Observation of tumour thickness and resection margin at surgical excision of primary oral squamous cell carcinoma--assessment by ultrasound

Tumour thickness and the status of resection margins are of prognostic significance in the treatment of oral cancer. In a single blind prospective study, 14 patients with biopsy proven oral squamous cell carcinoma had intraoral ultrasound imaging done preoperatively to measure tumour thickness, and intraoperatively to measure the deep surgical margin half way during resection. The cut surface was demonstrated on ultrasound by placing a metal, ultrasound-reflective, retractor into the surgical cut. The ultrasound measurements were compared to the subsequent histological measurements. Using the threshold of 5mm as indicator of margin clearance, there was agreement in 10 out of 14 cases between ultrasound and histology. Ultrasound detection of close surgical margins had a sensitivity of 83% and a specificity of 63%. For preoperative tumour thickness measurement, ultrasound imaging showed a high degree of correlation with histology (Pearson correlation coefficient=0.95, P<0.01). This original paper demonstrates that high resolution ultrasound imaging applied intraorally is a reliable tool in objectively assessing both the tumour thickness and the surgical margin clearance at the time of surgery.     

Recent trends of saliva omics biomarkers for the diagnosis and treatment of oral cancer

BackgroundRecent advances in surgery, radiotherapy, and chemotherapy have no significant effect on oral cancer survival rates due to late diagnosis, poor tumor response to chemotherapy and radiotherapy, as well as a lack of effective biomarkers for early diagnosis.HighlightsTherefore, an investigative study aimed at identifying genomics, proteomics, metagenomics, and, metabolomics derived biomarkers for early diagnosis may improve the survival rate of oral cancer patients. Identification and application of saliva-based ‘‘omics’’ biomarkers may overcome painful invasive procedures currently being used for the diagnosis of oral cancer. One single biomarker may not be able to differentiate between oral squamous cell carcinoma (OSCC) and controls. Thus, multiple sensitive and specific biomarkers may be needed for screening high-risk patients and following them up for early signs of OSCC occurrence. Validation of these biomarkers in large patient cohorts is, however, required before they can be used in clinical practice.ConclusionIn this review, we summarize the potential of omics derived salivary biomarkers as diagnostic and prognostic tools in oral cancer detection and the future clinical benefits associated with these markers.     

吲哚菁绿荧光成像技术在口腔鳞癌治疗中的应用：中国专家共识

吲哚菁绿（indocyanine green,ICG）荧光成像是一种基于ICG增强的渗透性和滞留效应（enhanced permeability and retention effect,EPR）的活体组织实时近红外显像技术,临床上可对实体肿瘤及其周围组织进行差异显像,评估肿瘤范围及手术切缘。该荧光成像技术用于口腔鳞癌（oral squamous cell carcinoma,OSCC）外科治疗尚处于起步阶段,在适应证、操作流程、注意事项等方面均缺乏相应规范。在前期开展的ICG近红外荧光成像辅助OSCC外科治疗的多中心临床研究基础上,经国内多家医学院校口腔颌面外科专家的共同商讨,参考国内外相关文献,形成ICG荧光成像技术在OSCC治疗中的应用专家共识,以期指导OSCC外科治疗的临床实践。     

Marginal and segmental mandibulectomy in patients with oral cancer: a statistical analysis of 106 cases.

PURPOSE: The treatment of oral squamous cell carcinoma may require mandibular resection to secure adequate margin. This bone resection often is segmental or marginal mandibulectomy. The purpose of this work was to evaluate the local control and survival after surgical treatment of oral cancer, according to these 2 different mandibular resection procedures. PATIENTS AND METHODS: We conducted a retrospective study of a 20-year cohort of 106 patients who underwent marginal or segmental mandibulectomy for oral cancer. All patients had a biopsy-confirmed diagnosis of squamous cell carcinoma involving either the floor of the mouth, mandibular gingiva, retromolar trigone, tongue, buccal mucosa, or oropharynx. The type of mandibular resection and treatment outcome were compared, using an univariate analysis by the Pearson chi(2) test, logistic regression model for multivariate analysis, and Kaplan-Meier method to determine survival. RESULTS: The 5-year observed survival rate was 60.35%. The presence of histologic mandibular invasion increased the local recurrence rate. Early tumor stages (P =.02) were found to be associated with decreased local recurrence rates. Our findings indicate that tumor stage and size of mandibulectomy are more important than the type of mandibulectomy in predicting histologic bone involvement. The cases treated with a greater than 4 cm bone resection showed a lower survival rate than those treated with less than 4 cm mandibulectomy (P =.01). Patients in advanced stages (P =.006) and those with surgical margin (P =.0001) or the bone (P =.003) affected by the tumor showed a statistically significant lower survival rate. However, no statistically significant differences were found between patients treated by marginal or segmental mandibulectomy. CONCLUSIONS: Among the prognostic factors studied, the status of the surgical resection margin, the bony involvement and the size of mandibulectomy affected the prognosis for oral carcinoma. Mandibular conservation surgery is oncologically safe for patients with squamous carcinoma in early stages. The marginal technique was not associated with worse prognosis.     

