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13 Frostbite
105
known to be colonised with a resistant organism, then it may be appropriate to leave all blistered areas intact to reduce the risk of a potentially dev­astating tissue infection, and all such cases must be discussed with a specialised unit. Topical aloe vera is a commonly suggested therapy in minor frostbite cases due to its anti-prostaglandin actions, and whilst there is little evidence to rec­ommend its use, it may be considered in minor cases [1, 2].
13.6.2 Physiotherapy Protocols
Regardless of the clinical appearance, the affected area needs to be elevated in order to reduce venous stasis and tissue oedema. Similarly, all affected tissues will be fragile and easily dis­rupted through even gentle mechanical stresses; thus, all lower limb injuries must be placed on a strictly non-weight-bearing status to protect against ischaemia. These measures are designed to prevent extension of injury through progres­sive tissue oedema, thrombosis and ischaemia, and frequently areas that initially appeared non­salvageable will recover.
13.6.3 Surgery
Early surgical debridement of frostbite injuries is nearly always contraindicated, as the reversibility and progression of the frostbite injury cannot be quantied in the early stages. Debridement is best delayed until denitive demarcation of devi­talised tissues at approximately 6–8weeks post­injury. With appropriate management, surgery is frequently not required, despite the initial appear­ance of the injury. Similarly, it may be appropri­ate to leave demarked areas to auto-amputate if expert surgical input is not available or if the patient has substantial comorbidities making anaesthesia unsafe. Exceptions to this conserva­tive approach to surgery include injuries with uncontrolled severe infection, concurrent severe limb trauma and compartment syndrome, all of which may require urgent limb surgery. Fortunately, these are infrequent and are more commonly seen in freeze-thaw-refreeze injuries (Table13.4).
Adapted from Hallam etal. [1]
106
Table 13.4 Treatment algorithm for frostbite (Reproduced and adapted with permission from Hallam et al. [1], © BMJ, All Rights Reserved)
Frostbiteinjury
Rapidlyre-warm when
safe
M.-J. Hallam et al.
>24 hafter exposure
(orCItothromboly sis)
Tc99 or CT
Angiography
Iloprost infusion
Awaitdemarcation
Majorcases
<24 hafter exposure
Diagnostic CT
Angiography
Thrombolysis (ifnoCI)
Angiography every
24 h
Minorcases
Ibuprofen, Aloe vera &
dressings
Awaittissue
recovery/demarcation
Continue untiilsuccess
formaximum 72 h
Awaitdemarcation
13 Frostbite
107

13.7 Summary Points

• Prevention is paramount.
• Treat any serious or life-threatening condi­tions as a priority.
• Do not rewarm frozen tissues until there is no risk of refreezing occurring.
• Rewarm nonfreezing cold injuries slowly in air.
• Rewarm freezing cold injuries at 37–39°C or 40–41°C in a whirlpool device or foot spa for a minimum 30min with a mild antiseptic, and continue treatment twice daily until improve­ment is seen.
• Any patient with actual tissue loss should be given empirical broad-spectrum antibiotics.
• Discuss all signicant cases with a specialised unit.
• Consider treatment adjuncts such as throm­bolysis following discussion with a special­ised unit.
• Avoid early surgical debridement.

