Chronic Radiation Injury Research Articles

2nd Window NIR Imaging of Radiation Injury Mitigation Provided by Reduced Notch-Dll4 Expression on Vasculature.

Vascular endothelium plays a central role in the pathogenesis of acute and chronic radiation injuries, yet the mechanisms which promote sustained endothelial dysfunction and contribute to late responding organ failure are unclear. We employed 2nd window (> 1100nm emission) Near-Infrared (NIR) imaging using indocyanine green (ICG) to track and define the role of the notch ligand Delta-like ligand 4 (Dll4) in mediating vascular injury in two late-responding radiosensitive organs: the lung and kidney. Consomic strains of female Salt Sensitive or SS (Dll4-high) and SS with 3rd chromosome inherited from Brown Norway, SS.BN3 (Dll4-low) rats at ages 11-12weeks were used to demonstrate the impact of reduced Dll4 expression on long-term vascular integrity, renal function, and survival following high-dose 13Gy partial body irradiation at 42- and 90days post-radiation. 2nd window dynamic NIR fluorescence imaging with ICG was analyzed with physiology-based pharmacokinetic modeling and confirmed with assays of endothelial Dll4 expression to assess the role of endogenous Dll4 expression on radiation injury protection. We show that SS.BN3 (Dll4-low) rats are relatively protected from vascular permeability disruption compared to the SS (Dll4-high) strain. We further demonstrated that SS.BN3 (Dll4-low) rats have reduced radiation induced loss of CD31+ vascular endothelial cells, and increased Dll4 vascular expression is correlated with vascular dysfunction. Together, these data suggest Dll4 plays a key role in pathogenesis of radiation-induced vascular injury to the lung and kidney.

Cold atmospheric plasma alleviates radiation-induced skin injury by suppressing inflammation and promoting repair.

Currently, there is no effective treatment for chronic skin radiation injury, which burdens patients significantly. Previous studies have shown that cold atmospheric plasma has an apparent therapeutic effect on acute and chronic skin injuries in clinical. However, whether CAP is effective for radiation-induced skin injury has not been reported. We created 35Gy X-ray radiation exposure within 3 * 3cm2 region of the left leg of rats and applied CAP to the wound bed. Wound healing, cell proliferation and apoptosis were examined in vivo or vitro. CAP alleviated radiation-induced skin injury by enhancing proliferation and migration and cellular antioxidant stress and promoting DNA damage repair through regulated nuclear translocation of NRF2. In addition, CAP inhibited the proinflammatory factors' expression of IL-1β, TNF-α and temporarily increased the pro repair factor's expression of IL-6 in irradiated tissues. At the same time, CAP also changed the polarity of macrophages to a repair-promoting phenotype. Our finding suggested that CAP ameliorated radiation-induced skin injury by activating NRF2 and ameliorating the inflammatory response. Our work provided a preliminary theoretical foundation for the clinical administration of CAP in high-dose irradiated skin injury.

Angiotensin converting enzyme (ACE) inhibitors as radiation countermeasures for long-duration space flights

Angiotensin converting enzyme (ACE) inhibitors are effective countermeasures to chronic radiation injuries in rodent models, and there is evidence for similar effects in humans. In rodent models ACE inhibitors are effective mitigators of radiation injury to kidney, lung, central nervous system (CNS) and skin, even when started weeks after irradiation. In humans, the best data for their efficacy as radiation countermeasures comes from retrospective studies of injuries in radiotherapy patients. We propose that ACE inhibitors, at doses approved for human use for other indications, could be used to reduce the risk of chronic radiation injuries from deep-space exploration. Because of the potential interaction of ACE inhibitors and microgravity (due to effects of ACE inhibitors on fluid balance) use might be restricted to post-exposure when/if radiation exposures reached a danger level. A major unresolved issue for this approach is the sparse evidence for the efficacy of ACE inhibitors after low-dose-rate exposure and/or for high-LET radiations (as would occur on long-duration space flights). A second issue is that the lack of a clear mechanism of action of the ACE inhibitors as mitigators makes obtaining an appropriate label under the Food and Drug Administration Animal Rule difficult.

