Recent advances in cancer therapy-associated oral mucositis.

Oral mucositis (OM) is a common and debilitating toxicity of cancer treatments - chemotherapy, radiotherapy, hematopoietic cell transplant, or combinations. OM is associated with severe oral pain and has negative impacts on patient function and quality of life. Additionally, OM has accompanying systemic complications that may have critical implications. These local and systemic consequences can alter cancer treatment, and add an economic burden. This review covers the clinical presentation and course of OM, differential diagnosis, clinical and economic impacts, pathogenesis, risk factors, assessment measures, biomarkers and prediction of OM, management, research advances in the development of new drugs and treatments, and big data.

Guidance on mucositis assessment from the MASCC Mucositis Study Group and ISOO: an international Delphi study.

Background: Mucositis is a common and highly impactful side effect of conventional and emerging cancer therapy and thus the subject of intense investigation. Although common practice, mucositis assessment is heterogeneously adopted and poorly guided, impacting evidence synthesis and translation. The Multinational Association of Supportive Care in Cancer (MASCC) Mucositis Study Group (MSG) therefore aimed to establish expert recommendations for how existing mucositis assessment tools should be used, in clinical care and trials contexts, to improve the consistency of mucositis assessment. Methods: This study was conducted over two stages (January 2022-July 2023). The first phase involved a survey to MASCC-MSG members (January 2022-May 2022), capturing current practices, challenges and preferences. These then informed the second phase, in which a set of initial recommendations were prepared and refined using the Delphi method (February 2023-May 2023). Consensus was defined as agreement on a parameter by >80% of respondents. Findings: Seventy-two MASCC-MSG members completed the first phase of the study (37 females, 34 males, mainly oral care specialists). High variability was noted in the use of mucositis assessment tools, with a high reliance on clinician assessment compared to patient reported outcome measures (PROMs, 47% vs 3%, 37% used a combination). The World Health Organization (WHO) and Common Terminology Criteria for Adverse Events (CTCAE) scales were most commonly used to assess mucositis across multiple settings. Initial recommendations were reviewed by experienced MSG members and following two rounds of Delphi survey consensus was achieved in 91 of 100 recommendations. For example, in patients receiving chemotherapy, the recommended tool for clinician assessment in clinical practice is WHO for oral mucositis (89.5% consensus), and WHO or CTCAE for gastrointestinal mucositis (85.7% consensus). The recommended PROM in clinical trials is OMD/WQ for oral mucositis (93.3% consensus), and PRO-CTCAE for gastrointestinal mucositis (83.3% consensus). Interpretation: These new recommendations provide much needed guidance on mucositis assessment and may be applied in both clinical practice and research to streamline comparison and synthesis of global data sets, thus accelerating translation of new knowledge into clinical practice. Funding: No funding was received.

Emerging pharmacotherapy trends in preventing and managing oral mucositis induced by chemoradiotherapy and targeted agents.

INTRODUCTION: The introduction of targeted therapy and immunotherapy has tremendously changed the clinical outcomes and prognosis of cancer patients. Despite innovative pharmacological therapies and improved radiotherapy (RT) techniques, patients continue to suffer from side effects, of which oral mucositis (OM) is still the most impactful, especially for quality of life. AREAS COVERED: We provide an overview of current advances in cancer pharmacotherapy and RT, in relation to their potential to cause OM, and of the less explored and more recent literature reports related to the best management of OM. We have analyzed natural/antioxidant agents, probiotics, mucosal protectants and healing coadjuvants, pharmacotherapies, immunomodulatory and anticancer agents, photobiomodulation and the impact of technology. EXPERT OPINION: The discovery of more precise pathophysiologic mechanisms of CT and RT-induced OM has outlined that OM has a multifactorial origin, including direct effects, oxidative damage, upregulation of immunologic factors, and effects on oral flora. A persistent upregulated immune response, associated with factors related to patients' characteristics, may contribute to more severe and long-lasting OM. The goal is strategies to conjugate individual patient, disease, and therapy-related factors to guide OM prevention or treatment. Despite further high-quality research is warranted, the issue of prevention is paramount in future strategies.

Central giant cell granuloma of the jaws-long-term clinical and radiological outcomes of surgical and pharmacological management.

