Non-invasive visual tools for diagnosis of oral cancer and dysplasia: a systematic review

Background: Gold standard for the diagnosis of oral dysplasia (OD) oral squamous cell carcinoma (OSCC) and malignant lesions is the histological examination. Several adjunctive diagnostic techniques have been proposed in order to increase the sensitivity (SE) and specificity (SP) of conventional oral examination and to improve the diagnostic first level accuracy. The aim of this study is to perform a systematic review on non-invasive tools for diagnosis of OD and early OSCC. Material and Methods: Medline, Scopus, Web of Knowledge databases were searched, using as entry terms “oral dysplasia AND diagnosis” / ”oral cancer AND diagnosis”. Data extracted from each study included number of lesions evaluated, histopathological diagnosis, SE, SP, positive and negative predictive values (PPV and NPV), diagnostic accuracy (DA) and the main conclusions. Results: After title and abstract scanning of 11.080 records, we selected 35 articles for full text evaluation. Most evaluated tools were autofluorescence (AF), chemiluminescence (CL), toluidine blu (TL) and chemiluminescence associated with toluidine blue (CLTB). Conclusions: There is a great inhomogeneity of the reported values and there is no significant evidence of superiority of one tool over the other. Further clinical trials with a higher level of evidence are necessary in order to assess the real usefulness visual diagnostic tools

An Auto-Fluorescence guided surgical approach performed with Er:YAG laser and Nd:YAG Low Level Laser Therapy for Medication-Related Osteonecrosis of the Jaw

Medication-Related Osteonecrosis of the Jaw (MRONJ) therapy remains an unresolved problem. The proposed conservative and surgical treatment regimens are associated to contradictory success rates. Surgical approach with Er:YAG laser is associated to significant better results compared to medical treatment and traditional surgical approaches. Objective: To describe a new surgical approach that couples the advantages of the Er:YAG laser and the usefulness of the AF in highlighting surgical margins. One of the difficulties encountered during surgical removal of a MRONJ is the precise individuation of necrotic bone margins. Case Report: A case of Stage III mandibular osteonecrosis treated with a new surgical approach is presented. The aim is to describe an auto-fluorescence (AF) guided surgical approach performed with Er:YAG laser and Nd:YAG Low Level Laser Therapy (LLLT). After one month of follow-up, the complete mucosal healing was evident and symptoms was unobserved. Such a technique allowed a highly accurate and minimally invasive approach through the selective ablation of the non-/hypofluorescent areas. Conclusion: Taking into account the advantages of laser therapy and the possible effectiveness of the AF in highlighting surgical margins, this approach would probably achieve excellent outcomes.DOI: 10.14693/jdi.v22i2.48

An Auto-Fluorescence guided surgical approach performed with Er:YAG laser and Nd:YAG Low Level Laser Therapy for Medication-Related Osteonecrosis of the Jaw

Medication-Related Osteonecrosis of the Jaw (MRONJ) therapy remains an unresolved problem. The proposed conservative and surgical treatment regimens are associated to contradictory success rates. Surgical approach with Er:YAG laser is associated to significant better results compared to medical treatment and traditional surgical approaches. Objective: To describe a new surgical approach that couples the advantages of the Er:YAG laser and the usefulness of the AF in highlighting surgical margins. One of the difficulties encountered during surgical removal of a MRONJ is the precise individuation of necrotic bone margins. Case Report: A case of Stage III mandibular osteonecrosis treated with a new surgical approach is presented. The aim is to describe an auto-fluorescence (AF) guided surgical approach performed with Er:YAG laser and Nd:YAG Low Level Laser Therapy (LLLT). After one month of follow-up, the complete mucosal healing was evident and symptoms was unobserved. Such a technique allowed a highly accurate and minimally invasive approach through the selective ablation of the non-/hypofluorescent areas. Conclusion: Taking into account the advantages of laser therapy and the possible effectiveness of the AF in highlighting surgical margins, this approach would probably achieve excellent outcomes.DOI: 10.14693/jdi.v22i2.48

Mandibular metastasis from carcinoma of the bladder: Report of a case and literature review

Metastases represent about 1% of all malignant tumors of the oral region. Only 12 cases of metastases to the jawbones and 3 to the oral soft tissues from a carcinoma of the bladder are reported in the English literature. Here we report a case of an 86 year-old man with a metastasis to the anterior region of the lower jaw from a transitional cell carcinoma of the bladder treated 5 years before, all-together with a literature review

Pain and Health-Related Quality of Life After Oral Soft Tissue Surgical Interventions: The Advantages of Nd:Yag Laser

