthenia  of  George Miller Beard  rather than physiological conditions such as railway spine.  Even Erichsen himself agreed that his original cases were actually traumatic neurasthenia.  However, medical concern remained over these emotional damage claims regarding malingering and false claims. [ 29 ]


Railway companies pioneered the disciplines of  industrial medicine  and  occupational safety and health .  They were the first organisations to give physical examinations to prospective employees.  The motivation was partly to prevent fraudulent claims for pre-existing conditions, but also to improve rail safety.  The  Baltimore and Ohio Railroad  in 1884 was the first to do this and had a particularly thorough examination.  They rejected 7% of applicants.  Colour blindness  tests were introduced for all employees in most US railway companies in the 1880s because of the need for correct signal recognition.  Hearing tests  were also implemented. [ 30 ]


Colour blindness tests were a result of the 1875  Lagerlunda rail accident  in Sweden.  The accident was investigated by  Frithiof Holmgren  who concluded that the crash was a result of colour blindness of the driver. [ 31 ]   Holmgren created a test for use in the transportation industry based on matching coloured  skeins of yarn .  However, Holmgren's test was disliked by employees and there were many complaints of unfairness.  Many companies preferred to test with lamps and flags, but this led to conflict with the railway surgeons who were concerned that non-professionals were administering medical tests. [ 32 ]   Holmgren's identification of colour blindness as the cause of the Swedish crash has also been disputed. [ 33 ]


Railway companies increasingly improved the health of their employees with preventative measures against disease.  Vaccination schemes were introduced.  Sanitation aboard trains became an issue, as did the quality of water supplies.  In the 1920s the  Cotton Belt Railroad  succeeded in cutting hospitalization due to  malaria  of its workers from 21.5% to 0.2%.  They did this with a program that included suppressing mosquito populations, preventative  quinine  treatment, education, and blood tests. [ 34 ]


Railway surgery was particularly well-developed in the US in the nineteenth and early-twentieth centuries.  Early American railroads passed through vast, thinly populated regions with little possibility of finding local medical care.  At the same time American railways were uniquely dangerous.  Accident rates were far higher than European railways.  That, together with difficulty in retaining skilled staff and the risk of legal action by injured passengers resulted in American railway companies developing medical infrastructure and organisations to a degree that was not seen elsewhere. [ 35 ]


The difference in risk between the US and Europe was largely driven by economics.  With their higher population densities and shorter routes, European countries carried more freight per mile of track than in the US.  To be profitable, American railways needed to be built and run more cheaply.  This led to a host of safety issues.  American railways were poorly signalled compared to British railways; in the US there were no  signal boxes , instead signalling was largely the responsibility of staff on board trains.  Rails were laid on thin beds and badly secured leading to many derailments.  Most tracks in Europe were double tracks whereas in the US they were usually single track.  Poor control of single-track rails led to many collisions.  There was no fencing on American tracks, leading to many collisions with people and animals. [ 36 ]


Certainly, railway companies in other countries had railway surgeons.  In Australia and Canada railway surgeons were appointed during the construction of major lines in remote regions. [ 37 ]   British companies employed railway surgeons as consultants. [ 38 ]   However, only in the US were railway surgeons employed in such large numbers and as such an organised discipline. [ 39 ]   India is perhaps the closest to the US in widespread use of railway surgeons which continues to this day, but there they never seem to have organised themselves as a discipline with professional associations until the 2000s. [ 40 ]


Construction of railways in the US began in 1828, becoming significant by 1840. By 1900 the railways were the largest US industry employing over a million, far more than any other dangerous occupation. [ 41 ]   Many thousands of injuries occurred on these railroads throughout the 19th century.  From 1850 until World War I, American railroad companies developed their own medical arrangements in order to retain workers, care for their passengers and injured third parties, and avoid legal action.  The earliest example of a company railroad surgeon was James P. Quinn [ 42 ]  on the Baltimore and Ohio Railroad in 1834, but the practice did not become widespread until the 1850s.  By the end of the 1850s most companies had some kind of medical service. [ 43 ]


Legal claims for compensation in the nineteenth century under  tort  laws were weaker than under twentieth century compensation laws.  Railroad workers (the majority of injuries) were not usually able to claim.  Nor were trespassers on railway property.  Passengers, however, were able to claim, but payments were low and few victims got anything compared to modern standards.  Nevertheless, the large number of crashes still led to a substantial number of legal actions. [ 44 ]


These organisations pioneered industrial medical care and predated the provision of medical care in manufacturing industries (although some mining companies did so).  Railway surgery was an important sector of the medical profession; by World War I railway organisations employed 14,000 doctors, some 10% of the US total.  Railway surgery operated outside of the  American Medical Association  (AMA) which railway surgeons were not permitted to join.  Many in the medical profession opposed company doctors altogether on the grounds of ethical conflict between the needs of the patient and the needs of the company.  The AMA also disliked the practice of doctors bidding for local contracts with the railway companies as this also introduced commercial pressures. [ 45 ]


Early medical arrangements on the railroads were informal.  The  Philadelphia & Reading Railroad  in particular had no formal contracts as late as the 1870s.  This led to many disputes over payment.  By the 1880s, however, all railroads had more formal arrangements.  They appointed a salaried chief surgeon and the larger ones had salaried regional surgeons as well.  Local doctors were paid according to fixed fees under contract.  In the West, the lack of existing medical facilities led to employee-funded hospitals.  The first of these was set up by the  Central Pacific Railroad  around 1867 and modelled on the US  Marine Hospital Service .  It was funded by a fixed deduction from all employees, except Chinese employees, who were excluded from the service.  A different kind of arrangement was the  mutual benefit society .  The first of these was set up by the Baltimore & Ohio Railroad in 1880 following the  Great Railroad Strike of 1877 .  Other railroads started to follow this model, partly because of its effect of dampening industrial strife.  By World War I about 30% (around two million) of railroad workers were members. [ 46 ]


By 1896 there were twenty-five railway hospitals run by thirteen different railway companies.  Between them they treated 165,000 patients annually.  Some of these hospitals became important  teaching hospitals  and generally they were all well financed and well equipped. [ 47 ]


After World War I railway surgery began to decline as a separate discipline.  It lost its political influence in the 1930s during the  Great Depression  as industry, including the railroads, reduced their involvement in health care for their workers. [ 48 ]   At the same time accident risks were steadily falling.  Between 1890 and 1940 risks for passengers and workers fell by 90% and 80% respectively. [ 49 ]


