Radiation Injury and the Hand Surgeon

REVIEW ARTICLE

Radiation Injury and the Hand Surgeon James A. Chambers, MD, James N. Long, MD The human hand has been affected by ionizing radiation accidents than any other organ. Hand surgeons should understand the pathophysiology and appropriate management of various types of radiation injury. This article outlines the history and epidemiology of ionizing radiation injury to the hand, basic aspects of radiobiology, and principles of management for injury resulting from fluoroscopy, nuclear accidents or weapons, and other sources. (J Hand Surg 2008;33A:601 – 611. Copyright © 2008 by the American Society for Surgery of the Hand.) Key words Hand, injury, nuclear, radiation, upper extremity.

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HE HUMAN HAND HAS BEEN intimately linked to and uniquely affected by the discovery of ionizing radiation. Upper-extremity surgeons should be familiar with the management of hand radiation injuries, not simply because that organ has historically been most affected in industrial and medical radiation accidents, but also because of the possibility of terrorist or rogue nation use of nuclear radiation weapons, acknowledged by academia and U.S. federal government sources to be a serious national threat.1,2 Because of this, Congress and the Joint Commission of Accreditation of Hospitals concur that additional training in the medical aspects of weapons of mass destruction should be provided to U.S. physicians.3,4 This article will outline the following topics: the history and epidemiology of radiation injury to the hand; the nature and management of acute and chronic radiation injury to the upper extremity; and the occupational exposure risks for the hand surgeon.

HISTORY AND EPIDEMIOLOGY On February 14, 1896, Wilhelm Röntgen published his seminal report on x-ray images of his wife’s hand.5,6 Within months, x-rays were used to define hand anatomy and mechanism of the wrist joint by Bryce.7 Unfortunately, during the same year, multiple reports of radiation dermatitis of the hand and “x-ray finger” were published, describing tenderness, erythema, edema, stiffness, and bullae.5 From the Division of Plastic Surgery, University of Alabama at Birmingham, Birmingham, AL. Received for publication November 28, 2007; accepted in revised form January 29, 2008. No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. Corresponding author: J. Alan Chambers, MD, Division of Plastic Surgery, University of Alabama at Birmingham, Faculty Office Tower 1102, 510 20th Street South, Birmingham, AL 35294; e-mail: [email protected]. 0363-5023/08/33A04-0018$34.00/0 doi:10.1016/j.jhsa.2008.01.035

Within 2 years, the first lawsuit in the United States for x-ray injury was filed,5 and by 1902, radiation-associated squamous cell carcinoma had been reported.8 Another 5 years later, surgical literature reported numerous other cases of radiation-associated carcinoma requiring amputations from the metacarpophalangeal joint to the shoulder.9 Notable patients included scientists from Thomas Edison’s laboratory and Walter Cannon, professor of physiology at Harvard.5,10 With increasing clinical use of radiation, the epidemiology of ionizing radiation injury gradually shifted from the hands of physicists to those of physicians. In 1949, the Mayo Clinic reported a series of 135 cases of physician radiodermatitis; 93% involved the hands, similar to reports published the following decade by other institutions.5,10 The advent of the atomic age along with the development of nuclear reactors and particle accelerators dramatically changed the pattern and nature of radiation injuries. However, the hand remained the most commonly injured part of the body. In the United States since World War II, almost 1,500 persons have been involved in more than 240 radiation accidents, with 30 fatalities.4,11 Accidents in the United States have been largely in industrial settings and medical facilities, with 77% of cases involving the hand.11 Outside the United States, accidents have more frequently involved unwitting handling of improperly disposed or poorly controlled radioactive isotopes such as 60 Co and 192Ir.11,12 Notable exceptions have occurred, such as at Chernobyl. Even there, however, local injuries were observed in more than half the patients, particularly in the upper extremities.13 Virtually all patients with acute radiation syndrome had local tissue injury as well.13 ESSENTIAL RADIOBIOLOGY Ionizing radiation most commonly manifests in 5 forms: alpha, beta, gamma, x-ray, and neutron radiation (Fig. 1). It should be noted that the penetration and injury potential of certain forms (ie, x-rays) varies greatly with the amount of energy required to generate the radiation.14 Absorbed radiation dose is generally expressed in the Système International unit gray (Gy), which is equal to 1 joule of energy per kilogram of tissue. The conventional unit of rads equals 1/100 joule. The dose equivalent, measured in

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Types of Ionizing Radiation Radionuclide

Alpha: 1. Two protons, two neutrons, (+) charge. 2. Cannot penetrate stratum corneum. 3. Requires ingestion or inhalation to cause damage. 4. From radionuclides of plutonium, radium, uranium. 5. Shielding: intact skin or paper. Beta:

1. Essentially a free electron, (-) charge. 2. Penetrates 3-6 mm of skin. 3. Can cause cutaneous burns or other injury if ingested or inhaled. 4. From radionuclides of cobalt, iodine. 5. Shielding: aluminum, thick clothing, glasses.

