Tongue Carcinoma Research Articles

PO-1028 Inter-correlations between various high-risk pathological factors in squamous cell carcinoma tongue

PO-1028 Inter-correlations between various high-risk pathological factors in squamous cell carcinoma tongue

Electrochemotherapy with Mitomycin C Potentiates Apoptosis Death by Inhibiting Autophagy in Squamous Carcinoma Cells.

Simple SummaryInternationally, electrochemotherapy is considered an innovative therapeutic strategy capable of increasing the efficacy of lyophobic drugs in many solid tumors. Our study aimed to verify the potentiating effect of electroporation (EP), in combination with the drug mitomycin C (MMC), in oral and laryngeal cancer cells that exhibited intrinsic drug resistance. Our study showed that EP increased MMC cytotoxicity on both lines compared to single treatment; the mechanism of action was due to EP inhibition of the autophagic process induced by MMC, thus favoring apoptosis. EP plus MMC treatment was also performed on two veterinary patients demonstrating its efficacy, tolerability, and clinical feasibility.We investigated the chemosensitizing effect of electroporation (EP), which, using electrical pulses, permeabilizes cancer cells to drugs. The study involved two human hypopharyngeal and tongue carcinoma cell lines. The surface and intracytoplasmic expression of P-gp were evaluated by flow cytometry, demonstrating that both lines were intrinsically resistant. After establishing the optimal dose of mitomycin C (MMC) to be used, in combination with EP, we showed, by both MTT assay and optical and electron scanning microscopy, the potentiating cytotoxic effect of EP with MMC compared to single treatments. Flow cytometry showed that the cytotoxicity of EP + MMC was due to the induction of apoptosis. In addition to verifying the release of cytochrome C in EP + MMC samples, we performed an expression analysis of caspase-3, caspase-9, Akt, pAkt, HMGB1, LC3I, LC3II, p62, Beclin1, and associated proteins with both apoptotic and autophagic phenomena. Our results were confirmed by two veterinary patients in whom the EP + MMC combination was used to control margins after the resection of corneal squamous carcinoma. In conclusion, we affirmed that the effect for which EP enhances MMC treatment is due to the inhibition of the autophagic process induced by the drug in favor of apoptosis.

Long-term functional outcomes and quality of life after partial glossectomy for T2 squamous cell carcinomas

IntroductionPartial glossectomy and reconstruction strategy for malignant tongue tumors influences speech and swallowing. ObjectiveThe aim of this retrospective study was to evaluate long-term functional outcomes after partial glossectomy for pT2 mobile tongue carcinomas with a maximum dimension between 2 and 3cm. Different reconstruction strategies (with or without pedicled flap) were compared. MethodsTwenty-two patients with at least 12 months followup were included. Clinician-based and self-reported instruments were used to analyze tongue motility, speech intelligibility and articulation, swallowing, and quality of life. ResultsPatients with a higher tongue motility had better articulation and lower dysphagia. Avoiding pedicled flap reconstruction seemed to guarantee lower impairment of speech and swallowing. Worse functional outcomes induced a lower quality of life. ConclusionPartial glossectomy results in tongue motility impairment and consequently alterations of oral functions. Since the type of reconstruction impacts long-term outcomes, it should be adequately planned before surgery.

Curbing the Deregulation of Glycosylation in Tongue Carcinoma Cells with Natural Compounds.

