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Objectives: To evaluate the characteristics of laryngopharyngeal reflux (LPR) in patients with different hypertrophic laryngeal diseases and to explore the relationship between LPR and these diseases., Methods: A retrospective analysis was performed. The clinical data of 154 patients were collected. According to their diagnoses, patients were divided into 3 groups. Group 1 included 49 patients with vocal cord polyps. Group 2 contained 52 patients with vocal cord leukoplakia. Group 3 included 53 patients with laryngeal carcinoma. The reflux symptom indexes (RSIs), reflux finding scores (RFSs), and Ryan scores of all patients were evaluated and compared., Results: Patients with vocal cord polyps were the youngest of the 3 groups, and those with laryngeal carcinoma were the oldest. A male preponderance emerged in each group. In total, 128 patients (83.12%) had positive RSI/RFS values and 60 (60/146, 41.1%) patients had positive Ryan scores. The positive RSI/RFS rates of both groups 1 and 2 (89.80% and 92.16%, respectively) were significantly higher than that of group 3 (69.81%). Moreover, the positive Ryan score rates in both groups 1 and 2 (39.58% and 53.85%, respectively) were significantly higher than that of group 3 (28.26%)., Conclusions: Laryngopharyngeal reflux occurs in many patients with vocal cord polyps, vocal cord leukoplakia, and vocal cord carcinoma, indicating that LPR may be important in the pathogenesis of these diseases. Laryngopharyngeal reflux occurs more common in patients with vocal cord polyps and leukoplakia and less common in those with laryngeal carcinoma, suggesting the role of LPR on these diseases may be different.

Objectives: To investigate the existing published evidence supporting the role of laryngopharyngeal reflux (LPR) in the development of the select nonfunctional laryngeal diseases of laryngotracheal stenosis, granuloma, leukoplakia, and laryngeal infections., Data Sources: PubMed, Cochrane Library, and Scopus., Review Methods: A systematic review was performed by 3 independent investigators for studies providing information about the prevalence and role of LPR in the development of laryngotracheal stenosis, granuloma, leukoplakia, and laryngeal infections. Diagnostic criteria and clinical outcome evaluation of included studies were analyzed with PRISMA criteria., Results: Of the 64 relevant publications, 27 clinical and 4 basic science studies were included. Ten studies used objective reliable examinations for LPR diagnosis (eg, dual- or triple-probe or oropharyngeal pH monitoring, multichannel intraluminal impedance-pH monitoring, or pepsin detection). According to the bias analysis and the results of studies, the association between LPR and laryngotracheal stenosis, leukoplakia, laryngeal papillomatosis, or vocal fold granuloma remains poorly demonstrated. There is a notable heterogeneity among included studies regarding their inclusion criteria, diagnostic methods, and clinical outcome evaluation. Although some experimental findings support the involvement of bile salts and other gastroduodenal proteins active in alkaline pH, no included clinical studies assessed the role of nonacid and mixed reflux through multichannel intraluminal impedance-pH monitoring., Conclusion: The involvement of LPR in the development of leukoplakia, laryngotracheal stenosis, vocal fold granuloma, and laryngeal papillomatosis is currently not demonstrated. The potential relationship between LPR and these select nonfunctional laryngeal diseases must be confirmed through future clinical and experimental studies considering acid, nonacid, and mixed LPR.

Oral potentially malignant disorders refer to oral mucosal disorders with increased risk for malignant transformation, primarily to oral squamous cell carcinoma (SCC). Leukoplakia and erythroplakia are the most common of these disorders, but others have been identified. Transformation rates to oral cancer vary based on multiple factors. Healthcare providers should be aware of risk factors and clinical manifestations of these disorders and should intervene early to monitor and/or treat them to reduce the potential for malignant transformation.

Objective: To study the mechanism of vocal mucosal barrier damage mediated by NF-κB and NF-κB-regulated signaling pathway via probing the expression of inflammatory factors and essential proteins for node of NF-κB signaling pathway. Methods: The patients suffering from vocal leukoplakia accompanied with larygopharyngeal reflux(LPR) were treated with oral administration of proton pump inhibitor(PPI). Mucosal specimens of vocal cord were collected from all patients before PPI treatment. And the mucosal specimens of vocal cord were collected from the patients with suspected recurrence at 8 weeks after PPI treatment. HE staining was used to observe the histopathological changes of the mucosa. ELISA was utilized to detect the levels of inflammatory factors including tumor necrosis factor(TNF)-α, interleukin(IL)-1 and IL-6. Western blot was used to detect the expression of p-p65, p-IKK and p-IκB. Immunofluorescence method was adopted to detect the entrance of p65 to cell nucleus.Data was analyzed by SPSS 23.0 software. Results: In PPI untreated group, the expressions of IL-1β, TNF-α and IL-6 in the specimens of 8 weeks after operation were not different significantly from those obtained during operation.But in the PPI-treated group, the expressions were down-regulated.The expression of p-p65 in the middle and high grade heterogenous hyperplasia group was higher than that of low level heterogenous hyperplasia group.The difference of p65 and p-p65 expression between 8 weeks after surgery and surgery in PPI-untreated group was statistically insignificant ( P >0.05). The difference of p65 expression between PPI-treated group and PPI pre-treatment group was statistically insignificant ( P >0.05). The expression of p-p65 in the PPI-treated group was lower than that of the PPI pre-treatment group ( P <0.05). The expressions of IL-1β, TNF-α and IL-6 were positively related with that of NF-κB-p65. Immun of luorescence method revealed the entrance of p65 to cell nucleus in PPI pre-treatment group, which meant that NF-κB was activated. In the PPI-treated group, few activated p65 could be observed in the cell nucleu. Conclusion: The possible mechanism of vocal mucosal barrier damage in vocal leukoplakia accompanied with LPR maybe the vocal mucosal inflammation mediated by NF-κB and NF-κB-regulated signaling pathway activated with refluxed materials.

