Randomized trial of fenretinide (4-HPR) to prevent recurrences, new localizations and carcinomas in patients operated on for oral leukoplakia: long-term results

We assessed the efficacy of fenretinide at preventing relapses, new lesions and carcinomas after surgical excision of oral leukoplakia. In a controlled multicenter study, 170 patients operated on for oral leukoplakias with benign postoperative histology were randomized to 200 mg fenretinide daily for 1 year vs. no intervention. Preliminary analysis indicated that fenretinide had good tolerability and was effective at preventing relapses and new lesions during treatment. Analysis after 5-year follow-up suggested that fenretinide protected against relapses and new lesions up to 19 months after randomization, with both limits of the 95% hazard ratio CI for fenretinide vs. control below 1 for 7 months after randomization. There was also a protective effect against all first events, including cancer, for 25 months, with both limits of the 95% CI below 1 up to 11 months after randomization. Subsequently, risk ratio estimates were unstable. Fenretinide was well tolerated and effective at preventing relapses and new leukoplakias during treatment and after. The trial had to be stopped prematurely for very low recruitment and had insufficient power to reveal any protective effect against oral carcinoma; nevertheless, continuing studies on this promising chemopreventive are justified.     

HSP70在喉乳头状瘤和声带白斑组织中的表达及其临床意义

目的: 探讨热休克蛋白70(HSP70)及其上游调控因子HSF1在喉乳头状瘤和声带白斑中的表达,阐明其在喉癌发生中的作用。方法:应用免疫组织化学法检测6例声带白斑 (声带白斑组)、6例喉乳头状瘤（喉乳头状瘤组）和7例声带息肉（对照组）的组织标本中HSP70和HSF1蛋白的表达。结果： HSP70和HSF1蛋白在喉乳头状瘤、声带白斑中的表达高于声带息肉,差异有统计学意义（P<0.05或P<0.01）;声带白斑在所有组织中表达最高。对声带息肉、喉乳头状瘤、声带白斑中HSP70蛋白表达量与HSF1表达的关系进行直线回归分析,结果显示,HSP70蛋白表达量与HSF1的变化呈现正的直线相关（r=0.867,P<0.01）。结论：HSP70和HSF1在声带白斑中的高表达可能与喉癌的发生密切相关,且HSP70和HSF1可能成为喉癌早期诊断的指标。
     

Oral candidosis and oral hairy leukoplakia as predictors of HAART failure in Brazilian HIV-infected patients

INTRODUCTION: Oral candidosis (OC) and hairy leukoplakia (OHL) are important markers of Human Immunodeficiency Virus (HIV) infection immune status. OBJECTIVES: to evaluate if OC and/or OHL should be considered clinical predictors of immune and virologic failure on HIV-infected Brazilian adults undergoing Highly Active Antiretroviral Therapy (HAART). METHODS: 124 HIV-infected patients who used HAART for a minimum of six months were prospectively evaluated. All of them under-took oral examination and serum CD4+ count and viral load (VL), being divided in two groups, P and A, respectively according to the presence or absence of OC and/or OHL. During a six month period, patients belonging to group A were followed. They were re-examined for new oral lesions. New blood samples were collected and they were subdivided into groups P6 and A6. CD4+ count and VL were compared between groups at baseline and after the six months period. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and relative risk (RR) were obtained in order to assess the accuracy of using OC and OHL as predictors of immune and virologic failure, at baseline and after a six month period. RESULTS: At baseline and after six months, patients with OC and OHL have mean CD4+ count lower and mean VL higher than patients of group A and A6 (p < 0.001). OC had high PPV for immune failure and a moderated PPV for virologic failure. OHL had low PPVs for both measures. DISCUSSION AND CONCLUSIONS: OC and OHL still indicate low serum CD4+ count and high VL, but OC seems to be a better predictor of immune and virologic failure in patients undergoing HAART than OHL.     

高效液相色谱法测定三维樟柳碱膜中氢溴酸樟柳碱含量

目的建立测定三维樟柳碱膜中氢溴酸樟柳碱含量的高效液相色谱法。方法采用WatersC18色谱柱（250mm×4．6mm,5μm）,流动相为乙腈-pH=3．5的0．02mol／L磷酸二氢钾溶液（7：93）,流速为1．0mL／min,检测波长为210nm,进样量为100μL。结果樟柳碱质量浓度在0．799～7．990μg／mL范围内与峰面积呈良好的线性关系,r=0．9999（n=6）,平均回收率为99．95％,RSD=1．38％（n=9）。结论所用方法简单、专属性强,可用于三维樟柳碱膜中氢溴酸樟柳碱含量的测定。     

Oral cancer prediction by noninvasive genetic screening

Oral squamous cell carcinomas (OSCCs) develop in genetically altered epithelium in the mucosal lining, also coined as fields, which are mostly not visible but occasionally present as white oral leukoplakia (OL) lesions. We developed a noninvasive genetic assay using next-generation sequencing (NGS) on brushed cells to detect the presence of genetically altered fields, including those that are not macroscopically visible. The assay demonstrated high accuracy in OL patients when brush samples were compared with biopsies as gold standard. In a cohort of Fanconi anemia patients, detection of mutations in prospectively collected oral brushes predicted oral cancer also when visible abnormalities were absent. We further provide insight in the molecular landscape of OL with frequent changes of TP53, FAT1 and NOTCH1. NGS analysis of noninvasively collected samples offers a highly accurate method to detect genetically altered fields in the oral cavity, and predicts development of OSCC in high-risk individuals. Noninvasive genetic screening can be employed to screen high-risk populations for cancer and precancer, map the extension of OL lesions beyond what is visible, map the oral cavity for precancerous changes even when visible abnormalities are absent, test accuracy of promising imaging modalities, monitor interventions and determine genetic progression as well as the natural history of the disease in the human patient.     

