Early Oral Carcinoma Research Articles

865P Molecular analysis of surgical margins in early oral carcinomas (OSCC)

865P Molecular analysis of surgical margins in early oral carcinomas (OSCC)

Relationship between Thickness of Early Oral Tongue Carcinoma (T1, T2) with Cervical Lymph Node Metastasis

Background: Carcinoma of oral tongue is the most common oral cancer and because of its structure and function is prone for early local and regional spread of cancer. The final outcome of a primary tongue carcinoma patient depends upon various prognostic factors like thickness of tumor, depth of invasion, size of lesion and neck node 67metastasis. Risk of metastasis and spread to neck nodes increases with increase in tumor thickness
 Methods: This prospective observational study was carried out in the Department of Otolayngology- Head & Neck Surgery, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka for 18 months. Thirty patients with early oral tongue carcinoma i.e.T1 & T2 as per UICC and AJC criteria were included in this study by purposive non-randomized sampling technique. Result of the study were expressed as mean, standard deviation (+SD), frequency and percentages. Unpaired Student’s t-test and Pearson’s correlation co-efficient (r) test were performed.
 Results: Result of the study showed the mean (+SD) thickness of the tumor was 3.62 (+1.46) mm. Minimum thickness 1.1mm and maximum thickness 7.8mm. Only 21 (70%) subjects neck node were metastasized from tongue and mean (+SD) tumor thickness of the positive neck node metastasis was 5.54 (+1.07) mm and negative neck node metastasis was 2.87 (+0.75) mm. This indicated a significant difference between the groups. Pearson’s correlation co-efficient r (+0.981) which indicated tumor thickness was positively correlated with neck node metastasis.
 Conclusion: Tumor thickness of the early oral carcinoma positively correlated with neck node metastasis. Correlation between thickness and metastatic lymph node can help planning the treatment regimen and indicate the disease prognosis.
 Bangladesh J Otorhinolaryngol; April 2021; 27(1): 25-35

Masseter muscle flap for reconstruction of intra-oral defects in patients with early cancer of posterior-inferior parts of the oral cavity

IntroductionEarly carcinomas of the oral cavity in the posterior-inferior regions poses a challenge for reconstruction due to the lack of muscle support underneath and the limited space available to use some of the frequently-used flaps. ObjectiveThis study was done to evaluate the efficacy of the superiorly based masseter muscle flap in reconstruction of intra-oral post- ablation defects in patients with early oral carcinoma of the posterior-inferior part of the oral cavity. MethodsA superiorly based masseter muscle flap were used to reconstruct the post-surgical intra- oral defect in 60 patients with early squamous cell carcinoma (T<4cm) of the posterior-inferior part of the oral cavity. The patients were followed up at 1-week and 1-month postoperatively to check for flap viability, complications, change in mouth opening and deviation of the mandible on mouth opening. To rule out any recurrence in the oral cavity masseter flaps, the patients were followed up for 1 year. ResultsThe flap was viable in all patients and underwent mucosalization. 7/60 patients had postoperative infections, while 2/60 patients developed an oro-cutaneous fistula which required a secondary corrective procedure. The mean±standard deviation of change in mouth opening at 1 week postoperatively was +1.917±3.36mm, which increased to +2.633±2.95mm at 1 month after surgery. The Friedman test revealed that there was a statistically significant change in mouth opening from preoperative period to the1 week and 1 month postoperative periods (p=0.000). Female patients showed better improvement in mouth opening postoperatively. The ipsilateral deviation of the mandible on mouth opening was between 0–5mm in 39 patients, 5–10mm in 17 patients and more than 10mm in 4 patients. There were no recurrences noted in the masseter flaps used. ConclusionThe study infers that the superiorly based masseter muscle flap is a reliable method for reconstruction in early oral cancer patients yielding good functional results and acceptable cosmesis with nominal postoperative complications.

