Radiation-induced Skin Lesions Research Articles

Inhibition of cutaneous heat-sensitive Ca2+ -permeable transient receptor potential vanilloid 3 channels alleviates UVB-induced skin lesions in mice.

Ultraviolet B (UVB) radiation causes skin injury by trigging excessive calcium influx and signaling cascades in the skin keratinocytes. The heat-sensitive Ca2+ -permeable transient receptor potential vanilloid 3 (TRPV3) channels robustly expressed in the keratinocytes play an important role in skin barrier formation and wound healing. Here, we report that inhibition of cutaneous TRPV3 alleviates UVB radiation-induced skin lesions. In mouse models of ear swelling and dorsal skin injury induced by a single exposure of weak UVB radiation, TRPV3 genes and proteins were upregulated in quantitative real-time PCR and Western blot assays. In accompany with TRPV3 upregulations, the expressions of proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were also increased. Knockout of the TRPV3 gene alleviates UVB-induced ear swelling and dorsal skin inflammation. Furthermore, topical applications of two selective TRPV3 inhibitors, osthole and verbascoside, resulted in a dose-dependent attenuation of skin inflammation and lesions. Taken together, our findings demonstrate the causative role of overactive TRPV3 channel function in the development of UVB-induced skin injury. Therefore, topical inhibition of TRPV3 may hold potential therapy or prevention of UVB radiation-induced skin injury.

Evaluation of Response and Toxicity in Patients with Locally Advanced Rectal Cancer Treated with Neoadjuvant Chemoradiation

Purpose: To study the response after neoadjuvant chemoradiation in patients with locally advanced rectal cancer with capecitabine 825 mg/m2 daily PO bid with radiation at a dose of 45Gy/20#/4 weeks, to study the clinical profile of different patients with locally advanced rectal cancer, and to assess the toxicity of patients treated with neoadjuvant chemoradiationtherapy. Materials and Methods: A prospective observational study was conducted in 60 patients with histopathologically proven locally advanced rectal carcinoma from October 2018 to April 2020 . Neoadjuvant chemoradiation was planned with capecitabine 825 mg/m2 PO bid with radiation at a dose of 45 Gy/20#/4 weeks. Radiological response was assessed 6 weeks after treatment completion, and surgery was planned according to the response. Results: Thirty-seven patients underwent definitive surgery. Pathological complete response was observed in one patient, near complete response in seven, partial response in 27, and poor or no response in two patients. Of 37 patients who have undergone surgery, 30% of patients received sphincter preserving surgery. Radiation-induced acute skin and lower gastrointestinal tract lesions were observed. Capecitabine-induced diarrhea, hematological toxicities, and a few patients with hand foot syndrome were observed. Conclusion: In locally advanced rectal cancer, preoperative radio-chemotherapy with capecitabine improves local control and reduces the risks of acute and late toxicity compared to postoperative radiochemotherapy. Thus, preoperative radiochemotherapy with capecitabine is safe and well tolerated in locally advanced rectal cancer, especially in tumors of the lower and middle rectum.

Cutaneous Radiation-Associated Angiosarcoma After Treatment of Carcinoma Penis: First Report from Tertiary Cancer Centre of North India.

Cutaneous radiation-associated angiosarcoma (cRAA) is a rare and aggressive secondary cutaneous angiosarcoma (cAS) with poor survival. cRAA has been mostly reported in breast carcinoma patients. Owing to its rarity, there is scanty literature available and no treatment guidelines. To the best of our knowledge, this is the first report of cRAA after multimodality treatment of carcinoma penis. A sixty-eight-year-old gentleman, a known case of carcinoma penis, underwent total penectomy with perineal urethrostomy and bilateral radical inguinopelvic lymph node dissection 6 years ago. He received adjuvant radiotherapy to the pelvis and bilateral groin. He presented with a bleeding plaque-like lesion with ulceration over the left lower abdomen (within previous radiation field) which rapidly progressed in size over the past 2 months. On examination, the lesion bled profusely on touch. Contrast MRI was suggestive of lobulated exophytic enhancing cutaneous lesion free from underlying muscle. Wedge biopsy was suggestive of cutaneous angiosarcoma. He underwent wide local excision with local perforator flap reconstruction from the right lower abdomen. Histopathology was suggestive of cutaneous angiosarcoma which showed immunoexpression of CD31, ERG1, cMYC suggestive of cRAA. cRAA is a very aggressive disease with 5-year survival of15-34%. To the best of our knowledge, this is the first ever reported case of cRAA of lower abdomen after multimodality management of carcinoma penis. It masquerades with other benign and less aggressive radiation-induced skin lesions. cMYC immunoexpression is specific for secondary cAS. Wide local resection with negative margin provides the best outcome.