The new technology such as the neodymium-doped yttrium aluminum garnet (Nd:YAG) laser has been used for oral soft tissue surgery. Previous study shown that laser surgery resulted in lower morbidity and complication rates. Objective: This study aims to evaluate the differences in the post-operative course associated to the use of Nd:YAG laser and to cold blade after oral soft tissue surgery. Methods: One-hundred and eighteen comparable surgical interventions were evaluated. Group 1 (G1) included 77 interventions performed with Nd:YAG laser; group 2 (G2) 41 with cold blade. Acute post-operative pain was evaluated with visual analogue scale (VAS), numeric rating scale (NRS) and verbal rating scale-6 (VRS-6) on the same day of surgery, and at 1, 3 and 7 days after surgery.The HRQoL was evaluated on day 7 using a 0-45 score range questionnaire. Data were analyzed using the software STATA 12 (StataCorp LP, College Station, Texas, USA). Results: No statistically significant differences could be highlighted in VAS and NRS scores. The VRS-6 scores resulted statistically significant at days 1 and 3. At day 1, 47.14% of patients in G1 and 13.16% in G2 had no pain; at day 3, 62.86% in G1 and 21.05% in G2 had no pain. The HRQoL in G1 was statistically higher than G2. Conclusion: The better HRQoL and the lower post-operative pain observed in laser-treated patients may be associated to the possible bio-modulating effect of the laser

Odontogenic myxofibroma: a concise review of the literature with emphasis on the surgical approach

Purpose : The aim of this work is to report a review of the literature concerning epidemiology, clinical and radiographic features as well as treatment of odontogenic myxofibroma (MF). Methods : The PubMed database was searched using the following keywords: “odontogenic myxofibroma”, “odontogenic fibromyxoma”, “myxofibroma of the jaw” and “fibromyxoma of the jaw”. Results : Fifteen articles reporting the experience with 24 patients were identified. Male/female ratio was 1:1.4 and the average age was 29.5 years. The most frequent location was the mandible. In 66.7% of the cases the radiographic appearance was a multilocular radiolucency. Swelling was observed in 13 patients (92.86%), varying degrees of pain in 5 (35.71%) and paresthesia in only one patient (7.14%). Six out of 24 patients (26.09%) were treated with radical surgery and 17 (73.91%) with a conservative approach. In two out of 21 cases (9.52%) a recurrence was reported. Conclusions : MF is an extremely rare tumor and no agreement exists on the causes of its development. According to the present review, the choice of treatment should depend on variables such as localization, presence of a primary or of a recurrent lesion, age, general medical conditions and aesthetic needs of the patien

Self-healing CD30- T-clonal proliferation of the tongue: report of an extremely rare case

The etiology of traumatic ulcerative granulomas with stromal eosinophilia (TUGSE) is not clear, traumatic irritation having advocated as the most likely cause. TUGSEs are typically self-limiting slow-healing lesions of the oral mucosa with unclear pathogenesis, commonly manifesting as a rapidly developing, long-lasting ulcer

Pain and Health-Related Quality of Life After Oral Soft Tissue Surgical Interventions: The Advantages of Nd:Yag Laser

The new technology such as the neodymium-doped yttrium aluminum garnet (Nd:YAG) laser has been used for oral soft tissue surgery. Previous study shown that laser surgery resulted in lower morbidity and complication rates. Objective: This study aims to evaluate the differences in the post-operative course associated to the use of Nd:YAG laser and to cold blade after oral soft tissue surgery. Methods: One-hundred and eighteen comparable surgical interventions were evaluated. Group 1 (G1) included 77 interventions performed with Nd:YAG laser; group 2 (G2) 41 with cold blade. Acute post-operative pain was evaluated with visual analogue scale (VAS), numeric rating scale (NRS) and verbal rating scale-6 (VRS-6) on the same day of surgery, and at 1, 3 and 7 days after surgery.The HRQoL was evaluated on day 7 using a 0-45 score range questionnaire. Data were analyzed using the software STATA 12 (StataCorp LP, College Station, Texas, USA). Results: No statistically significant differences could be highlighted in VAS and NRS scores. The VRS-6 scores resulted statistically significant at days 1 and 3. At day 1, 47.14% of patients in G1 and 13.16% in G2 had no pain; at day 3, 62.86% in G1 and 21.05% in G2 had no pain. The HRQoL in G1 was statistically higher than G2. Conclusion: The better HRQoL and the lower post-operative pain observed in laser-treated patients may be associated to the possible bio-modulating effect of the laser

