Computed tomography/magnetic resonance imaging for mandibular boundary invasion of oral squamous cell carcinoma assessment.

BACKGROUND: The range of mandibular invasion by a tumour needs to be determined accurately to minimize unnecessary damage to the mandible. This study aimed to compare tumour boundary lines on computed tomography/magnetic resonance (CT/MR) images with those from pathological findings during the preoperative assessment of mandibular invasion by oral squamous cell carcinoma (OSCC). By comparing the methods, the potential of CT/MR for this application could be further elucidated. METHODS: Eight patients with OSCC were imaged with CT/MR, mandibular specimens were collected, and the material site was measured. Haematoxylin-eosin staining was used for histopathological assessment. The presence and boundaries of bone invasion were evaluated. The CT/MR and histopathological boundaries of bone invasion were delineated and merged to compare and calculate the deviation of CT/MR and histopathological boundaries using the Fréchet distance. RESULTS: The mean Fréchet distance between the CT and pathological tumour boundaries was 2.69 mm (standard error 0.46 mm), with a minimum of 1.18 mm, maximum of 3.64 mm, median of 3.10 mm, and 95% confidence interval of 1.40-3.97 mm. The mean Fréchet distance between the tumour boundaries on the MR and pathological images was 3.07 mm (standard error 0.56 mm), with a minimum of 1.53 mm, maximum of 4.74 mm, median of 2.90 mm, and 95% confidence interval of 1.53-4.61 mm. CONCLUSIONS: CT/MR imaging can provide an effective preoperative assessment of mandibular invasion of OSCC. Pathology images can be positioned on CT/MR scans with the help of computer software to improve the accuracy of the findings. The introduction of the Fréchet distance to compare tumour boundary lines is conducive to computer image diagnosis of tumour invasion of jaw boundaries.

Paradigm Change for Intraoperative Surgical Margin Assessment for Oral Squamous Cell Carcinoma.

OBJECTIVE: Achieving clear surgical margins is one of the primary surgical goals in treating oral squamous cell carcinoma (OSCC) and thus aiming to improve overall and disease-specific survival. Therefore, we developed the Goal-Oriented Assessment for Intraoperative Margin ('GAIM') protocol, a novel intraoperative approach for margin assessment, and present here our 5-year experience and outcomes. METHODS: 'GAIM' is a 7-step procedure comprising systematic ruler-aided resection of labeled tumor-bed margins, frozen section (FS) co-produced by both pathologists and operating surgeons, and immediate extension of resection according to FS findings. Data from all patients operated using the 'GAIM' protocol at a single tertiary center between 2018 to 2022 were analyzed, including margin status on FS and final pathology (FP) records, recurrence, and mortality. RESULTS: A total of 196 patients were included, 56.6% (n = 111) stages I-II, and 43.4% (n = 85) stages III-IV. Using the 'GAIM' protocol, we achieved an overall 94.4% of clean and revised clean surgical margins. Patients with a 2-year and longer follow-up (n = 141) had local recurrence in 3.5% when both FS and final margins were clean, 8.1% when FP margins were clean, and 16.7% with close/positive final margins. CONCLUSIONS: The proposed 'GAIM' protocol is a novel, effective, reproducible, and safe approach for margin evaluation that can be systematically applied. It can increase the rate of final clean surgical margins and potentially improve patients' outcomes. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:1725-1732, 2024.

Assessment of brush biopsy findings and salivary LDH levels in oral mucosal lesions of tobacco users.

Introduction: The oral brush cytology is an alternative method developed to improve the efficacy of conventional cytology in oral potentially malignant disorder (OPMD), and salivary lactate dehydrogenase (LDH) which is a cytoplasmic enzyme has been widely used as a marker for diagnosing various diseases. The purpose of the study is to evaluate the brush biopsy findings and salivary LDH levels for the early diagnosis of premalignant and malignant lesions of the oral cavity. Materials and Methods: Patients with deleterious habits including tobacco-related lesions such as leukoplakia, tobacco pouch keratosis, and oral cancer were included in the study. For each patient, saliva sample was collected, brush biopsy was done and smears were prepared. Collected saliva samples were analysed for salivary LDH levels and prepared smears were analysed for dysplastic changes and statistical analysis was performed. Results: Out of 80 samples, 30 were leukoplakia, 45 were tobacco pouch keratosis and 5 were oral cancer, and 13 samples showed positive dysplastic changes, 26 samples showed atypical dysplastic changes and 41 samples showed no signs of dysplastic changes and concluded as negative. On comparing the results of brush biopsy findings and salivary LDH levels, the mean salivary LDH value for positive dysplasia was elevated and the P value was statistically significant (P value: 0.00). Conclusion: Brush biopsy showed good potential in detecting premalignant lesions and salivary LDH levels showed a marked increase which can be used as a diagnostic biomarker and serve as a potent diagnostic aid for early detection of malignancy.

