Treatment Of Osteoradionecrosis Research Articles

Virtual Surgical Planning Facilitates Surgical Resection in Mandibular Osteoradionecrosis and Optimize Reconstructive Outcomes

Background: Mandibular osteoradionecrosis (ORN) is a devastating complication of radiotherapy for oropharyngeal malignancy. Despite advancements in ORN treatment, risk of ORN recurrence remains high following surgical resection. Virtual surgical planning (VSP) for ORN treatment is an evolving application that may not only inform bony reconstruction but also therapeutic surgical margins, which remain inconclusively defined in the literature. Methods: A retrospective review was performed of 25 cases in which patients underwent VSP-guided resection of mandibular ORN followed by immediate free fibula flap reconstruction. Surgical margins of 1-cm from radiologically evident disease were taken. VSP accuracy was quantified by comparing measured anatomic parameters between the virtually planned outcomes and the final outcomes on postoperative imaging. Statistical analyses were performed to assess associations between preoperative factors and postoperative complications including ORN recurrence. Results: The mandibular body was most frequently affected by ORN in this series of patients. Among risk factors, only the presence of a preoperative orocutaneous fistula was predictive of a complication, specifically partial flap failure (β = 1.41; P = .013). Intended anatomic parameters were achieved with the exception of the intergonial distance (x difference = 0.53 cm; P = .03). Finally, there were no cases of ORN recurrence after a mean follow-up of 27.4 months. Conclusions: VSP of free fibula flaps for mandibular reconstruction following ORN is a valid tool for effecting accurate anatomical outcomes. Furthermore, we demonstrate that a 1-cm margin around radiographically evident ORN may effectively implement a curative outcome free from relapse.

Delayed reconstructive plastic surgery in patients with tumors of the maxillofacial region: literature review

Introduction. The main treatment option for malignant neoplasms of the head and neck is combined. However, survival rates are still relatively unchanged. The surgical stage of treatment leads to extensive defects that are eliminated through reconstructive technologies. Despite the priority of performing reconstruction at the same time, delayed reconstructions are still being discussed 6–12 months after surgical treatment; therefore, it is necessary to develop new methodological and practical approaches.Aim. To determine the features of the delayed reconstructive-plastic stage in patients with malignant tumors maxillofacial region, evaluation of possible solutions for optimizing the stage.Material and methods. The analysis of available literature sources was taken in the database Medline, Pubmed, eLibrary, etc. The 101 studies were found, 60 were used to write a systematic review.Results. Delayed reconstructive plastic surgery should take into the possibility more complex and larger defects of soft and bone tissues during the reconstructive stage, previous surgery and/or radiation therapy create significant difficulties for the identification of recipient vessels. Computer-aided design (CAD)/computer-aided manufacturing (CAM) technologies allow projecting the design and positioning of reconstructive material at the preoperative stage. Mandibular reconstruction is the most difficult, that isn’t achieve only an aesthetic result, but also to restore the biomechanics of the temporomandibular joint. The development of specific complications hinders the improvement of the patient’s quality of life. In the early postoperative period is may develop necrosis of the flap, thrombosis of vascular pedicle, hematoma; in the late postoperative period plate extrusion is still one of the common complications, planning delayed reconstruction an important aspect is prevention or treatment of osteoradionecrosis. The combination of precarbohydrate loading and dalargin will allow to reduce the frequency of perioperative complications and improve the long-term results of surgical treatment.Conclusion. Reconstructive treatment in patients with defects requiring postponed reconstructive surgeries is a complex problem which requires development of an integrated approach with detailed analysis of the existing defect and previous antitumor therapy.

Osteoradionecrosis treatment in head and neck cancer patients: An overview of systematic reviews.

Evaluate the existing evidence of osteoradionecrosis (ORN) treatment in adults with head and neck cancer, the methodological quality and the evidence grade within systematic reviews (SRs). An extensive systematic literature search of SRs that addressed ORN in head and neck cancer patients was conducted with screening of eligible studies, data extraction, methodological (AMSTAR 2) and evidence quality assessment (GRADE) of the SRs by independent and calibrated authors. A total of six SRs were enrolled. Based primarily on studies from the 1990s, there is critically low- or moderate-quality evidence that hyperbaric oxygen therapy (HBO) improves ORN healing. From 2005 onward, evidence has been discovered in relation to treatment with pentoxifylline and tocopherol (PENTO). The SRs indicate that the management of ORN with PENTO appears to be promising. The greatest rates of healing are seen in mild and moderate stages of ORN. However, the quality of evidence regarding PENTO, surgery and other treatments remains critically low. There is no standardized protocol to treat ORN. PENTO appears to be the most promising conservative treatment; however, the current level of evidence regarding PENTO is still critically low. More robust clinical studies are needed to establish the best treatment for ORN.

