Scoring irradiation mucositis in head and neck cancer patients

Irradiation mucositis is defined as an inflammatory-like process of the oropharyngeal mucosa following therapeutic irradiation of patients who have head and neck cancer. Clinically, it is a serious side effect because severe mucositis can cause generalized problems (weight loss, nasogastric tube feedings) and interferes with the well-being of the patient seriously. Grading mucositis is important for the evaluation of preventive and therapeutic measures. The object of this study was to develop a scoring method based on local mucositis signs only. Four clinical local signs of mucositis were used in this score: white discoloration, erythema, pseudomembranes and ulceration. Mucositis of the oral cavity was calculated during conventional irradiation protocol for 8 distinguishable areas using the 4 signs and their extent. A prospective evaluation of this method in 15 irradiated head and neck cancer patients displayed an S-curve reflecting a symptomless first irradiation week, followed by a rapid and steady increase of white discoloration, erythema and pseudomembranes during the second and third week. Oral candidiasis, generalized symptoms such as weight loss and the highest mucositis scores were seen after 3 weeks irradiation. The novel mucositis scoring method may be of value in studying the effect of hygiene programs, topical application of disinfectants or antibiotics on oral mucositis.     

1例表现为非典型性血管增生的放射性口腔黏膜炎

放射性口腔黏膜炎是因放射线电离辐射引起的口腔黏膜损伤,常表现为口腔黏膜充血、糜烂和溃疡,表现为非典型性血管增生的情况国内外未见报道。本文首次报道1例颌面部恶性肿瘤放疗后发生口腔黏膜非典型性血管增生改变的病例,结合该病例的诊治情况及既往文献报道,讨论了颌面部放射治疗导致口腔黏膜出现非典型性血管增生的发生机制及其治疗方案。     

Cytomegalovirus (CMV) and Helicobacter pylori(HP) found in oral mucosal ulcers

The possible involvement of Cytomegalovirus (CMV) and Helicobacter pylori (HP) in oral mucosal ulcers is suggested by their role in the development of ulceration at other mucosal sites of the gastrointestinal tract. A series of 29 incisional biopsies from 29 consecutive and apparently immunocompetent patients attending the clinic for oral ulceration were examined by routine histopathology as well as by in situ hybridisation (ISH) with biotinylated CMV and HP DNA probes. In 14/29 biopsies, Giemsa staining disclosed spiral bacteria. Six (20.7%) of these 14 Giemsa-positive samples showed HP DNA on ISH and 3 ulcers (10.3%) contained CMV DNA. In none of the specimens were CMV and HP detected simultaneously. Two of the ulcers containing CMV DNA were found on the labial mucosa and one on the posterior palatal mucosa, whereas all HP DNA-positive ulcers were located on the buccal mucosa. The results indicate that CMV and HP DNA can be found in separate oral mucosal ulcers in apparently immunocompetent adults.     

Chemotherapy‐induced oral mucositis and associated infections in a novel organotypic model

Oral mucositis is a common side effect of cancer chemotherapy, with significant adverse impact on the delivery of anti‐neoplastic treatment. There is a lack of consensus regarding the role of oral commensal microorganisms in the initiation or progression of mucositis because relevant experimental models are non‐existent. The goal of this study was to develop an in vitro mucosal injury model that mimics chemotherapy‐induced mucositis, where the effect of oral commensals can be studied. A novel organotypic model of chemotherapy‐induced mucositis was developed based on a human oral epithelial cell line and a fibroblast‐embedded collagen matrix. Treatment of organotypic constructs with 5‐fluorouracil (5‐FU) reproduced major histopathologic characteristics of oral mucositis, such as DNA synthesis inhibition, apoptosis and cytoplasmic vacuolation, without compromising the three‐dimensional structure of the multilayer organotypic mucosa. Although structural integrity of the model was preserved, 5‐FU treatment resulted in a widening of epithelial intercellular spaces, characterized by E‐cadherin dissolution from adherens junctions. In a neutrophil transmigration assay we discovered that this treatment facilitated transport of neutrophils through epithelial layers. Moreover, 5‐FU treatment stimulated key proinflammatory cytokines that are associated with the pathogenesis of oral mucositis. 5‐FU treatment of mucosal constructs did not significantly affect fungal or bacterial biofilm growth under the conditions tested in this study; however, it exacerbated the inflammatory response to certain bacterial and fungal commensals. These findings suggest that commensals may play a role in the pathogenesis of oral mucositis by amplifying the proinflammatory signals to mucosa that is injured by cytotoxic chemotherapy.     