The necessity of IIb dissection in T1\u2013T2N0M0 oral squamous cell carcinoma: protocol for a randomized controlled trial

BackgroundThere is a growing debate on the relationship between health-related quality of life (HRQoL) and patient survival which has been going on for the last few decades. The greatest wish of clinicians is to extend the latter while improving the former. Following neck dissection of early-stage oral carcinoma, “shoulder syndrome” appears due to traction of the accessory nerve during removal of level IIb, which greatly affects patient quality of life. Since occult metastasis in level IIb of early-stage oral carcinoma is extremely low, some surgeons suggest that level IIb can be exempt from dissection to improve the HRQoL. However, other surgeons take the opposite view, and thus there is no consensus on the necessity of IIb dissection in T1–2N0M0 oral squamous cell carcinoma (OSCC).MethodsWe designed a parallel-group, randomized, non-inferiority trial that is supported by Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China. We will enroll 522 patients with early oral carcinoma who match the inclusion criteria, and compare differences in 3-year overall survival, progression–free survival (PFS) and HRQoL under different interventions (retention or dissection of level IIb). The primary endpoints will be tested by means of two-sided log-rank tests. Analysis of overall and progression-free survival will be performed in subgroups that were defined according to stratification factors with the use of univariate Cox analysis. In addition, we will use post-hoc subgroup analyses on the basis of histological factors that were known to have effects on survival, such as death of invasion of the primary tumor. To evaluate HRQoL, we will choose the Constant–Murley scale to measure shoulder function.DiscussionCurrently, there are no randomized controlled trials with large sample sizes on the necessity of IIB dissection in T1–T2N0M0 OSCC. We designed this noninferiority RCT that combines survival rate and HRQoL to assess the feasibility of IIb neck dissection. The result of this trial may guide clinical practice and change the criteria of how early-stage oral cancer is managed. The balance between survival and HRQoL in this trial is based on early-stage breast cancer treatment and may provide new ideas for other malignancies.Trial registrationChinese Clinical Trial Registry, ChiCTR1800019128. Registered on 26 October 2018.

Quality of Life After High-dose Brachytherapy in Patients with Early Oral Carcinoma

The prevalence of head and neck tumors has continually increased over the past decades, which is a serious medical and social problem. This study retrospectively assessed the quality of life of patients with early-stage oral cavity tumors after high-dose rate (HDR) brachytherapy. Quality of life was evaluated in 14 patients with early-onset oral cavity tumors who underwent HDR brachytherapy at the Department of Oncology and Radiotherapy, University Hospital Hradec Kralove. The standardized EORTC QLQ-C30 and EORTC QLQ-H&N 35 questionnaires were used. Patients completed these questionnaires at 12 months after treatment. The general health status was scored 70 points using the EORTC QLQ-C30 questionnaire. Fatigue, insomnia, loss of appetite, dyspnea, and financial problems were the most severe problems reported. The main problems identified by the EORTC QLQ-H&N 35 questionnaire were weight gain, coughing, pain, sticky saliva, and difficulties eating in public. On the contrary, patients did not significantly suffer weight loss, speech impairments, difficulties in mouth opening or swallowing, or sensory problems. HDR brachytherapy is an effective treatment for early oral cancer that leaves patients with an acceptable quality of life. A prospective, multicentric study focused on the quality of life of patients with head and neck tumors is required.Key worlds: oral cancer - brachytherapy - quality of life This article was supported by grant PROGRES Q 40/13. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 17. 1. 2018Accepted: 4. 2. 2018.

Sentinel node biopsy in relation to survival in floor of the mouth carcinoma

Promising results have been obtained with sentinel node biopsy (SNB) in early oral carcinoma, but the floor of the mouth remains a site at risk of misdiagnosis. A retrospective and prospective study was designed to test the safety of SNB by comparing survival among patients with early stage carcinoma of the floor of the mouth (FOM) undergoing SNB, to a control group managed traditionally by a combination of clinical observation and elective neck dissection (END). A total of 63 patients with early stage carcinoma of the FOM were treated between 1991 and 2005. In the control group, 26 patients were managed with END and nine by close observation. In the test group, 28 patients were managed prospectively with SNB. Regional recurrence occurred in 23% (8/35) of control patients and 25% (7/28) of test patients. Approximately 25% of patients were successfully treated by salvage surgery. Disease-specific survival was 65.5% for control patients and 85% for SNB patients; the difference was not statistically significant. The use of SNB in the management of cancers of the FOM did not adversely affect survival and prevented 69.5% of patients undergoing unnecessary neck dissections, while clinical progress was better in the SNB group than in controls.