Qualitative Assessment of Collagen and Elastic Fibers in Oral Submucous Fibrosis (OSMF), OSMF with Dysplasia and Oral Squamous Cell Carcinoma Arising from OSMF: A Histochemical Study.

BACKGROUND: Oral submucous fibrosis (OSMF) is a habit related potentially malignant disorder seen mainly in South Asian people. The malignancy arising from OSMF has been regarded as low grade with better outcome. The present study was orchestrated to histochemically analyze collagen and elastic fibres in OSMF without dysplasia, OSMF with dysplasia and OSMF turning malignant. MATERIALS AND METHODS: 100 cases (80 cases and 20 healthy controls) were included after obtaining clearance from ethical committee. All cases were subjected to Van Gieson staining for collagen and a novel simple method for elastic fibres (Orcein staining). Data were analyzed using SPSS software. RESULTS: Controls showed haphazard arrangement of collagen and elastic fibres. The collagen bundles were parallelly arranged in OSMF without dysplasia and OSMF with dysplasia; the collagen was however haphazard in cases of OSMF turning malignant. As with collagen, elastic fibres were also haphazardly arranged in the control group; in contrast, the elastic fibres were predominantly arranged in a criss-cross pattern in the other study groups. The difference in orientation and density among the groups was statistically significant. CONCLUSION: With advancement of stage there is increased collagenization of OSMF, as the condition acquires dysplastic changes and turns malignant, microenvironment alters resulting in increased activity of collagenases. However, the arrangement of more resistant elastic fibres depicts the better outcome, once OSMF shows malignant transformation, limiting locoregional and distant spread.

Contribution of FDG-PET in the diagnostic assessment of cervical lymph node metastasis in Oral Cavity Squamous Cell Carcinoma (OCSCC).

INTRODUCTION: The main objective of this study was to evaluate the contribution of FDG-PET in the diagnostic assessment of cervical lymph node metastasis in Oral Cavity Squamous Cell Carcinoma (OCSCC) and to advance a diagnostic threshold value for SUVmax in carcinomatous cervical lymph node. METHODS: 47 patients with OCSCC and suspicious cervical lymph node involvement (cN+) on FDG-PET were included in this retrospective study. The primary outcome was cervical lymph node SUVmax based on histological cervical metastatic disease (« gold standard ¼). RESULTS: Among the 77 cervical lymph nodes considered suspicious on patients' FDG-PET, 50 were really metastatic on histological examination. The lymph node SUVmax with metastatic involvement on histological examination was 4.6 ± 3.9 [2.6 - 23.7] versus 3.6 ± 1.2 [2 - 7.3] without carcinomatous involvement (p = 0.004). The lymph node size was not statistically significant according to metastatic disease (p = 0.28). DISCUSSION: A cervical lymph node SUVmax value of less than 2.6 on FDG-PET would suggest non-metastatic lymph node involvement. Supra Omohyoid Neck Dissection (SOHND) could therefore be performed in OCSCC when the SUVmax of the cervical lymph node is below this value in order to reduce the surgical morbidity of dissection of the lower internal jugular chain (Level IV).

Margin Assessment Methods in Oral Cavity Squamous Cell Carcinoma and Recurrence: Tumor Bed vs Resection Specimen Sampling.