Reconstruction of mandibular defects in osteoradionecrosis and medication-related osteonecrosis of the jaw using fibula free flap and management of postoperative wound infections.

Complications from osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ) include oro-cutaneous fistulas, necrotic bone exposure, soft-tissue defects, and pathologic fractures. The fibula free flap (FFF) is a common free flap method used to reconstruct the mandible in severe cases. Recently, we have used the FFF successfully for the reconstruction of ORN and MRONJ mandibular defects. We report this method as a recommended technique for the treatment of ORN and MRONJ and the management method of postoperative infections. Four patients who were diagnosed with ORN of the mandible and 3 patients who were diagnosed with MRONJ of the mandible were included in the study. Among the 7 patients, 3 patients also had pathologic fractures. Partial mandibulectomy and FFF reconstruction were performed at the Department of Oral and Maxillofacial Surgery, Samsung Medical Center from April 2019 to March 2021. All 7 patients recovered following the reconstruction of the defect by FFF. Four patients experienced infections after surgery and pus cultures were performed. All were well healed without flap damage after changing the antibiotics by consultation with infectious medicine experts. FFF is a widely used method and can provide an extensive flap to reconstruct the mandible, especially those affected by ORN or MRONJ. If an infection occurs after surgery, appropriate antibiotic changes should be made through cooperation with the infectious medicine department. Therefore, FFF is a well-established and recommended method even in cases of challenging reconstruction.

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

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. 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. 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. 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. 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).

IS ANTIMICROBIAL PHOTODYNAMIC THERAPY EFFECTIVE AS AN ADJUNCT MANAGEMENT FOR OSTEORADIONECROSIS? - A CASES SERIES

Management of osteoradionecrosis (ORN) has not yet reached a consensus, so it remains complex and difficult to manage, with a poor prognosis. The objective was to report the treatment of ORN based on a protocol including antimicrobial photodynamic therapy (aPDT), irrigation with 0.12% chlorhexidine, surgical debridement, and application of 0.2% chlorhexidine gel. Fifteen patients were enrolled in this case series comprising 100% men; 66.6% were submitted to conformational radiotherapy, 86.6% underwent chemotherapy as part of the treatment, 86.6% were smokers, and 73.3% were alcohol addicts. The diagnosis was made both in clinical and imaging exams. Of the 15 cases, 73.3% had mucosal healing without pathological fracture, 13.3% had no wound healing and/or pathological fracture, and 6.6% had pathological mandible fracture without area healing. It was concluded that aPDT management associated with 2% chlorhexidine gel and 0.12% chlorhexidine solution plus surgical debridement was effective in 86.6% of ORN cases reaching no pathologic fracture and/or mucosal healing.

Osteoradionecrosis of the jaws: A retrospective cohort study.

Radiotherapy (RT) combined with chemotherapy and surgery is the indicated treatment for head and neck cancers. Even with the advent of modern technological advances in RT and improved oral hygiene awareness, osteoradionecrosis (ORN) still remains as one of the most debilitating side effects of RT. This is a retrospective review assessing 72 patients aged over 18 years of age reporting in the Dental Department, for treatment of ORN from April 2010 to July 2019. Each patient was clinically examined and treated according to standard protocol. The stage of ORN was noted at the diagnosis and at follow-up. The demographic data, the tumor characteristics, and the treatment of patients were evaluated using descriptive statistics. At the time of diagnosis, 84.7% of the study population was found to have Epstein Type II chronic persistent nonprogressive lesions and 11.1% of the cohort had Type III active progressive lesions. Statistically significant correlation (P = 0.00) was found for ORN grade at diagnosis and at follow-up. ORN being a chronic pathology, stabilization of the disease was observed in 72.3% of cases. The resolution of the necrotic lesion and down staging of the disease was seen only in 2.8% of patients. ORN is mainly a chronic long standing pathology which is difficult to treat completely. Stabilization of symptoms and preventing further spread of the necrotic lesion should be the ultimate aim of the treatment to improve the quality of life of the patients.

Advances and Controversies in the Management of Osteoradionecrosis After Head and Neck Cancer Treatment: A Narrative Review.