Reduced expression of nuclear factor kB in oral mucosa undergoing preoperative chemoradiotherapy

Radiotherapy as well as chemotherapy in head and neck cancer induces severe oral mucositis. Even after healing of the mucositis, however, the oral mucosa looking atrophic is known to be susceptible to injury and infection. In order to investigate such vulnerability of mucosa, we immunohistochemically studied the expressions of Ki-67, proliferating cell nuclear antigen (PCNA), cyclin D₁, nuclear factor (NF)-kB, and keratinocyte growth factor (KGF) receptor in the oral mucosal keratinocytes undergoing preoperative concurrent chemoradiotherapy for oral cancer, compared with those of the oral mucosa without such therapy. As a result, the expressions of Ki-67, PCNA, and cyclin D₁ were decreased in the chemoradiotherapy-treated oral keratinocytes. Interestingly, NF-kB expression, which is known to be enhanced in oral mucositis, was reduced after chemoradiotherapy. The chemoradiotherapy had no effect on the expression of KGF receptor in oral keratinocytes. In conclusion, the vulnerability of oral mucosa undergoing chemoradiation may be associated with reduced NF-kB expression and impaired growth activity.     

Reverse smoking and palatal mucosal changes in Filipino women. Epidemiological features

A bstract — The habit of reverse smoking is practised in various parts of the world including the Philippines. In this pilot, community-based, cross-sectional study carried out in the region of Cabanatuan City in the Philippines, 61 Filipina reverse smokers and 30 Filipina conventional smokers were interviewed and clinically examined. Seven demographic variables and twelve habit variables were compared in the two study groups.
The majority (96.7 per cent) of reverse smokers exhibited palatal mucosal changes including leukoplakia, mucosal thickening, Assuring, pigmentation, nodularity, erythema and ulceration. In comparison, only 26.7 per cent of conventional smokers exhibited mucosal changes predominantly focal pigmentation and mild erythema. This difference was statistically significant at a X² value of 47.28 (p<.001). Analysis of the other variables indicated that the two study groups differed significantly with regard to age (p<.05), educational attainment (p<.01), use of filtered versus non-filtered cigarettes (p<.001) and duration of smoking in years (p<.01).     

Leukaemia in children. Part I: Orofacial complications and side-effects of treatment

Significant orofacial complications of leukaemia in children include lymphadenopathy, spontaneous gingival bleeding, labial and lingual ecchymoses and mucosal petechiae, ulceration, gingival swelling, and infections. The dentist may be the first to notice signs of the illness. Treatment of leukaemia can result in serious orofacial problems which include oral mucositis and ulceration, infections, spontaneous gingival bleeding, neuropathy, xerostomia, and gingival hypertrophy. A prompt diagnosis leading to early intervention can decrease the morbidity and mortality of the disease and its treatment.     

造血干细胞移植预处理诱发口腔黏膜炎模型的建立

目的探讨建立造血干细胞移植预处理诱发口腔黏膜炎大鼠模型的可行性。方法采用马利兰和环磷酰胺预处理方案结合左颊黏膜搔刮建立大鼠口腔黏膜炎模型。设立模型组和对照组，从自然过程、口腔黏膜炎指数、血象、骨髓象、病理检查等指标动态观察口腔黏膜炎的发生、发展过程。结果模型组大鼠于第7天开始出现口腔黏膜炎表现，发生率为80．00％；口腔黏膜炎指数在第11天达到峰值（2．04±1.80），4级以上口腔黏膜炎占39．29％（11／28）；第18～21天病损基本恢复，期间大鼠体重持续下降，白细胞计数于第10天下降至最低点，骨髓增生度低下。结论成功建立了造血干细胞移植预处理诱发口腔黏膜炎的大鼠模型。     