Gamma: 1. Form of electromagnetic radiation, uncharged. 2. Can penetrate whole body. 3. Can cause myelosuppression and acute radiation syndrome. X-rays: properties similar to gamma radiation.

4. From radionuclides of cesium, cobalt.

Neutron radiation: uncharged particles that generate alpha, beta, or gamma

5. Shielding: thick concrete, lead.

radiation from interaction with atoms. Can induce radioactivity in stable elements such as N, Na, Al, S, Cl, and P. Optimal shielding is provided by water, paraffin, oil, lithium, boron, or cadmium.

FIGURE 1: Types of ionizing radiation. (Reproduced from Chambers J, Purdue G. Radiation injury and the surgeon. J Am Coll Surg 2007; 204:128 –139, with permission of Elsevier.)

TABLE 1: Radiation Units of Measurement4 Measured Quantity

SI Unit

Conventional Unit

Dose: amount of energy absorbed Gray (Gy) per unit mass Dose equivalent: amount of biological Sievert (Sv) damage from a radiation dose (⫽ dose ⫻ QF) Activity: radioactive emission per Becquerel (Bq) ⫽ 1 unit mass disintegration per second

Equivalents

Rads (1 Gy ⫽ 100 rads)

1 Gy ⫽ 1 J/kg

Rem* (1 Sv ⫽ 100 rem)

Sv ⫽ Gy ⫻ QF

Curie (Ci) ⫽ 3.7 ⫻ 1010 disintegrations per second

1 Bq ⫽ 3.7 ⫻ 1010 Bq

QF ⫽ quality factor: adjusts for the amount of biological damage caused by a given radiation type. The QF of x-ray, gamma, and beta is 1; the QF of alpha radiation is 20 for internal exposure; and the QF of neutrons ranges from 3 to 20 depending on the energy. Particulate radiation such as alpha and neutrons are more densely ionizing per unit length of tissue exposed than are nonparticulate radiation such as x-rays and gamma rays. Higher ionizing forms of radiation are said to have a high linear energy transfer (LET). *For external beta, gamma, or x-ray exposure, 1 rad ⫽ 1 rem.

sieverts (Sv), quantifies the biologic damage to tissue from ionizing radiation, which varies with the type of radiation. Table 1 provides details for conversion and other commonly used units of measurement. Clinically, radiation exposure results may be classified as 1

of 2 types. Whole-body irradiation (WBI) denotes marked exposure to a large portion of the body involving at least one third of the bone marrow. Sequelae are generally related to bone-marrow suppression (thrombocytopenia, leukopenia, etc). Local irradiation refers to exposure of a

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TABLE 3: Signs and Symptoms of ARS4

TABLE 2: Estimation of Whole-Body Dose by Prodromal Symptoms4

Signs/Symptoms Dose (Gy)

Onset (h)

Duration (h)

0.5–2 2–3 3–5.5 ⬎5.5

Absent to 6 2–6 1–2 Minutes to 1

⬍24 12–24 24 48

Latency Absent to 3 weeks 2–3 weeks 1.0–2.5 2–4 days

relatively limited portion of the body with injury restricted to directly exposed tissues, not resulting in myelosuppression. Whole-body irradiation and marked local injury may coexist; at Chernobyl, the majority of patients with acute radiation sickness and virtually all with ⬎4 Gy WBI had considerable skin injury in the extremities.13 A marked or “significant” radiation exposure may be defined as WBI 0.25 Gy or local dose of 6 Gy. For perspective, 1 chest x-ray results in 0.2 mSv (20 mrem), and the mean lethal dose (LD50) for WBI is 3 to 4.5 Gy.15 Radiation primarily injures organisms through the generation of ions and free radicals, which cause increased membrane permeability and DNA damage. DNA misreads, and lethal chromosomal aberrations lead to somatic or germ cell mutation or death.15,16 EFFECTS OF WHOLE-BODY IRRADIATION Whole-body irradiation can potentially result in 2 distinct problems for the hand surgeon. The first is acute radiation syndrome (ARS), which may manifest as a hematologic syndrome, gastrointestinal syndrome, or neurovascular syndrome. Hematologic syndrome requires a threshold exposure dose of 3 Gy, approaching the mid lethal range for untreated patients. Myelosuppression results in substantial risk of infectious and bleeding complications, which has been thoroughly discussed in other articles addressed to surgeons.4 The gastrointestinal syndrome follows doses in excess of 6 Gy, and the neurovascular syndrome is seen after at least 15 Gy WBI; these 2 forms are currently lethal.17 Morbidity and mortality for a given dose of exposure may be substantially increased by synergistic effects of concomitant thermal burns or other trauma.18 –20 The prodromal symptoms, laboratory findings, and medical management of ARS are beyond the scope of this article but have been addressed for surgical readers elsewhere.4 Refer to Tables 2 and 3 for a brief overview of early symptoms associated with WBI syndromes. Kumar has demonstrated that in mice, as little as 2 Gy of WBI impairs soft tissue wound healing, particularly if irradiated soon after rather than before wounding.21 Other studies also indicate that irradiation profoundly delays wound healing, especially during the first 2 weeks.22 Interestingly, several laboratory studies suggest that