References

1. Hallam M-J, Cubison T, Dheansa B, Imray C.Managing frostbite. BMJ. 2010;341:c5864. http://
www.ncbi.nlm.nih.gov/pubmed/21097571
2. Grieve AW, Davis P, Dhillon S, Richards P, Hillebrandt D, Imray CHE.A clinical review of the management of frostbite. J R Army Med Corps. 2011;157(1):73–8.
http://www.ncbi.nlm.nih.gov/pubmed/21465915
3. Cauchy E, Chetaille E, Marchand V, Marsigny B.Retrospective study of 70 cases of severe frostbite lesions: a proposed new classication scheme. Wild Environ Med. 2001;12(4):248–55. http://www.ncbi.
nlm.nih.gov/pubmed/11769921
4. Cauchy E, Marsigny B, Allamel G, Verhellen R, Chetaille E.The value of technetium 99 scintigraphy in the prognosis of amputation in severe frostbite injuries of the extremities: a retrospective study of 92 severe frostbite injuries. J Hand Surg. 2000;25(5):969–78.
http://www.ncbi.nlm.nih.gov/pubmed/11040315
5. State of Alaska Cold-Injury Guidelines. 2003:1–60.
www.chems.alaska.gov
6. Imray C, Grieve A, Dhillon S.Cold damage to the extremities: frostbite and non-freezing cold injuries. Postgrad Med J. 2009;85(1007):481–8. http://www.
ncbi.nlm.nih.gov/pubmed/19734516
7. Bruen KJ, Ballard JR, Morris SE, Cochran A, Edelman LS, Safe JR. Reduction of the incidence of ampu­tation in frostbite injury with thrombolytic therapy. Arch Surg (Chicago, Ill: 1960). 2007;142(6):546–51; discussion 551–3. http://www.ncbi.nlm.nih.gov/ pubmed/17576891
8. Cauchy E, Cheguillaume B, Chetaille E.A controlled trial of a prostacyclin and rt-PA in the treatment of severe frostbite. N Engl J Med. 2011;364(2):189–90.
http://www.ncbi.nlm.nih.gov/pubmed/21226604
9. Robson MC, Heggers JP. Evaluation of hand frost­bite blister uid as a clue to pathogenesis. J Hand Surg. 1981;6(1):43–7. http://www.ncbi.nlm.nih.gov/
pubmed/7204918
Open Access This chapter is licensed under the terms of the Creative Commons Attribution-NonCommercial­NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by- nc- nd/4.0/), which permits any non­commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if you modied the licensed material. You do not have permission under this license to share adapted material derived from this chapter or parts of it.
The images or other third party material in this chapter are included in the chapter's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the chapter's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
How toManage Radiation Injuries
ChikakoSenju, MasakiFujioka, KatsumiTanaka, andSadanoriAkita
14

14.1 Introduction

Complex chronic ulcers due to irradiation are sometimes seen in patients who have undergone radiation therapy for malignancies or X-ray uo­roscopic procedures for ischemic heart disease or radiation accidents. Radiation-induced ulcers are difcult to treat because of the poor state of the wound bed. Radiation of tissues results in insuf­cient vascularity and tissue damage, leading to erythema and dermal atrophy with resultant tis­sue necrosis, infection, and later brosis, all of which are characteristics of chronic radiation injury syndrome [1]. More specically, 95% of cancer patients receiving radiation therapy will develop some form of radiodermatitis, including erythema, dry desquamation, and moist desqua-
C. Senju (*) Department of Plastic and Reconstructive Surgery, Specied Medical Corporation Yuhakukai Senju Hospital, Nagasaki, Japan
M. Fujioka Department of Plastic and Reconstructive Surgery, National Hospital Organization Nagasaki Medical Center, Nagasaki, Japan
K. Tanaka Department of Plastic and Reconstructive Surgery, Nagasaki University Hospital, Nagasaki, Japan
S. Akita Department of Plastic and Reconstructive Surgery,
Hospital, Tokushima, Japan
Fukushima Medical University, Fukushima, Japan
mation [2]. These undesirable complications cause continuous distress for patients and impair their quality of life.

14.2 Ionizing Radiation

Exposure to ionizing radiation generates a burst of free radicals, causing damage to deoxyribo­nucleic acid (DNA) and altering proteins, lipids, carbohydrates, and complex molecules [3]. The most sensitive cells are those that divide rapidly, such as the cells of the skin, bone marrow, and gastrointestinal tract. The severity of radiation­induced morbidity depends on the dose received, the time over which the dose is received, the vol­ume of tissue irradiated, and the quality or type of radiation [4]. There are individual differences in the appearance of radiation-induced symptoms. Symptoms of acute radiation injury such as red­ness, blisters, sores, and skin ulcers occur within a few weeks after treatment. In contrast, late complications such as skin ulceration, tissue necrosis, and osteomyelitis may take months or years to develop and are often permanent.
The technique of radiation therapy for malig­nant tumors is improving, and the number of patients who develop radiation ulcers is thus decreasing. The technique of cardiac catheteriza­tion has advanced in recent years, and the proce­dure has become complicated. As a consequence, the irradiation time has become longer, and the number of people who develop radiation ulcers is
© The Author(s) 2024 L. Téot et al. (eds.), Skin Necrosis, https://doi.org/10.1007/978-3-031-60954-1_14
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increasing. Therefore, despite these advance­ments, patients still experience the clinical conse­quences of radiation ulcers.