Betel chewer's mucosa - a review

Betel chewer's mucosa (BCM) was first described and defined in 1971. Its clinical appearance is characterised by a brownish-red discolouration of the oral mucosa with an irregular epithelial surface that has a tendency to desquamate or peel off. The buccal mucosa is most frequently affected. The prevalence of BCM varies between 0.2% and 60% in different studies from South and Southeast Asia. Women are more frequently affected than men. Betel chewer's mucosa may be found together with other oral mucosal lesions such as leukoedema, leukoplakia and ulceration. The histological features are characteristic. The epithelium is often hyperplastic, and brownish amorphous material derived from the betel quid may be demonstrated not only on the epithelial surface but also intra- and inter -cellularly. Ballooning of epithelial cells may occur. The etiology is traumatic and possibly chemical. Betel chewer's mucosa is most likely not precancerous. Differential diagnoses include cheek biting, with which it has a number of similarities, and other predominantly white lesions that may have taken up stains from tobacco and other substances. The natural history of BCM should be studied in more detail and its association with other oral mucosal diseases, particularly of a precancerous nature, should be the aim of further investigations.     

60 Coγ射线照射大鼠建立放射性口腔黏膜炎模型的初步研究

目的：建立大鼠放射性口腔黏膜炎模型,观察并分析黏膜组织炎症变化过程。方法：选择SD大鼠45只,随机分为9组：空白对照组;实验组8组均用60 Coγ射线以35 Gy剂量单次照射口鼻部。观察大鼠口腔黏膜状况,对炎症期间拒食的大鼠进行灌注流食喂养。分别于放射后1、3、5、7、10、14、21及28 d处死1组实验组大鼠,对照组于28 d处死,取口腔黏膜组织进行HE染色和光镜下观察。结果：放射后5～6 d,大鼠口腔黏膜出现红肿伴有小面积溃疡;7～8 d小溃疡逐渐融合成大面积溃疡,并持续到9～13 d;14 d开始,溃疡逐渐缩小并愈合;21～28 d溃疡完全愈合。 HE染色显示放射后第5 d,黏膜下层出现大量炎性细胞浸润,但上皮层连续完整;第7、10 d,上皮层崩解、脱落;第14 d溃疡底部可见新生肉芽组织及新生毛细血管;第21、28 d,溃疡处有新的上皮组织出现,基底层排列紧密。结论：经60 Coγ射线照射成功建立放射性口腔黏膜炎大鼠模型,炎症从5～8 d开始,第9～13 d达到高峰,14 d左右开始缓解恢复,21～28 d恢复正常。     

Aqueous hydrocortisone mouthwash solution: clinical evaluation

Patients often experience difficulties in applying topical steroids in orabase to the oral mucosa, particularly when large areas need to be covered. An aqueous hydrocortisone mouthwash solution has been developed, one that was anticipated to be more acceptable to patients. The solution contains hydrocortisone (0.3% w/v) in a 4.5% (w/v) 2-hydroxypropyl-β-cyclodextrin solution. Hydroxypropylmethylcellulose (0.5% w/v) was used to increase the viscosity of the solution and to promote the hydrocortisone±cyclodextrin complex. One hundred and two patients with aphthous ulceration, lichen planus, and other mucosal conditions used the mouthwash in an open clinical efficacy study. Most patients reported some or considerable improvement following a 2-week course of treatment with the mouthwash: 26 of 33 (78.8%) patients with aphthous ulceration were `much better', as were 26 of 54 (48.1%) patients with lichen planus and 5 of 16 (31.3%) patients with other mucosal lesions. No serious side effects were reported. Aqueous mouthwash solutions offer a potential vehicle for topical steroid therapy of oral mucosal lesions.     