Aberrant glycosylation has been recently considered as a major hallmark of cancer. Furthermore, we have reported that aberrant glycosylation, mainly sialylation and fucosylation, plays a major role in oral cancer progression and metastasis. In the present study, we evaluated the role of tobacco compounds (4-NQO, NNK, Benzopyrene), natural compounds (Curcumin, Butein and Piceatannol) and commonly used chemotherapeutic compound (Cisplatin) on sialylation and fucosylation transcript levels in the tongue cancer cell line (SAS). The SAS cells were treated with the tobacco compounds, natural compounds and Cisplatin after obtaining their IC50 values using MTT assay. After 24 hr treatment of the compounds, RNA was isolated from the cells and converted to cDNA. RT-qPCR was performed for mRNA expression of glycosylation transcripts. The treatment of tobacco compounds on the SAS cells resulted in increased mRNA levels of ST3GAL1, NEU3, FUT5 and FUT6 in a dose-dependent manner. The treatment of Curcumin and Butein resulted in lower mRNA levels of FUT8, whereas dose-dependent higher mRNA levels of FUT3 were also observed after the treatment of Curcumin. SAS cells exhibited a dose-dependent decrease in ST3GAL2, FUT5 and FUT8 mRNA after Piceatannol treatment. Furthermore, Cisplatin treatment on the SAS cells resulted in increased mRNA levels of FUT3 as the concentration increased from 100 μM to 200 μM. While, treatment of Cisplatin resulted in decreased mRNA levels of ST3GAL2, ST3GAL3, FUT5 and FUT8 in a dose-dependent manner. All together, the data revealed Piceatannol as a potent synergistic for Cisplatin to target the altered glycosylation for better treatment management of tongue carcinoma. The study provides a normal approach of targeting aberrant glycosylation with natural compounds, which may open the possibility of newer therapeutic strategies using natural compounds alone or in combination with other conventional therapies.

Epidemiologic distinctions between base of tongue and tonsil oropharyngeal carcinomas.

Human papillomavirus (HPV)-positive tonsil and base of tongue (BOT) cancers have been considered together. However, important differences may exist. Demographic and tumor characteristics, and survival, were compared by oropharyngeal cancer subsite from 2004 to 2016 in the National Cancer Database (NCDB). Trends in tonsillectomy from the National Health and Nutrition Examination Survey (NHANES) 2011-2014 were examined. HPV-positive BOT (N=13 081) were older than HPV-positive tonsil patients (N=16 874; mean 61.5 vs. 58.4 years, p < 0.001), and individuals 70+ years were significantly more likely to have BOT tumors compared with individuals <50 (adjusted odd ratio [aOR]=2.9, 95%confidence interval=2.6-3.2). BOT patients were also more likely to be white, male, and have advanced tumor classification. Among 7418 NHANES participants, tonsillectomy was associated with older age and white race. There are epidemiologic and tumor-related differences among HPV-positive tonsil and BOT carcinomas. Demographic differences may be attributable to tonsillectomy trends.

The Role of Infrahyoid Flap in Tongue Defect Reconstruction Following Tumour Excision.

Carcinoma tongue is one of the commonest cancer of head and neck in India. Various pedicled and free flaps have been used to reconstruct the tongue defect following glossectomies. In this era of free flaps various loco- regional pedicled flaps have been overlooked and infrahyoid flap is one of them. This flap meets the functional and cosmetic acceptance of the tongue defect reconstruction with minimal morbidity to the donor site. This paper presents author's experience of using infrahyoid flap in 10 patients of carcinoma tongue. In all the patient's tongue defect was closed with the infrahyoid flap, in 1 case flap necrosed fully and in 1 partially. Functional outcome and quality of life in all the patients were acceptable.

Role of Adjuvant Radiotherapy in Early Stage Tongue Cancer: Need for Establishing Stringent Guidelines.

The primary objective of this study was to determine, using population-based data, whether the addition of postoperative radiotherapy (RT) provides an overall survival benefit in patients with early primary squamous cell carcinoma (SCC) of tongue. The study included the data of tongue cancer patients treated between January 2016 and July 2019 retrieved from our hospital database. Tumours limited to pathologic T1 and T2 category managed with primary surgery with or without postoperative external beam RT were included. Overall survival (OS) and disease-free survival (DFS) were the main outcomes of interest. A total of 211 cases of oral cancer were evaluated and all the patients had clear surgical and pathological margins. Postoperative adjuvant therapy (PORT) was received by 16 patients. Comparison of DFS and OS at 2-year follow-up depicted a similar outcome (p = 0.582 and p = 0.312 respectively). Findings from our study suggest that in the absence of any absolute advantage on quantifiable survival and disease control, it is necessary to define stringent criteria when advocating PORT in early tongue cancer.