Involved surgical margins in oral and oropharyngeal carcinoma—an anatomical problem?

A previous audit conducted in the West of Scotland (WoS) suggested that anatomical factors accounted for a substantial proportion of invaded surgical margins after resection of an oral or oropharyngeal squamous cell carcinoma (SCC). Since then a number of technical improvements have taken place, the most important of which has been advanced digital imaging that has enabled better surgical planning. In this study we compare the incidence of involved surgical margins in a recent group with those found in the earlier audit. The earlier (WoS) group comprised a consecutive series of patient operated on for a primary SCC of the oral cavity or oropharynx between November 1999 and November 2001 (n = 296). The later series comprised 178 patients operated on for oral or oropharyngeal SCC at the Southern General Hospital (SGH), Glasgow, between 2006 and 2009. A total of 245 patients in the WoS cohort had information available on the invasion of the margins of whom 68 (28%) had an invaded margin. Of 177 patients in the SGH group, 9 (5%) had an invaded margin (p = 0.001). An anatomical approach to the resection of oral and oropharyngeal SCC is appropriate, as it results in a rate of invaded margins of less than 10% irrespective of size and site of the primary lesion.     

Specimen‐driven intraoperative assessment of resection margins should be standard of care for oral cancer patients

With an incidence of 350.000 new cases per year, cancer of the oral cavity ranks among the 10 most common solid organ cancers. Most of these cancers are squamous cell carcinomas. Five‐year survival is about 50%. It has been shown that clear resection margins (>5 mm healthy tissue surrounding the resected tumor) have a significant positive effect on locoregional control and survival. It is not uncommon that the resection margins of oral tumors are inadequate. However, when providing the surgeon with intraoperative feedback on the resection margin status, it is expected that obtaining adequate resection margins is improved. In this respect, it has been shown that specimen‐driven intraoperative assessment of resection margins is superior to defect‐driven intraoperative assessment of resection margins. In this concise report, it is described how a specimen‐driven approach can increase the rate of adequate resections of oral cavity squamous cell carcinoma as well as that it is discussed how intraoperative assessment can be further improved with regard to the surgical treatment of oral cavity squamous cell carcinoma.     

Role of oral microbiome in oral oncogenesis,tumor progression,and metastasis

Squamous cell carcinoma is the most common malignant tumor of the oral cavity and its adjacent sites, which endangers the physical and mental health of patients and has a complex etiology. Chronic infection is considered to be a risk factor in cancer development. Evidence suggests that periodontal pathogens, such as Porphyromonas gingivalis, Fusobacterium nucleatum, and Treponema denticola, are associated with oral squamous cell carcinoma (OSCC). They can stimulate tumorigenesis by promoting epithelial cells proliferation while inhibiting apoptosis and regulating the inflammatory microenvironment. Candida albicans promotes OSCC progression and metastasis through multiple mechanisms. Moreover, oral human papillomavirus (HPV) can induce oropharyngeal squamous cell carcinoma (OPSCC). There is evidence that HPV16 can integrate with host cells’ DNA and activate oncogenes. Additionally, oral dysbiosis and synergistic effects in the oral microbial communities can promote cancer development. In this review, we will discuss the biological characteristics of oral microbiome associated with OSCC and OPSCC and then highlight the mechanisms by which oral microbiome is involved in oral oncogenesis, tumor progression, and metastasis. These findings may have positive implications for early diagnosis and treatment of oral cancer.     

