Expression and significance of p53 and mdm2 in patients with leukoplakia cancer

Objective:To study the relationship of the expressions of p53 and mdm2 in leukoplakia cancer.Methods:RT-PCR was used to detect the mRNA of p53,mdm2 in patients with leukoplakia cancer.The frequencies of p53,mdm2 in peripheral blood were detected by flow cytometric analysis.Results:The expression of p53mRNA in normal oral mucosa,simple oral leukoplakia,no-simple oral leukoplakia and leukoplakia cancer were 7.7%,27.3%,33.3%,56.8%,respectively.The frequencies of p53 in normal oral mucosa,simple oral leukoplakia,no-simple oral leukoplakia and leukoplakia cancer were(0.3±0.1)%,(l.6±0.9)%,(1.9±1.1)%,(3.4±1.8)%.The expression of mdm2 mRNA in normal oral mucosa,simple oral leukoplakia,no-simple oral leukoplakia and leukoplakia cancer were 0.0%,6.8%,11.1%,37.8%,respectively.The frequencies of mdm2 in normal oral mucosa,simple oral leukoplakia,no-simple oral leukoplakia and leukoplakia cancer were(0.1±0.1)%,(0.8±0.6)%,(1.2±0.8)%,(1.2±0.8)%.There was a positively correlation between p53 mRNA and mdm2 mRNA.Conclusions:The positive rate of p53 and mdm2 cells in the peripheral blood increases in patients with leukoplakia cancer tissue and has positive correlation with the severity of leukoplakia cancer.

Photodynamic therapy of oral leukoplakia and orallichen planus using methylene blue:A pilot study

Premalignant lesions like oral lichen planus(OLP),oral leukoplakia(OL)has a fair probability of transforming into malignancy and they are perverse toward conventional therapies.Photody-namic therapy(PDT)has been considered as an alternative/complimentary therapeutic mo-dality for the management of premalignant lesions.In this study,methylene blue mediated photodynamic therapy(MB-PDT)was used as a possible alternative method for the treatment of OLP and OL.A total of 15 OLP lesions and 13 OL lesions were enrolled in the study.The patients were irradiated 1using metal halide lamp filtered at 630土10nm,with a light exposure dose of 120 J/cm^(2) per stting.For the OLP lesions,MB-PDT was performed once a week for four weeks and for the OL lesions,MB-PDT was performed twice a week for three weeks.Lesions were evaluated pre-and post-and at follow-u sessions by changes in sign and symptom scores,and size of lesions.We have observed a 53.3%of complete reduction in the treated OLP lesions and their decrease in size,sign and symptom score after treatment and at follow-up session was statistially signifcant.We have also observed complete response for one OL lesion of the 13 treated lesions.The result indicates that MB-PDT is an effective modality in management of OLP and OL.Among the two types of premalignancies treated with MB-PDT,OLP lesions responded much better than that of OL.

Upregulation of epidermal growth factor receptor 4 in oral leukoplakia

In the present study,we investigate the expression profile of the epidermal growth factor receptor family,which comprises EGFR/ ErbBl,HER2/ErbB2,HER3/ErbB3 and HER4/ErbB4 in oral leukoplakia(LP).The expression of four epidermal growth factor receptor (EGFR) family genes and their ligands were measured in LP tissues from 14 patients and compared with levels in 10 patients with oral lichen planus(OLP) and normal oral mucosa(NOM) from 14 healthy donors by real-time polymerase chain reaction(PCR) and immunohistochemistry.Synchronous mRNA coexpression of ErbBl,ErbB2,ErbB3and ErbB4 was detected in LP lesions.Out of the receptors,only ErbB4 mRNA and protein was more highly expressed in LP compared with NOM tissues.These were strongly expressed by epithelial keratinocytes in LP lesions,as shown by immunohistochemistry.Regarding the ligands,the mRNA of Neuregulin2 and 4 were more highly expressed in OLP compared with NOM tissues.Therefore,enhanced ErbB4 on the keratinocytes and synchronous modulation of EGFR family genes may contribute to the pathogenesis and carcinogenesis of LP.