Nausea and/or vomiting and some blood count derangement within 2 days Marked leukocyte and lymphocyte count derangement within 3 days Diarrhea within 4 days and marked platelet derangement within 6 to 9 days Nausea, vomiting, diarrhea within minutes or ataxia, disorientation, shock or coma within minutes to hours

Implication Minor hematologic syndrome Major hematologic syndrome Gastrointestinal syndrome

Neurovascular syndrome

wounding 1 day before irradiation may increase survival compared with irradiation alone. This may reflect neurohumoral amelioration of the stress response to radiation injury by wounding immediately before; this effect diminishes if wounding occurs postirradiation day 4 or later, after which consistently worse wound healing and survival result.22 Whole-body irradiation affects bone repair as well, as much as doubling the length of fracture healing time.23 EFFECTS OF LOCAL RADIATION As with WBI, local irradiation impairs wound healing. Studies in rats demonstrate most severe problems manifesting days 3 to 9 after irradiation in those wounds that ultimately do heal.14 Irradiated wounds produce less granulation tissue, less exudate, fewer inflammatory cells, and manifest diminished epithelialization and increased bleeding early in wound healing.14 Radiation increases the number of apoptotic cells and percentage of cells in G0/G1 phase and decreases the percentage in S-phase cells during postirradiation days 3 to 9.14 Notable local effects typically require proximity to a point source such as a gamma emitter within 1 to 3 cm usually for a period of hours to days.4,24 Focused rays such as from electron accelerators can cause considerable damage in less than a minute, however, and at a much greater distance from the source.25–27 Different tissue types in the upper extremity possess varying sensitivity to radiation. Bone marrow is most sensitive, followed by skin, endothelium, fat, bone, muscle, and nerve.5 Clinically obvious effects most frequently represent injury to the epidermis, particularly the stratum basale, with arrest of mitosis, loss of cohesion, and shortened life-span of progenitor cells.28 –30 Vacuolization at this point is a harbinger of necrosis.30 Vascular damage manifests with progressive vascular

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TABLE 4: Presentation of Local Irradiation by Dose5,12,24 Local Dose (Gy) Acute 0.5–10 Acute 10–20

Acute ⬎20 (Generally requires direct handling of fission products or exposure to electron accelerators) Acute massive (⬎50) (Generally associated with fatal WBI) Chronic, low-dose exposures Cumulative dose ⬎10 to 15

Manifestation

Latency Period

Transient erythema ⫾ pruritus or epilation (Usually no important long-term problems) Transient early erythema which reappears after 1–2 weeks Desquamation, restricted motion (tendon/ synovial edema) (Usually heal with local wound care; chronic skin changes vulnerable to breakdown, ulceration) Intense pain, erythema

1–3 weeks

Radionecrosis of tissues Erythema, swelling

Within 1 month Almost immediate

Eczematoid skin changes, ulceration

Years

occlusion from thromboses and obliterative endarteritis and endophlebitis, particularly at the junction of skin and subcutaneous tissue.28,31 With time, capillary dilatation and small vessel telangiectasias develop along with “coal spots” (sloughed venule and arteriole thromboses) and tissue necrosis.10,31,32 Clinically, the earliest sign of local injury is transient erythema and/or edema (from capillary dilatation and fluid extravasation) during the first week,30 possibly followed by pruritus, stiffness, “pin pricking” sensation, and tenderness.28 However, severe exposure may result in relatively early “dermatitis, bullae, and pain beyond description,” as reported 100 years ago.9,10 With 3 Gy, epilation and diminished sebaceous and eccrine function occur within 2 to 3 weeks. Doses of 6 Gy result in transient erythema that reappears with tenderness within weeks or resolves with residual hyperpigmentation or hypopigmentation 4 to 8 weeks later30 (P. Stern, presented at Medical Planning and Care in Radiation Accidents Course, Oak Ridge Institute for Science and Education and Radiation Emergency Assistance Center/Training Site, Oak Ridge, TN, 2001). Dry desquamation (response of germinative epidermal layer with diminished mitotic activity) may appear within 2 to 3 weeks after a threshold dose of 10 to 15 Gy, whereas moist desquamation (exposed dermis with fibrinous exudate) requires 20 to 50 Gy.30 Exposure ⬎50 Gy generally results in radionecrosis and deep ulceration.30 Injury evolution depends not only on the surface dose but on deeper penetration as well, which varies with the energy and type of radiation.30 The initial appearance of skin and area injured does not necessarily correspond with tissue damage, and

