Extranodal natural killer/T cell lymphoma nasal type simulating osteoradionecrosis with metachronic B lymphoma in the pelvis: Case report.

Extranodal Natural Killer/T Cell Lymphoma Nasal Type (EN-NK/T-CL-NT) is a non-Hodgkin extranodal lymphoma of unfavorable prognosis due to its aggressive nature. This neoplasm mainly affects the paranasal sinuses, nasopharynx, oropharynx, oral cavity, palate, and rarely intestinal, gastric and skin regions. 50-year-old female with a history of lymphoma in nasal and pelvic region. At four years of tumors-free, has facial asymmetry, accompanied by sub-palpebral, nasal and lip edema. Intraoral examination revealed a large ulceration suggestive of osteoradionecrosis. Gum biopsy shows Extranodal NK/T Cell Lymphoma Nasal Type (EN-NK/T-CL-NT). In this case we highlight the characteristics of EN-NK/T-CL-NT with a presentation of osteoradionecrosis-like. Unfortunately, the nature of this tumor led to the patient's death. Clinical follow-up of patients with cancer is imperative to mend and/or decrease treatment complications, as well as to identify second primary tumors or the spread of the underlying disease.

Microstructural changes in the irradiated and osteoradionecrotic bone: a SEM study.

Radiation exposure is a major health concern due to bone involvement including mandible, causing deleterious effects on bone metabolism, and healing with an increasing risk of infection and osteoradionecrosis. This study aims to investigate the radiotherapy-induced microstructural changes in the human mandible by scanning electron microscopy (SEM). Mandibular cortical bone biopsies were obtained from control, irradiated, and patients with osteoradionecrosis (ORN). Bone samples were prepared for light microscopy and SEM. The SEM images were analyzed for the number of osteons, number of Haversian canal (HC), diameter of osteon (D.O), the diameter of HC (D.HC), osteonal wall thickness (O.W.Th), number of osteocytes, and number of osteocytic dendrites. The number of osteons, D.O, D.HC, O.W.Th, the number of osteocytes, and osteocytic dendrites were significantly decreased in both irradiated and ORN compared to controls (p < .05). The number of HCs decreased in irradiated and ORN bone compared to the control group. However, this was statistically not significant. The deleterious effect of radiation continues gradually altering the bone quality, structure, cellularity, and vascularity in the long term (>5 years mean radiation biopsy interval). The underlying microscopic damage in bone increases its susceptibility and contributes further to radiation-induced bone changes or even ORN.

Radiologic findings of osteonecrosis, osteoradionecrosis, osteomyelitis and jaw metastatic disease with cone beam CT.

PURPOSE: The purpose of this study was to assess CBCT scans of patients with medication related osteonecrosis of the jaws (MRONJ), osteoradionecrosis (ORN), osteomyelitis (OM) and jaw metastatic disease (JM), evaluate the presence and extent of radiologic findings, identify radiologic parameters that may distinguish the four entities and last, introduce a new modified radiographic index (CRIm), in order to contribute to the diagnosis of these conditions. METHODS: Τwo major databases were retrospectively searched for fully documented and diagnosed CBCT scans of MRONJ, ORN, OM and JM from 2006 to 2019. 335 CBCT scans met the inclusion criteria and were assessed under standardized viewing conditions blindly by 2 observers. The CRIm index proposed in this study evaluates: lytic changes, sclerosis, periosteal bone formation, sequestration, non-healing extraction sockets and other findings which included: sinus implication, inferior alveolar canal implication and jaw fracture. Lytic changes, sclerosis, periosteal bone formation, sequestration and non-healing extraction sockets were scored as: absent (0), localized/single (1) and extensive/multiple (2). Each one of other findings were scored individually as: absent (0) and present (1). For statistical analysis t-test, Pearson's r correlation coefficient, one-way ANOVA and Bonferonni were performed. RESULTS: Extensive lytic changes were the most common finding, especially for ORN, where it occurred in all CBCT scans (100%). The mean value of the CRIm index differs significantly between CBCT scans with MRONJ and JM, as well as between those with OM and JM (Bonferroni p < 0.001). CONCLUSIONS: The new modified Composite Radiographic Index introduced in this study, appears to have improved an objective approach to the previously used Composite Radiographic Index by means of cumulative radiologic features. Τhe predominance of certain radiologic features in one or more of these entities may lead the diagnostician towards the correct diagnosis.

[A Case of Reconstruction of the Osteoradionecrosis of the Jaw Using the Patient-Specific Custom-Made Cutting Guide and Mandibular Reconstruction Plate].