The first inter-city railway passenger service in the world was the  Liverpool and Manchester Railway , opened in 1830. [ 50 ]   By 1860, the UK had 10,000 miles of track and employed 180,000 people. [ 51 ]   Despite being the pioneer, British railways (and European railways in general) were much safer than American lines and consequently had fewer injuries, although early injury rates were still high by modern standards. [ 52 ]   Furthermore, British lines did not pass through vast, thinly populated regions.  Medical infrastructure was already well developed in the country.  Railway companies still employed surgeons.  Page at the London and North Western has already been mentioned.  Another example is  Thomas Bond  who was retained as surgeon by both the  Great Eastern  and  Great Western Railways .  However, Bond's function for the railways was primarily as medico-legal consultant regarding injury claims rather than practical surgery. [ 53 ]   He did, however, treat the injured of an overturned train on which he was himself a passenger.  Bond's last major work for the railways was investigations in connection with the  Slough rail accident  of 1900. [ 54 ]   Bond also wrote a lengthy article on railway injuries for Heath's  Dictionary of Practical Surgery . [ 55 ]   There is a similar picture with James O. Fletcher, surgeon to the  Manchester, Sheffield and Lincolnshire  and  Great Northern Railways , who wrote the book  Railways in Their Medical Aspects .  Fletcher's book discusses numerous cases where he examined or treated patients post-surgery and discusses medico-legal issues at length.  However, he does not cite a single example of his own, or railway colleagues', emergency surgery. [ 56 ]


The first dedicated  accident and emergency  (A&E) service in Britain was associated with the building of the  Manchester Ship Canal , 1887–1894, rather than railways.  However, the  civil engineer  in charge,  Thomas A. Walker , had a background in railway construction around the world, particularly in Canada where he had experience of employing British  navvies .  He was also responsible for construction of the  District Railway  in London.  Walker predicted, correctly, that there would be a high incidence of accidents during the canal construction.  He had a chain of A&E hospitals and first aid stations built and staffed along the route to service the 17,000 workers.  These were linked to the construction sites by purpose built railways.  The service was financed by compulsory worker contributions.  In total, there were 3,000 injuries and 130 deaths during construction. [ 57 ]


Railways in India began to be built during the  British India  period.  The first passenger service opened between  Mumbai  and  Thane  in 1853. [ 58 ]   As in many parts of the US, there was no pre-existing medical infrastructure.  Medical facilities had to be entirely provided by the railways themselves.  This, along with other social needs, led to the establishment of railway "colonies" to house the railway workers and their families.  For instance, the railway colony of  Jamalpur  was established in 1862. [ 59 ]   By 1869, one railway surgeon and four assistants were employed at Jamalpur by the  East Indian Railway Company  to cover the 800 inhabitants of the colony and over 200 miles of railway line.  This section had around 200 accidents per year to deal with but that was not their only duty.  They also acted as  general practitioners  for the colony, including attending at childbirth. [ 60 ]


By 1956, the railways had established 80 hospitals and 426 dispensaries.  Additionally, mobile railway surgeons served railway staff posted along the line. [ 61 ]   This infrastructure of railway colonies, medical staff, and hospitals is still maintained by the railways.  A major example of a railway colony is the colony at  Kharagpur , West Bengal, established 1898–1900. [ 62 ]   It serves one of the largest railway workshops in India. [ 63 ]   A major example of a railway hospital is the  Southern Railway Headquarters Hospital  at  Chennai .  Southern Railway  also maintain divisional hospitals such as the  Divisional Railway Hospital, Golden Rock  as do the other zones of  Indian Railways . [ 64 ]


Hospital trains  were in use early in the railway age, but usually in wartime, starting in the  Crimean War  in 1855. [ 65 ]   For normal civilian use, they were a fairly late development in the railway surgery period.  In the US, a hospital car came into use on several railways that could be coupled to a train to transport the surgeon and staff to the scene of an incident along with all the required equipment.  It contained an  operating theatre  and a number of beds for patients in a  recovery room .  Hospital cars significantly improved the outcomes for victims. [ 66 ]   These mobile hospitals were the forerunner of the US Army's  mobile army surgical hospitals . [ 67 ]


Indian Railways introduced the  Lifeline Express  hospital train in 1991.  Its purpose was to serve the needs of rural poor in India.  In 2007 a modernised hospital train, the New Lifeline Express replaced it. [ 68 ]


From the 1880s onwards specific societies were formed for railway surgery.  The first of these was the Surgical Society of the Wabash, formed in 1881 and organised by the chief surgeon of the  Wabash Railroad .  The inaugural meeting had only twenty-two attendees with two papers presented.  This was soon followed by many other company centred organisations.  The  Pennsylvania Railroad  organisation was the prime mover in forming the  National Association of Railway Surgeons  (NARS) in 1888.  The inaugural meeting had two hundred attendees and by 1891 the membership had grown to nearly a thousand. [ 69 ]   However, NARS was short-lived, dying out in the 1920s as industrial expansion caused the railways to no longer be unique in their medical needs.  Nevertheless, there were still practising railway surgeons for some time after this. [ 70 ]


In 1891, the journal  Railway Age  began a column on railway surgery, including the proceedings of NARS.  The editor, R. Harvey Reed, was a  charter member  of NARS but left to form the more exclusive  American Academy of Railway Surgeons .  The two organisations remained rivals until 1904 when they merged to form the  American Association of Railway Surgeons  (AARS).  The  Railway Surgeon  was launched in 1894 and took over from  Railway Age  as the official journal of NARS, but it also carried articles from the American Academy. [ 71 ]   It was the official journal of NARS, 1894–1897; of the  International Association of Railway Surgeons , 1897–1904; and of the AARS, 1904–1929. [ 72 ]


The changing names and affiliations of the  Railway Surgeon  across the years reflects the absorption of railway surgery into the more general occupational health and the spread of industrial medicine.   Railway Surgeon  (1894–1904), became  Railway Surgical Journal  (1904–1921), [ 73 ]  became  Surgical Journal Devoted to Traumatic and Industrial Surgery  (1921–1929), [ 74 ]  absorbed by  International Journal of Medicine and Surgery  (1923–1935), [ 75 ]  with  Industrial Medicine  (1932–1935), [ 76 ]  became  International Journal of Industrial Medicine and Surgery  (1935–1949), became  Industrial Medicine and Surgery  (1949–1967), [ 77 ]  became  IMS, Industrial Medicine and Surgery  (1968–1973), [ 78 ]  became  The International Journal of Occupational Health and Safety  (1974–1975), [ 79 ]  became  Occupational Health and Safety  (1976–present). [ 80 ]


Criticism of Erichsen and "railway spine" was particularly strident in the US with NARS and its journal, the  Railway Surgeon  leading the attack.  So much effort was devoted to discrediting the condition as medically valid that one writer claimed the issue was the reason for existence of the association.  Prominent in NARS for speaking out against Erichsen was  Warren Bell Outten , chief surgeon for the Missouri Pacific Railway. [ 81 ]


In India, the  Association of Railway Surgeons of India  held its first annual meeting in 2001. [ 82 ]


Surgical oncology  is the branch of  surgery  applied to  oncology ; it focuses on the surgical management of  tumors , especially  cancerous  tumors.


