Sensitivity and specificity of sentinel lymph node biopsy in patients with oral squamous cell carcinomas using indocyanine green fluorescence imaging

Purpose

The purpose of this clinical study was to evaluate the sensitivity and specificity of cervical sentinel lymph node biopsy after mapping with indocyanine green fluorescence (ICG) for imaging early-stage oral cancer.

Histologic grading and nucleolar organizer regions in oral squamous cell carcinomas

Objective

The purposes of this study were to histologically assess different types of oral squamous cell carcinoma and the silver-binding nucleolar organizer region (AgNOR) morphology in neoplastic cells, as well as to quantify the number of AgNORs in each type of carcinoma in order to relate AgNOR count and histologic grading.

Material and Methods

Twenty-eight cases of oral squamous cell carcinoma were divided into 4 groups, namely well-differentiated, moderately differentiated, poorly differentiated, and undifferentiated. For NOR study, 3-µm-thick sections were stained with 50% aqueous silver nitrate solution. The predominant microscopic pattern of NORs was determined. Quantitative analyses of NORs were obtained of all cells present on each histological field using a 0.025 mm² eyepiece graticule. Different histological fields were analyzed until the total number of NORs was 120 cells for each tumor. Kruskall-Wallis test was applied to compare the groups of sample data at a significance level of p=0.05.

Results

The mean number of AgNORs per nucleus was 3.20 for the well-differentiated group, 5.33 for the moderately differentiated one, 8.27 for the poorly differentiated one, and 10.08 for the undifferentiated one. AgNOR count was significantly different (p<0.05) among all of the studied groups.

Conclusion

AgNOR staining technique seems to be a useful diagnostic tool since differences in AgNOR numeric values can be identified in the different types of oral squamous cell carcinoma. This technique is easy to handle and inexpensive, thus justifying its large use in histopathology.     

Surgery for maxillary oral squamous cell carcinoma: the effect of surgical resection margins and elective neck dissection on oncological outcomes

Maxillary oral squamous cell carcinoma (OSCC) is uncommon. Surgical resection is challenging due to the anatomy, and the role of elective neck dissection (END) is not well-defined. A retrospective cohort study of patients with maxillary OSCC treated with primary surgery between 2007 and 2019 was conducted. Primary tumours of sinonasal origin with extension into the oral cavity were excluded. Survival analysis was performed using Kaplan–Meier and Cox proportional hazards models. Sixty-seven patients were included; mean follow-up was 55 months. On univariate analysis, clear (≥5 mm) margins were associated with higher disease-free (68% vs 36%, P = 0.019) and overall survival (75% vs 36%, P = 0.004) than close/involved (<5 mm) margins. In clinically node-negative patients, the risk of occult cervical metastasis in tumours with depth of invasion (DOI) ≥ 3 mm and T2–4 tumours was 22% and 25%, respectively. END in these groups was associated with a lower rate of loco-regional recurrence (DOI ≥3 mm subgroup: 5% vs 38%, P = 0.029; T2–4 subgroup: 6% vs 50%, P = 0.028) and longer time to recurrence (DOI ≥3 mm subgroup: 119 months vs 96 months, P = 0.042; T2–4 subgroup: 117 months vs 56 months, P = 0.031) than observation of the neck. On multivariate analysis, close/involved margins were associated with an increased risk of overall mortality (hazard ratio 3.4, 95% confidence interval 1.0–11.3, P = 0.043) and disease recurrence (hazard ratio 2.8, 95% confidence interval 1.1–7.1, P = 0.031). In maxillary OSCC, a ≥ 5 mm histological margin should remain the goal of ablative surgery. END should be considered in tumours with DOI ≥ 3 mm.     

Treatment delay in early-stage oral squamous cell carcinoma and its relation to survival

The aim of this study was to investigate the impact of a prolonged treatment delay on survival in patients with primary oral squamous cell carcinoma. The investigators hypothesized that treatment delay affects survival, supposing a poor outcome in patients with prolonged treatment initiation. In addition, a critical treatment delay should be defined.Inclusion criteria were a histopathological diagnosis of primary squamous cell carcinoma of the oral cavity and a surgery-based treatment of the tumor. Patients with a history of previously diagnosed malignancies and patients with distant metastasis at the time of diagnosis were excluded from this protocol. Common clinical and histopathological data were assessed retrospectively. Treatment delay was analyzed for the interval between initial presentation and the date of surgery.A total of 484 patients could be included. Considering early-stage patients, the risk of death increases by 1.8% for each day that the treatment delay is prolonged if all other characteristics do not change (p = 0.0035). In patients with advanced disease, a prolonged treatment delay does not affect the risk of death (p = 0.9134). In terms of progression-free survival, treatment delay tends to be associated with a higher risk of recurrence in early-stage disease, but without being statistically significant (p = 0.0718). For patients with early-stage disease, a treatment delay of 20 days is critical regarding overall survival (p = 0.011). For patients with advanced-stage disease, no significant differences have been observed.As patients with early-stage oral squamous cell carcinoma profit from early treatment initiation, we suggest an acceptable maximum treatment delay of no more than 20 days in the surgical management of these patients.     