Modulation of radiation-induced intestinal injury by radioprotective agents: a cellular and molecular perspectives.

The gastrointestinal (GI) system has rapidly proliferating and differentiating cells, which make it one of the most radiosensitive organs in the body. Exposure to high dose of ionising radiation (IR) during radiotherapy may generate a variety of reactive oxygen species (ROS) and reactive nitrogen species (RNS) including radicals, cause some side effects such as nausea, vomiting, diarrhoea, pain, ulceration, mal-absorption etc. Irradiation disrupts GI system by damaging proliferating stem cells of the crypts that alters the histology and physiology of intestine. Radiation damage reflects the qualitative and quantitative changes in intestinal epithelial stem cells like enterocytes, enteroendocrine cells, goblet cells and Paneth cells. The damaging effects of radiation to bio-molecules and cellular structures can alter gene signalling cascades and grounds genomic instability, protein modifications, cell senescence and cell death. The signalling pathways of GI tract includes Wnt, BMP, Hedgehog, PTEN/PI3K and Notch plays an important role in self-renewal of intestinal stem cells (ISCs) and maintaining the balance between self-renewal and differentiation of ISCs. Various radiation countermeasures including radioprotectors and mitigators are under development phase globally but still not approved for clinical applications during any radiation emergencies. In view of above, present review highlights cellular and molecular interruptions of GI system due to acute and chronic GI radiation injury, role of radioprotectors in signalling cascade modulations in GI epithelium and involvement of ISC markers in radioprotection.

Dilemma and strategy in surgery of chronic radiation intestinal injury

Chronic radiation intestinal injury denotes the repeated and prolonged damage of intestine caused by radiotherapy to pelvic malignancy, which usually occurs after three months of radiotherapy. Surgical intervention is indicated when the progressive intestinal injury leads to the development of massive intestinal hemorrhage, obstruction, perforation, fistula and other late complications. However, there is no consensus on the surgical procedures. We illustrate the dilemma in surgical treatment from the points of pathological mechanism and the frequent sites of radiation intestinal injury. Meanwhile, we discuss the surgical alternatives of radiation intestinal injury based on the literature and our experience. The pathological mechanism of chronic radiation injury is progressive occlusive arteritis and parenchymal fibrosis. The frequently involved sites are distal ileum, sigmoid colon and rectum based on the radiotherapy region. The morbidity and mortality are high in surgery of chronic radiation injury due to poor ability of tissue healing, pelvic fibrosis, multiple organ damage, and poor physical condition. Definitive intestinal resection is one of the most common surgical procedures. Extended resection of diseased bowel to ensure that there is no radiation damage in at least one end of the anastomotic bowels is the key to decrease the risk of complications related to anastomotic sites.

Increasing Fat Graft Retention in Irradiated Tissue after Preconditioning with External Volume Expansion.

Fat grafting is an adjuvant that may improve the quality of radiation-damaged tissue. However, fat grafting for volume restoration in irradiated sites may be less effective because of a poorly vascularized fibrotic recipient bed. External volume expansion has emerged as a potential technique to prepare the recipient sites for improved survival of grafted fat. The authors previously demonstrated increased vasculature with external volume expansion stimulation of irradiated tissues. The authors now hypothesize that external volume expansion's improvements in recipient-site vascularity will increase the volume retention and quality of fat grafts in fibrotic irradiated sites. Athymic mice were irradiated until development of chronic radiation injury. Then, the irradiated site was stimulated by external volume expansion (external volume expansion group), followed by subcutaneous fat grafting. Grafts in an irradiated site without external volume expansion stimulation (irradiated control group) and grafts in a healthy nonirradiated (nonirradiated control group) site were used as controls. All grafts were monitored for 8 weeks and evaluated both histologically and by micro-computed tomography for analysis of volume retention. Hyperspectral imaging confirmed a 25 percent decrease in vascularity of irradiated tissue (irradiated control group) compared with nonirradiated tissue (nonirradiated control group). Grafts in the irradiated control group retained 11 percent less volume than grafts in the nonirradiated control group. The experimental external volume expansion group achieved a 20 percent (p = 0.01) increase in retained graft volume compared with the irradiated control group. External volume expansion stimulation can mitigate the effects of irradiation at the recipient site and in turn help preserve fat graft volume retention. Possible mechanisms include increased vascularity, adipogenic conversion, and increased compliance of a fibrotic recipient site.

