Pilot study: protective effect on mucosal tissue using dental waterjet and dexpanthenol rinsing solution during radiotherapy in head and neck tumor patients Abstract Purpose Radiogenic side effects are frequently seen in patients undergoing radiotherapy for head and neck tumors. Intensified dental and mucosal care reduce oral hygienic deficits. The aim of this study was the optimization of mouth hygiene using dexpanthenol rinsing solution applied with a dental waterjet system (DWS). Methods 30 consecutive head and neck tumor patients (44–75 years) were analyzed, who received intensity-modulated radiation treatment (IMRT; total dose range: 54–66 Gy) with helical Tomotherapy HiArt II. The group under investigation (n = 10) additionally received a professional DWS using dexpanthenol mouthrinse (Bepanthen). The first control group received dexpanthenol mouthrinse alone. The second control group only performed the standardized mouth hygiene protocol. Grade of xerostomia, taste, dysphagia, thrush, and mucositis was evaluated on a daily basis. Results 29 of 30 patients completed radiation therapy. Change in taste occurred in all patients in all groups, however, with a delay in the study group. The occurrence of grade III stomatitis and Xerostomia grade II was significantly reduced in the study arm. No patient suffered from grade III xerostomia in the study arm versus four patients in the control groups. Dysphagia grade II was observed significantly less frequent in the study group (p = 0.0004). Thrush occurrence showed a delay in the study group. Conclusions Our study underlines the importance of an intensified mouth hygiene during radiation therapy. The combination of dexpanthenol rinsing solution + DWS reduces the incidence of high-grade early side effects which often lead to a reduced quality of life and abortion of the treatment.

Identification of stably expressed genes for normalization of gene expression data in oral tumors: a preliminary analysis Abstract Aim We sought to identify stably expressed genes in tumors of gingivo-buccal region and tongue from untreated as well as treated patients. Background The study was undertaken in view of the ambiguity with regards to the choice of reference genes for normalization of gene expression data from gingivo-buccal region and tongue. This aspect was also examined in tumors from treated patients since it could provide clues for such analyses in the assessment of treatment modalities in the future. Methods Expression of ten candidate housekeeping genes, identified in array-based studies, was tested using TaqMan based semi-quantitative real-time PCR. Thirty-five buccal mucosa derived (18 from treated patients) and 15 tongue tumors (8 from treated patients) were studied. Most stable genes were identified based on the consensus between the results of the three methods, Comparative δCt, BestKeeper and NormFinder, used for data analysis. Results CHMP2A and VPS29 were identified as the most stably expressed genes suitable for normalization of data from buccal-mucosa tumors, whereas RPS13 and PSMB2 were indicated for similar specimens from treated patients. The same criteria identified stable expression of PSMB2 and PUM1 in tumors from tongue and OAZ1 and RPS13 for the post-treatment tongue tumors. Conclusion We have identified stably expressed genes in common oral cancers which can be used for normalization of the gene expression data. Results also established differences in tumors arising at different sites of the oral cavity and highlighted further changes following exposure to therapy.

Next generation sequencing identifies novel diagnostic biomarkers for head and neck cancers Abstract Purpose Salivary microRNAs (miRNAs) could potentially serve as biomarkers for the diagnosis and prognosis of various types of oral cancer but the significance of it is yet to be fully elucidated. This article reports our study results on the role of salivary miRNAs and their potential use as biomarkers in head and neck cancer (HNC) diagnosis with an emphasis on oral cancers (OC). Methods Supernatant saliva samples from 24 subjects, including 12 OC patients and 12 healthy individuals as a control group, were initially profiled using next generation sequencing (NGS). A novel miR-7703 was further validated in 160 samples collected from OC patients (n = 80) and controls (n = 80) by quantitative real-time polymerase chain reaction (qRT-PCR) assays. Results Data analysis revealed that 373 miRNA expressions were significantly decreased and 265 miRNA expressions were significantly increased in patients with OC (p ≤ 0.05). Of the 638 miRNA, twenty-seven were non-redundant miRNAs associated with OC (p ≤ 0.0001). Validation of the novel miR-7703 showed a significant increase in the OC group when compared to the control group. Most importantly, this pattern of increased expression was also positively correlated with tumour stage, lymph node metastasis status, and clinical stage. Conclusion This study identified twenty-seven non-redundant, differentially expressed miRNAs associated with OC. These signatures include a number of novel miRNAs as well as those that have been previously reported in either oral or other cancers. However, miR-7703 is a previously uncharacterised miRNA with the potential to be a significant biomarker for the diagnosis of OC.