As one of several modalities in the  management of cancer , the specialty of surgical oncology has evolved in steps similar to medical oncology ( pharmacotherapy  for cancer), which grew out of  hematology , and  radiation oncology , which grew out of  radiology . The Ewing Society—known today as the Society of Surgical Oncology—was started by surgeons interested in promoting the field of oncology. In 2011, the  American Board of Surgery  ratified Complex General Surgical Oncology via a specialty Board certification. [ 1 ]  The field was expected to continue expanding via the proliferation of cancer centers, as well as advanced minimally invasive techniques,  palliative surgery , and neo-adjuvant treatments.


Whether surgical oncology constitutes a medical specialty  per se  is the topic of a heated debate. Today, some would agree that it is simply impossible for any one surgeon to be competent in the surgical management of  all  malignant disease [ 2 ]   There are currently 19 surgical oncology fellowship training programs in the United States that have been approved by the Society of Surgical Oncology and this number is expect to grow. [ 3 ]  While many general surgeons are actively involved in treating patients with malignant neoplasms, the designation of "surgical oncologist" is generally reserved for those surgeons who have completed one of the approved fellowship programs.  However, this is a matter of semantics, as many surgeons who are thoroughly involved in treating cancer patients may consider themselves to be surgical oncologists. [ 4 ]


Most often,  surgical oncologist  refers to a general surgical oncologist (a subspecialty of  general surgery ), but thoracic surgical oncologists, gynecologic oncologists and so forth can all be considered surgeons who specialize in treating cancer patients.


The importance of training surgeons who sub-specialize in cancer surgery lies in evidence, supported by a number of  clinical trials , [ 5 ]  that outcomes in surgical cancer care are positively associated to surgeon volume—i.e., the more  cancer  cases a surgeon treats, the more proficient he or she becomes, and his or her patients experience improved survival rates as a result. This is another controversial point, but it is generally accepted—even as common sense—that a surgeon who performs a given operation more often, will achieve superior results when compared with a surgeon who rarely performs the same procedure. This is particularly true of complex cancer resections such as,  Breast Cancer Surgery ,  pancreaticoduodenectomy  (Whipple procedure) for pancreatic cancer, and  gastrectomy  with extended (D2)  lymphadenectomy  for gastric cancer.  In the United States and Canada, fellowship trained surgical oncologists have among the longest training periods of any physicians/surgeons. In some areas like  Breast Diseases  and  Breast Cancer  there we know as Breast Surgeon the specialist that only works with patients with  breast diseases  and  breast cancer . A training period (clinical and research) of 6 to 8 years is typical and 8–10 years is not uncommon.


These are the most common types and forms of oncological surgery: [ 6 ]


Newer surgical techniques are less invasive, use different types of surgical instruments, and lead to less pain and shorter recovery times. The most effective surgical oncology techniques are:


One of the first text books dedicated to surgical oncology was written by the American-Irish surgeon, Theodore O'Connell in 1981. [ 9 ]  Many publications in surgical oncology are also appearing. The majority are large reference textbooks that seemingly combine specialties that are not generally practiced by a single practitioner but cover the academic subject. A number of practical handbooks such as "surgical oncology" in the well read Oxford Handbooks series, have recently been published, perhaps alluding to the evolving practicality of this emerging discipline. [ citation needed ]


Adrenalectomy  (Latin root  Ad  "near/at" +  renal  "related to the kidneys" + Greek  ‑ectomy  “out-cutting”; sometimes written as  ADX  for the procedure or resulting state) [ 1 ] [ 2 ]  is the surgical removal of one ( unilateral ) or both ( bilateral )  adrenal glands . It is usually done to remove  tumors of the adrenal glands  that are producing excess hormones or is large in size (more than 2 inches or 4 to 5 centimeters). Adrenalectomy can also be done to remove a cancerous tumor of the adrenal glands, or cancer that has spread from another location, such as the kidney or lung. Adrenalectomy is not performed on those who have severe  coagulopathy  or whose heart and lungs are too weak to undergo surgery. The procedure can be performed using an open incision ( laparotomy ) or minimally invasive  laparoscopic  or  robot-assisted  techniques. [ 3 ]  Minimally invasive techniques are increasingly the gold standard of care due to shorter length of stay in the hospital, lower blood loss, and similar complication rates. [ 3 ] [ 4 ]


One  adrenal gland  sits above each  kidney . The two adrenal glands produce  hormones  ( steroid hormones  and  catecholamines ) that help regulate  blood pressure ,  blood sugar level ,  metabolism ,  immune system ,  stress  and other essential functions. If one adrenal gland is removed, the other adrenal gland will take over the hormone-producing role. If both adrenal glands are removed, the patient will require lifelong  steroid  supplementation. [ 5 ]


Most adrenal tumors are noncancerous ( benign ), often found incidentally as a mass via imaging such as  CT scans ,  MRI , or  ultrasound  that were taken for other health workups (see  incidentaloma ). Although these adrenal masses do require evaluation, the majority of them (approximately 80% [ 7 ] ) do not require adrenalectomy. However, due to the hormone-producing function of the adrenal glands, some noncancerous adrenal tumors may produce too much hormones, such as  aldosterone  (called  primary aldosteronism ),  cortisol  (called  Cushing's disease  or  Cushing's syndrome ), or  catecholamines  (called  pheochromocytoma ). These hormone-producing tumors may need adrenalectomy. Additionally, adrenal tumors that are larger than 4 centimeters in size, regardless of whether they produce hormones, also require adrenalectomy due to increased risk of adrenal cancer. Rarely (5–12%), the adrenal tumor may be cancerous ( adrenocortical carcinoma ), requiring adrenalectomy. Rarer still, the mass may be a  metastatic cancer that spread from another location , such as the kidney or lung. If the metastasis is isolated to the adrenal gland, it may be a candidate for adrenalectomy. [ 5 ] [ 7 ]