Recurrent Genomic Alterations of FHIT Gene with Impact on Lymphatic Metastasis in Early Oral Carcinoma

Objectives: Determine the role of genetic factors related to the lymph node metastasis (LNM) in early oral squamous cell carcinoma (OSCC). Methods: Array-based comparative genomic hybridization with individual gene-level resolution using primary tumor materials from 14 early OSCC patients with (n = 7) or without (n = 7) cervical LNM. To confirm the genomic copy number alterations, immunohistochenical stain was conducted in 30 early OSCC specimens. Results: The number of recurrent (&gt;25%) copy number alterations with LNM group is 34, whereas that without LNM group is 23 by array-based comparative genomic hybridization in the first cohort. We detected 10 recurrently altered regions (10 losses) associated with cervical LNM ( P &lt; 0.05). Among them, loss of 3p14.2 for the FHIT gene was the most frequent one (5 out of 7 patients with LNM, 71.4%) and significantly associated with a worse disease specific survival ( P = 0.005). In the independent validation cohort of 30 early OSCC cases, loss of FHIT determined by an immunohistochemical analysis was associated with cervical LNM ( P = 0.032) and disease specific survival ( P = 0.045). Conclusions: Copy number alterations of FHIT are associated with LNM and poor prognosis, and risk stratification based on the copy-number status of this gene is useful to select the optimal treatment strategy in early OSCC patients.

Sentinel node biopsy as an alternative to elective neck dissection for staging of early oral carcinoma

We report the outcome of sentinel node biopsy (SNB) for staging the neck in a consecutive cohort of 34 patients with T1/2 clinically N0 oral carcinoma. SNB was performed along with resection of primary tumor. Neck dissection was reserved for failure of SNB or pathologically positive sentinel nodes (pN+). Sentinel node identification was successful in 32 of 34 patients (94%); 2 patients with unsuccessful SNB underwent immediate neck dissection. Seven patients (21%) were pN+, 6 by SNB and 1 by elective neck dissection (END). Among 29 patients who were pN0 on SNB, nodal recurrence developed in 2 patients; both were surgically salvaged. Local failure developed in 1 patient. Two-year overall and disease-free survival was 87% and 80%, respectively. Successful eradication of lymphatic metastasis noted in this study suggests that SNB may be a safe alternative to END for neck staging in patients with early oral carcinoma.

Sentinel node biopsy for early oral carcinoma

Sentinel node biopsy (SNB) in oral squamous cell carcinomas (OSCCs) has been under investigation since more than a decade. Numerous published studies and recent important scientific data support its role as an alternative standard of care apart from elective neck dissection. During the past 2 years, a large-scale multicentric validation trial and long-term follow-ups of major observational trials have demonstrated the accuracy and oncological safety and efficacy of SNB to stage a cN0 early stage OSCC. Histologic and molecular parameters of the primary tumors possibly predicting occult disease in the neck have been evaluated, but SNB with the use of step-serial sectioning and immunohistochemistry remains the most accurate staging method. SNB has been shown to be clearly superior to elective neck dissection with regard to complications and morbidity. The modern technique of quantitative real-time reverse transcriptase-polymerase chain reaction has been successfully used for the rapid intraoperative assessment of the sentinel nodes, allowing a one-stage procedure in all patients. The procedure of SNB is currently expanding to other areas like the supraglottic larynx and the previously treated neck. SNB in OSCC is a minimally invasive and highly reliable staging method of the cN0 neck and has become the standard of care in many centers throughout the world. Recent developments have led to a wider clinical application and improved acceptance.

Effectiveness of autofluorescence to identify suspicious oral lesions—a prospective, blinded clinical trial

Regular screening through white light inspection of the entire oral mucosa is the most important examination method to identify precancerous lesions and early oral carcinoma. Additionally, the physiologic autofluorescence of the oral mucosa has been described as a novel screening method for the detection of mucosal lesions that are not visible by white light. This study aimed to evaluate the sensitivity and specificity of the autofluorescence examination. Seventy-eight patients were examined in this study. All of them suffered from suspicious oral mucosal lesions. Two different investigation methods were applied: the standard examination by white light and an examination by a novel light source of 400nm that evoked a green light emission (>500nm) in normal mucosa. It was proposed that malignant oral mucosal lesions show different autofluorescence characteristics than the green autofluorescence of healthy mucosa. Red autofluorescence indicated SCC with a sensitivity of 20% and a specificity of 98%. The results showed that dysplasia and carcinoma could be identified with a sensitivity of 96% and a specificity of 18% by using the autofluorescence method. The sensitivity decreased according to the grade of mucosal keratosis and was influenced by the localisation of the lesion. In conclusion, benign as well as malignant oral lesions could not be distinguished by a diminished autofluorescence signal. A red autofluorescence signal, however, could indicate cancerous processes of the oral mucosa.