Importance: Positive margins and margin clearance are risk factors for recurrence in oral cavity squamous cell carcinoma (OCSCC), and these features are used to guide decisions regarding adjuvant radiation treatment. However, the prognostic value of intraoperative tumor bed vs resection specimen sampling is not well defined. Objective: To determine the prognostic implications of intraoperative margin assessment methods (tumor bed vs resection specimen sampling) with recurrence among patients who undergo surgical resection for OCSCC. Design, Setting, and Participants: This was a retrospective study of patients who had undergone surgical resection of OCSCC between January 1, 2000, and December 31, 2021, at a tertiary-level academic institution. Patients were grouped by margin assessment method (tumor bed [defect] or resection specimen sampling). Of 223 patients with OCSCC, 109 patients had localized tumors (pT1-T2, cN0), 154 had advanced tumors, and 40 were included in both cohorts. Disease recurrence after surgery was estimated by the cumulative incidence method and compared between cohorts using hazard ratios (HRs). Data analyses were performed from January 5, 2023, to April 30, 2023. Main Outcome and Measures: Recurrence-free survival (RFS). Results: The study population comprised 223 patients (mean [SD] age, 62.7 [12.0] years; 88 (39.5%) female and 200 [90.0%] White individuals) of whom 158 (70.9%) had defect-driven and 65 (29.1%) had specimen-driven margin sampling. Among the 109 patients with localized cancer, intraoperative positive margins were found in 5 of 67 (7.5%) vs 8 of 42 (19.0%) for defect- vs specimen-driven sampling, respectively. Final positive margins were 3.0% for defect- (2 of 67) and 2.4% for specimen-driven (1 of 42) margin assessment. Among the 154 patients with advanced cancer, intraoperative positive margins were found in 29 of 114 (25.4%) vs 13 of 40 (32.5%) for defect- and specimen-driven margins, respectively. Final positive margins were higher in the defect-driven group (9 of 114 [7.9%] vs 1 of 40 [2.5%]). When stratified by margin assessment method, the 3-year rates of local recurrence (9.7% vs 5.1%; HR, 1.37; 95% CI, 0.51-3.66), regional recurrence (11.0% vs 10.4%; HR, 0.85; 95% CI, 0.37-1.94), and distant recurrence (6.4% vs 5.0%; HR, 1.10; 95% CI, 0.36-3.35) were not different for defect- vs specimen-driven sampling cohorts, respectively. The 3-year rate of any recurrence was 18.9% in the defect- and 15.2% in the specimen-driven cohort (HR, 0.93; 95% CI, 0.48-1.81). There were no differences in cumulative incidence of disease recurrence when comparing defect- vs specimen-driven cases. Conclusions and Relevance: The findings of this retrospective cohort study indicate that margin assessment methods using either defect- or specimen-driven sampling did not demonstrate a clear association with the risk of recurrence after OCSCC resection. Specimen-driven sampling may be associated with reduced surgical margin positivity rates, which often necessitate concurrent chemotherapy with adjuvant radiation therapy.

Individualized risk assessment of distant metastases in oral cavity carcinoma: a validated predictive-score model.

BACKGROUND: We aimed to develop and validate a risk-scoring system for distant metastases (DMs) in oral cavity carcinoma (OCC). METHODS: Patients with OCC who were treated at 4 tertiary cancer institutions with curative surgery with or without postoperative radiation/chemoradiation therapy were randomly assigned to discovery or validation cohorts (3:2 ratio). Cases were staged on the basis of tumor, node, and metastasis staging according to the eighth edition of the American Joint Committee on Cancer/Union for International Cancer Control guidelines. Predictors of DMs on multivariable analysis in the discovery cohort were used to develop a risk-score model and classify patients into risk groups. The utility of the risk classification was evaluated in the validation cohort. RESULTS: Overall, 2749 patients were analyzed. Predictors (risk score coefficient) of DMs in the discovery cohort were the following: pathological stage (p)T3-4 (0.4), pN+ (N1: 0.8; N2: 1.0; N3: 1.5), histologic grade (G) 3 (G3, 0.7), and lymphovascular invasion (0.4). The DM risk groups were defined by the sum of the following risk score coefficients: high (>1.7), intermediate (0.7-1.7), and standard risk (<0.7). The 5-year DM rates (high/intermediate/standard risk groups) were 30%/15%/4% in the discovery cohort (C-index = 0.79) and 35%/16%/5% in the validation cohort, respectively (C-index = 0.77; both P < .001). In the whole cohort, this predictive model showed excellent discriminative ability in predicting DMs without locoregional failure (29%/11%/1%), later (>2 year) DMs (11%/4%/2%), and DMs in patients treated with surgery (20%/12%/5%), postoperative radiation therapy (34%/17%/4%), and postoperative chemoradiation therapy (39%/18%/7%) (all P < .001). The 5-year overall survival rates in the overall cohort were 25%/51%/67% (P < .001). CONCLUSIONS: Patients at higher risk for DMs were identified by use of a predictive-score model for DMs that included pT3-4, pN1/2/3, G3, and lymphovascular invasion. Identified patients may be evaluated for individualized risk-adaptive treatment escalation and/or surveillance strategies.