Sexual Dimorphism of Gut Microbiota Dictates Therapeutics Efficacy of Radiation Injuries.

Accidental or iatrogenic ionizing radiation exposure precipitates acute and chronic radiation injuries. The traditional paradigm of mitigating radiotherapy‐associated adverse side effects has ignored the gender‐specific dimorphism of patients' divergent responses. Here, the effects of sexual dimorphism on curative efficiencies of therapeutic agents is examined in murine models of irradiation injury. Oral gavage of simvastatin ameliorates radiation‐induced hematopoietic injury and gastrointestinal tract dysfunction in male mice, but adversely deteriorates these radiation syndromes in female animals. In a sharp contrast, feeding animals with high‐fat diet (HFD) elicites explicitly contrary results. High‐throughput sequencing of microbial 16S rRNA, host miRNA, and mRNA shows that simvastatin or HFD administration preventes radiation‐altered enteric bacterial taxonomic structure, preserves miRNA expression profile, and reprogrammes the spectrum of mRNA expression in small intestines of male or female mice, respectively. Notably, faecal microbiota transplantation of gut microbes from opposite sexual donors abrogates the curative effects of simvastatin or HFD in respective genders of animals. Together, these findings demonstrate that curative efficiencies of therapeutic strategies mitigating radiation toxicity might be dependent on the gender of patients, thus simvastatin or HFD might be specifically useful for fighting against radiation toxicity in a sex‐dependent fashion partly based on sex‐distinct gut microbiota composition in preclinical settings.

Oncologic outcomes and radiation safety of nipple-sparing mastectomy with intraoperative radiotherapy for breast cancer.

Nipple-sparing mastectomy combined with breast reconstruction helps to optimize the contour of the breast after mastectomy. However, the indications for nipple-sparing mastectomy are still controversial. Local radiation to the nipple-areola complex may play some roles in improving the oncological safety of this procedure. From January 2014 to December 2017, 41 consecutive patients who underwent nipple-sparing mastectomy combined with Intrabeam intraoperative radiotherapy to the nipple-areola complex flap and breast reconstruction were enrolled in this prospective study. The prescribed radiation dose at the surface of the spherical applicator was 16Gy. In eight cases, carcinomas were in the central portion of the breast. Partial necrosis of the nipple-areola complex occurred in three cases. Over 90% of patients reported "no or poor sensation" of the nipple-areola complex postoperatively. With a median follow-up time of 26 months, no recurrences or metastases were identified; however, breast-cancer mortality occurred in one patient. Pathologic evaluation of paraffin-embedded sections showed ductal carcinoma in situ in the remaining tissues deep to the nipple-areola complex flap in two patients. Although no further treatment was administered to the nipple-areola complexes postoperatively, no recurrences or metastases were identified 20 months and 24 months later, respectively. Optical microscopy and transmission electron microscopy revealed changes in some normal tissues immediately after Intrabeam intraoperative radiotherapy. Karyopyknosis were observed in gland tissues, and the collagenous fibers became sparse and arranged chaotically. As assessed by thermoluminescence, radiation doses at different sites in the nipple-areola complex flap varied considerably and were about 10Gy at the areola surface. No Intrabeam intraoperative radiotherapy-related acute or chronic radiation injuries of the lung, heart or bone marrow were identified. Our findings indicate that Intrabeam intraoperative radiotherapy during nipple-sparing mastectomy combined with breast reconstruction is safe and feasible. The current study was approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University (registering order 201750). All participants gave their written informed consent.