An absolute  contraindication  (a reason not to do the surgery under any situation) for adrenalectomy are patients who are generally unsuited to surgery: having severe coagulopathy and poor cardiopulmonary performance due to the stress to the body that surgery will produce. In addition,  American Association of Clinical Endocrinologists  and  American Association of Endocrine Surgeons  guidelines state minimally-invasive techniques should be avoided when there is a large tumor size (larger than 6 cm) due to difficulties in maneuvering around a large mass, and in adrenocortical carcinoma where there is a risk of not fully removing the cancerous tissue. [ 3 ] [ 7 ]  However, at least one meta-analysis of 898 patients has found shorter length of stay, less blood loss, and no higher rates of complications even in large (>5 cm) tumors using minimally-invasive techniques. [ 8 ]


Techniques for adrenalectomy is largely divided into two types: open surgical  laparotomy  versus  minimally invasive  techniques.


Surgeons usually reserve open surgery for large (larger than 6 cm) or cancerous tumors where there is a risk of not fully removing the cancerous tissue. They perform open surgery using traditional instruments and cuts (incisions). [ 7 ]


Minimally invasive techniques may be  laparoscopic , where several small cuts (incisions) are made to allow for the surgeon to directly control surgical instruments with their hands while visualizing the surgery via a tiny camera that provides a magnified, 3D view of the surgical site. Laparoscopic surgery has many benefits. For example, this surgery has smaller scars, less pain, less blood loss, similar complication rates, and a shorter recovery period than traditional open surgery. [ 8 ] [ 3 ]  Traditionally, this has been through the laparoscopic transperitoneal approach (LTA) where the small cuts are made in the abdomen to reach the adrenal glands through the  peritoneum  from the front-side.


However, an alternative approach is possible called retroperitoneoscopic adrenalectomy (PRA), where the adrenal glands are reached through small cuts made in the back. Studies have shown that both LTA and PRA are equally safe and effective, though some suggest advantages of PRA over LTA in terms of lower intensity of postoperative pain, shorter hospital stay, faster recovery, and lower early morbidity. A 2018  systematic review  suggests that laparoscopic retroperotenial adrenalectomy appears to reduce late morbidity, time to oral fluid or food intake and time to ambulation when compared to laparoscopic transperitoneal adrenalectomy; however, there is uncertainty about these effects due to very low-quality evidence. [ 9 ]  For outcomes such as all-cause mortality, early morbidity, socioeconomic effects, and operative and postoperative parameter, the evidence is uncertain about the effects of either interventions over the other. [ 9 ]  PRA involves high pressure CO₂ within a limited  retroperitoneal space , and therefore may cause kidney injury in those at high risk. [ 4 ]


Sometimes surgeons perform  robot-assisted  adrenalectomies. They perform the surgery through small cuts (incisions) using robotic arms with a camera and instruments attached. The camera gives doctors a high-definition, magnified, 3D view of the surgical site. No significant differences were found between laparoscopic and robot-assisted adrenalectomy in two meta-analyses for complications, blood loss, or mortality, however robotic adrenalectomy had shorter hospital stays at the cost of longer operating time and higher cost of surgery. [ 4 ] [ 10 ] [ 3 ]


Postoperative care is highly dependent on what the adrenalectomy was performed for. After adrenalectomy for a  cortisol -producing adenoma, patients should be treated with exogenous  glucocorticoids  such as  cortisone  or  hydrocortisone  until the  hypothalamic-pituitary-adrenal (HPA) axis  has recovered. This process may take 6 to 18 months after unilateral adrenalectomy. Similarly, for patients who have undergone adrenalectomy for (subclinical)  Cushing syndrome , perioperative glucocorticoid therapy and postoperative assessment of HPA axis recovery are necessary. For patients who have undergone adrenalectomy for a pheochromocytoma, long-term followup is necessary because 10-15% of patients may have recurrence. [ 7 ]  For those with high blood pressure ( secondary hypertension ) from primary aldosteronism, adrenalectomy provides a clinical cure rate of approximately 27.1%. [ 11 ]


If both adrenal glands are removed, the patient can no longer create the adrenal hormones necessary for life ( primary adrenal insufficiency ). Signs and symptoms include volume depletion, hypotension, hyponatremia, hyperkalemia, fever, abdominal pain. This requires lifetime treatment with the hormones produced by the removed adrenal glands, including glucocorticoids and  mineralocorticoids  ( fludrocortisone ). The glucocorticoid dose needs to be increased when in  stress  or during  infections  or else  adrenal crisis  may occur. [ 5 ] [ 12 ]


For women with deficiency in androgens as a result of the loss of androgen production from the adrenal glands following adrenalectomy,  dehydroepiandrosterone (DHEA)  replacement can be considered. The signs and symptoms include low libido, depressive symptoms, and/or low energy levels despite optimized glucocorticoid and mineralocorticoid replacement. [ 7 ] [ 5 ]


Complications from an adrenalectomy can include insufficient  cortisol  production,  acute kidney injury , post-operative bleeding, damage to nearby organs, and post-operative infection.


Annals of Surgical Oncology  is a  peer-reviewed   medical journal  published by  Springer International Publishing  on behalf of the  Society of Surgical Oncology . It is an official journal of the Society of Surgical Oncology, and the  American Society of Breast Surgeons . [ 1 ]  The  editor-in-chief  is  Kelly M. McMasters  ( University of Louisville School of Medicine ).


The journal is abstracted and indexed in  Index Medicus / MEDLINE / PubMed , [ 2 ]   Current Contents /Clinical Medicine, [ 3 ]   Excerpta Medica , and the  Science Citation Index . [ 3 ]  According to the  Journal Citation Reports , the journal has a 2020  impact factor  of 5.344. [ 4 ]


This article about an  oncology   journal  is a  stub . You can help Wikipedia by  expanding it .


A  bowel resection  or  enterectomy  ( enter-  +  -ectomy ) is a  surgical procedure  in which a part of an intestine (bowel) is removed, from either the  small intestine  or  large intestine . Often the word  enterectomy  is reserved for the  sense  of small bowel resection, in distinction from  colectomy , which covers the sense of large bowel resection. Bowel resection may be performed to treat  gastrointestinal cancer , bowel  ischemia ,  necrosis , or  obstruction  due to  scar  tissue, volvulus, and hernias. Some patients require  ileostomy  or  colostomy  after this procedure as alternative means of  excretion . [ 1 ]  Complications of the procedure may include anastomotic leak or dehiscence, hernias, or adhesions causing partial or complete bowel obstruction. Depending on which part and how much of the intestines are removed, there may be  digestive  and  metabolic  challenges afterward, such as  short bowel syndrome .