Objective: To investigate the etiology, clinical and pathological characteristics of laryngeal leukoplakia and the predictive risk factors of recurrence and malignant transformation. Methods: Clinical data of 263 patients with laryngeal leukoplakia between January 2000 and December 2015 were analyzed retrospectively. Results: The pathological diagnoses included squamous epithelial hyperplasia (54.4%), mild dysplasia (17.9%), moderate dysplasia (12.2%), severe dysplasia and carcinoma in situ (12.5%), and invasive carcinoma (3.0%). Age and the extent of lesion were statistically different among different pathological groups ( P <0.05). Gender, smoking and alcohol consumption did not show statistical differences among different pathological groups ( P >0.05). Follow-up of 215 patients, excluding 6 cases of invasive carcinoma. The recurrence rate was 20.6%(43/209), and the malignant transformation rate was 5.3%(11/209). Multivariate analysis showed that pathological classification of moderate to severe dysplasia was the independent risk factor for recurrence and malignant transformation of laryngeal leukoplakia ( P <0.05). In patients with severe dysplasia and carcinoma in situ, the recurrence proportion of conservative treatment, vocal cords (partial) resection and radiotherapy were 8/10, 0/10 and 2/11 respectively. Conclusions: Laryngeal leukoplakia occurs frequently in elderly men with long-term smoking history. Pathological diagnoses are different. The grade of dysplasia is the predictive risk factor for the recurrence and malignant transformation of laryngeal leukoplakia. More aggressive treatment and closer follow-up should be warranted for patients with moderate dysplasia, severe dysplasia and carcinoma in situ.

Objective: To investigate the pathogenic factors of vocal leukoplakia and its clinical and pathological features. Methods: Eighty-one patients with vocal cord leukoplakia who underwent surgery between February 2010 and December 2016 and 160 volunteers without pharyngeal symptoms designed as controls were included in this case control study. The clinicopathological characteristics of 81 patients were summarized and analyzed synthetically. Results: There was statistical significance in reflux symptom index(RSI), reflux finding score(RFS), smoking index, and drinking index between case group and control group( Z =-5.35, -4.82, -4.76, -2.44, P <0.05). The voice-using duration per day in case group was significantly longer than that of control group.There was no statistical significance in hospital anxiety and depression scale for anxiety(HADA) scores、hospital anxiety and depression scale for depression(HADD) scores between case group and control group( P >0.05). In 42 patients who received 24-hour dual probe pH monitoring the prevalence of pathologic LPR was 42.8%. In 81 patients, 39(48%)patients were pathologically diagnosed as squamous cell hyperplasia, 18(22%)patients as mild dysplasia, 12(15%)sides as moderate dysplasia , 10(12%)patients as severe dysplasia and 2(2%)patients as carcinoma in - situ . The average age of high-risk pathological vocal leukoplakia was significantly higher than that of low-risk leukoplakia( t =-2.73, P <0.01). The propotion of speckled leukoplakia in high-risk leukoplakia was significantly higher than that of low-risk leukoplakia(χ(2)=23.81, P <0.01). There was no statistical significance between high-risk leukoplakia and low-risk leukoplakia in the prevalence of pathologic LPR( P >0.05). The bilateral lesions, speckled leukoplakia were more likely to relapse(χ(2)=4.27, 12.17, P <0.05). The more serious the pathology, the more likely it was to relapse ( Z =-2.168, P =0.03). There was no statistical significance between recurrence group and non-recurrence group in the prevalence of pathologic LPR( P >0.05). Conclusions: LPR, smoke constitute the risk factors of vocal cord leukoplakia. Drinking, voice abuse are related to vocal cord leukoplakia. Senile, speckled leukoplakia are more likely to be malignancy. A speckled leukoplakia, bilateral leukoplakia, severe pathological degree are important factors to predict recurrence.

Objective: To observe the incidence and to determine the significance of laryngopharyngeal reflux (LPR) in laryngeal cancer and vocal leukoplakia. Methods: The patients who had been diagnosed as laryngeal cancer or vocal leukoplakia between January 2014 and June 2017 were included in this study. All of them received 24-hour multichannel intraluminal impedance-pH monitoring. The prevalence of LPR and numerous parameters from the 24-hour pH monitoring in laryngeal cancer patient and vocal leukoplakia patient groups were analyzed. The chi-square test was used for counting data, t test and Mann-Whitney U were used for measuring data. Results: In the 91 laryngeal cancer patients, the prevalence of pathologic LPR was 28.6%(26/91), the median number[ P (25), P (75), P (95)]of acid reflux events was 0[0, 3, 5], time of acid exposure was 0[0, 14, 234]s, number of weakly acidic reflux events was 3[0, 6, 11]. In the 54 vocal leukoplakia patients, the prevalence of pathologic LPR was 29.6%(16/54), the number of acid reflux events was 0[0, 3, 4], time of acid exposure was 0[0, 13, 118]s, number of weakly acidic reflux events was 1.5[0, 5, 9]. The incidence of LPR did not vary in the laryngeal cancer patient and vocal leukoplakia patient groups, but were both higher than healthy Chinese volunteers according to a report in the other literature. Furthermore, all the three patients with no history of tobacco or alcohol existed acid or weakly acidic reflux episodes. Conclusions: Laryngopharyngeal reflux might play a role as an etiologic factor in laryngeal cancer and vocal leukoplakia.