Oral necrotizing microvasculitis in a patient affected by Kawasaki disease

Kawasaki disease (KD) was first described in 1967 by Kawasaki, who defined it as "mucocutaneous lymph node syndrome". KD is an acute systemic vasculitis, which mainly involves medium calibre arteries; its origin is unknown, and it is observed in children under the age of 5, especially in their third year. The principal presentations of KD include fever, bilateral nonexudative conjunctivitis, erythema of the lips and oral mucosa, changes in the extremities, rash, and cervical lymphadenopathy. Within KD, oral mucositis - represented by diffuse mucous membrane erythema, lip and tongue reddening and lingual papillae hypertrophy with subsequent development of strawberry tongue - can occur both in the acute stage of the disease (0-9 days), and in the convalescence stage (>25 days) as a consequence of the pharmacological treatment. KD vascular lesions are defined as systemic vasculitis instead of systemic arteritis. This study analyzed the anatomical-pathological substrata of oral mucositis in a baby affected by Kawasaki disease and suddenly deceased for cardiac tamponade caused by coronary aneurysm rupture (sudden cardiac death of a mechanical type).     

Effect of local application of the antimicrobial peptide IB-367 on the incidence and severity of oral mucositis in hamsters.

OBJECTIVE: The purpose of this animal study was to determine whether IB-367, an antimicrobial peptide, is able to ameliorate oral mucositis by reducing microflora densities on the mucosal surfaces of the mouth. STUDY DESIGN: Oral mucositis was induced in hamsters by intraperitoneal injection of 5-fluorouracil followed by superficial abrasion of the buccal mucosa. A test formulation was applied topically to the buccal mucosa 5 or 6 times per day starting 6 to 8 hours before abrasion. RESULTS: Mucositis scores were significantly lower (P < .05) in hamsters given formulations containing 0.5 or 2.0 mg/mL of IB-367 than in placebo-treated controls. Treatment with IB-367 produced a more than 100-fold reduction in oral microflora densities. In a second experiment, treatment of hamsters with a formulation containing IB-367 at 0.12, 0.5 or 2.0 mg/mL resulted in a dose-dependent reduction in mucositis severity. CONCLUSION: The results indicate that reduction of local microflora densities through use of IB-367 may improve clinical outcomes in patients at risk for the development of oral mucositis.     

An animal model for mucositis induced by cancer chemotherapy

Mucositis induced by chemotherapy is a painful and often dose-limiting side effect of cancer therapy. Furthermore, loss of the integrity of the oral epithelium often provides a microbial portal of entry and leads to sepsis. The present study describes the first animal model for chemotherapy-induced mucositis. The combination of three intraperitoneal injections of 5-fluorouracil at 5-day intervals and superficial mechanical mucosal irritation resulted in clinical breakdown of the oral mucosa characterized by ulcerative mucositis in Golden Syrian hamsters. Both clinical and histologic evaluation demonstrated that these changes were similar to those described in human beings and followed a pattern influenced by the degree of myelosuppression. This model should be of significance in establishing the stomatotoxicity of new chemotherapeutic agents, in evaluating medicaments to treat mucositis, and in studying the influence of oral mucosal breakdown on sepsis in myelosuppressed persons.     

Oral ulceration with bone sequestration

Oral mucosal ulceration is a common manifestation of various disease processes. Identification of the aetiological factor(s) involved greatly facilitates the management of such conditions. This report describes oral ulceration of the mucosa overlying the lingual shelf and mylohyoid ridge of the mandible and, less commonly on tori and exostoses, in association with bone sequestration. Trauma, which involves the subjacent periosteum resulting in a focus of ischaemic bone necrosis, in conjunction with local anatomical and perhaps other systemic predisposing factors, forms the aetiopathogenesis for this particular type of focal ulcerative lesion.     