Rectal Necrosis: A Rare Complication of Palliative Radiotherapy for Sacral Spine Metastasis

Radiation proctocolitis is a common side effect of radiation therapy. In rare cases, chronic radiation injury can be severe enough to cause rectal necrosis. In this study, a case of rectal necrosis after sacral spine radiotherapy was presented. Anterior rectal wall necrosis and rectovaginal fistula is thought to be rare, severe and challenging rectal long-term complication of the previous sacral spine irradiation. Although, rectovaginal fistula which resulted in intractable rectal bleeding seems to be a rare side-effect of radiotherapy, physicians must not forget about this complication, as it can be fatal in patients who often have been cured of cancer. © 2018, Journal of Clinical and Diagnostic Research. All rights reserved.

Hyperbaric Oxygen Therapy and Quality of Life: A Systematic Review

Objective: Hyperbaric oxygen therapy (HBOT) involves breathing pure oxygen in a high-pressure chamber. HBOT is a well-established treatment for several diseases, such as serious infections, chronic diabetic foot ulcer, radiation injury, and hidradenitis suppurativa. There are various troublesome diseases that decrease pleasure in life in patients. HBOT has excellent effects in improving QOL in patients with acute and chronic diseases. The present study aimed at assessing the researches that focus on improving the QOL after HBO treatments. Methods: A systematic quest was conducted to evaluate English papers (clinical trials) that were published before April 2017. We searched PubMed, institute of scientific information (ISI), SCOPUS, Web of Science, Ovid, Science direct, ProQuest, Wiley, Cochran, Ebsco host, and Google Scholar. The reference lists of all the articles and electronic journals were searched for further studies. The JAMA users guide evaluation scales for RCTs was used to assess quality of the researched articles. Inclusion and exclusion criteria were extracted according to the scientific criteria. Sample size was 806 patients. Results: Finally, 15 published articles were extracted. Most researches were done in UK (26.7%), Israel (20%), and Sweden (20%). The mean age in HBOT group was 41.88, with a male to female ratio of 1.52. The mean age in the control group was 38.29, with a male to female ratio of 2.14. The most frequent clinical trials were those on the treatment of diabetic foot ulcer (20%), post-concussion syndrome (13.3%), pelvic radiotherapy (13.3%), and chronic arm lymphedema after radiotherapy (13.3%). The most QOL questionnaires used were SF-36 (21.4%), EORTC (European organization for research and treatment of cancer) QLQ-C30, head and neck cancer module (H&N35), and performance status scale (PSS). Conclusions: A significant effect of HBOT on improving QOL in patients’ outcomes and symptoms was found compared with the control group. We found improved QOL in patients with diabetic foot ulcer, post-concussion syndrome, pelvic radiotherapy, post stroke, hidradenitis suppurativa, tonsillar fossa tumor radiotherapy, jaw osteonecrosis, and fibromyalgia syndrome. We suggest that HBOT be added to conventional treatment of these patients as an adjuvant.

Transplantation of Endothelial Cells to Mitigate Acute and Chronic Radiation Injury to Vital Organs.