14.3 Radiation Ulcers

Radiation causes endothelial damage and bro­sis, leading to impairment of vascular and lym­phatic ow. This impairment produces hypoxic, hypocellular, and hypovascular tissue that is unable to maintain normal tissue turnover, result­ing in tissue necrosis, infection, and ulceration [5]. The naturally progressive wound-healing stage, which includes the hemostasis, inamma­tory, proliferative, and remodeling phases, is impaired by collagen deposition and excessive extracellular matrix and brogenesis [6]. If wound healing is unsuccessful, a serious radia­tion ulcer will occur.
14.4 Management ofRadiation Ulcers
Conservative treatments are not effective in most patients when a wound does not heal naturally. In such cases, surgical procedures are often required.
14.4.1 Debridement
Radiation ulcers are intractable and difcult to heal naturally because of the progression of necrosis. The underlying ischemia sets in motion a cycle of infection and necrosis, leading to the development of additional ulcers in the surround­ing tissue and nally to gangrene. The principle of treatment is to perform sufcient excision including the surrounding red and pigmented tis­sue affected by radiation. However, there is no established index for the excision range, and it is often difcult to determine how much debride­ment should be performed. When the damage
extends deep into the muscles and bones, exten­sive wound resection should extend to the area that has soft and sufcient blood ow. Although magnetic resonance imaging can help to diag­nose infected bone presenting as osteomyelitis [7], it is generally difcult to determine the extent of bone resection required. Checking for bleed­ing from the bone marrow during surgery will allow the surgeon to determine the extent of resection required. If important tissues such as large blood vessels or nerves are damaged, as much tissue as possible should be excised with­out leaving any serious dysfunction. In case of calcication, resection including the calcied tis­sue will be required [8]. In addition, refractory radiation ulcers may require histological exami­nation because they may include radiation­induced squamous cell carcinoma, skin cancer such as sarcoma, or recurrence of the original tumor [9, 10].
14.4.2 Methods ofWound Closure
After debridement, proper treatment that aids wound closure by surgery or stem cell transplan­tation is required.
14.4.2.1 Surgical Treatment
Local cutaneous aps located within the radiation eld are unreliable; they result in partial necrosis and rarely provide stable wound closure because of the poor blood ow of the surrounding skin [11]. Because skin grafts lack blood ow, adequate blood ow in the wound bed is required for skin engraft­ment. Thus, one of the two conditions is necessary: either thorough debridement to expose muscle with adequate blood ow or formation of good granula­tion tissue for successful skin engraftment [11, 12]. The most widely recommended method to heal these complex wounds is placement of musculocu­taneous aps harvested from nonirradiated areas; such aps provide good blood circulation for effec­tive results. This technique is also useful when
14 How toManage Radiation Injuries
111
important organs such as the carotid artery, nerves, or bronchi are exposed [9]. Additionally, free aps are useful for covering wounds. However, if the blood vessel on the recipient side is within the irra­diation range, the condition of the vascular endothe­lial cells may be poor, and the blood vessel may be clogged. Therefore, to the greatest extent possible, it is necessary to perform anastomosis with a well­conditioned blood vessel outside the irradiation range on the recipient side [13].
14.4.2.2 Stem Cell Therapy
Many studies have conrmed that stem cells can improve tissue damage and dysfunction and that they may have clinical applications. Adipose- derived stem cells can differentiate into broblasts, keratinocytes, and endothelial cells. They can also secrete some cytokines that may promote their proliferation and migra­tion. This increases angiogenesis and granula­tion, which promote wound healing [14]. Autologous adipose- derived regenerative cells (ADRCs) comprise several types of stem and regenerative cells, including adipose-derived stem cells. ADRCs can be collected via mini­mally invasive surgery by liposuction through a small incision [15]. When articial dermis is used in combination with adipose stem cells, the articial dermis becomes a scaffold for wounds, and the stem cells enter the articial dermis to perform wound healing. By this pro­cess, intractable ulcers such as radiation ulcers can be healed [16].