Micronucleus—an upcoming marker of genotoxic damage

This study was conceived for the early detection of oral precancer and cancer lesions using a noninvasive reliable technique. Micronucleus assay was performed on oral exfoliated cells of chosen subjects having leukoplakia and squamous cell carcinoma (SCC) using fluorescent (Acridine Orange) and conventional (Feulgen) stainings. The results were analyzed using Mann–Whitney U test, Kruskal–Wallis test, Spearman’s Correlation and SPSS statistical package. The frequency of mean percentage occurrence of micronucleated cells increased significantly in comparison to controls with leukoplakia and squamous cell carcinoma. Subjects with synergism of abnormal oral habits also showed increased micronucleated cells. Fluorescent staining was found to be more sensitive than the conventional one for micronucleus detection. The results clearly demonstrate that micronucleus assay in oral exfoliated cells can be used as a simple reliable marker to assess the genotoxicity and for the early diagnosis of premalignant and malignant lesions. Micronucleus assay is, thus, an easy tool for early detection of cancer.     

Diagnostic aids in detection of oral cancer: An update

Oral cancer is the sixth most common malignancy with almost 500000 new cases reported worldwide annually. The diagnosis of oral cancer at an early stage has a good prognosis as the survival rate is high (around 80%). However, the majority of oral cancer cases are diagnosed at a later stage with a considerably poor 5-year survival rate of 50% according to World Health Organization statistics. Thus, an effective management strategy for oral cancer will depend on its early identification and intervention which would pave the way for superior prognosis. Despite the obvious advantage of earlier diagnosis of oral cancer, no approach has yet proven to be a reliably successful in diagnosis of oral cancer at an early stage. Currently; the primary line of screening of oral cancer is performed by visual inspection, which is a subjective examination. Among the screening tests or diagnostic aids now available for oral cancer, few (toluidine blue, brush biopsy, salivary and serum bio-markers) have been utilised and studied for many years while others have recently become commercially available. The authors in the present article review all the modalities of screening aids used in oral cancer detection and provide an update on the latest screening tools used in oral cancer detection.     

Laser ionization mass spectrometry in oral squamous cell carcinoma

Biomarker research in oral squamous cell carcinoma (OSCC) aims for screening/early diagnosis and in predicting its recurrence, metastasis and overall prognosis. This article reviews the current molecular perspectives and diagnosis of oral cancer with proteomics using matrix‐assisted laser desorption ionization (MALDI) and surface‐enhanced laser desorption ionization (SELDI) mass spectrometry (MS). This method shows higher sensitivity, accuracy, reproducibility and ability to handle complex tissues and biological fluid samples. However, the data interpretation tools of contemporary mass spectrometry still warrant further improvement. Based on the data available with laser‐based mass spectrometry, biomarkers of OSCC are classified as (i) diagnosis and prognosis, (ii) secretory, (iii) recurrence and metastasis, and (iv) drug targets. Majority of these biomarkers are involved in cell homeostasis and are either physiologic responders or enzymes. Therefore, proteins directly related to tumorigenesis have more diagnostic value. Salivary secretory markers are another group that offers a favourable and easy strategy for non‐invasive screening and early diagnosis in oral cancer. Key molecular inter‐related pathways in oral carcinogenesis are also intensely researched with software analysis to facilitate targeted drug therapeutics. The review suggested the need for incorporating ‘multiple MS or tandem approaches’ and focusing on a ‘group of biomarkers’ instead of single protein entities, for making early diagnosis and treatment for oral cancer a reality.     

口腔黏膜鳞癌术后复发挽救性再手术的近期疗效观察

目的：观察不同分期复发性口腔黏膜鳞癌挽救性外科再手术的近期疗效。方法：对47例复发性口腔黏膜鳞癌患者临床再分期后实行挽救性外科再切除手术,并对受试者的复发因素进行分析讨论并跟踪随访。结果：复发性口腔黏膜鳞癌的复发早期组的总生存时间和无瘤生存时间以及1年生存率和1年无瘤生存率要明显长于复发进展期组,而复发早期组的术后复发率低于复发进展期组。结论：在临床再分期的基础上实行挽救性外科再切除手术是治疗复发性口腔黏膜鳞癌的首选方法。术后复发的因素集中于肿瘤部位、手术方法、输血和激素的应用等。为减少复发,应注意少输血和尽早撤离激素。     

Factors affecting surgical mortality of oral squamous cell carcinoma resection

Survival rates for oral squamous cell carcinoma (OSCC) has remained stagnant in recent years and improving surgical mortality could be an avenue to enhance outcomes. This systematic review aims to identify the causes of mortalities, determine both the modifiable and non-modifiable factors involved and target a reduction in postoperative 30-day mortality. In May 2019, a comprehensive search of key databases including PubMed, EMBASE, Cochrane Library was conducted. Blinded selection by two researchers identified papers that included participants who received oral squamous cell carcinoma resection and suffered an in-hospital or 30-day mortality. Selection identified two relevant papers that meet the inclusion criteria. One study had one death in its population sample but only had the cause of death described. Another study had an overall surgical mortality rate of 1% in a population of 21,681. Patients with multiple factors had the highest mortality rates; 4.6% in patients >85 years old and have a T4 diagnosis, 3.9% in patients with a Comorbidity Index ≥1 and a T4 diagnosis. These studies did not determine relationships between factors and causes of death. There are significant knowledge gaps in the literature, that can be addressed through further population analysis studies.     