Laryngopharyngeal reflux (LPR) may contribute to the development of laryngeal diseases including vocal fold leukoplakia. Clinical methods of determining LPR are limited. Pepsin, as an exogenous protein, is considered as a biomarker of LPR. The aim of the current study was, therefore, to detect pepsin by immunohistochemistry in the biopsies from patients with vocal fold leukoplakia, and by which, to determine the potential association of LPR and vocal leukoplakia. A total of 26 biopsies from patients with vocal fold leukoplakia were examined in comparison with 20 vocal fold biopsies from control subjects. We found that 2 out of 26 patients (7.7%) were strongly positive, 4 of the 26 (15.4%) patients were positive, 11 of the 26 (42.3%) patients were weakly positive, and 9 of the 26 (34.6%) were negative staining for pepsin. In contrast, only 4 of the 20 (20.0%) control subjects were weakly positive and the rest (16; 80.0%) were negative staining for pepsin. There was significant difference between the two groups in terms of positivity of pepsin staining (χ 2  = 24.181, P <0.001). These findings suggest that pepsin immunohistochemical staining could be a biomarker of LPR and that LPR may be a risk factor for the development of vocal fold leukoplakia., (Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Papillomavirus infection is one of the most common sexually transmitted infections. The aim of the study was to study the etiologic significance of the papillomavirus infection in the development of background diseases of the cervix and neoplasia. Under observation were 62 patients aged 18 to 55 years infected with human papillomavirus. All patients underwent complex clinical and anamnestic, laboratory and instrumental examination. Also, a review and advanced colposcopy was performed. As a result of the study, 53 (85.4%) women under observation were found to have various pathologies of the cervix. Dysplasia of mild degree (CIN 1 degree) was found in 12 (57.1%), moderate dysplasia (CIN 2 degree) - in 9 (42.9%) women. With further examination, it was found that patients along with dysplasia of varying severity had concomitant pathology of the cervix uteri. Cervical dysplasia was most often diagnosed in combination with another pathology of the cervix, which accounted for 85.7% of cases. It has been established that squamous epithelial lesion of the cervix is most often a consequence of late diagnosis and an untreated background process. At the same time, modern diagnostics requires a whole range of diagnostic measures to establish a diagnosis in the early stages of development and conduct differential diagnosis of a benign or malignant process.

Background: An epidemiological study on the oral mucosal lesions (OMLs) in general population from China was scarce. The objective of this study was to investigate the prevalence and distribution of OMLs in Shanghai, China and to evaluate their association with demographic factors and smoking/drinking habits based on a large scaled population on a wide spectrum., Methods: In this population-based cross-sectional study, 11054 community-dwelling individuals (M/F: 5140/5914; age range, 1-96 years) were randomly selected and examined according to WHO criteria., Results: The prevalence of OMLs was 10.8% in this study. A total of 1192 (M/F: 543/649; mean age, 56.9 years) individuals were presented with different types of OMLs. The most common type of OMLs was fissured tongue (prevalence of 3.15%), followed by recurrent aphthae (1.48%), traumatic ulcer (1.13%), and angular cheilitis (0.86%). The two most common potentially malignant disorders were oral lichen planus (0.81%) and leukoplakia (0.22%). Regression analysis revealed that the elderly age, smoking, and alcohol intake were statistically significant risk factors of OMLs with emphasis on leukokeratosis, leukoplakia, and lichen planus., Conclusion: The prevalence and distribution of OMLs were elucidated in an eastern area of China, and the importance of tobacco and alcohol in the pathogenesis of OMLs was evidenced. Our data have provided baseline information about epidemiologic aspects of OMLs that can be valuable in organized program targeting on oral health and hygiene., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Polymorphic variants of DNA repair and damage response genes play major role in carcinogenesis. These variants are suspected as predisposition factors to Oral Squamous Cell Carcinoma (OSCC). For identification of susceptible variants affecting OSCC development in Indian population, the "maximally informative" method of SNP selection from HapMap data to non-HapMap populations was applied. Three hundred twenty-five SNPs from 11 key genes involved in double strand break repair, mismatch repair and DNA damage response pathways were genotyped on a total of 373 OSCC, 253 leukoplakia and 535 unrelated control individuals. The significantly associated SNPs were validated in an additional cohort of 144 OSCC patients and 160 controls. The rs12515548 of MSH3 showed significant association with OSCC both in the discovery and validation phases (discovery P-value: 1.43E-05, replication P-value: 4.84E-03). Two SNPs (rs12360870 of MRE11A, P-value: 2.37E-07 and rs7003908 of PRKDC, P-value: 7.99E-05) were found to be significantly associated only with leukoplakia. Stratification of subjects based on amount of tobacco consumption identified SNPs that were associated with either high or low tobacco exposed group. The study reveals a synergism between associated SNPs and lifestyle factors in predisposition to OSCC and leukoplakia.

Kidney transplantation is the best option of treatment for patients with end-stage renal failure. However, following kidney transplantation many stomatological abnormalities are frequently reported. It is mainly due to immunosuppressive therapy and subsequent impaired immune response. There is an increased risk of infections and malignancies. The most frequent findings in the oral cavity include: aphthae, erosions of bacterial, viral and fungal origin, lichen-like or leukoplakia-like changes. The another type of change is gingival hyperplasia and its periodontologial consequences. In this review etiology, clinical symptoms of periodontological changes are described together with algorithm of pre- and posttransplant management of oral healthy is provided.