The matrix metalloproteinase system in oral squamous cell carcinoma

BACKGROUND: The matrix metalloproteinase (MMP) system is responsible for degradation of tissue in both normal and pathological processes, including tumour invasion and metastasis. AIM: To compare tissue concentrations of components of the MMP system between tumour tissue and normal tissue in patients with oral squamous cell carcinoma, and to correlate concentrations with pathological grade of tumour. METHODS: Thirty-eight paired tissue samples from tumours and normal tissue were analysed by three laboratory techniques: firstly, enzyme linked immunosorbent assays (ELISA) in ng/mg protein for MMP-1, MMP-3, and tissue inhibitors of metalloproteinases (TIMPs) -1 and -2. Secondly, gelatinase activity assays to measure concentrations of total and endogenous active gelatinases, MMP-2 and MMP-9 (ng/mg protein). And thirdly to use quenched fluorescent substrate hydrolysis to measure total MMP activity (pM/min). RESULTS: The concentration of all MMPs was significantly higher in tumour than in normal oral tissue (p < 0.05, Mann-Whitney U-test). Tissue concentrations of some of these factors correlated with clinical and pathological indices of aggressiveness of tumours, including T-stage, N-stage, tumour differentiation, and anatomical level of involved nodes. However, the study was not powered to show statistical significance. CONCLUSION: It is the balance between proteinases and their inhibitors that controls tissue degradation at each stage of tumour invasion and metastasis. Measurement of MMPs in oral mucosal biopsy samples may establish the invasive potential of tumours at their initial presentation.     

口腔颌面-头颈鳞癌的分子生物学研究

口腔颌面-头颈鳞癌是发病率和死亡率较高的全球性疾病。临床常用的TNM分期不能对其遗传学特征和生物学特性作出正确的判断：肿瘤的分子特点对治疗方案选择、降低死亡率和提高生存率有一定帮助。特异基因表达谱的应用．能改善诊断方法．为个体化治疗提供基础；头颈鳞癌分子谱型的应用，可以对淋巴结转移和手术切缘作出正确的诊断．以便正确指导手术范围的确定。2000～2005年，约有40多篇有关头颈鳞癌基因表达谱的研究报道，本文就研究中发现有变化的基因进行综述和分析。结果表明，在肿瘤和非肿瘤之间，存在多个基因的变化。GO分类分析结果表明．这些基因涉及22种生理功能；进一步对这些变化基因进行基因组、蛋白组和功能的研究，将对揭示头颈鳞癌的分子病理学发生机制产生积极作用。     

The prognostic relevance of lymph node ratio in patients with oral squamous cell carcinoma treated with neoadjuvant therapy regimen and radical surgery

Background

This study aims at investigating the prognostic significance of lymph node ratio (LNR) in a cohort of patients with oral squamous cell carcinomas (OSCC), treated with neoadjuvant radiochemotherapy followed by radical surgery.

cN0期头颈肿瘤哨位淋巴结活检术的研究进展

目前,国内、外对哨位淋巴结活检术在cN0期肿瘤诊治中的研究方兴未艾,在乳腺癌的分期与治疗中,哨位淋巴结活检术已经成为一种常规的方法。但在头颈肿瘤的诊治中,哨位淋巴结活检术尚处于研究阶段。本文对哨位淋巴结活检术的研究状况做一综述。     

Review of the literature and a recommended system of malignancy grading in oral squamous cell carcinomas

Abstract – A review of histologic classification systems for grading of malignancy in squamous cell carcinomas of the head and neck region is presented. Reasons behind the varying results obtained in studies using his tomorphologic grading schemes are presented and potential errors involved in this type of clinical research are discussed. Requirements for the study of correlations between malignancy grade scoring, and recurrence and survival rates are presented. These include factors as patient selection, clinical staging, and follow-up principles. Special attention must be given to treatment modalities, establishment of negative surgical margins and occurrence of regional lymph node and/or distant metastases.     