Osteoradionecrosis (ORN) is a painful and debilitating serious late complication following treatment for head and neck cancer (HNC) often requiring surgical resection of the jaw and complex multidisciplinary management. An important aggravating factor for mandibular ORN is surgical trauma, commonly dental extractions or implant placement following head and neck radiotherapy. The evidence on the treatment protocols ranges from conservative management to more radical surgical strategies including the use of hyperbaric oxygen therapy. The available evidence on the preventive approaches for ORN includes prophylactic dental care prior to radiotherapy, the use of hyperbaric oxygen (HBO) treatment and prophylactic antibiotics for post-radiotherapy extractions. However, the efficacy of hyperbaric oxygen therapy has been questioned recently signifying poor understanding of the pathophysiology of the condition and therapies targeting the fibroatrophic process have become a focus of ORN treatment. Implementing recent IMRT radiation techniques has also shown evidence to reduce the incidence of ORN. This review provides an insight into the variations in definition and classification of the ORN, the controversies in its pathophysiology and the advances in the prevention and management.

Use of hyperbaric oxygen therapy in the treatment of osteoradionecrosis of the maxilla in patients with head and neck cancer

This study aimed to understand how hyperbaric oxygen therapy can act in the treatment of osteoradionecrosis of the jaws in patients with head and neck cancer. A total of 266 publications were found. After applying the inclusion and exclusion criteria, 19 articles were selected. Osteoradionecrosis is a condition with great potential for bone destruction, and therefore, many methods for treatment have been vehemently studied. Although the mechanism of action of hyperbaric oxygen therapy is not fully understood, it is known that the physiochemistry that drives the action is a result of two factors: 100% inspired oxygen and exposure to high atmospheric pressure. In addition, oxygen when present in larger quantities in the body can act to heal necrotic regions, oxygenating regions where hypoxia and hypoperfusion have occurred. However, this therapy is not totally innocuous and has significant issues for the patient, among them, the limitation of its access, and with this, the cost for oxygen therapy is very high. The negative impact that osteoradionecrosis has on oncology patients can be seen, and how hyperbaric therapy can act in the treatment of necrosis caused by oncotherapy in patients with head and neck cancer, due to its numerous effects on oxidative metabolism. In contrast, it is necessary to correctly evaluate the indication of the treatment, because the therapy has relevant adverse effects that deserve attention.

Pentoxifylline-Tocopherol and A-PRF Associated with Sequestrectomy for the Treatment of Severe Mandibular Osteoradionecrosis: Case Report and Long-Term Follow-Up

Osteoradionecrosis treatment is challenging for clinicians. Throughout history, the study of osteoradionecrosis and its pathophysiological understanding has given the guidelines for managing this pathology. Currently, osteoradionecrosis is understood as a radiation-induced fibro-degenerative process, so its management focuses on reducing the molecular mediators involved during the process. We present the case of a 61-year-old male patient with multiple comorbidities and medical history of the floor of mouth cancer treated with radiotherapy. After extracting a mandibular tooth, osteoradionecrosis with pathologic fracture and orocutaneous fistula developed in the mandibular body. Due to multiple advanced inferior extremities atheromatosis and comorbidities, a fibula microvascular free flap was contraindicated.

The Potential Therapeutic Role of Mesenchymal Stem Cells-Derived Exosomes in Osteoradionecrosis.

As one of the most serious complications of radiotherapy, osteoradionecrosis (ORN) seriously affects the quality of life of patients and even leads to death. Vascular injury and immune disorders are the main causes of bone lesions. The traditional conservative treatment of ORN has a low cure rate and high recurrent. Exosomes are a type of extracellular bilayer lipid vesicles secreted by almost all cell types. It contains cytokines, proteins, mRNA, miRNA, and other bioactive cargos, which contribute to several distinct processes. The favorable biological functions of mesenchymal stem cells-derived exosomes (MSC exosomes) include angiogenesis, immunomodulation, bone regeneration, and ferroptosis regulation. Exploring the characteristic of ORN and MSC exosomes can promote bone regeneration therapies. In this review, we summarized the current knowledge of ORN and MSC exosomes and highlighted the potential application of MSC exosomes in ORN treatment.

Overview and Emerging Trends in the Treatment ofOsteoradionecrosis.