Hours to days

1–2 weeks

Within 30 minutes

microcirculatory disturbances often affect much larger areas than initially perceived. This is particularly true of injury from highly penetrating radiation types.33 Vascular injury frequently results in chronic ischemia and fibrosis, ulceration, infection, necrosis, and impaired wound healing (P. Stern, presented at Medical Planning and Care in Radiation Accidents Course, Oak Ridge Institute for Science and Education and Radiation Emergency Assistance Center/ Training Site, Oak Ridge, TN, 2001). During the initial phase, additional vascular compromise results from edema and adrenergic effects in the injured area.28 Progressive superficial changes include epithelial and subcutaneous fat atrophy, epidermal fragility, hypopigmentation, and loss of skin appendages.32 Hair follicles and sebaceous glands are vulnerable to 10 Gy, and sweat glands are destroyed by 25 Gy. These losses result in skin dryness, rhytid formation, vulnerability to infection, hyalinization of collagen-rich tissues, stiffness, tenderness, ulceration, cold/heat hypersensitivity, hyperkeratosis, and lack of durability.5,10,24,25,30 –32 Scarring of dermal collagen contributes to subcutaneous fibrosis and decreased elasticity.30,32 Progression of skin changes (telangiectasias, keratosis, etc) may continue for decades, with malignant degeneration reported as soon as 3 years and up to 25 or more years later.10,25 As dorsal skin is much thinner (7 mm) than palmar skin (40 mm), it is often more severely affected than the latter.28 Refer to Table 4 for a summary of local changes from irradiation. Despite being relatively radioresistant, nerves may demyelinate and degenerate, and severe pain may result as they become incarcerated in scar tissue.12 In children, the centers of bone growth are relatively radiosensitive;

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Madelung deformity has been reported after distal forearm exposure in infancy.32 Even in adults, however, intense local radiation may devitalize mature bone from obliteration of vessels in periosteum and endosteum.34 Muscle may be damaged as well, replaced by scar after vacuolization.32 In counseling patients and planning treatment, it should be borne in mind that “. . . the dose of radiation which is totally incompatible with tissue viability in a composite organ, such as the hand, is not known.”27 Limb salvage can frequently be anticipated with acute local exposures less than 20 Gy, although numerous variables affect this threshold.4 INITIAL PATIENT CARE AND EVALUATION Initial management of possibly irradiated patients should focus on resuscitation. Treatment of life-threatening injuries takes precedence over decontamination and dose-estimation, and this prioritization has never resulted in injury to health care workers in the United States.35 Radiation exposure may occur through direct skin exposure, inhalation, or ingestion and result in irradiation only, contamination of the patient, or incorporation of radioactive material. Early consultation with a hematologist and health physicist is essential. Separating the patient from the contamination source, removing clothes, washing with soap and water, and drying with absorbent material generally achieves 95% decontamination.36 Open wounds may be further decontaminated by copious irrigation and surgical debridement with end points of ⬍1,000 disintegrations/ minute for alpha radiation and ⬍1 milliRoentgen/h (10 ␮Sv/h) for beta radiation.4 Tourniquet use and/or use of chelating agents (via irrigation or intravenously; potentially useful for transuranic elements such as americium and plutonium) such as diethylenetriamine pentaacetate (available through the U.S. Department of Energy) before debridement may minimize absorption from further tissue disruption5 (Voelz et al., presented at the Health Physics Society 1994 Summer School, 1994). Other adjunctive medical measures may be appropriate depending on the radioisotope.4 Depending on the type of exposure, dose estimation is achieved with a combination of history, radiation probe evaluation, whole-body counting (effective for gamma radiation, x-rays, or high-energy beta particles only), nasal/ lung irrigation, collection of excreta, complete blood count, and lymphocyte culture.4 Among these, the complete blood count differential pattern is the most predictive early test for WBI. Lymphocyte decrease by 50% to ⬍1,000/mm3 within 48 hours indicates at least a moderate radiation dose.37,38 An absolute neutrophil count (ANC) of 500/␮L to 1,000/␮L at 48 hours indicates severe injury, and ⬍500/␮L represents severe to lethal injury as does continued fall after 48 hours.37,38 Conversely, an elevated granulocyte count that continues to rise after 24 hours portends unfavorable outcome.37,38 Lymphocyte culture is the most sensitive assay for whole-body exposure (detects as little as 1 cGy exposure) but requires 4 to 5 days for results.39