OBJECTIVES: To compare long-term results of different treatment modalities in central giant cell granuloma of the maxillofacial-skeleton. Primary resection may result in major defects. Alternative treatments include pharmacological agents. As yet there has been no consensus on the use of the variety of treatment options, and few studies have reported clarifying long-term results. MATERIALS AND METHODS: This retrospective study on 22 patients with 25 lesions evaluated clinical, radiological and histological features, treatment preformed and lesion recurrence. Success was defined as regression/calcification and failure as recurrence, progression or un-responsiveness. RESULTS: Of the presenting patients, 77% were under age 40. Lesion prevalence was higher in the anterior mandible and left posterior maxilla. Most cases exhibited pain, tooth-mobility or mucosal-expansion. The appearance was predominantly unilocular in the maxilla and multilocular in the mandible, which also exhibited higher prevalence of cortical perforation. Up to 80% of lesions were classified as aggressive. Intralesional steroids/calcitonin were used in 7 cases. Mean follow-up was 39.8 months. Two cases showed recurrence. In 71% of the cases treated pharmacologically, calcification/regression were observed. CONCLUSIONS: Our analysis indicates better outcomes using a combined approach, including both pharmacological and surgical treatments in large aggressive lesions. Pharmacological treatment resulted in decreased size or well-defined lesions, thus reducing the need for extensive bone resection. Dual treatment with corticosteroids and calcitonin showed no superior outcomes, but a larger cohort should be assessed. CLINICAL RELEVANCE: There are several protocols for treatment of central-giant-cell-granuloma lesions, but most are not fully established. It is important to report results that contribute to the establishment of proven protocols. This report attempts to establish the relevance of the combined approach: pharmacological treatment followed by surgical resection.

Clinical use of photobiomodulation for the prevention and treatment of oral mucositis: the real-life experience of MASCC/ISOO members.

AIM: To assess clinical use and patient outcome of photobiomodulation (PBM) for oral mucositis (OM) prevention and treatment among specialized practitioners. METHODS: A poll was emailed to the members of the Mucositis Study Group of MASCC/ISOO. The PBM parameters used by the respondents were analyzed using exploratory statistical methods to identify combinations of PBM parameters (patterns) that characterize the variance in the protocols (principal component analysis). RESULTS: Responses were received from 101 MSG members, with 78 providing analyzable data. Most of the responders were dental practitioners or oral medicine specialists. PBM was used by 59% of the responders for OM or targeted therapy stomatitis. Technical parameters varied widely. Most responders used wavelengths ∼650 nm intra-orally. The spot-size and distance from the tissue were the main factors driving the variation. All PBM users noted that PBM relieved pain, either immediately or a delayed effect. High likelihood of pain relief (measured as responder's report of pain relief in 67-100% of patients) was reported by 22% and 19% of PBM users for immediate pain relief and delayed pain relief, respectively. The most common reported barriers to using PBM were financial considerations, time constraints, lack of training or experience and concern about the potential for malignant transformation or increased risk of cancer recurrence. CONCLUSIONS: The use of PBM for OM prevention or treatment is in early phases of adoption in practices, facing some obstacles to implement it. A wide variation in technical parameters was found. Nonetheless, responses indicate that PBM provided pain relief.

Deep convolutional neural network algorithm for the automatic segmentation of oral potentially malignant disorders and oral cancers.

This study aimed to develop an algorithm to automatically segment the oral potentially malignant diseases (OPMDs) and oral cancers (OCs) of all oral subsites with various deep convolutional neural network applications. A total of 510 intraoral images of OPMDs and OCs were collected over 3 years (2006-2009). All images were confirmed both with patient records and histopathological reports. Following the labeling of the lesions the dataset was arbitrarily split, using random sampling in Python as the study dataset, validation dataset, and test dataset. Pixels were classified as the OPMDs and OCs with the OPMD/OC label and the rest as the background. U-Net architecture was used and the model with the best validation loss was chosen for the testing among the trained 500 epochs. Dice similarity coefficient (DSC) score was noted. The intra-observer ICC was found to be 0.994 while the inter-observer reliability was 0.989. The calculated DSC and validation accuracy across all clinical images were 0.697 and 0.805, respectively. Our algorithm did not maintain an excellent DSC due to multiple reasons for the detection of both OC and OPMDs in oral cavity sites. A better standardization for both 2D and 3D imaging (such as patient positioning) and a bigger dataset are required to improve the quality of such studies. This is the first study which aimed to segment OPMDs and OCs in all subsites of oral cavity which is crucial not only for the early diagnosis but also for higher survival rates.

Radiographic findings of space-occupying lesions in sialo-CBCT of the major salivary glands.

