Oral leukoplakia and the long-term risk of upper gastrointestinal cancer deaths in the Linxian dysplasia population.

BACKGROUND: To investigate oral leukoplakia (OL) and risk of upper gastrointestinal (UGI) cancer deaths in the Linxian Dysplasia Nutrition Intervention Trial (NIT) cohort. METHODS: A total of 3318 subjects with esophageal squamous dysplasia enrolled on 1 May 1985, and were followed up until 30 September 2015. Participants with OL at baseline were treated as an exposed group, while the remainder was selected as a control group. All subjects were followed monthly and reviewed quarterly by the Linxian Cancer Registry. Cox proportional hazard model was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs). RESULTS: During the 30-year follow-up, a total of 902 UGI cancer deaths occurred, including 541 esophageal squamous cell carcinoma (ESCC) related, 284 gastric cardia carcinoma (GCC) related, and 77 gastric noncardia carcinoma (GNCC) related deaths. Relative to subjects without OL, the long-term risk of ESCC mortality in participants with OL increased by 26.1% (HR = 1.26, 95% CI: 1.05-1.52). In the subgroup analyses, adverse effects of OL on ESCC mortality were observed especially in younger subjects (HR = 1.48, 95% CI: 1.11-1.97), females (HR = 1.44, 95% CI: 1.11-1.89), non-smokers (HR = 1.44, 95% CI: 1.15-1.81), nondrinkers (HR = 1.28, 95% CI: 1.04-1.57), and individuals with a family history of cancer (HR = 1.37, 95% CI: 1.05-1.79). No associations were observed between OL and risk of GCC and GNCC mortality. CONCLUSIONS: OL may increase the long-term risk of ESCC mortality, especially in younger subjects, females, nondrinkers, non-smokers, and subjects with a family cancer history. Future studies are needed to explore the potentially etiological mechanism.

Proliferative verrucous leukoplakia and its tumor markers: Systematic review and meta-analysis.

BACKGROUND: The aim was to update information on oral proliferative verrucous leukoplakia (PVL), a disease of verrucous-like lesions with high risk of malignancy, and its biomarkers. METHODS: A systematic search of literature on PVL and its biomarkers showed 22 biomarkers that were investigated in 19 papers. A meta-analysis was possible for human papillomavirus (HPV), aneuploidy, Ki-67, and p53. RESULTS: Aneuploidy was found consistently (I2 = 0%, P = 0.61) in 92% (95% CI 80%-99%) of the PVL cases. P53 positivity prevalence was 27% (95% CI 15%-40%) in two available studies (I2 = 0%, P = 0.64). With HPV and Ki-67, the most outlying studies needed to be removed and after that the pooled HPV positivity prevalence (I2 = 24%, P = 0.27) was 5% (95% CI 0%-14%) and for Ki-67 (I2 = 9%, P = 0.33) 14% (95% CI 6%-26%). CONCLUSIONS: With the evidence of the current literature, aneuploidy could value as a biomarker of PVL but should be further validated.

Impact of oral potentially malignant disorders on quality of life.

BACKGROUND: Oral potentially malignant disorders (OPMDs) could have a significant psychological impact on patients, principally because of the unknown risk of malignant transformation, while the physical and functional impairments could differ. This study aimed to assess the impact of three different OPMDs and their disease stages on the quality of life (QoL) of affected patients. METHODS: Oral leukoplakia (OL), oral lichen planus (OLP) and oral submucous fibrosis (OSF) patients who were undergoing treatment at an oral medicine clinic of a dental teaching hospital in India were the study population. All subjects completed the recently developed OPMDQoL questionnaire and a short form 12 item (version 2) health survey questionnaire (SF-12v2). OPMDQoL questionnaire consists of 20 items over four dimensions. A higher score denotes poor OHRQoL. SF-12v2 has two components, a Physical Component Summary (PCS) and Mental Component Summary (MCS). RESULTS: A total of 150 subjects (50 each of OL, OLP and OSF) participated. OL patients (37.7 ± 7.9) reported significantly better OPMDQoL scores than OLP (47.3 ± 5.8) and OSF (45.4 ± 9.2) patients. OLP patients reported significant problems in obtaining a clear diagnosis for their condition, more so than the other OPMDs. OL patients reported fewer problems for the dimension, "physical impairment and functional limitations" than the OLP and OSF patients. A significant trend was observed with the overall OPMDQoL and MCS, deteriorating as the disease stage increased. CONCLUSIONS: OLP and OSF have a significant impact on the QoL of affected individuals: OL less so. Increasing stage of the disease is associated with worsening QoL.