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BENIGN WOUND MANAGEMENT Acute Early wound closure is performed whenever possible to minimize the risk of septic complications.18 Particularly in patients with WBI, surgery should be avoided days 3 to 60 after irradiation or when the wound is hyperemic.4 This recommendation arises from observed wound and systemic complications in laboratory animals and from anecdotal reports of human injuries. Initial goals are preventing infection, minimizing contractures, and ameliorating pain.24 Open wounds may be dressed with Xeroform (Tyco Healthcare/Kendall, Mansfield, MA) and/or topical antibiotics.4,5 Splinting and physical therapy are essential to maintain joint motion and prevent characteristic contractures of wrist flexion, metacarpophalangeal joint extension, and thumb adduction4,5 (P. Stern, presented at Medical Planning and Care in Radiation Accidents Course, Oak Ridge Institute for Science and Education and Radiation Emergency Assistance Center/Training Site, Oak Ridge, TN, 2001). Range of motion exercises help ameliorate pain.27 Thromboxane inhibitors such as Aloe vera gel have been recommended for both analgesia and to help prevent keratosis.12,25 Aspirin and pentoxifylline may help prevent capillary occlusion. Angiotensin-converting enzyme inhibitors have been demonstrated in laboratory mammals to decrease radiation-induced cellular proliferation within renal and pulmonary vascular beds, but clinical effects in humans is uncertain.28 Relatively early skin grafting may be appropriate to relieve pain and improve function.24,27,32 In cases of superficial, predictable lesions (low-voltage x-ray or beta radiation), consider excision and grafting after the first wave of erythema demarcation—this has the advantage of avoiding complications such as ulceration, pain, and malignancy.5,9,10,12 Acute radiodermatitis may be followed by progressive changes culminating in gangrene. This has led some to advocate early amputation (ie, initial days or weeks) to avoid the complications of delay.27 However, waiting to amputate may assist the patient accept the loss psychologically as the extremity often initially appears salvageable (P. Stern, presented at Medical Planning and Care in Radiation Accidents Course, Oak Ridge Institute for Science and Education and Radiation Emergency Assistance Center/ Training Site, Oak Ridge, TN, 2001). Chronic (Benign) If radiation changes heal within 4 to 8 weeks, no intervention other than wound protection is needed. Unfortunately, no medical intervention currently exists to prevent the inexorable chronic changes after marked doses.9 Excision and grafting is indicated in several scenarios and when done for relatively superficial disease (ie, from lowenergy x-rays and beta radiation) can provide durable coverage for decades.9,12

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Ulcers that fail to heal or recur after 3 months should be excised with healthy margins.5,8,9 Resection and graft coverage of painful lesions almost invariably affords near immediate relief from suffering not relieved by conservative measures.9,27,32,40 The fragile, scarred skin of chronic radiation dermatitis should be considered a premalignant lesion and replaced with split-thickness skin graft5,31 (P. Stern, presented at Medical Planning and Care in Radiation Accidents Course, Oak Ridge Institute for Science and Education and Radiation Emergency Assistance Center/Training Site, Oak Ridge, TN, 2001). Fingernail scarring, deep grooving from injury to follicle and bed, is also best treated by excision of nail follicle and split- or fullthickness skin grafts.5 Because of scar entrapment of vessels in an irradiated bed, bleeding may be difficult to control in recipient bed after debridement. Delaying graft placement (no later than) 24 to 48 hours has thus been advocated by some, followed by ranging 5 to 7 days later5 (P. Stern, presented at Medical Planning and Care in Radiation Accidents Course, Oak Ridge Institute for Science and Education and Radiation Emergency Assistance Center/Training Site, Oak Ridge, TN, 2001). When determining the limits of excision, copious bleeding from a few points of scarred base is not proof of adequate resection as arterioles cannot contract in scar bed. Rather, softness and suppleness of tissues is recommended as a guide.6 Pedicled or free flaps are indicated to cover bone, cartilage, tendon, nerves, joints, or where one plans reconstructive surgery on tendons or nerves.10 Flaps are particularly useful in that, in addition to providing coverage, they augment regional blood flow, improving perfusion to surrounding tissues as well5 (P. Stern, presented at Medical Planning and Care in Radiation Accidents Course, Oak Ridge Institute for Science and Education and Radiation Emergency Assistance Center/Training Site, Oak Ridge, TN, 2001). As an example, flaps have been demonstrated to help heal pathologic fractures from irradiation.5 Flap coverage may be provided from the same hand,5 as demonstrated in a series of 12 patients with severe local exposure (20 –50 Gy) in Moscow.33 Over a 2-year period, all but 2 patients were successfully managed with debridement followed by definitive single procedure (2 patients required 2 operations). Successful procedures included distal phalanx amputation, cross-finger flap, H-shaped thenar flap, first web space free foot flap (neurovascular anastomoses), neurovascular wraparound flap from big toe, deep circumflex iliac artery flap with vascularized skin and iliac crest bone graft, radial free forearm flap, and scapular flap.33 Adjunctive therapies may also provide benefits. Hyperbaric oxygen improves tissue oxygenation, stimulates neovascularization, and can reduce fibrosis. Its successful use has been reported for late (not acute) radiation.41 However, as hyperbaric oxygen may cause generalized vasospasm, one should consider performing sympathectomy beforehand.28,41