Clinical assessment of a low-cost, hand-held, smartphone-attached intraoral imaging probe for 5-aminolevulinic acid photodynamic therapy monitoring and guidance.

Significance: India has one of the highest rates of oral squamous cell carcinoma (OSCC) in the world, with an incidence of 15 per 100,000 and more than 70,000 deaths per year. The problem is exacerbated by a lack of medical infrastructure and routine screening, especially in rural areas. New technologies for oral cancer detection and timely treatment at the point of care are urgently needed. Aim: Our study aimed to use a hand-held smartphone-coupled intraoral imaging device, previously investigated for autofluorescence (auto-FL) diagnostics adapted here for treatment guidance and monitoring photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence (FL). Approach: A total of 12 patients with 14 buccal mucosal lesions having moderately/well-differentiated micro-invasive OSCC lesions (<2 cm diameter and <5 mm depth) were systemically (in oral solution) administered three doses of 20 mg/kg ALA (total 60 mg/kg). Lesion site PpIX and auto-FL were imaged using the multichannel FL and polarized white-light oral cancer imaging probe before/after ALA administration and after light delivery (fractionated, total 100 J/cm2 of 635 nm red LED light). Results: The handheld device was conducive for access to lesion site images in the oral cavity. Segmentation of ratiometric images in which PpIX FL is mapped relative to auto-FL enabled improved demarcation of lesion boundaries relative to PpIX alone. A relative FL (R-value) threshold of 1.4 was found to segment lesion site PpIX production among the patients with mild to severe dysplasia malignancy. The segmented lesion size is well correlated with ultrasound findings. Lesions for which R-value was >1.65 at the time of treatment were associated with successful outcomes. Conclusion: These results indicate the utility of a low-cost, handheld intraoral imaging probe for image-guided PDT and treatment monitoring while also laying the groundwork for an integrated approach, combining cancer screening and treatment with the same hardware.

Isolation, Culture and Morphological Assessment of Primary Cell Lines from Human Primary Oral Squamous Cell Carcinoma Using Explant Technique.

BACKGROUND: Due to many uses of cell culture in cell biology, biotechnology, and medical research, this technique has evolved into a widely used and accepted methodology. The isolation of primary cells from primary cancer tissue is a crucial step in cell culture technology since it offers a trustworthy source for studying the biology, morphology, and molecular evaluation of cancer cells, just like in the oral cavity tissue of patients. Therefore, the technique used for the isolation, culture, and evaluation of these cells is crucial. AIM: The aim of the present study is to isolate and culture the cells from human primary Oral Squamous Cell Carcinoma [OSCC] tissue and evaluate them for morphological variations using an explant method. MATERIALS AND METHODS: The patients with OSCC who were undergoing surgery provided the tissue samples. An explant technique was used to achieve the isolation of cells from tissue samples. Following that, the cells were maintained, subcultured, and stored in accordance with the standard American Type Culture Collection [ATCC] protocol. Routine Hematoxylin & Eosin and crystal violet stains were used. These cells were morphologically studied, and the results were assessed for further studies. RESULTS: We were able to successfully isolate and culture cells from 4 different tissue samples using the explant method. Morphological analysis revealed that one tissue had a significantly distinct presentation of epithelial and stromal cells, whereas the other three tissues had only minor morphological differences predominantly stromal cells. Two tissues were discarded after showing contamination. CONCLUSION: Tissue culture should be done very meticulously specially when oral cavity tissue is used as it is house for millions of microorganisms. The technique must also be thoroughly followed and adjusted accordingly. Using common, inexpensive stains like Hematoxylin and Eosin and crystal violet, which are of great help for examining the morphology of cells routinely.

The Clinical Utility and Cost of Routine Staging Exam under Anesthesia for Oral Cavity Squamous Cell Carcinoma.