The prognostic implications of comorbidity and risk factors for (post)operative complications,days spent in the intensive care unit (ICU), and length of hospitalization in patients with oral squamous cell carcinoma: A prospective study

BackgroundThis study aimed to investigate the prognostic implications of comorbidity/risk factors in a cohort of patients with OSCC.MethodsThe prospective study included patients with biopsy-proven primary OSCC. The impact of potential predictors on (post)operative complications, days spent in the ICU, and length of hospitalization was analyzed using both univariate and multivariate analysis.ResultsUsing a microvascular free flap (p = 0.009) and tobacco abuse (p = 0.005) had statistically significant impacts on postoperative complications in univariate, but not in multivariate, analysis. The duration of anesthesia (p < 0.001), type of neck dissection (p = 0.014), reconstruction type (p < 0.001), and red blood cell transfusion during operation (p = 0.007) had statistically significant impacts on spending ≥ 3 days in ICU in univariate analysis, with reconstruction type (p = 0.022) and red blood cell transfusion during operation (p = 0.034) having similar impacts in multivariate analysis. The duration of anesthesia (p < 0.001), pT (p = 0.009), type of neck dissection (p = 0.046), reconstruction type (p < 0.001), and microvascular free flap (p < 0.001) had a statistically significant impacts on length of hospitalization in univariate analysis, with reconstruction type (p < 0.001) also having a significant impact in multivariate analysis.ConclusionNone of the investigated variables showed a significant effect on the prediction of (post)operative complications according to the Clavien-Dindo classification. The type of reconstruction proved to be a valid predictor for the time spent in ICU as well as for the overall length of hospitalization. Red blood cell transfusion during operation further predicted the time spent in ICU after operation. Both variables should be taken into account when performing a comprehensive planning of the patients’ hospitalization.     

Identification and characterization of novel human papillomaviruses in oral rinse samples from oral cavity and oropharyngeal cancer patients

ObjectivesThe objectives of this study were to: I) discover novel human papillomaviruses (HPVs) using next generation sequencing (NGS) technology in oral rinse samples collected from oral cavity cancer (OCC) and oropharyngeal cancer (OPC) patients; II) determine the prevalence of novel HPVs in archived OCC and OPC tissue samples; and III) examine the frequency of novel oncogenic HPVs in cancer and non-cancer oral rinse samples using real-time PCR.MethodsOral rinse samples were collected from 100 head and neck cancer patients, and 110 healthy individuals. NGS techniques were used to detect novel HPVs.ResultsThree potentially new types of HPV were discovered. Novel virus (NV) 14.4 was closely related to HPV76 with an 89% homology and is a member of the genus Beta-papillomavirus (β-PV); NV69.1 was distantly related to the genus Alpha-papillomavirus (α-PV), and NV95 was closely related to HPV147 with a 65–77% homology and is part of the genus Gamma-papillomavirus (γ-PV). In archived oral tissue samples, NV14.4 was detected in a single patient with OCC. Of the oral rinse samples, NV69.1 was more prevalent than the other two NVs.ConclusionsOur results demonstrated that there are novel HPVs present in oral rinse samples that may be associated with OCC and OPC. These novel HPVs can be identified and characterized using NGS techniques.     

Immunohistochemical evidence of PTEN in oral squamous cell carcinoma and its correlation with the histological malignancy grading system.

PTEN is a tumor suppressor gene that encodes a dual phosphatase protein capable of modulating membrane receptors and interaction of the cell and extracellular stimuli. PTEN regulates cell physiology such as division, differentiation/apoptosis and also migration and adhesion. The expression of PTEN was evaluated by immunohistochemistry in OSCC and compared to a well-established histological malignancy grading system. The well-differentiated OSCC were 59.1% and poorly differentiated were 40.9%. According to PTEN expression, the cases were 45.5% positive (the entire tumor showed stained), 22.7% mixed (both negative and positive cells were present) and 31.8% negative (no staining was seen in the tumor cells). PTEN expression in OSCC was related to the malignancy grade (P < 0.0005). Aggressive tumors with a high score of malignancy did not express PTEN, and clearly, the PTEN expression was present in the epithelium adjacent to the tumor. Negative cells were in the invasion border of the tumor. This result suggests that PTEN is related to histologic pattern and biological behavior of OSCC and may be a used as a prognostic marker in the future. The role of PTEN during carcinogenesis and as a biomarker should be further investigated.     

A review of post-operative feeding in patients undergoing resection and reconstruction for oral malignancy and presentation of a pre-operative scoring system

Percutaneous endoscopic gastrostomy (PEG) and nasogastric tubes (NGT) are routine after resection and reconstruction of oral cancer. The selection of the most appropriate method of feeding can be challenging, as both methods carry morbidity. This makes correct selection paramount. The objectives of this retrospective review were to identify the benefits and complications of feeding with PEG and NGT in patients with oral malignancy. We retrospectively reviewed 144 patients who had undergone oral cancer resection and reconstruction, to compare PEG and NGT feeding and to identify the key factors that aid selection of the most appropriate feeding method. We used these factors to develop the Key to Appropriate Replacement Enteral Nutrition (KAREN) scoring system. One hundred and twenty of the 144 patients were managed with PEG, and of these, 9 used it for less than 28days. The mean (range) duration of use was 13 (5-63) days, and 1.9 (1-5) tubes/patient were used. The KAREN scoring system assigned the correct method of feeding in 92% of cases. The scoring system requires prospective validation but could provide clinicians with a tool to assist in a sometimes difficult decision.     