Osteoradionecrosis (ORN) of the mandible is a rare but devastating complication which occurs following radiation therapy for head and neck malignancies. Left untreated, ORN often results in pathologic fracture of the mandible leading to pain, trismus, difficulty eating, and overall poor quality of life. Historically, early intervention relied on hyperbaric oxygen and local debridement. Patients whose disease progressed despite therapy required segmental resection of the mandible with osseous free flap reconstruction, a highly invasive operation. Patients that presented with a moderate disease without pathologic fracture were often doomed to fail non-operative management, ultimately leading to disease progression and fracture. The traditional dichotomous treatment paradigm left a void of options for patients with moderate disease. The ideal intervention for this category of patients would provide renewed vascularity to the diseased tissue bed allowing for the osteogenesis and reestablishment of strong, load-bearing bone. The innovative technique termed the vascularized fascia lata "rescue flap" has proven to be an effective treatment for moderate ORN and will likely transform dated treatment algorithms.

Pentoxifylline and tocopherol (vitamin E) with/without clodronate for the management of osteoradionecrosis: A scoping review.

Treatment of osteoradionecrosis (ORN) is not a straightforward task, and it is unpredictable. However, a combination of pentoxifylline; an antioxidant drug, and tocopherol (vitamin E) works as a potent antifibrotic agent and have shown recently both significant and impressive results. This scoping review aims to investigate the most prescribed regimen of pentoxifylline and tocopherol with/without clodronate for the management of ORN. Ovid MEDLINE and EMBASE databases were used to retrieve eligible studies using planned search keywords. PROSPERO and Cohcarne library were also searched for ongoing or published systematic reviews, respectively. Included articles were grouped thematically according to the type of studies and accordingly they were summarized. A total of 27 articles met the inclusion criteria and included in the data analyses. All the included articles were published between 1997 and 2020. Of these 27 included studies, two were randomized control trials, two were systematic reviews, six were retrospective studies, five were observational studies, seven were narrative reviews, four were case reports, and lastly one was an in-vitro study. Treatment by PENTO (800mg of pentoxifylline+1000IU of tocopherol) once daily for an early established ORN or PENTOCLO (PENTO regimen+1600mg of clodronate) once daily for the refractory/severe cases of ORN appears to be the most prescribed regimen used for the treatment of ORN using these drugs. These drugs appear safe, effective and inexpensive for the treatment of ORN.

The diagnosis and management of a pathological fracture: a case report

A 64 year old female patient presented to the Accident and Emergency (A&E) department at the Royal Lancaster Infirmary (RLI) with a significant left sided jaw pain. This patient reported paraesthesia and a shooting pain radiating down her left mandible. There was also marked trismus on examination. Her medical history included a history of a previously diagnosed Squamous Cell Carcinoma (SCC) of the left soft palate. This was staged at T2N0M0 and treated with radiotherapy and chemotherapy. Following a clinical examination, special investigations via imaging were obtained prior to a formal diagnosis of pathological fracture of the left mandible following previous radiotherapy for her SCC treatment.
 This case report will discuss the incidence, background, management and treatment of osteoradionecrosis (grade 3) (ORN) of the mandibular jaw bone as well as the associated pathological fractures and the detrimental effects following the use of radiotherapy to the head and neck region.

English

BACKGROUND The maxillofacial region has several congenital and acquired defects. Because of its abundant blood supply and proximity to different intraoral abnormalities, the buccal fat pad flap (BFP) is a simple and reliable flap that can be used to repair a variety of these abnormalities. BFP has remarkable qualities as a scaffold and autogenous dressing in the healing of intraoral defects after excision of oral cavity intraoral lesions. Filling and allowing slippage of fascial spaces between muscles of facial expression, advancement of intermuscular motion, isolating mastication muscles from one another, counteracting negative pressure during suction in the newborn, protection and cushioning of neurovascular bundles from injuries are among the functions of BFP. It also has a dense venous network that facilitates exoendocranial blood flow via the pterygoid plexus. For many years, the BFP was considered a surgical annoyance due to its incidental encounter during various surgeries in the pterygomaxillary space or following injuries to the craniofacial region. However, various clinical applications of BFP have been introduced in recent years. We looked at BFP and its anatomical foundation, surgical procedures, and clinical applications in this review article. The surgical method is easy and effective in a wide range of clinical situations, including oroantral fistula closure, congenital defect rectification, Osteoradionecrosis treatment, and reconstruction of tumor or cyst defect. Thus BFP is a dependable flap that may be used in a variety of therapeutic conditions. KEY WORDS Buccal Fat Pad Flap; Oral Mucosa; Reconstruction; Defect.

P-256 Efficacy of Hyperbaric Oxygen in the Treatment of Osteoradionecrosis of the Mandible. Results from the combined clinical trials DAHANCA-21 and NWHHT2009-1

P-256 Efficacy of Hyperbaric Oxygen in the Treatment of Osteoradionecrosis of the Mandible. Results from the combined clinical trials DAHANCA-21 and NWHHT2009-1

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.