INTRODUCTION: The standard complete evaluation of patients with head and neck squamous cell carcinoma (HNSCC) has included a staging exam under anesthesia (EUA) since the 1970s. The EUA for all sites of HNSCC has historically consisted of panendoscopy for the purpose of diagnostic biopsy, accurate staging of primary disease, and identification of second primary tumors. However, due to the accessibility of the oral cavity, the sole purpose of EUA for tumors of this site is to identify second primary tumors. Since the EUA became the gold standard for evaluation of HNSCC, there have been significant advancements in less invasive technologies such as CT, PET-CT, MRI, and fiberoptic examination. In this study, we sought to determine the value to patient care and cost-effectiveness of EUA in patients with oral cavity squamous cell carcinoma (OCSCC). METHODS: A retrospective chart review identified 77 patients who underwent EUA for OCSCC. RESULTS: The most common subsites were the oral tongue and floor of mouth (59.7% and 24.7% respectively). All underwent direct laryngoscopy, 94.8% underwent esophagoscopy, and 20.8% underwent flexible transnasal examination in clinic prior to EUA. For 90.9% of patients, the EUA did not change initial T-staging based on clinical examination and imaging. The remaining 9.1% of patients were upstaged after EUA, however this change did not impact the treatment plan. Second primary tumors were identified in 3.9% of patients, all were found in either the oral cavity or oropharynx, and were also identified with clinical examination or imaging. Analysis of patient charges determined an average cost of $8,022.93 per patient under the current paradigm involving EUA, however with a new algorithm eliminating mandatory EUA average cost decreases to $1,448.44. CONCLUSION: Formal EUA has historically been the gold standard for all HNSCC tumors. However, when performed for cases of oral cavity carcinoma, it is safe and cost effective to limit its use to select clinical scenarios.

Surgical outcomes of T4b oral cancers: assessment of prognostic factors and a need to re-evaluate the current staging system.

T4b oral cancer is a broad umbrella term for all advanced oral cancers, the prognosis of which varies drastically for disease of the same stage, according to the extent of the masticator space involvement. This was a retrospective observational study including all consecutive T4b oral squamous cell carcinoma patients treated surgically between January 2015 and January 2016 and followed up until January 2020. The disease was classified as upper disease or lower disease based on the anatomical location in relation to an imaginary plane passing through the base of the retromolar trigone. The prime objective was to evaluate overall survival and prognostic factors affecting overall survival. The projected 5-year overall and disease-free survival rates were 40.7% and 35.6%, respectively. The assessment of prognostic factors revealed that lower disease (lower anatomical subsites), bone invasion, and lymph nodal spread significantly affected survival. Patients with disease in an upper anatomical location without bone and nodal involvement can achieve fairly good survival (projected 5-year overall survival of 64.2%) when compared to the other subsets of patients. We propose a re-evaluation of the current staging system based on the prognostic features, so that all patients are not considered under a single stage, since their survival differs significantly.

Ultrasonography in the Assessment of Tumors of the Cheek: Water Mouth Distension Technique.

PURPOSE: To describe a new B-mode ultrasound examination technique to assess cheek tumors. MATERIALS AND METHODS: 30 cheek oral cavity lesions of different histological types (11 benign and 19 malignant) from 23 patients (11 women and 12 men, 7-82 years old, mean age of 49.5 years) were analyzed. Transcutaneous oral B-mode ultrasound (5-12 MHz transducer) was carried out in two stages. Initially it was performed conventionally with an empty mouth. Next, the patient was asked to keep their oral cavity filled with water (like when using a mouthwash) during imaging for the new test examination technique. The anatomical layers of this region and the characteristics of the tumors were evaluated. Lesions were classified as ill defined, partially defined, or defined. Conventional findings were compared to those of the new technique using the Wilcoxon signed-rank test. Ultrasound results were compared to histological findings analyzed by an independent team. RESULTS: The conventional empty mouth technique was able to confidently define lesion extension in only 6 of the 30 lesions, while the water-filled mouth technique was able to confidently define lesion extension in 29 of the 30 lesions (p<0.00001). CONCLUSION: We present a novel technique that dramatically improves ultrasound staging of cheek oral cavity tumors. In addition to the increase in ultrasound accuracy, this technique does not require any special equipment or extra cost, is very well tolerated by patients, and thus should be considered in the evaluation of every patient undergoing transcutaneous cheek ultrasound for oral cavity lesion characterization.