Current therapeutic approaches for treatment of exposure to radiation involve the use of antioxidants, chelating agents, recombinant growth factors and transplantation of stem cells (e.g., hematopoietic stem cell transplantation). However, exposure to high-dose radiation is associated with severe damage to the vasculature of vital organs, often leading to impaired healing, tissue necrosis, thrombosis and defective regeneration caused by aberrant fibrosis. It is very unlikely that infusion of protective chemicals will reverse severe damage to the vascular endothelial cells (ECs). The role of irradiated vasculature in mediating acute and chronic radiation syndromes has not been fully appreciated or well studied. New approaches are necessary to replace and reconstitute ECs in organs that are irreversibly damaged by radiation. We have set forth the novel concept that ECs provide paracrine signals, also known as angiocrine signals, which not only promote healing of irradiated tissue but also direct organ regeneration without provoking fibrosis. We have developed innovative technologies that enable manufacturing and banking of human GMP-grade ECs. These ECs can be transplanted intravenously to home to and engraft to injured tissues where they augment organ repair, while preventing maladaptive fibrosis. In the past, therapeutic transplantation of ECs was not possible due to a shortage of availability of suitable donor cell sources and preclinical models, a lack of understanding of the immune privilege of ECs, and inadequate methodologies for expansion and banking of engraftable ECs. Recent advances made by our group as well as other laboratories have breached the most significant of these obstacles with the development of technologies to manufacture clinical-scale quantities of GMP-grade and human ECs in culture, including genetically diverse reprogrammed human amniotic cells into vascular ECs (rAC-VECs) or human pluripotent stem cells into vascular ECs (iVECs). This approach provides a path to therapeutic EC transplantation that can be infused concomitantly or sequentially with hematopoietic stem cell transplantation more than 24 h after irradiation to support multi-organ regeneration, thereby improving immediate and long-term survival, while limiting long-term morbidity resulting from nonregenerative damage repair pathways.

Editorial introductions

Editorial introductions

Acute and Chronic Radiation Injury to the Lower Gastrointestinal Tract

Radiation is an integral part of therapy for many pelvic cancers, including rectal, prostate, cervical, and uterine cancers, and has been shown to decrease local recurrence and increase patient survival. Radiation injury is a sequela of treatment that manifests different symptoms depending on the organ affected. This review covers disease pathology, risk factors, disease prevention, clinical presentation, medical therapy, endoscopic therapy, and surgical therapy. Tables outline risk factors predisposing patients to the development of radiation injury, investigated prophylactic therapies to prevent radiation injury, reported frequencies of symptoms of chronic radiation proctitis, pharmacologic therapies that have demonstrated clinical benefit in randomized trials, and a scoring system for symptoms and endoscopic and histologic results. A management algorithm details evaluation and treatment of radiation-induced gastrointestinal injury. A microscopic section shows diffuse ulceration and granulation tissue formation. Photographs depict the rectal wall thickened by dense white tissue and severe perianal dermatitis. Endoscopic views of radiation proctitis with ulceration, severe radiation proctitis, mild radiation proctitis, prominent telangiectasia, anal necrosis due to radiation, actively bleeding telangiectasia, and argon plasma coagulation are provided. Other figures include computed tomographic scans of an inflamed rectum and the rectal wall with thin mucosa, and magnetic resonance imaging of the pelvis. This review contains 13 figures, 5 tables, and 89 references.

Adipose-derived stem cells in radiotherapy injury: a new frontier.

Radiotherapy is increasingly used to treat numerous human malignancies. In addition to the beneficial anti-cancer effects, there are a series of undesirable effects on normal host tissues surrounding the target tumor. While the early effects of radiotherapy (desquamation, erythema, and hair loss) typically resolve, the chronic effects persist as unpredictable and often troublesome sequelae of cancer treatment, long after oncological treatment has been completed. Plastic surgeons are often called upon to treat the problems subsequently arising in irradiated tissues, such as recurrent infection, impaired healing, fibrosis, contracture, and/or lymphedema. Recently, it was anecdotally noted – then validated in more robust animal and human studies – that fat grafting can ameliorate some of these chronic tissue effects. Despite the widespread usage of fat grafting, the mechanism of its action remains poorly understood. This review provides an overview of the current understanding of: (i) mechanisms of chronic radiation injury and its clinical manifestations; (ii) biological properties of fat grafts and their key constituent, adipose-derived stem cells (ADSCs); and (iii) the role of ADSCs in radiotherapy-induced soft-tissue injury.