XRCC1 (rs25487) polymorphism is associated with severe oral mucositis and poor treatment response after radiotherapy for oropharyngeal carcinoma Abstract Aim To investigate the association of Single Nucleotide Polymorphisms of DNA repair genes and patient-specific clinical characteristics with the risk of developing severe acute radiotoxicities and treatment response in Oropharyngeal Carcinoma. Methods 179 cases of Oropharyngeal Carcinoma treated with 2-D radical radiotherapy were evaluated for acute radiotoxicity end-points viz; oral mucositis, dermatitis, dysphagia, and xerostomia; and the resultant requirement of nasogastric feeding tube, significant (> 10%) weight loss during treatment and treatment break(s). Eleven Single Nucleotide Polymorphisms of DNA repair genes were analyzed using Polymerase Chain Reaction and Restriction Fragment Length Polymorphism and correlated with the severity of these radiotoxicities (Common Toxicity Criteria for Adverse Events v4.0 grading) and the treatment response. Clinical parameters like age, Karnofsky Performance Status, smoking and tobacco chewing, etc. were also analysed in relation to the above. Results Homozygous AA genotype of XRCC1 (rs25487) (p = 0.024*, OR 2.629, 95% CI 1.136–6.087), Karnofsky Performance Status < 80 (p = 0.050*, OR 2.723, CI 1.000–7.418) and history of tobacco chewing (p = 0.030*, OR 2.615, 95% CI 1.099–6.222) were independent predictive factors for increased risk of severe (≥ grade 3) mucositis. Also, the presence of Homozygous AA genotype of XRCC1(rs25487) was significantly associated with poor response to radiotherapy in these patients (p = 0.014, OR 2.235, 95% CI 1.074–5.744). Conclusion Our findings illustrate that patients with Homozygous AA genotype of XRCC1 (rs25487) and certain clinical characteristics are likely to develop severe acute mucositis after radiotherapy for Oropharyngeal Carcinoma and the presence of this polymorphism is also associated with poor response to treatment.

Challenges in multi-unit reconstruction: a framework perspective Abstract Background Locally advanced or recurrent head and neck cancer can present both oncologic and reconstructive challenges. There are no current guidelines for reconstruction of multi-unit defects, yet reconstructive goals should serve the purpose of providing a safe healing environment for both adjuvant therapy and functional rehabilitation. In light of a younger head and neck cancer population, reconstructive methods aimed at preserving form and function over a long survivorship period are optimal. Methods The review of the literature regarding use of single or double free flaps, with or without locoregional reconstructive options, and new techniques for multi-unit defects is described. Results Managing complex defects with multiple units involves determining a framework of critical, optimal, and optional elements for each reconstruction with consideration of the medical tolerance of the patient and long-term functional rehabilitation. Conclusion Multi-unit reconstruction should involve distinction of critical, optimal, and optional aspects to provide a safe healing environment for both adjuvant therapy and functional rehabilitation fit for long-term survivorship.

Small molecule inhibition of matrix metalloproteinases as a potential therapeutic for metastatic activity in squamous cell carcinoma Abstract Purpose One strategy for treating cancer is to prevent metastatic spread. Matrix metalloproteinase are considered potential targets for cancer therapy because of their role in degrading the extracellular matrix and fostering tumor progression. In some cancer models, the small molecule 1,2,3,4,6-Penta-O-galloyl-β-d-glucose (PGG) exhibited inhibitory properties against matrix metalloproteinase (MMP) related metastatic activity. This study explored whether PPG may limit the potential for metastatic spread in oral squamous cell carcinoma. Materials and methods This study used Cal-27 cells, a cell line derived from a squamous cell carcinoma line of human tongue origin, and antibodies for MMP-1, -2, -3, -9, -13, MT1-MMP signal transducers and activators of transcription 3 (Stat3), and pStat3. Cells were treated with PGG at different concentrations to evaluate MMP and Stat3 activation. Expansion assays were performed using Matrigel matrixes to measure Cal-27 invasiveness in the presence of PGG. Results PGG decreased the expression of MMP-2, -9 and -13 in the Cal-27 cell line, decreased phosphorylation of Stat3 and reduced gene expression of MMP-2, -9 and -13. As observed in Matrigel expansion assays, PGG limited the invasiveness of Cal-27 cells in a dose-dependent manner. Conclusion PPG is a small molecule inhibitor with the potential to reduce the expression of the matrix metalloproteinases and to limit the invasiveness of the squamous cell carcinoma line, Cal-27. By controlling the expression of molecules responsible for metastasis, PPG may offer a new therapeutic option for treating oral squamous cell carcinoma.

