Feasibility and Colonoscopy Yield Using the Fecal Immunochemical Test (FIT)-Based Colorectal Cancer Screening in a Latin America Country.

BACKGROUND & AIMS: Organized colorectal cancer (CRC) screening is not widely practiced in Latin America and the results of regional studies may help overcome barriers for implementation of national screening programs. We aimed to describe the implementation and findings of a fecal immunochemical test (FIT)-based program in Brazil. METHODS: In a prospective population-based study, asymptomatic individuals (50-75 years old) from Sao Paulo city were invited to undergo FIT for CRC screening. Participants with positive FIT (≥10 µg Hb/g feces) were referred for colonoscopy. Subjects were classified into groups according to the presence of CRC, precursor lesions, and other benign findings, possibly related to bleeding. RESULTS: Of a total of 9881 subjects, 7.8% had positive FIT and colonoscopy compliance was 68.9% (n = 535). Boston scale was considered adequate in 99% and cecal intubation rate was 99.4%. CRC was diagnosed in 5.9% of the cases, adenoma in 63.2%, advanced adenoma in 31.4%, and advanced neoplasia in 33.0%. Age was positively associated with CRC (P = .03). Higher FIT concentrations were associated with increased detection of CRC (P < .008), advanced adenoma (P < .001), and advanced neoplasia (P < .001). CONCLUSIONS: Implementation of a FIT-based CRC screening program was feasible in a low-resource setting, and there was a high yield for neoplasia in individuals with a positive FIT. This approach could be used as a model to plan and disseminate organized CRC screening more broadly in Brazil and Latin America.

Alteration of oral bacteriome of smokeless tobacco users and their association with oral cancer.

Smokeless tobacco (SLT) is certainly one of the major risk factors associated with oral cancer. Disruption of oral microbiota-host homeostasis contributes to the progression of oral cancer. Here, we profiled SLT users' oral bacterial composition and inferred their functions by sequencing 16S rDNA V3-V4 region and PICRUSt2, respectively. Oral bacteriome of SLT users (with or without oral premalignant lesions), SLT with alcohol co-users, and non-SLT consumers were compared. Oral bacteriome is shaped primarily by SLT use and the incidence of oral premalignant lesions (OPL). A significantly increased bacterial α-diversity was monitored in SLT users with OPL compared to in SLT users without OPL and non-users, whereas ß-diversity was significantly explained by OPL status. Overrepresented genera were Prevotella, Fusobacterium, Veillonella, Haemophilus, Capnocytophaga, and Leptotrichia in SLT users having OPL. LEfSe analysis identified 16 genera as a biomarker that were differentially abundant in SLT users having OPL. The functional prediction of genes significantly increased for several metabolic pathways, more importantly, were nitrogen metabolism, nucleotide metabolism, energy metabolism, and biosynthesis/biodegradation of secondary metabolites in SLT users having OPL. Furthermore, HPV-16 and EBV, but not HPV-18, were considerably connected with the SLT users having OPL. Overall, this study provides evidence that SLT utilization and OPL development are associated with oral bacteriome dysbiosis indicating the enrichment of bacterial species known for their contribution to oral carcinogenesis. Therefore, delineating the cancer-inducing bacterial population in SLT users will facilitate the future development of microbiome-targeted therapies. KEY POINTS: • SLT consumption significantly elevates oral bacterial diversity. • Prevalent significant genera are Prevotella, Veillonella, and Haemophilus in SLT users with OPL. • SLT promotes the occurrence of the cancer-inducing bacterial population.

Expression of Mucin1 in saliva in oral squamous cell carcinoma and oral potentially malignant disorders (case control study).