Quantificazione spettrofotometrica dell'autofluorescenza come potenziale strumento diagnostico per lesioni maligne della cute e della mucosa orale

L'autofluorescenza (AF) è definita come l'emissione di fluorescenza osservata quando determinate molecole sono eccitate da raggi UV o luce visibile di lunghezze d'onda adeguate. Quando una molecola viene illuminata ad una lunghezza d'onda di eccitazione, assorbirà questa energia e verrà attivata dal suo stato fondamentale a quello eccitato. La molecola (fluoroforo) può quindi rilassarsi dallo stato eccitato a fondamentale generando energia sotto forma di fluorescenza, a lunghezze d'onda di emissione più lunghe di quella di eccitazione. I fluorofori endogeni sono molecole ampiamente distribuite in cellule e tessuti, come proteine ​​contenenti aminoacidi aromatici, flavine e lipopigmenti. I principali fluorofori della cute sana si trovano nell'epitelio (ad es. cheratina, nicotinamide adenine dinucleotide o NADH e flavin adenine dinucleotide o FAD) e nella sottomucosa (ad es. collagene ed elastina). Queste molecole, quando irradiate tra le lunghezze d'onda da 375 a 440 nm, mostrano fluorescenza nell'intervallo spettrale del verde. Il non-melanoma skin cancer (NMSC) è il tumore maligno più comune al mondo. Lo sviluppo dei NMSC è accompagnato da cambiamenti istopatologici nell'epidermide come perdita di maturazione cellulare, alterazione della produzione di cheratina, ispessimento generale dello strato epiteliale e alterazioni biochimiche (riduzione del NADH). I NMSC sono anche accompagnati da cambiamenti istopatologici nello stroma e nella sottomucosa sottostanti, tra cui la neovascolarizzazione e la distruzione del legame crociato di collagene da parte delle proteasi. Queste alterazioni portano ad una generale riduzione dell’AF dovuta all'alterazione della distribuzione dei fluorocromi e in particolare al NADH e al collagene. Negli ultimi due decenni, gli studi riguardanti ll’AF cellulare e tissutale hanno avuto un notevole aumento. Sono stati condotti studi sull’AF sia in vitro che in vivo, per lo studio dei tessuti normali e per la discriminazione tra tessuti normali e lesioni neoplastiche di mucosa orale, cute, esofago, colon, polmone, bronchi, cervello e vescica. I metodi utilizzati sono sia il direct visual fluorescence examination (DVFE) sia lo spettrofotometria. In particolare, il DVFE è stato ampiamente utilizzato per studi clinici sulla mucosa orale. Per quanto riguarda l’AF della cute, questa è stata studiata più frequentemente usando lo spettrofotometria. Il principio è la scansione e l'analisi della luce emessa dalla cute dopo l'esposizione a una fonte di luce attivante. Tuttavia, ad oggi non sono emersi metodi che fossero traducibili nella pratica clinica. L'obiettivo principale di questo studio è quello di analizzare la correlazione tra la misurazione spettrale dell’AF cutanea e le caratteristiche istopatologiche della cute maligna e pre-maligna nel campo dei NMSC. Dopo la rimozione chirurgica, verrà eseguita una valutazione ex vivo dell’AF. Il campione verrà irradiato con una sonda che emette una luce nello spettro blu (lunghezza d'onda 400-440 nm) e la fluorescenza emessa dal tessuto verrà misurata mediante uno spettrofotometro in modalità spot standardizzata. Eventuali modifiche rilevate verranno riportate sul campione chirurgico con l'applicazione di un repere. Verrà eseguito un esame istopatologico della lesione e eventuali cambiamenti nel pattern di fluorescenza saranno correlati con possibili alterazioni del pattern istopatologico, facendo riferimento ai reperi chirurgici. Le alterazioni delle misure spettrali sono correlate alle alterazioni istopatologiche dei NMSC. La misurazione spettrale può essere un nuovo supporto per la diagnosi precoce dei NMSC, una guida per le biopsie incisionali mirate, uno strumento per la definizione dei margini chirurgici intraoperatori e per il follow-up dei pazienti trattati.Autofluorescence (AF) is defined as the fluorescence emission observed when certain cell molecules are excited by UV or visible light of suitable wavelenghts. When a biologic molecule is illuminated at an excitation wavelength within the absorption spectrum of that molecule, it will absorb this energy and be activated from its ground state to an excited state. The molecule (fluorophore) can then relax back from the excited to the ground state by generating energy in the form of fluorescence, at emission wavelengths, which are longer than that of the excitation wavelength. The most important endogenous fluorophores are molecules widely distributed in cells and tissues, like proteins containing aromatic aminoacids, flavins and lipopigments. The main fluorophores of healthy skin are located in the epithelium (eg. keratin, nicotinamide adenine dinucleotide or NADH and flavin adenine dinucleotide or FAD) and the submucosa (e.g. collagen and elastin). These molecules when irradiated between the wavelengths from 375 and 440 nm, show fluorescence in the green spectral range. Nonmelanoma skin cancer (NMSC) is the most common malignancy worldwide. The developement of NMSC is accompanied by histopathological changes in epidermis such as loss of cellular maturation, alteration in keratin production, overall thickening of the epithelial layer and biochemical alterations (NADH decrease). NMSC is also accompanied by histopathological changes in the underlying stroma and submucosa, including neovascularization and destruction of the collagen cross-link by proteases. These alterations lead to a general decrease in AF due the alteration in distribution of the fluorochromes and in particular to NADH and collagen. In the last two decades, studies concerning cell and tissue AF has had a dramatic increase. AF studies have been performed both in vitro and in vivo, for the study of normal tissue and for the discrimination between normal tissues and neoplastic lesions of oral mucosa, skin, esophagus, colon, lung, bronchi, brain and bladder. The methods used are both direct visual fluorescence examination (DVFE) and spectrophotometry. In particular, DVFE has been widely used for clinical studies on oral mucosa. Regarding AF of the skin, this has been studied more frequently by using spectrophotometry. The principle is scanning and analyzing reflected light from the skin after exposure to an activating light source. AF spectroscopy is a very sensitive technique for quantitative measurements of tissue constituents. However, to date no methods have emerged that can be translated into clinical practice. The primary objective of this study is to investigate the correlation between spectral mesurement of cutaneous AF and the histopathological characteristics of malignant and pre-malignant skin in NMSC. Following surgical removal of the cancer, an ex vivo evaluation of the AF will be performed. The specimen will be irradiated with a probe that emits a light in the blue spectrum (wavelength 400-440 nm) and the fluorescence emitted by the tissue will be measured using a spectrophotometer in a standardized spot modality. Any changes detected will be reported on the surgical specimen with the application of a surgical mark. Histopathological examination of the lesion will be performed and any changes in the fluorescence pattern will be correlated with possible alterations in the histopathological pattern, referring to surgical marks. Alterations in AF spectral measurement correlate with histopathological alterations in NMSC. the spectral measurement can be a new support for the early diagnosis of NMSCs, a guide for the targeted incisional biopsies, a tool for the definition of the intraoperative surgical margins, and for the follow-up of treated patients

