Concomitant-chemoradiotherapy-associated oral lesions in patients with oral squamous-cell carcinoma

Objective:Oral squamous-cell carcinoma(OSCC)accounts for >90% of oral cancers affecting adults mostly between the fourth to seventh decades of life.The most common OSCC treatment is concomitant chemoradiotherapy(CCRT)having both locoregional and distant control,but CCRT has acute and chronic toxic effects on adjacent normal tissue.This study aimed to determine the side effects of CCRT on the oral mucosa and to characterize the clinicopathology of oral lesions in patients with OSCC.Methods:This descriptive,cross-sectional study was certified by the Ethical Review Committee(UHS/Education/126-12/2728)of the University of Health Sciences,Lahore,Pakistan.OSSC patients(n=81)with various histological subtypes,grades,and stages were recruited,and findings on their oral examination were recorded.These patients received 70,90,and 119 Gy of radiotherapy dosages in combination with the chemotherapy drugs cisplatin and 5-fluorouracil.Data were analyzed using SPSS 20.0.Results:The most common presentation of OSCC was a nonhealing ulcer(63%) involving tongue(55.6%).Clinical findings included mucositis(92.6%)and xerostomia of mild,moderate,and severe degrees in 11.1%,46.9%,and 35.8% cases,respectively.Ulcers(87.7%),palpable lymph nodes(64.2%),limited mouth opening(64.2%)and fistula(40.7%) were also observed.In females,the association of radiotherapy dosage with limited mouth opening,xerostomia,and histological grading was statistically significant(P<0.05).The association of chemotherapy drugs with xerostomia(P=0.003)was also statistically significant.Conclusions:CCRT induced mucositis,xerostomia,and trismus in patients with OSCC.

Angina bullosa hemorrhagica an enigmatic oral disease

Angina bullosa hemorrhagica(ABH) is an enigmatic oral disorder described for the first time by Badham in 1967 to define blisters with a hematic content in the oralcavity and oropharynx unrelated to any hematological, dermatological or systemic disease. The ABH is an uncommon disease of the oral cavity distinctively affecting adults, with the highest incidence over the 5th decade of life. This process is considered nowadays to have a multifactorial etiopathogenesis, where mild oral traumatisms can trigger the blisters in susceptible individuals. Certain association on the onset of the lesion with the chronic use of inhaled steroids and, more controversially, with triggering systemic disorders, such as, diabetes or hypertension has been described. Characteristically, the ABH blisters are acute and are located on the lining mucosa, more frequently on the soft palate. Usually, the lesions are solitary and rupture easily, resulting in a superficial ulceration that heals quickly without scarring. The histopathological analysis shows a subepithelial blister containing blood and direct immunofluorescence on the epithelium is negative. The differential diagnosis should consider all oral vesiculobullous disorders with hematic content, including mucocutaneos, hematological or cystic pathology. The diagnosis of ABH is clearly clinical, although the biopsy might be helpful on atypical or abnormally recurrent cases. The general prognosis of ABH is good and the treatment is symptomatic.

The oncofetal protein IMP3 is an indicator of early recurrence and poor outcome in mucoepidermoid carcinoma of salivary glands

Objective: Mucoepidermoid carcinoma(MEC) is the most common primary malignancy of the salivary glands. Insulin-like growth factor-II m RNA-binding protein-3(IMP3) is an important prognostic factor in some cancers and a tool that differentiates between benign and malignant pancreatic lesions. This study aimed to identify a relationship between the expression of IMP3 and the outcome of salivary gland MEC, as well as to differentiate MEC from pleomorphic adenoma(PA).Methods: Tissue specimens from 70 cases of salivary gland MEC, 40 cases of PA, and 10 cases with normal salivary gland were examined immunohistochemically for IMP3. The association among the expression of IMP3, clinicopathological characteristics and patient's survival was assessed.Results: IMP3 was present in 51.4% of MEC but absent in PA and normal salivary gland tissues. IMP3 expression was associated with age > 60 years, submandibular gland tumors, tumor size > 4 cm, high-grade tumors, lymph node metastasis, involvement of surgical margins, perineural invasion, distant metastasis, advanced TNM stage, tumor relapse, and death(P<0.05). Increased expression of IMP3, tumors of the submandibular gland, and lymph node metastasis were independent prognostic factors of disease-free survival(DFS). In addition, IMP3 was a strong predictor of overall survival(OS) together with distant metastasis and intermediate and high-grade tumors.Conclusions: IMP3 expression is highly important in evaluating the outcome of MEC. IMP3 can be used to differentiate MEC from PA of salivary glands.