Multidisciplinary treatment, combining ablative surgery and reconstruction, radiotherapy, and chemotherapy, is used to treat advanced oral cancers. In this study, we report a case of extensive osteoradionecrosis of the mandible following multidisciplinary treatment for tongue cancer, in which a computer-assisted, patient-specific custom-made cutting guide and reconstruction plate(TruMatch® )were used to improve the patient's facial morphology and oral-maxillofacial functioning. A 70-year-old man received multidisciplinary treatment for squamous cell carcinoma of the left side of the tongue (cT3N2bM0, cStage ⅣA)at a previous hospital. Seven years postoperatively, bilateral osteoradionecrosis of the mandible developed, and the patient was referred to our department for further treatment. Since the lesions were extensive, we planned reconstructive surgery using the TruMatch® system in collaboration with the plastic surgery department of our hospital. Surgery was performed precisely and accurately according to the preoperative simulation. Postoperatively, the patient's recovery was uneventful. The TruMatch® system enables us to achieve good morphological and comprehensive functional oral-maxillofacial reconstruction.

Immune microenvironment: novel perspectives on bone regeneration disorder in osteoradionecrosis of the jaws.

Osteoradionecrosis of the jaws (ORNJ) is a severe complication that occurs after radiotherapy of head and neck malignancies. Clinically, conservative treatments and surgeries for ORNJ exhibited certain therapeutic effects, whereas the regenerative disorder of the post-radiation jaw remains a pending problem to be solved. In recent years, the recognition of the role of the immune microenvironment has led to a shift from an osteoblasts (OBs) or bone marrow mesenchymal stromal cells (BMSCs)-centered view of bone regeneration to the concept of a complicated microecosystem that supports bone regeneration. Current advances in osteoimmunology have uncovered novel targets within the immune microenvironment to help improve various regeneration therapies, notably therapies potentiating the interaction between BMSCs and immune cells. However, these researches lack a thorough understanding of the immune microenvironment and the interaction network of immune cells in the course of bone regeneration, especially for the post-operative defect of ORNJ. This review summarized the composition of the immune microenvironment during bone regeneration, how the immune microenvironment interacts with the skeletal system, and discussed existing and potential strategies aimed at targeting cellular and molecular immune microenvironment components.

Salvage endoscopic surgery for skull base osteoradionecrosis in nasopharyngeal carcinoma patients: A prospective, observational, single-arm clinical study.

BACKGROUND: Postradiation skull base osteoradionecrosis (ORN) is a severe complication that occurs after radiotherapy in patients with nasopharyngeal carcinoma (NPC) that can severely affect quality of life (QOL) and be life threatening. Only 13.4% - 28.6% of patients can be cured by traditional repeated endoscopic debridement. Here, we introduced salvage endoscopic surgery for skull base ORN patients and evaluated its clinical efficacy. METHODS: This was a prospective, observational, single-arm clinical study. Clinical data from 18 skull base ORN patients who underwent radical endoscopic necrectomy followed by reconstruction using a septal pedicled mucosal flap or temporal muscle flap were included in the study. The endpoint was an overall survival (OS) of 2 years. The numeric rating scale (NRS) scores for pain and foul odor were analyzed to determine the efficacy and safety of this surgery. RESULTS: A total of 21 patients were recruited, 18 of whom completed the study and were analyzed. All surgeries were successfully performed. During the 2-year study, the OS rate of the entire cohort was 75%. The median NRS score for pain decreased from 6.44 +- 2.62 to 0.50 +- 0.71, and the NRS score for foul odor decreased from 1.89±1.08 to 1 after surgery. CONCLUSIONS: Salvage endoscopic necrectomy followed by construction using a septal pedicled mucosal flap or temporal muscle flap is a novel, safe, and effective treatment for ORN in patients with NPC. CLINICAL TRIAL REGISTRATION: This study was approved by the independent ethics committee of the Eye, Ear, Nose and Throat Hospital of Fudan University (IEC No. 2019095-1). Written informed consent was obtained from all patients. The study was registered with the Chinese Clinical Trial registry (ChiCTR2000029327).

Osteoradionecrosis of the cervical spine: an analysis of the literature.