Serum lactate dehydrogenase in the prognostic assessment of patients with oral squamous cell carcinoma.

Background: Lactate dehydrogenase (LDH) has been proven to be a diagnostic marker in oral squamous cell carcinoma (OSCC). However, the prognostic value of serum LDH in OSCC is yet to be explored. The purpose of this study is to correlate the level of serum LDH with the degree of OSCC and to evaluate the role of serum LDH as a prognostic marker in OSCC. Methods: The investigators designed and implemented a prospective cohort study composed of patients with OSCC (n = 66) sub-grouped as follows: 2A-well-differentiated (n = 22), 2B-moderately differentiated (n = 22), 2C-poorly differentiated OSCC (n = 22), and normal healthy controls (n = 40). The primary outcome variable was the serum LDH measured at baseline (pre-treatment) and 2 and 12 months post-treatment in OSCC patients. The statistical analysis was performed using the student t-test and analysis of variance, and the P value was set at 0.05. Results: The habit of alcohol consumption alone as a single habit was found only in males (17.5%) (P = 0.3343), whereas betel quid chewing was more common among females (P = 0.0182). A significant difference was observed in the mean serum LDH between OSCC subjects (pre-treatment) (831.56 ± 93.43 IU/L) and controls (188.82 ± 25.53 IU/L), P < 0.00001. The baseline serum LDH was significantly higher in subgroup 2C (933.41 ± 46.1969 IU/L) than in the 2A (742.59 ± 46.5676 IU/L) and 2B (818.68 ± 58.1643 IU/L) subgroups (P = 0). There was a significant decline in the serum LDH within 2 months after treatment, and a further decrement was observed during a 12-month follow-up among the survivors of all three subgroups; P < 0.00001. Conclusion: Serum LDH can play a dual role as a reliable indicator of the degree of OSCC for decision-making in treatment modalities and as a prognostic marker of response to therapy.

HIF - 1α as a marker of risk assessment for malignant transformation in oral submucous fibrosis: An immunohistochemical study.

Background: Oral submucous fibrosis (OSMF) is a potentially malignant disorder associated with habit of chewing betel quid containing arecanut. Morphological features of OSMF especially fibrosis suggests a possibility of the hypoxic environment in diseased tissues. The adaptation of cells to hypoxia appears to be mediated via hypoxia inducible factor-1α (HIF-1α) which is also said to be associated with malignant transformation of epithelial cells in various other carcinomas like prostate and cervical carcinoma. Therefore, the main objective of this study was to investigate the role of HIF-1α in progression and malignant transformation of OSMF. Materials and Methods: The study group consisted of histo-pathologically diagnosed 30 cases of oral submucous fibrosis and 10 cases of OSCC were taken as control. The immunohistochemistry was carried out on neutral buffered formalin-fixed paraffin-embedded tissue sections by using the monoclonal antibody of HIF-1α. Statistical analysis was done using SPSS software version 2.0. Results: A gradual and significant rise in the expression of HIF-1α was observed in various grades of OSMF and OSCC cases. HIF 1α expression was increased in cases showing hylanization and constricted blood vessels. A cut off value of 39.6% of HIF-1α positive cells was determined statistically to categorize the cases into high risk and low risk group for malignant transformation. Conclusion: Overexpression of HIF-1α may contribute to the progression and malignant transformation of OSMF. Cases expressing more than 40% of HIF-1α positive cells are at a greater risk for malignant transformation.

Comparison of narrow band and fluorescence molecular imaging to improve intraoperative tumour margin assessment in oral cancer surgery.