下颌舌侧松解入路在舌癌间室性切除中的应用研究

目的：评价下颌舌侧松解入路在中晚期舌体癌间室外科切除中术野显露的充分性,以及在保留口腔功能及面部外形等方面的优越性。方法收集我科自2012年3月至今收治的23例接受舌颌颈联合根治术的中晚期舌体癌患者,对入组患者进行术中评价、定期随访、问卷调查和功能测定,在手术显露的彻底性、术后的功能恢复、面部外形等方面进行研究。结果下颌舌侧松解入路在原发灶的显露方面效果良好,术中切缘阳性率为8.70%,能达到切除肿瘤的显露目的,符合无瘤操作的原则。在面部外形及口腔功能恢复等方面具有优势,不存在颏神经损伤及钛板排异的风险。对接受术后放疗的患者,下颌舌侧松解入路手术不存在骨愈合不良及钛板外露的风险,术后并发症少。结论下颌舌侧松解入路在中晚期舌体癌原发灶的间室外科切除中能够暴露充分,符合无瘤原则,在保留和恢复面部外形及口腔功能方面具有较大优势。     

K_v3.4在口腔扁平苔藓和口腔鳞状细胞癌中的表达

目的:研究钾离子通道蛋白kv3.4在正常口腔黏膜(normal oral mucosa,NOM)、口腔扁平苔藓(oral lichen planus,OLP)、口腔鳞状细胞癌(squamous cell carcinoma,OSCC)中的表达及意义。方法:免疫组织化学技术检测16例NOM、20例OLP和30例OSCC组织中kv3.4的表达,采用Wilcoxon秩和检验,α=0.05。结果:kv3.4在OSCC中的表达强度高于OLP(P<0.05),kv3.4在OLP组织的表达高于正常组织(P<0.05),且糜烂型OLP中的表达高于非糜烂型OLP(P<0.05),差异均具有统计学意义。结论:kv3.4可能与OLP及OSCC的发生、发展有一定的关系。     

Can radiological examination of mandibular bone invasion accurately predict the need for mandibular resection in oral squamous cell carcinoma?

Bone invasion by oral squamous cell carcinoma necessitates jaw resection, with preoperative imaging ideally able to guide the resection. A retrospective review of 109 patients with oral squamous cell carcinoma who underwent mandibular resection was performed. Eighty-three had preoperative computed tomography (CT) imaging and 72 underwent magnetic resonance imaging (MRI). The presence of bone invasion on imaging was compared to histopathology. Bone invasion was detected in 44 of 109 resection specimens (40.4%) and was identified on CT in 31 of 83 cases (37.4%) and on MRI in 35 of 72 cases (48.6%). The sensitivity and specificity of CT for detecting bone invasion was 69.0% and 79.6%, respectively, while for MRI was 87.1% and 80.5%, respectively. Histological detection of bone invasion was associated with greater disease-specific mortality (P = 0.002), as was MRI detection of bone invasion (P = 0.027). CT detection was not significant (P = 0.240). Negative prediction of bone invasion was 95% accurate for both modalities in clinically non-invaded mandibles. Survival was reduced in patients who underwent marginal mandibular resection when bone invasion was detected histologically (33.3% vs. 70.5%, P = 0.277) and with CT, although this was not statistically significant. More data are required to determine whether more aggressive resection is warranted when bone invasion is detected preoperatively.     