OBJECTIVES: When performing CBCT sialography (sialo-CBCT), space-occupying lesions may be identified incidentally. The objective was to describe their radiologic-clinical-histopathologic correlations. METHOD AND MATERIALS: The archive of sialo-CBCT scans was retrospectively searched for suspected space-occupying lesions. Based on the scan and clinical-histopathologic data, the cases were divided into "pathologic" vs "normal," "intra-parenchymal" vs "extra-parenchymal," and "benign" vs "malignant." Two precalibrated, blinded radiologists performed a survey of the radiographic features of each scan. Cohen kappa, chi-square, Kruskal-Wallis, and Mann-Whitney tests assessed inter-observer agreement and radiologic-clinical-histopathologic correlations. RESULTS: In total, 27 (1.5%) suspected space-occupying lesions were found in 1,758 reports. Full follow-up data were available for 15 cases: four were "malignant," six were "benign," and the remaining five were "normal." Kappa showed substantial inter-observer agreement (0.8 to 1.0). Constant swelling correlated with "pathologic" cases (P = .003). Lesion diameter was greater in "pathologic" than "normal" (P < .001) cases, with a cut-off of 12.6 mm. Clinical and radiographic features were similar in "benign" and "malignant" lesions. "Intra-parenchymal" and "extra-parenchymal" space-occupying lesions correlated with "no-fill-region" (P = .01) and "main-duct-displacement" (P = .002), respectively. CONCLUSIONS: Suspected space-occupying lesions in sialo-CBCT with a diameter greater than 12.6 mm are likely to be "pathologic." No radiographic features were able to differentiate between "malignant" and "benign" space-occupying lesions.

Is Open Reduction Internal Fixation Using Titanium Plates in the Mandible as Successful as We Think?

ABSTRACT: Titanium plats are the gold-standard for fracture fixation. Titanium is considered biocompatible, corrosion resistant with an elasticity-modulus closest to bone. Nonetheless, titanium plates are not always as inherent as hoped. The authors investigated morbidity associated with titanium plates in mandibular fractures. A retrospective study of mandibular fractures treated between 2000 and 2018 using internal-fixation was conducted. Data included age, gender, complications, and location. Predictor-variable was location. Outcome-variable was plate removal. A total of 571 patients were included, 107 resulted in plate removal (18.7%). Body was the most prevalent location of fracture (29.3%). Symphysis/para-sym-physis showed the highest removal rate (24.1%), followed by body and angle (21.3/19.8%). A total of 23.4% of double-plating cases resulted in plate removal, upper-border in 15% and lower-border in 8.8%, all reconstruction-plates. Exposure was the most frequent complication leading to removal. Although titanium plates are the gold standard, almost every fifth patient returns for plate removal. Age-distribution emphasizing 41 to 50 with decrease towards extremities may imply better healing in the young and soft-tissue elasticity and less complaints in the elderly. Significantly more complications in double-plating compared to lower border suggests proximity to the oral-cavity as a risk-factor for removal. Complication rates and patterns are not negligible and perhaps should encourage clinicians to consider using biodegradable-systems for upper-border plates.

Caries experience, periodontal status, and metabolic morbidity in patients with psychiatric disorders.

OBJECTIVES: To investigate the association of psychiatric disorders with (1) caries experience, (2) periodontal status, and (3) metabolic syndrome (MetS) components. METHOD AND MATERIALS: This 7-year cross-sectional study retrospectively analyzed the medical records of 504 individuals aged 18 to 90 years who attended the student dental clinic. Collected data included: demographics, smoking habits, systolic and diastolic blood pressures, pulse, waist circumference, full-mouth plaque score (FMPS), full-mouth bleeding score (FMBS), maximal pocket probing depth (PPD), average and maximal radiographic bone loss (RBL), the sum of the number of decayed (D), missing (M), and filled (F) teeth (DMFT score), and presence of MetS components, consequences and related conditions including diabetes, hypertension, hyperlipidemia, ischemic heart disease, heart failure, s/p stroke, and cancer. RESULTS: 68 (13.5%) had psychiatric disorders with an average age of 53.42 ± 15.71 years. Psychiatric disorders were positively associated with smoking (P = .008), smoking pack-years (P = .004), DMFT score (P = .005), and negatively associated with hypertension (P = .046). Psychiatric disorders had no statistically significant associations with all periodontal indices studied and with other components of MetS. Following multivariate analysis, psychiatric disorders retained a statistically significant positive association with smoking (odds ratio [OR] and 95% confidence interval [CI] = 2.24 [1.28 to 3.92]) and with DMFT (OR and 95% CI = 1.08 [1.02 to 1.14]), and a statistically significant negative association with hypertension (OR and 95% CI = 0.46 [0.25 to 0.84]). CONCLUSIONS: Psychiatric disorders were positively associated with smoking and caries experience but not with periodontal status and metabolic morbidity. Communication between dental and medical professionals is needed to address the higher smoking consumption and caries morbidity in psychiatric patients. (Quintessence Int 2021;52:516-526; doi: 10.3290/j.qi.b1044091).