OBJECTIVE: New techniques have emerged to aid in preventing inadequate margins in oral squamous cell carcinoma (OSCC) surgery, but studies comparing different techniques are lacking. Here, we compared narrow band imaging (NBI) with fluorescence molecular imaging (FMI), to study which intraoperative technique best assesses the mucosal tumour margins. MATERIALS AND METHODS: NBI was performed in vivo and borders were marked with three sutures. For FMI, patients received 75 mg of unlabelled cetuximab followed by 15 mg cetuximab-800CW intravenously-two days prior to surgery. The FMI borders were defined on the excised specimen. The NBI borders were correlated with the FMI outline and histopathology. RESULTS: Sixteen patients were included, resulting in 31 NBI and 30 FMI measurements. The mucosal border was delineated within 1 mm of the tumour border in 4/31 (13 %) of NBI and in 16/30 (53 %) FMI cases (p = 0.0008), and within 5 mm in 23/31 (74 %) of NBI and in 29/30 (97 %) of FMI cases (p = 0.0048). The median distance between the tumour border and the imaging border was significantly greater for NBI (3.2 mm, range -6.1 to 12.8 mm) than for FMI (0.9 mm, range -3.0 to 7.4 mm; p = 0.028). Submucosal extension and previous irradiation reduced NBI accuracy. CONCLUSION: Ex vivo FMI performed more accurately than in vivo NBI in mucosal margin assessment, mainly because NBI cannot detect submucosal extension. NBI adequately identified the mucosal margin especially in early-stage and not previously irradiated tumours, and may therefore be preferable in these tumours for practical and cost-related reasons.

Assessment of the association of OCT3/4 with GLUT1 and CD105 in oral squamous cell carcinoma using dual immunohistochemistry.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the most common cancer affecting the oral and maxillofacial region. This study aimed to investigate the role of cancer stem cells (CSCs) in angiogenesis and hypoxic response in OSCC. METHODS: This retrospective observational study evaluated 56 cases of OSCC using dual immunohistochemistry. Octamer-binding transcription factor 3/4 (OCT3/4) marker was used to evaluate CSC activity. Glucose transporter 1 (GLUT1) marker was used to evaluate the hypoxic response and angiogenesis, while endoglin (CD105) was used to evaluate the late stage of angiogenesis and blood vessel formation. RESULTS: Co-expression of OCT3/4 and GLUT1 was noted in 11 of 12 patients with grade III OSCC. However, we did not observe co-expression of these markers in 13 of 22 patients with grade I OSCC. Although we observed a significant correlation between co-expression of GLUT1 and OCT3/4 and tumor grade, there was no significant correlation between co-expression of OCT3/4 and CD105 and different grades of OSCC. CONCLUSIONS: CSCs could play important roles in the initial stages of hypoxic response and angiogenesis. Our result reported that in higher grades of OSCC, GLUT1 as a first response to hypoxic situations might be a result of CSCs. Further studies are required to discover other biomarkers, their roles, and associated pathways of CSCs in OSCC.

Oral brush biopsy using liquid-based cytology is a reliable tool for oral cancer screening: A cost-utility analysis: Oral brush biopsy for oral cancer screening.

BACKGROUND: This study aimed to assess the diagnostic utility and associated cost of oral liquid-based brush cytology (OLBC) in the diagnosis of oral cancer and oral potentially malignant disorders (OPMDs). METHODS: A total of 284 patients with oral mucosal lesions were included. OLBC samples were collected from all patients immediately before undergoing surgical biopsies. A liquid-based cytology slide was prepared from each OLBC sample for cytological evaluation using the modified 2014 Bethesda cytology system. The results and the cost were compared with the histopathological outcomes. RESULTS: The level of agreement between the two approaches was very good (weighted kappa = 0.824). The accuracy of OLBC in differentiating between the different diagnostic groups was 91.69%, whereas the associated sensitivity and specificity were 79.23% and 94.81%, respectively. The estimated cost of each OLBC sample was at least 26% less than the cost of a single biopsy and more than 42% less in cases of multiple biopsied lesions. CONCLUSIONS: The proposed modifications of the Bethesda system can be adopted as a standardized system for oral cytological assessment. Our findings support OLBC as a reliable adjunct to surgical biopsy in the diagnosis of OPMDs. This tool has potential for oral cancer-finding and surveillance programs.

Comparison of CT, MRI, and F-18 FDG PET/CT for initial N-staging of oral squamous cell carcinoma: a cost-effectiveness analysis.