Morbidity in Patients with Nasopharyngeal Carcinoma and Radiation-Induced Skin Lesions: Cause, Risk Factors, and Dermatitis Evolution and Severity.

Radiation-induced skin injuries such as lesions (RSLs) and dermatitis are the most common complication during radiotherapy (RT) for nasopharyngeal carcinoma, but little is known about risk factors unique to oncology. This study sought a greater understanding of these risk factors to stratify patients based on risk and guide clinical decision-making. Investigators analyzed the data of 864 consecutive patients referred to the RT center of the Southern Theater General Hospital for a new RSL from 2013 to 2019. These patients were followed up for an average of approximately 16 months until their death or March 30, 2020, whichever came first. Multivariate logistic regression analysis and Cox proportional hazards model were used to identify predictors of grade 3 or 4 dermatitis. The main causes of treatment interruption included dermatitis and oral mucositis. Significant patient-specific risk factors for RSLs included current smoking, current drinking, and lower Karnofsky Performance Scale score and significant procedure-specific risk factors included receiving intensity-modulated radiation therapy (IMRT), hyperfractionated RT, induction chemotherapy, multicycle chemotherapy, and taxol- and cisplatin-based drugs. The three factors that independently predicted risk of RSL were IMRT, lower Karnofsky Performance Scale score, and multicycle chemotherapy. Comparing predictive factors among patients with severe RSL revealed that patients who received IMRT were more likely to develop grade 3 or 4 dermatitis. Oncology providers should note that IMRT is an aggressive technique with a trend toward increased RSL. Providers should pay special attention to adverse effects to skin in patients with nasopharyngeal carcinoma.

Supportive use of platelet-rich plasma and stromal vascular fraction for cell-assisted fat transfer of skin radiation-induced lesions in nude mice

BackgroundExternal radiotherapy has become indispensable in oncological therapies. Unfortunately, radiation is responsible for serious side effects, such as radiodermatitis. The skin is weakened and ulcerated. Our study aimed to evaluate the subcutaneous transfer of microfat (MF) alone and two mixes: MF+Platelet-rich plasma (PRP) and MF+stromal vascular fraction (SVF) to treat radiation-induced skin lesions. MethodWe defined randomly five experimental groups of nine mice: 1 healthy control group and 4 irradiated (60 Grey) and treated groups. The skin lesions were treated 3 months after irradiation by MF, MF+PRP (50%–50%), MF+SVF (90%–10%) or Ringer-lactate subcutaneous injections. Wound healing was evaluated at 1, 2 and 3 months post-injection and histological wound analysis at 3 months, after euthanasia. ResultsAll the irradiated mice presented with wounds. After sham-injection, the wound area increased by 91.1±71.1% versus a decrease of 15.9±23.1% after MF alone (NS), 27.3±23.8% after MF+SVF (NS) and 76.4±7.7% after MF+PRP (P=0.032). A significative reduction of skin thickness in wound periphery was measured for the three treated groups compared to sham-injection (P<0.05) but not in the healed wounds (NS). The most important subcutaneous neo-vessel density was shown after MF+SVF injection. ConclusionThe MF+PRP mix was the most efficient product to increase healing. The MF+SVF mix showed the highest rate of neo-angiogenesis but was disappointing in terms of healing. Level of evidenceNot gradable.

Successful Rescue of the Victim Exposed to a Super High Dose of Iridium-192 during the Nanjing Radiological Accident in 2014.

Here we report on the interventions taken to treat a patient exposed to high-dose radiation and provide a protocol for treating such patients in the future. The patient, Mr. Wang, was a 58-year-old male janitor who was accidentally exposed to a 192Ir source with an activity of 966.4 GBq or 26.1 Ci. The dose estimated to the lower right limb was 4,100 Gy, whereas the whole-body effective dose was 1.51 Gy. The diagnosis was made according to the results of the patient dose estimation and clinical manifestations. Systemic treatment included stimulating bone marrow hematopoietic cells, enhancing immunity, anti-infection and vitamin supplements. The treatment of radiation-induced skin lesions consisted of several debridements, two skin-flap transplantations and application of mesenchymal stem cells (MSCs). Skin-flap transplantations and MSCs play important roles in the recovery of skin wound. A combination of antibiotics and antimycotic was useful in reducing inflammation. The application of vacuum sealing drainage was effective in removing necrotic tissue and bacteria, ameliorating ischemia and hypoxia of wound tissue, providing a fresh wound bed for wound healing and improving skin or flap graft survival rates. The victim survived the accident without amputation, and function of his highly exposed right leg was partially recovered. These results demonstrate the importance of collaboration among members of a multidisciplinary team in the treatment of this patient.

