Genetic determinants of periosteum-mediated craniofacial bone regeneration: a systematic review.

BACKGROUND: Periosteum-mediated bone regeneration (PMBR) is a recognized method for mandibular reconstruction. Despite its unpredictable nature and the limited degree to which it is understood, it does not share the concerns of developmental changes to donor and recipient tissues that other treatment options do. The definitive role of the periosteum in bone regeneration in any mammal remains largely unexplored. The purpose of this study was to identify the genetic determinants of PMBR in mammals through a systematic review. METHODS: Our search methodology was designed in accordance with the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) guidelines. We conducted a quality assessment of each publication, and evaluated the differences in gene expression between days 7 and 15. RESULTS: A total of four studies satisfied the inclusion criteria. The subjects and tissues examined in these studies were Wistar rat calvaria in two studies, mini-pigs in one study, and calves and mice in one study. Three out of the four studies achieved the necessary quality score of ≥ 3. Gene expression analysis showed increased activity of genes responsible for angiogenesis, cytokine activities, and immune-inflammatory responses on day 7. Additionally, genes related to skeletal development and signaling pathways were upregulated on day 15. Conclusions: The results suggest that skeletal morphogenesis is regulated by genes associated with skeletal development, and the gene expression patterns of PMBR may be characterized by specific pathways.

Whole genome DNA methylation and mutational profiles identify novel changes in proliferative verrucous leukoplakia.

OBJECTIVE: Proliferative verrucous leukoplakia (PVL) is a rare form of oral leukoplakia with a relatively high transformation rate resulting in oral squamous cell carcinoma (OSCC). Molecular analysis of PVL at the genome level is limited and has only identified molecular similarities between PVL and OSCC. However, the clinical profile of PVL suggests that molecular differences may be more important. STUDY DESIGN: Whole exome sequencing of 5 PVL-associated OSCC (PVL-OSCC) and paired blood samples was used to identify somatic mutations common to the tumors. Whole methylome analysis of samples from 4 PVL-associated OSCC and 3 OSCC of non-PVL origin samples was conducted to explore differential methylation. RESULTS: In contrast to conventional OSCC, PVL-associated OSCC showed infrequent TP53 mutation and altered spectra of PIK3CA and NOTCH1 mutations. Unsupervised hierarchical clustering identified 63 probes that discriminated between PVL-associated OSCC and OSCC of non-PVL origin. Differences in methylation were most significant for divalent metal ion transport, particularly calcium movement. CONCLUSIONS: Specific differences in mutation and methylation profiles between PVL-derived OSCC and OSCC of non-PVL origin suggest differences in their transformation pathways. Further studies of early PVL lesions may identify markers of transformation that are also applicable to more common oral premalignant disorders such as oral epithelial dysplasia.

SARS-CoV-2 saliva testing using RT-PCR: a systematic review.

OBJECTIVES: There remain challenges in using SARS-CoV-2 RNA diagnostic assays in the respiratory tract in a pandemic. More so certain countries such as Hong Kong have already included saliva as part of their mass-testing protocol. The aim of this study was to conduct a systematic review on the alternate use of saliva as a SARS-CoV-2 RNA testing specimen in the context of mass screening with reverse transcription polymerase chain reaction. METHODS: Our search methodology was modeled after the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist, and the risk of bias of the selected studies was qualitatively assessed. The percentage individual positive and percentage agreement of both index (saliva) and reference (nasopharyngeal swab), in preference to specificity and sensitivity, were estimated using Kappa statistics. RESULTS: A total of 44 studies met the inclusion criteria. The average percentage positive saliva cases was 72.7% (95% confidence interval), which was lower but not substantially different from the percentage positive NPS of 78.7% (95% confidence interval), and there was an average overall agreement of 89.7% (95% confidence interval). CONCLUSION: Although the literature supports nasopharyngeal swab as a superior testing specimen, an alternative clinical specimen in saliva may offer potential benefits such that a potentially reduced accuracy may be tolerated, especially in low socioeconomic regions.

Salivary Cortisol as a Stress Monitor During Third Molar Surgery.