Low expression of angiotensinogen and dipeptidyl peptidase 1 in saliva of patients with proliferative verrucous leukoplakia

AIM To elucidate the profile of the salivary proteome.METHODS Unstimulated whole mouth saliva was collected from 30 volunteers [15 proliferative verrucous leukoplakia(PVL) patients and 15 controls] and proteins were submitted for mass spectrometry-based proteomics using the discovery approach,followed by analyses of variance and logistic regression tests.RESULTS A total of two hundred and eighty-three proteins were confidently identified in saliva.By combining two low abundance proteins from the PVL group,angiotensinogen(AGT) and dipeptidyl peptidase 1(DPP1),a model for group differentiation was built with a concordance index of 94.2%,identifying both proteins as potential etiologic biomarkers for PVL.CONCLUSION This study suggests that both AGT and DPP1 may be involved in developmental mechanisms of PVL.

Critical review of topical management of oral hairy leukoplakia

Oral hairy leukoplakia(OHL) is a disease associated with Epstein-Barr virus and human immunodeficiency virus infections. OHL is usually an asymptomatic lesion, but in some cases treatment is recommended to reestablish the normal characteristics of the tongue, to eliminate pathogenic microorganisms, to improve patient comfort and for cosmetic reasons. Proposed treatments for this condition include surgery, systemic antiviral treatment and topical management. Topical treatment is an inexpensive and safe therapy that is easy to apply, noninvasive, free of systemic adverse effects and effective over a long period of time. The aim of this study was to present a review of the literature for topical therapy for OHL. Gentian violet, retinoids, podophyllin, acyclovir and podophyllin associated with topical antiviral drugs were used to treat OHL. Reports with this focus are limited, and since 2010, no new studies have been published that discuss the efficacy of topical treatments for OHL. Podophyllin with acyclovircream was found to be effective, causing regression of lesions with no recurrences. Additional searches are necessary to provide clinical evidence of topical man agement effectiveness.

The use of traditional Chinese medicine internally and externally combined with auricular acupuncture point bloodletting in the treatment of vulvar leukoplakia

Vulvar leukoplakia refers to the chronic disease of degeneration and hypopigmentation of the skin and mucous membrane of the vulva with unbearable itching in women, seriously affecting the quality of life. The main treatment of western medicine for vulvar leukoplakia is the external use of glucocorticoids or estrogen, resulting to the high recurrence rate and side effects. Traditional Chinese medicine (TCM) has the characteristics of the overall concept and dialectical treatment with a variety of ways. Literature review in recent years found that the treatment of TCM decoction combined with external therapies, such as external fumigation, acupuncture and other treatments, or the combination of TCM decoction and external western medicine hormone ointment, can obtain good effects in vulvar leukoplakia. During the clinical practice, we found that the use of TCM internally and externally combined with auricular acupuncture point bloodletting was highly effective with unique advantages in the treatment of vulvar leukoplakia, providing the ideas guidance for clinicians.

C-Ha-ras Oncogene in Oral Leukoplakia Tissues

The amplification and the G-T mutation at codon 12 of the C-Ha-ras oncogene in oral leukoplakia tissues were analyzed by using polymerase chain reaction (PCR) and molecular biologic technique. The results showed that these tissues had no amplification of Ha-ras oncogene. Only one case harbored G-T mutation in 11 oral leukoplakias, but this mutation was absent in 10 normal oral mucosal tissues. The possible role and significance of C-Ha-ras oncogene in oral precancerous lesions were also discussed.

Proliferative verrucous leukoplakia may initially mimic lichenoid reactions

Proliferative verrucous leukoplakia is an intriguing disease, which occurs particularly in women aged greater than 60 years, is not associated with tobacco and alcohol, and has a high risk of recurrence and malignant transformation. Although it is well known that the typical presentation is characterized by multifocal and verrucous white lesions, there is no description that its initial clinical presentation may simulate a lichenoid reaction.

Biomarkers of malignant transformation in oral leukoplakia:from bench to bedside

Oral leukoplakia is a common precursor lesion of oral squamous cell carcinoma,which indicates a high potential of malignancy.The malignant transformation of oral leukoplakia seriously affects patient survival and quality of life;however,it is difficult to identify oral leukoplakia patients who will develop carcinoma because no biomarker exists to predict malignant transformation for effective clinical management.As a major problem in the field of head and neck pathologies,it is imperative to identify biomarkers of malignant transformation in oral leukoplakia.In this review,we discuss the potential biomarkers of malignant transformation reported in the literature and explore the translational probabilities from bench to bedside.Although no single biomarker has yet been applied in the clinical setting,profiling for genomic instability might be a promising adjunct.