OBJECTIVES: Overexpression of mucin1 is found in head and neck squamous cell carcinoma tissues compared with adjacent non-neoplastic tissues and higher levels are associated with metastasis and invasion. The expression level of mucin1 in saliva of normal individuals, oral potentially malignant disorders and oral squamous cell carcinoma patients and its correlation to clinical and histological variables was evaluated. SUBJECTS AND METHODS: Forty oral potentially malignant disorders, 40 oral squamous cell carcinoma subjects, and 20 age matched-controls were included. Stimulated salivary samples were collected from all participants, and mucin1 expression was measured by real-time PCR. RESULTS: Mucin1 expression in saliva was significantly elevated in oral potentially malignant disorders when compared with controls. Similarly, mucin1 expression was significantly elevated in oral squamous cell carcinoma group when compared with oral potentially malignant disorders and controls. Mucin1 expression in OSCC patient showed significant positive correlations with T classification and distant Metastasis. Mucin1 expression in oral potentially malignant disorders patients showed significant positive correlations with degree of dysplasia. CONCLUSIONS: The expression level of mucin1 in saliva might be a potential biomarker for diagnosing oral potentially malignant disorders and oral squamous cell carcinoma.

Designing a Mucoadhesive ChemoPatch to Ablate Oral Dysplasia for Cancer Prevention.

Oral cancer has a high mortality rate, and its treatment often causes debilitating complications. More than 90% of oral cancers are oral squamous cell carcinomas (OSCCs) that may develop from clinically recognizable oral premalignant lesions (OPLs). To eradicate OPLs before they turn into cancers, a non-invasive topical formulation is developed based on a novel combination of synergistically acting oxaliplatin (OXP) and mycophenolate (MPS) embedded in a controlled-release mucoadhesive patch fabricated by computer-aided 3D printing. After multiple rounds of testing and optimization, a v6.4 ChemoPatch is designed, which shows sustained release of OXP and MPS in vitro, minimal side leakage of drugs, an average elastic modulus of 2.38 MPa, and suitable drug stability at 4 °C or below for up to 12 months. In vivo analyses show almost all patches adhere to the dorsal tongue surface for 4 hours, and display a sustained release of OXP and MPS to tongue tissue for 3-4 hours. When applied in the 4-nitroquinoline-1-oxide-induced OPL rat model, the OXP-MPS patch significantly ablates dysplastic lesions with no damage to normal epithelial cells and minimal systemic absorption and side effects. This study reports the design of a novel mucoadhesive ChemoPatch as a noninvasive therapy to treat OPLs.

Characterisation of dysplastic liver nodules using low-pass DNA sequencing and detection of chromosome arm-level abnormalities in blood-derived cell-free DNA.

High-grade dysplasia carries significant risk of transformation to hepatocellular carcinoma (HCC). Despite this, at the current standard of care, all non-malignant hepatic nodules including high-grade dysplastic nodules are managed similarly. This is partly related to difficulties in distinguishing high-risk pathology in the liver. We aimed to identify chromosome arm-level somatic copy number alterations (SCNAs) that characterise the transition of liver nodules along the cirrhosis-dysplasia-carcinoma axis. We validated our findings on an independent cohort using blood-derived cell-free DNA. A repository of non-cancer DNA sequences obtained from patients with HCC (n = 389) was analysed to generate cut-off thresholds aiming to minimise false-positive SCNAs. Tissue samples representing stages from the multistep process of hepatocarcinogenesis (n = 184) were subjected to low-pass whole genome sequencing. Chromosome arm-level SCNAs were identified in liver cirrhosis, dysplastic nodules, and HCC to assess their discriminative capacity. Samples positive for 1q+ or 8q+ arm-level duplications were likely to be either HCC or high-grade dysplastic nodules as opposed to low-grade dysplastic nodules or cirrhotic tissue with an odds ratio (OR) of 35.5 (95% CI 11.5-110) and 16 (95% CI 6.4-40.2), respectively (p < 0.0001). In an independent cohort of patients recruited from Nottingham, UK, at least two out of four alterations (1q+, 4q-, 8p-, and 8q+) were detectable in blood-derived cell-free DNA of patients with HCC (n = 22) but none of the control patients with liver cirrhosis (n = 9). Arm-level SCNAs on 1q+ or 8q+ are associated with high-risk liver pathology. These can be detected using low-pass sequencing of cell-free DNA isolated from blood, which may be a future early cancer screening tool for patients with liver cirrhosis. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

The potential role of Photodynamic therapy in oral premalignant and malignant lesions: A systematic review.