Primary Neuroendocrine Carcinoma Combined with Squamous Cell Carcinoma of the Soft Palate: A Case Report and Review of Literature

Background: Neuroendocrine carcinomas (NECs) are rare neoplasms that widely occur in various organs. They are heterogeneous and vary from low to high grade malignant. NEC presenting with a squamous cell carcinoma (SCC) component is referred to as a composite tumor. Thus far, few cases of this composite tumor in the oral cavity have been reported in the literature;thus, the histogenesis remains unclear. ase Presentation: We encountered a rare case of a primary NEC combined with SCC, occurring at the soft palate in a 59-year-old man. A resected specimen of the tumor was composed of two components: NEC and SCC. The NEC area contained small round to oval atypical cells arranged in nests with a glandular-like-pattern, hyperchromatic molded nuclei, a high nuclear-to-cytoplasmic ratio, and a scant eosinophilic cytoplasm. The SCC area was composed of non-keratotic, dysplastic oval to spindle-shaped squamous cells with indistinct cell borders and large nuclei that were hyperchromatic and pleomorphic. Immunohistochemically, the tumor cells of the NEC component were positive for chromagranin A, synaptophysin, CD56, and p16, whereas those of the SCC component were positive for 34βE12, p63, and p16. Conclusion: In consideration of the morphological and immunohistochemical results, the final diagnosis was a primary NEC combined with SCC of the soft palate.

Assessment of the effect of wound closure technique on postoperative sequaele and complications after impacted mandibular third molar extraction

Aims and Objectives: The aim of the study was to compare the effect of complete and partial wound closures on postoperative sequelae and complications after surgical removal of impacted mandibular third molars. Patients and Methods: One hundred and twenty patients who required 121 surgical extractions of mandibular impacted third molars were included in the study. Patients were randomly divided into 2 groups based on wound closure after surgery. In group 1 (complete wound closure, n1 = 60) patients had their extraction sockets completely closed by mucosal flap while in group 2 (partial wound closure, n2 = 60) patients had their extraction sockets partially closed. Data collected included maximum inter-incisal distance (MID) and facial width which were recorded both preoperatively and postoperatively. What also recorded were postoperative pain intensity and postoperative complications. Results: There were 50 (41.7%) males and 70 (58.3%) females (male to female ratio of 1:1.4);age range was 18-40 years and the mean was 26 ± 10 years. The mean ages of patients in both groups showed no significant difference (group 1 = 26.5 ± 7.2;group 2 = 27.1 ± 8.1). The pain was maximal at the first postoperative day review and it gradually reduced in intensity towards the preoperative values for both groups. The pain perceptionsin patients in group 2 were however significantly lower than those of group 1 on days 1 and 3 but not statistically different on day 7. The mean difference in the postoperative and preoperative MID was greatest on the 1st postoperative day and gradually became smaller on the subsequent review days. Comparison of this mean difference between the 2 groups however showed a significant difference in the 2 groups only on day 7. Maximal swelling was noted in both groups on the third postoperative day. A comparison of the mean facial width between the two groups showed no statistically significant difference on all the review days. The postoperative complication rate was 5% in both groups. Conclusions: The results of the study indicate that there was a comparative reduction in postoperative sequelae namely pain and trismus after impacted mandibular third molar surgery when a partial wound closure technique was done. However, there was no significant difference in the postoperative complication rate between the two groups.