Hyperbaric oxygen therapy for chronic radiation-induced tissue injuries: Australasia's largest study

Chronic radiation injuries, although uncommon, are associated with poor quality of life in oncology patients. The present study assesses the efficacy and safety of hyperbaric oxygen therapy in the management of chronic radiation-induced tissue injuries. A retrospective analysis was performed in 276 consecutive patients treated with hyperbaric oxygen therapy for chronic radiation-induced tissue injuries at the Hyperbaric Medicine Unit, Townsville, Queensland, between March 1995 and March 2008. Of these patients, 189 (68%) had complete follow-up data and were assessed. A total of 265 events of chronic radiation tissue injury were experienced by the 189 patients treated with hyperbaric oxygen therapy. Osteoradionecrosis prophylaxis due to radiation-induced dental disease had an overall response rate of 96% (P=0.00003; Wilcoxon matched-pairs signed-rank test). The overall response rates for established osteoradionecrosis of mandible, soft tissue necrosis of head and neck, and xerostomia were 86% (P=0.00001), 85% (P=0.002) and 64% (P=0.0001), respectively. The overall response rates for soft tissue necrosis at other sites, chronic radiation proctitis and hemorrhagic cystitis were 84% (P=0.03), 95% (P=0.0001) and 85% (P=0.03), respectively. The total complication rate after hyperbaric oxygen therapy was 15.9%, comprising reversible ear barotrauma (10.6%), reversible ocular barotrauma (4.2%), dental complications (0.5%) and myocardial infarction (0.5%). Our study demonstrates that hyperbaric oxygen therapy can be effectively used in a variety of chronic radiation-induced tissue injuries; its favorable risk profile suggests it should be considered for patients with radiation-induced tissue injuries.

2013 Dade W. Moeller lecture: medical countermeasures against radiological terrorism.

Soon after the 9-11 attacks, politicians and scientists began to question our ability to cope with a large-scale radiological terrorism incident. The outline of what was needed was fairly obvious: the ability to prevent such an attack, methods to cope with the medical consequences, the ability to clean up afterward, and the tools to figure out who perpetrated the attack and bring them to justice. The medical response needed three components: the technology to determine rapidly the radiation doses received by a large number of people, methods for alleviating acute hematological radiation injuries, and therapies for mitigation and treatment of chronic radiation injuries. Research done to date has shown that a realistic medical response plan is scientifically possible, but the regulatory and financial barriers to achieving this may currently be insurmountable.

Breast Reconstruction After Radiotherapy

It was once common practice in the treatment of breast cancer for total mastectomy and axillary lymph node dissection to be conventionally performed. However, breast-conserving surgery is increasingly being performed with marked improvement in a multidisciplinary treatment approach, including surgery, chemotherapy, irradiation, and antihormonal therapy. We must choose the optimal reconstructive methods with the reduction of the excision range. Furthermore, we also consider the local chronic radiation injury after adjuvant radiotherapy on breast reconstruction. As for breast reconstruction, the use of autologous tissues or artificial prostheses is common. However, after radiotherapy or if radiotherapy is planned, the complications such as infection, skin necrosis, or exposure of the implant are increased in breast reconstruction with implants. Therefore, the breast is reconstructed with autologous tissue mainly with radiotherapy using an autologous flap transfer. Meanwhile, the autologous fat transfer with adipose-derived regenerative cells for repair and regeneration has recently been investigated in reconstructive surgery. We discuss the autologous flap and fat transfer for breast reconstruction.