Importance of complementary data to histopathological image analysis of oral leukoplakia and carcinoma using deep neural networks

Background Oral cancer is one of the most common types of cancer in men causing mortality if not diagnosedearly.In recent years,computer-aided diagnosis(CAD)using artificial intelligence techniques,in particular,deepneural networks have been investigated and several approaches have been proposed to deal with the automateddetection of various pathologies using digital images.Recent studies indicate that the fusion of images with thepatient’s clinical information is important for the final clinical diagnosis.As such dataset does not yet exist fororal cancer,as far as the authors are aware,a new dataset was collected consisting of histopathological images,demographic and clinical data.This study evaluated the importance of complementary data to histopathologicalimage analysis of oral leukoplakia and carcinoma for CAD.Methods A new dataset(NDB-UFES)was collected from 2011 to 2021 consisting of histopathological imagesand information.The 237 samples were curated and analyzed by oral pathologists generating the gold standardfor classification.State-of-the-art image fusion architectures and complementary data(Concatenation,MutualAttention,MetaBlock and MetaNet)using the latest deep learning backbones were investigated for 4 distincttasks to identify oral squamous cell carcinoma,leukoplakia with dysplasia and leukoplakia without dysplasia.We evaluate them using balanced accuracy,precision,recall and area under the ROC curve metrics.Results Experimental results indicate that the best models present balanced accuracy of 83.24%using images,demographic and clinical information with MetaBlock fusion and ResNetV2 backbone.It represents an improvement in performance of 30.68%(19.54 pp)in the task to differentiate samples diagnosed with oral squamous cellcarcinoma and leukoplakia with or without dysplasia.Conclusion This study indicates that cured demographic and clinical data may positively influence the performance of artificial intelligence models in automated classification of oral cancer.

喉白斑的窄带成像内镜下诊断与病理分析

目的 探讨通过窄带成像(narrow band imaging,NBI)电子喉镜下观察喉黏膜上皮内的毛细血管袢形态,能否指导喉白斑患者治疗方法的选择。方法 选取2019年6月~2021年9月临床诊断为喉白斑的68例患者为研究对象,根据NBI电子喉镜的诊断结果,将患者分为两组:良性病变组(52/68)和恶性病变组(16/68)。比较NBI喉镜诊断与病理检查结果的一致性。结果良性病变组中病理确诊为鳞状上皮增生伴角化35例(67.31%),轻度不典型增生9例(17.31%),中度不典型增生3例(5.77%),原位癌5例(9.62%),恶性病变组中病理确诊为中度不典型增生2例(12.50%),重度不典型增生1例(6.25%),原位癌9例(56.25%),浸润癌4例(25.00%)。采用Kappa一致性检验法,k=0.687,P<0.001,说明NBI电子喉镜诊断结果和病理检查结果存在一致性。结论 NBI电子喉镜能很好的分辨喉白斑的性质,对喉白斑治疗方法的选择和随访观察喉白斑的进展有较高的指导意义。

基于皮肤镜的外阴白斑无创诊断与疗效评估

外阴白斑是妇科常见病,临床上可以通过患者症状、体征对该病作出临床诊断,但外阴活组织病理检查(外阴活检)是诊断的金标准,也是疗效评价的客观指标。鉴于外阴活检的有创性和女性外阴的特殊性,无论是基于诊断目的的初次活检还是基于疗效评估目的的再次活检在临床应用的阻力都非常大,同时有违人道精神和微无创的医学发展理念。有鉴于此,团队结合近三十年使用自制中药膏无创治疗该病的经历、经验,率先提出使用皮肤镜对该病进行无创诊断和疗效评估的理念并进行了系列开创性研究,取得相应研究结果。本文即根据外阴白斑研究现状和团队的研究结果撰写的一篇述评,希望借此引起妇产科学界对皮肤镜用于外阴白斑无创诊断与疗效评估的重视,逐渐提高其研究、应用的普及率、准确性,服务临床、造福患者。