Background: Procedures in oral surgery, especially surgical extraction of the impacted mandibular third molar is often considered anxiety-producing and stressful. This study evaluated the effect of oral sedation (5 mg diazepam) on the physiological stress level in subjects that underwent surgical extraction of the mandibular third molar by measuring the change in salivary cortisol concentration. Subjects and methods: 204 salivary samples were collected from 102 subjects between 9.00 am and 12.00 pm to standardise the diurnal variations of cortisol secretion. Saliva samples were collected 45 min before and 15 min after surgical extraction from each subject in either group. The samples were stored in the freezer (- 20 °C) until analysis was done in the laboratory using salivary cortisol ELISA kits (DiaMetra S.r.l., Eagle Biosciences, Italy), and the cortisol concentration was measured with a microplate reader. Results: There was a statistically significant change (p = <0.001 between the pre-surgical extraction salivary cortisol concentration of all subjects with a median of 7 ng/ml and post-surgical extraction salivary cortisol concentration of both the study and the control groups with a median of 17 ng/ml and 15 ng/ml, respectively. Only 11.8% of subjects in the study group had a reduction in post-surgical salivary cortisol concentration, while in the control group, 3.9% of subjects had a reduction in post-surgical salivary cortisol concentration. There was no statistically significant difference between the two groups (p = 0.135). Conclusions: Hence, oral sedation has no significant impact on physiological stress during the surgical extraction of the mandibular third molar. However, salivary cortisol concentration can adequately reflect the stress induced by surgical extraction in subjects and its usefulness as a biomarker in stress research. Furthermore, the type of disimpaction of mandibular third molar affects salivary cortisol concentration, with distoangular disimpaction having the highest cortisol concentration and more stressful to subjects when compared to other types of disimpaction.

Genetic Polymorphism of Head and Neck Cancers in African Populations: A Systematic Review.

OBJECTIVE: Head and neck cancers are mostly composed of head and neck squamous cell carcinoma (HNSCC). The incidence and mortality of HNSCC are higher in countries with emerging health care systems, particularly Africa. Given that they are more genetically diverse, characterization of polymorphism in African HNSCC may result in the identification of distinct molecular targets as compared with the known HNSCC candidate genes. This study objective is to review the current evidence of genetic data on HNSCC among African populations as well as to demonstrate any distinctions as compared with known candidate genes and to appraise any research gaps. DATA SOURCES: Publications that interrogated susceptible gene polymorphisms to African-based populations with cancer were reviewed for this study. REVIEW METHODS: Our search methodology was modeled after the Cochrane systematic review protocol, which included MeSH terms and keywords related to cancer, polymorphisms, and African countries. RESULTS: Seven articles studying 2 HNSCC cancer types in 3 of 54 African countries met the inclusion criteria. Thirteen polymorphisms from 10 genes were screened (NOS3, CYP1A1, CYP2D6, NAT1, NAT2, NQO1, IL-10, IL-12, IL-8, COX2). All articles were screened for polymorphisms based on a polymerase chain reaction-based technique. All polymorphs suggested association to HNSCC, with 10 of 13 polymorphs demonstrating a statistically significant association. CONCLUSION: Studies on known HNSCC candidate genes should be undertaken in Africa, particularly among sub-Saharan Africans. Importantly, these studies should be large scale with multiple HNC sites and with use of high-throughput methods.

Genetic variants association with cancers in African-based populations: A systematic review.

BACKGROUND: Cancer is the single leading cause of human deaths worldwide. The highest incidence and mortality are recorded from Africa. The last two decades have witnessed extensive research which has led to emerging prognosis and new gene therapy technologies. Cancer therapy in Africa is derived with little input from African population data. While a number of cancer studies on African populations have suggested varied susceptible variant, no comprehensive review of these studies has been undertaken to assess their coverage across Africa. METHODS: This study aimed to undertake a review of all molecular genetic studies that interrogated the genetic variants of cancers in African-based populations. Our search methodology was modelled after the Cochrane systematic review protocol, which included MeSH terms and related keywords. RESULTS: Ninety-seven articles studying 13 cancer types, were reviewed. 91 articles screened for polymorphisms using PCR-based techniques while three used SNP array, two used whole exome sequencing and one used pyrosequencing. North African (NA) countries undertook 51/97 (53 %) studies on 12/13 (92 %) cancer types while the Sub Saharan Africa (SSA) countries undertook 46/97 (47 %) studies on 7/13 (54 %) cancer types. Twelve out of these thirteen cancer type studies suggested susceptibility to their target polymorphism (p > 0.05). No study replicated or validated variants detected. CONCLUSION: Research on genetic determinants in African-based population cancer offers translational benefits. We recommended large scale, multi-national genome association studies using high throughput techniques. SSA needs to receive more attention due to the shortage of this type of study and data in the region.

Non-vascularised iliac crest bone graft for immediate reconstruction of lateral mandibular defect.