Types of enterectomy are named according to the relevant bowel segment:


The anatomy and surgical technique for bowel resection varies based on the location of the removed segment and whether or not the surgery is due to malignancy. The below sections describe resection for non-malignant causes. Malignancy may require more extensive tissue resection beyond what is described here.


Bowel resection may be done as an open surgery, with a long incision in the abdomen. It may also be done laparoscopically or robotically by creating several small incisions in the abdomen through which surgical instruments are inserted. [ 2 ] [ 3 ] [ 4 ]  Once the abdomen is accessed by one of these methods the surgery may proceed.


Once the abdomen is accessed, the surgeon "runs" the small bowel, viewing the entire small bowel from the  ligament of treitz  to the  ileocecal valve . This allows for total evaluate of the small bowel to identify any and all pathologic sections. Once the area of concern is located, two small holes are created in the  mesentery  on either end of the segment. These holes are used to place a  surgical stapler  across the bowel and separate the segment of injured bowel from the healthy bowel on each end. Then bowel is then dissected away from the mesentery. Following this the remaining bowel is observed to verify continued blood flow. After resection the surgeon will create an  anastomosis  between the two ends of the bowel. Following this the hole in the mesentery created by removing the section of bowel is closed with sutures to prevent internal herniation. The resected section of bowel will then be removed from the abdomen and the abdomen closed. This concludes the procedure. [ 5 ] [ 6 ]


The right and left colon sit in the  retroperitoneum . To access this space an incision is made along the  line of Toldt . The colon is then mobilized from the retroperitoneum. Care is taken to avoid injury to the  ureters  and  duodenum . The surgery then follows the same steps as small bowel resection. However, due to the colon's placement in the retroperitoneum, more dissection is often required to allow for tension free anastomosis. [ 5 ] [ 6 ]


Small bowel  or  colon cancer  may require surgical resection. [ 7 ]


Small bowel cancer often presents late in the course due to non-specific symptoms and has poor survival rates. Risk factors for small bowel cancer include genetically inherited polyposis syndromes, age over sixty years, and history of Crohn's or Celiac disease. Cases that present before stage IV show survival benefit from surgical resection with clear margins. It is recommended that surgical resection also include lymph node sampling of a minimum of 12 nodes with some groups extolling more extensive resection. When evaluation determines cancer to be stage IV, surgical intervention is no longer curative, and is only used for symptom relief. [ 7 ]


Colon cancer is the third most common cancer and the second most common cause of cancer death in the USA. [ 8 ]  Due to its prevalence, screening protocols have been created for prevention of disease. Screening colonoscopies with or without polypectomy have been shown to decrease cancer morbidity and mortality. [ 9 ]  When cancer is more advanced and polypectomy is not possible surgical resection is necessary. Using imaging and pathologic evaluation of resected tissue the tumor may be staged using AJCC stages. [ 9 ]  Surgical resection of tumors for staging and for curative purposes requires removal of local blood vessel and lymph nodes. Standard lymph node resection includes three consecutive levels of lymph nodes and is known as a D3 lymphadenectomy. [ 10 ]  In addition to surgery adjuvant chemotherapy may be used to decrease risk of recurrence. Chemotherapy is standard with stage III cancer, case dependant in stage II and palliative in stage IV. [ 11 ]  Diet high in processed food and sugary drinks has also been shown to increase recurrence of stage III colon cancer. [ 12 ]


Bowel obstructions are commonly secondary to  adhesions ,  hernias , or cancer. Bowel obstruction can be an emergency requiring immediate surgery. Original testing and imaging include blood tests for electrolyte levels, and abdominal X-rays or CT scans. Treatment often begins with IV fluids to correct electrolyte imbalances. Obstructions may be complicated by ischemia or perforation of the bowel. These cases are surgical emergencies and often require bowel resection to remove the cause of obstruction. [ 13 ]  Adhesions are a common causes of obstruction, and frequently resolve without surgery. [ 14 ]


Other causes of bowel obstruction include  volvulus ,  strictures , inflammation and  intussusception . This is not an exhaustive list.


Bowel perforation presents with abdominal pain, free air in the abdomen on standing X-ray, and sepsis. [ 15 ] [ 16 ] [ 17 ]  Depending on the cause and size, perforations may be medically or surgically managed. Some common causes of perforation are cancer,  diverticulitis , and  peptic ulcer disease .


When caused by cancer, bowel perforation typically requires surgery, including resection of blood and lymph supply to the cancerous area when possible. When perforation is at the site of the tumor, the perforation may be contained in the tumor and self resolve without surgery. However, surgery may be required later for the malignancy itself. Perforation before the tumor usually requires immediate surgery due to release of fecal material into the abdomen and infection. [ 15 ]


Perforated diverticulitis often requires surgery due to risks of infection or recurrence. Recurrent diverticulitis may required resection even in the absence of perforation. Bowel resection or repair is typically initiated earlier in patients with signs of infection, the elderly, immunocompromised, and those with severe comorbidities. [ 16 ]


Peptic ulcer disease may cause perforation of the bowel but rarely requires bowel resection. Peptic ulcer disease is caused by stomach acid overwhelming the protection of mucus production. Risk factors include  H. pylori  infection, smoking, and NSAID use. The standard treatment is medical management, endoscopy followed by surgical omental patch repair. In rare cases where omental patch fails bowel resection may become necessary. [ 17 ]


Traumatic injuries , whether blunt force such as car accidents or penetrating wounds such as gunshot wounds, or stabbings, may also cause bowel perforation or ischemia requiring emergency surgery. Initial evaluation in trauma includes a  FAST  ultrasound exam followed by contrast CT abdomen in stable patients. The most common bowel injury in trauma is perforation and is repaired rather than resected if the injury involves less than half the bowel circumference and does not involve loss of blood supply. Resection is indicated with more extensive or ischemic injuries. [ 18 ]


Bowel ischemia is caused by decreased or absent blood flow through the Celiac, Superior Mesenteric, and Inferior Mesenteric arteries or any combination thereof. Untreated  acute mesenteric ischemia  can cause bowel  necrosis  in the affected area. This requires emergent surgery as survival without endovascular or operative intervention is around 50%. Ischemic bowel injury often requires multiple surgeries days apart to allow bowel recovery and increase odds of successful  anastomosis . [ 19 ]