Ex vivo photodynamic diagnosis to detect malignant cells in oral brush biopsies

In this study we proved the efficiency of the fluorimetric detection of a minimum number of malignant cells ex vivo. The goal of this work was to investigate whether the combination of photodynamic diagnosis (PDD) with oral brush biopsy might become a suitable chair-side tool to detect early oral carcinoma. Small numbers (100-500) of established human tumour cells-small cell lung carcinoma (OAT 75), transitional cell carcinoma of the bladder (SW1710) and human embryonic kidney cells (HEK293)-were incubated with 2 mM 5-aminolaevulinic acid (5-ALA). In addition, 50 brush biopsies from volunteers were prepared. After 2 h and 3 h of incubation, all samples were investigated by spectrofluorometry. Measurements were performed in capillaries. For excitation (405 nm) and detection of fluorescence spectra, a fibre microprobe-spectrofluorometer system (fibre 400 microm) was used. A minimum of 100 malignant cells and 3 h of incubation with ALA were needed to detect a typical spectrum for protoporphyrin IX (PPIX). Some epithelial samples from brush biopsy showed strong (bacteria related) PPIX autofluorescence, which increased after the addition of 5-ALA. From the testing of various antibiotics and antiseptics it emerged that 0.4 mM chlorhexidine strongly reduced fluorescence in brush biopsies from healthy volunteers, whereas the fluorescence signal of established cancer cell lines decreased only a little. The experiments revealed that, by means of an optical microprobe, very few cancer cells (100) can be detected. The addition of chlorhexidine before the incubation of brush biopsies with 5-ALA increases the reliability of the test by largely reducing the autofluorescence signal due to the presence of bacteria. Chair-side diagnostics of epithelial carcinoma seem feasible.

S170 – Neck Recurrences in T1 Oral Carcinomas

Objectives To evaluate the regional recurrences in 48 cases of T1 SCC of tongue and floor of mouth. Methods Retrospective review of 48 cases of T1 SCC of tongue and floor of mouth treated primarily with local resection of the tumor. All the cases were reviewed concerning the tumor site, size and thickness, presence of perineural invasion, desmoplastic reaction, outcome and follow-up. Results There was a predominance of male patients (83.3%) with a mean age of 55.4 years old. All but 7 cases were tobacoo consumers and only 10 patients did not use alcohol. The floor of mouth was the primary site in 54.20% of cases. The mean diameter of tumors was 0.86cm and the mean thickness were 0.6mm. Neck recurrences occurred in 10 cases (20.83%) and in 2 of these cases there were local recurrence. All but 1 recurrent cases were treated with salvage surgery and 4 cases died of disease in a mean time of 11.7 months. Conclusions The high rate of neck recurrences in early oral carcinomas must be considered during the treatment planning of these cases and the need of neck dissection should be considered, even in tumors with less than 2.0cm.

The selective cytotoxic effect of carotenoids and α-Tocopherol on human cancer cell lines in vitro

This study compares the toxic effects of the carotenoids, β-carotene and canthaxanthin, and α-tocopherol (vitamin E) on human tumor cells and their normal counterparts in vitro. Seven different malignant cell lines were examined: oral carcinoma (two cell lines), breast (two cell lines), lung carcinoma (two cell lines), and malignant melanoma. The in vitro cell culture assays showed a consistent morphologic change in the affected tumor cells following treatment with carotenoid or vitamin E. A rounding of the tumor cells and eventual lifting off the tissue culture plate were observed. These changes were apparent after 1 to 5 hours of treatment depending on the tumor cell line. Associated with these observable cellular changes were quantitative reductions in proliferation ( 3H-thymidine proliferation) and succinic dehydrogenase activity (MTT assay). In addition, there was a noticeable change in protein expression, with an increased expression of a 70-kD protein following treatment with β-carotene. This protein was associated with tumor cells showing a decrease in proliferation (oral carcinoma, malignant melanoma), but not with normal keratinocytes or melanocytes. These studies substantiate a selective cytotoxic effect on human tumor cell growth by carotenoids and α-tocopherol in vitro, and may provide an explanation of the therapeutic activity of these agents and their possible use in the treatment of premalignancy or early oral carcinoma.