14.5 Case Reports

14.5.1 Case 1
Seventeen months after irradiation, an inade­quate wound bed was observed after the necrotic tissue was removed (Fig. 14.1c). Debridement was performed, including adi­pose tissue and muscle that had been exposed to radiation, because healing had not occurred with conservative treatment (Fig. 14.1d). Nevertheless, the adipose tissue and muscle necrosis progressed (Fig.14.1e). Because the wound did not heal properly, the patient was referred for plastic surgery. Extensive, deep debridement of the skin, adipose tissue, and muscles was performed, including the normal tissue around the irradiated area, and the wound was covered with a latissimus dorsi musculocutaneous ap (Fig. 14.1f). One year after surgery, the patient showed favorable wound resurfacing and no recurrence of the skin ulcers (Fig.14.1g).
14.5.2 Case 2
A 66-year-old woman underwent radiation ther­apy 40 years previously for the treatment of breast cancer after ablation of the tumor. Redness of the skin was seen in the precordium, and a pus­draining stula reached the sternum (Fig.14.2a). Intraoperative examination revealed necrosis of the sternum and ribs, which were ablated with the parietal pleura (Fig. 14.2b). The thorax and pleura were restored using articial substances (Fig.14.2c). The wound was covered with a ver­tical rectus abdominis musculocutaneous ap. Nine months after surgery, the patient showed favorable wound resurfacing and no recurrence of skin ulcers (Fig.14.2d).
A 77-year-old man underwent cardiac cathe­terization. Nine months after irradiation, pig­mentation, redness, and dermal atrophy were observed at the irradiation site (Fig. 14.1a). Twelve months after irradiation, the skin inammation had progressed, resulting in the development of dry necrosis (Fig. 14.1b).
14.5.3 Case 3
A 77-year-old woman underwent radiation treat­ment for breast cancer after ablation of the tumor. Examination revealed chronic chest ulcers that formed stulae penetrating to the rib (Fig.14.3a). Intraoperative examination showed necrosis of
112
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ab
c
de
fg
Fig. 14.1 (a) A 77-year-old man who underwent cardiac catheterization had developed irradiation, pigmentation, and redness after 9months. (b) Twelve months after irra­diation, the skin inammation had progressed, leading to dry necrosis. (c) Seventeen months after irradiation, the necrotic tissue was removed. (d) Debridement was per-
the ribs, which were ablated with the parietal pleura. The pleura was restored using articial material (Fig.14.3b). The wound was covered by transfer of a latissimus dorsi musculocutaneous ap from the back (Fig.14.3c). Six months after surgery, the radiation ulcer was reconstructed without disruption of shoulder movement (Fig.14.3d).
formed. (e) Five days after debridement, progression of adipose tissue and muscle necrosis was observed. (f) The debridement excision was enlarged, and a latissimus dorsi musculocutaneous ap was constructed. (g) One year after the surgery, the wound was resurfaced
14.5.4 Case 4
A 52-year-old woman developed intractable chronic radiation wounds. The thyroid cartilage was exposed, and the carotid artery was adjacent to the exposed cartilage (Fig.14.4a). After surgi­cal debridement, the size of the defect was 25×17mm and reached partially to the left thy-
cd
14 How toManage Radiation Injuries
113
ab
de
c
Fig. 14.2 (a) A 66-year-old woman underwent radiation therapy 40 years previously for the treatment of breast cancer after ablation of the tumor. The necrotic sternum was exposed. (b) Intraoperative examination showed necrosis of the sternum and ribs. (c) After debridement,
the thorax and pleura were restored using articial sub­stances. (d) The radiation ulcer was reconstructed using a vertical rectus abdominis musculocutaneous ap. (e) Nine months after the surgery, the wound was resurfaced
ab
Fig. 14.3 (a) A 77-year-old woman underwent radiation treatment of breast cancer after ablation of the tumor. The necrotic rib was exposed. (b) After debridement, the pleura
was restored using articial substances. (c) A latissimus dorsi musculocutaneous ap was transferred from the back. (d) Six months after the surgery, the wound was resurfaced
114
abc
C. Senju et al.
Fig. 14.4 (a) The thyroid cartilage was exposed because of a neck radiation-induced injury. (b) After debridement, the wound defect measured 25 × 17mm. ADRCs were
roid cartilage. Approximately 335mL of adipose tissue containing 4.1×107 ADRCs was harvested by liposuction. Articial dermis was used, and ADRCs were injected into the debrided wound margin, wound base, and articial dermis (Fig.14.4b). The wound had healed completely by 75 days after surgery. Six months later, the injected subcutaneous lesion maintained its soft texture and exhibited thick and vascularized soft tissue (Fig.14.4c).