Sympathectomy was reported in a 1994 radiation injury to provide immediate relief of pain and improve (at least shortterm) perfusion to the affected extremity; further necrosis several months later may still occur, however.28 Radiation-induced brachial plexopathy is a rarely reported (⬃1% reported incidence) lesion occurring after external beam radiation for breast or chest wall malignancy.42 Incidence correlates with higher dose of radiation (⬎50 Gy), concomitant chemotherapy, and inversely with fractionation.42,43 Intrinsic nerve injury combined with perineural fibrosis leads to sensory and/or motor deficits accompanied by pain. Surgical therapy (neurolysis, flap coverage, etc) does not appear to be beneficial in most cases, although limited success has been reported.43,44 Physical therapy and transcutaneous electrical nerve stimulation for analgesia are possibly more useful.43 HIGH-ENERGY-EXPOSURE CASE STUDIES Most radiation injuries before 1960 involved medical fluoroscopy and relatively low-energy exposures. Generally, pain and dermatitis were satisfactorily addressed with skin grafts. A few patients developed bullae with injuries that did not require amputation and were successfully managed with skin graft (or less commonly, flaps) with almost immediate pain relief and ultimate return to acceptable function.45 One such case was reported in 1958 when severe local injury to bilateral palms from medical irradiation (treatment for verrucous lesions) resulted in erythema and edema the first week, followed by pain and bullae the second week. After 6 months of dressing changes, the left palm reepithelialized, but ulceration persisted on the right. This wound was successfully grafted despite surrounding pallor, telangiectasias, and desiccation. Another 6 months later, ulceration over the right thumb developed; this was treated with excision, local rotation flap, and skin graft of donor site.29 Seven months after this (more than 1½ years since injury), the patient developed an ulcer in the left palm at the base of the small finger with proximal interphalangeal joint contracture. Z-plasty, capsulotomy, and full-thickness skin grafting corrected the problem. Additional areas of unstable skin changes were excised and grafted 10 years after the original injury.29 Twenty-one years after her injury, the patient still demonstrated excellent pain-free hand function. Most reports since the 1960s have reflected much more devastating injury from industrial accidents in the United States (industrial fluoroscopy, electron accelerators, and nuclear reactors) and from unwitting handling of improperly disposed radiation waste in developing countries. These cases required a shift in management, and physicians who had previous success with split-thickness skin grafts were forced to adopt much different strategies.10,25 In 1967, Lanzl et al reported one of the first cases of this relatively new, profound injury pattern, which had occurred 2 years earlier.26 The patient’s right upper-extremity was exposed to a 10-MV electron beam, receiving an estimated dose of 40 to 240 Gy. Erythema followed within 4 hours, most intense over the thumb, but also present in the distal

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FIGURE 2: Hand exposed to ⬎50 Sv. (Reproduced from Schenck R, Gilberti M. Four-extremity radiation necrosis: surgical management. Arch Surg 1970;100:729 –734, with permission of the American Medical Association.)

forearm. The next day, the area of erythema was also swollen, and the patient noted a burning pain around the thumb. By day 3, the thumb felt cold, and by day 4, bullous lesions appeared over the dorsum of that digit.26 By day 8, swelling extended to the axilla, and no sensation other than pain was noted in the thumb. Additional bullae over the thenar and hypothenar eminences developed as well. Percutaneous cervical electrical cordotomy was performed with some success after analgesics failed to relieve the pain. After 2 weeks, the bullae ruptured, with the subsequent development of granulation tissue at wound edges; surgeons were optimistic that only the thumb would require amputation. Unfortunately, necrosis progressed to involve all tissue of the hand, followed by infection with Pseudomonas. The patient had below-the-elbow amputation almost 5 months after exposure. The authors lamented that they had been guided by literature on previous radiation injury from far less destructive exposures and retrospectively wished they had amputated sooner.26 The same year Lanzl and colleagues’ article was published, Schenk and Gilberti treated 3 industry technicians from Pittsburgh exposed to high-voltage x-rays. One patient, in addition to a WBI exposure of 6 Gy, received an estimated 59 Gy to his hands and 27 Gy to his feet.17,46 Erythema developed the first day, then subsided over the

next 5 days, only to reappear on day 10, along with tenderness, edema, and bullae.17 Three weeks later, epilation developed, soon followed by desquamation of the skin.17 Like Lanzl and colleagues, these authors were guided by the extant literature of the time, which reflected beta radiation and x-ray injury of much lower voltage, and deferred amputation, believing that skin grafting would be sufficient.45,46 Wounds were managed with Burow’s soaks and antibiotics for 4 months.17 Ultimately, the patient required 11 operations over 22 months. (See Fig. 2 for depiction of the progression of injury in the most severely affected hand.) The responsible surgeons retrospectively would have amputated at 2 to 3 months to decrease infection, minimize pain, expedite rehabilitation, and reduce hospital stay.46 They also noted that early erythema and especially bleb formation corresponded with final ulceration and demarcation, whereas epilation was not useful.46 It should also be noted that 6 Gy is in excess of the usual lethal dose of WBI; this patient fortunately had an identical twin, making an expeditious lifesaving bone marrow transplant possible. Two years after Schenk and Gilberti’s report was published, Krizek and Ariyan reported 2 notable hand injuries from industrial fluoroscopy.27 The estimated doses to the hands of the patients was 195 to 250 Gy to dorsal