BACKGROUND: Photodynamic therapy (PDT) is considered as a valid treatment option in various branches of dentistry. This systematic review aims to evaluate the usefulness of PDT for treatment of oral premalignant and malignant lesions. METHODS: The MeSH terms "Photodynamic therapy" and "PDT," in combination with other terms, have been searched by three search engines (PubMed, ISI Web of Science, and the Cochrane Library), and a systematic review has been performed. The Population, Intervention, Comparison, Outcomes, and Study design (PICOS) has been applied as method to outline our study eligibility criteria. Risk of Bias in Non-randomized Studies of Intervention (ROBINS-I) has been performed too. RESULTS: Initial results were 1513. Definitely, 27 studies met our selection criteria. CONCLUSIONS: Topical PDT is an easy to perform technique, well-tolerated treatment and it appears to be an effective method with encouraging achievements in the treatment of premalignant and malignant lesions of the soft tissues of the oral cavity; nevertheless more studies are required to integrate the up-to-date experience of this application.

A PIK3CA transgenic mouse model with chemical carcinogen exposure mimics human oral tongue tumorigenesis.

Oral cancer causes significant global mortality and has a five-year survival rate of around 64%. Poor prognosis results from late-stage diagnosis, highlighting an important need to develop better approaches to detect oral premalignant lesions (OPLs) and identify which OPLs are at highest risk of progression to oral squamous cell carcinoma (OSCC). An appropriate animal model that reflects the genetic, histologic, immunologic, molecular and gross visual features of human OSCC would aid in the development and evaluation of early detection and risk assessment strategies. Here, we present an experimental PIK3CA + 4NQO transgenic mouse model of oral carcinogenesis that combines the PIK3CA oncogene mutation with oral exposure to the chemical carcinogen 4NQO, an alternate experimental transgenic mouse model with PIK3CA as well as E6 and E7 mutations, and an existing wild-type mouse model based on oral exposure to 4NQO alone. We compare changes in dorsal and ventral tongue gross visual appearance, histologic features and molecular biomarker expression over a time course of carcinogenesis. Both transgenic models exhibit cytological and architectural features of dysplasia that mimic human disease and exhibit slightly increased staining for Ki-67, a cell proliferation marker. The PIK3CA + 4NQO model additionally exhibits consistent lymphocytic infiltration, presents with prominent dorsal and ventral tongue tumours, and develops cancer quickly relative to the other models. Thus, the PIK3CA + 4NQO model recapitulates the multistep genetic model of human oral carcinogenesis and host immune response in carcinogen-induced tongue cancer, making it a useful resource for future OSCC studies.

Extracellular Vesicles in Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders: A Systematic Review.

Extracellular vesicles (EVs) are secreted from most cell types and utilized in a complex network of near and distant cell-to-cell communication. Insight into this complex nanoscopic interaction in the development, progression and treatment of oral squamous cell carcinoma (OSCC) and precancerous oral mucosal disorders, termed oral potentially malignant disorders (OPMDs), remains of interest. In this review, we comprehensively present the current state of knowledge of EVs in OSCC and OPMDs. A systematic literature search strategy was developed and updated to December 17, 2019. Fifty-five articles were identified addressing EVs in OSCC and OPMDs with all but two articles published from 2015, highlighting the novelty of this research area. Themes included the impact of OSCC-derived EVs on phenotypic changes, lymph-angiogenesis, stromal immune response, mechanisms of therapeutic resistance as well as utility of EVs for drug delivery in OSCC and OPMD. Interest and progress of knowledge of EVs in OSCC and OPMD has been expanding on several fronts. The oral cavity presents a unique and accessible microenvironment for nanoparticle study that could present important models for other solid tumours.

Role of Cyclooxygenase-2 in Head and Neck Tumorigenesis.