Early and Late Protective Effect of Bone Marrow Mononuclear Cell Transplantation on Radiation-Induced Vascular Dysfunction and Skin Lesions

Skin lesions caused by accidental exposure to radiation or by radiotherapy are a major clinical challenge. We evaluated the effect of bone marrow mononuclear cells (BMMNC) on collagen remodeling and vascular function in radiation-induced skin lesions in the acute and late phases in mice. We studied the effect of BMMNC transplantation in a mouse model of cutaneous radiation injury combining local skin gamma-irradiation and biopsy punch wound. Mice were first irradiated, punched and then BMMNC were intramuscularly administered. Seven days after injury, BMMNC promoted wound healing by (i) increasing re-epithelialization, tissue collagen density and mRNA levels of collagens 1A1, 1A2, and 3A1, and (ii) inhibiting the radiation-induced vascular activation and limiting interactions between leukocytes and the vascular endothelium compared with control. Importantly, BMMNC did not amplify the inflammatory response despite the infiltration of neutrophils and macrophages associated with the expression of IL-6 and MCP-1 mRNAs in the tissue. Remarkably, the beneficial effects of BMMNC therapy on matrix remodeling were maintained for 2 months. Furthermore, BMMNC injection restored vascular function in skin tissue by increasing vascular density and vascular permeability. This therapeutic strategy based on BMMNC injection protects against radiation-induced skin lesions by preventing vascular dysfunction and unfavorable remodeling in the acute and late phases.

The healing effect of hydrogen-rich water on acute radiation-induced skin injury in rats.

This study aimed to determine the healing effect of hydrogen-rich water (HRW) on radiotherapy-induced skin injury. Rats were irradiated with a 6 MeV electron beam from a Varian linear accelerator. After skin wound formation, rats were individually administrated with distilled water, HRW (1.0 ppm) or HRW (2.0 ppm). We measured the healing time and observed the healing rate of the wounded surface. After irradiation, the malondialdehyde (MDA) content and the superoxide dismutase (SOD) activity in the wounded tissues were evaluated, as determined using an MDA and SOD assay kit. Interleukin-6 (IL-6) and epidermal growth factor (EGF) levels were assessed by enzyme-linked immunosorbent assay (ELISA). Models of skin damage were successfully established using a 44 Gy electronic beam. The healing time was shortened in the two HRW-treated groups (P < 0.05). Furthermore, interventions of HRW resulted in a marked reduction in the MDA (P < 0.05) and IL-6 levels (P < 0.01). Additionally, the SOD activity in the two HRW-treated groups was higher than that in the distilled water group at the end of the 1st, 2nd and 3rd weeks (P < 0.001). The EGF level was also significantly increased at the end of the 1st and 2nd weeks (P < 0.05). Compared with the HRW (1.0 ppm) group, the healing rate was higher and the healing time was reduced in the HRW (2.0 ppm) group. A significant decrease was observed in the IL-6 level at the end of the 1st, 3rd and 4th weeks (P < 0.05) and in the EGF content at the end of the 1 week after the HRW administration (P < 0.01). Collectively, our data indicate that HRW accelerates wound healing of radiation-induced skin lesions through anti-oxidative and anti-inflammatory effects, suggesting that HRW has a healing effect on acute radiation-mediated skin injury, and that this is dependent on the concentration of the hydrogen.

0453: Incidence of radiation-induced skin lesions after percutaneous coronary intervention

Percutaneous coronary interventions (PCIs) use significant doses of ionizing radiation, especially when treating complex lesions. Ionizing radiation may lead to adverse acute or delayed skin lesions in this setting, for which the incidence is not well known. To assess the incidence of radiation-induced skin lesions following PCI. We conducted a prospective, observational, single-centre study on the incidence of radiation-induced skin lesions at 3-5 days (acute) and at 6 months (subacute) after PCI with a dose-area product (DAP) ≥200Gy.cm 2 , between 1 January and 31 December 2013. Patients consenting to participate were given information on potential skin lesions and were interviewed at 5-7 days and at 6 months after the PCI. 1168 PCIs were performed; the radiation dose was available for 937 patients. Of these, 102 underwent PCI with DAP≥200Gy.cm 2 . High body mass index (BMI; OR 6.2, 95% CI 2.8-13.9) and elective (vs emergency) procedures (OR 2.0, 95% CI 1.1-3.4) were independently associated with DAP ≥200Gy.cm 2 . Three patients (3%, 95% CI 0.6-8.4) were diagnosed with acute lesions (DAP of 485Gy.cm 2 , 205Gy.cm 2 , and 201Gy.cm 2 ), two of whom also presented with subacute lesions following PCI with DAP of 485Gy.cm2 (Fig.) and 205Gy.cm 2 . One patient presented with a subacute lesion (DAP 280Gy.cm 2 ) only. Four patients presented with a skin lesion, which represents 4% (95% CI 1.1-9.7) of patients with DAP ≥200Gy.cm 2 and 0.4% (95% CI 0.1-1.1) of all the patients who underwent PCI, irrespective of DAP dose. The incidence of radiation-induced acute and subacute skin lesions developing after PCI in this single-centre study was 4% in patients with DAP ≥200Gy.cm 2 , with a total incidence of 0.4%. These data may suggest the need for systematic assessment of skin lesions after high-dose radiation PCI.