Pachyonychia Congenita: A Spectrum of KRT6a Mutations in Australian Patients.

BACKGROUND: Pachyonychia congenita (PC) is a rare inherited disorder of keratinization characterised by hypertrophic nail dystrophy, painful palmoplantar blisters, cysts, follicular hyperkeratosis and oral leukokeratosis. It is associated with mutations in five differentiation-specific keratin genes, KRT6A, KRT6B, KRT6C, KRT16, or KRT17. OBJECTIVES: Living with Pachyonychia Congenita can be isolating. The aim of this paper is to document a single patient's experience within a national context. METHOD: We report the case of a 2 year old female with an atypical presentation of PC due to a mutation in KRT6A with severely hypertrophic follicular keratoses, skin fragility, relative sparing of nail hypertrophy on one hand and failure to thrive in early infancy. In collaboration with the International Pachyonychia Congenita Research Registry (IPCRR), a database search was performed using Australian residency and KRT6A mutation as inclusion criteria. The IPCRR database was also searched for a matching KRT6A mutation. Six Australian patients were identified in addition to one patient with an identical mutation residing in the United States. The detailed standardized patient questionnaire data was manually collated and analysed. RESULTS: Fingernail hypertrophy and oral leukokeratosis were the most common features. There was no recording of asymmetric distribution in any other Australian patient. Trouble nursing as an infant and follicular hyperkeratosis also occurred in the American patient, however they did not have asymmetric distribution and the oral leukokeratosis appeared later in life. CONCLUSION: This case has unique features. Sharing information can assist patients navigating life with this condition.

Establishment of a new OSCC cell line derived from OLK and identification of malignant transformation-related proteins by differential proteomics approach.

Oral squamous cell carcinoma (OSCC) is usually preceded by the oral premalignant lesions, mainly oral leukoplakia (OLK) after repeated insults of carcinogens, tobacco. B(a)P and DMBA are key carcinogens in tobacco smoke. In the present study, for the first time we established the cancerous cell line OSCC-BD induced by B(a)P/DMBA mixture and transformed from dysplastic oral leukoplakia cell line DOK. Cell morphology, proliferation ability, migration ability, colony formation, and tumorigenicity were studied and confirmed the malignant characteristics of OSCC-BD cells. We further identified the differential proteins between DOK and OSCC-BD cells by stable isotope dimethyl labeling based quantitative proteomic method, which showed 18 proteins up-regulated and 16 proteins down-regulated with RSD < 8%. Differential proteins are mainly related to cell cycle, cell proliferation, DNA replication, RNA splicing and apoptosis. Abberant binding function, catalysis activity and transportor activity of differential proteins might contribute to the malignant transformation of OLK. Of the 34 identified differential proteins with RSD < 8%, 13 novel cancer-related proteins were reported in the present study. This study might provide a new insight into the mechanism of OLK malignant transformation and the potent biomarkers for early diagnosis, meanwhile further facilitate the application of the quantification proteomics to carcinogenesis research.

Oral health-related quality of life of patients with oral lichen planus, oral leukoplakia, or oral squamous cell carcinoma.