14.6 Conclusion

Radiation ulcers impair blood circulation in the irradiation eld. The resulting wound becomes intractable because the natural healing process is unsuccessful. Radiation ulcers require treatment with adequately deep and wide debridement of the necrotic skin, adipose tissue, muscle, and sometimes bone. After debridement, healing must be promoted by covering the wound with well-circulated tissue or using adipose stem cells.

References

1. Olascoaga A, Vilar-Compte D, Poitevin-Chacón A, Contreras-Ruiz J. Wound healing in radiated skin: pathophysiology and treatment options. Int Wound J. 2008;5(2):246–57.
injected around the wound and into the articial dermis. (c) Six months after the surgery, the wound was resurfaced
2. Singh M, Alavi A, Wong R, Akita S.Radiodermatitis: a review of our current understanding. Am J Clin Dermatol. 2016;17(3):277–92.
3. Denham JW, Hauer-Jensen M. The radiotherapeu­tic injury—a complex ‘wound’. Radiother Oncol. 2002;63(2):129–45.
4. Gieringer M, Gosepath J, Naim R.Radiotherapy and wound healing: principles, management and pros­pects (review). Oncol Rep. 2011;26(2):299–307.
5. Wei KC, Yang KC, Mar GY, Chen LW, Wu CS, Lai CC, et al. STROBE—radiation ulcer: an over­looked complication of uoroscopic intervention: a cross-sectional study. Medicine (Baltimore). 2015;94(48):e2178.
6. Bentzen SM.Preventing or reducing late side effects of radiation therapy: radiobiology meets molecular pathology. Nat Rev Cancer. 2006;6(9):702–13.
7. Pineda C, Espinosa R, Pena A.Radiographic imaging in osteomyelitis: the role of plain radiography, com­puted tomography, ultrasonography, magnetic reso­nance imaging, and scintigraphy. Semin Plast Surg. 2009;23(2):80–9.
8. Nakanishi T, Kuwahara M, Sasaki C, Ando J, Harada M, Takeuchi M. A radiation ulcer that required par­tial lung resection and recurred in a small residual area of ectopic calcication. Int J Surg Case Rep. 2021;85:106201.
9. Fujioka M. Surgical reconstruction of radia­tion injuries. Adv Wound Care (New Rochelle). 2014;3(1):25–37.
10. Kuwahara M, Yurugi S, Ando J, Takeuchi M, Miyata R, Harada M, etal. Squamous cell carcinoma devel­oped in a chronic radiation-induced chest wall ulcer that is difcult to undergo thorough preopera­tive histological examination. Int J Surg Case Rep. 2020;72:467–70.
11. Wei KC, Yang KC, Chen LW, Liu WC, Chen WC, Chiou WY, etal. Management of uoroscopy-induced
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radiation ulcer: one-stage radical excision and imme­diate reconstruction. Sci Rep. 2016;6:35875.
12. Winaikosol K, Punyavong P, Jenwitheesuk K, Surakunprapha P, Mahakkanukrauh A. Radiation ulcer treatment with hyperbaric oxygen therapy and haemoglobin spray: case report and literature review. J Wound Care. 2020;29(8):452–6.
13. Ma X, Jin Z, Li G, Yang W.Classication of chronic radiation-induced ulcers in the chest wall after sur­gery in breast cancers. Radiat Oncol. 2017;12(1):135.
14. Huang SP, Huang CH, Shyu JF, Lee HS, Chen SG, Chan JY, et al. Promotion of wound healing using adipose-derived stem cells in radiation ulcer of a rat model. J Biomed Sci. 2013;20(1):51.
15. Akita S. Treatment of radiation injury. Adv Wound Care (New Rochelle). 2014;3(1):1–11.
16. Akita S, Yoshimoto H, Ohtsuru A, Hirano A, Yamashita S. Autologous adipose-derived regenera­tive cells are effective for chronic intractable radiation injuries. Radiat Prot Dosim. 2012;151(4):656–60.
Open Access This chapter is licensed under the terms of the Creative Commons Attribution-NonCommercial­NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by- nc- nd/4.0/), which permits any non­commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if you modied the licensed material. You do not have permission under this license to share adapted material derived from this chapter or parts of it.
The images or other third party material in this chapter are included in the chapter's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the chapter's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.