OBJECTIVES: The purpose of this manuscript is to review the current literature on osteoradionecrosis of the cervical spine (C-ORN) and to summarize the risk factors, presenting symptoms and management strategies of this rare condition. STUDY DESIGN: A systematic review of the literature on C-ORN was completed using PubMed. Nineteen articles met criteria; 97 patient cases were identified. Statistical analysis was completed from the patient cases. RESULTS: Of the analyzed patients, 72% are male and 28% are female with an average age of 57.7 years. Nasopharyngeal carcinoma was the most common initial diagnosis (72%). Thyroid and other lower neck cancers were associated with a later onset of C-ORN compared with other cancers. C-ORN more commonly occurred in the clivus to C2 (55.3%, P = .004). Onset of C-ORN significantly differed for men (n = 6.99 years) and women (n = 17.5 years) (P = .022). CONCLUSION: C-ORN can be a devastating complication of head and neck radiation therapy. C-ORN is associated with nasopharyngeal carcinoma, and most commonly affects the area of the clivus to cervical vertebrae C2. Cancers of the lower neck and female sex are associated with later onset. Initial presentation ranges from asymptomatic to severe neurologic deficits; the degree of intervention should be congruent with the severity of presenting symptoms. As long-term survival of patients with head and neck cancer increase, this complication may become more prevalent.

Comparison of maximum and mean standardized uptake values of jaw pathologies with bone SPECT/CT: an especial focus on medication-related osteonecrosis of the jaw.

OBJECTIVES: To investigate the comparison of maximum and mean standardized uptake values (SUVs) of jaw pathologies with bone Single-photon emission computed tomography/computed tomography (SPECT/CT), and a special focus on medication-related osteonecrosis of the jaw (MRONJ). METHODS: Eighty-nine patients with jaw pathologies (63 MRONJ, 13 chronic osteomyelitis, 11 osteoradionecrosis and 2 primary intraosseous carcinoma) underwent bone SPECT/CT scans acquisition at 4 h after intravenous injection of Tc-99m hydroxymethylene diphosphonate in this prospective study. The evaluation of mean and maximum SUVs of jaw pathologies were performed using Q. Metrix and Xeleris workstation and defined the data automatically. Statistical analyses were performed by Pearson's correlation coefficient for comparison of maximum and mean SUVs and Mann-Whitney U-test for SUVs of MRONJ. A P value lower than 0.05 was considered to indicate statistical significance. RESULTS: Maximum SUVs of MRONJ, chronic osteomyelitis, osteoradionecrosis and primary intraosseous carcinoma were 17.6 ± 8.4, 21.7 ± 7.1, 11.9 ± 4.8 and 26.6 ± 7.0, respectively. Mean SUVs of MRONJ, chronic osteomyelitis, osteoradionecrosis and primary intraosseous carcinoma were 10.1 ± 4.9, 11.9 ± 3.3, 7.0 ± 2.8 and 10.1 ± 4.5, respectively. The maximum SUV of jaw pathologies was significantly correlated with the mean SUV (Y = 0.494X + 1.228; R2 = 0.786; P < 0.001). Furthermore, maximum and mean SUVs of MRONJ had significant differences in underlying diseases, medication and staging. CONCLUSION: The maximum and mean SUVs with bone SPECT/CT can be an effective tool for the quantitative evaluation of jaw pathologies, especially MRONJ.

Platelet-rich fibrin as a treatment option for osteoradionecrosis: A literature review.

The aim of this review is to establish the usefulness and effectiveness of using platelet-rich fibrin (PRF) in the treatment of osteoradionecrosis (ORN) lesions. A review of the literature was performed using keywords through the PubMed-Medline and Cochrane Library search engine. Inclusion criteria were: (1) original publication in either the French or the English language, (2) studies conducted in humans, (3) presence of ORN lesions following head and neck radiotherapy (RT), (4) use of PRF or derivates in the treatment of ORN lesions, (5) clinical variables and outcomes mentioned in the study. Overall, four case reports were retained. Two publications were removed from the initial seven results after application of the inclusion criteria. A recent randomised clinical trial was not considered since the group analysed the effectiveness of leukocyte-enriched Plasmas-Rich-Fibrin (LPRF) in preventing ORN, but not in treating it. Therefore, four publications were retained for analysis. Results suggest that using PRF as an adjunct to surgical therapy is beneficial in treating ORN lesions although no controlled studies were found. Therefore, additional controlled clinical studies are warranted to better define the effectiveness and recommendation of this approach.

Refining the mandibular osteoradionecrosis rat model by in vivo longitudinal µCT analysis.