计算机辅助下自体荧光图像定量结果与口腔白斑病上皮异常增生等级的相关性

目的·探究计算机辅助下自体荧光图像定量结果与口腔白斑病上皮异常增生等级的相关性。方法·纳入2016年4月—2024年1月于上海交通大学医学院附属第九人民医院口腔黏膜病科就诊的口腔白斑病患者357例。利用手持自体荧光仪器获取患者病损的自体荧光图像,将自体荧光图像转为灰度图像,获得量化指标。在Python中拟合有序多元Logistic回归模型,绘制累积概率图。将数据集划分训练集和测试集,生成决策树,调整不同的超参数,获得最佳的模型效果。计算准确度、精确度和F1分值。利用混淆矩阵对模型性能进行可视化呈现。结果·随着上皮异常增生程度的增加,相对色阶平均值呈现下降趋势。在上皮异常增生二分类中累积概率图不同类别曲线之间无重叠,在四分类中仅上皮重度异常增生与其他类别曲线有重叠,说明模型的区分能力较好。在二分类病理等级中,当训练集和测试集比例为4∶1、决策树最大深度为2时,准确度、精确度、F1分值可达到较高,分别为0.792、0.801和0.795。在四分类病理等级中,当训练集和测试集比例为9∶1、决策树最大深度为4时,准确度、精确度、F1分值可达到较高,分别为0.611、0.537和0.569。结论·口腔黏膜病专科医师可将计算机辅助下自体荧光图像定量结果作为参考依据,预测口腔白斑病患者上皮异常增生程度,监控患者癌变风险。

声带白斑术后复发影响因素探究及预测模型的建立

目的研究声带白斑术后复发的影响因素并建立临床预测模型。方法回顾性分析2016年2月~2020年2月手术治疗的声带白斑患者386例的临床资料。根据随访结果,将患者分为复发组(89例)和未复发组(297例),应用单因素分析和Logistic回归分析筛选出声带白斑术后复发的影响因素,建立Logistic风险预测模型,并采用R软件以Boostrap法对模型进行内部验证。结果年龄(OR=1.082)、饮酒(OR=1.946)、滥用嗓音(OR=2.436)、咽喉反流(OR=2.054)、中度异型增生(OR=2.383)和重度异型增生/原位癌(OR=3.304)是声带白斑术后复发的影响因素。模型的内部验证AUC为0.777,95%CI为0.663~0.825,模型拟合度较好。结论声带白斑术后复发与患者年龄、白斑范围、病理形态、咽喉反流等有关。

内镜检查对声带白斑病理诊断的预测价值研究

目的旨在确定内镜下白光成像(white lighting imaging,WLI)和窄带成像(narrow band imaging,NBI)对声带白斑(vocal cord leukoplakia,VCL)病理类型进行诊断的最佳截断点,以提高非侵入性预测VCL病理性质的准确性,并为VCL患者是否需要手术干预及手术时机提供参考依据。方法纳入96例确诊病理性质为VCL患者。术前分别进行WLI模式及NBI模式下的图像采集,并对病变进行WLI模式Chen分型和NBI模式Ni分型的评定。通过比较受试者操作特征曲线的约登指数得出分型的最佳截断值。通过比较2种临床分型的曲线下面积(area under the curve,AUC)、最佳截断值下的准确度、敏感度、特异性、阳性预测值及阴性预测值评价不同临床分型对VCL病理性质的诊断效能。结果WLI模式Chen分型、NBI模式Ni分型与病理等级间均存在相关性(rs=0.513、0.653,P<0.001)。WLI模式Chen分型的最佳截断值为3,即光滑平坦型及光滑隆起型为良性病变,粗糙型为恶性病变;NBI模式Ni分型的最佳截断值为5,即Ⅰ~Ⅳ型为良性病变,Ⅴ型、Ⅵ型为恶性病变。WLI模式Chen分型、NBI模式Ni分型的AUC分别为0.815,0.875。最佳截断值的准确度、敏感度、特异性、阳性预测值及阴性预测值Chen分型为79.51%,84.62%,75.71%,72.13%,86.89%;Ni分型为85.25%,76.92%,91.42%,86.96%,84.21%。结论NBI模式Ni分型及WLI模式Chen分型的诊断效能均较高,但NBI模式Ni分型对VCL病理性质的诊断效能高于白光模式Chen分型。

光动力疗法治疗口腔白斑的研究进展

口腔白斑(oral leukoplakia, OLK)指发生于口腔黏膜上不能被擦去、也不能以临床或组织病理学方法诊断为其他可定义的疾病的白色损害,是一种口腔黏膜癌前病变。现有治疗OLK的方法中,非手术治疗如药物治疗缺乏其防止OLK恶性转化和复发的确切证据;而手术治疗则存在适应证窄、术后口腔形态及功能受损等不足;光动力疗法(photodynamic therapy, PDT)是一种现代的非侵入性疗法,可用于治疗包括口腔白斑在内的各种肿瘤及非肿瘤病变,由于其良好的组织形态及功能保存潜能,现已成为治疗口腔白斑的一种新型且前景广阔的治疗选择。该文就PDT治疗口腔白斑应用的光敏剂、光源及其辅助治疗手段作一综述。