The cyclooxygenase-2 (COX-2) is a potent enzyme that converts arachidonic acid to prostaglandins (PG), including PGE2, a key mediator of inflammation and angiogenesis. Importantly, COX-2 is activated in response to inflammatory stimuli, where it is also believed to promote the development and progression of head and neck cancers (HNC). COX-2 can mediate its protumorigenic effect through various mechanisms, such as inducing cell proliferation, inhibition of apoptosis, and suppressing the host's immune response. Furthermore, COX-2 can induce the production of vascular endothelial growth factors, hence, promoting angiogenesis. Indeed, the ability of COX-2 inhibitors to selectively restrict the proliferation of tumor cells and mediating apoptosis provides promising therapeutic targets for cancer patients. Thus, in this comprehensive review, we summarized the reported differential expression patterns of COX-2 in different stages of head and neck carcinogenesis-from potentially premalignant lesions to invasive carcinomas. Furthermore, we examined the available meta-analysis evidence for COX-2 role in the carcinogenesis of HNC. Finally, further understanding of the biological processes of COX-2 and its role in orchestrating cell proliferation, apoptosis, and angiogenesis may give therapeutically beneficial insight to develop the management plan of HNC patients and improve their clinical outcomes.

Cold Atmospheric Pressure Plasma (CAP) as a New Tool for the Management of Vulva Cancer and Vulvar Premalignant Lesions in Gynaecological Oncology.

Vulvar cancer (VC) is a specific form of malignancy accounting for 5-6% of all gynaecologic malignancies. Although VC occurs most commonly in women after 60 years of age, disease incidence has risen progressively in premenopausal women in recent decades. VC demonstrates particular features requiring well-adapted therapeutic approaches to avoid potential treatment-related complications. Significant improvements in disease-free survival and overall survival rates for patients diagnosed with post-stage I disease have been achieved by implementing a combination therapy consisting of radical surgical resection, systemic chemotherapy and/or radiotherapy. Achieving local control remains challenging. However, mostly due to specific anatomical conditions, the need for comprehensive surgical reconstruction and frequent post-operative healing complications. Novel therapeutic tools better adapted to VC particularities are essential for improving individual outcomes. To this end, cold atmospheric plasma (CAP) treatment is a promising option for VC, and is particularly appropriate for the local treatment of dysplastic lesions, early intraepithelial cancer, and invasive tumours. In addition, CAP also helps reduce inflammatory complications and improve wound healing. The application of CAP may realise either directly or indirectly utilising nanoparticle technologies. CAP has demonstrated remarkable treatment benefits for several malignant conditions, and has created new medical fields, such as "plasma medicine" and "plasma oncology". This article highlights the benefits of CAP for the treatment of VC, VC pre-stages, and postsurgical wound complications. There has not yet been a published report of CAP on vulvar cancer cells, and so this review summarises the progress made in gynaecological oncology and in other cancers, and promotes an important, understudied area for future research. The paradigm shift from reactive to predictive, preventive and personalised medical approaches in overall VC management is also considered.

Diagnostic yield of endoscopic ultrasound with fine-needle aspiration in pancreatic cystic lesions. / Rendimiento diagnóstico de la punción mediante ultrasonografía endoscópica de las lesiones quísticas del páncreas.

INTRODUCTION: Despite advances in imaging techniques, in many cases they are insufficient to establish the diagnosis of pancreatic cystic lesions (PCL). There are few publications in our setting that evaluate the combination of several methods obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). The aim of the study was to evaluate the overall utility of EUS-FNA in the diagnosis of PCL. MATERIAL AND METHODS: Retrospective study based on a database updated prospectively of a cohort of patients referred for EUS-FNA due to PCL detected in an imaging test. The sensitivity, specificity and diagnostic yield of carcinoembryonic antigen (CEA), cytology and viscosity were studied to detect mucinous lesions. RESULTS: From November 2013 to April 2018, 122 EUS were performed for PCL. EUS-FNA was performed in 94/122 (77%) and 21/122 (17.2%) patients were operated on. We included 33/122 patients who had diagnostic confirmation by histology, imaging (serous cyst with typical pattern) or clinical evolution. The study of the ROC curve determined the cutoff point ≥419 ng/ml to differentiate mucinous/non-mucinous cystic lesions. The diagnostic yield of CEA was 87.5% (21/24), cytology 81.8% (27/33) and viscosity 84.4% (27/32). The three parameters in combination obtained the best result (30/33, 90.9%). CONCLUSION: The combination of CEA analysis, cytology and viscosity of pancreatic fluid obtained by EUS-FNA increases the performance in the diagnosis of mucinous pancreatic cystic lesions, with it being greater than 90%.