An evaluation of the definition of close margin in squamous cell carcinoma of the oral tongue and its possible prognostic significance

An evaluation of the definition of close margin in squamous cell carcinoma of the oral tongue and its possible prognostic significance

P-144 Tongue Carcinoma Case Treated with a Pull Through Procedure Approach with Better Esthetic Outcomes

P-144 Tongue Carcinoma Case Treated with a Pull Through Procedure Approach with Better Esthetic Outcomes

The prognostic role of the pre-treatment neutrophil to lymphocyte ratio (NLR) and tumor depth of invasion (DOI) in early-stage squamous cell carcinomas of the oral tongue.

The appropriate surgical management of early-stage oral tongue squamous cell carcinoma (OTSCC) remains a debated topic. The aim of this study is to investigate the role of the pre-treatment neutrophil to lymphocyte ratio (NLR) and tumor depth of invasion (DOI) in predicting the presence of occult neck metastases in early-stage OTSCC. A retrospective analysis of patients affected by early-stage (cT1-T2 cN0) OTSCC who were submitted to elective neck dissection (END) was performed. Tumors were classified retrospectively according to the 8th TNM classification, the DOI was assessed on the pre-operative magnetic resonance imaging, and the pre-treatment NLR was calculated for each patient. A logistic regression model to estimate the probability π (x) of cervical metastases by studying the NLR and DOI was carried out. Next, the correlation between the two variables, the NLR and DOI, was preliminarily studied. A cohort of 110 patients was analyzed (mean age, 62years old; male to female ratio 1.2:1). The patients were staged as cT1 in 53 cases and cT2 in 57 cases. A DOI greater than 5.4mm and a NLR greater than 2.93 are associated with an increased risk of presenting occult cervical metastases. Furthermore, the variables NLR and DOI are linearly associated with a positive correlation, proved by Spearman's rank correlation coefficient rho of 0.64, with a unitary increase in the DOI of 1mm directly associated with an increase of 0.47 in the NLR. The DOI and NLR can be effectively used to predict the occurrence of occult neck metastasis and therefore to plan an END in early-stage OTSCC.

Pattern and localization of perineural invasion predict poor survival in oral tongue carcinoma.

Survival rate for oral tongue squamous cell carcinoma (OTSCC) is still poor and, despite Tumor-Node-Metastasis staging system has been recently updated, patients included under the same stage still show difference in prognosis. Perineural invasion (PNI) emerged to be an indicator of tumor aggressive behavior and unfortunate events. In this study, we investigate the clinic and prognostic value of PNI in a cohort of OTSCC patients. About 200 patients with OTSCC were retrospectively evaluated the presence of PNI. PNI was furtherly descripted as uni-/multifocal and as intra-/peritumoral. Disease-Specific and Relapse-Free Survival (DSS; RFS) were estimated; moreover, we included PNI in the current AJCC 8th Staging System, improving the prognostication model. Perineural invasion was found in 40.5% of patients. Intratumoral PNI predicted patients at high risk of being diagnosed with lymph-node metastasis. Tumors with positive PNI reported a worse DSS (Hazard Ratio=1.878, p-value=0.008). Moreover, patients exhibiting both multifocal intra- and peritumoral PNI reported poorest DSS (Hazard Ratio=2.409, p-value=0.010). Patients were reclassified in a new staging system in case of multifocal PNI, providing better stratification capacity. Perineural invasion might serve as an additional prognostic factor in OTSCC, and by integrating PNI in the staging system, further improvements in prognostication might be reached.