A multi-centre evaluation of 566 cases of ameloblastoma in Nigeria by the African Oral Pathology Research Consortium Abstract Background Ameloblastoma is a locally aggressive odontogenic tumour (OT) that arises from odontogenic epithelium without neoplastic involvement of odontogenic ectomesenchyme. It is the commonest OT in developing countries, especially in Africa, and, hence, a clinically significant lesion among Africans. It has been suggested that the biologic behaviour of ameloblastoma in black Africans is different from the other populations. The high incidence of ameloblastoma in Africans warrants further evidence-based research. Method In this descriptive cross-sectional study, AOPRC employed a multi-centre approach to retrieve archival demographic and clinicopathological data on ameloblastoma from five major tertiary health institutions in South–West and South–South regions of Nigeria. Data were generated using a standardized data extraction format and analysed using Epi-info (version 7.0). Result From the five centres, a total of 566 cases met our study criteria. We observed that there was a slight male preponderance on ameloblastoma among the cases studies. For all types of ameloblastoma, mandibular lesions were found more frequently than maxillary ones. Most patients presented within 1–5 years of onset of jaw swelling (45.94%). There was a statistically significant higher mean duration for unicystic variants as compared to multi-cystic ameloblastoma (p = 0.0215). Overall, we also observed that the plexiform variants were the most frequently occurring and that the acanthomatous variant was significantly more common in females than males (p = 0.01). Conclusion The current study serves as primer and justification for the application of emerging novel molecular techniques to understand the pathobiology and basis for clinic-pathological disparity of ameloblastoma among men of African descent.

Chronic disease comorbidity in patients with oral leukoplakia Abstract Oral leukoplakia represents the most common oral potentially malignant disorder. While a number of risk factors have been identified, its aetiology remains incompletely understood, and prediction of disease progression, stability or regression, a significant challenge. While excision is often the recommended treatment to reduce the risk of malignancy, this is not always possible and ultimately numerous disease and patient characteristics impact on the decision to initiate treatment or recommend surveillance. At present, the coexistence and impact of chronic diseases in oral leukoplakia patients remains largely unexplored, yet has the potential to significantly impact on diagnosis, treatment decisions, treatment outcomes and prognosis. Exploration of comorbid conditions in oral leukoplakia may additionally lead to greater insight of risk factors and disease pathogenesis and potentially offer more opportunities for screening and early disease detection. The aim of this review is to stimulate discussion about the role of chronic diseases comorbidity in oral leukoplakia.

Factors affecting postoperative removal of nasogastric tube and tracheostomy tube in oral cancer: a retrospective analysis of 234 cases Abstract Introduction Prolonged use of nasogastric and tracheostomy tubes in the postoperative period is a major cause of morbidity after surgery for oral cancer and prolongs discharge from hospital. In this study, we sought to determine the variables that predict prolongation of nasogastric and tracheostomy tubes in patients undergoing surgery for squamous cell carcinoma of the oral cavity. Methods Data from 234 patients who underwent surgery for oral squamous cell carcinoma were retrospectively analyzed for patient variables including oral cavity sub-site, T stage, extent of surgical resection, need and type of reconstruction and adjuvant treatment. Results and discussion The sample was composed of 234 patients with a mean age of 53.08 years (range 24–85 years) and 29% were women. Median duration for removal of nasogastric tube and tracheostomy tube after surgery was 15 days (n = 234, range 6–897 days) and 7 days (n = 111, range 2–160 days), respectively. Performance of reconstructive procedures (15 vs 9 days, p = 0.003) was the only significant factor affecting nasogastric tube removal. Tracheostomy tube removal was affected by age and tongue as the primary site (19 vs 7 days, p = 0.009). Delay in removal of tracheostomy tube and nasogastric tube delayed discharge of the patients from hospital (12 mean days, range 1–35 days). Conclusion Use of flaps for reconstruction impedes oral feeding in postoperative period, while delayed decannulation is seen in older patients and in patients operated for carcinoma of the tongue. Delay in decannulation and nasogastric tube removal prolonged the hospital stay of the patients.

Mouth Cancer Control Program in the State of Pernambuco, Brazil Abstract Purpose Oral cancer persists as a public health problem. Thus, mechanisms that ensure active involvement of the population must be created. Methods Within this context, the Mouth Cancer Control Program of the University of Pernambuco (UPE) has been updating and training professionals in the prevention, and differential and early diagnosis of oral cancer since 1998 by performing educational, preventive, and diagnostic activities without interruptions. CAAE: 0201.0.097.000-08. Results From January 2002 to January 2017, 1400 students from UPE and 300 students from other educational institutions participated in the development of the activities. A total of 8600 professionals were trained in 63 cities in Pernambuco and 59,600 individuals participated in the educational/preventive activities designed to improve self-care, prevention, and the early detection of oral cancer. A total of 2984 individuals were examined during the training. Among the oral lesions identified and investigated by biopsy, 33% were potentially malignant lesions and 12% were malignant lesions (cancer). Conclusions Health education is an excellent tool for the popularization and diffusion of technical–scientific knowledge, demystifying the disease and bringing its description closer to the population, thus permitting the identification of risk factors and the search for prevention and early detection. Brazil still faces some challenges, but education and guaranteed access to and greater effectiveness of health services will provide better conditions for the prevention, early detection, and reduction of disabilities and death since oral cancer can be prevented and cured when diagnosed at an early stage.