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skin and 19.5 to 25 to bone.27 Both patients noted erythema and pain within a few hours, then bullae within 10 days.27 Spontaneous healing of weeping areas was followed by localized skin breakdown. At the time of transfer to the authors’ institution, the patients hands were erythematous and ulcerated in several areas. No active range of motion was noted in the involved digits.27 X-rays reported diffuse demineralization and subarticular radiolucency “consistent with osteonecrosis.”27 Physical therapy with range of motion exercises, dynamic splinting, and gentamicin (the second patient had positive wound cultures for Pseudomonas) dressings led to a gradual relief of discomfort, diminished narcotic requirement, and marked improvement in range of motion in both hands.27 The first patient had excision of affected skin over the radial half of the dorsal right hand 2 weeks later. Surgeons encountered scarring and ulceration into finger extensor mechanisms, marked tissue edema, and brisk bleeding after tourniquet release. A split-thickness skin graft was placed and ranging begun postoperative day 10. The patient was discharged postoperative day 12, reporting that pain had virtually resolved.27 One year later, the patient had achieved almost full range of painless motion with good wound healing of grafted skin. Some sensory deficit remained, but otherwise the result was very functional. Follow-up x-rays were read as normal, which serves to caution against basing management decisions on initial plain films, which may reflect osteopenia of disuse or other changes less ominous than radionecrosis.27 The second patient (who had bilateral injury) had excision deep into the dorsal aspect of the right hand first web space and to the extensor mechanism of index and long finger; this was covered with a pedicled left thoracoacromial flap that was divided at 3 weeks. This resulted in immediate pain relief and good range of motion at 4 weeks.27 Five months after injury, skin of the left hand was excised. Ulceration in the index down to the entire extensor mechanism and joints was treated with ray amputation. The thumb, first web space, and dorsum of the long finger were covered with a right thoracoacromial flap, which was divided and inset 3 weeks later with minor subsequent revision. Postoperative arteriograms demonstrated considerable collateral circulation.27 The patient healed uneventfully except for a paronychia in the unoperated skin of the right thumb 14 months after surgery. This was excised and resurfaced with redundant flap skin. A case report from Turkey demonstrates the difficulty in timing of definitive procedure due to the evolution of injury, particularly when the treating surgeons did not see the patient initially.41 A patient with estimated 35 to 70 Gy dose to the left hand several weeks earlier presented with small finger necrosis, palmar ulceration, and hand edema that had begun as erythema. The fifth ray was resected, and a posterior interosseous flap was used for coverage. Although the flap survived, the fourth finger necrosed, requiring amputation. The flap edge then necrosed. Eventually, the

patient developed complex regional pain syndrome after hyperbaric oxygen and sympathectomy. Ten months after the original operation, necrosis of the volar aspect of the left index finger and right small finger was excised and covered with full-thickness skin grafts.41 From the above reports, we observe that “significant injury results in skin necrosis within a month,” also noted by Fryer and Brown who reported extensively on radiation injury from lower-energy sources.31 However, Krizek and Ariyan rightly point out that although acute radiodermatitis results in progressive changes, amputation is not necessarily inevitable, due to variability in depth of injury.27 Faculty from the Radiation Emergency Assistance Center/Training Site in Oak Ridge, Tennessee, have summarized the historical results of these accidents, writing “. . . there is little doubt that both time and money would be saved if the allegedly irradiated part were to be removed promptly, but most of the cases in the REAC/TS registry have been treated conservatively. . . . In cases where no necrosis occurs (⬍20 Gy?) this conservatism has been rewarded with spontaneous uncomplicated repair.”12 For most cases of radionecrosis, it appears that amputation should be pursued within the 5 months of injury, although the patient should understand that further revisions may be necessary. The ideal reconstructive approach is likely early debridement and necrosectomy followed by immediate graft or flap coverage of painful, scarred deformities.33 Interestingly, of the few U.S. case reports requiring amputation, a large percentage mention Pseudomonas infection preceding amputation.26,27,46 It is unclear whether (a) Pseudomonas commonly colonized or infected other wounds as well but was not detected, (b) wounds resulting from massive doses of radiation compromised local and/or systemic immunity enough to facilitate Pseudomonas infection, or (c) the insult from Pseudomonas infection of the wound acted synergistically to cause terminal tissue necrosis. Patients typically present with a predominant clinical picture of either WBI or severe local injury, but occasionally both are present. In such cases, amputation is usually required. In the 1967 Pittsburgh accident described previously, the most severe of the 3 exposures resulted in 6 Gy WBI and local injury of 59 Gy to the hands and 27 Gy to the feet.46 The patient received a bone-marrow transplant from an identical twin but went on to have 4-extremity amputation. A criticality accident in Belgium in 1965 resulted in WBI of 5 Gy and 50 Gy to left lower extremity; midthigh amputation was required 6 months later (Jammet et al., presented at the First International Congress of Radiation Protection, 1966). MALIGNANCY Malignancy associated with local irradiation was first reported in 1902.27 Squamous cell carcinoma, basal cell carcinoma, and, to a much lesser extent, osteosarcoma have all been linked to medical and industrial ionizing radiation exposure.8,47 As early as 1907, Porter and White recommended excision and grafting chronic radiation