Skin Perfusion and Oxygenation Changes in Radiation Fibrosis

Ionizing radiation is known to have deleterious chronic effects on skin, including fibrosis and poor wound healing, hypothesized as mediated by ischemia and hypoxia. Past studies have been unable to simultaneously investigate changes in perfusion and oxygenation as separate parameters. Hyperspectral imaging has emerged as a tool with which to concurrently measure skin perfusion and oxygenation. The authors investigated the use of hyperspectral imaging in a novel murine model of chronic radiation injury. Areas of flank skin (n = 20) on hairless mice were exposed to a 50-Gy dose of beta-radiation. Hyperspectral imaging acquisition was performed at select points through 8 weeks. Immunohistochemical staining and gene expression analysis were performed to evaluate cutaneous vascular density, epidermal cell hypoxia, and angiogenic factors. All irradiated areas developed a chronic-phase wound by day 28. Hyperspectral imaging demonstrated a 21 percent decline in perfusion on day 56 (p < 0.001), whereas oxygenation levels were unchanged. A 1.7-fold reduction in blood vessel density was measured in irradiated skin compared with control tissue (p < 0.001), but no difference in epidermal cell hypoxia was observed. Vascular endothelial growth factor and related receptor expression were significantly lower in irradiated tissue. The authors' analysis does not support the presence of hypoxia in chronic-phase irradiated skin but suggests that hypoperfusion may be a predominant characteristic. The concurrent states of hypoperfusion and normoxia may be explained by the lower metabolic demands of fibrosed tissue.

Gastrointestinal radiation injury: Prevention and treatment

With the recent advances in detection and treatment of cancer, there is an increasing emphasis on the efficacy and safety aspects of cancer therapy. Radiation therapy is a common treatment for a wide variety of cancers, either alone or in combination with other treatments. Ionising radiation injury to the gastrointestinal tract is a frequent side effect of radiation therapy and a considerable proportion of patients suffer acute or chronic gastrointestinal symptoms as a result. These side effects often cause morbidity and may in some cases lower the efficacy of radiotherapy treatment. Radiation injury to the gastrointestinal tract can be minimised by either of two strategies: technical strategies which aim to physically shift radiation dose away from the normal intestinal tissues, and biological strategies which aim to modulate the normal tissue response to ionising radiation or to increase its resistance to it. Although considerable improvement in the safety of radiotherapy treatment has been achieved through the use of modern optimised planning and delivery techniques, biological techniques may offer additional further promise. Different agents have been used to prevent or minimize the severity of gastrointestinal injury induced by ionising radiation exposure, including biological, chemical and pharmacological agents. In this review we aim to discuss various technical strategies to prevent gastrointestinal injury during cancer radiotherapy, examine the different therapeutic options for acute and chronic gastrointestinal radiation injury and outline some examples of research directions and considerations for prevention at a pre-clinical level.

Autologous adipose-derived regenerative cells are effective for chronic intractable radiation injuries

Effective therapy for chronic radiation injuries, such as ulcers, is prone to infection. Stiffness is expected since the therapeutic radiation often involves wider and deeper tissues and often requires extensive debridement and reconstruction, which are not sometimes appropriate for elderly and compromised hosts. Autologous adipose-derived regenerative cells (ADRCs) are highly yielding, forming relatively elderly aged consecutive 10 cases, 63.6±14.9 y (52-89 y), with mean radiation dose of 75.0±35.4 Gy (50-120 Gy) were included with at least 10-month follow-up. Minimal debridement and ADRC injection in the wound bed and margin along with the injection of mixture of fat and ADRCs in the periphery were tested for efficacy and regenerated tissue quality by clinically as well as imaging by computed tomography and magnetic resonance imaging. Uncultured ADRCs of 1.6±1.3×10(7) cells were obtained. All cases healed uneventfully after 6.6±3.2 weeks (2-10 weeks) post-operatively. The done site morbidity was negligible and without major complications, such as paralysis or massive haematoma. The regenerated tissue quality was significantly superior to the pre-operative one and the mixture of fat and ADRCs connected to the intact tissue was very soft and pliable. Mean follow-up at 1.9±0.8 y (0.9-2.9 y) revealed no recurrence or new ulceration after treatment. Thus, the ADRCs treatment for decades-long radiation injuries is effective, safe and improves the quality of wounds.