Nivolumab monotherapy after induction chemotherapy, bioradiotherapy, and cetuximab monotherapy leading to complete remission of locoregional advanced tongue cancer: A case report

AbstractHerein, we report on a 66‐year‐old woman with locoregional advanced tongue cancer. She was diagnosed with left side tongue carcinoma and achieved complete remission using nivolumab monotherapy after induction chemotherapy (IC) with docetaxel, cisplatin, and 5‐fluorouracil, followed by intensity‐modulated bioradiotherapy and cetuximab monotherapy. Following bioradiotherapy, she was administered 70 cycles of cetuximab monotherapy. Both IC and bioradiotherapy exerted antitumor effects. However, primary tumor recurrence occurred. She received nivolumab, and the recurrent lesion disappeared after 18 cycles. She has been alive and well for &gt;5 years, showing a successful locoregional control for advanced tongue cancer during this period.

Long-Term Survival and Recurrence in Oropharyngeal Squamous Cell Carcinoma in Relation to Subsites, HPV, and p16-Status.

Simple SummaryLong-term survival in patients with oropharyngeal cancer is sparsely studied, but atypical recurrences in human papillomavirus-positive (HPV+) oropharyngeal cancer have been indicated. Furthermore, while the role of HPV is well established in tonsillar and base of tongue cancer, the dominant oropharyngeal subsites, its role in the minor oropharyngeal sites (the oropharyngeal walls, the uvula, and the soft palate) is not fully elucidated. The aim of this retrospective study was therefore to assess long-term outcome in relation to oropharyngeal sub-sites and HPV/p16 status. We confirm the prognostic role of p16+ in tonsillar and base of tongue cancer, but not the other sites. We find that combined HPV/p16-status gives better prognostic information than p16 alone. Lastly, we show that p16− cancer has more locoregional and late recurrences compared to p16+ cancer. Consequently, only combined HPV/p16 positivity in patients with tonsillar and tongue base cancer should be used in future treatment de-escalation trials.Long-term survival data in relation to sub-sites, human papillomavirus (HPV), and p16INK4a (p16) for patients with oropharyngeal squamous cell carcinoma (OPSCC) is still sparse. Furthermore, reports have indicated atypical and late recurrences for patients with HPV and p16 positive OPSCC. Therefore, we assessed long-term survival and recurrence in relation to oropharyngeal subsite and HPV/p16 status. A total of 529 patients with OPSCC, diagnosed in the period 2000–2010, with known HPVDNA and p16-status, were included. HPV/p16 status and sub-sites were correlated to disease-free and overall survival (DFS and OS respectively). The overexpression of p16 (p16+) is associated with significantly better long-term OS and DFS in tonsillar and base of tongue carcinomas (TSCC/BOTSCC), but not in patients with other OPSCC. Patients with HPVDNA+/p16+ TSCC/BOTSCC presented better OS and DFS compared to those with HPVDNA−/p16− tumors, while those with HPVDNA−/p16+ cancer had an intermediate survival. Late recurrences were rare, and significantly more frequent in patients with p16− tumors, while the prognosis after relapse was poor independent of HPVDNA+/−/p16+/− status. In conclusion, patients with p16+ OPSCC do not have more late recurrences than p16−, and a clear prognostic value of p16+ was only observed in TSCC/BOTSCC. Finally, the combination of HPVDNA and p16 provided superior prognostic information compared to p16 alone in TSCC/BOTSCC.

A first-in-human phase I dose escalation of YH001, an anti-CTLA-4 monoclonal antibody (mAb) in combination with toripalimab (anti-PD-1 mAb) in patients with advanced solid tumors.