Molecular evidence supporting the precursor nature of atypical adenomatous hyperplasia of the prostate.

Atypical adenomatous hyperplasia (AAH) of the prostate is characterized by lobular proliferation of closely packed small acini. It is hypothesized that AAH is a precursor lesion for low-grade prostate cancer arising from the transition zone. Telomere dysfunction is common during malignant transformation of epithelia. In this study, we investigate telomere shortening in AAH (n = 93), high-grade prostatic intraepithelial neoplasia (HGPIN) ( n = 68), and prostatic adenocarcinoma (PCA) ( n = 70) using quantitative fluorescence in situ hybridization. Twenty percent (19 of 93) of AAH specimens, 68% (46 of 68) of HGPIN, and 83% (58 of 70) of PCA showed significant telomere shortening. Thirty-two percent of AAH lesions had α-methylacyl-CoA racemase (AMACR) expression, a sensitive and specific marker for HGPIN and PCA. AMACR expression in AAH was seen more frequently in AAH foci with telomere shortening or coexisting PCA. Our findings indicate that a subset of AAH lesions have telomere shortening and AMACR expression, suggesting that these foci may be precursors for PCA.

Nicotine induces oral dysplastic keratinocyte migration via fatty acid synthase-dependent epidermal growth factor receptor activation.

Despite advances in diagnostic and therapeutic management, oral squamous cell carcinoma (OSCC) patient survival rates have remained relatively unchanged. Thus, identifying early triggers of malignant progression is critical to prevent OSCC development. Traditionally, OSCC initiation is elicited by the frequent and direct exposure to multiple tobacco-derived carcinogens, and not by the nicotine contained in tobacco products. However, other nicotine-containing products, especially the increasingly popular electronic cigarettes (e-cigs), have unknown effects on the progression of undiagnosed tobacco-induced oral premalignant lesions, specifically in regard to the effects of nicotine. Overexpression of fatty acid synthase (FASN), a key hepatic de novo lipogenic enzyme, is linked to poor OSCC patient survival. Nicotine upregulates hepatic FASN, but whether this response occurs in oral dysplastic keratinocytes is unknown. We hypothesized that in oral dysplastic keratinocytes, nicotine triggers a migratory phenotype through FASN-dependent epidermal growth factor receptor (EGFR) activation, a common pro-oncogenic event supporting oral carcinogenesis. We report that in oral dysplastic cells, nicotine markedly upregulates FASN leading to FASN-dependent EGFR activation and increased cell migration. These results raise potential concerns about e-cig safety, especially when used by former tobacco smokers with occult oral premalignant lesions where nicotine could trigger oncogenic signals commonly associated with malignant progression.

The Clinicopathological Correlations of hTERC Amplification with Esophageal Squamous Cell Precursor Lesions.