BACKGROUND AND PURPOSE: Treatment of oral squamous cell carcinoma (OSCC) is based on clinical exam, biopsy, and a precise imaging-based TNM-evaluation. A high sensitivity and specificity for magnetic resonance imaging (MRI) and F-18 FDG PET/CT are reported for N-staging. Nevertheless, staging of oral squamous cell carcinoma is most often based on computed tomography (CT) scans. This study aims to evaluate cost-effectiveness of MRI and PET/CT compared to standard of care imaging in initial staging of OSCC within the US Healthcare System. METHODS: A decision model was constructed using quality-adjusted life years (QALYs) and overall costs of different imaging strategies including a CT of the head, neck, and the thorax, MRI of the neck with CT of the thorax, and whole body F-18 FDG PET/CT using Markov transition simulations for different disease states. Input parameters were derived from literature and willingness to pay (WTP) was set to US $100,000/QALY. Deterministic sensitivity analysis of diagnostic parameters and costs was performed. Monte Carlo modeling was used for probabilistic sensitivity analysis. RESULTS: In the base-case scenario, total costs were at US $239,628 for CT, US $240,001 for MRI, and US $239,131 for F-18 FDG PET/CT whereas the model yielded an effectiveness of 5.29 QALYs for CT, 5.30 QALYs for MRI, and 5.32 QALYs for F-18 FDG PET/CT respectively. F-18 FDG PET/CT was the most cost-effective strategy over MRI as well as CT, and MRI was the cost-effective strategy over CT. Deterministic and probabilistic sensitivity analysis showed high robustness of the model with incremental cost effectiveness ratio remaining below US $100,000/QALY for a wide range of variability of input parameters. CONCLUSION: F-18 FDG PET/CT is the most cost-effective strategy in the initial N-staging of OSCC when compared to MRI and CT. Despite less routine use, both whole body PET/CT and MRI are cost-effective modalities in the N-staging of OSCC. Based on these findings, the implementation of PET/CT for initial staging could be suggested to help reduce costs while increasing effectiveness in OSCC.

Risk assessment of malignant transformation of oral leukoplakia in patients with previous oral squamous cell carcinoma.

The aim of this study was to identify the risk factors associated with developing oral squamous cell carcinoma (OSCC) from surgically excised oral leukoplakia (OL) in patients with previous oral cavity cancer. Clinicopathological data of 84 patients who were treated for OL between July 2002 and July 2020 and who had previously received treatment for OSCC were reviewed retrospectively. The follow-up time ranged from 0.69 to 17.99 years (mean 6.78 ± 4.25 years). The overall cumulative malignant transformation rate was 25% and the annual transformation rate was 5.73%. Kaplan-Meier survival analysis and the log-rank test showed that Candida infection (P = 0.010) was a risk factor associated with malignant transformation. In the multivariate Cox regression analysis, tongue and floor of the mouth as the location of the leukoplakia (P = 0.039), multifocal lesions of OL (P = 0.047), and Candida infection (P = 0.018) were the three independent prognostic factors related to the development of OSCC from the treated OL. A cautious approach to OL of the tongue with Candida infection or multifocal disease in this group of patients would be appropriate.

Sentinel lymph node biopsy versus selective neck dissection in patients with early oral squamous cell carcinoma: A cost analysis.

OBJECTIVE: Sentinel lymph node biopsy (SLNB) has been proved to be as efficient as selective neck dissection (SND) for the treatment of occult metastases in T1-T2cN0 oral squamous cell carcinoma (OSCC). The aim of our study was to assess and compare the cost of these two surgical procedures. PATIENTS AND METHODS: This retrospective cost analysis includes consecutive patients treated between 2012 and 2017 in two French hospitals either by SLNB or SND. Hospital cost (hospital stay for initial surgery and re-hospitalizations over a period of 60 days after the initial surgery), the length of hospital stay for the initial surgery and the perioperative management were described and compared between the two techniques. The propensity score regression adjustment method was used to address selection bias. RESULTS: Ninety-four patients underwent SLNB procedure and seventy-seven patients underwent SND. The length of hospital stay for initial surgery was lower in SLNB group: 5.8 days (SD: 3.8) versus 9.2 days (SD: 5) in the SND group. Hospital costs were lower in SLNB group: €7 489 (standard deviation: €3 691) versus €8 886 (standard deviation: €4 381) but this difference was not significant after propensity score regression adjustment. The rate of complication, the delay of full oral feeding and postoperative drainage were lower in SLNB group. CONCLUSION: SLNB in T1-T2cN0 OSCC is less invasive than SND with fewer complications, a shorter length of hospital stay and favorable perioperative management. This study shows that this technique could be also less expensive than SND.