Polymorphisms at loci controlling cellular processes such as cell cycle, DNA repair, and apoptosis may modulate the risk of cancer. We examined the association of two linked polymorphisms (G4C14-A4T14) at p73 and one polymorphism (309G > T) at MDM2 promoter with the risk of leukoplakia and oral cancer. The p73 and MDM2 genotypes were determined in 197 leukoplakia patients, 310 oral cancer patients and in 348 healthy control subjects. The p73 GC/AT genotype increased the risk of leukoplakia (OR = 1.6, 95% CI = 1.1-2.3) and oral cancer (OR = 2.4, 95% CI = 1.7-3.3) but the 309G > T MDM2 polymorphism independently could not modify the risk of any of the diseases. Stratification of the study population into subgroups with different tobacco habits showed that the risk of the oral cancer is not modified further for the individuals carrying p73 risk genotype. However, leukoplakia patients with smokeless tobacco habit showed increased risk with combined GC/AT and AT/AT (OR = 3.0, 95% CI = 1.3-7.0) genotypes. A combined analysis was done with our previous published data on p53 codon 72 pro/arg polymorphism. Analysis of pair wise genotype combinations revealed increase in risk for specific p73-MDM2 and p73-p53 genotype combinations. Finally, the combined three loci analyses revealed that the presence of at least one risk allele at all three loci increases the risk of both leukoplakia and oral cancer.

Background: Chronic laryngitis may be a predisposing factor for laryngeal carcinoma., Method: 100 consecutive chronic laryngitis patients were assessed for associated factors for this disease. Voice assessment was undertaken, including objective measurement, subjective assessment of sound and a self-assessment by questionnaire--the so-called Voice Handicap Index (VHI). When laryngostroboscopy of the vocal cords was suspicious, then microlaryngoscopy with biopsy and histological examination was undertaken., Results: The main associated factors were found to be nicotine abuse (50 patients), gastro-esophageal/laryngo-esophageal reflux (35 patients) and inhaled corticosteroid therapy (25 patients). Subjectively, all patients considered their voices to be relatively healthy (VHI less than 15). Objective voice parameters and subjectively listening were of no prognostic significance. Indirect microscopic examination could diagnose chronic laryngitis in 31 of cases, rising to 69 when leucoplakia was present. In 6 patients the mucosal wave was found stroboscopically to be abnormal. Additionally these patients underwent direct laryngoscopy and biopsy. On histological examination one of them had a high grade dysplasia and two of them had a carcinoma in situ., Conclusion: Patients with chronic laryngitis or development of vocal cord leucoplakia often abuse nicotine, use inhaled corticosteroids for bronchial asthma or suffer from acid reflux. As many patients with chronic laryngitis/leucoplakia subjectively often do not experience any voice limitations, stroboscopic investigation is useful for the early recognition of malignant change.

Purpose: Morsicatio mucosae oris (MMO) presents as white papules and plaques that may resemble leukoplakia, and are often biopsied. The objective of this study is to document the clinical features and histopathology of MMO and to reevaluate the prevalence of dysplasia and/or cancer when this frictional keratosis is removed from the category of leukoplakia., Materials and Methods: Cases that were submitted to a single laboratory with a provisional diagnosis of "leukoplakia," "hyperkeratosis," or "white lesion" were evaluated., Results: Fifty-six lesions of MMO from 56 patients were identified out of 584 white lesions. Most cases occurred in the third to sixth decades of life. Thirty (53.6%) and 18 (32.1%) out of 56 lesions were located on the lateral tongue and buccal mucosa, respectively. The lesions showed hyperparakeratosis with a characteristic frayed, shaggy, peeling surface, and acanthosis with insignificant inflammation. When MMO is removed from the category of leukoplakia, the percentage of true leukoplakia that are dysplastic or malignant increased by 12.9%., Conclusions: MMO is a form of chronic oral frictional keratosis that has no malignant potential, and should be signed out as such and not merely "hyperparakeratosis and acanthosis" so that it can be removed from the category of leukoplakia where it does not belong.

Individual cancer susceptibility is the result of several host factors, including differences in lifestyle habits and genetic susceptibility. There is a correlation between CYP1A1 polymorphism (MspI) and oral cancer susceptibility. Individuals carrying the deletions of GSTM1 and GSTT1 are at high risk of developing oral cancers. In the present study on healthy tribal and nontribal individuals of Assam, we found that the genetic variation of GSST polymorphisms is evident (p = 0.20) with differential dose of toxic exposure. Prevalence of different polymorphic alleles of CYP1A1 also proves the same result. A mini-case-control study with very small sample size showed no marked increase in the risk of developing oral cancer as the frequencies of the studied GST genotypes did not show any statistical significance. But GSTT1-null genotypes were found to have higher risk of developing leukoplakia (OR 1.94, 95% CI 2.61-18.54). CYP1A1 genotype m2 allele was also not found to be associated with the risk of developing leukoplakias in the population.

At a workshop coordinated by the WHO Collaborating Centre for Oral Cancer and Pre-cancer in the UK issues related to potentially malignant disorders of the oral cavity were discussed by an expert group. The consensus views of the Working Group are presented in a series of papers. In this report we review the literature on the epidemiology and natural history of potentially malignant disorders (PMD), detailing those characteristics of the patients and lesions thought to be associated with future development of oral squamous cell carcinoma (OSCC). Older patients, particularly females are more at risk than younger patients; the duration of PMD may be important. Those who have never used tobacco seem at greater risk than smokers. OSCC is more likely with PMD on the lateral and ventral tongue, floor of mouth and retromolar/soft palate complex than with those elsewhere. The vast majority of PMD in which OSCC develop are non-homogenous although 5% of homogenous PMD will develop carcinoma. Large lesions covering several intraoral subsites also appear more at risk.