INTRODUCTION: Mandibular defect reconstruction is extremely important to achieving an improved quality of life of patients as this bony defect influences facial harmony and aesthetics. Reconstruction of mandibular defects at our centre comprises use of reconstruction plate, non-vascularised anterior iliac crest graft and vascularised fibula flap. Despite the large mandibular defect recorded in our developing environment, non-vascularised iliac crest graft continues to play a role in its exclusive use for lateral mandibular defects. The aim of this study was to analyse the role, complications and outcomes of the use of non-vascularised iliac crest graft for mandibular reconstruction in a free flap-enabled centre. PATIENTS AND METHOD: This was a retrospective case cohort from study institution's records of mandibular reconstruction following mandibular surgery for benign tumours. Eligibility for study inclusion comprised case cohort with head and neck diseases requiring mandibular surgery and reconstruction with either reconstruction plate, non-vascularised iliac crest graft or vascularised fibula flap. RESULTS: A total of 18 subjects underwent iliac crest grafting. Of the 18 subjects with iliac crest graft, 7 (39 %) were females while 11 (61 %) were males. Ten of the 18 subjects with iliac crest grafting were diagnosed with ameloblastomas. Six (33.3 %) subjects had class H (Jewer's classification) mandibular defect. The average graft length was 5.4 cm and height was 2.3 cm. Three cases experienced graft site complications of which two grafts were lost. All 18 cases experienced good to acceptable clinical outcomes. Predictors of graft outcome were not statistically significant. CONCLUSION: Despite our small sample size, it is suggestible that non-vascularised iliac crest graft be considered for lateral mandibular defect reconstruction, considering the reduced graft failure rate and satisfactory clinical outcomes from this study.

Spontaneous Regeneration of the Mandible: An Institutional Audit of Regenerated Bone and Osteocompetent Periosteum.

PURPOSE: Childhood mandibular lesions are frequently benign; this allows for a conservative surgical approach to their management. Two of the most common approaches for reconstruction of acquired mandibular defects in adolescents are vascularized and nonvascularized osseous flaps or grafts. A third, less commonly used treatment option often used in developing parts of the world that some Western centers are considering as part of their treatment algorithm is spontaneous bone regeneration. This study reports on the authors' experiences with spontaneous bone formation of the resected young mandible. It also attempts to quantify any relation between spontaneous bone regeneration and an aging osteocompetent periosteum. PATIENTS AND METHODS: This was a retrospective study based on consecutive data collated from records of the oral and maxillofacial surgery departments from 2 tertiary institutions. Eligible patients were no older than 18 years and had benign mandibular neoplasms. The surgical procedure was mandibulectomy with subperiosteal dissection and intermaxillary fixation. Regenerated bone evaluation was by clinical examination and periodic panoramic radiographs. RESULTS: Sixteen consecutive cases with mandibular lesions were seen at the 2 institutions, 8 of which met the inclusion criteria. The average age was 10.75 years. The predominant pathology was unicystic ameloblastoma. All cases exhibited spontaneous bone regeneration, with 2 cases exhibiting "incomplete" bone regeneration. CONCLUSION: Immediate reconstruction can be delayed to allow for spontaneous bone regeneration of defects in young patients. In the absence of regeneration, secondary reconstruction can be considered. Although the literature reports more young patients with bone regeneration than adults, increasing age during childhood and adolescence might not necessarily indicate a decrease in periosteal bone-regenerating potential.

Clinical Outcome of Parotidectomy with Reconstruction: Experience of a Regional Head and Neck Cancer Unit.

BACKGROUND: Salivary gland pathologies represent a histologically diverse group of benign and malignant neoplasms. Currently, World Health Organization recognizes 13 benign and 24 malignant variants of all salivary gland neoplasms. Surgery continues to remain the main-stay for treatment of parotid gland neoplasms. The aim of this study was to document our experiences of the patients treated for parotid tumors and find out if any compelling variable predicted the relative clinical outcomes. MATERIALS AND METHODS: This was a retrospective study, from records of parotidectomies performed at the operating theatre by the head and neck cancer division of the study institution between 2010 and 2013. Eligibility for study inclusion included cases with benign or malignant parotid neoplasms requiring surgical management with or without adjunct radiotherapy. The predictors of postoperative complications, overall survival (OS), and disease-free survival (DFS) were analyzed. RESULTS: A total of 20 patients underwent parotidectomy. The mean age was 42 years. Tumors were located on the left parotid in 13 cases (65%) and the right parotid in 7 cases (35%). The surgical procedures comprised 16 superficial parotidectomies, 1 total parotidectomy, and 3 radical parotidectomy (inclusive of facial nerve sacrifice) and 2 neck dissections levels II-V. The reconstructive procedures were 2 facial nerve branch cable grafts, 1 end-to-end facial-facial nerve branch anastomoses, and 2 facial re-animation surgeries (temporalis muscle suspensions). A total of five cases (33.3%) had postoperative complications. 2 variables (length of surgery and neck dissection) were found to have an impact on postoperative complications that were statistically significant. Additionally, length of surgery was a significant predictor on the 2 years OS and DFS. CONCLUSION: The result of this study showed good clinical outcome, especially in the benign cases. The comprehensive clinical outcome of the malignant cases could not be objectively assessed, as the OS and DFS were 50% at 2-years follow-up. It is our submission that a larger sample size is utilized in subsequent studies and quality of life evaluation is included in the methodology.