BACKGROUND: Esophageal squamous cell precursor lesions remain one of the most controversial topics in pathology and clinical management. AIMS: To analyze the dysregulation of human telomerase RNA component (hTERC) in esophageal squamous cell precursor lesions and the clinicopathological correlations with the characteristics of esophageal squamous cell precursor lesions. METHODS: Florescence in situ hybridization was performed to detect hTERC amplification in different gradings of esophageal squamous cell precursor lesions. With retrospective follow-up data, clinicopathological correlations between hTERC and esophageal squamous cell precursor lesions were subjected to logistic regression analysis. RESULTS: hTERC amplification gradually increased with upgrading of dysplasia, reaching the highest level in high-grade intraepithelial neoplasia, and there was a significant difference between the low-grade intraepithelial neoplasia group and the high-grade intraepithelial neoplasia group (P = 0.00). Logistic regression analysis showed that hTERC amplification was correlated with both dysplasia grading and ulcer characteristics of esophageal squamous cell precursor lesions (P < 0.05). CONCLUSIONS: hTERC amplification with increasing grading of esophageal squamous cell precursor lesions and the presence of ulcer characteristics might provide an important molecular and pathological marker for the diagnosis and clinical prognosis of esophageal squamous cell precursor lesions, especially for those ambiguous cases with more divergence in classification.

Chemoprevention of oral cancer in leukoplakia patients: A systematic review and meta-analysis.

The systematic review and meta-analysis of published randomised controlled trials (RCTs) was conducted to review the effectiveness of current chemopreventive agents in the treatment of oral leukoplakia lesions (OPLs) and prevention of their progression to oral cancer. Material was identified through a retrospective literature search of the electronic PubMed database, Embase and Cochrane Library between 2008 and 2016.Eight RCTs were included for systematic review. The pooled estimate showed a 14% greater chance of responding for those randomised to interventions compared with placebo (Risk Ratio [RR] 1.14, 95% confidence interval [CI] 0.72 to 1.81). The CI from individual studies overlapped. The results suggested that there were no significant differences in comparing clinical responses between chemopreventive agents with placebo in treatment of OPLs. It is time to investigate new agents for oral cancer chemoprevention.

Adjunctive screening devices for oral lesions: their use by Canadian Dental Hygienists and the need for knowledge translation.

Screening for oral cancer and other mucosal conditions is a knowledge-to-action objective that should be easy: there is supportive evidence, it is fast and non-invasive, and the oral cavity is easy to visualize. However, over 60% of oral cancers are diagnosed late, when treatment is complex and prognosis poor. Adjunctive screening devices (ASDs), e.g. toluidine blue (TB), fluorescence visualization (FV), chemiluminescence (CL) and brush biopsies, were designed to assess risk of oral lesions or aid in identification and localization of oral premalignant and malignant lesions. Little is known on how clinicians feel about using ASDs. OBJECTIVES: To evaluate use and level of comfort in using ASDs for oral cancer screening among dental hygienists. METHODS: Online email survey of a stratified random sample of nearly 3000 dental hygienists from four Canadian provinces. RESULTS: A total of 369 hygienists responded about ASDs. Ninety-three (25%) had used an ASD. Use was associated with six or more continuing education (CE) courses per year (P = 0.030), having a CE course in oral pathology within the last 3 years (P = 0.003) and having a screening protocol (P = 0.008). The most commonly used ASD is FV, which was the tool hygienists felt most comfortable using. Few used brush biopsies. Older graduates were more comfortable using TB (P = 0.014) and CL (0.033). CONCLUSION: Current evidence and education through CE appears to bolster knowledge translation efforts for hygienists to become more comfortable in the use of ASDs. ASDs with minimal supporting evidence and not specifically targeted to hygienists, such as the brush biopsies, are not well utilized.

Clonal relationships between lobular carcinoma in situ and other breast malignancies.

BACKGROUND: Recent evidence suggests that lobular carcinoma in situ (LCIS) can be a clonal precursor of invasive breast cancers of both the ductal and lobular phenotypes. We sought to confirm these findings with an extensive study of fresh frozen breast specimens from women undergoing mastectomy. METHODS: Patients with a history of LCIS presenting for therapeutic mastectomy were identified prospectively. Frozen tissue blocks were collected, screened for lesions of interest, and subjected to microdissection and DNA extraction. Copy number profiling, whole-exome sequencing, or both were performed. Clonal relatedness was assessed using specialized statistical techniques developed for this purpose. RESULTS: After exclusions for genotyping failure, a total of 84 lesions from 30 patients were evaluated successfully. Strong evidence of clonal relatedness was observed between an LCIS lesion and the invasive cancer for the preponderance of cases with lobular carcinoma. Anatomically distinct in situ lesions of both ductal and lobular histology were also shown to be frequently clonally related. CONCLUSIONS: These data derived from women with LCIS with or without invasive cancer confirm that LCIS is commonly the clonal precursor of invasive lobular carcinoma and that distinct foci of LCIS frequently share a clonal origin, as do foci of LCIS and ductal carcinoma in situ.