Osteoradionecrosis (ORN) is one of the most feared side effects of radiotherapy following cancers of the upper aero-digestive tract and leading to severe functional defects in patients. Today, our lack of knowledge about the physiopathology restricts the development of new treatments. In this study, we refined the ORN rat model and quantitatively studied the progression of the disease. We tested the impact of radiation doses from 20 to 40 Gy, delivered with incident 4MV X-ray beams on the left mandible of the inbred Lewis Rat. We used micro-computed tomography (µCT) to obtain in vivo images for longitudinal bone imaging and ex vivo images after animal perfusion with barium sulphate contrast agent for vessel imaging. We compared quantification methods by analyzing 3D images and 2D measurements to determine the most appropriate and precise method according to the degree of damage. We defined 25 Gy as the minimum irradiation dose combined with the median molar extraction necessary to develop non-regenerative bone necrosis. µCT image analyses were correlated with clinical and histological analyses. This refined model and accurate methods for bone and vessel quantification will improve our knowledge of the progression of ORN pathology and allow us to test the efficacy of new regenerative medicine procedures.

Pentoxifylline, tocopherol, and sequestrectomy are effective for the management of advanced osteoradionecrosis of the jaws-a case series.

BACKGROUND: The aim of the present study was to evaluate the efficacy of pentoxifylline and tocopherol for the management of osteoradionecrosis of the jaws. METHODS: Twenty-five patients diagnosed with osteoradionecrosis of the jaws treated with pentoxifylline 400 mg + tocopherol 400 mg three times daily (tid) were evaluated. Clinical records and image tests were reviewed. All patients were previously submitted to head and neck radiation therapy and presented with a clinical and radiographic diagnosis of osteoradionecrosis of the jaws. RESULTS: Following therapy with pentoxifylline and tocopherol, 76% (19/25) of the patients showed complete mucosal healing, in which 47.3% (9/19) did not undergo sequestrectomy. From this particular group, 77.7% (7/9) were in stage I and 33.3% (3/9) used the protocol for up to 3 months. Among those who underwent to sequestrectomy, complete mucosal healing was observed in 52.7% (10/19). Among these, 60% (6/10) were in stage I and 100% of the patients were using the protocol for more than 3 months. In all other patients, partial healing of the mucosa was observed since they presented advanced disease. These represented 24% of the sample (6/25), 66.6% (4/6) were in stage III, and 60% (4/6) used the protocol for over 6 months. CONCLUSION: Pentoxifylline and tocopherol may provide effective management of osteoradionecrosis of the jaws, and the association with sequestrectomy may avoid major surgical procedures.

18F-FDG PET/CT in Osteoradionecrosis of the Hyoid.

Osteoradionecrosis (ORN) is a well-documented complication following radiation treatment for head and neck malignancy. Facial bones, mainly the mandible, laryngeal cartilage, and skull, are frequently involved sites for ORN. A rare site for ORN is the hyoid, with very limited cases described in the literature. Recognition of the imaging pattern of hyoid ORN is critical to avoid misdiagnosis of recurrent disease, prompting early treatment.

ODONTOLOGICAL EFFECTS OF IONIZING RADIATION (review). / ODONTOLOGIChNI EFEKTY IONIZUIuChOGO VYPROMINIuVANNIa (ogliad).

BACKGROUND: Odontological effects of ionizing radiation (IR) as a result of radiotherapy, the consequences of accidents at nuclear power plants and industry, individual occupational exposure, etc. deserve significant attention interns of radiation medicine and radiation safety. OBJECTIVE: to analyze and summarize clinical and experimental data on the odontological radiation effects. OBJECT: the pathological changes in the hard tissues of teeth, pulp, periodontium, mucousmembranes of the mouth and jaws due to exposure to IR. METHOD: search in the PubMed / MEDLINE, Google Scholarabstract medical and biological databases, scientific libraries of the relevant sources of scientific information. RESULTS: Radiobiological effects of IR due to its direct and indirect action are manifested throughout the period ofodontogenesis and formation of the facial skeleton. Experimental and clinical data (in children and adults) indicatethe increased risk of dental caries, reduction of pain threshold and vascularization of tooth pulp along with its fibrosis and atrophy, periodontal dysfunction, which predispose to a high probability of tooth loss. Abnormalities in theactivity of osteoblasts and cementoblasts of dental periosteum and osteoblasts of alveolar process in combinationwith circulatory disorders due to endothelial cell death, hyalinization, thrombosis and vascular obliteration increasethe risk of jaw osteoradionecrosis. Children who have undergone a prenatal exposure to IR as a result of theChornobyl NPP accident have a premature change of teeth. Deterioration of periodontal tissues and early development of acute and complicated dental caries are typical for children and adults affected by the Chornobyl disaster. CONCLUSIONS: Summarized data on the effects of radiation exposure under different conditions on teeth primordia(i.e. immature teeth), their formation and eruption in experimental and clinical settings, as well as on the odontological radiation effects in adults are summarized. Condition of the teeth in the Chornobyl NPP accident survivorsis described. Understanding and taking into account the radiobiological odontological effects is necessary in thelight of planning, preparing, and conducting local radiation therapy and developing the standards of radiation safety and measures to protect professionals and the public in the event of possible radiation accidents at the nuclearpower plants and industry facilities.

