放射性颌骨坏死术后感染预警模型的建立与验证

目的: 构建预测放射性颌骨坏死（osteoradionecrosis of the jaw,ORNJ）术后出现手术部位感染（surgical site infection,SSI）风险的列线图模型,并对该模型进行外部验证,评估其预测能力。方法: 纳入1993年3月—2014年10月于中山大学附属口腔医院手术治疗的507例ORNJ患者作为建模组,另纳入2000年1月—2021年11月于南方医科大学口腔医院手术治疗的112例ORNJ病例作为验证组,收集临床资料。采用SPSS 22.0软件包的单因素及多因素Logistic回归模型,分析ORNJ患者并发SSI的影响因素;应用R软件建立预测ORNJ患者并发SSI风险的列线图模型,并进行内部和外部验证。结果: Logistic回归分析显示,性别、放疗间隔时间≤2年、开口度≤1 cm、术前感染程度、手术方式是ORNJ患者并发SSI的独立影响因素。对列线图模型进行验证,其在建模组与验证组的Harrell一致性指数（C-index）分别为0.745和0.751;校准曲线显示该模型具有良好的区分度与精准度;ROC曲线显示该模型在建模组与验证组预测ORNJ患者并发SSI风险的曲线下面积分别为0.7446（95%CI：0.6934~0.7959）和0.7514（95%CI：0.6556~0.8473）。结论: 结合性别、放疗间隔时间、开口度、术前感染程度、手术方式等因素所构建的列线图可以较准确地预测ORNJ患者术后围术期发生SSI的风险,具有较高的临床应用价值。     

Actinomyces in infected osteoradionecrosis--underestimated?

Infected osteoradionecrosis (IORN) is a severe complication of radiation therapy for head and neck cancer. Infected osteoradionecrosis can lead to fracture and often requires subsequent jaw resection. It is known that irradiated bone is highly susceptible to infections, mainly with Candida species and cariogenic bacteria. Only very few data exist on Actinomyces in IORN. The study population consisted of 31 patients (7 female, 24 male; median age, 58.3 years). All patients exhibited clinical and radiological signs of IORN (infection, mucosa or skin fistula, and sequestrated bone). To detect Actinomyces colonies, histological examination was performed using several staining procedures (hematoxylin-eosin, Gram, Grocott, periodic acid-Schiff). In addition, a semi-nested polymerase chain reaction (PCR) approach was designed targeting the 16S ribosomal RNA gene. We found prominent Actinomyces colonies in 20 (64.5%) of 31 patients. Most of these lesions were localized in the mandible (16/20). Most interestingly, Actinomyces were almost exclusively found attached to the necrotic bone. PCR testing confirmed the presence of Actinomyces-specific DNA sequences (Actinomyces israelii). We show that Actinomyces is considerably more frequent in IORN than previously demonstrated. We suggest that these organisms are involved in the chronic, nonhealing inflammatory processes and the purulent discharge, which are known as characteristics of IORN. It remains to be investigated whether Actinomyces could be involved in the osteolytic mechanisms. From the histopathologic perspective, detection of Actinomyces is important because these bacteria have been shown to be associated with prolonged treatment duration.     

Lack of osteoradionecrosis of the mandible after intensity-modulated radiotherapy for head and neck cancer: likely contributions of both dental care and improved dose distributions

PURPOSE: To assess the prevalence and dosimetric and clinical predictors of mandibular osteoradionecrosis (ORN) in patients with head and neck cancer who underwent a pretherapy dental evaluation and prophylactic treatment according to a uniform policy and were treated with intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: Between 1996 and 2005, all patients with head-and-neck cancer treated with parotid gland-sparing IMRT in prospective studies underwent a dental examination and prophylactic treatment according to a uniform policy that included extractions of high-risk, periodontally involved, and nonrestorable teeth in parts of the mandible expected to receive high radiation doses, fluoride supplements, and the placement of guards aiming to reduce electron backscatter off metal teeth restorations. The IMRT plans included dose constraints for the maximal mandibular doses and reduced mean parotid gland and noninvolved oral cavity doses. A retrospective analysis of Grade 2 or worse (clinical) ORN was performed. RESULTS: A total of 176 patients had a minimal follow-up of 6 months. Of these, 31 (17%) had undergone teeth extractions before RT and 13 (7%) after RT. Of the 176 patients, 75% and 50% had received >or=65 Gy and >or=70 Gy to >or=1% of the mandibular volume, respectively. Falloff across the mandible characterized the dose distributions: the average gradient (in the axial plane containing the maximal mandibular dose) was 11 Gy (range, 1-27 Gy; median, 8 Gy). At a median follow-up of 34 months, no cases of ORN had developed (95% confidence interval, 0-2%). CONCLUSION: The use of a strict prophylactic dental care policy and IMRT resulted in no case of clinical ORN. In addition to the dosimetric advantages offered by IMRT, meticulous dental prophylactic care is likely an essential factor in reducing ORN risk.     