低温等离子消融治疗声带白斑的临床疗效观察

目的:分析低温等离子消融治疗声带白斑的临床疗效。方法:选取2014年4月~2018年4月在本院采用低温等离子消融进行治疗的39例患者作为研究对象进行回顾性分析,统计病变上皮鳞状细胞不典型增生情况以及相应的治疗有效率。结果:39例患者中有16例患者为上皮角化不伴鳞状细胞不典型增生,有11例患者为上皮角化伴鳞状细胞轻度不典型增生,有12例患者为上皮角化伴鳞状细胞中度以及重度不典型增生,相应的治疗有效率分别为100.00%(16/16)、90.91%(10/11)和83.33%(10/12)。结论:低温等离子消融在声带白斑治疗中具有较高的应用价值,相对来说患者病变上皮鳞状细胞不典型增生情况越轻,其治疗有效率越高。     

口腔黏膜上皮癌变过程中内皮素Ⅰ表达的定量研究

目的 了解正常口腔黏膜,癌前病变及癌组织中内皮素I(ET-I)表达特点及其变化规律。方法采用免疫组化和图象分析技术,对人正常口腔黏膜(NOR)10例、口腔黏膜下纤维化(OSF)10例、鳞状细胞癌(SCC)15例上皮细胞的ET-I含量进行图像分析。结果 ①ET-I在OSF、OLK、SCC组织中的表达增强,阳性物质主要位于上皮棘细胞、基质细胞的胞浆胞膜上,且ET-I含量显著高于正常对照组(p<0.01)。②OLK、SCC上皮细胞ET-I含量呈显著增加趋势(p<0.05)。③OSF上皮细胞ET-I含量显著高于OLK(p<0.05),与SCC相比无显著性差异(p>0.05)。结论 ET-I含量在口腔癌前病变至癌变过程中可能存在一种量变关系,OSF中ET-I过量表达可能提示其上皮细胞的癌变潜能。     

PTEN、p27在口腔粘膜白斑和口腔癌组织中的表达及意义

目的　探讨抑癌基因PTEN、p2 7在口腔粘膜白斑 (oralleukoplakia ,OLK)和口腔癌 (oralsquamouscellcancer,OSCC)组织中的蛋白表达及意义。方法　应用免疫组化S -P法检测 10例正常口腔粘膜、2 5例口腔粘膜白斑 (其中白斑伴上皮异常增生 15例 ,白斑不伴上皮异常增生 10例 )及 32例口腔癌组织中抑癌基因PTEN和p2 7的蛋白表达情况。结果　正常口腔粘膜和白斑不伴上皮异常增生组织中PTEN和 p2 7蛋白全部阳性表达 ;白斑伴上皮异常增生组织中PTEN和 p2 7蛋白阳性表达率分别为93.3%、73.3%。OSCC组织中PTEN蛋白阳性表达率为71.9% ,其中高、中、低分化OSCC组织中PTEN蛋白阳性表达率分别为 85 .7%、75 %和 33.3% ,统计学分析表明PTEN在OSCC组织中的蛋白表达与组织分化程度明显相关 (P <0 .0 5 )。OSCC组织中 p2 7蛋白的阳性表达率为4 0 .6 % ,其中高、中、低分化OSCC组织中p2 7蛋白的阳性表达率分别为 4 2 .9%、4 1.7%和 33.3% ,统计学分析表明p2 7在OSCC组织中的蛋白表达与组织分化程度无明显相关 (P >0 .0 5 )。结论　OSCC组织中PTEN和 p2 7蛋白的阴性表达率较高 ,说明PTEN和 p2 7基因突变或缺失在OSCC的发生发展过程中起重要作用。     

Dietary factors in oral leukoplakia and submucous fibrosis in a population-based case control study in Gujarat, India

OBJECTIVES: To investigate the relationship of specific nutrients and food items with oral precancerous lesions among tobacco users.
DESIGN: A population-based case-control study. SETTING: Villages in Palitana taluk of Bhavnagar district, Gujarat, India.
SUBJECTS AND METHODS: An interviewer-administered food frequency questionnaire, developed and validated for this population, was used to estimate nutrient intake in blinded, house-to-house interviews. Among 5018 male tobacco users, 318 were diagnosed as cases. An equal number of controls matched on age (±5 years), sex, village, and use of tobacco were selected.
MAIN OUTCOME MEASURES: Odds ratios (OR) from multiple logistic regression analysis controlling for relevant variables (type of tobacco use and economic status).
RESULTS: A protective effect of fibre was observed for both oral submucous fibrosis (OSF) and leukoplakia, with 10% reduction in risk per g day^-1 ( P < 0.05). Ascorbic acid appeared to be protective against leukoplakia with the halving of risk in the two highest quartiles of intake (versus the lowest quartile: OR = 0.46 and 0.44, respectively; P < 0.10). A protective effect of tomato consumption was observed in leukoplakia and a suggestion of a protective effect of wheat in OSF.
CONCLUSION: In addition to tobacco use, intake of specific nutrients may have a role in the development of oral precancerous lesions.