The authors describe the results of examination and endoscopic treatment of 278 patients with clinical symptoms of gastroesophageal reflux disease. The method of fibroesophagoduodenoscopy with 3% Lugol aqueous solution chromoscopy was introduced in medical-diagnostic algorithm of the patients. Inclusion of chromoendoscopy in the program of examination and treatment of patients with gastroesophageal reflux disease allowed higher detection of severe epithelial dysplasia (to 10.3%), leukoplakia (to 62.1%) and esophagus cancer (to 3.5%) and improvement of the results of endoscopic treatment.

Multiple tobacco smoke-related premalignant and malignant lesions develop synchronously or metachronously in various organ sites, including the oral cavity. Both field cancerization and clonal migration seem to contribute to the occurrence of multiple tumors. Although the importance of endogenous factors (e.g., oncogenes) in regulating clonal migration is well established, little is known about the role of exogenous factors. Hence, the main objective of this study was to elucidate the mechanism by which tobacco smoke stimulated the migration of cells through extracellular matrix (ECM). Treatment of MSK-Leuk1 cells with a saline extract of tobacco smoke induced the migration of cells through ECM. Tobacco smoke induced the expression of urokinase-type plasminogen activator (uPA), resulting in plasmin-dependent degradation of ECM and increased cell migration. AG1478, a small-molecule inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, a neutralizing antibody to EGFR, or an antibody to amphiregulin, an EGFR ligand, also blocked tobacco smoke-mediated induction of uPA and cell migration through ECM. PD98059, an inhibitor of mitogen-activated protein kinase (MAPK) kinase activity, caused similar inhibitory effects. Taken together, these results suggest that tobacco smoke activated the EGFR-->extracellular signal-regulated kinase 1/2 MAPK pathway, causing induction of uPA. This led, in turn, to increased plasmin-dependent degradation of matrix proteins and enhanced cell migration through ECM. These data strongly suggest that chemicals in tobacco smoke can mimic the effects of oncogenes in regulating uPA-dependent cell invasion through ECM. These findings also strengthen the rationale for determining whether inhibitors of EGFR tyrosine kinase reduce the risk of tobacco smoke-related second primary tumors.

The incidence of tuberculosis has progressively decreased in developed countries after the advent of antituberculous chemotherapy, but has recently been increasing again mainly due to migratory flows. Although common in the past and considered to be a prelethal event, laryngeal involvement has become a rarity. We report the case of a 52-year-old female smoker who complained of persistent aphonia. Videostroboscopy showed bilateral vocal fold erythroleukoplakias. A chest X-ray and CT scan aroused the suspicion of lung tuberculosis, which was confirmed by Ziehl-Neelsen staining for acid-alcohol-fast bacilli on bronchoalveolar lavage. Antituberculous chemotherapy rapidly improved the quality of her voice and led to complete disappearance of the vocal fold lesions. In conclusion, laryngeal tuberculosis may mimic an early glottic multifocal carcinoma and should therefore, despite its rarity, always be considered in the differential diagnosis of erythroleukoplakia-like lesions in order to avoid improper surgical treatment and voice damage.

While heavy drinking is a risk factor for oral leukoplakia, the effects of moderate drinking and of different alcoholic beverages are unclear and were investigated in this case-control study. 187 leukoplakia patients, aged 40-65 years, who were not heavy drinkers and did not change their drinking/smoking habits over the last decade, were age/gender matched to 187 controls. The effect of regular, moderate, overall alcohol, beer, wine, spirit drinking, adjusted for the effects of heavy smoking and other important co-variables, were assessed using conditional logistic regression analysis. Overall alcohol (OR, 0.22), wine (OR, 0.20), spirits (OR, 2.93) were significantly associated to leukoplakia. A statistically significant interaction wine/heavy smoking was also found. Such different effects could be explained by the ethanol antagonising potential of other drink components, such as polyphenols, abundant in red wine and scarce in spirits. Among heavy smokers, the preventive effect of wine was more than multiplicative.

The role of 3 p53 polymorphisms (16 bp duplication at intron 3, codon 72 Arg/Pro and intron 6 NciI RFLP at np 13494) as potential markers for indicating cancer risk remains inconclusive. In our case-control study consisting of 197 leukoplakia and 310 oral squamous cell carcinoma (SCC) patients and 348 controls, genotype frequencies at these 3 p53 loci were determined by PCR-RFLP method and analyzed by multiple logistic regression to determine the risks of the diseases. The 2/2 genotype at codon 72 of p53 was at risk for developing leukoplakia (OR = 1.6, 95% CI 1.1-2.3), whereas the combination of 1/2 and 2/2 genotypes at intron 3 and 1/1 and 1/2 genotypes at intron 6 conferred a protective effect against leukoplakia and oral SCC development, respectively (OR = 0.5, 95% CI 0.4-0.8 and OR = 0.6, 95% CI 0.5-0.9, respectively). When subjects were stratified according to specific tobacco habit, the risk/protection estimates improved significantly in some cases. Specifically, the exclusive smokers with p53 codon 72 2/2 genotype showed a higher risk of developing leukoplakia (OR = 2.7, 95% CI 1.2-6.3). Furthermore, a particular p53 haplotype 1-2-2 was at risk for both tobacco-associated leukoplakia and oral SCC (OR = 1.5, 95% CI 1.1-1.9 and OR = 1.3, 95% CI 1.1-1.7, respectively). Our results show that both specific p53 genotype and haplotype can indicate risk of tobacco-associated leukoplakia, but risk of development of tobacco-associated oral SCC can be predicted by specific p53 haplotype only., (Copyright 2005 Wiley-Liss, Inc)