窄带成像技术不同分型诊断声带白斑良恶性的价值

目的探讨电子喉镜下白光模式及窄带成像(NBI)模式分型鉴别诊断声带白斑(VCL)性质的价值。方法136例VCL患者均接受白光模式、NBI模式检查,比较不同病变性质患者的病理特征,分析不同分型诊断VCL性质的价值。结果良性组的吸烟、病变累及前联合、累及范围≥50%占比均低于恶性组(P<0.05)。NBI模式的NI分型诊断VCL病变性质的准确度最高,其次为白光模式下的CHEN分型;NBI模式的NI分型鉴别VCL性质的Kappa值最高。结论电子喉镜下白光模式及NBI模式对VCL性质鉴别均具有一定的价值,其中NBI模式下NI分型与病理检查的一致性最高。

激光剥离与器械剥离声带白斑的疗效对比研究

目的 研究对比CO_(2)激光剥离术与器械剥离术治疗声带白斑的疗效。方法 回顾性分析2017年5月~2022年6月在浙江省中医院接受手术治疗的声带白斑患者158例。根据手术方法将患者分为激光剥离组(n=85)和器械剥离组(n=73),比较两组的治疗效果、嗓音功能和声带功能。结果 激光剥离组痊愈率为96.5%,有效率为2.4%,总有效率为97.6%,复发率为1.2%。器械剥离组痊愈率为94.5%,有效率为1.4%,总有效率95.9%,复发率为4.1%。两组总有效率及复发率差异均无统计学意义(P>0.05)。两组术后嗓音功能和声带功能均有改善(P<0.05),激光剥离组在基频微扰、振幅微扰、嗓音障碍严重指数、声带振动对称性评分和声带黏膜波评分方面优于器械剥离组(P<0.05)。结论 CO_(2)激光剥离术治疗声带白斑总体效果优于器械剥离术,对患者嗓音起到积极的改善效果。

马大正外洗方联合电刺激治疗外阴白斑临床研究

目的:观察马大正教授外洗方联合低频电刺激治疗外阴白斑的临床疗效。方法:收集2021年1月—2022年9月温州市中医院妇科治疗的外阴白斑患者,共40例。所有患者均采取马大正教授自拟的外洗方联合仿生物电刺激治疗。外洗方治疗,隔天1次,每次15 min,治疗10次为1个疗程,共治疗2个疗程。电刺激治疗与外洗方治疗交替进行,隔天1次,治疗10次为1个疗程,共2个疗程。经期停止外洗方及电刺激治疗。比较治疗前后外阴瘙痒程度、外阴皮肤弹性、外阴病变范围、外阴皮肤颜色情况评分,以及生活质量评分,观察随访3个月后的疗效。结果:治疗后,患者外阴瘙痒程度、外阴皮肤弹性、外阴病变范围、外阴皮肤颜色情况的评分均较治疗前降低,差异均有统计学意义(P<0.05);治疗后,生活质量评分较治疗前升高,差异有统计学意义(P<0.05)。随访3个月后,临床疗效总有效率为85.0%。结论:马大正外洗方联合电刺激治疗外阴白斑可有效改善患者的症状与体征。

Improvement in the risk assessment of oral leukoplakia through morphology-related copy number analysis

Oral leukoplakia is the most common type of oral potentially malignant disorders and considered a precursor lesion to oral squamous cell carcinoma.However,a predictor of oral leukoplakia prognosis has not yet been identified.We investigated whether copy number alteration patterns may effectively predict the prognostic outcomes of oral leukoplakia using routinely processed paraffin sections.Comparison of copy number alteration patterns between oral leukoplakia with hyperplasia(HOL,n=22)and dysplasia(DOL,n=21)showed that oral leukoplakia with dysplasia had a higher copy number alteration rate(86%)than oral leukoplakia with hyperplasia(46%).Oral leukoplakia with dysplasia exhibited a wider range of genomic variations across all chromosomes compared with oral leukoplakia with hyperplasia.We also examined a retrospective cohort of 477 patients with oral leukoplakia with hyperplasia with detailed follow-up information.The malignant transformation(MT,n=19)and leukoplakia recurrence(LR,n=253)groups had higher frequencies of aneuploidy events and copy number loss rate than the free of disease(FD,n=205)group.Together,our results revealed the association between the degree of copy number alterations and the histological grade of oral leukoplakia and demonstrated that copy number alteration may be effective for prognosis prediction in oral leukoplakia patients with hyperplasia.