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dermatitis to help prevent neoplastic degeneration, and the value of this has been verified by several other authors.8,24 Modern use of fluoroscopy does not appear to confer marked risk for skin cancer induction, although radiation treatment for benign conditions in the past was clearly associated with increased risk.47,48 It is unusual for carcinomas to develop until the cumulative dose exceeds 10 Gy8,47 and generally is preceded by radiodermatitis after a lag period of 20 years or more.8,24,47 Malignancies arising after irradiation should be managed as other skin neoplasms, although radiationinduced squamous cell carcinoma may metastasize at a lower rate than does other squamous cell carcinoma, possibly due to fibrosis of tissues blocking lymphatics.8 Although more aggressive than basal cell or squamous cell carcinoma, osteosarcoma is fortunately much less common. Approximately 3.4% to 5.5% of all osteosarcomas appear to be associated with ionizing radiation exposure (usually for Hodgkin’s disease or soft tissue carcinomas).49,50 Although it is difficult to establish causality, the overall incidence after external-beam radiation therapy is ⬍0.05%.27,48 Fibrohistiocytic is the most common type, followed by osteoblastic and chondroblastic.48 –50 Osteosarcoma is most associated with local doses approaching 60 Gy, but exposures as low as 12 Gy have been implicated.48,49 For WBI without marked local effects, the risk is even lower: an exposure of 1 Gy confers a lifetime risk of osteosarcoma of ⬍0.1%.48 Concomitant chemotherapy, particularly alkylating agents, may lower the threshold and shorten the latency period (usually 5–25 years) for development of osteosarcoma.49 –51 Incorporation of certain radionuclides is also a risk factor for malignancy. Data from the Mayak nuclear facility in Russia indicates that internal, and possibly external, plutonium exposure is risk factor for osteosarcoma in humans; in laboratory animals, osteosarcoma incidence increases with inhalation of plutonium.52 In laboratory animals, radiation to chronically infected or inflamed tissue is more carcinogenic than is radiation to healthy tissue.27 The most common malignancy associated with WBI is lymphocytic leukemia, with an excess relative risk of 2.2 per Gy.53 The lowest dose for which there is reasonable evidence for increased risk is between 10 and 50 mGy.54,55 As with other neoplasms, the risk is highest for exposure during youth, decreasing dramatically after adulthood.48,55–57 HAND SURGEON RADIATION EXPOSURE Recent reports have addressed the actual radiation exposure to surgeons and patients from modern fluoroscopy units, providing useful guidelines to minimize risk. Specific recommendations include use of mini C-arm instead of standard C-arm (results in 2 to 10 times less exposure); narrowing the diaphragm as well as removing the antiscatter grid; coning down the image to include only the area of immediate interest; minimize time spent in the primary beam; use of tungsten or lead gloves; surgeon positioning closer to image intensifier than to source; adjusting contrast and

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brightness before increasing power settings; beam collimation; and use of single-shot and last-image-hold techniques.58–60 Intraoperative mini C-arm use results in 20 mrem to the hands (approximately the same dose as a chest x-ray) over 51 seconds in an average hand surgery case involving fluoroscopy.60 It should be noted that even with doses 7 orders of magnitude greater than this, adult exposure poses no convincing risk for malignancy, even for relatively susceptible tissue such as thyroid.61 Authorities have recommended not exceeding 30 mSv on exams for patient benefit unless absolutely necessary; a standard fluoroscopy dose results in less than 1/1,000,000 of this.62 For occupational exposures, the National and International Councils on Radiation Protection have set the hand limit to 50,000 mrem per year, and although some authors contend this is overly conservative, a surgeon would have to perform more than 2,500 cases using the mini C-arm to exceed the limit.58,60 Typical mini C-arm exposure over a year to the groin, chest, and thyroid to operating surgeons also falls far below the National Council of Radiation Protection and Measurement’s limits.58 Physicians caring for the hands have historically had a uniquely important role in treating and at times being treated for radiation injury. Ionizing radiation, through myelosuppression and/or local effects, can cause or complicate upper-extremity lesions. Exposure may result from sources such as industrial fluoroscopy, nuclear accidents, improper handling of radioactive waste, or weaponized use from state or terrorist sources. Appropriate management depends on effective interaction with multiple specialties (health physicist, surgeon, possibly hematologist, etc) to determine the nature and extent of exposure as well as the therapeutic plan. The character of the insult determines the optimal time window for surgical intervention and the best procedural option, which may include skin graft, flap coverage, or amputation along with adjuvant therapies that range from physical therapy to bone marrow transplantation. REFERENCES 1.Bunn M, Wier A. Securing the bomb 2005: the new global imperatives. Project on Managing the Atom. Washington, DC: Harvard University and the Nuclear Threat Initiative, 2005. 2.Commission on Presidential Debates. The first Bush-Kerry presidential debate. Coral Gables, FL, 2004. Washington, DC: Commission on Presidential Debates. 3.Congressional Advisory Panel to Assess Domestic Response Capabilities for Terrorism Involving Weapons of Mass Destruction. Third annual report to the President and Congress of the Advisory Panel to Assess Domestic Response Capabilities for Terrorism Involving Weapons of Mass Destruction. Washington, DC: Advisory Panel to Assess Domestic Response Capabilities for Terrorism Involving Weapons of Mass Destruction, 2001. 4.Chambers J, Purdue G. Radiation injury and the surgeon. J Am Coll Surg 2007;204:128 –139. 5.Hansen F, Edgerton M. Burns and frostbites: radiation burns.

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