Background: Many cancer risk factors are correlated with one another, and the presence of 1 risk factor may be a marker for other unhealthy behaviors. In this article, we focus on smokeless tobacco (ST), a known risk factor for oral leukoplakia and oral cancer, and the cancer risk factors associated with its use., Methods: We analyzed cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) I and the 1982-1984 NHANES I Epidemiologic Follow-up Study. Risk factor information was available on individuals 25-74 years of age, most of whom would be middle age or elderly today., Results: Older subjects, Black males, and those living in the Southern Unite States had the highest prevalence of ST use. ST use was associated with current smoking (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.1-1.5), former smoking (OR, 1.6; 95% CI, 1.4-2.0), low fruit and vegetable intake, low SES, increased alcohol consumption (among nonsmoking ST users), and increased body mass index, all of which elevate cancer risk. CONCLUSION. Physicians and dentists should ask their patients about current or former ST use. Identification of ST users should prompt the physician or dentist to inquire about other chronic disease risk factors that the patient may have and to educate the ST using patient about ways to reduce their risk of cancer.

This article reviews the epidemiology, etiologic risk factors, clinical presentation, recognition, and diagnosis of oral precancer and cancer. The actual treatment and complications from treatment of oral cancer are discussed only briefly.

The natural history of the three-stage process from normal, oral leukoplakia to oral cancer in relation to betel quid chewing, smoking and drinking is rarely addressed. The aim of this study was to simultaneously quantify the effects of three risk factors on occurrence of oral leukoplakia and malignant transformation to oral cancer. A hospital-based case-control study design derived from three retrospective cohorts from 1988 to 1998 was conducted. A total of 74 oral cancer patients, 164 patients with oral leukoplakia and 187 controls were interviewed to collect information on their betel chewing, smoking and drinking habits. The effects of the three risk factors on the progression rates of the three-stage disease process were estimated using the three-state Markov model. Subjects who chewed betel quid were at greater risk of leukoplakia (adjusted odds ratio (OR) 17.7 (9.03-34.5)) but there was no significant effect on malignant transformation (OR 1.04 (0.61-1.76)). Smoking played a major role in the onset of leukoplakia (OR 4.26 (2.21-8.23)) but a minor role in malignant transformation (OR 1.36 (0.69-2.68)). Alcohol was positively associated with malignant transformation (OR 2.37 (1.47-3.82)) but unrelated to occurrence of leukoplakia (OR 0.76 (0.04-1.43)). We concluded that smoking and betel quid were two significant risk factors for the occurrence of leukoplakia, whereas alcohol was significantly responsible for malignant transformation.

Cyclosporine A (CsA) is one of the basic and often used immunosuppressive agents. It is used to prevent rejection of allogenic transplants and to cure many diseases with autoimmunological components. The development of transplantology and frequent presence of autoaggressive disorders causes increased use of CsA, which intensifies problem of side-effects. Gingival overgrowth, oral mucosa pathologies related with bacterial, viral and fungal infections and neoplasma are described as most frequent side-effects of cyclosporine A in the oral cavity. The aim of this study was to assess the frequency of presence of different types of oral mucosa lesions in cyclosporine A-treated patients after renal transplantation. Thirty renal transplant recipients aged 11-64 years (including 13 females and 17 males) with cyclosporine treatment period from 6 months to 10 years were examined. Pathological changes on the oral mucosa were noted in 18 patients (60%). The fungal infections were the most often observed pathology (46.7% of examined persons). In mycological tests Candida albicans was most often isolated. Other species: C. kefyr, C. parapsilosis and C. tropicalis were also found. In 4 cases cheilitis angularis was additionally diagnosed. In 16.7% of CsA-treated patients, pathological changes of epithelium with homogenic leucoplakia features were observed. Hypertrophic lesions of oral mucosa in 10% of cases and many small erosions of inflamed mucosa of hard palate in 1 case were also noted. Our observations show connection between incidence of oral mucosa pathologies and immunosuppressive treatment. This suggests that interdisciplinary cooperation is necessary for early start of prevention and treatment program.

Laryngopharyngeal reflux is now of major interest as an aetiologic factor in chronic inflammatory and neoplastic lesions of upper digestive tract. However, reports in the literature refer only to the irritating action of the acid component of reflux, while possible damaging action of other reflux components remains unknown. Aim of this study was to verify the hypothesis that alkaline-bile reflux could also be involved in onset of inflammatory, precancerous and neoplastic laryngeal lesions. A total of 40 consecutive gastrectomized patients coming to our Clinic from Gastroenterology Outpatient Unit for an anamnestic and clinical evaluation with videolaryngoscopy of upper digestive airways, entered the study. All presented bile or alkaline reflux as a direct consequence of gastroduodenal anastomosis (Billroth I) and gastrojejunal anastomosis (Billroth II) performed over a time span > 20 years. Oesophagogastroduodenoscopy revealed the presence of bile in the residual gastric cavity in all operated patients objectively confirming duodenogastric reflux. Examination of data showed that 3 patients (7.5%) had undergone CO2 laser cordectomy in the 3 years prior to the study for squamous cell laryngeal carcinoma, 3 patients (7.5%) had leukoplakia, 8 (20%) vocal cord chronic oedema with signs of chronic diffuse laryngitis, 6 (15%) posterior laryngitis, 8 (20%) interarytenoid oedema while only 12 (30%) showed no ENT lesions. Statistical analysis revealed a significant correlation between incidence of inflammatory and neoplastic laryngeal lesions and type of surgery (Billroth II and total gastrectomy) with respect to other types of gastric resection. There was also a significant increase in presence and severity of laryngopharyngeal lesions in relation to time elapsed after surgery. These results, although preliminary, seem to confirm that some components of reflux (duodenal content), other than the acid component, play a damaging role involved in the onset of multiple clinical signs and symptoms of laryngopharyngeal reflux disease. It is concluded that systematic use of bile measurement, together with 24-hour pH monitoring, is advisable in subjects with clinical signs and symptoms of laryngopharyngeal reflux, but unresponsive to classic medical treatment, and in gastrectomized patients in order to confirm, on larger series, this fascinating aetiopathogenetic hypothesis.