Incidence of radiation-induced skin lesions after percutaneous coronary intervention

Background Percutaneous coronary interventions (PCIs) use significant doses of ionizing radiation, especially when treating complex lesions. Ionizing radiation may lead to adverse acute or delayed skin lesions in this setting, for which the incidence is not well known. Purpose To assess the incidence of radiation-induced skin lesions following PCI. Methods We conducted a prospective, observational, single-centre study on the incidence of radiation-induced skin lesions at 3–5 days (acute) and at 6 months (subacute) after PCI with a dose–area product (DAP) ≥ 200 Gy/cm 2 , between 1 January and 31 December 2013. Patients consenting to participate were given information on potential skin lesions and were interviewed at 5–7 days and at 6 months after the PCI. Results In total, 1168 PCIs were performed; the radiation dose was available for 937 patients. Of these, 102 underwent PCI with DAP ≥ 200 Gy/cm 2 . High body mass index (BMI; OR 6.2, 95% CI 2.8–13.9) and elective (vs emergency) procedures (OR 2.0, 95% CI 1.1–3.4) were independently associated with DAP ≥ 200 Gy/cm 2 . Three patients (3%, 95% CI 0.6–8.4) were diagnosed with acute lesions (DAP of 485 Gy/cm 2 , 205 Gy/cm 2 , and 201 Gy/cm 2 ), two of whom also presented with subacute lesions following PCI with DAP of 485 Gy/cm 2 ( Fig. 1 ) and 205 Gy/cm 2 . One patient presented with a subacute lesion (DAP 280 Gy/cm 2 ) only. Four patients presented with a skin lesion, which represents 4% (95% CI 1.1–9.7) of patients with DAP ≥ 200 Gy/cm 2 and 0.4% (95% CI 0.1–1.1) of all the patients who underwent PCI, irrespective of DAP dose. Conclusions The incidence of radiation-induced acute and subacute skin lesions developing after PCI in this single-centre study was 4% in patients with DAP ≥ 200 Gy/cm 2 , with a total incidence of 0.4%. These data may suggest the need for systematic assessment of skin lesions after high-dose radiation PCI.

Serum Proteome Analysis for Profiling Predictive Protein Markers Associated with the Severity of Skin Lesions Induced by Ionizing Radiation.

The finding of new diagnostic and prognostic markers of local radiation injury, and particularly of the cutaneous radiation syndrome, is crucial for its medical management, in the case of both accidental exposure and radiotherapy side effects. Especially, a fast high-throughput method is still needed for triage of people accidentally exposed to ionizing radiation. In this study, we investigated the impact of localized irradiation of the skin on the early alteration of the serum proteome of mice in an effort to discover markers associated with the exposure and severity of impending damage. Using two different large-scale quantitative proteomic approaches, 2D-DIGE-MS and SELDI-TOF-MS, we performed global analyses of serum proteins collected in the clinical latency phase (days 3 and 7) from non-irradiated and locally irradiated mice exposed to high doses of 20, 40 and 80 Gy which will develop respectively erythema, moist desquamation and necrosis. Unsupervised and supervised multivariate statistical analyses (principal component analysis, partial-least square discriminant analysis and Random Forest analysis) using 2D-DIGE quantitative protein data allowed us to discriminate early between non-irradiated and irradiated animals, and between uninjured/slightly injured animals and animals that will develop severe lesions. On the other hand, despite a high number of animal replicates, PLS-DA and Random Forest analyses of SELDI-TOF-MS data failed to reveal sets of MS peaks able to discriminate between the different groups of animals. Our results show that, unlike SELDI-TOF-MS, the 2D-DIGE approach remains a powerful and promising method for the discovery of sets of proteins that could be used for the development of clinical tests for triage and the prognosis of the severity of radiation-induced skin lesions. We propose a list of 15 proteins which constitutes a set of candidate proteins for triage and prognosis of skin lesion outcomes.