Solitary Extraosseous Neurofibroma in a 5-Year-Old Child - A Case Report.

Rationale: Neurofibroma (NF) is the most common benign peripheral nerve sheath tumour that most often occurs as a solitary tumour. A clinical and imaging diagnosis may be challenging since no distinctive features are unique for this lesion. Solitary NFs are treated by complete resection that may sometimes require a nerve sacrifice, ending with a neurological deficit. Patient Concerns: A 5-year-old girl with mild asymptomatic slow-growing swelling in the vestibulum of her right mandible. Diagnosis: A solitary variant of extraosseous NF involving the right mental branch of the inferior alveolar nerve. Treatment: Surgical removal of the lesion while fully preserving the mental branch. Outcomes: No sensory deficit was identified during a 3-month follow-up. Take-Away Lessons: Ultrasonography is a valuable tool for evaluating soft-tissue masses of the oral cavity. A solitary extraosseous NF involving the mental branch can be surgically removed without nerve deficit.

Important radiographic features in the identification of osseous dysplasia-related osteomyelitis.

OBJECTIVES: The aims of this study were to identify radiographic features that distinguish osseous dysplasia-related osteomyelitis (OD-related OM) from OD without OM and to detect possible causes of OD-related OM. STUDY DESIGN: Seventeen OD cases with and without OM were examined on planar and volumetric (cone beam computed tomography or multidetector computed tomography) imaging. Cases were divided into 3 groups based on clinical data: symptomatic OM, incidental (asymptomatic) OM, and control (OD without OM). Images were reviewed by 3 precalibrated observers, blinded to clinical information, for OD characteristics (location and extent); radiographic features of OD-related OM; and possible causes. Radiographic features of OD-related OM chosen by at least 2 observers were statistically analyzed within and between groups. RESULTS: Discontinuity of the cortical plates, widening of the radiolucent rim, decreased attenuation of the radiolucent rim, and sequestrum formation were significantly more common in symptomatic and incidental OM groups than in the control group (P ≤ .05). Two causes, atrophy of the edentulous ridge and presence of a periapical lesion, were also correlated with OD-related OM (P ≤ .05, P ≤ .01, respectively). CONCLUSIONS: Radiographic features can distinguish OD-related OM from OD. Familiarity with these radiographic features and possible causes may help improve the identification of secondarily infected OD.

An artificial intelligence system using machine-learning for automatic detection and classification of dental restorations in panoramic radiography.

OBJECTIVES: The aim of this study was to develop a computer vision algorithm based on artificial intelligence, designed to automatically detect and classify various dental restorations on panoramic radiographs. STUDY DESIGN: A total of 738 dental restorations in 83 anonymized panoramic images were analyzed. Images were automatically cropped to obtain the region of interest containing maxillary and mandibular alveolar ridges. Subsequently, the restorations were segmented by using a local adaptive threshold. The segmented restorations were classified into 11 categories, and the algorithm was trained to classify them. Numerical features based on the shape and distribution of gray level values extracted by the algorithm were used for classifying the restorations into different categories. Finally, a Cubic Support Vector Machine algorithm with Error-Correcting Output Codes was used with a cross-validation approach for the multiclass classification of the restorations according to these features. RESULTS: The algorithm detected 94.6% of the restorations. Classification eliminated all erroneous marks, and ultimately, 90.5% of the restorations were marked on the image. The overall accuracy of the classification stage in discriminating between the true restoration categories was 93.6%. CONCLUSIONS: This machine-learning algorithm demonstrated excellent performance in detecting and classifying dental restorations on panoramic images.

Necrotizing sialometaplasia of the palate in a young bodybuilder with anabolic androgenic steroids abuse.

Necrotizing sialometaplasia is a benign, self-limiting, inflammatory disease of salivary glands, mainly involving the minor salivary glands in the palate. This lesion can mimic a malignant neoplasm, both clinically and histopathologically, manifesting as a submucosal swelling or as an ulcer of the palate. This report presents a case of an otherwise healthy bodybuilder with anabolic androgenic steroids abuse with bilateral necrotizing sialometaplasia in the palate, and discusses computed tomography findings in the pre-ulceration phase. Literature review revealed another two cases of necrotizing sialometaplasia with preoperative imaging, both performed in the ulceration phase. The importance of radiographic findings as an aid in differential diagnosis is further discussed, as well as the role of possible predisposing factors including anabolic androgenic steroids abuse in the pathogenesis of necrotizing sialometaplasia.