The concept of a two-step process of cancer development in the oral mucosa, i.e., the initial presence of a precursor subsequently developing into cancer, is well-established. Oral leukoplakia is the best-known precursor lesion. The evidence that oral leukoplakias are pre-malignant is mainly derived from follow-up studies showing that between < 1 and 18% of oral pre-malignant lesions will develop into oral cancer; it has been shown that certain clinical sub-types of leukoplakia are at a higher risk for malignant transformation than others. The presence of epithelial dysplasia may be even more important in predicting malignant development than the clinical characteristics. Three major problems, however, are attached to the importance of epithelial dysplasia in predicting malignant development: (1) The diagnosis is essentially subjective, (2) it seems that not all lesions exhibiting dysplasia will eventually become malignant and some may even regress, and (3) carcinoma can develop from lesions in which epithelial dysplasia was not diagnosed in previous biopsies. There is, therefore, a substantial need to improve the histologic assessment of epithelial dysplasia or, since epithelial dysplasia does not seem to be invariably associated with or even a necessary prerequisite for malignant development, it may be necessary to develop other methods for predicting the malignant potential of pre-malignant lesions. As a consequence of these problems, numerous attempts have been made to relate biological characteristics to the malignant potential of leukoplakias. Molecular biological markers have been suggested to be of value in the diagnosis and prognostic evaluation of leukoplakias. Markers of epithelial differentiation and, more recently, genomic markers could potentially be good candidates for improving the prognostic evaluation of precursors of oral cancer. As yet, one or a panel of molecular markers has not been determined that allows for a prognostic prediction of oral pre-cancer which is any more reliable than dysplasia recording. However, these new markers could be considered complementary to conventional prognostic evaluation.

Hypothesis: At present, main factors considered responsible for the onset of squamous cell carcinoma are tobacco smoking, alcohol abuse, and exposure to viral and toxic agents. In last years, great interest has been focused on gastroesophageal reflux as independent carcinogenic factor and co-carcinogen in association with smoking and alcohol assumption., Study Design: Initially, the aim of this study was to objectively evaluate the presence of distal and proximal esophageal reflux with multielectrode pH measurement in patients with cancer of the larynx and/or hypopharynx (group A). However, in the course of the study, pharyngolaryngeal cancer was also observed in 4 patients with achlorhydria; therefore, the hypothesis that alkaline reflux might be involved in the onset of laryngeal cancer was tested (group B)., Methods: Twenty-one consecutive patients with laryngeal or hypopharyngolaryngeal squamous cell carcinoma (group A) entered the study. Twenty-one patients without laryngo-pharyngeal diseases were used as control subjects. A validated questionnaire of the clinical history was completed by all patients who underwent 24-hour pH monitoring. Group B included 40 consecutive gastrectomized patients (28 males and 12 females) in whom biliary or alkaline reflux was directly consequent to Billroth I or Billroth II operation. The control group was composed of 40 non-gastrectomized dyspeptic patients. The clinical history was controlled and obtained; EDGS and ENT examination with videolaryngoscopy was performed in all patients., Results: In group A, pH measurement showed pathological reflux in 80.9% (17 of 21) of patients with no typical symptoms in 63.7% of them. The difference was significant with respect to the control group. In group B, 6 of 40 (15%) had preneoplastic lesions or a history of laryngeal tumor. The difference was significant with respect to the control group. A total of 7.5% of group B patients had previously undergone CO2 laser cordectomy for laryngeal squamous cell carcinoma and 7.5% had leukoplakia. We found a significantly higher incidence (<.05) of neoplastic and preneoplastic disease of the larynx in patients undergoing Billroth II and total gastrectomy than in those undergoing Billroth I and Roux-en-Y resection. We also found a significant increase (<.01) in ENT lesions in the group of patients who had undergone gastrectomy more than 20 years previously., Conclusions: In agreement with literature reports, results obtained in group A confirmed that gastroesophageal reflux is often present in patients with neoplastic lesions of the pharynx and larynx. Furthermore, gastric resection is indicated for the first time as an additional risk factor or cofactor of precancerosis and squamous cell carcinoma of the pharynx or larynx. Further studies are necessary to establish the cause and effect relationship between biliary reflux and pharyngo-laryngeal tumors.

The present study evaluates and analyzes anamnestic and clinical findings of 100 consecutively referred patients with oral mucosal lesions. The mean age of the cohort was 50.5 years (range 8-91 years) with a female rate of 60 percent. A total of 9 malignant neoplasia were found among the 100 mucosal lesions, including 7 squamous cell carcinomas and 2 mucoepidermoid carcinomas. In addition, 11 cases presented with leukoplakia and 4 cases with lichen planus, both recognized as possible precancerous conditions. These figures support the essential role of the dentist with respect to initial diagnosis and prevention of oral cancer. In addition, stomatologic follow-up examinations are recommended to be performed by each and every general practitioner. In the near future, the dentist will assess oral mucosal lesions more frequently due to the increasing number of elderly patients and to the fact that elderly people present with more lesions compared to younger patients. consistent to literature data, patients with leukoplasia and squamous cell carcinoma had the highest rates of tobacco and alcohol consumption. Therefore, the dentist may also become active in giving preventive information to the patient. the results of the present study showed, that--by employing a standardized examination--a correct clinical diagnosis was identical to the final diagnosis established by laboratory techniques.