Cervical spine osteoradionecrosis or bone metastasis after radiotherapy for nasopharyngeal carcinoma? The MRI-based radiomics for characterization.

BACKGROUND: To develop and validate an MRI-based radiomics nomogram for differentiation of cervical spine ORN from metastasis after radiotherapy (RT) in nasopharyngeal carcinoma (NPC). METHODS: A radiomics nomogram was developed in a training set that comprised 46 NPC patients after RT with 95 cervical spine lesions (ORN, n = 51; metastasis, n = 44), and data were gathered from January 2008 to December 2012. 279 radiomics features were extracted from the axial contrast-enhanced T1-weighted image (CE-T1WI). A radiomics signature was created by using the least absolute shrinkage and selection operator (LASSO) algorithm. A nomogram model was developed based on the radiomics scores. The performance of the nomogram was determined in terms of its discrimination, calibration, and clinical utility. An independent validation set contained 25 consecutive patients with 47 lesions (ORN, n = 25; metastasis, n = 22) from January 2013 to December 2015. RESULTS: The radiomics signature that comprised eight selected features was significantly associated with the differentiation of cervical spine ORN and metastasis. The nomogram model demonstrated good calibration and discrimination in the training set [AUC, 0.725; 95% confidence interval (CI), 0.622-0.828] and the validation set (AUC, 0.720; 95% CI, 0.573-0.867). The decision curve analysis indicated that the radiomics nomogram was clinically useful. CONCLUSIONS: MRI-based radiomics nomogram shows potential value to differentiate cervical spine ORN from metastasis after RT in NPC.

Mesenchymal Stem Cell Therapy for Osteoradionecrosis of the Mandible: a Systematic Review of Preclinical and Human Studies.

BACKGROUND: Osteoradionecrosis (ORN) of the mandible is a severe complication of radiotherapy for head and neck cancer and is arduously difficult to manage. Current treatment options carry risks with some patients remaining incurable. Mesenchymal stromal/stem cell (MSC) therapy has shown promising results supporting osteogenesis and regeneration of radiotherapy-damaged tissues. The aim of this study was to systematically review the literature on the safety and efficacy of MSCs in treating ORN. METHODS: A systematic search was performed on MEDLINE, Embase, Cochranes Library online databases, and clinicaltrials.gov to identify preclinical and clinical studies examining the effect of MSCs on osseous healing of ORN. The preclinical studies were assessed according to the SYRCLEs guidelines and risk of bias tool. RESULTS: Six studies (n = 142) from 5 countries were eligible for analysis. Of these four were preclinical studies and two clinical case studies. Preclinical studies found MSC treatment to be safe, demonstrating bone restorative effects and improved soft tissue regeneration. In the clinical cases, healing of bone and soft tissue was reported with no serious adverse events. CONCLUSION: The evidence from the included studies suggests that MSCs may have beneficial regenerative effects on the healing of ORN. None of the studies reported adverse events with the use of MSCs. More carefully controlled studies with well-identified cells are however needed to demonstrate the efficacy of MSCs in a clinical setting. Graphical abstract.

Regeneration of mandibular osteoradionecrosis with autologous cross-linked serum albumin scaffold.

Osteoradionecrosis is one of the most severe complications of radiotherapy administered for head and neck tumors. We present the first two cases of advanced and refractory mandibular osteoradionecrosis treated by application of a novel autologous cross-linked 3D serum matrix. Patients were followed clinically and radiographically up to 24 months. Complete wound healing and intact mucosal cover were achieved in both cases. At 12 months, the radiographic values showed an almost complete regeneration of the bone defect, which continued a favourable progression increased to the maximum by 24 months after surgery. The use of an autologous serum-derived scaffold proved to be a quick, predictable, cost-effective and safe adjunct to the conservative surgical treatment of this pathology.