PURPOSE: To compare oral health-related quality of life (OHRQoL) of patients with oral lichen planus (OLP), oral leukoplakia (OL), or oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Seventy-three patients with OLP, 44 with OL, and 37 with OSCC participated in this prospective study. The German version of the 14-item Oral Health Impact Profile (OHIP-G 14) was used to measure OHRQoL. Descriptive statistics and multivariate analysis of clinical forms, age, gender, alcohol consumption, and smoking habits were evaluated. RESULTS: No association to cumulative OHIP-14 score (P = .086) among the 3 groups was found. However, patients with OLP showed a higher "physical pain" score and a lower "social disability" score (P = .026) than patients with OSCC, followed by patients with OL. Women with OLP had a lower OHRQoL than men. After differentiation of clinical forms of OLP (symptomatic vs asymptomatic), an impact on these patients' OHRQoL in the dimensions "physical pain" and "physical disability" was found. CONCLUSION: Patients with OLP or OSCC and high OHIP-G 14 scores reported physical pain, which emphasizes the need for physical therapy. For improved OHRQoL, patients with symptomatic forms of OLP would gain more from a treatment compared with those with asymptomatic forms. In contrast, patients with asymptomatic OLP or OL and thus with a minimal impact on their OHRQoL might be at risk of delayed consultation, diagnosis, and treatment of their condition.

Proliferative verrucous leukoplakia: recognition and differentiation from conventional leukoplakia and mimics.

The majority of conventional leukoplakia remains constant and only a subset progress to high-grade dysplasia or invasive carcinoma. A less recognized form known as proliferative verrucous leukoplakia (PVL) represents a unique progressive and elusive variant. Identifying patients with this form can only be achieved through the keen clinical observation of the temporal gross and histologic progression in individual patients with squamous cell carcinoma. The difficulty in the early diagnosis of PVL stems from the overlapping clinical and pathologic features with conventional multifocal leukoplakia with dysplasia. We present the current view on the clinicopathologic and biological characteristics of PVL and discuss their diagnosis, differential diagnosis, and management.

Oral cancer development in patients with leukoplakia--clinicopathological factors affecting outcome.

BACKGROUND: Oral leukoplakia (OL) is the best-known potentially malignant disorder. The objective of the current study was to evaluate the clinicopathological factors predictive of outcome in a large cohort of patients with OL, and report our experience in the early detection of malignant events. METHODS: A total of 320 patients with biopsy-proven OL were retrospectively reviewed from the study institution who had a mean follow-up of 5.1 years. Data on patient and lesion at initial diagnosis and patient underwent sequential biopsies were reviewed. Multiple biopsies indicates > = 3 times sequential biopsies. Oral cancer-free survival rate (OCFS) was determined by the Kaplan-Meier method and significant factors were identified by Cox regression analysis. RESULTS: The 3-year and 5-year OCFS was 86.6% and 82.0%, respectively. A new binary system of grading oral dysplasia was performed and Kaplan-Meier analysis indicated that high-grade dysplasia had significantly higher malignant incidence than low-grade dysplasia (5-year OCFS, 90.5% vs 59.0%; P<0.001), especially during the first 2-3 years of follow-up. Multivariate analysis revealed that the 4 factors including patient aged >60 years, lesion located at lateral/ventral tongue, non-homogenous lesion, high-grade dysplasia were independent significant indicators for OL malignant transformation. In addition, significant positive correlation between the multiple biopsies and these 4 factors and malignant outcome was established. CONCLUSIONS: Elderly patients with OL located at lateral/ventral tongue and who had non-homogenous lesion with high-grade dysplasia correlated much higher risk of transformation. This high-risk subpopulation was suggested to undergo sequential biopsies and histologic examination contributing to early detection of malignant event.

Oral cancer genesis and progression: DNA near-diploid aneuploidization and endoreduplication by high resolution flow cytometry.