Methodological approaches have been developed toward raising the informative value of cytological diagnosis. There have been identified pathogenetic variants of background and precancerous affections of the vulva, their leading factors being viral infection, function disorders of the hypothalamic centres, hypoestrogenemia, hepatic and thyroidal abnormalities. The effectiveness of the treatment scheme developed with taking account of the above-stated items is 97.3%.

It is essential to identify intermediate marker endpoints of carcinogenesis for the evaluation of the effectiveness of cancer-chemopreventive agents. We have observed that levels of proteolytic activities (as detected by 4 different substrates) are increased 2-3-fold (P < 0.003) in oral buccal mucosa cells of smokers and patients with oral leukoplakia or erythroplakia as compared to a nonsmoking comparison group. In addition, proteolytic activity levels in the buccal cells were increased nearly 3-fold in patients with oral trauma (P < 0.01) or diabetes (P < 0.02), as well as pregnant women (P < 0.04). Excluding these subgroups of patients in epidemiological studies increase the differences in levels of proteolytic activities between both the nonsmoking comparison group and smokers and between the comparison group and patients with oral leukoplakia or erythroplakia. Evaluation of prerandomization levels of proteolytic activities of patients in cancer chemoprevention trials will increase the statistical power by allowing stratified randomization based on levels of proteolytic activities. The observed increases in levels of proteolytic activities in tissues at higher than normal risk of cancer development suggest that levels of proteolytic activities should be used as immediate marker endpoints in human cancer prevention trials using protease inhibitors as potential anticarcinogenic agents.

Background: Renal-transplant recipients are known to have increased rates of skin cancer associated with exposure to the sun. Little is known, however, about the prevalence and histologic features of lesions of the lips in these patients, or about risk factors for such lesions., Methods: We examined the lips of 160 renal-transplant recipients (105 men and 55 women; mean [+/- SD] age, 48 +/- 13 years) and 160 normal subjects matched with the transplant recipients for age, sex, and skin type. The mean length of time between transplantation and the examination was 69 +/- 52 months; 58 percent of the recipients had received their grafts more than 60 months earlier., Results: Among the 160 renal-transplant recipients, 21 (13 percent) had leukoplakia; in 2 (1.2 percent) the leukoplakia contained squamous-cell carcinoma. In contrast, only one normal subject (0.6 percent) had leukoplakia. Histologically, 13 of the 21 leukoplakias (62 percent) in the renal-transplant recipients who underwent biopsy were dysplastic, and 2 (10 percent) contained squamous-cell carcinoma. Actinic change was evident in 91 percent of the dysplastic lesions but not in the nondysplastic lesions (P < 0.001). Exposure to the sun and smoking were risk factors for dysplastic and malignant lip lesions in the renal-transplant recipients (P < 0.001 and P = 0.003, respectively). Among these recipients, only men had dysplastic or malignant lip lesions (P = 0.006); lipstick was used frequently by 73 percent of the women. The clinical appearance of lip lesions did not predict the presence of dysplasia or cancer., Conclusions: Renal-transplant recipients have an increased prevalence of leukoplakia, dysplasia, and cancer of the lip.

Early intervention guidelines in HIV infection require knowledge of CD4+ lymphocyte count; however, CD4+ determinations require special laboratory procedures and may not be readily available in all situations. Using data from 207 HIV-seropositive homosexual men without AIDS, we evaluated the association of difference clinical conditions or serologic tests with CD4+ count. Men with conditions including seborrheic dermatitis, hairy leukoplakia, oral candidiasis and chronic diarrhea, and men with beta2-microglobulin levels greater than or equal to 4.0 mg/l had significantly lower CD4+ counts. However, the probability that a subject with such parameters had less than 200 x 10(6)/l CD4+ cells was limited (25-63%). Although the probability that a subject with such parameters had less than 500 x 10(6)/l CD4+ cells was better (76-88%), the probability that a person without these parameters had greater than or equal to 500 x 10(6)/l CD4+ cells was only 45-50%. Clinical and serologic parameters may provide important prognostic information, but cannot be used to reliably determine the level of CD4+ cells.

Leukoplakia of the bladder is a rare condition. It is characterized by squamous metaplasia of the transitional epithelium and keratinization. The etiology and possible pathogenetic factors are discussed. Up to 42% develop carcinoma which makes early diagnosis important. The clinical diagnosis is difficult. The patients present with symptoms of vesical irritation and the passage of flakes is pathognomonic. Diagnosis is made by cystoscopy with biopsies. Characteristic cystoscopic findings are described. Treatment and a follow-up programme are outlined. As conservative treatment remains unsatisfactory radical extirpation or cystectomy is recommended for extensive lesions.

A palatal lesion resembling "nicotine" stomatitis was found in a woman who did not smoke. However, the patient frequently drank extremely hot beverages. After she was instructed to reduce the temperature of the beverages, the lesion almost completely resolved. This suggests that heat was the primary cause of this lesion and also implicates heat as the major cause of nicotine stomatitis.

Levels of tropic hormones of the pituitary, glucocorticoids and male and female sex hormones were assayed in 17 cases of kraurosis and leukoplakia of the vulva prior to treatment. Most patients revealed an abnormally high androgen/estrogen ratio, elevated level of glucocorticoids and low concentrations of thyrotropic hormone, prolactin and T3. The above disturbances are closely related and interdependent.