2577 Background: YH001 is a humanized anti -hCTLA-4 IgG1 mAb that relieves CTLA-4-mediated immunosuppression, and thereby enhances the T-cell-mediated antitumor immune response. Pre-clinical data have shown potent anti-cancer activity when combined with anti-PD-1 mAb. Methods: This is an ongoing phase 1 dose-escalation study. Patients (pts) with advanced solid tumors received YH001 by IV administration at 0.05 to 6.0 mg/kg for 1 cycle (21 days) then in combination with Toripalimab (anti-PD-1 mAb) at 240 mg Q3W for 4 cycles. An accelerated titration method followed by the standard “3+3” design was utilized to evaluate safety, tolerability and preliminary efficacy. Results: As of 31-Dec-2020 data cut-off, 10 pts were enrolled and treated at 0.05 mg/kg (n = 2), 0.1 mg/kg (n = 3), 0.3 mg/kg (n = 3) and 1 mg/kg (n = 2). The median age was 62 years (range 46-74). Baseline ECOG scores were 0 (n = 8), 1(n = 2) with all pts progressed after a median of 2 prior lines of available standard therapy (range 1-4) including 1 pt progressed after immunotherapy of pembrolizumab. There were no dose limiting toxicities (DLT) observed. No severe adverse events (SAEs), Grade (G) 3 or above adverse events (AEs) and AEs leading to treatment discontinuation were reported. Twelve drug related AEs were all G1/2 events including 2 G2 AEs (1 rash maculopapular at 0.05mg/kg, 1 hypothyroidism at 0.1mg/kg), 10 G1 AEs (1 hypotension, 1 dry skin, 1 pruritus at 0.05mg/kg; 1 rash, 1 rash macular, 1 hyperthyroidism, 2 rash pruritus at 0.1mg/kg, 2 fatigues at 0.3mg/kg). Among 7 patients having imaging tumor assessment by RECIST v1.1, there were 4 SD, including 1 at 0.05 mg/kg with tongue carcinoma at week 8 assessment, 1 at 0.1 mg/kg with nasopharyngeal carcinoma at week 8 and 15 assessment, 2 at 0.3 mg/kg with gastroesophageal junction cancer and uterus leiomyosarcoma at week 8. Conclusions: YH001 combined with Toripalimab is safe and tolerable up to 1 mg/kg dose level. Updated safety and preliminary efficacy data will be presented. Clinical trial information: NCT04481009.

Clinicopathological Significance of FOXO4 Expression and Correlation with Prx1 in Head and Neck Squamous Cell Carcinoma.

Objective Forkhead box O 4 (FOXO4), a key albumen in the forkhead box O (FOXOs) family, plays crucial roles as a tumor suppressor in the cancer development. In our previous study, Peroxiredoxin1 (Prx1) promoted the development of oral cancer and was predicted to bind to FOXO4. The aim of this study was to investigate the clinicopathological significance of FOXO4 expression and its potential mechanism in head and neck squamous cell carcinomas (HNSCC). Methods The function of FOXO4 correlation with HNSCC prognosis was analyzed via ONCOMINE, UALCAN, Human Protein Atlas, and cBioPortal. The expression of FOXO4 was detected in Prx1 silenced CaL27 and SCC9 cell lines by Western blot. FOXO4 protein expression was observed via immunohistochemistry (IHC) and the binding of Prx1 to FOXO4 measured by Duolink analysis in a 4-nitro-quinoline-1-oxide- (4NQO-) induced tongue carcinogenesis model in Prx1+/+ and Prx1+/− mice. Results By the analysis of Bioinformation Databases, there was a significant interaction of FOXO4 down expression to clinical tumor stages and pathological grades in the patients with HNSCC. Reduced mRNA and protein expression of FOXO4 were found to be significantly correlated with the poor overall survival (OS) of HNSCC patients. FOXO4 expression is negatively related to Prx1 significantly in HNSCC tissues. By employing a 4NQO-induced oral carcinogenesis mouse model, we confirmed that FOXO4 expression was reduced in 4NQO-induced squamous cell carcinoma (SCC) tongue tissues compared with those in normal tissues. Prx1 knockdown resulted in the upregulation of FOXO4 expression in the SCC tissues and CaL27 and SCC9 cell lines. Furthermore, the interaction of Prx1 with FOXO4 was observed in mouse tongue tissues by Duolink analysis. Conclusion FOXO4 plays an important role in the development of HNSCC. The lower expression of FOXO4 is significantly correlated with the shorter OS in patients with HNSCC. FOXO4 is negatively regulated via interaction with Prx1. FOXO4 could be a potential molecular target for the treatment and prognosis of HNSCC.