α2巨球蛋白对大鼠下颌骨放射性骨坏死的预防作用

目的: 观察和分析在X线照射前于大鼠下颌骨体局部注射α2巨球蛋白（alpha2-macroglobulin, α2M）是否对大鼠下颌骨放射性骨坏死（osteoradionecrosis,ORN）具有预防作用。 方法: 健康SD雄性大鼠18只,随机分为3组,每组6只。其中A组为空白对照组,B组为单纯X线照射组,C组为X线照射前左侧下颌骨局部注射α2M组。大鼠均经麻醉后使用3D打印装置固定,B、C组使用X线生物学辐照器对其左侧下颌骨进行精准照射,每天7 Gy,连续照射5 d;A组假照射;C组在第1次X线照射前30 min于大鼠左侧下颌骨体部骨膜下局部注射0.5 mL 2000 mg/L的α2M,A、B组在同样部位注射等量无菌生理盐水（normal saline,NS）。照射完成后第7天,拔除大鼠左侧下颌3颗磨牙。照射完成后第28天处死所有大鼠,从大体、影像学、病理学等方面系统评估各组大鼠的放射损伤。采用SPSS 13.0软件包对数据进行统计学分析。 结果: B组5只大鼠大体上体重明显减轻、照射区黏膜重度溃疡、受照侧颊部脱毛、咬合关系紊乱;影像学显示明显的骨质缺损;病理观察发现照射区皮质骨空白骨陷窝增多、死骨形成、纤维增生等骨坏死典型症状,证实发生下颌骨ORN,发生率为5/6;与B组相比,C组大鼠大体上仅表现为轻度体重下降及照射区脱毛,影像学上未见明显骨质缺损,病理观察仅见骨髓腔内轻微炎症,皮质骨无明显破坏,骨陷窝空虚率较B组显著降低（P<0.001）;C组大鼠下颌骨ORN发生率为零。 结论: X线照射前注射α2M对下颌骨ORN的发生具有较好的预防作用。     

Nomogram model to predict postoperative relapse after mandibular osteoradionecrosis surgery

Purpose

Osteoradionecrosis of the mandible (ORNM) is one of the most devastating complications following radiotherapy. Postoperative relapse (POR) occurs with high incidence even if a radical resection is performed. The current investigation was designed to identify prognostic factors for POR and to establish a nomogram model to estimate the risk for the onset of POR of ORNM.

Can we predict which patients are likely to develop severe complications following reconstruction for osteoradionecrosis?

High morbidity has been reported for free vascularised reconstruction for osteoradionecrosis (ORN) and there are no apparent risk factors. A single nucleotide polymorphism in the transforming growth factor beta 1 gene (TGF-β1) has been implicated in the cause of ORN and may also predict these complications. We studied a series of 30 consecutive patients who had had reconstruction for severe ORN with free tissue transfer in relation to their outcomes and complications for a number of risk factors including TFG-β1 genotype, age, sex, comorbidities, site and stage of tumour, type of initial operation, and dose of radiotherapy or chemoradiotherapy. Two patients died and 2 flaps failed. Using the Clavien–Dindo classification, 16 patients developed grade III complications and 6 grade II. Median (IQR) duration of inpatient stay was 19.5 (12–25) days and the median (IQR) duration of outpatient treatment was 6 (4–11) weeks. No specific risk factors for postoperative complications were identified. In view of the severity and unpredictability of the complications, careful preoperative counselling of patients is essential.     

Pentoxifylline and tocopherol in the management of patients with osteoradionecrosis, the Portsmouth experience

Osteoradionecrosis of the jaw remains the most problematic consequence of radiotherapy for the management of head and neck cancer. Treatment is often complex and multimodal. New theories on its pathophysiology have allowed the development of potential treatment modalities, including the use of pentoxifylline and tocopherol. In this retrospective case series we examined the outcomes of patients with ORN prescribed pentoxifylline and tocopherol.     

颌骨放射性骨坏死治疗进展

放射治疗是头颈部肿瘤常用的辅助治疗方法 ,其往往与化学治疗同时进行,可为晚期或无法手术切除的肿瘤提供治疗可能。但放射线作用于肿瘤细胞时,可杀伤正常组织细胞,发生临床上最严重的并发症即放射性骨坏死(osteoradionecrosis,ORN)。而针对ORN,目前缺乏有效的治疗手段。本文就ORN的研究进展作一概述,希望能为今后ORN的有效治疗提供新的思路。