淋巴显像技术在口腔鳞癌哨位淋巴结活检中的应用

目的:评价淋巴显像技术在口腔鳞癌哨位淋巴结活检中的价值。方法:应用颈淋巴显像技术结合蓝染法及SPECT/CT同机融合技术,对21例临床NO(cNO)口腔鳞癌患者的哨位淋巴结(sentinel lymph node,SLN)进行研究。结果:全组患者SLN检出率为100％,21例中有7例SLN活检阳性,颈清术后标本同样证实有颈淋巴结转移,无假阴性结果,SLN活检对全组病例颈淋巴结转移状况预测的准确性为100％。结论:颈淋巴显像技术结合蓝染法及SPECT/CT同机融合技术能有效地对口腔鳞癌SLN进行定位,从而准确预测颈淋巴结转移状况。     

大数据时代口腔癌精准诊疗的思考

现代科学技术的进步使得医学数据越来越复杂、丰富和多样,生物医学已然进入大数据时代.在大数据时代背景下,当前主流的循证医学模式可能被精准医学模式替代,肿瘤的诊疗策略也在发生重大变革.本文将评述大数据时代背景下口腔癌精准诊疗策略的进展,包括口腔癌的筛查、早期诊断、分子分型、预后判断和治疗方案的选择、转移和化疗敏感性的预测等,以期为口腔癌的精准诊疗提供新的思路.     

Risk factors in securing successful surgical resection of oral squamous cell carcinoma

The purpose of this retrospective study was to analyze the factors that had a significant effect on securing a successful surgical resection (surgical margin) in oral cancer surgery. One hundred forty-eight consecutive patients who underwent planned radical resection of oral squamous cell carcinoma (SCC) were analyzed. Successful resection was judged if pathological examination of the surgical specimen revealed a clear surgical margin (no SCC within 5 mm, n = 116), while an unsuccessful resection was judged if there was a close and involved surgical margin (SCC within 5 mm, n = 21; and SCC at margin, n = 11). Univariate analyses showed that gender, age, and T-classification had significant influence on successful surgical resection. The results of multivariate logistic regression analysis showed that age (odds ratio [OR] = 1.042, 95% CI = 1.001-1.084), T-classification (OR = 1.656, 95% CI = 1.060-2.587), and the presence of preoperative treatment (OR = 2.868, 95% CI = 1.047-7.85) had significant effects on successful surgical resection. The results of this study suggested that successful resection of oral SCC was difficult in patients with either older age or advanced (T4) tumor. It is also suggested that preoperative therapy had a positive effect on securing a pathologically clear surgical margin.     

Health-related quality of life of patients treated with primary chemoradiotherapy for oral cavity squamous cell carcinoma: a comparison with surgery

Our aim was to document the health-related quality of life (QoL) of patients with squamous cell carcinoma (SCC) of the oral cavity who were treated with chemoradiotherapy, and to compare it with that of patients treated with conventional surgery with or without adjuvant treatment. All patients who presented with SCC of the oral cavity treated with chemoradiotherapy alone at the Royal Brisbane & Women's Hospital between 2000 and 2011 and who were alive without disease were included. Health-related QoL was assessed by the University of Washington QoL questionnaire version 4, and the European Organisation for the Research and Treatment of Cancer (EORTC) QoL questionnaires C30 and HN35. The questionnaires were sent to all survivors. Those who responded to chemoradiotherapy were matched with patients who were treated by conventional surgery with or without adjuvant treatment by age, sex, subsite of tumour, and TNM stage. Sixteen patients completed the questionnaires (8 in each group). There was no significant difference between the 2 groups in any of the domains of any of the questionnaires. The overall outcome scores for both treatments in all 3 groups were reasonably high, which suggests that both treatments provided acceptable health-related QoL. The surgical group recorded higher scores than the chemoradiotherapy alone group in all domains of the UW-QoL except shoulder and anxiety. They recorded lower scores in all scales and items of EORTC HN35. There was no significant difference in health-related QoL between the 2 groups. Conventional surgery with or without adjuvant treatment recorded higher scores in most QoL domains including chewing, swallowing, saliva, and speech, issues most important to patients with SCC of the oral cavity.