An anastomotic leak is a fault in the surgical connection between the two remaining sections of bowel after a resection is performed. This allows the bowel contents to leak into the abdomen. Anastomotic leaks may cause infection, abscess development, and organ failure if untreated. Surgical steps are taken to prevent leaks when possible. These include creating anastomoses with minimal tension on the connection and aligning the bowel to prevent twisting of the bowel at the anastomosis. However, it is believed that most leaks are caused by poor healing, not surgical technique. Risk factors for poor healing of anastomosis include obesity, diabetes mellitus, and smoking. [ 20 ]  Treatment of the leak includes antibiotics, placement of a drain near the leak or developing abscess, stenting of the anastomosis, surgical repair, or creating of an  ileostomy  or  colostomy . [ 21 ]


Any abdominal surgery may result in an incisional hernia where the abdomen was accessed. Hernias develop when the fascia of the abdominal cavity separates after the surgical closure. This may be due to suture failure, poor wound healing. Other risk factors include obesity and smoking. [ 22 ]  Smaller closure stitches and the use of mesh when closing open surgeries may decrease the risk of hernia occurrence. However, the use of mesh is limited by the surgery performed and contamination or risk infection. [ 23 ]


When colon is resected hernias may form through the mesenteric defect. This is more common with  gastric bypass surgery . Internal hernias may cause ischemia and require emergency surgery to resolve.


A common complication of all abdominal surgeries is adhesions. Adhesions are bands of scar tissue that form after surgery or injury to the abdomen. They can displace or obstruct areas of the bowel. Approximately 1 in 5 emergency surgeries are due to adhesive bowel obstruction. When possible this is managed without surgery with IV fluids, and NG tube to drain the stomach and intestines, and bowel rest (not eating) until the obstruction resolves. If signs of bowel ischemia or perforation are present then emergency surgery is required. Laparoscopic adhesiolysis is the most common surgery used when bowel rest and medical management fail to resolve the obstruction. [ 14 ]


When large amounts of small bowel are resected it can cause short bowel syndrome. Short bowel syndrome is a failure of absorption of nutrients due to resection of portions of the small bowel. It can be limited to a single nutrient or it can be total malabsorption. If the distal ileum is resected it commonly causes a mild form of short bowel syndrome with deficiency of only vitamin B12. When the entire small bowel is resected it can cause chronic complications. [ 24 ] [ 25 ]


The acute form lasts up to one month following bowel resection. Symptoms include diarrhea, malabsorption, and metabolic derangements. This is treated primarily by IV fluids and electrolyte replacement. Acute short bowel syndrome is followed by the adaptation phase which can last up to two years. During this time the small bowel slows movement of bowel contents to allow for more absorption. About half of all patients with short bowel syndrome progress to chronic disease.  Chronic short bowel syndrome may require  total parenteral nutrition  and chronic  central line  use. These may cause complications such as bacteremia and sepsis. Other complications of short bowel syndrome are chronic diarrhea or high output from the ostomy site, intestinal failure associated liver disease, and electrolyte level abnormalities. [ 24 ]


Short bowel syndrome is rare and usually follows extensive ischemic bowel caused by internal hernias, volvulus, or mesenteric ischemia where the remaining small bowel is under 200 cm long. [ 24 ] [ 26 ]


Cervical conization  refers to an excision of a cone-shaped portion of tissue from the  mucous membrane  of the  cervix . Conization is used for diagnostic purposes as part of a  biopsy  and for therapeutic purposes to remove pre-cancerous cells ( cervical intraepithelial neoplasia ) or early stage  cervical cancer . [ 1 ]


Types include: [ 2 ] [ 3 ]


Cervical conization effectively reduces the risk of cancer developing or spreading but it causes an increased risk of  premature birth  in future pregnancies. [ 2 ] [ 3 ]


The chances of cancer recurrence and premature birth depends on the type of conization. Cold knife conization is associated with 7% chance of the cancer recurring and 16% chance of premature birth, laser conisation comes with 6% cancer recurrence and 13% premature birth, and loop excision comes with 10% recurrence and 11% premature birth. [ 2 ] [ 3 ]


Coccygectomy  is a surgical procedure in which the  coccyx  or tailbone is removed. It is considered a required treatment for  sacrococcygeal teratoma  and other  germ cell tumors  arising from the coccyx. Coccygectomy is the treatment of last resort for  coccydynia  (coccyx pain) which has failed to respond to nonsurgical treatment.  Non surgical treatments include use of seat cushions, external or internal manipulation and massage of the coccyx and the attached muscles, medications given by local injections under fluoroscopic guidance, and medications by mouth. [ 1 ]


To remove the coccyx, an incision is made from the tip of the coccyx to its joint with the sacrum. The coccyx is cut away from the surrounding tissues, cut off at the joint with the sacrum, and removed. If the tip of the sacrum is rough, it is filed down. The wound is closed in layers. [ 2 ] [ 3 ]


As with any operation under anaesthetic, there are risks associated with  general anaesthesia  itself. An additional possible complication of coccygectomy is infection at the surgical site, due to the site's proximity to the anus, leading to contamination by bacteria from the patient's feces. An analysis of 24 studies of coccygectomy (covering 702 patients) [ 4 ]  reported that 19 studies (covering 493 patients) reported the post-surgery infection rate, while the other five studies gave incomplete information. Among the patients in the 19 studies with full information, the infection rate was 12%. In most cases the infection was superficial, but 4% of operations caused an infection that required repeat surgery to treat the infection. However, the use of prophylactic antibiotics, preoperative rectal enema, closure of the wound in two layers and use of a topical skin adhesive have been shown to reduce the rate of infection to 0%. [ 3 ]


In adults who undergo coccygectomy, one rare complication is a subsequent  perineal hernia  or coccygeal hernia. In these hernias, bowel or other pelvic contents bulge downward and out of the pelvis through a weakened pelvic floor. This complication has not been reported in persons who underwent coccygectomy while a baby or child. A milder version of hernia is when someone just has prolapse (sagging) of the pelvic floor. To repair these hernias, a variety of surgical techniques have been described. [ 5 ] [ 6 ] [ 7 ]


The coccygectomy operation had a poor reputation in the past, and some doctors still advise that the surgery should be avoided. However current data from clinical trials reports success rates of 50 up to 90%, a percentage that rises to 80-90% in patients that are considered to be 'good candidates' for this kind of surgery. A study that was published in 2001 covering a total of 702 patients found good or excellent results in 83% of cases. [ 4 ]


Colectomy  ( col-  +  -ectomy ) is the  surgical  removal of any extent of the  colon , the longest portion of the  large bowel . Colectomy may be performed for prophylactic, curative, or palliative reasons. Indications include cancer, infection, infarction, perforation, and impaired function of the colon. Colectomy may be performed  open ,  laparoscopically , or  robotically . Following removal of the bowel segment, the surgeon may restore continuity of the bowel or create a  colostomy .  Partial or subtotal colectomy refers to removing a portion of the colon, while total colectomy involves the removal of the entire colon. Complications of colectomy include anastomotic leak, bleeding, infection, and damage to surrounding structures.