Low potential of circulating interleukin 1 receptor antagonist as a prediction marker for squamous cell carcinoma of the head and neck.

Circulating markers are attractive molecules for prognosis and management of cancer that allow sequential monitoring of patients during and after treatment. Based on previous protein profiling data, circulating interleukin 1 receptor antagonist (IL-1Ra) was evaluated as a potential diagnostic and prognostic marker for squamous cell carcinomas of the head and neck (SCCHN). In this study, we aimed at confirming the clinical relevance of plasma IL-1Ra in SCCHN and exploring its potential as a prediction marker for SCCHN. Plasma from 87 patients with SCCHN, control plasma from 28 healthy individuals and pre-diagnostic plasma from 44 patients with squamous cell carcinoma of the oral tongue (SCCOT) and 88 matched controls were analysed with IL-1Ra electrochemiluminescence immunoassays from mesoscale diagnostics. Plasma IL-1Ra was found to be up-regulated in patients with oral tongue, gingiva and base of tongue tumours compared to healthy individuals (p<0.01). IL-1Ra levels positively correlated with tumour size (p<0.01) and body mass index (p=0.013). Comparing pre-diagnostic plasma to the matched controls, similar IL1-Ra levels were seen (p=0.05). The anti-inflammatory cytokine IL-1Ra could be a diagnostic marker for SCCHN, whereas its potential as a cancer prediction marker was not supported by our data.

Elective node dissection versus observation for management of patients with early-stage cT1/T2N0 tongue carcinoma: A systematic review and meta-analysis of prospective studies.

To carry out a meta-analysis of prospective literature comparing the clinical efficacy of elective neck dissection (END) vs observation (OBS) in patients with early-stage cT1/T2N0 tongue carcinoma. We systematically reviewed four databases from inception to 30-October-2020. We considered all studies meeting the following PICOS conditions: (a) Patients: early-stage cT1/T2N0 tongue carcinoma, (b) Intervention: END, (c) Comparator: OBS, (d) Outcomes: local tongue recurrence, cervical nodal recurrence, disease-specific survival (DSS) rate, and disease-free survival (DFS) rate and (e) Study design: prospective reports. We pooled dichotomous data as relative risks (RRs) with 95% confidence intervals (CIs). Four studies (one case-control study and three randomised controlled trials) met our inclusion criteria. There were 448 eligible patients (225 and 223 patients were treated with END and OBS, respectively). END significantly correlated with improved DSS rate (RR=1.15, 95% CI: 1.04-1.27, P=.007). Nonetheless, there were no significant differences between END and OBS groups regarding the rates of local tongue recurrence (RR=1.23, 95% CI: 0.50-3.03, P=.65), cervical nodal recurrence (RR=0.45, 95% CI: 0.16-1.27, P=.13) and DFS rate (RR=1.08, 95% CI: 0.91-1.27, P=.38). Pooled analysis for cervical nodal recurrence was heterogeneous, and sensitivity analysis revealed a significantly lower cervical nodal recurrence rate in favour of END group (RR=0.30, 95% CI: 0.13-0.67, P=.004). END correlated with a significant decrease in cervical nodal recurrence and improved DSS rate. END might be superior to OBS in patients with early-stage cT1/T2N0 tongue cancer.

Prognostic Role of Tumor-Infiltrating Lymphocytes and Tumor Budding in Early Oral Tongue Carcinoma.