Pravastatin Limits Radiation-Induced Vascular Dysfunction in the Skin

About half of people with cancer are treated with radiation therapy; however, normal tissue toxicity still remains a dose-limiting factor for this treatment. The skin response to ionizing radiation may involve multiple inflammatory outbreaks. The endothelium is known to play a critical role in radiation-induced vascular injury. Furthermore, endothelial dysfunction reflects a decreased availability of nitric oxide. Statins have been reported to preserve endothelial function through their antioxidant and anti-inflammatory activities. In this study, wild type and endothelial nitric oxide synthase (eNOS)(-/-) mice were subjected to dorsal skin irradiation and treated with pravastatin for 28 days. We demonstrated that pravastatin has a therapeutic effect on skin lesions and abolishes radiation-induced vascular functional activation by decreasing interactions between leukocytes and endothelium. Pravastatin limits the radiation-induced increase of blood CCL2 and CXCL1 production expression of inflammatory adhesion molecules such as E-selectin and intercellular adhesion molecule-1, and inflammatory cell migration in tissues. Pravastatin limits the in vivo and in vitro radiation-induced downregulation of eNOS. Moreover, pravastatin has no effect in eNOS(-/-) mice, demonstrating that eNOS plays a key role in the beneficial effect of pravastatin in radiation-induced skin lesions. In conclusion, pravastatin may be a good therapeutic approach to prevent or reduce radiation-induced skin damage.

Human mesenchymal stem cells favour healing of the cutaneous radiation syndrome in a xenogenic transplant model

It has been suggested that human mesenchymal stem cells (hMSC) could be used to repair numerous injured tissues. We have studied the potential use of hMSC to limit radiation-induced skin lesions. Immunodeficient NOD/SCID mice were locally irradiated to the leg (30 Gy, dose rate 2.7 Gy/min) using a (60)Co source to induce a severe skin lesion. Cultured bone marrow hMSC were delivered intravenously to the mice. The irradiated skin samples were studied for the presence of the human cells, the severity of the lesions and the healing process. Macroscopic analysis and histology results showed that the lesions were evolving to a less severe degree of radiation dermatitis after hMSC transplant when compared to irradiated non-transplanted controls. Clinical scores for the studied skin parameters of treated mice were significantly improved. A faster healing was observed when compared to untreated mouse. Immunohistology and polymerase chain reaction analysis provided evidence that the human cells were found in the irradiated area. These results suggest a possible use of hMSC for the treatment of the early phase of the cutaneous radiation syndrome. A successful transplant of stem cells and subsequent reduction in radiation-induced complication may open the road to completely new strategies in cutaneous radiation syndrome therapy.

Increase of surface dose using wound dressings during percutaneous radiotherapy with photons and electrons

Different wound dressings are used for the supportive treatment of patients with radiation-induced skin lesions. Depending on beam quality and energy, an increase of the dose administered to the skin and thus an aggravated skin reaction is to be expected during percutaneous irradiation. The increase of the skin dose during irradiation with photons (Co60,6 MV, 42 MV) and electrons (7 MeV, 20 MeV, 42 MeV) was determined using thermoluminescence dosimetry. The use of wound dressings during electron irradiation and during soft irradiation therapy does not significantly increase the dose administered to the skin and does not therefore cause any problems. During irradiation with high energy photons only extremely thin dressings should be used; if there is an aggravated skin reaction, the dressing should be taken off before irradiation commences.

Ultraviolet radiation-induced skin lesions in laboratory opossums (Monodelphis domestica) exposed from the weanling stage

After repeated exposure to ultraviolet radiation, adult laboratory opossums (Monodelphis domestica) may develop hyperplasia and neoplasia of the shaved skin. We exposed opossums from the weanling stage (8-10 weeks after birth) and compared the incidence of lesions at designated time points with those observed following introduction of adults (around 5 months old) to the same irradiation protocol (125 J/m2 of UVB three times each week for up to 40 weeks). The overall incidence of hyperplasia and neoplasia among opossums exposed from the weanling stage was markedly lower than among animals first exposed as adults, and hyperkeratosis and sarcoma were not observed. Although freckling was widespread, cutaneous melanocytic nevi were rare among animals first exposed as weanlings; however, one animal without freckling developed malignant melanoma with presumptive metastasis to the spleen. The basis of the lowered lesion incidence among weanling-introduced animals is not clear; it may be that cutaneous immunity to ultraviolet radiation damage is more efficient in juveniles than in adults.