Synthetic Three-Dimensional Scaffold for Application in the Regeneration of Bone Tissue

Bone tissue engineering aims to use biodegrade able scaffolds to replace damaged tissue. This scaffold must be gradually degraded and replaced by tissue as similar as possible to the original one. In this work a hybrid porous scaffold containing chitosan, polyvinyl alcohol and bioactive glass was successfully obtained and subsequently characterized by scanning electron microscopy. The scaffold presented satisfactory pore size range and open interconnected pores, which are essential for tissue ingrowth. A cytotoxicity assay showed that this biomaterial allows adequate cell viability, so that it was considered suitable for an in vivo experiment. Promising results were obtained with the implant of the scaffold in an experimental model of a New Zealand rabbit femur bone lesion. Clinical and biochemical parameters measured such as complete blood count, total serum proteins, albumin, alanine aminotransferase and aspartate aminotransferase were similar between animals in the control group at all time periods studied. Histological and histometric studies showed that the scaffold was coated with a cement-like substance, exhibiting many areas of mineralized structures. Very few osteocyte-like cells or lining-like cells were found inside the amorphous mineralized deposit. In vivo results allow us to consider this scaffold as a promising biomaterial to be applied in bone tissue engineering.

Cardiac stem cells: Current knowledge and future prospects

Regenerative medicine is the field concerned with the repair and restoration of the integrity of damaged human tissues as well as whole organs.Since the inception of the field several decades ago,regenerative medicine therapies,namely stem cells,have received significant attention in preclinical studies and clinical trials.Apart from their known potential for differentiation into the various body cells,stem cells enhance the organ's intrinsic regenerative capacity by altering its environment,whether by exogenous injection or introducing their products that modulate endogenous stem cell function and fate for the sake of regeneration.Recently,research in cardiology has highlighted the evidence for the existence of cardiac stem and progenitor cells(CSCs/CPCs).The global burden of cardiovascular diseases’morbidity and mortality has demanded an in-depth understanding of the biology of CSCs/CPCs aiming at improving the outcome for an innovative therapeutic strategy.This review will discuss the nature of each of the CSCs/CPCs,their environment,their interplay with other cells,and their metabolism.In addition,important issues are tackled concerning the potency of CSCs/CPCs in relation to their secretome for mediating the ability to influence other cells.Moreover,the review will throw the light on the clinical trials and the preclinical studies using CSCs/CPCs and combined therapy for cardiac regeneration.Finally,the novel role of nanotechnology in cardiac regeneration will be explored.

<i>RASSF</i>1<i>A</i>Methylation Status and BRAF V600E Immunohistochemical Expression in Odontogenic Lesions

Background: The etiology and pathogenesis of odontogenic lesions remain to be determined. Previous studies have identified epigenetic and genetic alterations that may be relevant to lesions progression and development. Hypermethylation of the Ras association domain family protein 1A (RASSF1A) has been observed in a variety of human cancers. However, the methylation status of RASSF1A in odontogenic lesions remains unknown. Thus, the aim of this study was to investigate the prevalence of RASSFA promoter hypermethylation and v-raf murine sarcoma viral oncogene homolog B V600E mutant (BRAF V600E) expression as well as the correlations between these alterations and clinicopathological features of patients with odontogenic lesions. Methods: We subjected 66 formalin-fixed, paraffin-embedded odontogenic lesions [ameloblastoma (AM), 21;ameloblastic carcinoma (AC), 6;odontogenic keratocyst (OKC), 19;and dentigerous cyst (DC), 20] to methylation-specific polymerase chain reaction to determine RASSF1A hypermethylation and immunohistochemistry to detect BRAF V600E protein expression. Results: We observed RASSF1A hypermethylation in 20% (4/20;methylation could not be detected in one lesion), 100% (6/6), 26.3% (5/19), and 5% (1/20) of AM, AC, OKC, and DC samples, respectively. RASSF1A methylation was significantly more frequently observed in AC relative to AM, OKC, and DC (p < 0.001). Moreover, 85.7% (18/21) and 83.3% (5/6) AM and AC samples, respectively, were BRAF V600E-positive, whereas all OKC and DC sample were BRAF V600E-negative. No correlations of RASSF1A methylation and BRAF V600E expression with clinicopathological features were observed. Conclusions: Concomitant RASSF1A methylation and positive BRAF V600E expression are commonly observed in AC, which may contribute to AC tumorigenesis.