Objectives/HypothesisOccult lymph metastasis is an important prognosticator for the treatment of early oral tongue squamous cell carcinoma (SCC). The objective of this study was to evaluate the prognostic significance of tumor‐infiltrating lymphocytes (TILs) in early oral tongue SCC. The combination of the TIL subtype and intermediate‐ or high‐grade budding scores was investigated as a prognostic marker for occult neck metastases.Study DesignRetrospective study.MethodsSpecimens from 62 patients with early oral tongue SCC treated with only primary surgery were analyzed by immunohistochemistry for CD4+, CD8+, FoxP3+, and CD45RO+ T cells and CD163+ macrophages. The highest number of each TIL subtype was counted in two areas of parenchyma and stroma in the tumor (Tumor) and peripheral stroma of the invasion margin.ResultsBased on multivariate analysis, a high density of Tumor CD163+ macrophages served as the poorest prognostic factor for regional control (RC) and disease‐free survival (DFS). Patients with both a high density of Tumor CD163+ macrophages and an intermediate‐ or a high‐grade budding score had a poor prognosis for RC according to the log‐rank test.ConclusionsIn summary, each TIL subtype may use different mechanisms during early and advanced stages of oral tongue SCC. A high density of Tumor CD163+ macrophages was determined to be a risk factor for RC and DFS as well as an additional stratification factor for RC in patients with intermediate‐ or high‐grade budding scores. Therefore, identifying TIL subtypes in daily clinical practice can help determine a more successful and individualized therapeutic approach for early oral tongue SCC.Level of EvidenceStep 4 (Level 4) Laryngoscope, 131:2512–2518, 2021

MMP8 increases tongue carcinoma cell\u2013cell adhesion and diminishes migration via cleavage of anti-adhesive FXYD5

Matrix metalloproteinases (MMPs) modify bioactive factors via selective processing or degradation resulting in tumour-promoting or tumour-suppressive effects, such as those by MMP8 in various cancers. We mapped the substrates of MMP8 to elucidate its previously shown tumour-protective role in oral tongue squamous cell carcinoma (OTSCC). MMP8 overexpressing (+) HSC-3 cells, previously demonstrated to have reduced migration and invasion, showed enhanced cell-cell adhesion. By analysing the secretomes of MMP8 + and control cells with terminal amine isotopic labelling of substrates (TAILS) coupled with liquid chromatography and tandem mass spectrometry (LC-MS/MS), we identified 36 potential substrates of MMP8, including FXYD domain-containing ion transport regulator 5 (FXYD5). An anti-adhesive glycoprotein FXYD5 has been previously shown to predict poor survival in OTSCC. Cleavage of FXYD5 by MMP8 was confirmed using recombinant proteins. Furthermore, we detected a loss of FXYD5 levels on cell membrane of MMP8 + cells, which was rescued by inhibition of the proteolytic activity of MMP8. Silencing (si) FXYD5 increased the cell-cell adhesion of control but not that of MMP8 + cells. siFXYD5 diminished the viability and motility of HSC-3 cells independent of MMP8 and similar effects were seen in another tongue cancer cell line, SCC-25. FXYD5 is a novel substrate of MMP8 and reducing FXYD5 levels either with siRNA or cleavage by MMP8 increases cell adhesion leading to reduced motility. FXYD5 being a known prognostic factor in OTSCC, our findings strengthen its potential as a therapeutic target.

ANAESTHETIC MANAGEMENT OF SURGERY FOR ORAL CANCER IN A MORBIDLY OBESE PATIENT WITH DIFFICULT AIRWAY AND OBSTRUCTIVE SLEEPAPNOEA - A CASE REPORT

We are reporting a case of a 39 year old morbidly obese gentleman (117Kg BMI:38.9) with history of obstructive sleep apnoea (OSA) who was presented for surgery for carcinoma tongue under general anaesthesia (GA). As the patient had features strongly suggestive of difcult intubation and difcult ventilation, we decided to secure his airway under awake bre optic bronchoscopy (FOB). General anaesthesia was induced as per routine departmental protocol. Fentanyl infusion at 20 mcg/hr for both perioperative analgesia and endotracheal tube tolerance. Patient was extubated on POD 1 and given non Invasive ventilation as he was extremely drowsy and not maintaining a saturation above 91% in spite of oxygen supplementation. Since we judged this patient to be a typical case of cannot intubate, cannot ventilate situation, we decided against giving a trial laryngoscopy after induction and instead opted to proceed straight away with awake intubation under airway anaesthesia.