Where periodontitis meets metabolic syndrome-The role of common health-related risk factors.

OBJECTIVES: To analyse and compare associations between metabolic syndrome (MetS) and its components in periodontitis compared to control patients. METHODS: This 7-year cross-sectional study retrospectively analysed medical records of 504 individuals aged 18-90 who attended the student dental clinic between 2008 and 2014. Demographics, smoking habits, blood pressure, waist circumference, as well as presence of: periodontitis, MetS, diabetes, hypertension, hyperlipidaemia, stroke, heart disease, cancer and psychiatric disorders were recorded. RESULTS: The study population composed of 231 (45.8%) males and 273 (54.2%) females, with an average age of 55.79 ± 16.91 years. A patient profile associated with periodontitis was identified and included male sex, older age, smoking, higher smoking pack-years, abdominal obesity, higher systolic and diastolic blood pressures, the presence of MetS or its components, hypertension, hyperlipidaemia, diabetes or diseases associated with its consequences such as ischaemic heart disease and stroke. Following multivariate logistic regression analysis, age and smoking retained a significant association with periodontitis, whereas the systemic disorders did not. CONCLUSIONS: The association between periodontitis and MetS may be explained by shared common profile and risk factors. An appropriate risk factors management approach should be adopted by both dental and general health clinicians and health authorities, to control common high-risk behaviours.

Ameloblastoma incidentally detected in cone-beam computed tomography sialography: A case report and review of the literature.

BACKGROUND AND OVERVIEW: Cone-beam computerized tomographic (CBCT) imaging is increasingly used in the maxillofacial region for various purposes. The volumetric dataset created by means of CBCT increases the possibility of detecting incidental findings. CASE DESCRIPTION: In this case report, the authors describe an otherwise healthy 45-year-old man who was referred from the Sjogren's Syndrome Center in Jerusalem, Israel, for bilateral parotid CBCT sialographic imaging owing to xerostomia lasting for 4 months. CBCT sialographic imaging using iodine contrast material showed normal glandular structure and activity according to the postcannulation panoramic imaging. CBCT sialographic imaging routine volume interpretation revealed a lesion in the mandibular area causing destruction and perforation of the cortical plates, partial disappearance of adjacent lamina dura, and resorption of adjacent teeth, suggesting an aggressive benign tumor. Histopathologic examination confirmed mural cystic ameloblastoma, which was resected with preservation of the mental nerve and the lower mandibular border. The patient received bone graft and implants, with regular follow-ups and no recurrence after 4 years. CONCLUSIONS AND PRACTICAL IMPLICATIONS: This case strengthens the need for thorough examination of the whole CBCT imaging volume within and outside the region of interest to detect incidental findings with clinical importance.

Characterization of pain originating from oral mucosal lesions.

OBJECTIVE: The aim of the study was to characterize pain associated with oral mucosal lesions. STUDY DESIGN: A cross-sectional study was performed in patients diagnosed with localized mucosal pain originating from acute ulcers (AUs), herpes infections (HIs), and immune-mediated chronic diseases (IMCDs). Pain-related features, including intensity (VAS-I), perceived unpleasantness (VAS-U), functional impairment (VAS-F), and effect on quality of life (VAS-Q), were recorded using a 10-cm visual analogue scale (VAS). Waking from sleep, provoking, and alleviating factors were assessed by questionnaires. RESULTS: Sixty-three patients aged 19 to 82 years (47.22 ± 17.20 years) were examined over the study period. These included 18 patients with AUs, 21 with HIs, and 24 with IMCDs. At rest, VAS-U was significantly higher than VAS-I for all groups, and VAS-F was higher for lesions located on the tongue or lips. Up to 80% of patients described the pain as "burning." Differences between groups were not observed for all other parameters measured. Pain woke the patients from sleep in almost half of cases. VAS-I and VAS-U were not related to size or number of lesions. CONCLUSIONS: Mucosal pain is generally burning in quality, with a higher level of pain-related unpleasantness than pain intensity. In about half of the cases, pain awakens the person from sleep, a feature that correlated to female gender and pain intensity. Pain intensity or unpleasantness was not related to the size or number of lesions.