Molecular markers in the surgical margin of oral carcinomas

Background:  Local or regional lymph node recurrence is the most common pattern of treatment failure in oral squamous cell carcinoma (SCC). The local recurrence rate is 30% even when the surgical resection margin is diagnosed as tumour free. Accumulation of genetic changes in histologically normal epithelium in the surgical resection margin may explain the local recurrence rate. The purpose of this study is to investigate the presence of senescence markers, which may represent early malignant changes in the margin that in routine pathological evaluations are classified as histologically normal.
Methods:  Formalin-fixed, paraffin-embedded surgical specimens from 16 consecutive patients with oral SCC and a clear surgical margin were obtained. The margin was analysed by immunohistochemistry for p53, p16, Chk2, Laminin-5 and glycosylated oncofetal fibronectin.
Results:  Two patterns of p53 expression were found in the histologically normal epithelium in the surgical resection margin. One was characterized by no protein expression in the majority of cells, except for small clusters of basal and parabasal cells with nuclear staining. The other was characterized by p53 expression in the nuclei of most basal cells. The expression of p16 was confined to small groups of cells in the basal cell layer whereas Chk2 was only seen in one case. Upregulation of the stromal proteins, Laminin-5 or glycosylated oncofetal fibronection, was only seen at regions of invasion.
Conclusion:  Small groups of cells expressing p53 and p16 were found in the surgical resection margin that appeared to be histologically normal and may represent early malignant changes.     

表面增强激光解吸-电离质谱法筛选唾液中口腔鳞状细胞癌蛋白标志物

目的 在唾液中筛选口腔癌前病变、鳞状细胞癌、转移癌并与健康人鉴别的肿瘤蛋白标志物.方法 在CM-10蛋白质芯片上采用表面增强激光解吸-电离(Surface enhanced laser desorption/ionization(SELDI)质谱法技术对口腔白斑(6例)、鳞状细胞癌(17例)、转移癌(7例)和健康者(15人)的非刺激性全唾液中的蛋白标志物进行检测,支持向量机法建立指纹图谱诊断模式.结果 口腔鳞状细胞癌和健康人唾液蛋白鉴别模式:蛋白质荷比峰(简称:质荷比)5797、2902、3883和4951组合,敏感性为88.24%、特异性为93.33%;口腔鳞状细胞癌和白斑鉴别模式:质荷比为5818、4617和3884的组合,敏感性为100.00%、特异性为100.00%;口腔鳞状细胞癌和局部转移癌的鉴别模式:质荷比为55 809和5383的组合,敏感性为94.12%、特异性为85.71%.结论 通过SELDI质谱法技术筛选出的肿瘤标志物可以辅助口腔鳞状细胞癌的早期诊断,预测白斑向鳞状细胞癌转化及癌局部转移的潜能.     

Assessing the patient at risk for oral squamous cell carcinoma

Patients and health care workers require continuing education to promote knowledge of the signs, symptoms, and risk factors for oral cancer. This paper reviews the literature assessing diagnostic tools that are currently available or being developed, in order to assist in the biopsy site selection and subsequent diagnosis of patients at risk for oral cancer. There is a general consensus that oral examination of patients at risk for oral squamous cell carcinoma (SCC) should be conducted on a routine basis. However, there can be false-positive and false-negative findings. Toluidine blue has been shown to be useful as an adjunct to the clinical examination when used by experienced clinicians. Exfoliative cytology is not currently used as a routine measure for the evaluation of lesions of the oral mucosa, but further development and the application of biologic markers to cytologic specimens may increase its value. Fluorescent imaging of malignant lesions of the oral mucosa has been shown to be sensitive and specific in animal models but thus far has been reported in only one human trial.
The sensitivity and specificity of these techniques when used by general practitioners need to be assessed. Further, none of the above procedures has yet been shown to be a cost-effective public health measure in screening for oral cancer.     

The feasibility of locating the affected bone of BRONJ with indocyanine green

The morbidity of bisphosphonate‐related osteonecrosis of the jaw (BRONJ) is also increasing with the use of bisphosphonates (BPs). Removing affected bone accurately is the most effective treatment. This study aimed to explore the feasibility of Indocyanine green (ICG)‐based Near‐Infrared fluorescence (NIF) imaging to remove BRONJ affected bone. Firstly, the rat model of BRONJ was constructed. And 5 mg/kg ICG were injected via tail vein, after 12 hr, the affected and healthy bone were dissected for ICG‐based NIF imaging and quantification detection of fluorescence intensity. Finally, all the bone samples were sent for further pathological examination. All the affected bone tissues in rat BRONJ model were fluorescence developed with ICG. And the fluorescence developed regions were further confirmed as affected bone tissues with pathological examination. The fluorescence intensity in affected bone tissues, adjacent, and opposite bone tissues was 1.93*107 ± 2.08*106, 1.19*106 ± 2.33*105, and 1.24*106 ± 1.57*105, respectively (p < .05). Conclusions It was feasible that the extent of affected bone in rat model with BRONJ could be estimated intraoperative via ICG‐based NIF imaging. This novel approach would become an auxiliary method in the treatment of patients with BRONJ in the future.