Expression of Yes-associated protein 1 gene and protein in oral squamous cell carcinoma

Background Oral squamous cell carcinoma （OSCC） is one of the most common malignancies in the oral and maxillofacial region. Yes-associated protein 1 （YAP1） has been implicated as a bona fide oncogene in solid tumors. We seek to elucidate the role of YAP1 in OSCC tissue. Methods We identified YAP1 gene and protein overexpression in 30 OSCC patients and 10 normal oral mucosa tissues by immunohistochemistry, Western blotting and reverse transcription polymerase chain reaction （RT-PCR）. Results In the normal oral mucosa by immunohistochemical staining, YAP1 mainly located in both the cytoplasm and nucleus mainly the nuclei of the basal cells. In OSCC, the expression of YAP1 translocated from the nucleus to cytoplasm YAP1 being mainly located in both the cytoplasm and nucleus of the adjacent mucosa. The expression of YAP1 gradual increased in normal oral mucosa, tumor adjacent mucosa and low grade, middle grade, high grade OSCC tissue by Western blotting. Significant difference was found between the expressions of the normal oral mucosa and OSCC tissue （P 〈0.05）. The coincidence was detected between the normal oral mucosa and OSCC tissue by RT-PCR （P 〈0.05）. Conclusions YAP1 is involved in the carcinogenesis and development of OSCC. There is a transformation between nucleus and cytoplasm.

Bioactive 3D-printed chitosan-based scaffolds for personalized craniofacial bone tissue engineering

Regeneration of craniofacial bone defects is a key issue in the bone regeneration field.Hence,novel treatment strategies,such as tissue engineering using porous scaffolds,have been developed.An ideal tissue-engineered scaffold for bone tissue regeneration should possess pores to facilitate nutrients transmission and support repar-ative tissue ingrowth,bioactivity for osteoconduction and osseointegration,and biocompatibility to improve cell attachment,proliferation,and extracellular matrix formation.In the present study,we manufactured chitosan-based hydrogels substituted with alginate with optimized properties by extrusion-based three-dimensional(3D)printing.3D printing of the scaffolds enables the designing and developing of complex architectures for cranio-facial reconstruction using computer-aided design(CAD).Different ratios(2.5,5,and 10%)of hydroxyapatite were added to the hydrogel,printed,and subsequently lyophilized to augment the physical and biological char-acteristics of the scaffolds.Hydroxyapatite incorporation into the chitosan-based scaffolds increased the porosity and pore size of the printed scaffolds.In addition,the presence of hydroxyapatite amplified apatite formation and decreased the size of formed apatite crystals.All the scaffold samples showed biocompatible properties and did not have toxicity toward rat bone marrow mesenchymal stem cells.Furthermore,the scaffolds containing 5%w/w hydroxyapatite exhibited significant growth in cell viability compared to the control.Overall,it is concluded that chitosan-based scaffolds adorned with hydroxyapatite are considerable for regenerating craniofacial bone defects.

Ionic liquid-loaded microcapsules doped into dental resin infiltrants

Resin infiltrants have been effectively applied in dentistry to manage non-cavitated carious lesions in proximal dental surfaces.However,the common formulations are composed of inert methacrylate monomers.In this study,we developed a novel resin infiltrant with microcapsules loaded with an ionic liquid(MC-IL),and analyzed the physical properties and cytotoxicity of the dental resin.First,the ionic liquid 1-n-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide(BMI.NTf2)was synthesized.BMI.NTf2 has previously shown antibacterial activity in a dental resin.Then,MC-IL were synthesized by the deposition of a preformed polymer.The MC-IL were analyzed for particle size and de-agglomeration effect via laser diffraction analysis and shape via scanning electron microscopy(SEM).The infiltrants were formulated,and the MC-IL were incorporated at 2.5%,5%,and 10 wt%.A group without MC-IL was used as a control.The infiltrants were evaluated for ultimate tensile strength(UTS),contact angle,surface free energy(SFE),and cytotoxicity.The MC-IL showed a mean particle size of 1.64(±0.08)μm,shriveled aspect,and a de-agglomeration profile suggestive of nanoparticles’presence in the synthesized powder.There were no differences in UTS among groups(p>0.05).The incorporation of 10 wt%of MC-IL increased the contact angle(p<0.05),while the addition from 5 wt%reduced the SFE in comparison to the control group(p<0.05).The human cell viability was above 90%for all groups(p>0.05).The incorporation of microcapsules as a drug-delivery system for ionic liquids may be a promising strategy to improve dental restorative materials.