Clinical Differences in Autofluorescence Between Viable and Nonvital Bone: A Case Report With Histopathologic Evaluation Performed on Medication-Related Osteonecrosis of the Jaws

Medication-related osteonecrosis of the jaws (MRONJ) is an adverse side effect of several drug therapies, including bisphosphonates (BPs). Osteonecrosis of the jaw specifically related to BP therapy is usually referred to using the acronym BRONJ. However, no consensus has yet been reached regarding the most appropriate management of BRONJ. The greatest success rates have been recorded with surgical removal of necrotic bone. In particular, erbium:yttrium-aluminum-garnet (Er:YAG) laser-assisted surgery has shown significantly better results than conventional surgical approaches. According to a position paper reported by the American Association of Oral and Maxillofacial Surgeons in 2007, the identification of necrotic bone margins during osteonecrosis removal can be very difficult. In 2015, a review of treatment perspectives for MRONJ reported that both surgical debridement and resection cannot be standardized owing to the lack of guidance to define the necrotic margins. Recently, the use of autofluorescence (AF) of the bone as a possible suitable guide to visualize necrotic bone during surgical debridement or resection was proposed. It seems that vital bone could be highlighted by its very strong AF. In contrast, necrotic bone loses AF and, thus, appears much darker. The molecular sources of the phenomenon of AF are the specific amino acids of the collagen molecules that show AF when irradiated by ultraviolet or blue light. The use of AF as an intraoperative diagnostic tool is entirely new in the management of MRONJ, although it has been used for several years in other fields (eg, intervertebral disc surgery). The aim of the present report was to describe a case of mandibular BRONJ treated with a new surgical approach performed with an Er:YAG laser and guided by AF. The histopathologic evaluation of the removed hypofluorescent bone block and hyperfluorescent surrounding bone has also been reported in detail