Antibiotic therapy for the prevention of osteoradionecrosis following tooth extraction in head-and-neck cancer patients postradiotherapy: An 11-year retrospective study.

Introduction:One of the most important complications of radiotherapy (RT) for head-and-neck cancer (HNC) is osteoradionecrosis (ORN) of the jaws, which mostly arises from tooth extractions. The ORN treatment still represents a great challenge; therefore, the prevention is of paramount importance. Thus, the present study aimed to evaluate retrospectively a perioperative systemic antibiotic therapy protocol for the prevention of ORN following tooth extraction in head-and-neck patients post-3D conformal RT.Materials and Methods:A retrospective medical record review was performed considering HNC patients submitted to RT in the period between 2008 and 2019. They necessarily received oral antibiotic therapy with Clindamycin 300 mg every 8 h for 10 days, with the first dose 3 days before the tooth extraction.Results:Forty-nine patients met the study criteria, with a total of 107 teeth extracted. Regarding the 47 patients who did not develop ORN, 103 tooth extractions were identified (96.3%). Only two patients developed ORN at two adjacent teeth sites (3.7%).Conclusion:The proposed perioperative systemic antibiotic therapy protocol seems to be efficient to prevent ORN following tooth extraction in postirradiated HNC patients.

Surgical Management of Skull Base Osteoradionecrosis in the Cancer Population - Treatment Outcomes and Predictors of Recurrence: A Case Series.

Skull base osteoradionecrosis (ORN) is a challenging treatment-related complication sometimes seen in patients with cancer. Although ORN management strategies for other anatomic sites have been reported, there is a paucity of data guiding the management of skull base ORN. To report a single-center tertiary care series of skull base ORN and to better understand the factors affecting ORN recurrence after surgical management. We conducted a retrospective cohort study of patients with skull base ORN treated at our center between 2003 and 2017. Univariate and multivariate binary logistic regressions were performed to identify predictors of recurrence. A total of 31 patients were included in this study. The median age at ORN diagnosis was 61.1 yr (range, 32.8-84.9 yr). Of these 31 patients, 15 (48.4%) patients were initially treated medically. All 31 patients underwent surgery. Three (14.3%) of 21 patients treated with a free flap and 4 (50.0%) of 8 patients who underwent primary closure experienced recurrence. Cox regression analysis revealed that reconstruction with local tissue closure (P=.044) and ongoing treatment for active primary cancer (P=.022) were significant predictors of recurrence. The median overall survival from index surgery for ORN treatment was 83.9 mo. At 12-mo follow-up, 78.5% of patients were alive. In this study, we assess the outcomes of our treatment approach, surgical debridement with vascularized reconstruction, on recurrence-free survival in patients with skull base ORN. Further studies with larger cohorts are needed to assess current treatment paradigms.

Twelve-year experience in mandibular reconstruction using osteo-muscular dorsal scapular pedicled flaps

Primary mandibular reconstruction after tumor removal or osteoradionecrosis treatment is a standard procedure. The most common reconstruction techniques are fibula, scapula, and iliac crest free flaps. Nevertheless, all patients are not eligible for microsurgery.In this study, we assess 12 years of mandibular reconstruction using an osteo-muscular dorsal scapular pedicled flap (OMDS). We included 40 patients operated on using an OMDS flap. We collected parameters such as length of hospital stay, recurrence risk, and need for secondary flap for oral cutaneous fistula (OCF) treatment. Flap bone volume was assessed by segmenting the scapula on postoperative CT-scans using dedicated software.Forty patients were included. Indications for OMDS flaps were severe cardiovascular history (27%), preoperative radiotherapy with a radiation neck and potentially unreliable blood vessel sutures (20%), previous fibula free flap failure (15%), and patient refusing free tissue transfer (8%). Aside from these medical indications, OMDS flaps were performed in 30% of cases due to organizational concerns. The mean flap length was 73±16 mm, with a maximum of 109 mm. Flap bone volume was stable over time, with negligible resorption (p = 0.761). Secondary pedicled flaps were used to treat OCF in 5 patients (12%). Secondary esthetic procedures were performed in 9 patients (22%). None of the 40 flaps were removed. None of the patients had long-term scarring complications in donor sites.OMDS flaps merit consideration for mandibular reconstruction when free tissue transfer is contraindicated or impossible due to organizational issues.