Ultrasound screening for cholangiocarcinoma could detect premalignant lesions and early-stage diseases with survival benefits: a population-based prospective study of 4,225 subjects in an endemic area.

BACKGROUND: Thailand has a high incidence of cholangiocarcinoma (CCA), particularly in the north and northeastern regions. Most CCA patients come at a late, unresectable stage and presently no optimal screening test for CCA has been established. We determined the prevalence of CCA in a remote northern village and explored if screening could lead to early detection and survival benefits. METHODS: A 5-year population-based study was started in October, 2011 for consented Thai individuals, aged 30-60 years. The screening program comprised blood testing, stool examination and serial ultrasonography every 6 months. RESULTS: During the first 3 years, 4,225 eligible individuals were enrolled. CCA was detected in 32 patients, with a mean age of 51.9 years (41-62 years), and 21/32 cases were at a curative resectable stage. The prevalence rate of CCA was 165.7 per 100,000 and one- and two-year incidence rate was 236.7/100,000 and 520.7/100,000, respectively. One- and 2-year overall survival rates of CCA patients were 90.9 and 61.5 %, respectively. Prognosis was better in resectable cases with 100 % 1-year and 77.8 % 2-year survival rates. Interestingly, premalignant pathological lesions (stage 0) were identified in 11 cases with 100 % 3-year survival rate. Serum biomarkers and alkaline phosphatase were not sufficient to detect early-stage disease. In 22 patients, stool samples were positive for Opistorchis viverrini, based on polymerase chain reaction. CONCLUSION: Detection of premalignant lesions and early-stage resectable CCA by ultrasonography resulted in improved clinical outcome. Ultrasonography should be offered as a first screening tool for CCA in an endemic area until other useful biological markers become available.

Comparison of spatula and cytobrush cytological techniques in early detection of oral malignant and premalignant lesions: a prospective and blinded study.

BACKGROUND: The use of oral cytology to diagnose malignant and premalignant lesions at an early stage is considered crucial. The aim of this study was to evaluate the diagnoses of the spatula and the cytobrush techniques compared with the gold standard histopathological findings, analysed according to different diagnostic criteria. METHODS: Cytological smears were obtained from 76 suspicious oral malignant lesions and 116 oral leukoplakia lesions using two techniques: cytobrush plus cell collector and metal spatula. Subsequently, a surgical biopsy was performed on each lesion to achieve a histopathological diagnosis. Evaluation was conducted with respect to three different diagnostic criteria. RESULTS: The sensitivity for diagnosing carcinoma in clinically malignant cases was 89.58% and 60.42% for cytobrush and spatula techniques, respectively. Inclusion of severe dysplastic cases for 'high-risk' lesions increased the sensitivity up to 96.36% and 78.18% for two techniques, respectively. In leukoplakia lesions, malignant and severely dysplastic cells were diagnosed at a sensitivity of 88.89% in the cytobrush and 55.56% in the spatula techniques. Extending the criteria by defining malignant or any dysplastic findings as positive, sensitivity was increased to 98.02% and 89.11% for the spatula and the cytobrush techniques, respectively. Specificity for both techniques increased to 100%. The difference between the diagnoses of histopathology and the spatula cytology was statistically significant (P < 0.01), while no such difference was found with the cytobrush technique (P > 0.1). CONCLUSION: The cytobrush, unlike the spatula, is a useful screening instrument for early diagnosis of suspicious oral lesions and could therefore contribute to improved oral cancer prognosis.