Oral potentially malignant lesions (OPMLs) with dysplasia and aneuploidy are thought to have a high risk of progression into oral squamous cell carcinomas (OSCCs). Non-dysplastic "oral distant fields" (ODFs), characterized by clinically normal appearing mucosa sited at a distance from co-existing OPMLs, and non-dysplastic OPMLs may also represent an early pre-cancerous state. ODFs, OPMLs without and with dysplasia and OSCCs were investigated by high resolution DNA content flow cytometry (FCM). ODFs and OPMLs without dysplasia were DNA aneuploid respectively in 7/82 (8.5%) and 25/109 (23%) cases. "True normal oral mucosa" and human lymphocytes from healthy donors were DNA diploid in all cases and were used as sex specific DNA diploid controls. Dysplastic OPMLs and OSCCs were DNA aneuploid in 12/26 (46%) and 12/13 (92%) cases. The DNA aneuploid sublines were characterized by the DNA Index (DI not =1). Aneuploid sublines in ODFs and in non-dysplastic and dysplastic OPMLs were near-diploid (DI<1.4) respectively in all, 2/3 and 1/3 of the cases. DNA aneuploid OSCCs, instead, were characterized prevalently by multiple aneuploid sublines (67%), which were commonly (57%) high-aneuploid (DI> or =1.4). DNA near-diploid aneuploid sublines in ODFs and OPMLs appear as early events of the oral carcinogenesis in agreement with the concept of field effect. Near-diploid aneuploidization is likely to reflect mechanisms of loss of symmetry in the chromosome mitotic division. High DNA aneuploid and multiple sublines in OPMLs with dysplasia and OSCCs suggest, instead, mechanisms of "endoreduplication" of diploid and near-diploid aneuploid cells and chromosomal loss. High resolution DNA FCM seems to enable the separation of subsequent progression steps of the oral carcinogenesis.

Management of oral epithelial dysplasia: a review.

One of the goals of the fourth meeting of The World Workshop on Oral Medicine (WWOM IV) included a review of the pathophysiology and future directions for the clinical management of patients with oral epithelial dysplasia, excluding the lips and oropharynx. In the pathophysiology review of dysplasia since WWOM III (1998-2006), a wide range of molecular changes associated with progression of dysplasia to squamous cell carcinoma were found. These include loss of heterozygosity, dysregulation of apoptosis, aberrant DNA expression, and altered expression of numerous tissue markers. Based on the literature search, no single molecular pathway has been identified as the primary factor in progression of dysplasia to squamous cell carcinoma. A systematic review of medical (i.e., nonsurgical) management strategies for the treatment of dysplastic lesions has shown promising results in short-term resolution of dysplasia in the small number of studies that met eligibility criteria for review. However, because of the limited periods of follow-up reported in these studies, it remains unclear as whether resolution of dysplasia would actually be a long-term benefit of these interventions. This question is particularly germane when it is considered in the context of prevention of future development of squamous cell carcinoma. Because of the lack of randomized controlled trials that have shown effectiveness in the prevention of malignant transformation, no recommendations can be provided for specific surgical interventions of dysplastic oral lesions either.

Surgical treatment of erythroleukoplakia in lower lip with carbon dioxide laser radiation.

Erythroplakia is considered to represent a premalignant condition and is felt to be at high risk to progress to oral cancer development. When the lesion presents with red and white mucosal alterations concomitantly, the term erythroleukoplakia is used. However, in erythroleukoplakia lesions, the red or erythroplakia areas have been shown to be most likely to demonstrate dysplastic changes compared to the white hyperkeratotic areas. We present a case of patient with erythroleukoplakia involving the lower lip that was treating with carbon dioxide laser radiation (CO2) with 0.8 mm focus, 5 W, power density of 2.5 W/cm2 in continuous. After the surgery, the vaporized surface was protected with a fibrinolisine + chloramphenicol cream. To date, after 6 months, there has been no clinically evident recurrence on the vermilion area. The functional and esthetic results observed were judged to be excellent.

Estudio epidemiológico de la patología de la mucosa oral en pacientes de la Escuela de Estomatología de Oviedo / Epídemiological study of oral mucosal pathology in patients of the Oviedo School of Stomatology