Regional Myocutaneous Flaps for Head and Neck Reconstruction: Experience of a Head and Neck Cancer Unit.

BACKGROUND: Pectoralis major myocutaneous pedicle flap and other regional myocutaneous pedicle flaps (RMF), despite the superiority shown by free flaps, have remained relevant in the reconstruction of major head and neck oncologic defects. It has continued to find relevance as the preferred reconstruction of choice in some general head and neck reconstructive applications. While its role has been defined in developed environment, the same cannot be said for developing environment. The aim thus, was to review our experiences with RMFs in head and neck reconstructions, with a view to evaluating the indications and outcomes in a limited opportunity environment with some free flaps expertise. MATERIALS AND METHODS: This was a retrospective cohort study from records of RMF cases performed for head and neck reconstruction, at the study institution. Eligibility for study inclusion comprised case cohorts with advanced head and neck diseases requiring ablative surgery and reconstruction with pectoralis major flaps and other RMFs. RESULTS: A total of 17 cases were treated with RMFs. 10 were pectoralis major flaps while 7 were other RMFs. The main indications were failed free flaps and financial constraints. No regional pedicle flap failure was recorded; however, complication rate was 35.5% (6/17). CONCLUSION: Pectoralis major flaps and other RMFs were very reliable option for head and neck reconstruction. Free flap failure and financial constraints were the main indications for RMF reconstruction indications in head and neck reconstruction in a developing environment with some free flap expertise.

Quality of life of patients with segmental mandibular resection and immediate reconstruction with plates.

PURPOSE: The surgical management of some head-and-neck pathology affects a patient's form and fundamental function and, eventually, the quality of the individual's daily life. Restoring mandibular continuity after resection will improve form, function, and eventually, quality of life (QOL). The aim of this study was to evaluate the effect of our limited restoration with immediate plate reconstruction after segmental mandibular resection on the QOL of patients. PATIENTS AND METHODS: A total of 13 patients were included in the study. They were treated for benign but aggressive mandibular pathology. Treatment included segmental mandibular resection with immediate plate reconstruction. A modified University of Washington QOL questionnaire was used to assess QOL. Data on clinico-dermographic variables were also collated. A total of 17 surgeries were undertaken, with 16 implants placed. RESULTS: Patients with smaller tumors seemed to have better QOL scores than those with larger tumors. The overall QOL scores for younger patients seemed better than those of older patients. Spontaneous regeneration of the mandible, occurring in our younger patients, was an added reason for this seemingly better QOL. CONCLUSIONS: Patients with segmental mandibulectomy and spontaneous mandibular regeneration tended to have a better QOL than those with no reconstruction and immediate plate reconstruction.

Management of mandibular fractures in a developing country: a review of 314 cases from two urban centers in Nigeria.

BACKGROUND: This study was designed to establish the current demographic and treatment patterns of mandibular fractures in two urban centers (Lagos University Teaching Hospital, Lagos, and National Hospital, Abuja) in Nigeria. METHODS: All cases of mandibular fractures diagnosed and treated at the Department of Oral and Maxillofacial Surgery, Lagos University Teaching Hospital, Lagos (1998-2007) and Department of Oral and Maxillofacial Surgery, National Hospital, Abuja, Nigeria (2001-2007) were reviewed. Data collected included age, sex, etiology of fracture, anatomic site of fracture, associated maxillofacial fracture, types of treatment, and postoperative complications. RESULTS: The highest incidence of mandibular fractures (49.3%) occurred in the age group 21-30 years and the lowest in the age group 0-10 years, with male preponderance in nearly all age groups. Road traffic crashes (RTC) were the leading cause (67.5%), followed by assault (18.8%), and gunshot. Of the RTC cases, 85 (40%) were sustained from motorcycle-related crashes. The commonest site of fracture was the body of the mandible (n = 137), followed by the angle (n = 114). The majority (83.1%) were treated by closed reduction using intermaxillary fixation, 13.1% by open reduction and internal fixation, and 3.8% had conservative treatment. CONCLUSIONS: Mandibular fractures are commonest during the third decade of life and in men, with almost half of the cases due to of road traffic crashes. RTC was the leading cause of mandibular fractures in all age groups. Motorcycle-related mandibular fractures seem to be increasing in Nigeria. There is a need to enforce legislation designed to prevent RTC to reduce maxillofacial fractures in Nigeria.