Management of the oral sequelae of cancer therapy

Oral cancer and the oral sequelae of treatment for oral and other malignancies can significantly affect a patient's oral and systemic health, as well as have a profound impact on quality of life. Compromised oral health prior to, during, and following cancer therapy can affect treatment outcomes. Increasingly, dental professionals in the community are being called upon to provide care for these individuals. Radiation therapy is routinely used for tumors of the head and neck, delivering a concentrated radiation dose to the tumor, but also to the immediately surrounding tissue. Oral complications are related to the site radiated and the total radiation dose. Cancer chemotherapy is provided as a primary treatment for some cancers and as an adjunctive modality for other cancers. The goal is to eradicate the rapidly growing cells of the tumor, but chemotherapy is often toxic to other cells that rapidly divide normally including the oral mucosa. The use of combined chemotherapy and radiation is now considered standard for most locally advanced tumors of the head and neck. The toxicities of this combined therapy are essentially the same as with radiation alone, but develop more rapidly and are typically more severe when they reach maximum level. The most common oral sequelae of cancer treatment are: xerostomia, the sensation of a dry mouth as a result of damage to the salivary glands and/or medication; mucositis, the inflammation and ulceration of the oral mucosa; and infection as a result of the loss of mucosal integrity. Management of oral health during cancer therapy includes identifying at-risk patients, patient education, appropriate pretreatment interventions, and timely management of complications. Appropriate preventive and therapeutic measures will help minimize the risk of oral and associated systemic complications, improve treatment outcomes, and improve the patient's quality of life.     

A review and guide to drug‐associated oral adverse effects—Oral mucosal and lichenoid reactions. Part 2

Dental practitioners and other health professionals commonly encounter and manage adverse medicine effects that manifest in the orofacial region. Numerous medicines are associated with a variety of oral adverse effects. However, due to lack of awareness and training, these side effects are not always associated with medicine use and are underreported to pharmacovigilance agencies by dentists and other health professionals. This article aims to inform health professionals about the various oral adverse effects that can occur and the most commonly implicated drugs to improve the management, recognition and reporting of adverse drug effects. This article follows on from Part 1; however, the focus here is on lichenoid reactions and oral mucosal disorders including oral aphthous‐like ulceration, mucositis and bullous disorders such as drug‐induced pemphigus, pemphigoid, Stevens‐Johnson syndrome and toxic epidermal necrolysis.     

Toll样受体在放化疗诱导的消化道黏膜炎中的作用

黏膜炎是肿瘤患者进行放化疗时常见的消化道并发症,包括口腔黏膜炎和胃肠道黏膜炎,临床表现为口腔溃疡、呕吐、腹泻和疼痛等症状,严重降低患者的生活质量,甚至影响抗癌治疗。Toll样受体(Toll?like receptor,TLR)是参与天然免疫的重要受体,通过介导微生物与宿主之间的作用参与放化疗诱导黏膜炎的发生发展。文本针对现有TLR与黏膜炎相关研究予以综述。文献复习结果表明,不同TLR在放化疗诱导的黏膜炎中作用不同:TLR2是放化疗诱导的黏膜炎发生中炎性级联反应的重要受体;TLR4的激活能增加胃肠道黏膜炎症反应以及导致口腔上皮溃疡形成;TLR5激动剂能够降低放疗诱导的黏膜炎损伤程度;拮抗或敲除TLR9可减轻放化疗诱导的胃肠道黏膜炎。然而,目前尚未有TLR相关激动剂或抑制剂应用于临床,未来需要更多的研究对不同TLR在黏膜炎中的作用进行探讨,为放化疗性黏膜炎的精准防治提供参考。     

Oral mucositis

Oral mucositis refers to erythematous, erosive, and ulcerative lesions of the oral mucosa seen in two patient populations: (1) head and neck cancer patients undergoing radiation therapy to fields involving the oral cavity, and (2) patients receiving high-dose chemotherapy for cancer. Oral mucositis is a significant and dose-limiting toxicity of cancer therapy, with important clinical and economic implications. This article reviews the current knowledge on the pathogenesis, clinical presentation, diagnosis, and management of oral mucositis.