Fluoroscopy results in radiation exposures of 0.02–0.05 Gy every minute, and in extreme circumstances, reaches up to 0.5 Gy per minute. Image recording requires an even higher dose.[6
] The average radiation dose in routine cardiac catheterization is 2.5 Gy, whereas in percutaneous interventions, the dose rises to 6.4 Gy.[7
Skin damage can be caused by the cumulative dose from multiple procedures, each of which is individually insufficient to cause injury. For some patients with ischaemic heart diseases, multiple coronary angiography and angioplasty procedures are repeatedly performed. The same region of a patient's skin may be irradiated during years of subsequent procedures. Radiation dose evaluation mapping of the site is not easy and is often impossible, especially in repetitive fluoroscopy cases. This makes it more difficult to deal with these ulcers than the oncological radiation therapy-induced damage that can be evaluated with medical records. Scattering of X-rays also has to be accounted for.
When the tissue damage is shallow, adequate debridement and a simple free skin graft are good enough. However, when the damage extends deep into the underlining muscles or bones, which is often the case with γ-ray or X-ray irradiation, or when the total debridement of the affected tissue cannot be done, flap coverage should be performed. It is always a question, to what extent debridement should be done. Empirically, bleeding from the edge cannot be the index. Coverage with a contralateral side latissimus dorsi musculocutaneous flap may be an option. In these cases, the flap is within the site of X-ray exposure, because it is rare that fluoroscopy is performed only with one-sided view. Even though it seems intact on the surface, hidden radiation damage of the flap should not be underestimated. Furthermore, it is not rare to encounter vividly surviving flaps floating, not adhering to the irradiated wound bed. The lack of the wound-healing ability of the wound bed is speculated to be the cause.
Bone marrow cells, including the so-called stem cells, are gaining a good reputation for accelerating wound healing. They are also positively estimated to improve the ischaemic state of limbs.[8
] Delivery of bone marrow cells to the ischaemic heart is expected to encourage neovascularisation and cardiac muscle preservation.[11
] A successful investigation about the local administration of culture-expanded bone marrow cells to the radiation burns, in which conventional skin grafting failed, has been done.[12
] Bey et al
. observed poor healing, despite coverage with a latissimus dorsi muscle flap after failure with conventional excision, dermal substitute coverage, and skin grafting. They were able to cover the defect only after the local administration of culture-expanded bone marrow cells in combination with a radial forearm flap and skin grafting.[13
Platelet-rich plasma is also attracting attention as a good source of several growth factors that accelerate wound healing. There have been clinical reports about the effectiveness of PRP in treating chronic wounds.[2
The authors previously reported a method for concentrating bone marrow aspirate, which is a simple and low-cost procedure to enrich bone marrow cells (working cells) and platelets (reservoir of growth factors) simultaneously.[5
] Among the enriched cells, the relatively larger cells (e.g., multinucleated cells), which potentially cause inflammation, were confirmed to be reduced; in contrast to this, the smaller cells were concentrated. The growth factors contained in platelets derived from the bone marrow aspirate were at the same level as those in platelets derived from the peripheral blood.[5
] The local injection of bm-PRP into the wounds on rabbits’ persistent ischaemic limbs accelerated wound healing. Injected cells were confirmed to survive at least 4 weeks after transplantation (submitting to a journal).
Because the goal of this study was initially the wound closure, objective evaluation of the pain level was not performed. The mechanism of the devastating pain of the radiation-induced ulcer is still unclear. Local ischaemia and burden of bacteria, which cause inflammation, can be speculated as the causes. In a previous report of treating late radiation necrosis of the soft tissues with pentoxifylline, a haemorrheologic agent, all patients had pain relief.[14
] At least partly, improving the ischaemic state seems to reduce the pain. In our Case 1, severe pain remained even after wide debridement with the index of bleeding from the wound edge. The pain went away after flap coverage with bm-PRP. The pain-relieving effect of the operation, including bm-PRP injection, was remarkable also in the other cases. The anti-inflammatory activity of expanded bone marrow cells has been reported.[15
] The delivery of bone marrow cells might have some good effects on pain relief, coupled with the coverage with well-vascularized flap.
Small delayed necrosis of the flap edges was seen. The edges appeared to be vital for 5–7 days after the surgery, though they changed colors after that and finally necrosed. This phenomenon is not often seen in normal skin flaps. The flaps used for the coverage were located adjacent to the necrotic lesions. In addition, the necrosed edges were at the margins of the debridement where the radiation exposure and scattering ray might have been extended. It is not easy to define the extent of irradiation and damage to the tissues at the time of treatment. However, it is too early to attribute the edge necrosis only to the irradiation, considering patients’ back grounds and the tension. Closure of the necrosed area was seen within a certain period of time.
The injection of bm-PRP into the tissue without platelet activation, rather than spreading on, was selected because of the certainty for cell delivering. The calcium level will be gradually normalized, supplied from the surrounding tissue, and spontaneous activation of the platelets will take place, with the exposure to collagen and other activating factors.
No major complication with the aspiration of bone marrow and delivery of bm-PRP was observed. Harvesting bone marrow aspirate required extra 5min for the surgery. No additional time was needed for processing bm-PRP, because it was done while the surgical debridement was performed.
Through our experience, we propose a synergetic approach of debridement, flap coverage and bm-PRP supplementation for treating severe radiation ulcers. However, at this moment, there are not enough evidences to support the effectiveness of bm-PRP. Further investigation should be continued.