Objetivos: Los objetivos del presente estudio han sido: I) determinar la frecuencia de las lesiones de la mucosa oral y analizar su relación con los hábitos tóxicos tabáquico y alcohólico, y 2) determinar la prevalencia de la patología oral en pacientes portadores de prótesis, para establecer las necesidades de tratamiento y las medidas preventivas oportunas. Diseño del estudio: El estudio se realizó sobre pacientes que acudieron a la Escuela de Estomatología de la Universidad de Oviedo para recibir tratamiento de su patología dentarla, periodontal o prostodóncica y no por patología de la mucosa. Se examinaron 337 pacientes (140 varones y 197 mujeres). El rango de edad fue de 30 a 85 años. Se elaboró un protocolo clínico en el que se incluyeron las lesiones recogidas en estudios epidemiológicos previos. Resultados: El número de pacientes con lesiones fue de 198 (58,75 por ciento). La patología diagnosticada con más frecuencia fue la pigmentación melánica (n=83; 24,6 por ciento), seguida de la queratosis friccional (n=39; 11,5 por ciento), línea alba (n=34; 10,7 por ciento), mucosa mordisqueada (n=23; 6,8 por ciento) y úlcera traumática (n=16; 4,7 por ciento). En los pacientes portadores de prótesis, la patología más frecuente fue la hiperplasia (n=17; 5 por ciento) y la estomatitis (n=9; 2,6 por ciento).Registramos hallazgos estadísticamente significativos: entre la utilización de prótesis y queratosis traumática, leucoplasia y candidiasis pseudomembranosa. Entre el hábito tabáquico y la presencia de leucoplasia, queratosis friccional y pigmentación melánica. Entre el hábito alcohólico y la queratosis traumática. Conclusiones: Nuestros resultados han puesto de manifiesto la necesidad de explorar periódicamente a los pacientes portadores de prótesis, y de divulgar las medidas preventivas oportunas para erradicar la patología que ésta desencadena. El hallazgo de la asociación entre la queratosis traumática y dos factores relacionados con la etiopatogenia y pronóstico del cáncer oral ha de despertar un máximo interés en su correcto diagnóstico y tratamiento (AU)

Surgical management of actinic cheilitis.

OBJECTIVE: An analysis is made of the etiologic factors underlying actinic cheilitis and of the results obtained following surgical treatment of the disease in a series of 54 patients (32 males and 22 females). STUDY DESIGN: The case history was evaluated, along with the triggering factors, histopathological pattern and recurrence of lesions. A cold scalpel vermilionectomy was performed in 41 patients, followed by primary closure of the defect using an oral mucosal flap. The remaining 13 patients were subjected to carbon dioxide laser vermilion ablation. RESULTS: The history of the patients revealed liver disease associated to alcohol consumption in 35.2% of cases and tobacco smoking in 77.8%. As regards solar exposure, 53.1% of the men referred open-air professional activities, while 100% of the women presented important solar exposure. The most frequent clinical manifestations were bleeding and the presence of leukoplakia patches; pain was reported in only 16% of cases. Over 40% of the patients were asymptomatic. Following treatment, and after a follow-up period of at least 6 months, 90.7% of the subjects showed complete healing. Of the 5 patients reoperated upon, four healed and one evolved towards squamous cell carcinoma. CONCLUSION: Vermilionectomy is the recommended treatment for actinic cheilitis, using either a cold scalpel or carbon dioxide laser. A histological study of the lesion is indicated in all cases to secure early detection of possible malignization. The control of the possible etiologic factors is also essential.

[Analysis of relationship between risk factors of malignant transformation of oral leukoplakia and the LSCP system].