Common indications for colectomy include: [ 1 ] [ 2 ]


Before surgery, patients typically undergo preoperative bloodwork, including a complete blood count and type and screen of blood type. Diagnostic imaging may include colonoscopy or  CT  scans of the abdomen and pelvis. In cancer patients, lesions are commonly tattooed via colonoscopy before colectomy to give the surgeon an intraoperative visual guide. [ 1 ]  For non-emergent procedures, patients are typically instructed to follow a clear liquid diet or fast and take a  mechanical bowel preparation  (oral osmotic agents or laxative) to clear the bowels before surgery. [ 4 ] [ 1 ]  Antibiotics may also be prescribed ahead of surgery to reduce risk of post-operative infection. [ 2 ]


Traditionally, colectomy is performed via an abdominal incision, a technique known as  laparotomy . Minimally invasive colectomy using  laparoscopy  is a well-established procedure in many medical centers. [ 5 ] [ 6 ]  Robot-assisted colectomy is growing in scope of indications and popularity. [ 7 ]


As of 2012, more than 40% of colon resections in the United States are performed via a laparoscopic approach. [ 5 ]  For laparoscopic colectomy, the typical operative technique involves 4-5 separate incisions made in the abdomen.  Trochars  are introduced to gain access to the  peritoneal cavity  and serve as ports for the laparoscopic camera and other instruments. [ 8 ]   Studies have proven the feasibility of single port access colectomy, which would require only one small incision, but no clear benefit in terms of outcome or complication rate has been demonstrated. [ 6 ] [ 9 ]


Before removal, the portion of the bowel to be resected must be freed or mobilized. This is done by dissection and removal of the  mesentery  and other peritoneal attachments. Resection of any part of the colon entails mobilization and the cutting and sealing, or  ligation , of the blood vessels supplying the portion of the colon to be removed. [ 8 ]  A stapler is typically used to cut across the colon to prevent spillage of intestinal contents into the peritoneal cavity. [ 10 ]  Colectomy as treatment for colorectal cancer also includes  lymphadenectomy , or removal of surrounding lymph nodes, which may be done for staging of the cancer or removal of cancerous nodes. [ 11 ]  More extensive lymphadenectomy is sometimes accomplished by the removal of the  mesocolon , the fatty tissue adjacent to the colon, which contains blood supply, lymphatics, and nerves to the colon. [ 12 ] [ 13 ]


When the resection is complete, the surgeon has the option of reconnecting the bowel by stitching or stapling together the cut ends of the bowel (primary  anastomosis ) or performing a  colostomy  to create a  stoma , an opening of the bowel to the  abdominal wall  that provides an alternate exit for the contents of the  gastrointestinal tract . [ 1 ]  When colectomy is performed as part of damage control surgery in life-threatening trauma resulting in destructive colon injury, the surgeon may opt to leave the cut ends of the bowel sealed and disconnected for a short time to allow for further resuscitation of the patient before returning to the operating room for definitive repair (anastomosis or colostomy). [ 14 ]


In modern times,  surgical staplers  are typically used to create colorectal anastomoses, although hand sewn, or  sutured , anastomoses are still done today. Studies have shown that differences in rates of anastomotic leak and surgical site contamination for stapled vs. sutured anastomoses are not statistically significant. The increased speed and decreased human variability afforded by stapling make it an attractive option for most surgeons. [ 15 ]


Several factors are taken into account when deciding between anastomosis or colostomy, including:


Giving a patient a  colostomy  avoids the risk of a failed anastomosis. Still, it places a societal, psychological, and physical burden on the patient, as a stoma requires special care and consideration. [ 16 ]


All surgery involves a risk of serious complications, including bleeding, infection, damage to surrounding structures, and death. Additional complications associated with colectomy include:


An anastomosis carries the risk of  dehiscence  or breakdown of the surgical connection. Contamination of the  peritoneal cavity  with fecal matter as a result of the anastomotic leak can lead to  peritonitis ,  sepsis  or  death . In patients who underwent colectomy as a treatment for colorectal cancer, an anastomotic leak increases the risk of recurrence of cancer in the same area and reduces survival in the long term. Several factors influence the risk of anastomotic dehiscence, including preservation of blood supply to the cut ends of the bowel, tension on the anastomosis, and the patient's intestinal microbiome, which affects wound healing and potential for surgical site infection. [ 15 ]


The use of  NSAIDS  for analgesia following gastrointestinal surgery remains controversial, given mixed evidence of an increased risk of leakage from any bowel  anastomosis  created. This risk may vary according to the class of NSAID prescribed. [ 17 ] [ 18 ] [ 19 ]


Right hemicolectomy  and  left hemicolectomy  refer to the resection of the  ascending colon  (right) and the  descending colon  (left), respectively. When  middle colic vessels  and  transverse colon  are also resected, it may be referred to as an  extended hemicolectomy. [ 20 ]  Left hemicolectomy is most commonly indicated for cancer in the splenic flexure or descending colon, diverticular disease of the descending colon, and colovesicular or colovaginal  fistulas  that develop as a consequence of diverticular disease. [ 11 ]  The main limitation to performing a left extended colectomy is the difficulty of achieving a colorectal anastomosis afterward. Different techniques, such as Deloyer's or Rosi-Cahil's techniques, have been proposed to solve this issue. [ 21 ]  Right hemicolectomy is most commonly indicated for masses in the right, or ascending, colon but may also be performed for neoplasms of the cecum or appendix. Right-sided diverticulitis, cecal volvulus, inflammatory bowel disease, and  adenomatous polyps  are benign conditions that may require right hemicolectomy. [ 11 ]


Transverse colectomy  involves resection of the transverse colon, the segment of the colon between the hepatic flexure and the splenic flexure. Transverse colectomy is uncommon, as malignant pathologies of the transverse colon typically call for removal of the left colon or right colon as well as the transverse colon due to the variable contributions of the  ileocolic ,  right colic , and  left colic  blood vessels to  lymphatic  drainage of the transverse colon. Transverse colectomy is sometimes appropriate for focal benign pathologies such as local inflammation and local trauma or injury such as  perforation .  [ 11 ] [ 22 ]


Sigmoidectomy  is a resection of the last part of the colon, known as the sigmoid colon, and can include part or all of the rectum ( proctosigmoidectomy ). Precancerous polyps and sigmoid colon cancer are common indications for sigmoidectomy. Benign indications for sigmoidectomy include diverticular disease, especially when complicated by perforation or  fistulae ,  sigmoid volvulus , trauma, and ischemic or  infectious colitis . [ 11 ]  When a sigmoidectomy is followed by terminal colostomy and closure of the rectal stump; it is called a  Hartmann operation . This is usually done out of the impossibility of performing a "double-barrel" or Mikulicz colostomy, which is preferred because it makes "takedown" (reoperation to restore intestinal continuity using an anastomosis) considerably easier. [ 23 ]


When the entire colon is removed, this is called a  total colectomy , also known as Lane's Operation. [ 24 ]  Total colectomy may be indicated as a prophylactic measure in certain hereditary polyposis syndromes such as familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer. Total colectomy is also performed for certain forms of inflammatory bowel disease, severe acute colitis, slow-transit constipation, and cancer. [ 1 ] [ 11 ]  If the rectum is also removed, it is a  total proctocolectomy .  Sir William Arbuthnot-Lane  was one of the early proponents of the usefulness of total colectomies and was considered a pioneer of colon surgery for routinely performing this procedure. However, his overuse of the procedure called the wisdom of the surgery into question. [ 25 ] [ 26 ]


Subtotal colectomy  is resection of part of the colon or a resection of all of the colon without complete resection. [ 27 ]


The first concepts of colon surgery were thought to have originated in the 15th century as a means to relieve obstructed bowel. The first reported ostomy, performed in 1776 by Pillore of Rouen as an attempt to circumvent blockage caused by a rectal tumor, was done at the insistence of the patient despite opposition from other doctors. While this initial attempt resulted in the death of the patient after only 20 days, subsequent attempts in the following years were more successful. [ 25 ]  By the mid 1880's, hundreds of colectomies had been performed, with a fatality rate between 50 and 60% (lower for those performed in cases of cancer). Dr. Robert Weir suggested in his 1886 case report on the resection of a rectal tumor that shock from the operation and leakage of intestinal contents both during and after surgery contributed to these numbers. [ 28 ]  The introduction of exteriorization, where the intestinal segment of interest was brought out of the abdomen and resected after the abdomen was closed around it, decreased the morbidity of the procedure. [ 25 ]


Jean Francois Reybard performed the first successful end-to-end colonic anastomosis following sigmoid colon resection in 1823. Primarily criticized as dangerous, Reybard's procedure went against the standard protocol of the day: resection of the colon with stoma creation and distal closure. However, colonic anastomosis became more acceptable by the end of the 19th century. [ 25 ]


Many different methods and materials were used to join ends of the bowel in the early days of intestinal anastomosis, including animal  tracheas , artificial pipes made of reed, wood or other materials, cardboard, and rings of silver or wax. Absorbable vegetable plates or sutures became the preference of most by the 1990s. [ 25 ]  With the advent of the surgical stapler, most surgeons have moved on from hand sewing colorectal anastomoses. However, the dexterity and precision afforded by current robotic surgical technology have spurred new interest in the role of sutured anastomosis. [ 15 ]


A report of the first laparoscopically assisted colectomies was published by Jacobs et al. in 1991. [ 29 ] [ 30 ]  While initial concerns were raised about the incidence of port site reoccurrence of tumors after laparoscopic colectomy for cancer, it was later found to be similar to that of wound implant of tumor cells as a result of open colectomy for cancer. [ 29 ]  By the mid-2000s, several studies had been published demonstrating that laparoscopic colectomy was at least as safe as open colectomy and could lead to shorter post-operative recovery times when performed by a skilled surgeon. [ 29 ]


Luis Jose De Souza  is an Indian  surgical oncologist  and the founder of  Shanti Avedna Ashram , a charitable trust which runs a network of hospices in Mumbai and Goa. [ 1 ] [ 2 ]  He has also contributed to the establishment of  Indian Cancer Cell , an educational program co-sponsored by  Tata Memorial Centre , Union for International Cancer Control (UICC) and Indian Cancer Society, for creating cancer awareness in schools. [ 1 ]  The Government of India awarded him the fourth-highest civilian honour of the  Padma Shri  in 1992. [ 3 ]


De Souza was born to Luis Jose and Juliet Mary on 11 December 1943 in  Mumbai , in the western Indian state of  Maharashtra  and graduated in medicine (MBBS) from the  Grant Medical College and Sir Jamshedjee Jeejeebhoy Group of Hospitals   in 1967. [ citation needed ]  His master's degree was also obtained from the same institution in 1970 after which he joined  Tata Memorial Hospital , Mumbai and reached the position of the professor and head of the gastroenterology department. [ 4 ] [ 5 ]  Later, he moved to  P.D. Hinduja National Hospital and Medical Research Centre  as their consultant oncosurgeon. [ 6 ] [ 7 ]  He has also served as a consultant Oncologist to  Air India  and  Indian Airlines . [ 5 ]


In 1986, De Souza founded  Shanti Avedna Ashram , a charitable trust, and under the aegis of the trust, set up a network of hospices in Mumbai and Goa, reported to be the first such venture for the care of advanced and terminally ill cancer patients in India. [ 8 ]  Representing Tata Memorial Centre, he associated with  Union for International Cancer Control  (UICC) and the Indian Cancer Society in 1993 and founded the  Indian Cancer Cell , a national program for promoting cancer education in Indian schools. [ 8 ]  He has served as the associate editor of the  Indian Journal of Cancer , editorial consultant of  The Practitioner  and as a consultant editor of  Palliative Medicine . [ citation needed ]  He has written over 70 articles in peer reviewed journals, has delivered keynote addresses in conferences and has organised many medical conferences. [ 8 ] [ 9 ]


De Souza is married to Carmen Mary Julia Saldanha and the couple has three children. [ citation needed ]