OBJECTIVE: To explore the clinical significance of the LSCP (lesion size, site of lesion, clinical aspects, pathological aspects) classification and staging system through a comprehensive analysis of relationships between the risk factors of malignant transformation of 209 cases with oral leukoplakia and the LSCP classification and staging system. METHODS: Single factor Chi-square test was first performed to examine the associations between LSCP stages (I, II, III, IV) of oral leukoplakia and each of risk factors, including sex, site, size, numbers of lesion, alcohol and tobacco consumption, clinical classification and histopathological classification respectively, to select the most significant factors which influence the LSCP classification and staging. Then, the association of these selected factors with LSCP stages of oral leukoplakia (stage IV vs. I, II and III) was evaluated using multiple logistic regression analysis. RESULTS: Sex, site of lesions, clinical aspect and histopathological features of lesions were chosen as risk factors incorporated into the multiple logistic regression models. The results demonstrated that the risk of oral leukoplakia of the female patients classified as LSCP stage IV was 2.49 times as high as that of the male patients. The risk of lesions occurring in tongue and/or that floor of mouth was higher than that in other sites. Among the different clinical subtypes of lesions, the verrucous leukoplakia was the highest and 10.00 times as high as that of the homogeneous one. Among the different histopathological types, when hyperplasia and mild dysplasia were set as the basic level, the risk of severe dysplasia classified as LSCP stage IV was the highest and 499.55 times as high as the basic level, while that of moderate dysplasia was 276.48 times as high as the basic level. Pathological features with moderate and severe dysplasia were the most important contributory factors to the LSCP staging. CONCLUSIONS: The LSCP classification and staging system provides a comprehensive description of the features of oral leukoplakia, which is helpful in evaluating the overall risk of malignant transformation of oral lesion, and is valuable in clinical follow-up and developing the best treatment plan.

[Study of the permeability of oral leukoplakia]. / A szájüregi leukoplakia permeabilitásának vizsgálata.

The significant increase in the mortality rates of oral carcinoma speeded up the research on the mechanisms of tumor promoting and inhibiting factors. Results of previous studies in the USA showed different permeability between keratinized (hard palate, gingive) and non-keratinized (floor of the mouth) regions of the oral mucosa, and a corresponding difference in lipid composition. Aim of this study was, to compare the permeability and lipid composition of leukoplakia of the oral mucosa with healthy specimens from the same region, in order to assess a possible enhancement or inhibition in the barrier-function, in cases of pathological keratinization. Results of the measurements showed, that hyperplastic leukoplakia areas were more permeable for the NNN carcinogens contained in tobacco, and even clinically healthy sites showed a higher permeability, that oral mucosa of non-smokers. These data together with the results of lipid analysis, point to the possible generalized changes--caused by smoking--in the oral cavity, even before the appearance of clinical signs.

Quantitative evaluation of consistency of normal mucosa, leukoplakia and squamous cell carcinoma of the tongue.

The quantitative differences in consistency of normal mucosa, leukoplakia and squamous cell carcinoma of the tongue were studied. Forty-five patients with squamous cell carcinoma of the tongue, 26 with leukoplakia and 80 with normal tongues were examined using an instrument capable of measuring consistency as a function of the load (in grams) needed to displace tongue mucosa by 2.0 mm using a probe 2.0 mm in diameter. The mean value for consistency in tongue carcinoma, leukoplakia and normal tongue was 22.1 +/- 8.0 g, 8.3 +/- 2.0 g and 4.8 +/- 0.7 g, respectively. Differences in consistency among these entities were significant (P < 0.001). Furthermore, consistency in tongue carcinoma was significantly correlated to tumour thickness (r = 0.954, P < 0.001). It was concluded that the consistency in tongue lesions was objectively and quantitatively evaluated by this method, and this technique could measure the thickness of the tumorous lesions preoperatively.

[Oral hairy leukoplakia in patients with kidney transplantation]. / Orale Haarleukoplakie bei nierentransplantierten Patienten.

Oral hairy leukoplakia was initially reported only in HIV-infected patients and was considered pathognomonic for HIV infection. The presence of Epstein-Barr virus and the decrease in Langerhans cells seem to be necessary for the development of oral hairy leukoplakia. HIV antigen is not present in oral hairy leukoplakia. We report on seven renal transplant recipients with oral hairy leukoplakia. In six of these patients no HIV infection was present. All patients showed marked immunosuppression following a vigorous immunosuppressive regimen. Five patients each had several rejection episodes, which were treated with further immunosuppressive therapy in addition to the basic immunosuppressive regimen. One patient was infected with HIV from the renal graft and another suffered from liver cirrhosis with portal hypertension caused by chronic hepatitis B infection. We believe that oral hairy leukoplakia is a marker for severe immunosuppression that is not necessarily associated with HIV infection. Organ transplant recipients undergoing dermatological check-up should be examined for oral hairy leukoplakia.